ArticleLiterature Review

The aetiology of meconium-stained amniotic fluid: Pathologic hypoxia or physiologic foetal ripening? (Review)

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Abstract

Despite the many efforts to study the (patho)physiology of meconium release before delivery, it still remains an indistinct subject. Some studies have reported a relationship between hypoxia and MSAF, whilst others have not. The most common association found however, is between MSAF and the term of gestation. MEDLINE, EMBASE and the Cochrane library were electronically searched. Papers about the (patho)physiology of meconium-stained amniotic fluid in English were included. Papers about management strategies were excluded (see elsewhere this issue). Different theories have been proposed including acute or chronic hypoxia, physiologic foetal ripening and peripartum infection. We suggest that meconium-stained amniotic fluid should be regarded as a symptom rather than a syndrome becoming more prevalent with increasing term and which might be associated with higher levels of infection or asphyxia.

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... Meconium consistency is related to the onset and balance between passage and clearance of meconium in utero. Thin meconium is related to chronic hypoxic stress whereas thick meconium is associated with acute hypoxic stress or inflammation [27,28]. However, the assessment of MSAF consistency is subjective, and there is no standardized evaluation [29,30]. ...
... A significantly higher rate of MAS occurred in the thick group, who required significantly more ventilation support than the thin group. Infants with thick MSAF have a higher exposure to acute hypoxic events, which lead to a higher chance of developing respiratory problems [27]. A recent placental pathologic study by Saeed et al. [38] found higher a histologic stage of fetal inflammation in thick versus nonthick MSAF. ...
Article
Objective: To compare short-term outcomes of infants born with thick versus thin meconium stained amniotic fluid (MSAF) and to perform a systematic review of the topic. Methods: A retrospective, single center, cohort study of infants’ ≥34 weeks’ gestation born with MSAF between 1 June 2013 and 30 September 2016. Birth resuscitation and respiratory outcomes were compared between the groups. A systematic review was conducted of similar studies published between 1 January 2000 and 30 June 2019. Results: 1507 infants were eligible; 464 (30.8%) thick, 1,043 (69.2%) thin MSAF. The thick group required more respiratory support at birth and was 5.5-fold (95% CI: 2.51–11.95) more likely to and have meconium aspiration syndrome (MAS) and 2.1-fold more likely (95% CI: 0.89–4.83) to require either noninvasive respiratory support or intubation than the thin group. The thick group also had significantly higher oxygen supplementation >24 h (p < .001) and pneumothorax (p = .002). Across 12 studies included in the systematic review, infants with thick MSAF required more intensive birth resuscitation, ventilation support, with higher incidences of MAS. Study differences prohibited data comparisons and quantitative outcome evaluations. Conclusion: Infants with thick MSAF required more intensive birth resuscitation and ventilation support. Our findings need confirmation in robust, prospective cohort studies.
... Fetal hypoxia may stimulate colonic activity, leading to the passage of meconium, and also may stimulate fetal gasping movements that result in meconium aspiration [6,11]. As mentioned above, PIH can cause chronic placental insufficiency, which may proceed fetal hypoxia. ...
... Some studies disclosed that regular defecation in fetus is a normal physiological process rather than a pathological event [16,17]. However, fetal hypoxia could not only stimulate colonic activity but also impair normal clearance ability of meconium in amniotic fluid, which prolonged the presence of meconium stained in amniotic fluid [11,18]. Therefore, fetal hypoxia may play a role in the development of MAS. ...
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Objective: Meconium aspiration syndrome (MAS), possibly resulting from fetal hypoxia, is a respiratory distress disorder in the infant. Pregnancy-induced hypertension (PIH) can cause placental dysfunction and lead to fetal hypoxia, which may induce the development of MAS. Therefore, the aim of this study was to determine the association between PIH and MAS and to identify the predictive risk factors. Materials and methods: This was a retrospective cohort study. We selected patients with newly diagnosed PIH and a matched cohort group from the Taiwan National Health Insurance Research Database (NHIRD), from January 1, 2000 till December 31, 2013. For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. The incidence of meconium aspiration syndrome was assessed in both groups. Results: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients who experienced PIH had a higher incidence of MAS than did those without PIH. According to a multivariate analysis, PIH (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.49-1.93, p < 0.0001) was independently associated with increased risk of MAS. Additionally, age ≥30 years (OR = 1.26, 95% CI = 1.12-1.42, p = 0.0001), nulliparity (OR = 1.13, 95% CI = 1.01-1.27, p = 0.0367) and patients with diabetes mellitus (OR = 3.09, 95% CI = 1.35-7.09, p = 0.0078) were also independent risk factors of MAS. Conclusion: Patients with PIH obtained higher subsequent risk for the development of MAS than those without PIH. Besides, age ≥30 years, nulliparity and patients with diabetes mellitus are the independent risk factors of developing MAS.
... Almost all new-born infants who pass meconium are mature (term), however, in some cases; meconium passage may be associated with umbilical cord compression or increased sympathetic inflow during hypoxia and is also a potential toxin if the fetus aspirates this particulate matter with a gasping breath in utero or when it takes its first breaths following birth. In addition intrauterine exposure to meconium is associated with inflammation of tissues of the lung, chorionic plate and umbilical vessels and through various mechanisms may contribute to neonatal morbidity, independent of MAS [3][4][5][6][7]. ...
... Birth depression occurs in 20 to 33% of infants born through MSAF and is likely caused by chronic asphyxia and infection that may lead to passage of meconium and fetal gasping [9]. This suggest that meconiumstained amniotic fluid should be regarded as a symptom rather than a syndrome becoming more prevalent with increasing term and which might be associated with higher levels of infection or asphyxia [6]. ...
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Abstract Background: Meconium is not only a potential sign of fetal hypoxia but is also a potential toxin if the fetus aspirates particulate matters with a gasping breath in utero or when it takes its first breaths following birth. In addition to this the condition of the mother who gives birth in such circumstances is a concern. Methods: A hospital based cross-sectional descriptive study was carried out on labouring mothers with meconium stained amniotic fluid who delivered in the labor ward of Jimma University Specialized Hospital during October1, 2012 to December 30, 2012. All labouring mothers with meconium stained amniotic fluid (MSAF) during the period were included. Data on history of the patient, patient specific demographics and obstetric information was collected using pretested structured questionnaire. Relevant data was abstracted from the neonatal chart and the logbook in the neonatology ward. Statistical tests of association using SPSS (version 16.0, IBM Corporation) were employed at the level of significance of 5%. Results: The overall rate of meconium stained amniotic fluid was 15.4% (151/979) and 74.8% of the cases had moderate to thick meconium stained amniotic fluid. Mode of delivery in 70.2% of cases was operative delivery; and those mothers with a grade three meconium stained liquor had about 5 times increased risk of operative delivery when compared with mothers with grade 1 staining (OR=4.66, 95%CI:1.52-14.30). First minute Apgar score was less than 7 in 88% of the new born while it was less than 4 in 15% of the cases. However, there was no statistically significant association between the thickness of meconium and low first minute Apgar score. Those babies who were delivered with operative delivery had 16 times increased risk of low 5th minute Apgar score. Among the 27.1% of new born sent to the Neonatal Intensive Care Unit, 71.4% (19.9% of the total) were diagnosed to have Meconium Aspiration Syndrome with clinical examination alone. Those new-borns with first minute Apgar score<7 had three times increased risk of MAS (95% CI: 1.087-10.668) and the presence of meconium stained secretion in the oropharynx of a new born resulted in 9 times increased risk of Meconium Aspiration Syndrome. Conclusion: The study revealed that Moderate to thick meconium stained amniotic fluid was associated with increased risk of operative delivery, low 5th minute Apgar score and Meconium Aspiration Syndrome. Shortening the threshold for intervention for labor with fetal heart rate abnormalities in the presence of meconium stained amniotic fluid and introducing further fetal evaluation methods like fetal scalp PH analysis are recommended.
... Meconium passage is less common before 37 weeks of gestational age and increases steadily with gestational age [2]. It may represent the normal gastrointestinal maturation, or it may indicate an acute or chronic hypoxic event, thereby making it a potential warning sign of a fetal Compromise [3,4]. Though its controversial to differentiate physiologic or pathologic meconium staining of amniotic fluid, there are few shreds of evidence that indicates its association with increased meconium aspiration syndrome, operative delivery, respiratory distress, neonatal sepsis, need for resuscitation, neonatal intensive care admission, and low Apgar score [5][6][7][8]. ...
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Objective To determine the perinatal outcome of labouring mothers with meconium-stained amniotic fluid (MSAF) compared with clear amniotic fluid at teaching referral hospital in urban Ethiopia. Methods A prospective cohort study was conducted among labouring mothers with meconium-stained amniotic fluid from July 1 to December 30, 2019. Data was collected with pretested structured questionnaires. A Chi-square test used to check statistical associations between variables. Those variables with a p-value of less than 0.05 were selected for cross-tabulation and binary logistic regression. P-value set at 0.05, and 95% CI was used to determine the significance of the association. Relative risk was used to determine the strength and direction of the association. Result Among 438 participants, there where 75(52.1%) primigravida in a stained fluid group compared to112 (38.5%) of the non-stained fluid group. Labour was induced in 25 (17.4%) of the stained fluid group compared to 25(8.6%) of a non-stained fluid group and has a statistically significant association with meconium staining. The stained fluid group was twice more likely to undergo operative delivery compared with a non-stained fluid group. There were more low Apgar scores at birth (36.8% versus 13.2%), birth asphyxias (9% versus 2.4%), neonatal sepsis (1% versus 5.6%), neonatal death (1% versus 9%), and increased admissions to neonatal intensive care unit (6.2% versus 21.5%) among the meconium-stained group as compared to the non-stained group. Meconium aspiration syndrome was seen in 9(6.3%) of the stained fluid group. Conclusion Meconium-stained amniotic fluid is associated with increased frequency of operative delivery, birth asphyxia, neonatal sepsis, and neonatal intensive care unit admissions compared to clear amniotic fluid.
... Whereas neonates born with MSAF typically do well, ~5% develop meconium aspiration syndrome (MAS). (17,18) It is important to understand how MSAF and MAS affect long-term developmental outcomes. ...
Article
Objective: This study aims to determine whether fetal meconium passage is associated with autism. Study design: This retrospective birth cohort analysis of 9 945 896 children born in California 1991 to 2008 linked discharge diagnosis and procedure codes for prenatal stressors, meconium-stained amniotic fluid (MSAF) and meconium aspiration syndrome (MAS) with autism diagnoses for 47 277 children through 2012. We assessed the relative risk of autism by meconium status using logistic regression, adjusting for demographic and clinical features. Results: Children exposed to meconium (MSAF and MAS) were more likely to be diagnosed with autism in comparison with unexposed children (0.60% and 0.52%, vs 0.47%, respectively). In adjusted analyses, there was a small increase in autism risk associated with MSAF exposure (adjusted relative risk (aRR) 1.18, 95% confidence interval (CI) 1.12 to 1.25), and a marginal association that failed to achieve significance between MAS and autism (aRR 1.08, 95% CI 0.98 to 1.20). Conclusion: Resuscitation of neonates with respiratory compromise from in utero meconium exposure may mitigate long-term neurodevelopmental damage.Journal of Perinatology advance online publication, 3 November 2016; doi:10.1038/jp.2016.200.
... The presence of MSAF may represent the 1 1 1 2 1 1 normal maturation of the gastrointestinal tract. It may also be present in conditions of fetal distress due to an acute or chronic hypoxic event [4,6]. ...
Article
Objective The aim of this study was to determine the perinatal outcome of pregnant patients complicated with meconium-stained amniotic fluid (MSAF) compared with clear amniotic fluid. Methodology This prospective cross-sectional study was conducted in the Department of Obstetrics and Gynecology in collaboration with the Department of Pediatrics at Indira Gandhi Institute of Medical Sciences, Patna, India, from September 2016 to January 2018. A total of 200 patients were included in the study after taking their written consent. Out of these 200 patients, 100 patients had MSAF, and the other 100 patients with clear liquor were taken as controls after fulfilling the inclusion and exclusion criteria. These two groups of patients were compared regarding various maternal and neonatal parameters. These parameters were compared and tested statistically for significance. Results Among the 100 patients with MSAF, 20 patients had grade 1 meconium (X), 22 patients had grade 2 meconium (Y), and 58 patients had grade 3 meconium (Z). The majority of patients in the MSAF group were primigravida and more than 25 years of age. In addition, 47% of patients in the MSAF group had some associated high-risk factors and 50% of patients had non-reassuring fetal heart rate patterns, and among these, 39 patients had grade 3 MSAF (X). In the MSAF group, 49% of patients had undergone lower segment cesarean section (LSCS), whereas in the non-MSAF group, it was 37%. Also, 30% of babies in the MSAF group and 13% in the non-MSAF group had neonatal intensive care unit (NICU) admission; 22% of babies in the MSAF group and 12% of babies in the non-MSAF group had an adverse neonatal outcome. Meconium aspiration syndrome was present in 14% of the patients in the MSAF group, and among these, two babies had neonatal death and both had severe birth asphyxia. In the non-MSAF group, there was one neonatal death due to neonatal sepsis. However, after statistically analyzing the neonatal outcome in both the groups, there was no statistical difference between the two groups (p<0.001). Conclusion MSAF is associated with increased frequency of operative delivery, poor neonatal outcomes, and increased NICU admission. Management of labor with MSAF requires appropriate intrapartum care with continuous fetal heart rate monitoring, and this can reduce unnecessary cesarean sections in patients with MSAF.
... An accepted theory suggests that MSAF reflects fetal gastrointestinal tract maturation mainly supported by increasing incidence in post-term [5,6]. However, this theory is irrelevant when MSAF is encountered in preterm, implying an alternative association with fetal distress or hypoxia [4,7]. ...
Article
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Purpose: To determine whether meconium-stained amniotic fluid (MSAF) encountered in pregnancies complicated by preterm premature rupture of membranes (PPROM) is associated with adverse maternal and perinatal outcome. Methods: A retrospective cohort study of all singleton pregnancies with PPROM and MSAF who delivered in a tertiary hospital at 24 + 0-36 + 6 weeks of gestation between 2007 and 2017. Women with PPROM-MSAF (study group) were compared to women with PPROM and clear amniotic fluid (control group). Controls were matched to cases according to age, gravidity, parity and gestational age at delivery in a 3:1 ratio. Primary outcome was defined as neonatal intensive care unit admission. Secondary outcomes were neonatal adverse outcomes, chorioamnionitis and placental abruption diagnosed clinically or by placental cultures and histology. Results: Seventy-five women comprised the study group and were matched to 225 women representing the control group. A significantly higher rate of neonatal intensive care unit admissions was noted in the study group compared to controls (61.3% vs. 45.7%, p = 0.03). Multivariate analysis demonstrated that MSAF is an independent risk factor for neonatal intensive care unit admission (adjusted OR = 2.82, 95% CI 1.39-5.75, p = 0.004). MSAF was found to be associated to higher rates of cesarean and operative vaginal deliveries (30.7% vs. 24.4% and 5.3% vs. 2.7%, p = 0.057, respectively) as well as to chorioamnionitis and placental abruption (33.3% vs. 19.3%, p = 0.034 and 16.0% vs. 7.7%, p = 0.021, respectively). Conclusion: MSAF is associated with higher frequencies of adverse perinatal outcome when compared to clear amniotic fluid in pregnancies complicated by PPROM.
... It may indicate the physiologic process involving the mature fetal colon or acute/chronic hypoxic event, thereby making it a warning sign of a fetal compromise [16]. It may also lead to serious problems such as chorioamnionitis, intrauterine infection, meconium aspiration syndrome, cerebral palsy, bronchopulmoner dysplasia and perinatal mortality [17,18]. ...
Article
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Aim: We aimed to investigate the potential risk factors related to poor perinatal outcomes after cesarean section performing at full cervical dilatation. Material and Method: Fourty-nine women who underwent cesarean section at full cervical dilatation were enrolled in this retrospective case-control study. Women with poor perinatal outcome defined as the presence of admission to neonatal intensive care unit were the cases while the women without poor perinatal outcome were controls. Two groups were analyzed to determine possible risk factors for poor perinatal outcome with multivariate logistic regeression model. ROC curve analysis was used to find cut off point of duration of arrest at full cervical dilatation for poor perinatal outcomes with significant factors. Results: Of 49 women, 9 (18.4%) women constructed the case group while 40 (81.6%) women were in control group. In multivariate analysis persistent occiput posterior position was the only factor to be significant for the poor perinatal outcome after cesarean section at full cervical dilatation. The best cut-off point of duration of arrest at full cervical dilatation for poor perinatal outcome with persistent occiput posterior position established by the ROC curve was 1.25 hour, showing a sensitivity of 75.0 %, specificity of 50.0 %. Discussion: Persistent occiput posterior position may be a risk factor for adverse perinatal outcomes of cesarean section at full cervical dilatation. All obstetricians should be aware of duration of arrest at full cervical dilatation with persistent occiput posterior position and this interval should not be longer than 1 hour.
... Meconium passage is less common before 37 weeks of gestational age and increases steadily with gestational age [2]. It may represent the normal gastrointestinal maturation, or it may indicate an acute or chronic hypoxic event, thereby making it a potential warning sign of a fetal Compromise [3,4]. Though its controversial to differentiate physiologic or pathologic meconium staining of amniotic fluid, there are few shreds of evidence that indicates its association with increased meconium aspiration syndrome, operative delivery, respiratory distress, neonatal sepsis, need for resuscitation, neonatal intensive care admission, and low Apgar score [5][6][7][8]. ...
... 5 Similarly, the maturation of the GIT, vagal stimulation or the compression of the spinal cord may also cause the release of meconium in to the amniotic fluid. 6 Presence of meconium in the amniotic fluid could be a dangerous condition. It may increase the risk of bacterial infection, aspiration of meconium resulting in gasping breathing pattern causing hypoxia due to airway obstruction, chemical pneumonitis and pulmonary hypertension. ...
Article
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Black-green colored odorless material known as meconium is physiologically passed by new born babies with in 48 hours of birth. Presence of meconium in the amniotic fluid could be a dangerous condition. It may expose the baby to multiple condition depending upon the amount of meconium entering in to the respiratory track of the baby. The knowledge of association of various maternal and fetal associated factors with meconium aspiration syndrome is of immense importance for appropriate clinical judgments and decisions. The aim of the present study was to study various maternal and fetal parameters associated with meconium stained amniotic fluid. The present study was a prospective observational study. It was conducted in the Obstetrics and Gynecology department of Tertiary Hospital & Medical Collage & Research Centre, Ahmedabad, Gujarat, India during May 2016 to May 2018 on 200 laboring mothers with meconium stained amniotic fluid who delivered or underwent cesarean section in the institute were included in the study. Majority of them were between 20–30 years of age (59%). The women between 31–35 years of age were 27%. Participants either <20 years or >35 years were 9% and 5% respectively. There were 82 patients who had grade I MSL, 63 patient who had grade II MSL whereas 55 patients who had grade III MSL. Out of 200, there were 196 women who were having associated risk factors like prolonged labour, PROM, hypertension, postdatism, GDM, IUGR and anaemia. MSL as well as MAS has been strongly associated with the parity of the mother. It was also observed that patients who’s age was greater than 35 yrs. All (100%) presented with grade 3 MSL. Fetus whose gestational age was greater than 40 weeks has fewer chances of co-morbidities. It was concluded in the present study that multiparity, higher maternal age, presence of Maternal Risk Factors, C-section, IUGR, oligo-hydraminos, post-datism, GDM, non-reactive CTG, prolonged labor and PROM had significant association with higher grades of meconium stained Liquor. It is strongly recommend that in such patients early and appropriate care along with constant monitoring can prove to be highly beneficial.
... In the intrapartum treatment guideline, meconium-stained amniotic fluid is graded as an important MSL and non-important MSL, according to the Royal College of Obstetricians and Gynecologists (RCOG) [12]. Non-important MSL is classified as a thin yellow or greenish tinged fluid; it contains nonparticular meconium, while significant MSL is defined as a dense and stubborn, dark green or black amniotic fluid consisting of the meconium bumps [13]. ...
Article
Objective This study aimed to determine the association of Apgar score with meconium staining of amniotic fluid in labor. Methodology A retrospective observational study was carried out through the non-probability convenient sampling technique at the Department of Obstetrics and Gynecology for a duration of six months. Only those women were selected who had more than 24 weeks of gestation period. The women were excluded on the basis of risk factors for fetal distress and breech in late labor. Results A total of 216 pregnant women were selected from the labor room in this study. The mean age of the women was 26.57±4.28 years. The gestational age of the women was 36.09±4.11 weeks. Moreover, the mean parity of pregnant women was 1.68±2.53. It has been observed that the women who had meconium staining, the neonates of 144(77.4%) women showed the Apgar score of less than six at one minute. However, for the women without meconium staining, the neonates of only 15(50%) women showed the Apgar score of less than six at the one-minute interval with a significant association (p=0.02). With respect to age groups, a significant association of meconium staining with Apgar score was noted in the 21-30 years age group, whereas, no significant association was seen in other age groups. Similarly, a significant association of meconium staining and Apgar score was noted in primiparous women, whereas, no significant association was noted in multiparous women. No significant association of Apgar score and meconium staining was seen with respect to the mode of delivery. Conclusion The study has found a relation between the Apgar score and meconium staining of amniotic fluid and reported that the Apgar score of less than six at one minute was significantly associated with meconium staining of amniotic fluid.
... [1][2][3][4] This observation may support the theory that MSAF occurs independently of other obstetrical complications and represents a physiological phenomenon. 8,12,[22][23][24] Thus, we speculate that the subsequent morbidity associated with MSAF may be related to exposure in utero to meconium rather than the background risk factors associated with the pregnancy. ...
Article
Objective This study aims to determine the impact of meconium-stained amniotic fluid (MSAF) in low-risk pregnancies at term on pregnancy outcome. Study Design A retrospective cohort study of women with MSAF during labor who delivered in a tertiary hospital at 37 to 41⁺⁶ weeks of gestation (2007–2013). Exclusion criteria included: multiple gestations, noncephalic presentation, fetal structural/chromosomal anomalies, hypertensive disorders, diabetes, oligohydramnios, or small for gestational age. Pregnancy outcome of women with MSAF (N = 4,893) was compared with a control group of women without MSAF (N = 39,651). Neonatal respiratory morbidity was defined as the presence of any of the following: respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration syndrome, or need for ventilatory support. Results Overall, 10.9% of low-risk pregnancies at term were diagnosed with MSAF. Compared with the controls, women with MSAF had higher rates of nulliparity, gestational age at delivery ≥ 41 weeks, induction of labor, nonreassuring fetal heart rate, and operative deliveries. In multivariate analysis MSAF was associated with operative delivery (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.63–2.09; p < 0.001), cesarean section (OR, 1.48; 95% CI, 1.31–1.69; p < 0.001), respiratory morbidity (OR, 4.74; 95% CI, 3.87–5.82; p < 0.001), and increased risk for short-term neonatal morbidity. Conclusions MSAF is associated with a higher rate of adverse perinatal outcome even in low-risk pregnancies at term.
... Monen y colaboradores, proponen que la presencia de este se tome como un signo clínico más que como un síndrome comprendiendo que aumenta su prevalencia al aumentar la edad de gestación. 77 Clásicamente se describe en la fisiopatología del SAM: ...
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... Maternal factors, including maternal age, delivery mode, and the presence of medical conditions such as preeclampsia, diabetes, antepartum hemorrhage, PROM, polyhydramnios and oligohydramnios, and neonatal factors including gestational age, birth weight, sex of the infant, and the prevalence of hypoglycemia have all been reported to be associated with the presence of MSAF [14,21,22,25,78,[81][82][83][84][85]. Because thin meconium is reported to be associated with chronic hypoxic stress, whereas thick meconium is reported to be associated with acute hypoxic stress or inflammation [13,79], we hypothesize that fetal asphyxia that occurs before or during delivery in both groups may represent a confounding factor that might neutralize the power of statistical analyses in both groups, leading to the lack of significant differences in maternal factors between the two groups. ...
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Whether meconium-stained amniotic fluid (MSAF) serves as an indicator of fetal distress is under debate; however, the presence of MSAF concerns both obstetricians and pediatricians because meconium aspiration is a major contributor to neonatal morbidity and mortality, even with appropriate treatment. The present study suggested that thick meconium in infants might be associated with poor outcomes compared with thin meconium based on chart reviews. In addition, cell survival assays following the incubation of various meconium concentrations with monolayers of human epithelial and embryonic lung fibroblast cell lines were consistent with the results obtained from chart reviews. Exposure to meconium resulted in the significant release of nitrite from A549 and HEL299 cells. Medicinal agents, including dexamethasone, L-Nω-nitro-arginine methylester (L-NAME), and NS-398 significantly reduced the meconium-induced release of nitrite. These results support the hypothesis that thick meconium is a risk factor for neonates who require resuscitation, and inflammation appears to serve as the primary mechanism for meconium-associated lung injury. A better understanding of the relationship between nitrite and inflammation could result in the development of promising treatments for meconium aspiration syndrome (MAS).
... Risk factors that may cause foetal distress which leads to MSAF include placental ageing due to post-dated pregnancy, IUGR, oligohydramnios, hypertensive disorder of pregnancy, gestational diabetes, & maternal drug abuse. 9 MSAF at delivery is a potential sign of foetal compromise. The presence of meconium is an indication for continuous monitoring of the foetal heart rate (FHR) during labour and it lowers the threshold for making a diagnosis of foetal distress if FHR abnormalities are present. ...
Chapter
The respiratory system comprises the lips and palate, larynx, trachea, lungs, and diaphragm, and their development and abnormalities of development are described. Pulmonary cystic disease forms one such group of developmental abnormalities and includes congenital lobar emphysema, congenital pulmonary adenomatoid malformation (CPAM), and pulmonary sequestration. Maturation of the lung can be terminated if delivery occurs early, leading to respiratory distress clinically, which has been ameliorated by antenatal steroids and antioxidants and postdelivery surfactant therapy. The causes and pathology of respiratory distress in the newborn are described; these include hyaline membrane disease and meconium aspiration syndrome, as well as rarer entities such as surfactant protein deficiency and alveolar capillary dysplasia. The clinical and pathology characteristics of chronic lung disease have changed over the last 20 years, and bronchopulmonary dysplasia, “old” and “new,” are described.
Article
Background: Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately one of every seven pregnancies, but only 5% of neonates exposed to meconium-stained amniotic fluid (MSAF) develop meconium aspiration syndrome. A fundamental question is why some infants exposed to meconium develop MAS, and others do not. Patients with MSAF have a higher frequency of intra-amniotic infection/inflammation than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF. Objective: To investigate whether intra-amniotic inflammation and funisitis, the histopathological landmark of a fetal inflammatory response, predispose to MAS. Study design: A prospective cohort study was conducted from 1995-2009. Amniotic fluid (AF) samples (n=1,281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intra-amniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 (MMP-8) was >23 ng/ml. Funisitis was diagnosed upon histologic examination if inflammation was present in the umbilical cord. Results: The prevalence of MSAF was 9.2% (118/1,281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each p >0.1). Mothers whose newborns developed MAS had a higher median AF MMP-8 (456.8 ng/ml vs. 157.2 ng/ml; p<0.05). Newborns exposed to intra-amniotic inflammation had a higher rate of MAS than those who were not exposed to intra-amniotic inflammation [13.0% (10/77) vs. 0% (0/32), p=0.03], as were those exposed to funisitis [31.3% (5/16) vs. 7.3% (6/82), RR 4.3 (95%CI 1.5-12.3)]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intra-amniotic inflammation and funisitis than in those without intra-amniotic inflammation and funisitis [28.6% (4/14) vs. 0% (0/28), p=0.009], while the rate of MAS did not show a significant difference between patients with intra-amniotic inflammation alone (without funisitis) and those without intra-amniotic inflammation and funisitis [10.9% (5/46) vs. 0% (0/28); p=0.15)]. Conclusion: The combination of intra-amniotic inflammation with fetal systemic inflammation is an important antecedent of MAS. This concept has implications for the understanding of the mechanisms of disease responsible for MAS and for the development of prognostic models for this disorder, as well as therapeutic interventions.
Article
In developing countries, meconium aspiration syndrome (MAS) is an important cause of morbidity and mortality among neonates. The concepts of pathophysiology and management of meconium stained amniotic fluid (MSAF) and meconium aspiration syndrome have undergone tremendous change in recent years. Routine intranatal and postnatal endotracheal suctioning of meconium in vigorous infants is no longer recommended. Recent studies have challenged its role even in non-vigorous infants. Supportive therapy like oxygen supplementation, mechanical ventilation and intravenous fluids are the cornerstone in the management of meconium aspiration syndrome. Availability of surfactant, inhaled nitric oxide, high frequency ventilators and extracorporeal membrane oxygenation has made it possible to salvage more infants with meconium aspiration syndrome. In this review the authors have discussed the current concepts in the pathophysiology and management of MAS. Drugs in trials and future therapeutic targets are also discussed briefly.
Article
The focus of this article will be to critically assess the nursing care provided to an infant, “James”, with meconium stained aspiration (MAS) and persistent pulmonary hypertension (PPHN) with particular regard to James's hypercapnia, hypoxia, tachypnoea, low mean systemic blood pressure (BP), low pre and post ductal oxygen saturations and cool extremities. The hypercapnia, hypoxia and tachypnoea and underlying physiological mechanisms will be related to the pathophysiology of MAS, and the low mean systemic BP, oxygen saturations and cool extremities will be related to the PPHN. Knowledge of the underlying physiological mechanisms which will then be used to discuss the nursing care provided, and the impact it had on James's condition. The overarching aim of nursing care was to reduce James's need for respiratory support and return his blood gases to normal. The interventions that supported this such as positioning, fluid balance and comfort measures will be looked at in more detail. Other aspects, including drugs that were used will also be discussed.
Article
Objective: To assess the correlation between total Area Under the Curve (AUC) of decelerations and accelerations and neonatal acidemia in pregnancies complicated with meconium-stained amniotic fluid (MSAF). Methods: A retrospective cohort study was conducted among women who delivered with a diagnosis of MSAF. Electronic fetal monitoring (EFM) patterns 120 minutes before delivery were interpreted by a researcher blinded to fetal outcomes. The primary outcome was fetal acidemia, defined as umbilical artery pH below 7.10. The correlation was tested using the Spearman correlation coefficient. Results: There were 102 women included; 24 delivered infants with cord blood pH <7.20, and only 5 delivered infants with cord blood pH <7.10. A significant correlation was demonstrated between total AUC of decelerations and accelerations and cord blood pH (P=0.02). A sub-analysis according to gestational age at delivery (up to and beyond 40 weeks of gestation) was conducted. A significant correlation was demonstrated (P=0.02) only in the term group(N=37). Conclusion: A correlation was demonstrated between total AUC of decelerations and accelerations and cord blood pH in neonates with MSAF. This correlation was significant for neonates delivered before 40 weeks of gestation, but not for those delivered after 40 weeks of gestation.
Article
Purpose of study To assess the maternal and perinatal complications associated with meconium-stained amniotic fluid (MSAF) in low-risk women in labor. Methods This prospective cohort study was conducted at CMC Hospital, Vellore, India. Two hundred low-risk women who had artificial or spontaneous rupture of membranes after admission with MSAF were included in the study. Two hundred similar women with clear liquor were taken as controls. The primary outcomes considered were the incidence of chorioamnionitis and endomyometritis in the mothers. The secondary outcomes included postpartum hemorrhage and retained placenta in the mothers and respiratory distress, meconium aspiration, sepsis, and NICU admission in the newborn. Statistical analysis was done using Fischer exact test. Odds ratio, 95% confidence interval, and P value were estimated. Results Compared to controls, those with MSAF had significantly higher rates of chorioamnionitis (2 vs. 8%, P = 0.006) and endomyometritis (3 vs. 9.5% P = 0.007). Among the secondary end points, only neonatal respiratory distress (8.5 vs. 1.5%; P = 0.001) and meconium aspiration (4 vs. 0%; P = 0.007) were found to be significantly increased in the meconium group. Conclusion Statistically significant increased incidence of chorioamnionitis and endomyometritis in women with MSAF in labor established in our study strongly supports the use of prophylactic antibiotics in these women to prevent immediate and long-term consequences.
Article
Objective: To investigate the association between meconium-stained amniotic fluid (MSAF) and postcesarean surgical site infections. Methods: This was a secondary analysis of the Maternal Fetal Medicine Units Network (MFMU) Cesarean Registry. Women with a singleton pregnancy attempting labor or induction of labor, who ultimately had a cesarean delivery, were included in the study. Pregnancies complicated by MSAF (n = 4262) and those who did not have MSAF (n = 13 850) were compared. The primary outcome was the incidence of SSI. Results: A total of 18 112 patients were included in the study. 4262 (38%) had meconium-stained amniotic fluid. After accounting for potential confounders in a multivariable logistic regression, meconium-stained amniotic fluid was associated with an increased risk of postoperative surgical site infection (Odds Ratio 1.16, 95% CI 1.03–1.30). Conclusions: Meconium-stained amniotic fluid may be associated with an increased risk of postoperative surgical site infection.
Article
Background Movement complexity and the presence of fidgety movements (FMs) during general movements (GMs) both reflect aspects of neurological integrity in early infancy. Aim To assess interrelations between the degree of movement complexity and characteristics of FMs during typical GMs and to investigate associations between mildly impaired GMs and risk factors and neurodevelopmental condition. Study design Observational cohort study. Subjects 283 infants (25 born preterm) at 2–4 months corrected age, representative of the general Dutch population. Outcome measures GMs were classified in terms of GM-complexity (normal or mildly abnormal (MA)) and FMs (clearly present, sporadic, or exaggerated). Concurrent neurological, developmental and socio-emotional status were measured with the Standardized Infant NeuroDevelopmental Assessment (SINDA). Results Infants with MA GM-complexity had a higher risk of having sporadic FMs and exaggerated FMs. Perinatal complications were not associated with mildly impaired GMs. MA GM-complexity was associated with advanced maternal age (adjusted OR = 2.29 [1.11, 4.76]) and having a non-native Dutch mother (adjusted OR = 2.93 [1.29, 6.64]). It was also associated with atypical neurological (OR = 7.62 [3.51, 16.54]) and developmental scores (OR = 2.38 [1.16, 4.88]). Sporadic and exaggerated FMs were associated with low-to-middle maternal education (adjusted OR = 2.88, [1.45, 5.72]) and having a non-native Dutch father (adjusted OR = 7.16 [1.41, 36.32]), respectively. However, neither sporadic nor exaggerated FMs were associated with the SINDA outcomes. Conclusions GM-complexity and FMs are two interrelated but different aspects of GMs. Mild impairments in GM-complexity and FMs share a non-optimal socio-economic background as risk factor, but only MA GM-complexity is associated with a concurrent non-optimal neurodevelopmental condition.
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The first demonstrable meconium is found around the third month of the gestational age in the intestines of the fetus as black green color, odorless mass. Multiple conditions of intrauterine fetal distress is said to be causative reason for intrauterine passage of meconium in the amniotic fluid by the fetus. Aspiration of meconium stained amniotic fluid may lead to a gasping breathing pattern which induces hypoxia via airway obstruction, surfactant dysfunction, chemical pneumonitis, and pulmonary hypertension. The aim of the present study was to find the prevalence of various grades of meconium stained amniotic fluid as well as meconium aspiration syndrome according to gestational age and parity. The present study was a prospective observational study. It was conducted in the Obstetrics and Gynecology department of Tertiary Hospital & Medical Collage & Research Centre, Ahmedabad, Gujarat, India during May 2016 to May 2018 on 200 laboring mothers with meconium stained amniotic fluid who delivered or underwent cesarean section in the institute were included in the study. MSAF grade 1 cases were maximum 40/82(48.78%) in mothers having previous vaginal delivery. MSAF grade 2 cases were maximum 51/63(80.95%) in primigravid mothers. MSAF grade 3 cases were maximum 24/55(43.64%) in primigravid mothers. 3.96% of the primigravida patients were found to have MAS whereas 15.38% of the patients with previous vaginal delivery were having MAS. Maximum cases of grade 1 MSAF 64/82(78.05%), grade 2 MSAF 40/63(63.49%) as well as grade 3 MSAF 26/55(47.27%) were in mothers having gestational age between 37-40 weeks at the time of delivery of baby. 45.45% patients having gestational age less than 37 weeks, 4.62% of the patients having gestational age between 37-40 weeks, and 6.78% patients having gestational age greater than 40 weeks were having MAS.
Article
Background: The results differ among published studies regarding exposure to meconium and the risk of developing autism spectrum disorders (ASDs). Purpose: The present study pooled all of the epidemiologic studies retrieved from broader databases on the association between meconium exposure and risk of developing ASD in children. Methods: The Web of Science, PubMed, Scopus, and Google Scholar databases were searched without language restrictions for articles published between their inception to February 20, 2020, using relevant keywords. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated as random-effect estimates of the associations among studies. A subgroup analysis was conducted to explore any potential sources of heterogeneity among studies. Results: The pooled estimate of OR reported a weakly significant association between meconium exposure and ASD development in children (OR, 1.13; 95% CI, 1.03-1.24). There was low heterogeneity among the articles reporting risk for ASD among children (I2=19.3%; P=0.259). The results of subgroup analysis based on meconium exposure showed a significant association between a meconium-stained neonate and ASD development (OR, 1.18; 95% CI, 1.11-1.24). Conclusion: Meconium exposure was weakly associated with an increased risk of ASD. However, more evidence based on large prospective cohort studies is required to provide conclusive evidence about whether meconium exposure is associated with an increased risk of ASD development.
Article
Objective To evaluate the impact of prolonged exposure to meconium-stained amniotic fluid (MSAF), in women with term pre-labor spontaneous rupture of membranes (PROM), on pregnancy outcome. Methods A retrospective cohort study of women who gave birth in a single university-affiliated tertiary medical center (2011–2019). Eligibility was limited to singleton pregnancies at term who presented with PROM. Women with MSAF were immediately induced and were compared to low-risk pregnant women with clear amniotic fluid (CAF) at admission who underwent induction of labor 24 h after rupture of membranes. All women were stratified into 4-time frame groups from rupture of membranes to delivery: T0: 0–7 h, T1: 8–13 h, T2: 14–18 h, and T3: > 18 h for the MSAF group. The time frames for the CAF were: T0 – 24–31 h, T1: 32–38 h, T2: 40–44 h, and T3: > 44 h. The maternal adverse composite outcome included any of the following: intrapartum fever (IPF), prolonged second stage (PSS), need for manual removal of suspected retained placenta, postpartum hemorrhage, and readmission within 45 days after delivery. The adverse composite neonatal outcome included one or more of the following: meconium aspiration syndrome, neonatal asphyxia, need for respiratory support, and intracranial hemorrhage. Results Overall, 1631 women met the inclusion criteria (536 in the MSAF and 1095 in the CAF group). Both groups showed a gradual decrease in the rate of vaginal delivery over time, the vaginal delivery rate in the MSAF group was 75.7% at T0 in comparison to 61.6% at T3 (p < .001). In the CAF group, the vaginal delivery rate was 84.5% at T0 in comparison to 68.8% at T3 (p < .001). This decrease was in concomitance with an increase in the rates of prolonged second-stage and intrapartum fever. There were no significant differences in the rates of postpartum hemorrhage, suspected retained placenta, or readmission within 45 days between women with either MSAF or CAF. There was a significant gradual increase in the adverse composite neonatal outcome in the MSAF group (1.9% at T0, 5.2% at T1, 6.0% at T2, and 8.2% at T3. p = .038). No similar increase was found in the CAF group (2.5% at T0, 4.1% at T1, 2.6% at T2, and 4.1% at T3. p = .449). Conclusion Prolonged rupture of membranes in the presence of meconium does not affect maternal outcomes, however, prolonged exposure to meconium lead to an increased adverse neonatal outcome.
Article
Objective: Stillbirth is one of the most devastating adverse pregnancy outcome, but it is often associated with a missing post-mortem histological examination. We aimed at evaluating whether the staining of amniotic fluid reflects the fetal conditions surrounding the death and if it correlates with any histologic sign of fetal distress. Study design: Terminal gasping (represented by the massive presence of intra-alveolar squamous cells), thymic and adrenal cortex modifications were evaluated as histologic signs of fetal distress in stillbirths, and stratified according to the degree of staining of the amniotic fluid. Results: The presence of meconium-stained amniotic fluid did not correlate with the presence of gasping and/or thymic and/or adrenal cortex changes. Clear amniotic fluid was not associated with the absence of histologic signs of distress. Conclusions: The evaluation of the staining of the amniotic fluid fails to identify distressed fetuses. A histologic evaluation of fetal organs provides detailed information, irrespective of the presence/absence of meconium-stained amniotic fluid.
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To determine the foetal outcome and mode of delivery in patients with meconium stained liquor during labour. The observational study was carried out at the Obstetrics and Gynaecology Unit-II of Liaquat University of Medical Health Sciences from June to November 2007. The patients with gestational age more than 37 weeks who presented with meconium stained liquor and cephalic presentation were included and the foetal outcome and mode of delivery was assessed in all such subjects. The data was collected on pre-designed proforma and analysed using SPSS version 10. Chi square test was applied with 95% confidence interval and p-value < or = 0.05 was considered significant. A total of 75 patients with meconium stained liquor were identified during the study period. The patients with reactive cardiotocography (CTG) were 50 (66.7%) and with non-reactive CTG, 25 (33.36%). Of the total, 45 (60%) patients were delivered through normal vaginal delivery, while 30 (40%) were delivered by caesarean section. The rate of instrumental delivery was also increased which was 12 (26.7%). Among the neonates exposed to meconium stained liquor, 62 (82.7%) babies were delivered with apgar score > 7. Only 13 (17.3%) babies were delivered with apgar score < 7 in one minute. Meconium stained amniotic fluid is a common occurrence during labour and is associated with increased caesarean section rate and foetal morbidity and mortality.
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Objective: To determine the outcome of the babies in terms of mortality with the diagnosis of Meconium Aspiration Syndrome (MAS). Study Design: An observational study. Place and Duration of Study: The Neonatal Unit of Services Institute of Medical Sciences and Services Hospital, Lahore, Pakistan, from February 2008 to January 2009. Methodology: All the babies admitted to the neonatal unit during the period of study with the diagnosis of MAS were included. At admission, demographic, maternal, antenatal and natal data were recorded on a specific form. The progress of the baby, including need for ventilation, medications, complications and outcome were also followed and documented. Results: One hundred and nine babies admitted with MAS, 32% died. Most of the babies (n=73) were admitted from our obstetrical unit and the rest through the emergency department. Majority (60 of 109) were admitted within the 1st hour of life. Most (14 of 15) of the newborns requiring intubation within 1st hour of life, died. Forty four babies were ventilated and 35 of these babies succumbed. Of ventilated babies, 11 developed pneumothoraces. Seventy two percent (13 out of 18) of expired babies stayed for less than 24 hours. Conclusion: Mortality rate for MAS was higher in the study group as compared to international figures. It was especially high in babies requiring mechanical ventilation in 1st hour of life or with co-existing severe hypoxic ischemic encephalopathy.
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To determine the outcome of the babies in terms of mortality with the diagnosis of Meconium Aspiration Syndrome (MAS). An observational study. The Neonatal Unit of Services Institute of Medical Sciences and Services Hospital, Lahore, Pakistan, from February 2008 to January 2009. All the babies admitted to the neonatal unit during the period of study with the diagnosis of MAS were included. At admission, demographic, maternal, antenatal and natal data were recorded on a specific form. The progress of the baby, including need for ventilation, medications, complications and outcome were also followed and documented. One hundred and nine babies admitted with MAS, 32% died. Most of the babies (n=73) were admitted from our obstetrical unit and the rest through the emergency department. Majority (60 of 109) were admitted within the 1st hour of life. Most (14 of 15) of the newborns requiring intubation within 1st hour of life, died. Forty four babies were ventilated and 35 of these babies succumbed. Of ventilated babies, 11 developed pneumothoraces. Seventy two percent (13 out of 18) of expired babies stayed for less than 24 hours. Mortality rate for MAS was higher in the study group as compared to international figures. It was especially high in babies requiring mechanical ventilation in 1st hour of life or with co-existing severe hypoxic ischemic encephalopathy.
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To determine the effect of clear liquor and meconium stained liquor on mode of delivery, and to evaluate neonatal outcome. It was a Cross sectional analytical study, conducted in the department of Obstetrics and Gynaecology, Shaikh Zyed Federal Postgraduate Medical Institute/Hospital, Lahore and Shaikh Zaid Women Hospital Larkana, from April 2006 to March 2007. Two hundred and fifty patients from Larkana and 250 patients from Lahore in clear liquor group were included in the study. Similarly 125 patients from each city, that is 250 patients which had meconium stained liquor were included in group 2. The subjects with meconium stained amniotic fluid and clear amniotic fluid were registered as group 1 and 2. The socio demographic information, fertility history and gestational age of subjects were recorded. The investigations and information regarding mode of delivery and duration of labour were also noted. All babies delivered were attended by paediatricians. In this study 500 cases with clear liquor and 250 cases of meconium stained liquor were selected from two cities, Lahore and Larkana. Out of these 55 (22%) patients had grade I meconium stained liquor, 140 (56%) patients and 55 (22%) patients had grade II and grade III meconium stained liquor respectively. The mode of delivery is significantly affected by meconium staining of liquor. The effect of meconium stained liquor was significant on time of delivery. There were 40 (16%) post date deliveries in meconium stained liquor as compared to 1% in subjects with clear liquor. The effect of meconium staining of liquor was significant on Apgar score, neonatal admission, meconium aspiration syndrome and neonatal deaths. Meconium stained amniotic fluid (MSAF), is associated with increased neonatal morbidity and mortality. Caesarean sections were performed twice as frequently in women presenting with MSAF.
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According to the current concepts, the human fetus does not defecate, and passage of meconium into the amniotic fluid is an indicator of fetal distress. However, the literature consists of reports in which fetal defecation is postulated to be a physiologic event. In light of these reports and our observation, we have developed the hypothesis that fetal defecation is a physiologic event independent from fetal distress and associated with a clearance mechanism of the amniotic fluid. This hypothesis has been proved by a series of experimental studies. We have shown that goat fetuses defecate the contrast medium into the amniotic cavity in the absence of fetal distress. We have clearly demonstrated for the first time the transport of radioactive meconium through the gastrointestinal tract into the amniotic fluid by using a radiopharmaceutical agent. It is known that the clearance mechanism of the amniotic fluid is suppressed under fetal distress conditions. We suggest that meconium stained amniotic fluid is not related to meconium passage due to fetal distress; rather, it reflects impaired clearance of amniotic fluid containing meconium because of physiologic in utero defecation. This is discussed in detail with a review of the literature.
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Evidence exists that normal gestational length varies with ethnicity. This UK-based study compares gestational length amongst a cohort of white European, Black and Asian women. The cohort comprised 122 415 nulliparous women with singleton live fetuses at the time of spontaneous labour, giving birth in the former North West Thames Health Region, London, UK. The median gestational age at delivery was 39 weeks in Blacks and Asians and 40 weeks in white Europeans. Black women with normal body mass index (BMI) (18.5-24.9 kg/m(2)) had increased odds of preterm delivery (odds ratio [OR] = 1.33, 95% CI: 1.15, 1.56, adjusted for deprivation and BMI) compared with white Europeans. The OR of preterm delivery was also increased in Asians compared with white Europeans (OR = 1.45, 95% CI: 1.33, 1.56, adjusted for single unsupported status and smoking). Meconium stained amniotic fluid, which is a sign of fetal maturity, was statistically significantly more frequent in preterm Black and Asian infants and term Black infants compared with white European infants. This research suggests that normal gestational length is shorter in Black and Asian women compared with white European women and that fetal maturation may occur earlier.
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ACOG states meconium stained amniotic fluid (MSAF) as one of the historical indicators of perinatal asphyxia. Thick meconium along with other indicators is used to identify babies with severe intrapartum asphyxia. Lactate creatinine ratio (L:C ratio) of 0.64 or higher in first passed urine of babies suffering severe intrapartum asphyxia has been shown to predict Hypoxic Ischaemic Encephalopathy (HIE). Literature review shows that meconium is passed in distress and thin meconium results from mixing and dilution over time, which may be hours to days. Thin meconium may thus be used as an indicator of antepartum asphyxia. We tested L:C ratios in a group of babies born through thin and thick meconium, and for comparison, in a group of babies without meconium at birth. 86 consecutive newborns, 36 to 42 weeks of gestation, with meconium staining of liquor, were recruited for the study. 52 voided urine within 6 hours of birth; of these 27 had thick meconium and 25 had thin meconium at birth. 42 others, who did not have meconium or any other signs of asphyxia at birth provided controls. Lactate and creatinine levels in urine were tested by standard enzymatic methods in the three groups. Lactate values are highest in the thin MSAF group followed by the thick MSAF and controls. Creatinine was lowest in the thin MSAF, followed by thick MSAF and controls. Normal babies had an average L:C ratio of 0.13 (+/- 0.09). L:C ratio was more among thin MSAF babies (4.3 +/- 11.94) than thick MSAF babies (0.35 +/- 0.35). Median L:C ratio was also higher in the thin MSAF group. Variation in the values of these parameters is observed to be high in the thin MSAF group as compared to other groups. L:C ratio was above the cutoff of 0.64 of Huang et al in 40% of those with thin meconium. 2 of these developed signs of HIE with convulsions (HIE Sarnat and Sarnat Stage II) during hospital stay. One had L:C Ratio of 93 and the other of 58.6. A smaller proportion (20%) of those with thick meconium had levels above the cutoff and 2 developed HIE and convulsions with L:C ratio of 1.25 and 1.1 respectively. In evolving a cutoff of L:C ratios that would be highly sensitive and specific (0.64), Huang et al studied it in a series of babies with severe intrapartum asphyxia. Our study shows that the specificity may not be as good if babies born through thin meconium are also included. L:C ratios are much higher in babies with thin meconium. It may be that meconium alone is not a good indicator of asphyxia and the risk of HIE. However, if the presence of meconium implies asphyxia then perhaps a higher cut-off than 0.64 is needed. L:C ratios should be tested in a larger sample that includes babies with thin meconium, before L:C ratios can be applied universally.
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The goal of this study was to determine if meconium staining of the amniotic fluid (MSAF) is a marker for chorioamnionitis. In a retrospective, case-control investigation, we studied 100 patients with MSAF. Each patient was matched with a control who delivered during the same period but did not have MSAF. Subjects and controls were matched for age, parity, gestational age, mode of delivery, duration of rupture of membranes (ROM), length of internal monitoring, and number of examinations before and after ROM. The incidence of chorioamnionitis in controls and study patients was compared. The diagnosis of chorioamnionitis was based on clinical examination. Thirteen of the 200 patients [6.5%, 95% confidence interval (CI), 2.5-10.5%] developed chorioamnionitis. Of the 100 women with MSAF, 10 (10%, 95% CI, 4-16) were infected compared with only 3 controls (3%, 95% CI, 0-6, P = 0.04). The odds ratio (OR) for this comparison was 3.3, and the 95% CI was 1.02-10.63. MSAF is associated with an increased frequency of chorioamnionitis. Several factors could explain this association. Infection may cause fetal stress, leading to the release of meconium. MSAF may enhance the growth of bacteria by providing a rich medium of essential nutrients or growth stimulants. MSAF also may impair the host immune system so that chemotaxis or phagocytosis is diminished, thus allowing accelerated growth of microorganisms.
Article
Objective: To test the hypothesis that the presence of meconium-stained amniotic fluid (AF) is associated with maternal and neonatal infection, both before and after delivery. Methods: Nine hundred thirty-six laboring women were analyzed for the presence of meconium in amniotic fluid and occurrence of peripartum infection. Meconium was assessed clinically as thin, moderate, or thick. Intra-amniotic infection and endometritis were diagnosed by standard defini tions. All patients were tested for vaginal group B streptococcus, bacterial vaginosis, and other aerobic organisms. Results: Meconium-stained AF was present in 28% of the study participants (9% thin, 12% moderate, 7% thick). The presence of meconium was associated with increased intraamniotic fluid (17% versus 9%, relative risk [RR] 1.98, 95% confidence interval [CI] 1.3, 3.1), endometritis (10% versus 5%, RR 2.38, 95% CI 1.3, 4.4), and total infection (25% versus 13%, RR 2.19, 95% CI 1.5, 3.2). Thick meconium had higher infection rates than clear AF (44% versus 13%, RR 5.18, 95% CI 2.9, 9.3). Meconium was associated independently with peripartum infection by multiple logistic regression (RR 1.28, 95% CI 1.1, 1.6). Conclusion: Meconium-stained AF is associated with increased peripartum infection, independent of other risk factors for infection. Thick meconium, in particular, is associated with a marked increase in peripartum infectious morbidity.
Article
Objective: To show that meconium causes fetal morbidity and death at earlier gestations than reported previously. Methods: We searched for specimens from 1997 and 1998 with pathologic diagnosis of meconium-induced umbilical vascular necrosis in placentas of nonmalformed fetuses and newborns. Because intra-amniotic infection is known to activate cytokines, and blood pigment is often microscopically indistinguishable from meconium, we removed those confounding considerations by excluding placentas with chorioamnionitis and signs of intra-amniotic bleeding. Light microscopic identification of vacuolar amniotic epithelial degeneration was used to select specimens with meconium because blood does not cause that histopathologic abnormality. We used histochemical procedures to show absence of hemosiderin and presence of bilirubin, and immunocytochemical labeling with interleukin-1β to show cytokine. Results: Four cases had meconium-induced umbilical vascular necrosis. The gestational ages were 16, 19, 29, and 38 weeks. Two cases were abortuses, the third was stillborn, and the fourth was a small-for-gestational-age liveborn, delivered by cesarean because of repetitive variable decelerations. Luna-Ishak staining showed bilirubin in macrophages between umbilical vascular myocytes and in the Wharton's jelly. Immunocytochemical methods showed interleukin-1β in those same macrophages. Conclusion: Cytokines and other meconium-associated factors may contribute to the pathogenesis of fetal death. Survivors may suffer intraventricular hemorrhage, periventricular leukomalacia, and other morbidity. Exposure of umbilical and superficial placental vessels to intra-amniotic meconium is ultimately complicated by vascular necrosis.1,2 Clinicopathologic correlations found that those lesions are variably associated with persistent fetal circulation, anoxic-ischemic encephalopathy, renal hemorrhage, liver necrosis, myocardial ischemic lesions, and necrotizing enterocolitis.3 The mechanism of fetal damage probably includes vasoactivity of the vessels before development of vascular necrosis. Benirschke4 affirmed that histopathology when he wrote, “I have observed the lesion many times and it was always associated with prolonged meconium discharge before birth.” Recently we observed severe meconium-induced umbilical vascular necrosis in all three vessels of the umbilical cord of a fetus whose gestational age was 16 weeks. The present study reports that meconium-induced umbilical vascular necrosis can occur in immature fetuses and associated cytokines might cause their deaths during or beyond the second trimester.
Article
Objective: To show that meconium causes fetal morbidity and death at earlier gestations than reported previously. Methods: We searched for specimens from 1997 and 1998 with pathologic diagnosis of meconium-induced umbilical vascular necrosis in placentas of nonmalformed fetuses and newborns. Because intra-amniotic infection is known to activate cytokines, and blood pigment is often microscopically indistinguishable from meconium, we removed those confounding considerations by excluding placentas with chorioamnionitis and signs of intra-amniotic bleeding. Light microscopic identification of vacuolar amniotic epithelial degeneration was used to select specimens with meconium because blood does not cause that histopathologic abnormality. We used histochemical procedures to show absence of hemosiderin and presence of bilirubin, and immunocytochemical labeling with interleukin-1 beta to show cytokine. Results: Four cases had meconium-induced umbilical vascular necrosis. The gestational ages were 16, 19, 29, and 38 weeks. Two cases were abortuses, the third was stillborn, and the fourth was a small-for-gestational-age liveborn, delivered by cesarean because of repetitive variable decelerations. Luna-Ishak staining showed bilirubin in macrophages between umbilical vascular myocytes and in the Wharton's jelly. Immunocytochemical methods showed interleukin-lp in those same macrophages. Conclusion: Cytokines and other meconium-associated factors may contribute to the pathogenesis of fetal death. Survivors may suffer intraventricular hemorrhage, periventricular leukomalacia, and other morbidity. (C) 1999 by The American College of Obstetricians and Gynecologists.
Article
Abstract OBJECTIVE: To compare pregnancy outcome between deliveries complicated by new onset of meconium during labor following prior evidence of clear amniotic fluid and labors in which meconium was present to begin with. A retrospective cohort study of all singleton term (≥37+0 weeks) deliveries complicated by intrapartum meconium stained amniotic fluid in a tertiary referral medical center during the year 2012. Outcome was compared between deliveries with new onset of meconium during labor following prior evidence of clear amniotic fluid (secondary meconium group) and those in which meconium was already evident at the time of membranes rupture (primary meconium group). Of the 9,167 deliveries during the study period, 694 were eligible for the study group. Of these, 537 were complicated by primary meconium and 157 by secondary meconium. Only secondary meconium, but not primary meconium, was independently associated with an increased risk of operative vaginal delivery (OVD) and adverse neonatal outcome. Pregnancies complicated by secondary meconium were independently associated with a higher rate of OVD (28.0% vs. 11.4%, P<0.001), POP position of the fetal head (6.4% vs.2.6%, P=0.02), and adverse neonatal outcome (17.2% vs. 8.9%, P=0.003). Secondary meconium is associated with a higher rate of adverse obstetrical and neonatal outcome compared with primary meconium.
Article
Aim: To compare hepcidin and erythropoietin levels in the cord blood of neonates with meconium-stained amniotic fluid (MSAF) to levels obtained from age-, body mass index- and gravidity-matched neonates with clear amniotic fluid. Methods: A cross-sectional controlled study was conducted in secondary and tertiary care centers. Cord blood samples of 40 neonates following term gestations (≥37 weeks' gestation) with MSAF and 40 maternal age-, body mass index- and gravidity-matched controls with clear amniotic fluid were analyzed in this study. Demographic data, delivery outcomes and laboratory evaluations were recorded. Results: Cord blood pH levels were lower in fetuses with MSAF when compared to those with clear amniotic fluid (P=0.0001). Fetuses with MSAF had higher cord blood erythropoietin levels in comparison to those with clear amniotic fluid (P=0.0001). Delivery outcomes and hepcidin measurements were similar in both groups. Conclusions: We demonstrated a significant relationship between erythropoietin levels and meconium passage, but failed to show the existence of a relationship between hepcidin levels and meconium passage.
Article
The cause of meconium stained amniotic fluid in term healthy pregnancies is not clearly understood yet. The aim of this study was to investigate the placental ultrastructural changes and placental apoptosis in pregnancies complicated with meconium stained amniotic fluid. The study group was composed of mothers (n: 13) and their term, appropriate for gestational age newborns with meconium stained amniotic fluid but without meconium aspiration syndrome. The control group consisted of mothers (n: 24) and their term appropriate for gestational age babies. We studied placental ultrastructural changes by transmission electron microscopy and placental apoptosis by transmission electron microscopy and the TUNEL method. The incidence of placental apoptosis by the TUNEL method was significantly higher in the study group compared to the control group. Transmission electron microscopy investigation revealed more remarkable ultrastructural changes in the study group compared to the control group. The increased apoptosis and ultrastructural findings in placentas with meconium stained amniotic fluid may be related to the placental adaptation to the hypoxic fetuses.
Article
To determine the time trends and risk factors for intrapartum fetal death (IPFD). A case-control study comparing pregnancies with and without IPFD between the years 1988 and 2008 was conducted. A multiple logistic regression model was used to determine the risk factors for IPFD. During the study period, 204,102 singleton births were analyzed; of these, 110 IPFD cases occurred. The following independent risk factors were identified: Bedouin ethnicity (OR = 1.85, 95% CI 1.22-2.8), malpresentations (OR = 2.76, 95% CI 1.71-4.47), gestational age (OR = 0.72, 95% CI 0.69-0.76), polyhydramnios (OR = 3.49, 95% CI 1.94-6.26), meconium-stained amniotic fluid (OR = 3.18, 95% CI 2.01-5.05), umbilical cord prolapse (OR = 6.64, 95% CI 2.79-15.78), placental abruption (OR = 3.24, 95% CI 1.73-6.04), uterine rupture (OR = 38.59, 95% CI 10.58-140.71) and congenital malformations (OR = 2.41, 95% CI 1.47-3.97). A gradual decline over the years in the rate of IPFD was noted in the Bedouin population. No significant association was noted in the prevalence of IPFD during the weekends as compared to the week days (OR = 0.85; 95% CI 0.54-1.32; P = 0.475). Independent risk factors for IPFD are preterm birth, malpresentation, polyhydramnios, meconium-stained amniotic fluid, umbilical cord prolapse, placental abruption, uterine rupture, congenital malformations and Bedouin ethnicity. Weekends do not pose additional risk for the occurrence of IPFD.
Article
To test the hypothesis that the presence of meconium-stained amniotic fluid (AF) is associated with maternal and neonatal infection, both before and after delivery. Nine hundred thirty-six laboring women were analyzed for the presence of meconium in amniotic fluid and occurrence of peripartum infection. Meconium was assessed clinically as thin, moderate, or thick. Intra-amniotic infection and endometritis were diagnosed by standard definitions. All patients were tested for vaginal group B streptococcus, bacterial vaginosis, and other aerobic organisms. Meconium-stained AF was present in 28% of the study participants (9% thin, 12% moderate, 7% thick). The presence of meconium was associated with increased intra-amniotic fluid (17% versus 9%, relative risk [RRI 1.98, 95% confidence interval [CI] 1.3, 3.1), endometritis (10% versus 5%, RR 2.38, 95% CI 1.3, 4.4), and total infection (25% versus 13%, RR 2.19, 95% CI 1.5, 3.2). Thick meconium had higher infection rates than clear AF (44% versus 13%, RR 5.18, 95% CI 2.9, 9.3). Meconium was associated independently with peripartum infection by multiple logistic regression (RR 1.28, 95% CI 1.1, 1.6). Meconium-stained AF is associated with increased peripartum infection, independent of other risk factors for infection. Thick meconium, in particular, is associated with a marked increase in peripartum infectious morbidity.
Article
The purpose of this study was to determine whether there is a relationship between the frequency of meconium-stained amniotic fluid (MSAF) and the duration of labor in term singleton gestation. The clinical characteristics of women who delivered term singleton live newborns between 2001 and 2006 were examined. The cases involving neonates with major congenital anomalies were excluded. (1) The frequency of MSAF in term pregnancies was 18.4% (806/4376); (2) MSAF was found in only 2.8% (28/1008) of women who delivered by elective cesarean, but in 23.1% (778/3368) of women who delivered after the onset of labor (p < 0.001); (3) The longer the duration of labor (first stage, second stage, or total), the higher the frequency of MSAF (p < 0.001 for each); this remained significant after adjusting for other confounding variables such as parity, duration of rupture of membranes, gestational age at delivery, and mode of delivery (p < 0.001 for each). MSAF was found in only 2.8% (28/1008) of women who delivered before the onset of labor, but in 23.1% (778/3368) of women who delivered after the onset of labor. The longer the duration of labor, the higher the risk of MSAF in term singleton gestation.
Article
To estimate the rates of meconium-stained amniotic fluid (AF) and adverse outcome in relation to gestational age and racial group, and to investigate the predictors of meconium-stained AF. We studied 499,096 singleton births weighing at least 500 g, at 24 or more weeks of gestation, from 1988 to 2000. The predictors of meconium-stained AF from 37 weeks of gestation onward were determined using multiple logistic regression. The crude meconium-stained AF rates in preterm, term, and postterm births were 5.1% (95% confidence interval [CI] 4.9-5.4), 16.5% (95% CI 16.4-16.6), and 27.1% (95% CI 26.5-27.6), respectively; the rates in blacks, South Asians, and whites were 22.6% (95% CI 22.2-23.1), 16.8% (95% CI 16.5-17.1), and 15.7% (95% CI 15.6-15.8), respectively. Independent predictors of meconium-stained AF included being black (odds ratio [OR] 8.4, 95% CI 2.4-28.8), vaginal breech delivery (OR 4.7, 95% CI 4.2-5.3), being South Asian (OR 3.3, 95% CI 1.3-8.3), and being in an advancing week of gestation (OR 1.39, 95% CI 1.38-1.40). More blacks (17.9%, 95% CI 17.3-18.4) and South Asians (11.8%, 95% CI 11.5-12.1) with good outcome and no risk factors for fetal hypoxia had meconium-stained AF than did whites (11.2%, 95% CI 11.1-11.4). Using white neonates born at 40 weeks as reference, the absolute risk of adverse outcome at 41 and 42 weeks were 2% and 5% in whites, 3% and 7%, in South Asians, and 7% and 11% in blacks. Meconium-stained AF rates are different among races and across gestational age, and overall risk of adverse outcomes in meconium stained AF is low. II.
Article
Background: Chorioamnionitis is more likely to occur when meconium-stained amniotic fluid (MSAF) is present. Meconium may enhance the growth of bacteria in amniotic fluid by serving as a growth factor, inhibiting bacteriostatic properties of amniotic fluid. Many adverse neonatal outcomes related to MSAF result from meconium aspiration syndrome (MAS). MSAF is associated with both maternal and newborn infections. Antibiotics may be an effective option to reduce such morbidity. Objectives: The objective of this review is to assess the efficacy and side effects of prophylactic antibiotics for MSAF during labour in preventing maternal and neonatal infections. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014). Selection criteria: Randomised controlled trials (RCTs) comparing prophylactic antibiotics with placebo or no treatment during labour for women with MSAF. Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Main results: We included two studies with 362 pregnant women. Both studies compared ampicillin-sulbactam (N = 183) versus normal saline (N = 179) in pregnant women with MSAF. Prophylactic antibiotics appeared to have no statistically significant reduction in the incidence of neonatal sepsis (risk ratio (RR) 1.00, 95% CI 0.21 to 4.76), neonatal intensive care unit (NICU) admission (RR 0.83, 95% CI 0.39 to 1.78) and postpartum endometritis (RR 0.50, 95% CI 0.18 to 1.38). However, there was a significant decrease in the risk of chorioamnionitis (RR 0.36, 95% CI 0.21 to 0.62). No serious adverse effects were reported. Drug resistance, duration of mechanical ventilation and duration of admission to NICU/hospital were not reported. Most of the domains for risk of bias were at low risk of bias for one study and at unclear risk of bias for the other study. The quality of the evidence using GRADE was low for neonatal sepsis, postpartum endometritis, and neonatal mortality and morbidity prior to discharge (Neonatal intensive care admissions) and of moderate quality for chorioamnionitis. Authors' conclusions: Current evidence indicates that compared to placebo, antibiotics for MSAF in labour may reduce chorioamnionitis. There was no evidence that antibiotics could reduce postpartum endometritis, neonatal sepsis and NICU admission. This systematic review identifies the need for more well-designed, adequately powered RCTs to assess the effect of prophylactic antibiotics in the incidence of maternal and neonatal complications.
Article
The positive role and application of highly accurate mass measurements in proteomics is well documented. The new generation of hybrid FTMS and Q-TOF instruments, including the LTQ-Orbitrap (OT), is remarkable in their ability to routinely produce single-digit to subppm statistical mass accuracy while maintaining high analytical sensitivity. The use of mass calibrants (lock masses) to reduce the systematic error of mass-to-charge measurements has also been reported and, in some cases, incorporated in the instrument control software by the instrument manufacturers. We evaluated the use of one such calibrant in the OT (e.g., polydimethylcyclosiloxane, PCM) to study its impact on the rate of phosphopeptide annotation and found it to lack robustness under normal laboratory conditions. Therefore, we devised a strategy to improve its performance by increasing the external abundance of calibrant molecules in laboratory air. This resulted in a more robust performance of the preprogrammed lock mass recalibration feature as evidenced by improvements in both statistical mass accuracy and peptide annotation rates.
Article
Chronic fetal hypoxemia stimulates erythropoiesis and may result in a redistribution of fetal iron from plasma into erythrocytes. We studied the response of fetal plasma erythropoietin (Ep) to hypoxemia, the role of Ep in stimulating erythropoiesis in utero, and the effect of augmented erythropoiesis on fetal plasma Ep and iron and tissue cytochrome c concentrations in 19 chronically instrumented late-gestation fetal sheep. The fetuses were stimulated to produce 28 erythropoietic responses after exposure to 1) acute hypoxemia (1-5 days), 2) chronic hypoxemia (greater than 7 days), and/or 3) administration of 1,500 U recombinant human Ep concurrently during normoxemia. Plasma Ep peaked less than 12 h after the onset of hypoxemia or Ep bolus. Plasma iron decreased 24-48 h later and returned to baseline 48-96 h after normalization of Ep levels to baseline. The plasma iron response was directly related to the erythropoietin stimulus (r = 0.79, P less than 0.001) and inversely related to liver iron concentration at death (r = -0.84, P less than 0.001). Nine fetuses with depleted liver iron concentrations at autopsy had significantly lower heart and skeletal muscle iron concentrations compared with animals with 10% of control liver iron remaining. Skeletal muscle and heart iron and cytochrome c concentrations were significantly correlated. Ep has a potent biological effect on fetal erythropoiesis and iron metabolism. Augmented fetal erythropoiesis, mediated by Ep, results in decreased plasma iron, hepatic storage iron, and skeletal and cardiac muscle iron and cytochrome c. The model potentially explains the iron abnormalities found in newborn infants after fetal hypoxia.
Article
A new stress model in rats produced changes in intestinal function that resemble patterns of intestinal dysfunction associated with stress in humans: small intestinal transit was inhibited, large intestinal transit was stimulated, and fecal excretion was stimulated. To evaluate the role of corticotropin-releasing factor (CRF) in mediating the effects of stress on the intestine, we studied the actions of exogenous CRF on small and large intestinal transit in the rat and characterized the effects of pharmacological blockade of CRF receptors on stress-induced intestinal dysfunction. Administration of exogenous CRF (0.3-10.0 micrograms iv or icv) resulted in dose-related inhibition of gastric emptying, inhibition of small intestinal transit, stimulation of colonic transit, and stimulation of fecal excretion. The actions of exogenous CRF mimicked the effects of stress on the motor activity of the gastrointestinal tract. Administration of alpha-helical CRF-(9-41) (50 micrograms iv or icv), an antagonist of CRF, prevented the stress-induced increase in large intestinal transit and the associated increase in fecal excretion. These data suggest that endogenous CRF may mediate stress-induced changes in colonic function.
Article
Although the passage early in labor of thick amniotic fluid heavily stained with meconium is recognized as an indication of potential fetal asphyxia, the significance of late passage of meconium-stained fluid in labor is less certain. One hundren twenty-eight patients with late passage of meconium in labor and 134 control patients were examined, using chi 2 and discriminant analysis, to determine if any relationships existed between fetal heart rate (FHR) patterns, late passage of meconium in labor, and neonatal morbidity. In the group with late meconium passage, adequate baseline FHR variability and nonperiodic accelerations were predictive of high Apgar scores, and repeated (over 20) variable decelerations were predictive of low Apgar scores. In the control group, none of the FHR patterns examined were predictive of Apgar score. Thus, the combination of late passage of meconium in labor with other intrapartum signs may indicate a fetus at risk for asphyxia when neither sign alone is predictive. The presence of late meconium passage demands close observation of the patient in labor, including assessment by electronic FHR monitoring.
Article
Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid. Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid. All meconium-stained fluid was centrifuged, and the volume percentage of particulate matter (i.e., meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin levels were measured. Statistical analysis included Student t test and rank sum statistics where appropriate. Normal and Spearman correlation coefficients were also used. There were no significant differences in mean umbilical artery pH (7.26 +/- 0.06 vs 7.25 +/- 0.10), lactate levels (32.8 +/- 10 mg/dl vs 30.4 +/- 14.2 mg/dl), and hypoxanthine levels (13.4 +/- 6.7 mumol/L vs 14.0 +/- 6.0 mumol/L) in newborns with meconium (n = 28) compared with controls (n = 28). Erythropoietin levels were significantly greater in newborns with meconium (median 39.5 mIU/ml vs 26.8 mIU/ml, p = 0.039). There was no correlation between the amount of particulate matter and any marker of asphyxia. There was no correlation between markers of acute asphyxia (i.e., umbilical artery blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels were significantly elevated in newborns with meconium-stained amniotic fluid. This latter marker may better correlate with chronic asphyxia.
Article
The objective of this study was to determine the rate of intra-amniotic infection in patients with meconium-stained amniotic fluid compared to controls. With a retrospective case-controlled study design, we compared 100 pregnant women with meconium to 100 pregnant women without meconium for the development of intra-amniotic infection. Patients delivered between September 1 and December 31, 1990. Exclusion criteria were active infection prior to labor or antibiotic use within the 7 days prior to delivery. We diagnosed clinical intra-amniotic infection in patients with ruptured membranes by a maternal temperature 100.4 degrees F or higher and any two of the following: maternal or fetal tachycardia, uterine tenderness, white blood cell count 10,500 mm3 or more, or foul-smelling amniotic fluid. Demographic variables, labor characteristics, maternal infectious morbidity, and neonatal outcome were analyzed using the Wilcoxin rank test, chi-square test, or Fisher's exact test as appropriate. The rate of clinical intra-amniotic infection was significantly higher in women with meconium-stained amniotic fluid (8%) compared with women with no meconium (2%) (p = 0.05).
Article
An experimental study was performed to investigate the excretion function of the liver, gastrointestinal motility, and in utero defecation by radionuclide techniques in 24 New Zealand white rabbit fetuses at 25 days' gestation (fullterm, 31 to 32 days). 0.1 mL of technetium 99m (99mTc)-HIDA (a derivative of iminodiacetic acid) containing 1 mCi of radioactivity was injected into the gluteus muscle of each fetus which had been exposed through the uterus. After replacing the fetus and uterus into the abdomen, and beginning 1 hour after injection, a live fetus was killed each hour for 24 hours Tissue samples from the lung heart, stomach, kidney, bladder, liver, meconium in the proximal, mid and distal bowel, and amniotic fluid were taken. The radioactivity of each sample was determined by a gamma counter and the percentage uptake per gram of tissue was calculated. The very low radioactivity levels detected in the stomach, kidneys, and bladder indicated the in vivo stability of 99mTc-HIDA 99mTc-HIDA is predominantly trapped by the liver via systemic circulation and is excreted into the gastrointestinal tract through which it passes into the amniotic fluid. Demonstrated passage of excreted 99mTc-HIDA through the fetal liver and into the gastrointestinal tract and amniotic fluid strongly suggests that fetal defecation is a physiological event.
Article
To determine the prevalence and clinical significance of meconium stained amniotic fluid (MSAF) in a low risk population at term gestation and to investigate whether MSAF is a predictor for intrapartum and neonatal morbidity. A very low risk population including 37 085 consecutive deliveries at term composed the study population. A cross-sectional study was conducted and two groups of patients were identified according to the presence (n=6164) or absence (n=30921) of meconium in the amniotic fluid at delivery and the outcomes of the two groups compared. The prevalence of MSAF was 16.6%. The incidence of cesarean section (5.6% vs 2.3% P<0.01), instrumental deliveries (3.2% vs 1.8% P<0.01), fetal distress (6.5% vs. 2.1% P<0.01), clinical chorioamnionitis (0.2% vs. 0.1% P<0.01), post-partum infection (0.5% vs. 0.2% P<0.01), 1-minute Apgar score <3 (1.9% vs. 1.1% P<0.01), small for gestational age (7.4% vs. 6.4% P<0.01). was significantly higher in the MSAF compared with the clear amniotic fluid group. Intrapartum and neonatal mortality in this low risk population was significantly higher in the MSAF group (1.7/1000) compared with women with clear AF (0.3/1000). MSAF in a low risk population at term gestation is a predictor for adverse perinatal outcome and peripartum complications.
Article
To show that meconium causes fetal morbidity and death at earlier gestations than reported previously. We searched for specimens from 1997 and 1998 with pathologic diagnosis of meconium-induced umbilical vascular necrosis in placentas of nonmalformed fetuses and newborns. Because intra-amniotic infection is known to activate cytokines, and blood pigment is often microscopically indistinguishable from meconium, we removed those confounding considerations by excluding placentas with chorioamnionitis and signs of intra-amniotic bleeding. Light microscopic identification of vacuolar amniotic epithelial degeneration was used to select specimens with meconium because blood does not cause that histopathologic abnormality. We used histochemical procedures to show absence of hemosiderin and presence of bilirubin, and immunocytochemical labeling with interleukin-1beta to show cytokine. Four cases had meconium-induced umbilical vascular necrosis. The gestational ages were 16, 19, 29, and 38 weeks. Two cases were abortuses, the third was stillborn, and the fourth was a small-for-gestational-age liveborn, delivered by cesarean because of repetitive variable decelerations. Luna-Ishak staining showed bilirubin in macrophages between umbilical vascular myocytes and in the Wharton's jelly. Immunocytochemical methods showed interleukin-1beta in those same macrophages. Cytokines and other meconium-associated factors may contribute to the pathogenesis of fetal death. Survivors may suffer intraventricular hemorrhage, periventricular leukomalacia, and other morbidity.
Article
We sought to determine whether umbilical cord plasma erythropoietin levels were different in deliveries complicated by meconium passage and to determine whether this response is influenced by gestational age. Fetal erythropoietin levels were measured in 203 appropriately grown neonates at 37 to 43 weeks of gestation; among those, 70 had passed meconium. Meconium passage in the entire population was associated with elevated fetal erythropoietin levels (68 vs 31 mIU/mL; P <.001). Cord blood gases, pH, base deficit, and PO (2), as well as the 1- and 5-minute Apgar scores, were not different between the meconium and no-meconium groups. Gestational age and birth weights were significantly higher in the meconium group. Stepwise multiple regression analysis with meconium and gestational age used as the independent variables showed both meconium and gestational age to be independently associated with fetal erythropoietin levels (r = 0.356, F = 14.5; meconium, P <.001; gestational age, P <.01). These results suggest that meconium passage can be associated with chronic fetal hypoxia as demonstrated by elevated fetal erythropoietin levels, independent of gestational age.
Article
To evaluate the effect of meconium-stained amniotic fluid (AF) on perinatal outcome. A prospective observational study was performed, comparing perinatal outcome of parturients with thick and thin meconium-stained AF to those with clear AF. The rate of meconium-stained AF was 18.1% (106/586). Of those, 78 (13.3%) patients had thin and 28 (4.8%) had thick meconium-stained AF. The rate of oligohydramnios was significantly higher among pregnancies complicated with thick meconium-stained AF (OR 7.2, 95% Cl 2.1-24.1; p = 0.002). A significant linear association, using the Mantel-Haenszel test for linearity, was found between the thickness of the meconium and abnormal fetal heart rate patterns during the first and second stages of labor, low Apgar scores at 1 min and the risk for Cesarean section. A statistically significantly higher risk for neonatal intensive care unit admission was observed among patients with thick meconium as compared to those with clear AF (OR 11.4, 95% CI 2.0-59.3; p = 0.006), even after adjustment for oligohydramnios and abnormal fetal heart rate patterns. Thick, and not thin, meconium-stained AF, was associated with an increased risk for perinatal complications during labor and delivery. Therefore, thick meconium-stained AF should be considered a marker for possible fetal compromise, and lead to careful evaluation of fetal well-being.
Article
To estimate the prevalence of meconium-stained amniotic fluid and meconium aspiration syndrome, as well as the differences in case fatality from meconium aspiration syndrome, between non-Hispanic black and non-Hispanic white infants. We studied non-Hispanic black and non-Hispanic white live births with weights greater than 2.5 kg and gestational ages greater than 35 weeks, using the linked US birth and infant death cohorts for three periods: 1989-1991, 1995-1997, and 1998-2000. We used logistic regression to estimate the risks of meconium-stained amniotic fluid and meconium aspiration syndrome and to estimate the case fatality of meconium aspiration syndrome by maternal race, birth weight, period, and pregnancy complications. Risk of meconium-stained amniotic fluid was 80% higher in non-Hispanic blacks when compared with non-Hispanic whites (birth weight-adjusted odds ratio [OR], 1.81, 95% confidence interval [CI] 1.80, 1.82). The prevalence of pregnancy complications did not explain this racial disparity. Risk of meconium aspiration syndrome in non-Hispanic blacks was 67% higher when compared with non-Hispanic whites (birth weight-adjusted OR 1.67, 95% CI 1.64, 1.70). The case fatality rate of meconium aspiration syndrome was similar between non-Hispanic blacks and non-Hispanic whites in the three periods, with rates of 15.5, 15.2, and 11.2 per 1000 in non-Hispanic blacks and 13.5, 11.2, and 10.1 per 1000 in non-Hispanic whites in 1989-1991, 1995-1997, and 1998-2000, respectively. Our results suggest that when compared with non-Hispanic whites, non-Hispanic blacks are at significantly greater risk for meconium-stained amniotic fluid and meconium aspiration syndrome but not for meconium aspiration syndrome case fatality.
Article
Evidence of meconium-stained amniotic fluid (AF) during labor suggests implementation of close monitoring of fetal well-being. We have investigated whether the presence of meconium in the AF on admission for labor is as important a predictor of neonatal outcome as a change in AF color during labor. AF characteristics on admission for labor at term (37-42 weeks) and their changes during labor were recorded in all singleton pregnancies during an 8-year period (1992-1999). Excluded were stillbirths on admission, congenital anomalies, and elective cesarean sections. The presence of meconium and its consistency (light or thick) were documented on admission by inspection with transcervical amnioscopy in women with intact membranes or in the vaginal pool in those with ruptured membranes. Changes in AF color or consistency during labor were recorded and correlated with the obstetric and neonatal outcome. Statistical analysis utilized chi(2) for trend, with p < 0.05 considered significant. 19,090 women were admitted in labor at term during the study period and fulfilled the study inclusion criteria and had amniotic fluid evaluation available. The appearance of meconium or worsening in thickness of meconium during labor was associated with higher rates of Apgar scores <7 at 5 min (clear AF on admission and at delivery 0.6%; light or thick meconium on admission and no change at delivery 0.8%; clear AF on admission and light or thick meconium at delivery 3.2%, and light meconium on admission and thick meconium at delivery 2.5%; p < 0.001) and umbilical artery pH <7.10 (the respective rates in the four groups were 1.7, 1.8, 3.6, and 3.8%; p < 0.001). The appearance or thickening of meconium during labor has a greater predictive ability for depressed neonates than the presence of meconium on admission.
Article
Meconium passage in newborn infants is a developmentally programmed event normally occurring within the first 24 to 48 hours after birth. Intrauterine meconium passage in near-term or term fetuses has been associated with fetomaternal stress factors and/or infection, whereas meconium passage in postterm pregnancies has been attributed to gastrointestinal maturation. Despite these clinical impressions, little information is available on the mechanism(s) underlying the normal meconium passage that occurs immediately after birth or during the intrauterine period of fetal development. Birth itself is a stressful process and it is possible that fetal stress-mediated biochemical events may regulate the meconium passage occurring either during labor or after birth. Aspiration of meconium during intrauterine life may result in or contribute to meconium aspiration syndrome (MAS), representing a continued leading cause of perinatal death. This article reviews aspects of meconium passage in utero, its consequences, and management.
Article
A prospective cross-sectional study was carried out to determine the relationship and predictive value of umbilical cord blood pH for adverse neonatal outcomes. A total of 400 singleton term infants delivered by vaginal delivery or caesarean section were studied at a hospital in Kerman, Islamic Republic of Iran, in 2001. Mean (SD) umbilical cord blood pH was 7.25 +/- 0.14 and 81 cases had acidaemia (pH < 7.1). Apgar score at 1 minute and fetal distress were significantly related to acidaemia. There was also a significant relation between meconium-stained amniotic fluid and acidaemia. Logistic regression analysis showed that Apgar score < 7 at 1 minute, meconium-stained amniotic fluid and fetal distress were significant risk factors for acidaemia in newborn infants. Umbilical cord blood acid-base alterations are related to subsequent adverse outcome events for neonates.
Article
We sought to examine, in a large cohort of infants within a definable population of live births, the incidence, risk factors, treatments, complications, and outcomes of meconium aspiration syndrome (MAS). Data were gathered on all of the infants in Australia and New Zealand who were intubated and mechanically ventilated with a primary diagnosis of MAS (MASINT) between 1995 and 2002, inclusive. Information on all of the live births during the same time period was obtained from perinatal data registries. MASINT occurred in 1061 of 2,490,862 live births (0.43 of 1000), with a decrease in incidence from 1995 to 2002. A higher risk of MASINT was noted at advanced gestation, with 34% of cases born beyond 40 weeks, compared with 16% of infants without MAS. Fetal distress requiring obstetric intervention was noted in 51% of cases, and 42% were delivered by cesarean section. There was a striking association between low 5-minute Apgar score and MASINT. In addition, risk of MASINT was higher where maternal ethnicity was Pacific Islander or indigenous Australian and was also increased after planned home birth. Uptake of exogenous surfactant, high-frequency ventilation, and inhaled nitric oxide increased considerably during the study period, with >50% of infants receiving > or =1 of these therapies by 2002. Risk of air leak was 9.6% overall, with an apparent reduction to 5.3% in 2001-2002. The duration of intubation remained constant throughout the study period (median: 3 days), whereas duration of oxygen therapy and length of hospital stay increased. Death related to MAS occurred in 24 infants (2.5% of the MASINT cohort; 0.96 per 100,000 live births). The incidence of MASINT in the developed world is low and seems to be decreasing. Risk of MASINT is significantly greater in the presence of fetal distress and low Apgar score, as well as Pacific Islander and indigenous Australian ethnicity. The increased use of innovative respiratory supports has not altered the duration of mechanical ventilation.
Article
To estimate whether the acid-base status of neonates born to women with meconium-stained amniotic fluid varies across gestation. We carried out a retrospective cohort study of all pregnancies that were complicated by meconium-stained amniotic fluid in 2004. Cases were identified from a perinatal pathology database that contained data on all pregnancies complicated by meconium-stained amniotic fluid. Data abstracted from the charts included gestational age at delivery, umbilical arterial pH, birth weight, and the presence or absence of labor. Cases were stratified according to gestational age at delivery. The distribution of meconium-stained amniotic fluid across gestation was computed. The mean umbilical arterial pH values (with 95% confidence intervals) across gestation were assessed by analysis of variance. The mean umbilical arterial pH in women with meconium-stained amniotic fluid did not differ across gestation. The overall incidence of meconium-stained amniotic fluid was 12.0% (766 of 6,403 deliveries). The rates of meconium-stained amniotic fluid increased from 1.2% at 32 weeks to 100% at 42 weeks. The rising incidence of meconium-stained amniotic fluid with gestational age is consistent with the hypothesis that fetal maturation is a major etiologic factor in meconium passage. Also, the lack of variation of mean umbilical arterial pH across gestation suggests that fetal acidemia is not increased when meconium passage occurs earlier in pregnancy rather than at later gestational ages.
Article
Intrauterine meconium (MEC) passage and aspiration may result in significant newborn morbidity, though there is little understanding of the physiologic mechanisms for MEC passage. We hypothesized that stress induces fetal MEC passage via corticotrophin releasing factor (CRF), a known mediator of colonic motility in adult rats. Pregnant rats at e22 were subjected to acute hypoxia or normoxia for 35 min, after which rats were anesthetized and fetuses operatively delivered. Amniotic fluid bilirubin and intestinal alkaline phosphatase were measured as markers for MEC passage, and fetal and maternal plasma CRF and corticosterone levels determined. Hypoxic stress induced defecation in all dams and provoked visible MEC passage in all fetuses. Amniotic fluid bilirubin content was significantly higher in hypoxic fetuses versus controls (1.064 +/- 0.101 versus 0.103 +/- 0.003 O.D. at 410 nm) and intestinal alkaline phosphatase was consistently elevated in MEC stained amniotic fluid. Hypoxia significantly increased plasma CRF (maternal, 82 +/- 5 to 196 +/- 14 pg/mL; fetal, 284 +/- 15 to 1523 +/- 185 pg/mL) and corticosterone (maternal, 417 +/- 50 to 1150 +/- 50 ng/mL; fetal, 96 +/- 5 to 182 +/- 10 ng/mL) compared with controls. In view of the known action of CRF in adult colonic motility, these results suggest that hypoxic stress-mediated MEC passage in term fetal rats is mediated by a CRF dependent pathway.