Tine Brink Henriksen

• Professor MD PhD
• Aarhus University

Aim To compare less invasive surfactant administration (LISA) and intubation‐surfactant‐extubation (INSURE) in infants born before 28 weeks gestational age (GA) by the need for mechanical ventilation (MV). Methods LISA was introduced in 2017 in our unit without formal prior LISA‐specific training as an equal alternative to INSURE. Medical records...

Background The Less Invasive Surfactant Administration Assessment Tool (LISA-AT) was developed to support operator training and competence assessment. This study aimed to gather validity evidence in the simulated setting to support using the LISA-AT scores. Methods Validity evidence was gathered using the Messick framework. The lowest quartile (Q1...

Background Neonatal herpes simplex virus (HSV) infection is life-threatening, with a mortality of up to 70–80% when disseminated, often due to vague symptoms and delayed treatment. Neonatal screening using dried blood spot (DBS) samples is among the most impactful preventative health measures ever implemented, but screening for HSV has not been inv...

Introduction Timing of induction of labor (IOL) at term has been investigated in multiple settings. In Denmark, the ‘When to INDuce for OverWeight’ (WINDOW) study compares IOL at 39 weeks of gestation vs expectant management in low‐risk women with obesity. However, knowledge on women's expectations of and experience with IOL is sparse. The aim of t...

Background Early biomarkers are needed to improve diagnosis and support antibiotic stewardship in neonatal sepsis. Heart rate variability (HRV) is proposed as such a biomarker. However, there is a lack of studies in term newborns. Infusion of lipopolysaccharide (LPS) from Escherichia coli induces systemic inflammation comparable to sepsis in newbor...

To evaluate the risk of epilepsy in children who received neonatal phototherapy. A cohort of live singletons born at a Danish hospital (2002–2016) with a gestational age ≥ 35 weeks. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of epilepsy in children treated with neonatal phototherapy compared to childre...

Group B Streptococcus (GBS) disease in neonates occurs in two forms: early-onset disease (EOD), (day 0-6), and late-onset disease (LOD), (day 7-90). This review investigates that risk-based intrapartum screening and antibiotics have reduced the incidence of EOD, but not LOD, in Denmark. No clinical or laboratory tests can rule out GBS disease at sy...

Background Healthcare systems worldwide face challenges related to patient safety, quality of care, and interprofessional collaboration. Simulation-based team training has emerged as a promising approach to address some of these challenges by providing healthcare professionals with a controlled and safe environment to enhance their teamwork and com...

Objective Timing of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin concentrations in mothers and infants at birth...

Introduction Using pre-procedure analgesia with the risk of apnoea may complicate the Less Invasive Surfactant Administration (LISA) procedure or reduce the effect of LISA. Methods The NONA-LISA trial (ClinicalTrials.gov, NCT05609877) is a multicentre, blinded, randomised controlled trial aiming at including 324 infants born before 30 gestational...

Introduction Therapeutic hypothermia is the only proven neuroprotective treatment for hypoxic-ischemic encephalopathy. However, studies have questioned whether therapeutic hypothermia may benefit newborns subjected to infection or inflammation before a hypoxic-ischemic insult. We aimed to compare newborn piglets with lipopolysaccharide-sensitized h...

Maternal vitamin D may be important for several organ systems in the offspring, including the reproductive system. In this population-based follow-up study of 12,991 Danish boys and girls born 2000–2003, we investigated if maternal intake of vitamin D supplements during pregnancy was associated with pubertal timing in boys and girls. Information on...

Introduction Exposures in utero are suggested to play a role in the etiology of endometriosis and adenomyosis, although the current evidence is inconclusive. Knowledge about potential prenatal programming and early life exposures that may affect this risk is of high importance, to focus potential preventive strategies for the diseases already durin...

Background: In a country with a high-test frequency, societal lockdown, and pregnancy leave granted from 28 gestational weeks, we investigated SARS-CoV-2 infection in women admitted in labor and their newborn in the pre-vaccine period. Material and methods: A total of 1042 women admitted for delivery in two Danish hospitals agreed to a plasma sampl...

Objective To estimate the incidence of neonatal herpes simplex virus (HSV) infection and the number of neonates with suspected invasive bacterial infection (IBI) needed to treat (NNT) with acyclovir to ensure prompt treatment of invasive HSV infections. Design A nationwide population-based cohort study. Setting All neonatal and paediatric emergen...

Background Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children. Methods We conducted a follow-up study of 15 819 children bor...

Background: Folate is essential for normal foetal development as it plays an important role for gene expression during different periods of foetal development. Thus, prenatal exposure to folate may have a programming effect on pubertal timing. Objectives: To study the association between maternal intake of folate during pregnancy and pubertal ti...

Maternal vitamin D levels during pregnancy may be important for reproductive health in male offspring by regulating cell proliferation and differentiation during development. We conducted a follow-up study of 827 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, nested in the Danish National Birth Cohort to investigate if matern...

This study examines possible associations of maternal Persistent Organic Pollutants (POP) exposure during pregnancy, maternal hormone levels and fetal growth indices (FGI). During 1st trimester, we measured maternal thyroids, androgens and estrogens, lipophilic POP and perfluorinated-alkyl-acid (PFAA) levels in serum from nulliparous women. Adjuste...

Objective: In women with obesity, to compare full term induction of labor to expectant management by cesarean delivery and other adverse outcomes. Data sources: PubMed, EMBASE, Scopus, Clinicaltrials.gov and Cochrane Library. No time, language, or geographical restrictions. Study eligibility criteria: Studies were eligible if; 1) they were coh...

The purpose of this study was to examine the transfer rate of SARS-CoV-2 IgG antibodies in pregnancy and newborns. Two Danish labor wards screened all women for SARS-CoV-2 by PCR upon arrival. Women (n = 99) with a SARS-CoV-2 PCR–positive nasopharyngeal (NP) swab or with a household member with a positive swab at labor or any time during pregnancy,...

Aim Neurofilament light Chain (NfL) is a promising brain injury biomarker which may assist diagnosis and prognostication in hypoxic-ischemic encephalopathy (HIE). The aim of this study was to investigate serum NfL levels after hypoxia-ischemia (HI) in a newborn piglet model. Second, to characterize the influence of sex, weight, and treatment with r...

Background: Poor male fecundity is of concern, and a prenatal origin has been proposed. Folate, a methyl donor involved in DNA methylation, is essential for normal fetal development by regulating gene expression during different periods of fetal development. Thus, prenatal exposure to low maternal folate intake might have a programing function of...

BACKGROUND Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain. METHODS In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<2...

STUDY QUESTION Is there risk of selection bias in etiological studies investigating prenatal risk factors of poor male fecundity in a cohort of young men? SUMMARY ANSWER The risk of selection bias is considered limited despite a low participation rate. WHAT IS KNOWN ALREADY Participation rates in studies relying on volunteers to provide a semen s...

Decreased heart rate variability (HRV) may be a biomarker of brain injury severity in neonatal hypoxic-ischemic encephalopathy for which therapeutic hypothermia is standard treatment. While therapeutic hypothermia may influence the degree of brain injury; hypothermia may also affect HRV per se and obscure a potential association between HRV and hyp...

Background We have previously investigated neurological outcomes following remote ischemic postconditioning (RIPC) in a newborn piglet model of hypoxic-ischemic encephalopathy. The aim of this study was to further investigate potential mechanisms of neuroprotection by comparing newborn piglets subjected to global hypoxia-ischemia (HI) treated with...

Background Group B Streptococcus (GBS) infection in infants may result in both respiratory, cardiovascular, and neurological dysfunction and ultimately death of the infant. Surveillance of GBS strains in infants and their clinical characteristics guide development of effective vaccines and other potential treatments and may have implications for fu...

Background: Despite therapeutic hypothermia, neonates with hypoxic-ischemic encephalopathy still develop neurological disabilities. We have previously investigated neuroprotection by remote ischemic postconditioning (RIPC) in newborn piglets following hypoxia-ischemia (HI). The aim of this study was to further investigate potential effects of RIPC...

Neonatal herpes simplex disease (HSV) is a rare but life-threatening infection associated with high rates of morbidity and mortality. Recent studies indicate that the incidence rate has continued to rise over the past decades, while the mortality remains unchanged. Early clinical suspicion of HSV and parenteral antiviral treatment of acute disease...

Aim: Our aim was to investigate the rates of preterm births, live births and stillbirths, in Denmark during the first year of the COVID-19 pandemic. Methods: This was a national, cross-sectional registry-based study that used the Danish Newborn Quality database, which covers all births in Denmark. The proportions of preterm births were compared...

Introduction: Obesity is associated with many pregnancy complications, including both fetal macrosomia and prolonged labour. As a result, there is often also an increased risk of caesarean section. In other settings, labour induction near to term reduces adverse outcomes such as stillbirth and birth injury, without causing more caesarean deliverie...

Background Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and accumulate in humans. PFAS are suspected to affect the neuropsychological function of children, but only few studies have evaluated the association with childhood attention and executive function. Objectives To investigate the association between...

OBJECTIVES The rare event of handling critically ill children often challenge the emergency care team. Several studies have investigated effects of simulation-based team training to prepare for such events, but the body of evidence remains to be compiled. We performed a systematic review of the effects of simulation-based team training on clinical...

Introduction Emerging evidence shows that women with endometriosis face a higher risk of preterm birth. However, the pathways are unclear. The objective of this study is to further investigate at different gestational ages the association between endometriosis and different pathways of preterm birth including, medically indicated preterm birth, pre...

Purpose Hypospadias is one of the most frequent male congenital malformations. It remains controversial whether maternal lifestyle during pregnancy may affects the risk of having a son with hypospadias, especially for smoking with many suggesting lower risk. We assessed the individual and joint associations between maternal cigarette smoking, pre-p...

Purpose Parental separation may be a stressful life event with the potential to influence hormonal regulation of offspring reproductive health and thereby affect semen quality in young men. We aimed to study the association between parental separation in pregnancy or in childhood and semen quality in young men and to study whether the timing of par...

Background: Studies have suggested that neurological outcome may differ in newborns with encephalopathy with and without perinatal infection. We aimed to systematically review this association. Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies were obta...

Background Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal o...

Objective A theory has emerged, suggesting that abnormalities in the auditory system may be associated with sudden infant death syndrome (SIDS). However, current clinical evidence has never been systematically reviewed. Design A systematic review was conducted according to the guideline of Preferred Reporting Items for Systematic Reviews and Meta-...

ESPR Young Investigator Award Session 2nd prize

Purpose To study the occurrence of major congenital abnormalities in children of women with type 1 and type 2 diabetes and investigate the association between glycated haemoglobin (HbA1c) and major congenital malformations according to type 1 diabetes and type 2 diabetes separately. Patients and methods In this register-based study, all singletons...

Background: Epinephrine is an integral component of neonatal resuscitation guidelines, despite sparse evidence. The association between advanced cardiopulmonary resuscitation (CPR) and poor neurodevelopment is well known, and epinephrine may improve short-term survival but at the cost of poor neurologic outcome. Our objectives were to investigate t...

STUDY QUESTION Is fertility treatment with clomiphene citrate associated with an increased risk of childhood epilepsy, including specific subtypes of epilepsy? SUMMARY ANSWER Fertility treatment with clomiphene citrate may be associated with a small increased risk of idiopathic generalized epilepsy and focal epilepsy in childhood. WHAT IS KNOWN A...

( BJOG . 2020;127:1180–1188) Preterm birth is associated with higher risk of cerebral palsy (CP) and other complications. Magnesium sulfate (MgSO 4) may decrease risk of CP when taken immediately before preterm birth. A recent trial investigated the neuroprotective functions of MgSO 4 . This updated systematic review, meta-analysis and trial sequen...

Context: Several neonatal simulation-training programs have been deployed during the last decade, and in a growing number of studies, researchers have investigated the effects of simulation-based team training. This body of evidence remains to be compiled. Objective: We performed a systematic review of the effects of simulation-based team traini...

(Abstracted from BJOG 2020;127:1180–1188) Preterm delivery puts infants at risk of developing cerebral palsy (CP). Conventional meta-analyses have shown that administering magnesium sulfate (MgSO 4 ) at imminent preterm birth may help decrease this risk.

Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemor...

Children born preterm have an increased risk of severe morbidity, e.g. cerebral palsy (CP), compared to children born at term. CP cannot be treated, which is why a prophylactic approach is essential, as argued in this review. Six randomised controlled trials (RCTs) have provided data on MgSO4 treatment as CP neuroprotection in preterm birth, includ...

Only 30% of medication used for children and adolescents and 10% of the medication used for neonates has been evaluated for use in these populations. Infants and children differ from adults regarding pharmacodynamic and -kinetics, but they also differ from each other due to e.g. age, weight, and body composition, as we argue in this review. There i...

BackgroundA number of neonatal simulation-training programmes have been deployed during the last decade, and a growing number of studies have investigated effects of simulation-based team training. However, the body of evidence remains to be compiled. Therefore, we performed a systematic review on the effects of simulation-based team training on cl...

Objectives To estimate a possible association between coffee intake during pregnancy and risk of childhood acute leukemia by using a cohort design. Methods We included data from two birth cohorts; the Danish National Birth Cohort and the Aarhus Birth Cohort. Recruitment of 141,216 eligible pregnancies occurred from 1 August 1989 to 31 December 201...

Aim Our aim was to explore the under‐researched associations between an elective Caesarean section (C‐section) at early term or full term gestation and behaviour at 6‐8 years of age. Methods We identified 1220 eligible children born by elective C‐sections at Danish hospital from 2009‐2011. Their mothers were randomised to elective C‐sections at ei...

Background: Ordinary meta-analyses indicate that magnesium sulphate (MgSO4 ) treatment to women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g., by trial sequential analysis (TSA), for which there were previously insuffic...

Background: Early puberty is a risk indicator for adult diseases. Identification of modifiable causes of earlier puberty is, therefore, warranted. We estimate the association between childhood body mass index (BMI) and pubertal timing in a cohort study and in a sibling-matched study to adjust for unobserved time-stable confounders shared within fa...

Objective: To study the effect of antenatal magnesium sulphate (MgSO4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis. Design: Double-blind, randomised, placebo-controlled, multicentre trial. Setting: Fourteen Danish obstetric departments. Population: In total, 560 pregnant women...

Objective To describe the various combinations of medication used in Denmark in the latent phase of labor (i.e. for therapeutic rest) and to estimate the frequency of use. Methods An informal e-mail survey based on personal information from Danish midwives or staff obstetricians. The main outcome measures were type and dosage of medications used i...

Background Non‐participation in aetiologic studies of pubertal timing is frequent. However, little effort has been given to explore the risk and potential impact of selection bias in studies of pubertal timing. Objective We aimed to explore the risk of selection bias due to non‐participation in a newly established puberty cohort. Methods We evalu...

Hypoxic-ischaemic encephalopathy is a common cause of death and disability in newborns. Brain damage related to a perinatal insult is the result of a dynamic process, and its progressing development over time allows for specific interventions to reduce total damage, as described in this review. Despite therapeutic hypothermia which currently is the...

This review gives a summary of Danish preterm care, which has been defined by national adaptation of antenatal corticosteroids in the 1970ies and continuous positive airway pressure in the 1980ies. Today, preterm survival in Denmark is high, by international standards, but lower than in the neighbouring countries Sweden and Norway. The lack of a na...

In 2018, The Danish Society of Obstetrics and Gynecology and the Danish Paediatric Society agreed on a national consensus guideline on the treatment of imminent preterm delivery prior to 25 weeks. This review summarises the recommendations: at 22 weeks transfer to a tertiary hospital, at 23 weeks tocolysis, antenatal steroid and newborn resuscitati...

Introduction: Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of morbidity and mortality for both mother and fetus. It has been proposed that vitamin D affects a number of biological processes involved in the pathogenesis of hypertensive disorders of pregnancy. Therefore, a seasonal vari...

Aims: This study aimed to examine the feasibility of a web-based questionnaire when collecting information on alcohol consumption in pregnancy to identify women with risk drinking behaviour, and to describe factors associated with risk drinking behaviour, and the use of specialized care for prenatal risk drinking. Methods: In 2413 women referred...

Background Limited research has addressed whether maternal alcohol intake in early pregnancy increases the risk of spontaneous preterm birth. In the current study, we examined how alcohol binge drinking and weekly alcohol intake in early pregnancy were associated with spontaneous preterm birth in a contemporary cohort of Danish women. Methods We i...

Background Little is known about maternal alcohol intake in early pregnancy and the risk of attention‐deficit/hyperactivity disorder (ADHD) in children beyond 5 years of age. We examined the association between alcohol binge drinking and weekly alcohol intake in early pregnancy and the risk of ADHD in children followed from birth to 19 years of age...

Background: Maternal thyroid hormones are essential for fetal brain development in early gestation. Perfluoroalkyl substances (PFASs)-widespread and persistent pollutants-have been suggested to interfere with maternal thyroid hormones in the second or third trimesters, but evidence for an association in the early pregnancy period is sparse. Objec...

Background: The training required for accurate assessment of umbilical catheter placement by ultrasonography (US) is unknown. Objective: To describe the learning curve and provide an estimate of the accuracy of physicians' US examinations (US skills) and self-confidence when examining umbilical catheter tip placement. Methods: Twenty-one physi...

Background: Earlier pubertal timing has been observed in many countries. We aimed to explore if prenatal exposure to maternal obesity, smoking, and alcohol intake was associated with timing of puberty by use of a novel marker of pubertal timing: 'the height difference in standard deviations' (HD:SDS). Methods: HD:SDS is the difference between pu...

The purpose was to examine the association between exercise during pregnancy and intelligence score in offspring. We analysed data from 4008 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, recruited during pregnancy from July 1989 to November 1991 and their sons who were registered at conscription at 17‐20 years of age. The...

There are a variety of devices that quantify biological properties of cerebral tissue. Installing such device will cause a local insertion trauma, which will affect early measurements. Current literature proposes minimum one hour of observation before acquiring first measurements when using microdialysis. It is unknown whether this applies to other...

Introduction: Recent recommendations characterize deliveries at 37 weeks 0 days through 38 weeks 6 days as early term. We aimed to systematically review the literature on long-term cognition, school performance, and behavior in children born early term (37 weeks 0 days to 38 weeks 6 days) compared with full term (39 weeks 0 days to 40 weeks 6 days...

Background: In many countries, an increased prevalence of obesity in pregnancy has coincided with a declining pubertal age. We aimed to explore the potential effect of maternal pre-pregnancy overweight and obesity on timing of puberty in sons and daughters. Methods: Between 2012 and 2018, 15 819 of 22 439 invited children from the Danish Nationa...

Objectives: To estimate the association between fetal congenital heart defects (CHDs) and measures of brain size throughout pregnancy, from the end of the first trimester to birth. Study design: The cohort consisted of all fetuses scanned in Western Denmark in 2012 and 2013. Anthropometric measures in fetuses with isolated CHDs diagnosed within...

Background Higher concentrations of single perfluorinated alkyl acids (PFAAs) have been associated with lower birth weight (BW), but few studies have examined the combined effects of PFAA mixtures. PFAAs have been reported to induce estrogen receptor (ER) transactivity, and estrogens may influence human fetal growth. We hypothesize that mixtures of...