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Outcomes for Extremely Premature Infants
Abstract
Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for 7 years and is now approximately 11.39%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23 to 24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal estimated date of confinement. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (<1000 g) remain at high risk for death and disability with 30% to 50% mortality and, in survivors, at least 20% to 50% risk of morbidity. The introduction of continuous positive airway pressure, mechanical ventilation, and exogenous surfactant increased survival and spurred the development of neonatal intensive care in the 1970s through the early 1990s. Routine administration of antenatal steroids during premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91% and 95% (compared with 85%-89%) avoids excess mortality; however, final analyses of data from these trials have not been published, so definitive recommendations are still pending. The development of neonatal neurocritical intensive care units may improve neurocognitive outcomes in this high-risk group. Long-term follow-up to detect and address developmental, learning, behavioral, and social problems is critical for children born at these early gestational ages.The striking similarities in response to extreme prematurity in the lung and brain imply that agents and techniques that benefit one organ are likely to also benefit the other. Finally, because therapy and supportive care continue to change, the outcomes of extremely low birth weight infants are ever evolving. Efforts to minimize injury, preserve growth, and identify interventions focused on antioxidant and anti-inflammatory pathways are now being evaluated. Thus, treating and preventing long-term deficits must be developed in the context of a "moving target."
... The excluded conditions did not fit into a standardized feeding approach and required a more personalized approach based on co-morbidities and results of other tests and interventions. Patients were stratified based on GA into periviable (<24 weeks GA) [31,32], extremely preterm (24 to <28 weeks GA) [32] and very preterm (≥28 to 32 weeks GA) [32]. ...
... The excluded conditions did not fit into a standardized feeding approach and required a more personalized approach based on co-morbidities and results of other tests and interventions. Patients were stratified based on GA into periviable (<24 weeks GA) [31,32], extremely preterm (24 to <28 weeks GA) [32] and very preterm (≥28 to 32 weeks GA) [32]. ...
... The excluded conditions did not fit into a standardized feeding approach and required a more personalized approach based on co-morbidities and results of other tests and interventions. Patients were stratified based on GA into periviable (<24 weeks GA) [31,32], extremely preterm (24 to <28 weeks GA) [32] and very preterm (≥28 to 32 weeks GA) [32]. ...
Objective:
Ten-year data from the simplified, individualized, milestone-targeted, pragmatic, longitudinal and educational (SIMPLE) feeding initiative were examined by gestational age (GA) category to characterize the feeding milestones, length of hospital stays (LOHS), annual variability and predictive models for LOHS.
Study design:
Preterm infants (≤32 weeks GA, N = 434) in level-IV NICU had milestone-targeted feeding plans. Continuous data were analyzed for outcomes.
Results:
Over 93% successfully attained full oral feedings. Earlier acquisition of feeding milestones correlated with earlier discharge (P < 0.05). Year-wise analysis showed sustained maintenance of milestones (P < 0.05). Milestones and outcomes (P < 0.001) were significantly correlated with different GA categories. Prediction models for LOHS were derived using GA, BPD, age at full enteral, postmenstrual age (PMA) at 1st and full oral feeds.
Conclusions:
The SIMPLE feeding program minimized variability and promoted acquisition of feeding milestones consistently. LOHS is predictable using feeding milestones, co-morbidities, GA, and PMA at feeding milestones.
... 28 Human viability, defined as gestational age at which the chance of survival is 50%, is currently set at approximately 24-25 weeks in most developed countries, although there are NICUs where they could be set at 22-23 GW, with better survival of infant girls. 29 From the point of view of healthcare professionals involved in intensive care of those infants, viable infants are those whom most clinicians would treat, while nonviable are those whom most clinicians would not treat, and those in between are the so-called gray zone. 29,30 This subjective definition could be different in developed and in and the patent by the same author on AU have been submitted in the United States of America in 1954. ...
... 29 From the point of view of healthcare professionals involved in intensive care of those infants, viable infants are those whom most clinicians would treat, while nonviable are those whom most clinicians would not treat, and those in between are the so-called gray zone. 29,30 This subjective definition could be different in developed and in and the patent by the same author on AU have been submitted in the United States of America in 1954. 6 As the author of the patent stated in his application, "One of the objects of this invention is to provide an AU which will sustain an unborn fetus in a condition similar to that of the human uterus." ...
... 55 The historical perspective of the therapeutic modalities for the care of infants at the limits of viability in developed countries is shown in Table 1. 29 As Albert Einstein said-"We cannot solve our problems with the same thinking we used when we created them," 58 if applying it to the treatment of infants at the limits of viability, probably something should be changed in our way of thinking considering the care for those tiny infants. There are at least two reasons to make some changes-the first is that the limit of viability has been shifting towards 20 GW and beyond, and the second is that up to now, the intrauterine environment has been only partly considered in the care of the infants at the limits of viability because microgravity as possibly an important environmental factor has not been taken under consideration at all. ...
survival above 50% without major morbidity in some developed countries is possible at 22 gestational weeks (GW), while anecdotal
survival has been described even at 21 GW + 4 days. The possibility of extending the survival of the smallest premature infants
has been challenging for many decades. Good results of the survival of tiny and immature infants are improving in developed
countries, but survival without major morbidity is still stagnant. From the historical point of view, limits of viability changed in
the last 150 years for many medical, economic, ethical, and other reasons from 32 to 22 weeks of gestation, but always related
to already born infants. Almost 70 years ago and recently, treating extreme prematurity remains a difficult medical issue due to
many iatrogenic injuries which can hardly be avoided by using existing modes of therapy, including a modern way of thinking,
sophisticated technology, and drugs. Recent technological advancements may enable the translation of experimental models
of the artificial uterus (AU) and the artificial womb technology (AWT), termed ectogenesis which is the partial or complete
maturation of a developing embryo or fetus outside the human body, to clinical practice, raising many technical, medical, and
ethical dilemmas.
The AWT is investigated on animal models only, but even in the research model, microgravity and gravity (G), age, thermoregulation,
and oxygenation (GATO) hypotheses have not been mentioned or considered, although they might be important for the
development of the fetus at early gestations. It might be advisable to change the way of thinking and find the reasons pro and
contra of microgravity use in AWT research, which may improve care for fetuses born at the lower limits of viability.
Keywords: Artificial uterus, Limits of viability, Microgravity, Outcome, Prematurity, Treatment.
... The mortality rate of preterm infants has significantly decreased in recent years alongside the advances of neonatal healthcare and medical treatments [1][2][3], whereas preterm infants are still at a high risk of neurodevelopmental deficiency in early life as well as late Microorganisms 2023, 11, 814. https://doi.org/10.3390/microorganisms11030814 ...
... Preterm infants were included if they were: (1) 0-7 days old after birth, (2) born at 28 to 32 weeks of gestational age (28 0/7 to 32 6/7), and (3) had a negative drug exposure history (no illicit drug use during pregnancy). Exclusion criteria included: (1) infant mothers that were younger than 18 years old, (2) severe periventricular/intraventricular hemorrhage (≥Grade III), and (3) other known congenital anomalies. ...
Objectives:
The objective of this study is to investigate the impact of early life experiences and gut microbiota on neurobehavioral development in preterm infants during neonatal intensive care unit (NICU) hospitalization.
Methods:
Preterm infants were followed from NICU admission until their 28th postnatal day or until discharge. Daily stool samples, painful/stressful experiences, feeding patterns, and other clinical and demographic data were collected. Gut microbiota was profiled using 16S rRNA sequencing, and operational taxonomic units (OTUs) were selected to predict the neurobehaviors. The neurobehavioral development was assessed by the Neonatal Neurobehavioral Scale (NNNS) at 36 to 38 weeks of post-menstrual age (PMA). Fifty-five infants who had NNNS measurements were included in the sparse log-contrast regression analysis.
Results:
Preterm infants who experienced a high level of pain/stress during the NICU hospitalization had higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs and taxa belonging to seven genera, i.e., Enterobacteriaceae_unclassified, Escherichia-Shigella, Incertae_Sedis, Veillonella, Enterococcus, Clostridium_sensu_stricto_1, and Streptococcus with five belonging to Firmicutes and two belonging to Proteobacteria phylum. The enriched abundance of Enterobacteriaceae_unclassified (OTU17) and Streptococcus (OTU28) were consistently associated with less optimal neurobehavioral outcomes. The other six OTUs were also associated with infant neurobehavioral responses depending on days at NICU stay.
Conclusions:
This study explored the dynamic impact of specific OTUs on neurobehavioral development in preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress and feeding in the NICU. The gut microbiota and acute pain/stressful experiences dynamically impact the neurobehavioral development in preterm infants during their NICU hospitalization.
... According to the US National Institute of Health, the leading cause of infant death is a preterm (PT) birth (NICHD, 2017). As such, there have been many advances and improvements made by the medical field in neonatal care with a focus on reducing infant mortality rate, such that the survival rate of an infant born 4 weeks early was less than 60 % in 1980 but increased to over 80 % by the mid-2000 (Glass et al., 2015). In conjunction with the increase in survivability of premature birth infants, there is an increase in morbidity. ...
... In conjunction with the increase in survivability of premature birth infants, there is an increase in morbidity. Indeed, premature births are associated with approximately 50 % of all disabilities in children (Glass et al., 2015). Such morbidities include many neurodevelopmental abnormalities and delays in reaching motor skill milestones. ...
Though early intervention can improve outcomes for children with motor disabilities, delays in diagnosis can impact the success of intervention programs. Prior work indicates that spontaneous kicking patterns can be used to model typical infant motor development to assist in the early detection of motor delays. However, abnormalities in spontaneous movements are not well defined or readily observable through traditional functional assessments. In this research, a method is introduced for the early detection of delays through the assessment of spontaneous kicking data gathered using a wearable sensing suit. We present formulations of kinematic features identified in the clinical space, identify which features are significant predictors of infant age, and establish normative values. Finally, we offer an analysis of preterm (PT) infant data compared to normative values derived from term infants. Term and PT infants ranging in age from 1 to 10 months were studied. We found that frequency, duration, acceleration, inter-joint coordination, and maximum joint excursion metrics had a significant correlation with age. From these features, models of typical kicking development were created using data from term, typically developing infants. When compared to normative trends, PT infants display differing developmental trends.
... When it comes to Korean research, recent studies announced that lower GA is associated with elevated risk of adverse neurodevelopmental and respiratory outcome [15]. Furthermore, limit of viability and intact survival is not defined as same gestational age in worldwide, it can differ from country to country [25], and center to center [26,27]. Therefore, a multidisciplinary approach will help OBGYNs make appropriate decisions that suits individual situation. ...
Background
In twin pregnancies complicated by selective fetal growth restriction (sFGR), if the smaller twin is in the state of impending intra-uterine death (IUD), immediate delivery will reduce the risk of IUD of the smaller twin while exposing the larger twin to iatrogenic preterm birth (PTB). Therefore, the management options would either be to maintain pregnancy for the maturation of the larger twin despite the risk of IUD of the smaller twin or immediate delivery to prevent IUD of the smaller twin. However, the optimal gestational age of management transition from maintaining pregnancy to immediate delivery has not been established. The objective of this study was to evaluate the physician’s perspective on the optimal timing of immediate delivery in twin pregnancies complicated by sFGR.
Methods
An online cross-sectional survey was performed with obstetricians and gynecologists (OBGYN) in South Korea. The questionnaire asked the following: (1) whether participants would maintain or immediately deliver a twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin; (2) the optimal gestational age of management transition from maintaining pregnancy to immediate delivery in a twin pregnancy with impending IUD of the smaller twin; and (3) the limit of viability and intact survival in general preterm neonates.
Results
A total of 156 OBGYN answered the questionnaires. In a clinical scenario of dichorionic (DC) twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin, 57.1% of the participants answered that they would immediately deliver the twin pregnancy. However, 90.4% answered that they would immediately deliver the pregnancy in the same scenario for monochorionic (MC) twin pregnancy. The participants designated 30 weeks for DC twin and 28 weeks for MC twin pregnancies as the optimal gestational age of management transition from maintaining pregnancy to immediate delivery. The participants regarded 24 weeks as the limit of viability and 30 weeks as the limit of intact survival in general preterm neonates. The optimal gestational age of management transition for DC twin pregnancy was correlated with the limit of intact survival in general preterm neonates (p < 0.001), but not with the limit of viability. However, the optimal gestational age of management transition for MC twin pregnancy was associated with both the limit of intact survival (p = 0.012) and viability with marginal significance (p = 0.062).
Conclusions
Participants preferred to immediately deliver twin pregnancies complicated by sFGR with impending IUD of the smaller twin at the limit of intact survival (30 weeks) for DC twin pregnancies and at the midway between the limit of intact survival and viability (28 weeks) for MC twin pregnancies. More research is needed to establish guidelines regarding the optimal delivery timing for twin pregnancies complicated by sFGR.
... Approximately 50% of preterm infant's experience difficulties in executive functioning, learning, and behavior, often requiring special education services and supports [13]. Infants born with a BW less than 1500 grams, have an 11.6% increased risk of being diagnosed with intellectual disabilities, in comparison to full term infants [14]. ...
... Another common finding is the impact of fetal sex on preterm birth, with males at higher risk of prematurity [53], as observed in the present study. Prematurity is frequently associated with a worse outcome [53,54]. However, we did not find that male neonates had a worse NAO. ...
Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (β = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (β = −0.64 ± 0.27, p = 0.019; β = −0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processes.
... In this study, neonates who had oxygen saturation less than 90% had two times higher hazard of death than neonates with oxygen saturation ≥90%. This finding is supported by other studies done on preterm infants (35,36). This can be explained by the fact that low oxygen saturation in the blood can affect the oxygen concentration in the body's tissues, including the organs and muscles which results in cell death (37). ...
Background
Each year, approximately 2.7 million neonates die in their first month of life worldwide, and the majority of these deaths occur in low-income countries. According to the Global Burden of Disease estimation, 1.3 million annual incident cases of neonatal sepsis were reported worldwide, resulting in 203,000 sepsis-attributable deaths. Little is known about the time to death of neonates and predictors after admission with a diagnosis of sepsis. This study aimed to assess the incidence and predictors of death among neonates admitted to the neonatal intensive care unit with a diagnosis of sepsis in referral hospitals in Northwest Ethiopia.
Methods
A multicenter prospective follow-up study was conducted from November 11 to December 7, 2021. A stratified random sampling technique was employed to select 412 neonates. Neonates admitted with sepsis were followed until they develop event for a maximum of 28 days of age. A face-to-face interview was conducted with the mother of the neonate using a pretested and structured questionnaire, and neonatal charts were reviewed to collect baseline factors. Data were entered into Epi-data version 4.6 and exported to STATA version 14 for analysis. A bivariable and multivariable exponential Cox regression model was fitted to identify predictors of death. The adjusted hazard ratio (AHR) with 95% CI was calculated, and statistical significance was declared at a P-value of 0.05 in the multivariable analysis.
Results
A total of 75 (18.47%) neonates died during the study period, with a 95% CI of 14.82–22.60. The incidence rate of death was 28 (95% CI, 22, 35) per 1,000 person-days of observation, with a total follow-up time of 2,677 person-days of observation. Birth weight (<2,500 g) (AHR = 2.12, 95% CI: 1.01, 4.43), prematurity (AHR = 2.06, 95% CI: 1.02, 4.15), duration of labor >24 h (AHR = 3.89, 95% CI: 1.38, 11.01), breast feeding (AHR = 0.43, 95% CI: 0.23, 0.80), having respiratory distress syndrome (AHR = 1.77, 95% CI: 1.02, 306), oxygen saturation less than 90% (AHR = 2.23, 95% CI: 1.02, 306) were significant predictors of death among neonates admitted with sepsis.
Conclusion and recommendation
The incidence of neonatal mortality in this study was high. Early detection and appropriate management of patients’ presentations like respiratory distress syndrome and low oxygen saturation are necessary to reduce neonatal sepsis-related mortality. Special attention should be given to low birth weight and premature neonates and mothers should be encouraged to breastfeed their newborns after delivery.
... This showed that premature babies are at risk of heart defects, lung disorders, brain damage, and delayed development. 27 There will be physical and mental problems when women get pregnant at a young age or less than 20 years. This is because the uterus and pelvis have not developed optimally, which can lead to maternal as well as infant morbidity and also stop or inhibit the mother's growth and physical development. ...
Low birth weight (LBW) is one of the health problems that cause long-term and short-term consequences to a child, mainly due to maternal age, which is determined by very young or old maternal age. This study aims to determine maternal age's effect on LBW in a larger population while controlling for factors such as maternal education and occupation, residence area, socioeconomic status, iron consumption during pregnancy, Maternal and Child Health (MCH) book, gestational age, and ANC K4. The data for this study were obtained from the Basic Health Research 2018, and the unit of analysis was mothers with children under the age of five. A risk factor model approach was adopted to determine the association between maternal age variables and the incidence of LBW using multiple logistic regression with complex samples. The risk of LBW for mothers aged 20 or 35 years compared to mothers aged 21-34 years was 1.342 (95%CI:1.165-1.546). The final model equation included confounding variables such as socioeconomic status, MCH card ownership, gestational age, complete ANC, and CED in mothers. As a result, thus very young or old women were also at risk of having LBW children. The final multivariate analysis showed that maternal age at delivery had a highly significant association with LBW in Indonesia. This makes it necessary to educate pregnant women in particular and all levels of society to minimize the risk of LBW by preventing early marriage or delivering a baby at a very old age. Keywords: LBW, maternal age, Riskesdas, Indonesia ABSTRAK Berat Badan Lahir Rendah (BBLR) merupakan salah satu masalah kesehatan yang menyebabkan konsekuensi jangka panjang dan jangka pendek pada seorang anak, terutama karena usia ibu, yang ditentukan oleh usia ibu yang sangat muda atau tua. Penelitian ini bertujuan untuk mengetahui pengaruh usia ibu terhadap BBLR pada tingkat populasi yang lebih besar dan dikendalikan untuk beberapa karakteristik seperti pendidikan dan pekerjaan ibu, pendidikan dan pekerjaan ayah, daerah tempat tinggal, status sosial ekonomi, konsumsi zat besi selama kehamilan, kepemilikan buku KIA, usia kehamilan, dan ANC K4. Data yang digunakan diperoleh dari Riset Kesehatan Dasar 2018, dan unit analisisnya adalah ibu yang memiliki anak di bawah usia 5 tahun. Pendekatan model faktor risiko diadopsi untuk menentukan hubungan antara variabel usia ibu dan kejadian BBLR menggunakan regresi logistik berganda dengan kompleks sampel. Besarnya risiko ibu usia 20 atau 35 tahun untuk kejadian BBLR dibandingkan dengan usia ibu 21-34 tahun adalah 1,342 (95%CI: 1,165-1,546). Variabel perancu yang dimasukkan dalam persamaan model akhir adalah status sosial ekonomi, kepemilikan buku KIA, usia kehamilan, ANC lengkap, dan KEK pada ibu dengan demikian wanita usia sangat muda atau tua juga berisiko memiliki anak dengan BBLR. Hasil akhir analisis multivariat menunjukkan bahwa usia ibu saat melahirkan memiliki hubungan yang sangat signifikan dengan kejadian BBLR di Indonesia. Hal ini membuat perlu adanya edukasi bagi ibu hamil khususnya dan semua lapisan masyarakat untuk meminimalkan risiko BBLR dengan mencegah pernikahan dini atau melahirkan seorang bayi di usia yang sangat tua. Kata kunci: BBLR, usia ibu, Riskesdas, Indonesia
... Consequently, the focus of research has shifted from increasing survival rates to enhancing the quality of life and improving outcomes for these infants. It has been noticed that there is an increased risk of cognitive, behavioral, socio-emotional, speech, motor or sensory impairment in the long run [4][5][6][7]. Furthermore, long-term overall function depends on healthy socio-emotional functioning; at the same time, preterm children present more behavioral and emotional problems than their fullterm counterparts [8][9][10]. ...
Children born preterm (<37 weeks of gestation) are at increased risk of socio-emotional difficulties. This study aims to determine the effects of rehabilitation intervention on the emotional regulation of children born preterm through a systematic review. We conducted a systematic review according to PRISMA guidelines. The literature screening was carried out on PUBMED, SCOPUS and WEB OF SCIENCE in August 2022. An author identified eligible studies based on predefined inclusion criteria and extracted the data. RCT quality was assessed using the JADAD and PEDro scales. We selected five RCTs for qualitative synthesis, having the common objective of evaluating the changes in emotional regulation after a rehabilitation intervention. Evidence of benefits was found after parent training intervention (PCIT; p < 0.05). Moreover, there was an improvement in day-to-day executive life and fewer behavioral problems after mindfulness intervention. Clinical, but not statistical, efficacy was found for the group-based physiotherapy intervention. In conclusion, parent training and mindfulness interventions can be helpful rehabilitation techniques, but the relatively small sample limited statistical power, so the discovery needs to be interpreted cautiously. Further research on these aspects is recommended.
... Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infancy that results in an imbalance in lung tissue homeostasis and relatively immature repair systems within the developing lung (2)(3)(4). Chronic obstructive pulmonary disease (COPD) development can be linked to early life exposure to maternal cigarette smoke, respiratory illness, hyperoxia, and premature birth (5,6). Neutrophilic inflammation marked by increased protease activity and driven in part by increased proteobacteria has been recognized as a primary contributor to the development of chronic lung diseases of infancy and adulthood (7)(8)(9)(10)(11). ...
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature dominated by Proteobacteria abundance and Lactobacillus scarcity. However, the relationship between pulmonary microbial dysbiosis and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that a double-hit hyperoxia and LPS murine model of BPD would show heightened Ac-PGP pathway and neutrophil activity. Through gain- and loss-of-function studies in the same model we showed that Ac-PGP plays a critical role in driving BPD development. We tested a novel inhaled live biotherapeutic using active Lactobacillus strains to counteract lung dysbiosis in in vitro and in vivo models of BPD and COPD. The Lactobacillus LBP is effective in improving lung structure and function, reducing neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease. Live inhaled microbiome-based therapeutics show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.
... Among extreme preterm neonates, those born near viability have low survival rates, ranging from 28% at 23 weeks to 83% at 26 weeks [3] and a high rate of major sequelae, from 89% at 23 weeks to 71% at 26 weeks [4], including chronic lung and cardiovascular disease and motor and cognitive deficits [4]. These figures have only slightly improved over the recent decades [3,5]. One of the multiple reasons for the poor outcomes is the immature fetal pulmonary system, which represents a biological barrier for ventilationbased life support, as currently used in neonatal units. ...
Objective:
To describe the development of an artificial placenta (AP) system in sheep with learning curve and main bottlenecks to allow survival up to one week.
Methods:
A total of 28 fetal sheep were transferred to an AP system at 110-115 days of gestation. The survival goal in the AP system was increased progressively in three consecutive study groups: 1-3 h (n = 8), 4-24 h (n = 10) and 48-168 h (n = 10). Duration of cannulation procedure, technical complications, pH, lactate, extracorporeal circulation (EC) circuit flows, fetal heart rate, and outcomes across experiments were compared.
Results:
There was a progressive reduction in cannulation complications (75%, 50% and 0%, p = 0.004), improvement in initial pH (7.20 ± 0.06, 7.31 ± 0.04 and 7.33 ± 0.02, p = 0.161), and increment in the rate of experiments reaching survival goal (25%, 70% and 80%, p = 0.045). In the first two groups, cannulation accidents, air bubbles in the extracorporeal circuit, and thrombotic complications were the most common cause of AP system failure.
Conclusions:
Achieving a reproducible experimental setting for an AP system is extremely challenging, time- and effort-consuming, and requires a highly multidisciplinary team. As a result of the learning curve, we achieved reproducible transition and survival up to 7 days. Extended survival requires improving instrumentation with custom-designed devices.
... Bronchopulmonary dysplasia (BPD) is preterm infants' most common chronic lung disease [1] . In recent years, due to advances in perinatal medicine, the use of pulmonary surfactants and ventilators, the birth and survival rates of very low birth weight infants have increased signi cantly, and the incidence of BPD has been increasing year by year [2] , which has a serious impact on the survival and prognosis of preterm infants. However, there is still a lack of effective measures to prevent and treat BPD [3][4] . ...
AIM
To evaluate the association between hematological parameters on the first day and bronchopulmonary dysplasia (BPD) in preterm infants and to help with early warning, identification, and intervention in the development of BPD.
METHODS
This is a retrospective study of all premature infants admitted to neonatal intensive care From January 2017 to June 2022, BPD was diagnosed as hypoxia exposure over 28 days, and levels of neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio༈PLR༉, Platelet count༈PLT༉, Mean platelet volume༈MPV༉and Platelet mass index༈PMI༉ were determined in all groups. Multivariate analysis was conducted to evaluate the independence of the association between the hematological parameters on the first day and the risk of BPD.
RESULTS
In our research 76 cases of non-BPD and 48 cases of BPD were used as controls. Compared with the non-BPD group, NLR levels were considerably higher in the BPD group, nevertheless, PLT and MPI were lower than those of non-BPD. Logistic regression analysis suggested that NLR、PLT and PMI were independent risk factors for BPD(OR: 1.15; 95% CI: 1.04–1.28; P < 0.05; OR: 0.65; 95% CI: 0.47–0.89; P < 0.05; OR: 0.90; 95% CI: 0.81-1; P < 0.05).
CONCLUSION
Our findings suggest that hematologic parameters on the first day are different who will develop BPD. A higher NLR and a lower PLT, PMI on the first day may increase the risk of BPD.
... It is known that the chances of survival of premature infant have increased in the last thirty years with new technological developments, and the duration of stay in neonatal intensive care units (NICUs) has been prolonged. 1,2 Physical and motor disorders are more prominent in premature infants, and many risky situations such as cognitive, social-emotional and mental development problems are encountered. 3,4 Developmental care practices are used to reduce these risks. ...
... Minimizing the morbidity rate in surviving children has become a priority everywhere (1,(8)(9)(10). Infants born preterm or with a VLBW are at high risk of growth failure, developmental delays, neurological diseases like cerebral palsy (CP), and lower cognitive functioning in adulthood (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). ...
Background
Very low birth weight (VLBW) and extremely low birth weight (ELBW) infants are known to be at high risk of growth failure and developmental delay later in life. The majority of those infants are born in low and middle income countries.
Aim
Growth monitoring in a cohort of infants born with a VLBW up to 18 months corrected age was conducted in a low resource setting tertiary hospital.
Methods
In this prospective cohort study, 173 infants with a birth weight below 1,501 g admitted within their first 24 h of life were recruited and the 115 surviving until discharged were asked to follow up at 1, 3, 6, 12 and 18 months. Weight, height and head circumferences were recorded and plotted on WHO Z-score growth charts.
Results
Of the 115 discharged infants 89 were followed up at any given follow-up point (1, 3, 6, 12 and/or 18 months). By 12 months of corrected age another 15 infants had demised (13.0%). The infants' trends in weight-for-age z-scores (WAZ) for corrected age was on average below the norm up to 12 months (average estimated z-score at 12 months = −0.44; 95% CI, −0.77 to −0.11), but had reached a normal range on average at 18 months = −0.24; 95% CI, −0.65 to 0.19) with no overall difference in WAZ scores weight between males and female' infants ( p > 0.7). Similar results were seen for height at 12 months corrected age with height-for-age z-scores (HAZ) of the study subjects being within normal limits (−0.24; 95% CI, −0.63 to 0.14). The mean head circumference z-scores (HCZ) initially plotted below −1.5 standard deviations (S.D.), but after 6 months the z-scores were within normal limits (mean z-score at 7 months = −0.19; 95% CI, −0.45 to 0.06).
Conclusion
Weight gain, length and head circumferences in infants with VLBW discharged showed a catch-up growth within the first 6–18 months of corrected age, with head circumference recovering best. This confirms findings in other studies on a global scale, which may be reassuring for health systems such as those in South Africa with a high burden of children born with low birth weights.
... Very low birth weight premature infants remain vulnerable following discharge from the neonatal intensive care unit (NICU). Respiratory illness, feeding and growth issues, gastroesophageal reflux, developmental issues, and the need for surgical intervention are commonly encountered over the first year of life (Glass et al., 2015;Korvenranta et al., 2009). ...
Objective
Ongoing health care challenges, low breast milk intake, and the need for rehospitalization are common during the first year of life after hospital discharge for very low birth weight (VLBW) infants. This retrospective cohort study examined breast milk intake, growth, emergency department (ED) visits, and non-surgical rehospitalizations for VLBW infants who received specialized post-discharge follow-up in western Canada, compared to VLBW infants who received standard follow-up in central Canada.
Design
Data were collected from two neonatal follow-up programs for VLBW babies (n = 150 specialized-care; n = 205 standard-care). Logistic regression was used to examine odds of breast milk intake and generalized estimating equations were used for odds of growth, ED visits and non-surgical rehospitalization by site.
Results
Specialized-care was associated with enhanced breast milk intake duration; the odds of receiving breastmilk at 4 months in the specialized-care cohort was 6 times that in the standard-care cohort. The specialized-care cohort had significantly more ED visits and rehospitalizations. However, for infants with oxygen use beyond 36 weeks compared to those with no oxygen use, the standard-care cohort had over 7 times the odds of rehospitalization where as the specialized-care cohort with no increased odds of rehospitalization.
Conclusion
Specialized neonatal nursing follow-up was associated with continued breastmilk intake beyond discharge. Infants in the specialized-care cohort used the ED and were hospitalized more often than the standard-care cohort with the exception of infants with long term oxygen needs.
... Neonates born at a gestational age of fewer than 37 weeks are more likely to die because they are vulnerable to many risks. In a study conducted in Brazil's, the Rio Grande do Sul, the risk of death among neonates born less than 37 weeks of gestational age (GA) was 28.9 times higher than that of neonates born more than 37 weeks of gestational age (GA) 33 . ...
Background: Neonatal morbidity and mortality is a global burden despite management measures that has been developed. Approximately 75% of all newborn deaths occur in the first week of life. In 2018 alone, around 2.5 million neonates died globally as a result of preventable causes such as prematurity, complications at birth, infections, and congenital abnormalities. Objective: The objective of the study was to determine neonatal morbidity and mortality patterns, and factors associated with mortality among neonates admitted in Wajir County Referral Hospital. Methodology: A hospital-based retrospective cross-sectional study was conducted among all neonates admitted to the New Born Unit of the WCRH from 01 January 2019 to 31 December 2020. A consecutive sampling technique based on the inclusion criteria was used. A data abstraction tool was used to extract data from the medical records of neonates admitted to the New Born Unit of the hospital. Results: A total of 615 neonates were included in the study. There were 336 (54.6%) male and 279 (45.4%) female neonates. Almost all the deliveries 566 (92.0%) were performed at the health facility with a minority of about 49 (8%) delivered at home. The home deliveries and referrals admissions from tertiary hospitals together were 66 (10.7%). Neonatal morbidity included birth asphyxia 335 (54.5%), neonatal sepsis 144 (23.4%), 57 (9.3%) meconium aspiration syndrome and 52 (8.5%) low birth weight/preterm. Overall mortality in 2019 at the health facility was 45 (12.97%) and in 2020, 35 (13.06%) presenting no significant difference. The deaths that occurred in the first 24 hours of life was 36 (45%). Bivariate and multivariate analysis produced a significant association between the factors associated with neonatal mortality. The multivariate analysis with day of admission (OR 2.872, 95% CI 1.293, 6.375), Sex, (OR 1.02, 95% CI 1.0.627, 1.66) and Birth weight, (OR 0.936, 95% CI 0.423, 2.068) at p<0.05. The logistic regression model was statistically significant, χ2(7) = 20.770, p <0.001. The model explained 27% (Nagelkerke R2) of the variance in discharge outcome and correctly classified 87% of cases. The male gender were 1.02 times more likely to die than females while the place of delivery was 0.572 times likely to result in death. Conclusions: Birth asphyxia was found to be the leading cause of admission, followed by neonatal sepsis and meconium aspiration syndrome respectively. The leading cause of death was birth asphyxia and neonatal sepsis. The mortality rate at the facility was 13%. Neonatal fatality of the newborns admitted to NBU is high in Wajir County. Since majority of the deaths are from preventable causes, this offers chances to improve newborn survival. Key Words: Morbidity, Mortality, Neonates, Asphyxia
Objectives:
Describe characteristics of gastroenteritis, bacteremia, and meningitis caused by nontyphoidal Salmonella among US infants.
Methods:
We analyze national surveillance data during 1968-2015 and active, sentinel surveillance data during 1996-2015 for culture-confirmed Salmonella infections by syndrome, year, serotype, age, and race.
Results:
During 1968-2015, 190 627 culture-confirmed Salmonella infections among infants were reported, including 165 236 (86.7%) cases of gastroenteritis, 6767 (3.5%) bacteremia, 371 (0.2%) meningitis, and 18 253 (9.7%) with other or unknown specimen sources. Incidence increased during the late 1970s-1980s, declined during the 1990s-early 2000s, and has gradually increased since the mid-2000s. Infants' median age was 4 months for gastroenteritis and bacteremia and 2 months for meningitis. The most frequently reported serotypes were Typhimurium (35 468; 22%) for gastroenteritis and Heidelberg for bacteremia (1954; 29%) and meningitis (65; 18%). During 1996-2015 in sentinel site surveillance, median annual incidence of gastroenteritis was 120, bacteremia 6.2, and meningitis 0.25 per 100 000 infants. Boys had a higher incidence of each syndrome than girls in both surveillance systems, but most differences were not statistically significant. Overall, hospitalization and fatality rates were 26% and 0.1% for gastroenteritis, 70% and 1.6% for bacteremia, and 96% and 4% for meningitis. During 2004-2015, invasive salmonellosis incidence was higher for Black (incident rate ratio, 2.7; 95% confidence interval, 2.6-2.8) and Asian (incident rate ratio, 1.8; 95% confidence interval, 1.7-1.8) than white infants.
Conclusions:
Salmonellosis causes substantial infant morbidity and mortality; serotype heidelberg caused the most invasive infections. Infants with meningitis were younger than those with bacteremia or gastroenteritis. Research into risk factors for infection and invasive illness could inform prevention efforts.
Introduction:
There has been a notable increase in the number of neonates born 28 weeks gestational age or younger in the United States. Many of these patients require tracheostomy early in life and subsequent laryngotracheal reconstruction (LTR). Although extremely premature infants often undergo LTR, there is no known study to date examining their post-surgical outcomes.
Objectives:
To compare decannulation rates, time to decannulation and complication rates between LTR patients born extremely premature to those born preterm and term.
Methods:
We identified 179 patients treated at a stand-alone tertiary children's hospital who underwent open airway reconstruction from 2008 to 2021. A Chi Squared test was used to detect differences in categorical clinical data between the groups of patients. A Mann-Whitney test was used to analyze continuous data within these same groups. Time to decannulation analysis was performed using Kaplan Meier analysis and evaluated with log-rank and Cox proportional hazards regression.
Results:
Children born extremely premature were more likely to incur complications following LTR (OR = 2.363, p = 0.005, CI 1.295-4.247). There was no difference in time to decannulation (p = 0.0543, Log-rank) or rate of decannulation (OR = 0.4985, p = 0.05, CI 0.2511-1.008). Extremely premature infants were more likely to be treated with an anterior and posterior grafts (OR = 2.471, p = 0.004, CI 1.297-4.535) and/or an airway stent (OR = 3.112, p < 0.001, CI 1.539-5.987).
Conclusion:
Compared with all other patients, extremely premature infants have equivalent decannulation success, but are at an increased risk for complications following LTR.
Level of evidence:
3 Laryngoscope, 2023.
Background:
Retinopathy of prematurity (ROP), a leading cause of childhood blindness, is diagnosed through interval screening by paediatric ophthalmologists. However, improved survival of premature neonates coupled with a scarcity of available experts has raised concerns about the sustainability of this approach. We aimed to develop bespoke and code-free deep learning-based classifiers for plus disease, a hallmark of ROP, in an ethnically diverse population in London, UK, and externally validate them in ethnically, geographically, and socioeconomically diverse populations in four countries and three continents. Code-free deep learning is not reliant on the availability of expertly trained data scientists, thus being of particular potential benefit for low resource health-care settings.
Methods:
This retrospective cohort study used retinal images from 1370 neonates admitted to a neonatal unit at Homerton University Hospital NHS Foundation Trust, London, UK, between 2008 and 2018. Images were acquired using a Retcam Version 2 device (Natus Medical, Pleasanton, CA, USA) on all babies who were either born at less than 32 weeks gestational age or had a birthweight of less than 1501 g. Each images was graded by two junior ophthalmologists with disagreements adjudicated by a senior paediatric ophthalmologist. Bespoke and code-free deep learning models (CFDL) were developed for the discrimination of healthy, pre-plus disease, and plus disease. Performance was assessed internally on 200 images with the majority vote of three senior paediatric ophthalmologists as the reference standard. External validation was on 338 retinal images from four separate datasets from the USA, Brazil, and Egypt with images derived from Retcam and the 3nethra neo device (Forus Health, Bengaluru, India).
Findings:
Of the 7414 retinal images in the original dataset, 6141 images were used in the final development dataset. For the discrimination of healthy versus pre-plus or plus disease, the bespoke model had an area under the curve (AUC) of 0·986 (95% CI 0·973-0·996) and the CFDL model had an AUC of 0·989 (0·979-0·997) on the internal test set. Both models generalised well to external validation test sets acquired using the Retcam for discriminating healthy from pre-plus or plus disease (bespoke range was 0·975-1·000 and CFDL range was 0·969-0·995). The CFDL model was inferior to the bespoke model on discriminating pre-plus disease from healthy or plus disease in the USA dataset (CFDL 0·808 [95% CI 0·671-0·909, bespoke 0·942 [0·892-0·982]], p=0·0070). Performance also reduced when tested on the 3nethra neo imaging device (CFDL 0·865 [0·742-0·965] and bespoke 0·891 [0·783-0·977]).
Interpretation:
Both bespoke and CFDL models conferred similar performance to senior paediatric ophthalmologists for discriminating healthy retinal images from ones with features of pre-plus or plus disease; however, CFDL models might generalise less well when considering minority classes. Care should be taken when testing on data acquired using alternative imaging devices from that used for the development dataset. Our study justifies further validation of plus disease classifiers in ROP screening and supports a potential role for code-free approaches to help prevent blindness in vulnerable neonates.
Funding:
National Institute for Health Research Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and the University College London Institute of Ophthalmology.
Translations:
For the Portuguese and Arabic translations of the abstract see Supplementary Materials section.
We report the successful management of a difficult airway in an extremely low birth weight neonate (700 g) using a Kirschner wire as a substitute for an endotracheal tube stylet. Several intubation attempts were unsuccessful because of the difficulty in guiding a very small and malleable tube under the epiglottis. This study highlights that every maternity hospital should be prepared to manage airways in unexpected extremely low birth weight neonates. Appropriate size equipment and protocols should be readily available.
Objective Critically ill children may be transferred from the neonatal intensive care unit (NICU) to the pediatric intensive care unit (PICU) for further critical care, but the frequency and outcomes of this patient population are unknown. The aims of this study are to describe the characteristics and outcomes in patients transferred from NICU to PICUs. We hypothesized that a higher-than-expected mortality would be present for patients with respiratory or cardiovascular diagnoses that underwent a NICU to PICU transition and that specific factors (timing of transfer, illness severity, and critical care interventions) are associated with a higher risk of mortality in the cardiovascular group.
Study Design Retrospective analysis of Virtual Pediatric Systems, LLC (2011–2019) deidentified cardiovascular and respiratory NICU to PICU subject data. We evaluated demographics, PICU length of stay, procedures, disposition, and mortality scores. Pediatric Index of Mortality 2 (PIM2) score was utilized to determine the standardized mortality ratio (SMR).
Results SMR of 4,547 included subjects (3,607 [79.3%] cardiovascular and 940 [20.7%] respiratory) was 1.795 (95% confidence interval: 1.62–1.97, p < 0.0001). Multivariable logistic regression analysis demonstrated transfer age (cardiovascular: odds ratio, 1.246 [1.10–1.41], p = 0.0005; respiratory: 1.254 [1.07–1.47], p = 0.0046) and PIM2 scores (cardiovascular: 1.404 [1.25–1.58], p < 0.0001; respiratory: 1.353 [1.08–1.70], p = 0.0095) were significantly associated with increased odds of mortality.
Conclusion In this present study, we found that NICU to PICU observed deaths were high and various factors, particularly transfer age, were associated with increased odds of mortality. While the type of patients evaluated in this study likely influenced mortality, further investigation is warranted to determine if transfer timing is also a factor.
Key Points
Preterm infants have increased morbidity and mortality due to immature physiology and neonatal complications. Necrotizing enterocolitis (NEC) is a devastating gastrointestinal complication that affects morbidity and mortality in preterm infants. The authors present an adaptation of Neuman’s systems model called the NEC systems model to explore intrinsic and extrinsic factors leading to NEC in preterm infants. The literature was searched for theoretical models to guide exploration of neonatal disease influenced by the environment. Neuman’s Systems Model provides a holistic approach to care of the system, offering a foundation to develop frameworks to examine preterm infants in their environment with associated stressors.
Aim: To describe NR3C1 exon-1F methylation and cortisol levels in newborns. Materials & methods: Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). Results: 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Conclusion: Hypermethylated sites in NR3C1 at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.
Background:
Infants born at extremely low birthweight (ELBW: ≤1000 g) are vulnerable to intellectual disabilities, but the factors that may distinguish between ELBW survivors with and without these impairments are not well understood. In this study, prospective associations between neonatal factors and functional outcomes in childhood and adolescence were compared in ELBW survivors with and without borderline intellectual functioning (BIF).
Methods:
Borderline intellectual functioning was defined by IQ < 85, assessed at 8 years. Among 146 ELBW survivors, 48 (33%) had IQ scores under 85, and 98 (67%) had scores equal to or over 85. Group differences in demographic and risk factors were assessed via t-test, chi-squared analysis or non-parametric tests. Neonatal factors that differed between ELBW groups were tested for association with adaptive behaviour assessed at age 5 years, and reading and arithmetic skills assessed at ages 8 and 15 years, using hierarchical regression models.
Results:
Extremely low birthweight survivors with BIF had significantly lower birthweights than ELBW survivors without BIF (790 vs. 855 g, P < 0.01) and were more likely to be born to mothers with lower socioeconomic status (SES) (78% vs. 48%, P < 0.01). These ELBW survivors also were more likely to be diagnosed with significant neurosensory impairment (NSI; 35% vs. 19%, P < 0.04), experienced more bronchopulmonary dysplasia (56% vs. 38%, P < 0.04), received more days of respiratory support (median 33 vs. 14 days, P < 0.01) and remained in hospital for longer periods (median 81 vs. 63 days, P < 0.03). Birthweight, familial SES, NSI and duration of respiratory support were significant predictors for one or more outcomes. Across groups, lower familial SES was associated with lower academic scores (Ps < 0.05), and NSI predicted lower adaptive functioning (Ps < 0.001). Other associations were moderated by group: among ELBW survivors with BIF, heavier birthweights predicted better arithmetic skills, the presence of NSI was associated with poorer arithmetic skills and more ventilation days predicted poorer reading skills.
Conclusions:
At birth, ELBW survivors with BIF faced more physiological and social disadvantages and required more medical intervention than their ELBW peers without BIF. Smaller birth size, NSI burden and prolonged neonatal ventilatory support displayed gradients of risk for childhood and adolescent academic outcomes across groups. Whereas academic performance in ELBW survivors with BIF was sensitive to variation in birth size, NSI or ventilation days, ELBW survivors without BIF attained thresholds of intellectual ability that were sufficient to support higher levels of academic performance at both ages, regardless of their status on these factors. The findings are discussed in relation to Zigler's developmental theory of intellectual disability.
Objectives:
To describe the long-term outcomes related to breathing, feeding, and neurocognitive development in extremely premature infants requiring tracheostomy.
Study design:
Pooled cross-sectional survey.
Setting:
Multi-institutional academic children's hospitals.
Methods:
Extremely premature infants who underwent tracheostomy between January 1, 2012, and December 31, 2019, at four academic hospitals were identified from an existing database. Information was gathered from responses to a questionnaire by caregivers regarding airway status, feeding, and neurodevelopment 2-9 years after tracheostomy.
Results:
Data was available for 89/91 children (96.8%). The mean gestational age was 25.5 weeks (95% CI 25.2-25.7) and mean birth weight was 0.71 kg (95% CI 0.67-0.75). Mean post gestational age at tracheostomy was 22.8 weeks (95% CI 19.0-26.6). At time of the survey, 18 (20.2%) were deceased. 29 (40.8%) maintained a tracheostomy, 18 (25.4%) were on ventilatory support, and 5 (7%) required 24-h supplemental oxygen. Forty-six (64.8%) maintained a gastrostomy tube, 25 (35.2%) had oral dysphagia, and 24 (33.8%) required a modified diet. 51 (71.8%) had developmental delay, 45 (63.4%) were enrolled in school of whom 33 (73.3%) required special education services.
Conclusions:
Tracheostomy in extremely premature neonates is associated with long term morbidity in the pulmonary, feeding, and neurocognitive domains. At time of the survey, about half are decannulated, with a majority weaned off ventilatory support indicating improvement in lung function with age. Feeding dysfunction is persistent, and a significant number will have some degree of neurocognitive dysfunction at school age. This information may help caregivers regarding expectations and plans for resource management.
Introduction:
According to the World Health Organization, 11% of all children are born prematurely, representing 15 million births annually. An extensive analysis on preterm birth, from extreme to late prematurity and associated deaths, has not been published. The authors characterize premature births in Portugal, between 2010 and 2018, according to gestational age, geographic distribution, month, multiple gestations, comorbidities, and outcomes.
Methods:
A sequential, cross-sectional, observational epidemiologic study was conducted, and data were collected from the Hospital Morbidity Database, an anonymous administrative database containing information on all hospitalizations in National Health Service hospitals in Portugal, and coded according to the ICD-9-CM (International Classification of Diseases), until 2016, and ICD-10 subsequently. Data from the National Institute of Statistics was utilized to compare the Portuguese population. Data were analyzed using R software.
Results:
In this 9-year study, 51.316 births were preterm, representing an overall prematurity rate of 7.7%. Under 29 weeks, birth rates varied between 5.5% and 7.6%, while births between 33 and 36 weeks varied between 76.9% and 81.0%. Urban districts presented the highest preterm rates. Multiple births were 8× more likely preterm and accounted for 37%-42% of all preterm births. Preterm birth rates slightly increased in February, July, August, and October. Overall, respiratory distress syndrome (RDS), sepsis, and intraventricular hemorrhage were the most common morbidities. Preterm mortality rates varied significantly with gestational age.
Conclusion:
In Portugal, 1 in 13 babies was born prematurely. Prematurity was more common in predominantly urban districts, a surprise finding that warrants further studies. Seasonal preterm variation rates also require further analysis and modelling to factor in heat waves and low temperatures. A decrease in the case rate of RDS and sepsis was observed. Compared with previously published results, preterm mortality per gestational age decreased; however, further improvements are attainable in comparison with other countries.
The adverse impact of preterm birth on maternal mental health is well documented, yet there is limited available research regarding the subjective experiences of mothers of extremely preterm infants as a distinct cohort. The aim of this study was to explore the lived experiences of mothers of extremely preterm infants, born alive at less than 28 weeks gestation, in the UK. Three mothers of extremely preterm infants participated in a semi-structured interview conducted online, which invited them to share their experiences of pregnancy, their time in neonatal intensive care unit, the transition home and their present-day experiences. An interpretative phenomenological analysis explored a delayed transition to mothering and experiences relating to initial disconnection, missed moments and establishing a maternal connection. Owing to the traumatic experiences associated with an extremely preterm birth, it is concluded that mothers would benefit from health visitor support relating to attachment, mental health and connecting to parenting communities.
Prematurity comes with a varying range of complications, implying a high prevalence of complications and mortality and depending on the severity of prematurity and the sustained inflammation among these infants, which recently sparked an important scientific interest. The primary objective of this prospective study was to establish the degree of inflammation in very (VPIs) and extremely preterm infants (EPIs) in association with the histology findings of the umbilical cord (UC), while the secondary objective was to study the inflammatory markers in the neonates’ blood as predictors of fetal inflammatory response (FIR). A total of thirty neonates were analyzed, ten of them being born extremely premature (
Introduction
Premature birth has a causal relationship with hypertension and diabetes, which are significant risk factors for major cardiovascular disease. Nonetheless, little is known whether premature birth portends future risks of acquired heart diseases, for example, ischemic heart disease (IHD), heart failure (HF), and valvular heart disease (VHD).
Methods
We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to December 2021. Studies with prospective and retrospective cohort designs that reported the association between premature birth and acquired heart disease, including IHD, HF, and VHD, were included. Data from each study were combined with a random-effects model. The results were reported in the hazard ratio (HR) with 95% confidence intervals.
Results
The selected studies were comprised of 7 studies, with 5 studies involving premature birth and the development of IHD in adulthood and 2 studies involving premature birth and HF. No studies reporting the relationship between premature birth and VHD met our initial inclusion criteria. Our study did not find any association between premature birth and IHD in the adulthood (HR 1.14 95% CI 0.91-1.19, P = .16, I ² = 51%). We found the association between premature birth and acquired HF (HR 1.53 95% CI 1.08-2.16, P = .01, I ² = 0)
Conclusion
Premature birth was not statistically associated with IHD in adulthood, but there was a significant association between preterm and HF.
Introduction
Low birth weight (LBW), biological vulnerability that includes preterm birth (PTB) and small for gestational age (SGA), is associated with reduced maternal sensitivity (“making accurate inferences about an infant's physical and emotional needs and responding appropriately”) and impaired infant cognitive development. However, research does not examine if preterm birth, SGA, or both drive these associations. This study separated these measures of biological vulnerability to examine associations of LBW, PTB, and SGA with maternal sensitivity and infant cognitive development (controlling for maternal depression, breastfeeding, and demographic covariates).
Methods
The sample included 6900 9-month-old infants from the Early Childhood Longitudinal Study-Birth Cohort and used birth certificate data, maternal interviews, assessments of maternal sensitivity and infant cognitive development. Multiple linear regressions examined LBW, PTB, and SGA associations with concurrent measures of maternal sensitivity and infant cognition.
Results
Of the biological vulnerabilities, preterm birth had the strongest negative association with maternal sensitivity (F1,6450 = 29.48 versus 15.33 and 5.51, ps < .001) and infant cognitive development (F1,6450) = 390.65 versus 248.02 and 14.43, ps < .001). In the final regression model, preterm birth and maternal sensitivity were uniquely associated with infant cognitive development (R² = .05, p < .001), after controlling for maternal depression, breastfeeding, and demographics.
Conclusion
In this nationally representative infant sample infants, PTB had a stronger negative association with both maternal sensitivity and infant cognitive development in comparison to SGA or LBW. The LBW designation combines infants born preterm with SGA infants, potentially minimizing differences in developmental outcomes of PTB and SGA infants.
The incidence of sarcopenia continues to increase with age. The prevalence ranges from 5-13 percent in those aged 60-70 years and 11-50 percent in those aged >80 years. Decreased walking speed is one of the factors that can affect the status of weakness in the elderly. The purpose of the study was to analyze the intake of
vitamin D and the duration of exposure to the sun with the walking speed of the elderly. The research design was cross-sectional, at Panti Bhakti Kasih Siti Anna, Pangkalpinang City, 2020. The research sample was 22 of elderly. The results of the study stated that 68.2 percent of respondents were women with an average age
of 80 years. The category of obesity (36.4%) and slow walking speed (95.5%) were the dominant results. The average daily intake of vitamin D in the elderly is 241.8 IU with 30 minutes of sun exposure. The statistical analysis stated that there was a relationship between vitamin D intake and duration of sun exposure with the walking
speed of the elderly (p<0.05). The conclusion is that there is a relationship between vitamin D intake and duration of sun exposure with the walking speed of the elderly. Further research can be conducted regarding the relationship between diet and sarcopenia in the elderly aged more than 85 years and the role of vitamin D intervention in osteosarcopenia.
Keywords: vitamin D intake, sun exposure, walking speed, elderly
Introduction:
stillbirth is defined as a baby born with no signs of life. Globally, around 3.2 million stillbirths occur annually, of which, 98% are experienced in low and middle-income countries. Otjozondjupa Region topped the list of regions with high burden of stillbirth in Namibia in 2016. This study sought to elucidate risk factors for stillbirth.
Methods:
an unmatched 1:2 case-control study was conducted. A sample of 285, 95 cases and 190 controls were chosen using simple random sampling method. Bivariate and multivariate analyses were done to assess the risk factors of stillbirth.
Results:
maternal medical and obstetric factors significantly associated with stillbirth are: premature delivery (aOR 0.13 95% CI 0.05, 0.33, P < 0.001), gestational age (aOR 0.04, 95% CI 0.00, 0.25, P < 0.001), high-risk pregnancy (aOR 3.59, 95% CI 1.35, 9.55, P = 0.01), duration of labor (aOR 4.04, 95% CI 1.56, 10.43, P = 0.003) and antenatal care (ANC) attendance (aOR 0.07, 95% CI 0.00, 0.79, P = 0.03). Only low birth weight (≤ 2500 g) was associated with stillbirth amongst fetal related factors (aOR 16.58, 95% CI 8.71, 31.55, P < 0.001).
Conclusion:
this study concludes that stillbirth in Otjozondjupa Region was mostly associated with maternal medical and obstetric factors. It also concluded that attending antenatal care in Otjozondjupa did not improve birth outcome.
Background:
Infants show other movements and posture patterns during the fidgety movement period, including movement toward midline (MTM). Few studies have quantified MTM occurring during the fidgety movement period.
Aims:
This study aimed to examine the relationship between fidgety movements (FMs) and MTM frequency and occurrence rate per minute, from two video data sets (video attached to Prechtl video manual and accuracy data from Japan).
Study design:
Observational study.
Subjects:
It encompassed 47 videos. Of these, 32 were deemed normal FMs. The study amalgamated FMs that were sporadic, abnormal, or absent into a category of aberrant (n = 15).
Outcome measures:
Infant video data were observed. MTM item occurrences were recorded and calculated for occurrence percentage and MTM rate of occurrence per minute. The differences between groups for the upper limbs, lower limbs, and total MTM were statistically analysed.
Results:
Twenty-three infant videos of normal FMs and seven infant videos of aberrant FMs showed MTM. Eight infant videos of aberrant FMs showed no MTM, and only four with absent FMs were included. There was a significant difference in the total MTM rate of occurrence per minute between normal FMs versus aberrant FMs (p = 0.008).
Conclusions:
This study presented MTM frequency and rate of occurrence per minute in infants who showed FMs during the fidgety movement period. Those who showed absent FMs also demonstrated no MTM. Further study may need a larger sample size of absent FMs and information on later development.
For infants born at the border of viability, care practices and morbimortality rates vary widely between centers. Trends show significant improvement, however, with increasing gestational age and weight. For periviable infants, the goal of critical care is to bridge patients to improved outcomes. Current practice involves ventilator therapy, resulting in chronic lung injuries. Research has turned to artificial uterine environments, where infants are submerged in an artificial amniotic fluid bath and provided respiratory assistance via an artificial placenta. We have developed the Preemie-Ox, a hollow fiber membrane bundle that provides pumpless respiratory support via umbilical cord cannulation. Computational fluid dynamics was used to design an oxygenator that could achieve a carbon dioxide removal rate of 12.2 ml/min, an outlet hemoglobin saturation of 100%, and a resistance of less than 71 mmHg/L/min at a blood flow rate of 165 ml/min. A prototype was utilized to evaluate in-vitro gas exchange, resistance, and plasma-free hemoglobin generation. In-vitro gas exchange was 4% higher than predicted results and no quantifiable plasma-free hemoglobin was produced.
Background:
High-grade intraventricular hemorrhage (IVH), including grade III and grade IV IVH, is known to impact neurodevelopmental outcome of preterm infants, but prognosis remains difficult to establish due to confounding factors and significant variations in the reported outcomes. The aim of this study was to compare the neurodevelopmental outcome of preterm infants with or without severe IVH.
Methods:
A retrospective case-control study was conducted including preterm infants with gestational age <32 weeks hospitalized between 2009 and 2017 in a level III neonatal intensive care unit. This study included 73 cases with high-grade IVH and 73 controls who were matched to cases, based on the same gestational age, birth weight, sex, and year of birth. The neurodevelopmental outcome was compared at two years of age corrected for prematurity between cases and controls. Neurodevelopmental impairment was defined as cerebral palsy, hearing deficiency, visual impairment, or developmental delay. Multivariate analysis was used to identify whether high-grade IVH was an independent risk factor for neurodevelopmental impairment.
Results:
In univariate analysis, high-grade IVH was associated with death or poor neurodevelopmental outcome at two years of age corrected for prematurity (odds ratio [OR], 16.3; 95% confidence interval [CI], 5.93 to 57.8; P < 0.001), and this association remained significant after adjusting for confounding factors including neonatal infection and bronchopulmonary dysplasia in multivariate analysis (OR, 8.71; 95% CI, 2.48 to 38.09; P = 0.002).
Conclusions:
This study highlights the impact of high-grade IVH as an independent risk factor of poor neurodevelopmental outcomes in very preterm infants and suggests that early interventions could improve the prognosis of these infants.
Objectives:
Early screening and dynamic monitoring of pulmonary vascular disease (PVD) in bronchopulmonary dysplasia (BPD) high-risk infants is of great clinical significance. Pulmonary artery acceleration time (PAAT) is a reliable and non-invasive method for assessing PVD in children over 1 year, but to date, few studies have used PAAT to assess pulmonary hemodynamics of preterm infants, especially those with BPD. Through dynamic monitoring the main hemodynamic indicators reflected PVD after birth, this study aimed to assess the value of PAAT in evaluating early PVD in BPD infants.
Methods:
All 81 preterm infants at risk of BPD were divided into BPD and non-BPD groups according to whether BPD occurred. Clinical characteristics, PAAT, right ventricular ejection time (RVET) and other main hemodynamic indicators at four different time points after birth were studied and compared.
Results:
PAAT and PAAT/RVET increased gradually within 72 h after birth in the BPD group (p < .05), but the curve tended to be flat over time after 72 h (p > .05). At PMA32 and 36 weeks, the PAAT (49.7 ± 4.8 vs. 54.8 ± 5.7, p = .001; 50.0 ± 5.3 vs. 57.0 ± 5.3, p = .001) and PAAT/RVET (.33 ± .04 vs. .35 ± .03, p = .001; .34 ± .03 vs. .37 ± .04, p = .001) in BPD group were significantly lower than those in the non-BPD group.
Conclusions:
PAAT and PAAT/RVET in the BPD group infants showed different change patterns compared to non-BPD group infants. PAAT can be used as a noninvasive and reliable screening method for screening and dynamic monitoring of PVD in BPD high-risk infants.
Preterm birth is the leading cause of neonatal mortality and morbidity. Early diagnosis and interventions are critical to improve the clinical outcomes of extremely premature infants. Here, we have investigated the blood protein profiles during the first months of life in preterm infants to shed light on the role of early extrauterine development. The blood protein levels were analyzed using “next generation blood profiling” on 1335 serum samples, collected longitudinally at nine time points from birth to full term (40 weeks postmenstrual age) from 182 extremely preterm infants. We found a unified pattern of protein development for all included infants, regardless of gestational age and clinical characteristics, suggesting an age-dependent stereotypic development of blood proteins after birth. This knowledge should be considered in neonatal settings and might alter the clinical approach within neonatology, where postmenstrual age is today the most dominant age variable.
Surgery in neonatal, newborn and premature infants carries higher risk but the survival of premature, even extremely premature (<28 week gestation) and low (<1500 g) or extremely low birth weight (<1000 g) babies after surgery is on the rise due to the concerted efforts of technically skilled, experienced multidisciplinary team of neonatologist, surgeon, anaesthesiologist as well as nursing staff. Other factors contributing to their increased survival are availability of well-equipped ORs and NICUs with innovative and sophisticated gadgets which play a pivotal role in nursing the newborns preoperatively, not only in the developed world but also in developing countries, such as India. Babies are often born with various congenital anomalies involving major body systems with both anatomical and physiological implications, metabolic disorders, which makes them very much susceptible to developing complications, especially in the premature, such as respiratory distress syndrome, retinopathy of prematurity, intraventricular haemorrhage, and necrotising enterocolitis, that increase their morbidity and mortality. However, if diagnosed early at birth and treated accordingly, their survival improves. Though many critical surgeries are performed on neonates, much care is needed throughout the perioperative journey, to have a favourable outcome. General anesthesia is the preferred choice for most surgeries, but use of regional anaesthesia, use of noninvasive airway management greatly improves postoperative outcome. It must be kept in mind that premature babies are always at higher risk even after minor surgeries than healthy term neonates. A detailed preoperative evaluation, and optimization whenever possible, choice of anesthesia techniques and drugs, limiting preoperative nil per oral time (NPO), can greatly improve early recovery after anesthesia (ERAS) and help attain the outcome goals in the surgical neonate.
Introduction
Prematurity and low birth weight (LBW) are associated with higher health care needs and higher health care utilization in the first few years of life. The aim of this cross-sectional study was to determine how prematurity and LBW were correlated with access to a medical home later in childhood, at ages 6–17 years.
Methods
Data were analyzed from the 2016–2018 National Survey of Children's Health. Non-institutionalized US children 6–17 years of age who had been born preterm were classified as very low birth weight (VLBW, <1500 g), LBW (1500–2500 g), and normal weight (NBW, >2500 g). Term-born NBW children were included as a reference group. Medical home access was determined according to caregiver report.
Results
The analysis included 64,597 infants (preterm VLBW n = 737; preterm LBW n = 2869; preterm NBW n = 3942; and term NBW n = 57,049). Based on this sample, 44% of children ages 6–17 years were estimated to receive care meeting the criteria of a medical home. On multivariable analysis, none of the preterm groups had higher likelihood of receiving care in a medical home compared to children born at term and NBW (odds ratios ranging from 0.75 to 0.95).
Conclusions
School-aged children born preterm and LBW were equally or less likely to receive care meeting the criteria of a medical home than children born at term and NBW. Although prematurity and LBW are associated with increased health care use early in the life course, this does not appear sufficient to help children establish and maintain access to a medical home.
Objective:
To evaluate the implementation of a systematic approach to improve the resuscitation, stabilization, and admission of infants < 32 weeks gestation and also to ascertain its effect on organization, efficiency, and clinical outcomes during hospitalization.
Methods:
Retrospective study involving a multidisciplinary team with checklists, role assignment, equipment organization, step by step protocol, and real time documentation for the care of infants < 32 weeks gestation in the delivery room to the neonatal intensive care unit. Pre-data collection (cases) period was from Aug, 2015 to July, 2017, and post-data collection(controls) period was from Aug, 2017 to Aug, 2019.
Results:
337 infants were included (179 cases; 158 controls). Increase surfactant use in the resuscitation room (41% vs. 27%, p = 0.007) and reduction in median time to administer surfactant (34 minutes (range, 6-120) vs. 74 minutes (range, 7-120), p = 0.001) observed in control-group. There was a significant reduction in incidence of bronchopulmonary dysplasia (27% vs. 39%), intraventricular hemorrhage (11% vs. 17%), severe retinopathy of prematurity (3% vs. 9%), and necrotizing enterocolitis (4% vs. 6%), however these results were not statistically significant after controlling for severity of illness.
Conclusions:
A systematic approach to the care of infants < 32 weeks gestation significantly improved mortality rates and reduced rates of comorbidities.
Objetivo: Identificar e caracterizar a ocorrência de tremores e explorar a associação entre fatores clínicos e movimentos gerais com o número de membros acometidos e o tempo de tremor em recém-nascidos pretermo (RNPT) de uma Unidade de Terapia Intensiva Neonatal (UTIN). Métodos: Foi realizado um estudo transversal em uma UTIN com 26 leitos, com internação média anual de 120 RNPT. Os tremores foram identificados por observação de vídeos dos recém-nascidos, registrando-se o número de membros acometidos e o tempo máximo de tremor. Os fatores clínicos foram registrados a partir dos prontuários e a classificação dos movimentos gerais foi dicotomizada nas categorias normal e anormal, através da General Movements Assessment. A associação entre as variáveis foi verificada pelo teste de correlação de Spearman. Resultados: Foram avaliados 29 RNPT. Todos apresentaram tremor na 36a semana de idade gestacional. Foi verificada associação significativa entre o número de membros que apresentavam tremor e o uso de fenobarbital (rho=0,51; p=0,005) e entre o tempo de tremor e a classificação anormal dos movimentos gerais (rho=0,47; p=0,01). Conclusão: O uso de fenobarbital e a classificação anormal dos movimentos gerais foram associados às características dos tremores em RNPT da UTIN, o que endossa a importância de avaliar os movimentos gerais em lactentes com tremores e de realizar mais estudos para investigar o efeito do uso de medicações nessa população.
Background: The effect of gestational age (GA) on comorbidity prevalence, healthcare resource utilization (HCRU), and all-cause costs is significant for extremely premature (EP) infants in the United States. Objectives: To characterize real-world patient characteristics, prevalence of comorbidities, rates of HCRU, and direct healthcare charges and societal costs among premature infants in US Medicaid programs, with respect to GA and the presence of respiratory comorbidities. Methods: Using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, diagnosis and medical claims data from 6 state Medicaid databases (1997-2018) of infants born at less than 37 weeks of GA (wGA) were collected retrospectively. Data from the index date (birth) up to 2 years corrected age or death, stratified by GA (EP, ≤28 wGA; very premature [VP], >28 to <32 wGA; and moderate to late premature [M-LP], ≥32 to <37 wGA), were compared using unadjusted and adjusted generalized linear models. Results: Among 25 573 premature infants (46.1% female; 4462 [17.4%] EP; 2904 [11.4%] VP; 18 207 [71.2%] M-LP), comorbidity prevalence, HCRU, and all-cause costs increased with decreasing GA and were highest for EP. Total healthcare charges, excluding index hospitalization and all-cause societal costs (US dollars), were 2 to 3 times higher for EP than for M-LP (EP $74 436 vs M-LP $27 541 and EP $28 504 vs M-LP $15 892, respectively). Conclusions: Complications of preterm birth, including prevalence of comorbidities, HCRU, and costs, increased with decreasing GA and were highest among EP infants during the first 2 years in this US analysis.
Background: The effect of gestational age (GA) on comorbidity prevalence, healthcare resource utilization (HCRU), and all-cause costs is significant for extremely premature (EP) infants in the United States.
Objectives: To characterize real-world patient characteristics, prevalence of comorbidities, rates of HCRU, and direct healthcare charges and societal costs among premature infants in US Medicaid programs, with respect to GA and the presence of respiratory comorbidities.
Methods: Using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes, diagnosis and medical claims data from 6 state Medicaid databases (1997-2018) of infants born at less than 37 weeks of GA (wGA) were collected retrospectively. Data from the index date (birth) up to 2 years corrected age or death, stratified by GA (EP, ≤28 wGA; very premature [VP], >28 to <32 wGA; and moderate to late premature [M-LP], ≥32 to <37 wGA), were compared using unadjusted and adjusted generalized linear models.
Results: Among 25 573 premature infants (46.1% female; 4462 [17.4%] EP; 2904 [11.4%] VP; 18 207 [71.2%] M-LP), comorbidity prevalence, HCRU, and all-cause costs increased with decreasing GA and were highest for EP. Total healthcare charges, excluding index hospitalization and all-cause societal costs (US dollars), were 2 to 3 times higher for EP than for M-LP (EP $74 436 vs M-LP $27 541 and EP $28 504 vs M-LP $15 892, respectively).
Conclusions: Complications of preterm birth, including prevalence of comorbidities, HCRU, and costs, increased with decreasing GA and were highest among EP infants during the first 2 years in this US analysis.
Background:
Higher-order multiple (HOM) pregnancies are associated with significant maternal and neonatal morbidity, especially consequent to preterm birth. Multi-fetal pregnancy reduction (MFPR) may be provided, though its benefits in prolonging gestation and improving neonatal outcomes must be weighed against its risks.
Aims:
The aim was to compare outcomes of HOM pregnancies where expectant management was chosen (EM) with those where MFPR was provided.
Methods:
The method involved a retrospective study of HOM pregnancies referred to a single quaternary hospital between 2007 and 2016. The primary outcome was gestational age. Secondary outcomes included miscarriage, nursery admission, hospital stay, Apgar scores, early fetal loss, stillbirth, neonatal death and composite fetal loss.
Results:
Fifty-seven pregnancies were eligible for inclusion. Median gestation at birth (weeks) was significantly higher for MFPR (35.3 vs 33.1, P < 0.01). Pregnancies after MFPR were less likely to lead to preterm birth (63.2 vs 100.0%, P < 0.001), half as likely to birth before 34 weeks (31.6 vs 60.0%, P = 0.09) but similarly likely to extremely preterm birth (<28 weeks, 8.6 vs 10.5%, P = 0.58). Miscarriage was more likely after MFPR (13.6 vs 0%, P = 0.05). EM neonates were more likely to be admitted to the nursery (P < 0.01) and have longer hospital stay (29.6 vs 20.2 days, P = 0.05); however, they had similar Apgar scores.
Conclusion:
Our study demonstrates that MFPR is associated with an increase in gestational age, with a reduction by almost half of births before 34 weeks, but no difference in extremely preterm births; the latter represents the highest risk group. This should be used to guide management counselling for HOM pregnancies.
Background and purpose:
Multidynamic multiecho sequence-based imaging enables investigators to reconstruct multiple MR imaging contrasts on the basis of a single scan. This study investigated the feasibility of synthetic MRI-based WM signal suppression (syWMSS), a synthetic inversion recovery approach in which a short TI suppresses myelin-related signals, for the identification of early myelinating brainstem pathways.
Materials and methods:
Thirty-one cases of neonatal MR imaging, which included multidynamic multiecho data and conventionally acquired T1- and T2-weighted sequences, were analyzed. The multidynamic multiecho postprocessing software SyMRI was used to generate syWMSS data (TR/TE/TI = 3000/5/410 ms). Two raters discriminated early myelinating brainstem pathways (decussation of the superior cerebellar peduncle, medial lemniscus, central tegmental tract, and medial longitudinal fascicle [the latter 3 assessed at the level of the pons]) on syWMSS data and reference standard contrasts.
Results:
On the basis of syWMSS data, the decussation of the superior cerebellar peduncle (31/31); left/right medial lemniscus (31/31; 30/31); left/right central tegmental tract (19/31; 20/31); and left/right medial longitudinal fascicle (30/31) were reliably identified by both raters. On the basis of T1-weighted contrasts, the decussation of the superior cerebellar peduncle (14/31); left/right medial lemniscus (22/31; 16/31); left/right central tegmental tract (1/31); and left/right medial longitudinal fascicle (9/31; 8/31) were reliably identified by both raters. On the basis of T2-weighted contrasts, the decussation of the superior cerebellar peduncle (28/31); left/right medial lemniscus (16/31; 12/31); left/right central tegmental tract (23/31; 18/31); and left/right medial longitudinal fascicle (15/31; 14/31) were reliably identified by both raters.
Conclusions:
syWMSS data provide a feasible imaging technique with which to study early myelinating brainstem pathways. MR imaging approaches that use myelin signal suppression contribute to a more sensitive assessment of myelination patterns at early stages of cerebral development.
OBJECTIVES: This report presents 2013 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal age, live-birth order, race and Hispanic origin, marital status, attendant at birth, method of delivery, period of gestation, birthweight, and plurality. Birth and fertility rates are presented by age, live-birth order, race and Hispanic origin, and marital status. Selected data by mother's state of residence and birth rates by age and race of father also are shown. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.
METHODS: Descriptive tabulations of data reported on the birth certificates of the 3.93 million U.S. births that occurred in 2013 are presented.
RESULTS: A total of 3,932,181 births were registered in the United States in 2013, down less than 1% from 2012. The general fertility rate declined to 62.5 per 1,000 women aged 15-44. The teen birth rate fell 10%, to 26.5 per 1,000 women aged 15-19. Birth rates declined for women in their 20s and increased for most age groups of women aged 30 and over. The total fertility rate (estimated number of births over a woman's lifetime) declined 1% to 1,857.5 per 1,000 women. Measures of unmarried childbearing were down in 2013 from 2012. The cesarean delivery rate declined to 32.7%. The preterm birth rate declined for the seventh straight year to 11.39%, but the low birthweight rate was essentially unchanged at 8.02%. The twin birth rate rose 2% to 33.7 per 1,000 births; the triplet and higher-order multiple birth rate dropped 4% to 119.5 per 100,000 total births.
BACKGROUND:
The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used.
METHODS:
In three international randomized, controlled trials, we evaluated the effects of targeting an oxygen saturation of 85 to 89%, as compared with a range of 91 to 95%, on disability-free survival at 2 years in infants born before 28 weeks' gestation. Halfway through the trials, the oximeter-calibration algorithm was revised. Recruitment was stopped early when an interim analysis showed an increased rate of death at 36 weeks in the group with a lower oxygen saturation. We analyzed pooled data from patients and now report hospital-discharge outcomes.
RESULTS:
A total of 2448 infants were recruited. Among the 1187 infants whose treatment used the revised oximeter-calibration algorithm, the rate of death was significantly higher in the lower-target group than in the higher-target group (23.1% vs. 15.9%; relative risk in the lower-target group, 1.45; 95% confidence interval [CI], 1.15 to 1.84; P=0.002). There was heterogeneity for mortality between the original algorithm and the revised algorithm (P=0.006) but not for other outcomes. In all 2448 infants, those in the lower-target group for oxygen saturation had a reduced rate of retinopathy of prematurity (10.6% vs. 13.5%; relative risk, 0.79; 95% CI, 0.63 to 1.00; P=0.045) and an increased rate of necrotizing enterocolitis (10.4% vs. 8.0%; relative risk, 1.31; 95% CI, 1.02 to 1.68; P=0.04). There were no significant between-group differences in rates of other outcomes or adverse events.
CONCLUSIONS:
Targeting an oxygen saturation below 90% with the use of current oximeters in extremely preterm infants was associated with an increased risk of death. (Funded by the Australian National Health and Medical Research Council and others; BOOST II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry numbers, ACTRN12605000055606 and ACTRN12605000253606.)
Objectives-This report presents preliminary data for 2012 on births in the United States. U.S. data on births are shown by age, live-birth order, race, and Hispanic origin of mother. Data on marital status, cesarean delivery, preterm births, and low birthweight are also presented. Methods-Data in this report are based on 99.96% of 2012 births.Records for the few states with less than 100% of records received are weighted to independent control counts of all births received in state vital statistics offices in 2012. Comparisons are made with final 2011 data. Results-The preliminary number of births for the United States in 2012 was 3,952,937, essentially unchanged (not statistically significant) from 2011; the general fertility rate was 63.0 births per 1,000 women aged 15-44, down only slightly from 2011, after declining nearly 3% a year from 2007 through 2010. The number of births and fertility rate either declined or were unchanged for most race and Hispanic origin groups from 2011 to 2012; however, both the number of births and the fertility rate for Asian or Pacific Islander women rose in 2012 (7% and 4%, respectively). The birth rate for teenagers aged 15-19 was down 6% in 2012 (29.4 births per 1,000 teenagers aged 15-19), yet another historic low for the United States, with rates declining for younger and older teenagers and for nearly all race and Hispanic origin groups. The birth rate for women in their early 20s also declined in 2012, to a new record low of 83.1 births per 1,000 women. Birth rates for women in their 30s rose in 2012, as did the birth rate for women in their early 40s. The birth rate for women in their late 40s was unchanged. The nonmarital birth rate declined in 2012 (to 45.3 birth per 1,000 unmarried women aged 15-44), whereas the number of births to unmarried women rose 1% and the percentage of births to unmarried women was unchanged (at 40.7%). The cesarean delivery rate for the United States was unchanged in 2012 at 32.8%. The preterm birth rate fell for the sixth straight year in 2012 to 11.54%. The low birthweight rate also declined in 2012, to 7.99%. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.
Background
The safest ranges of oxygen saturation in preterm infants have been the subject of debate.
Methods
In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks’ gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial.
Results
After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001).
Conclusions
Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.)
Objective:
To provide instructive information on death and neurodevelopmental outcomes of infants born at 22 and 23 weeks' gestational age.
Methods:
The study cohort consisted of 1057 infants born at 22 to 25 weeks in the Neonatal Research Network, Japan. Neurodevelopmental impairment (NDI) at 36 to 42 months' chronological age was defined as any of the following: cerebral palsy, hearing impairment, visual impairment, and a developmental quotient <70. A systematic review was performed by using databases of publications of cohort studies with neonatal and neurodevelopmental outcomes at 22 and 23 weeks.
Results:
Numbers and incidences (%) of infants with death or NDI were 60 (80%) at 22 weeks and 156 (64%) at 23 weeks. In logistic regression analysis, gestational ages of 22 weeks (odds ratio [OR]: 5.40; 95% confidence interval [CI]: 2.48-11.76) and 23 weeks (OR: 2.14; 95% CI: 1.38-3.32) were associated with increased risk of death or NDI compared with 24 weeks, but a gestational age of 25 weeks (OR: 0.65; 95% CI: 0.45-0.95) was associated with decreased risk of death or NDI. In the systematic review, the medians (range) of the incidence of death or NDI in 8 cohorts were 99% (90%-100%) at 22 weeks and 98% (67%-100%) at 23 weeks.
Conclusions:
Infants born at 22 and 23 weeks' gestation were at higher risk of death or NDI than infants at born at 24 weeks. However, outcomes were improved compared with those in previous studies. There is a need for additional discussions on interventions for infants born at 22 or 23 weeks' gestation.
We report on 6 infants who underwent elective surgery and developed postoperative encephalopathy, which had features most consistent with intraoperative cerebral hypoperfusion. All infants were <48 weeks' postmenstrual age and underwent procedures lasting 120 to 185 minutes. Intraoperative records revealed that most of the measured systolic blood pressure (SBP) values were <60 mm Hg (the threshold for hypotension in awake infants according to the Pediatric Advanced Life Support guidelines) but that only 11% of the measured SBP values were <1 SD of the mean definition of hypotension (<45 mm Hg) as reported in a survey of members of the Society for Pediatric Anesthesia in 2009. Four infants also exhibited prolonged periods of mild hypocapnia (<35 mm Hg). One infant did not receive intraoperative dextrose. All infants developed new-onset seizures within 25 hours of administration of the anesthetic, with a predominant cerebral pathology of supratentorial watershed infarction in the border zone between the anterior, middle, and posterior cerebral arteries. Follow-up of these infants found that 1 died, 1 had profound developmental delays, 1 had minor motor delays, 2 were normal, and 1 was lost to follow-up. Although the precise cause of encephalopathy cannot be determined, it is important to consider the role that SBP hypotension (as well as hypoglycemia, hyperthermia, hyperoxia, and hypocapnia) plays during general anesthesia in young infants in the development of infantile postoperative encephalopathy. Our observations highlight the lack of evidence-based recommendations for the lower limits of adequate SBP and end-tidal carbon dioxide in anesthetized infants.
Objective:
To evaluate characteristics of unimpaired outcome in extremely low-birth-weight (ELBW) survivors.
Study design:
ELBW infants (n=714) with 30 months' assessments were analyzed. Logistic regression was used to develop a model for the binary outcome of unimpaired versus impaired outcome.
Result:
Thirty-three percent of infants had an unimpaired outcome. Seventeen percent of ELBW survivors had a Bayley II Mental Developmental Index score of ≥ 101 and 2% had a score of ≥ 116. Female gender, use of antenatal steroids (ANS), maternal education ≥ high school and the absence of major neonatal morbidities were independent predictors of unimpaired outcome. The likelihood of an unimpaired outcome in the presence of major neonatal morbidities was higher in infants exposed to ANS.
Conclusion:
The majority of unimpaired ELBW survivors had cognitive scores shifted toward the lower end of the normal distribution. Exposure to ANS was associated with higher likelihood of an unimpaired outcome in infants with major neonatal morbidities.
Background As a result of advances in perinatal care, more small preterm infants survive. There are concerns that preterm birth and its treatments may harm pulmonary development and thereby lead to chronic airway obstruction in adulthood.
Objective To assess the development of spirometric lung function variables from mid-childhood to adulthood after extreme preterm birth.
Methods Two population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g performed lung function tests at 10 and 18 and at 18 and 25 years of age, respectively, together with matched term-born controls. The results are presented as z scores, normalised for age, sex and height. Longitudinal development was compared for groups born at term and preterm, split by a history of absence (n=20), mild (n=38) or moderate/severe (n=25) neonatal bronchopulmonary dysplasia (BPD).
Results The preterm-born cohorts, particularly those with neonatal BPD, had significantly lower forced expiratory volume in 1 s and mid-expiratory flow than those born at term at all assessments (z scores in the range −0.40 to −1.84). Within each of the subgroups the mean z scores obtained over the study period were largely similar, coefficients of determination ranging from 0.64 to 0.82. The pattern of development for the BPD subgroups did not differ from each other or from the groups born at term (tests of interaction).
Conclusions Airway obstruction was present from mid-childhood to adulthood after extreme preterm birth, most evident after neonatal BPD. Lung function indices were tracking similarly in the preterm and term-born groups.
BACKGROUND: The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used.
METHODS: In three international randomized, controlled trials, we evaluated the effects of targeting an oxygen saturation of 85 to 89%, as compared with a range of 91 to 95%, on disability-free survival at 2 years in infants born before 28 weeks' gestation. Halfway through the trials, the oximeter-calibration algorithm was revised. Recruitment was stopped early when an interim analysis showed an increased rate of death at 36 weeks in the group with a lower oxygen saturation. We analyzed pooled data from patients and now report hospital-discharge outcomes.
RESULTS: A total of 2448 infants were recruited. Among the 1187 infants whose treatment used the revised oximeter-calibration algorithm, the rate of death was significantly higher in the lower-target group than in the higher-target group (23.1% vs. 15.9%; relative risk in the lower-target group, 1.45; 95% confidence interval [CI], 1.15 to 1.84; P=0.002). There was heterogeneity for mortality between the original algorithm and the revised algorithm (P=0.006) but not for other outcomes. In all 2448 infants, those in the lower-target group for oxygen saturation had a reduced rate of retinopathy of prematurity (10.6% vs. 13.5%; relative risk, 0.79; 95% CI, 0.63 to 1.00; P=0.045) and an increased rate of necrotizing enterocolitis (10.4% vs. 8.0%; relative risk, 1.31; 95% CI, 1.02 to 1.68; P=0.04). There were no significant between-group differences in rates of other outcomes or adverse events.
CONCLUSIONS: Targeting an oxygen saturation below 90% with the use of current oximeters in extremely preterm infants was associated with an increased risk of death. (Funded by the Australian National Health and Medical Research Council and others; BOOST II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry numbers, ACTRN12605000055606 and ACTRN12605000253606.).
Objective
To identify the association between birth weight (BW)-for-gestational age (GA) and pulmonary hypertension (PHTN) at 36 weeks in infants with moderate-severe bronchopulmonary dysplasia (BPD).
Study Design
In this retrospective cohort study, we followed 138 premature infants (≤28wks) with moderate and severe BPD (NIH consensus definition) born at Prentice Women’s Hospital between 2005 and 2009. BW percentiles were calculated using the Fenton growth curve for premature infants. PHTN was determined using a standardized algorithm of echocardiogram review at 36 weeks. Logistic regression was used to evaluate the associations between BW percentile subgroups and PHTN, taking into account antenatal and neonatal factors that were related to PHTN.
Results
PHTN was associated with small BW-for-GA, ranging from thresholds of <10th to <25th percentile (P<0.001). These associations remained significant when comparing BW <25th percentile to the reference group (50–89th percentile); after adjustment for GA, gender, multiple gestation, race/ethnicity (OR=4.2; 95% CI=1.5, 12.1); and after further adjustment for maternal vascular disease, intrauterine infection, oligohydramnios, and relevant postnatal factors (OR=5.7; 95% CI=1.5, 21.2). Longitudinal follow-up of this cohort showed a trend towards higher morbidity and death among PHTN infants with BW <25th percentile.
Conclusion
BW-for-GA is an important predictor of PHTN in premature infants with moderate/severe BPD. Our findings contribute to the growing evidence supporting fetal mechanisms of later onset pulmonary vascular disease.
Infants born prematurely at <37 weeks' gestation account for over 80% of infants weighing <2,500 g at birth-low birth weight (LBW) infants. This designation remains the surrogate marker for developmental origins of adult disease. Landmark studies spanning four decades have shown that individuals born with a LBW are more likely to develop cardiovascular and renal disease in later life, which is believed to be related to 'developmental programming' of such adult disease during vulnerable periods of growth in utero and in the early postnatal period. There has long been ambiguity regarding the distinction between infants with intrauterine growth restriction and preterm infants since both show a low nephron endowment that is associated with subsequent hypertension and chronic kidney disease. Knowledge is growing specific to the preterm infant and the developmental associations of being born preterm with the interruption of normal organogenesis relative to the vascular tree and kidney. Both systems develop by branching morphogenesis and interruptions lead to considerable deficits in their structure and function. These developmental aberrations can lead to endothelial dysfunction, hypertension, proteinuria and metabolic abnormalities that persist throughout life. This Review will examine the effect of preterm birth on the development of cardiovascular and kidney disease in later life and will also discuss potential early interventions to alter the progression of disease.
To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy(HIE).
Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews.
Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE.
Therapeutic hypothermia.
Death or major neurodevelopmental disability at 18 months.
Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability(risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability(RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93,respectively).
Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE.Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns.
Pulmonary hypertension is associated with bronchopulmonary dysplasia in extremely low birth weight (ELBW) infants and contributes to morbidity and mortality. The objective was to determine the prevalence of pulmonary hypertension among ELBW infants by screening echocardiography and evaluate subsequent outcomes.
All ELBW infants admitted to a regional perinatal center were evaluated for pulmonary hypertension with echocardiography at 4 weeks of age and subsequently if clinical signs suggestive of right-sided heart failure or severe lung disease were evident. Management was at discretion of the clinician, and infants were evaluated until discharge from the hospital or pre-discharge death occurred.
One hundred forty-five ELBW infants (birth weight: 755 ± 144 g; median gestational age: 26 weeks [interquartile range: 24-27]) were screened from December 2008 to February 2011. Overall, 26 (17.9%) were diagnosed with pulmonary hypertension at any time during hospitalization (birth weight: 665 ± 140 g; median gestational age: 26 weeks [interquartile range: 24-27]): 9 (6.2%) by initial screening (early pulmonary hypertension) and 17 (11.7%) who were identified later (late pulmonary hypertension). Infants with pulmonary hypertension were more likely to receive oxygen treatment on day 28 compared with those without pulmonary hypertension (96% vs 75%, P < .05). Of the 26 infants, 3 died (all in the late group because of cor pulmonale) before being discharged from the hospital.
Pulmonary hypertension is relatively common, affecting at least 1 in 6 ELBW infants, and persists to discharge in most survivors. Routine screening of ELBW infants with echocardiography at 4 weeks of age identifies only one-third of the infants diagnosed with pulmonary hypertension. Further research is required to determine optimal detection and intervention strategies.
Advances in the care of high-risk newborn babies have contributed to reduced mortality rates for premature and term births, but the surviving neonates often have increased neurological morbidity. Therapies aimed at reducing the neurological sequelae of birth asphyxia at term have brought hypothermia treatment into the realm of standard care. However, this therapy does not provide complete protection from neurological complications and a need to develop adjunctive therapies for improved neurological outcomes remains. In addition, the care of neurologically impaired neonates, regardless of their gestational age, clearly requires a focused approach to avoid further injury to the brain and to optimize the neurodevelopmental status of the newborn baby at discharge from hospital. This focused approach includes, but is not limited to, monitoring of the patient's brain with amplitude-integrated and continuous video EEG, prevention of infection, developmentally appropriate care, and family support. Provision of dedicated neurocritical care to newborn babies requires a collaborative effort between neonatologists and neurologists, training in neonatal neurology for nurses and future generations of care providers, and the recognition that common neonatal medical problems and intensive care have an effect on the developing brain.
Background. Our goal was to determine the effects of recent changes in delivery room and neonatal care, including surfactant and dexamethasone therapy, on survival, neonatal morbidity, and 20-month neurodevelopmental outcome of infants with birth weights of less than 750 g.
Methods. We compared the outcomes of 114 infants of 500 to 750 g birth weight delivered at our perinatal center between January 1990 and December 1992 (period II), when surfactant and postnatal dexamethasone were used, with the outcomes of 166 such infants born between July 1982 and June 1988 (period I).
Results. The rate of cesarean section increased from 17% to 27% and delivery room intubation increased from 54% to 72% during periods I and II, respectively. Survival increased from 23% during period I to 43% during period II. The increase in survival was significant at birth weights of 600 to 700 g and at 24 weeks' gestation and greater. During period II fewer infants died at less than 24 hours of age and more died at more than 28 days of life. Neonatal morbidity did not change appreciably; neither did 20-month neurodevelopmental outcomes. Twenty percent of the infants had subnormal cognitive function (Mental Development Indices < 70) and 10% had cerebral palsy during period II.
Conclusions. Despite an increase in survival during 1990 to 1992, the neonatal and early childhood outcomes of the survivors were unchanged. Physicians and parents anticipating the delivery of extremely low birth weight infants must be aware of these outcomes to make informed decisions as to the advisability of aggressive care at birth and thereafter.
To determine the survival and sensorineural disability rates in very preterm infants born in 1991–92, and to compare the results with contemporaneous normal birthweight controls and with preterm infants born in 1985–87.
This was a geographically determined cohort study in the state of Victoria, Australia of consecutive livebirths 23–27 weeks' gestational age born during 1991–92, and randomly selected contemporaneous normal birthweight (NBW) controls born during 1991–92 in the three level-III perinatal centres in the State. Consecutive livebirths 24–26 weeks gestational age born in the State during 1985–87 comprised another comparison group. The main outcome measures were survival and sensorineural disability rates at 2 years of age.
Of the 401 livebirths 23–27 weeks in 1991–92, 225 (56.1%) survived to 2 years of age. The survival rate for those 24–26 weeks was 57.4% (143/249), a statistically significant increase on the regional survival rate of 30.1% (95/316) in 1985–87. In 1991–92 births, the survival rate rose significantly with increasing gestational age, and was significantly higher than in 1985–87 at each of 24, 25, and 26 weeks. Of sensorineural impairments in preterm survivors at 2 years of age, the rate of blindness was significantly lower in 1991–92 (2.3%) compared with 1985–87 (8.4%), and the overall rates of sensorineural disability were not statistically different in 1991–92 compared with 1985–87. In 1991–92 preterm survivors, the survival rate free of disability rose significantly with increasing gestational age, and as a percentage of survivors the rate of disability overall fell with increasing gestational age. However, the rate of disability overall was much higher in preterm infants than NBW controls.
Survival rates of very preterm infants in this regional cohort have improved in the 1990s after the introduction of exogenous surfactant. Blindness at 2 years of age was significantly lower than in an earlier preterm cohort, but the rates of sensorineural disability still remain higher in very preterm survivors than for NBW controls. Although survival rates are lower and disability rates are higher with diminishing maturity, there is no obvious gestational age below which adverse neurological outcome in survivors would preclude active management on the basis of gestational age alone.
Objective: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital. Design: A prospective observational population based study. Setting: Nine regions of France in 1997. Patients: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation. Main outcome measure: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge. Results: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age. Conclusion: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.
Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40–50 years, its origins can begin very early in life. Different risk factors in very early life—ie, in utero and during early childhood—drive the development of clinically apparent chronic obstructive pulmonary disease in later life. In discussions of which risk factors drive chronic obstructive pulmonary disease, it is important to realise that the disease is very heterogeneous and at present is largely diagnosed by lung function only. In this Review, we will discuss the evidence for risk factors for the various phenotypes of chronic obstructive pulmonary disease during different stages of life.
Oxygen is one of the most widely used drugs in the neonatal period. A lack of knowledge of oxygen metabolism and toxicity has prompted guidelines to fluctuate from liberal use to treat respiratory distress to restriction to avoid retinopathy of prematurity. In recent years, studies performed in the immediate postnatal period have revealed that newly born infants achieve a stable saturation only several minutes after birth. Moreover, the time needed to reach a saturation plateau is inversely proportional to a newborn's gestational age. As a consequence, guidelines have changed and recommend an individualized supplementation in the first minutes after birth with the inspiratory fraction of oxygen titrated against preductal pulse oximetry. However, randomized controlled trials have concluded that, after postnatal stabilization, keeping preterm babies within a low-saturation target range (85-89%) may lead to increased mortality while keeping them in a higher saturation range (91-95%) increases the risk of retinopathy of prematurity. The present state of the art in the management of oxygen supplementation recommends that caregivers in the delivery room allow preductal oxygen saturation to spontaneously increase in the first minutes of life; however, if supplemented, it should be titrated according to pulse oximeter readings and kept within the safe margins of the nomogram. Thereafter, if oxygen is still needed, it should be kept within stringent security margins (90-95%) to avoid deleterious consequences. Importantly, in babies with chronic lung disease, oxygen should be supplemented to allow the patient to grow and develop. © 2014 S. Karger AG, Basel.
Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors.
To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age).
Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. MAIN OUTCOMES AND MEASURES: Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age.
At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001).
Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.
Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is a significant contributor to perinatal morbidity and mortality. Premature birth disrupts pulmonary vascular growth and initiates a cascade of events that result in impaired gas exchange, abnormal vasoreactivity, and pulmonary vascular remodeling that may ultimately lead to pulmonary hypertension (PH). Even infants who appear to have mild BPD suffer from varying degrees of pulmonary vascular disease (PVD). Although recent studies have enhanced our understanding of the pathobiology of PVD and PH in BPD, much remains unknown with respect to how PH should be properly defined, as well as the most accurate methods for the diagnosis and treatment of PH in infants with BPD. This article will provide neonatologists and primary care providers, as well as pediatric cardiologists and pulmonologists, with a review of the pathophysiology of PH in preterm infants with BPD and a summary of current clinical recommendations for managing PH in this population.
Bronchopulmonary dysplasia (BPD) is one of the most important sequelae of premature birth and the most common form of chronic lung disease of infancy. From a clinical standpoint BPD subjects are characterized by recurrent respiratory symptoms, which are very frequent during the first years of life and, although becoming less severe as children grow up, they remain more common than in term-born controls throughout childhood, adolescence and into adulthood. From a functional point of view BPD subjects show a significant airflow limitation that persists during adolescence and adulthood and they may experience an earlier and steeper decline in lung function during adulthood. Interestingly, patients born prematurely but not developing BPD usually fare better, but they too have airflow limitations during childhood and later on, suggesting that also prematurity per se has life-long detrimental effects on pulmonary function. For the time being, little is known about the presence and nature of pathological mechanisms underlying the clinical and functional picture presented by BPD survivors. Nonetheless, recent data suggest the presence of persistent neutrophilic airway inflammation and oxidative stress and it has been suggested that BPD may be sustained in the long term by inflammatory pathogenic mechanisms similar to those underlying COPD. This hypothesis is intriguing but more pathological data are needed. A better understanding of these pathogenetic mechanisms, in fact, may be able to orient the development of novel targeted therapies or prevention strategies to improve the overall respiratory health of BPD patients.
Objective: To investigate the changing prognosis for babies of less than 28 weeks' gestation. Design: A prospective, collaborative, population based survey. Setting: The former Northern Regional Health Authority. Subjects: All the births between 1983 and 1994 at 22 to 27 completed weeks' gestation to women normally resident in the region. Main outcome measures: Miscarriage, stillbirth, death in the first year of life, and disability in survivors. Results: There were 479 070 registered births in the study period. No baby of 22 weeks' gestation survived; only eight (4%) of the 197 babies of 23 weeks who were alive at the onset of labour survived for a year-a proportion that did not change during the study period. Survival among other babies of less than 28 weeks improved progressively between 1983-6 and 1991-4, but administration of artificial surfactant to babies requiring ventilation from mid-1990 was associated with further improvement in survival only in those over 25 weeks' gestation. Babies of 24 weeks required three times as much high dependency care per survivor as babies of 27 weeks (76 v 26 days). The rate of severe disability in the one year survivors of less than 26 weeks' gestation (30/123; 24%) was similar to that seen in the sampled survivors of 26 and 27 weeks (29/108; 27%); the proportion disabled did not change significantly during the study period. All the children born in 1983, 1987, and 1991 were later reassessed in greater detail: 10% (13/136) seemed destined for a continuing life of total dependency. Conclusions: Gestation, if accurately assessed, can give a woman facing very preterm delivery a clear indication of the prognosis for her baby and help her judge the appropriateness of accepting obstetric intervention and sustained perinatal support.
Objective:
To assess whether there was an adverse effect on brain growth after hydrocortisone (HC) treatment for bronchopulmonary dysplasia (BPD) in a large cohort of infants without dexamethasone exposure.
Study design:
Infants who received HC for BPD between 2005 and 2011 and underwent magnetic resonance imaging at term-equivalent age were included. Control infants born in Geneva (2005-2006) and Utrecht (2007-2011) were matched to the infants treated with HC according to segmentation method, sex, and gestational age. Infants with overt parenchymal pathology were excluded. Multivariable analysis was used to determine if there was a difference in brain volumes between the 2 groups.
Results:
Seventy-three infants treated with HC and 73 matched controls were included. Mean gestational age was 26.7 weeks, and mean birth weight was 906 g. After correction for gestational age, postmenstrual age at time of scanning, the presence of intraventricular hemorrhage, and birth weight z-score, no differences were found between infants treated with HC and controls in total brain tissue or cerebellar volumes.
Conclusions:
In the absence of associated parenchymal brain injury, no reduction in brain tissue or cerebellar volumes could be found at term-equivalent age between infants with or without treatment with HC for BPD.
Importance The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in preterm infants.
Objective To compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants.
Design, Setting, and Participants Randomized, double-blind trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel in which 1201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012.
Interventions Study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced 2 treatment groups with true target saturations of 85% to 89% (n = 602) or 91% to 95% (n = 599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%.
Main Outcomes and Measures The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury.
Results Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI, 0.85 to 1.37; P = .52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI, 0.80 to 1.54; P = .54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, −0.8 weeks; 95% CI, −1.5 to −0.1; P = .03) but did not alter any other outcomes.
Conclusion and Relevance In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months. These results may help determine the optimal target oxygen saturation.
Trial Registrations ISRCTN Identifier: 62491227; ClinicalTrials.gov Identifier: NCT00637169JAMA. 2013;309(20):2111-2120
Purpose of review:
Pulmonary hypertension contributes significantly to morbidity and mortality of chronic lung disease of infancy, or bronchopulmonary dysplasia (BPD). Advances in pulmonary vascular biology over the past few decades have led to new insights into the pathogenesis of BPD; however, many unique issues persist regarding our understanding of pulmonary vascular development and disease in preterm infants at risk for chronic lung disease.
Recent findings:
Recent studies have highlighted the important contribution of the developing pulmonary circulation to lung growth in the setting of preterm birth. These studies suggest that there is a spectrum of pulmonary vascular disease (PVD) in BPD rather than a simple question of whether or not pulmonary hypertension is present. Epidemiological studies underscore gaps in our understanding of PVD in the context of BPD, including universally accepted definitions, approaches to diagnosis and treatment, and patient outcomes. Unfortunately, therapeutic strategies for pulmonary hypertension in BPD are based on small observational studies with poorly defined endpoints and rely on results from older children and adult studies. Yet, unique characteristics of this population create other potential risks for the adoption of these strategies.
Summary:
Despite many recent advances, PVD remains an important contributor to poor outcomes in preterm infants with BPD. Substantial challenges persist, especially with regard to understanding mechanisms and the clinical approach to PVD. Future studies are needed to develop evidence-based definitions and clinical endpoints through which the pathophysiology can be investigated and potential therapeutic interventions evaluated.
