Tocolysis after preterm prelabor rupture of membranes and 5-year outcomes: a population-based cohort study.

BACKGROUND: The administration of tocolytics after preterm prelabor rupture of membranes remains a controversial practice. In theory, reducing uterine contractility should delay delivery and allow for optimal antenatal management, thereby reducing the risks for prematurity and adverse consequences over the life course. However, tocolysis may be associated with neonatal death or long-term adverse neurodevelopmental outcomes, mainly related to prolonged fetal exposure to intrauterine infection or inflammation. In a previous study, we showed that tocolysis administration was not associated with short-term benefits. There are currently no data available to evaluate the impact of tocolysis on neurodevelopmental outcomes in school-aged children born prematurely in this clinical setting. OBJECTIVE: This study aimed to investigate whether tocolysis administered after preterm prelabor rupture of membranes is associated with neurodevelopmental outcomes at 5.5 years of age. STUDY DESIGN: We used data from a prospective, population-based cohort study of preterm births recruited in 2011 (referred to as the EPIPAGE-2 study) and for whom the results of a comprehensive medical and neurodevelopmental assessment of the infant at age 5.5 years were available. We included pregnant individuals with preterm prelabor rupture of membranes at 24 to 32 weeks' gestation in singleton pregnancies with a live fetus at the time of rupture, birth at 24 to 34 weeks' gestation, and participation of the infant in an assessment at 5.5 years of age. Exposure was the administration of any tocolytic treatment after preterm prelabor rupture of membranes. The main outcome was survival without moderate to severe neurodevelopmental disabilities at 5.5 years of age. Secondary outcomes included survival without any neurodevelopmental disabilities, cerebral palsy, full-scale intelligence quotient, developmental coordination disorders, and behavioral difficulties. A propensity-score analysis was used to minimize the indication bias in the estimation of the treatment effect on outcomes. RESULTS: Overall, 596 of 803 pregnant individuals (73.4%) received tocolytics after preterm prelabor rupture of membranes. At the 5.5-year follow-up, 82.7% and 82.5% of the children in the tocolysis and no tocolysis groups, respectively, were alive without moderate to severe neurodevelopmental disabilities; 52.7% and 51.1%, respectively, were alive without any neurodevelopmental disabilities. After applying multiple imputations and inverse probability of treatment weighting, we found no association between the exposure to tocolytics and survival without moderate to severe neurodevelopmental disabilities (odds ratio, 0.93; 95% confidence interval, 0.55-1.60), survival without any neurodevelopmental disabilities (odds ratio, 1.02; 95% confidence interval, 0.65-1.61), or any of the other outcomes. CONCLUSION: There was no difference in the neurodevelopmental outcomes at age 5.5 years among children with and without antenatal exposure to tocolysis after preterm prelabor rupture of membranes. To date, the health benefits of tocolytics remain unproven, both in the short- and long-term.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. STUDY DESIGN: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. RESULTS: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." CONCLUSIONS: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

Impact of Latency Duration on the Prognosis of Preterm Infants after Preterm Premature Rupture of Membranes at 24 to 32 Weeks' Gestation: A National Population-Based Cohort Study.

OBJECTIVE: To assess the impact of latency duration on survival, survival without severe morbidity, and early-onset sepsis in infants born after preterm premature rupture of membranes (PPROM) at 24-32 weeks' gestation. STUDY DESIGN: This study was based on the prospective national population-based Etude Épidémiologique sur les Petits Ȃges Gestationnels 2 cohort of preterm births and included 702 singletons delivered in France after PPROM at 24-32 weeks' gestation. Latency duration was defined as the time from spontaneous rupture of membranes to delivery, divided into 4 periods (12 hours to 2 days [reference], 3-7 days, 8-14 days, and >14 days). Multivariable logistic regression was used to assess the relationship between latency duration and survival, survival without severe morbidity at discharge, or early-onset sepsis. RESULTS: Latency duration ranged from 12 hours to 2 days (18%), 3-7 days (38%), 8-14 days (24%), and >14 days (20%). Rates of survival, survival without severe morbidity, and early-onset sepsis were 93.5% (95% CI 91.8-94.8), 85.4% (82.4-87.9), and 3.4% (2.0-5.7), respectively. A crude association found between prolonged latency duration and improved survival disappeared on adjusting for gestational age at birth (aOR 1.0 [reference], 1.6 [95% CI 0.8-3.2], 1.2 [0.5-2.9], and 1.0 [0.3-3.2] for latency durations from 12 hours to 2 days, 3-7 days, 8-14 days, and >14 days, respectively). Prolonged latency duration was not associated with survival without severe morbidity or early-onset sepsis. CONCLUSION: For a given gestational age at birth, prolonged latency duration after PPROM does not worsen neonatal prognosis.

Apgar scores reported in personal child health records: validity for epidemiological studies?

AIM: In epidemiological studies on children, information in the neonatal period that might affect children's long-term health could be extracted from the personal child health record (PCHR), because the booklet exists in most countries. We aimed to assess, in individual children, the validity of Apgar scores reported in the PCHR using maternity medical records as the gold standard. METHODS: In two French hospitals, 435 women who had a child in January 2006 were recruited and 90% filled in a postal questionnaire 6 weeks after delivery, copying neonatal information (including Apgar scores) from the PCHR. This information was compared with data independently recorded at birth by physicians in maternity medical records. RESULTS: We found that the proportion of missing Apgar scores in the PCHR was higher when scores in the medical records were lower. Moreover, Apgar scores reported in the PCHR were overestimated when scores in the medical records were low. Using medical records as the gold standard, specificity for PCHR-reported 1-min Apgar score was 100% and sensitivity 33%. Similar trends were found for the 5-min score. This supports the hypothesis that information considered as 'socially sensitive' by physicians may be intentionally altered in PCHRs. CONCLUSIONS: Apgar scores reported in PCHRs may not yield reliable information for epidemiological studies. When the PCHR is the only source of information for the neonatal period in an epidemiological study, it would be preferable to use a composite neonatal indicator rather than the Apgar score.

Caesarean before labour between 34 and 37 weeks: what are the risk factors of severe neonatal respiratory distress?

OBJECTIVE: To assess the frequency of severe neonatal respiratory distress and identify its risk factors in caesarean deliveries before labour between 34 and 37 weeks' gestation. STUDY DESIGN: Retrospective study of children born by caesarean delivery before labour between 34 and 37 weeks, between 1999 and 2003 in a level 3 maternity unit. The frequencies of severe and mild neonatal respiratory distress were calculated. Univariate and multivariate analyses studied the factors potentially associated with severe respiratory distress: gestational age, type of pregnancy (singleton or multiple), condition of membranes, maternal diabetes, indication for caesarean, antenatal corticosteroid therapy, intrauterine growth retardation, infant's sex and birth weight. RESULTS: The 189 study subjects included 107 singletons and 82 twins: 28% required intensive care for severe respiratory distress and 30.2% developed mild respiratory distress. Gestational age was a significant risk factor (p = 0.01), especially before 36 weeks (adjusted OR = 2.1; 95% CI: 1.0-4.4). The multivariate analysis indicated that singleton pregnancies (adjusted OR = 3.2; 95% CI: 1.5-6.7) and caesareans for fetal indications (adjusted OR = 2.7; 95% CI: 1.2-5.7) are also risk factors and that premature rupture of the membranes is a "protective" factor against respiratory complications (adjusted OR = 0.2; 95% CI: 0.1-0.8). CONCLUSION: More than a quarter of the infants delivered by caesarean before labour between 34 and 37 weeks' gestation in our level 3 maternity unit had severe respiratory distress. Although our population may not be typical of the general population, this finding and the risk factors associated with it should be taken into account in determining the best time and place for delivery of each patient.

Ages and Stages Questionnaires: feasibility of postal surveys for child follow-up.

BACKGROUND: The Ages and Stages Questionnaire (ASQ), completed by parents and caregivers, has been shown to be an accurate tool for screening children who need further developmental assessment. AIMS: To assess the feasibility of using the French Canadian translation of the ASQ in an epidemiological cohort of children from the French general population. STUDY DESIGN: Follow-up study by postal questionnaire at 12 and 36 months, using the ASQ. SUBJECTS: 339 French families recruited at the birth of their child in 2006 in two hospitals in the Paris suburbs. OUTCOME MEASURE: Response rates and French ASQ results at 12 and 36 months. The ASQ was scored as indicated in the manual. RESULTS: A high response rate of 79% was observed at the children's 1st and 3rd birthdays. Parents were enthusiastic about participating; half of them wrote comments on the questionnaires, most of them positive. Low scores at the 12-month assessment were associated with birth characteristics such as prematurity and transfer to the neonatology unit after birth, whereas at 36 months they tended to be associated with both birth and family socio-demographic characteristics. CONCLUSIONS: Use of the French ASQ in a research cohort appears feasible as response rates were high. Moreover, known links between child development measured by ASQ and birth and social characteristics were observed. However, further French studies are needed to understand differences observed in 12-month ASQ gross motor scores compared with US norms. For research purposes, further analysis of the ASQ in innovative, quantitative approaches, is needed.

Perinatal factors reported by mothers: do they agree with medical records?

As perinatal events have been linked with diseases of later onset, epidemiological studies on child development and adult health require information on the perinatal period. When national neonatal registers do not exist, review of medical records may be impractical. However, neonatal information could be obtained by asking mothers to complete a postal questionnaire using data from the Personal Child Health Record (PCHR). We assessed agreement between medical records and mothers' reports for information on delivery and the newborn's condition at birth, based on the PCHR, a short time after delivery. Of 711 women giving birth in 3 French hospitals and invited to participate in the study, 580 (82%) completed a postal questionnaire 6 weeks after delivery, copying the data recorded in the PCHR when available. Information on pregnancy, delivery and the newborn's health at birth was independently extracted from medical records by physicians of the maternity departments. Agreement between medical records and maternal reports for a range of perinatal factors was assessed in 580 newborn-mother dyads using kappa coefficients. Agreement was excellent for first and second stages of delivery, gestational age, birth weight, birth size and head circumference (kappa coefficients 0.80-1.00) and good for hospitalization during pregnancy, but poor for Apgar scores. With this exception, mothers' reports appeared reliable when compared with medical records. As PCHRs exist in most developed countries, this approach could be used in epidemiological studies on child development to increase the reliability of mothers' reports of their newborn's condition at birth.