Publications

Abstract

Objective: To determine whether bladder size is associated with an unfavorable neonatal outcome, in the case of first-trimester megacystis.

Materials and methods: This was a retrospective observational study between 2009 and 2019 in two prenatal diagnosis centers. The inclusion criterion was an enlarged bladder (> 7 mm) diagnosed at the first ultrasound exam between 11 and 13+6 weeks of gestation. The main study endpoint was neonatal outcome based on bladder size. An adverse outcome was defined by the completion of a medical termination of pregnancy, the occurrence of in utero fetal death, or a neonatal death. Neonatal survival was considered as a favorable outcome and was defined by a live birth, with or without normal renal function, and with a normal karyotype.

Results: Among 75 cases of first-trimester megacystis referred to prenatal diagnosis centers and included, there were 63 (84%) adverse outcomes and 12 (16%) live births. Fetuses with a bladder diameter of less than 12.5 mm may have a favorable outcome, with or without urological problems, with a high sensitivity (83.3%) and specificity (87.3%), area under the ROC curve = 0.93, 95% CI (0.86-0.99), p< 0.001. Fetal autopsy was performed in 52 (82.5%) cases of adverse outcome. In the 12 cases of favorable outcome, pediatric follow-up was normal and non-pathological in 8 (66.7%).

Conclusion: Bladder diameter appears to be a predictive marker for neonatal outcome. Fetuses with smaller megacystis (7-10 mm) have a significantly higher chance of progressing to a favorable outcome. Urethral stenosis and atresia are the main diagnoses made when first-trimester megacystis is observed. Karyotyping is important regardless of bladder diameter.

Abstract

Objective: To compare the performance of estimated fetal weight (EFW) charts at the third-trimester ultrasound for detecting small and large for gestational age (SGA/LGA) newborns with adverse outcomes DESIGN: Nationally representative observational study.

Setting: French maternity units in 2016.

Population: 9940 singleton live births with an ultrasound between 30 and 35 weeks of gestation.

Methods: We compared three prescriptive charts (INTERGROWTH-21^st , World Health Organization (WHO), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)), four descriptive charts (Hadlock, Fetal Medicine Foundation, two French charts) and a French customised growth model (Epopé).

Main outcomes measures: SGA and LGA (birthweights <10^th and >90^th percentiles) associated with adverse outcomes (low Apgar score, delivery-room resuscitation, neonatal unit admission).

Results: 2.1% and 1.1% of infants had SGA and LGA and adverse outcomes, respectively. The sensitivity and specificity for detecting these infants with an EFW <10^th and >90^th percentile varied from 29%-65% and 84%-96% for descriptive charts versus 27%-60% and 83%-96% for prescriptive charts. WHO and French charts were closest to the EFW distribution, yielding a balance between sensitivity and specificity for SGA and LGA births. INTERGROWTH-21^st and Epopé had low sensitivity for SGA with high sensitivity for LGA. Areas under the receiving operator characteristics curve ranged from 0.62 to 0.74, showing low to moderate predictive ability, whereas diagnostic odds ratios varied from 7 to 16.

Conclusion: Marked differences in the performance of descriptive as well as prescriptive EFW charts highlight the importance of evaluating them for their ability to detect high-risk fetuses.

Abstract

Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts.

Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2-3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor’s/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years.

Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results.

Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.

Abstract

Background: The objective of this study was to describe labor duration of women managed with current obstetric practices in a French national population-based cohort and to assess the association of age and BMI on this duration.

Methods: All women in the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. Duration of labor was defined as time between admission to the labor ward and birth. Duration of total labor and first and second stage of labor were described. Then, duration of labor was estimated according to maternal age and BMI, using Kaplan-Meier’s method and compared with the log-rank test after stratification on parity. Intrapartum cesarean birth was considered as a censoring event. Multivariable modeling was performed using Cox’s proportional hazard’s method.

Results: Data of 3120 nulliparous and 4385 multiparous women were analyzed. Median labor duration was 6.1 hours ([5th; 95th percentile]) [1.4; 12.6] and 3.1 hours [0.3; 8.5] in nulliparous and multiparous women. Multivariable Cox analysis showed no independent association of maternal age and duration of labor. Nulliparous obese women had significantly lower odds of having a shorter labor than women with a BMI < 25 kg/m² , HR: 0.75; 95% CI [0.64-0.88], but BMI was not associated with labor duration in multiparous women.

Conclusions: Our study provides important information for both women and care practitioners on what to expect when entering the labor ward. There appears to be little association between maternal characteristics and labor duration, with the exception of BMI in nulliparous women.

Abstract

The human placenta is a transient organ essential for pregnancy maintenance, fetal development and growth. It has several functions, including that of a selective barrier against pathogens and xenobiotics from maternal blood. However, some pollutants can accumulate in the placenta or pass through with possible repercussions on pregnancy outcomes. Cerium dioxide nanoparticles (CeO₂ NPs), also termed nanoceria, are an emerging pollutant whose impact on pregnancy is starting to be defined. CeO₂ NPs are already used in different fields for industrial and commercial applications and have even been proposed for some biomedical applications. Since 2010, nanoceria have been subject to priority monitoring by the Organization for Economic Co-operation and Development in order to assess their toxicity. This review aims to summarize the current methods and models used for toxicology studies on the placental barrier, from the basic ones to the very latest, as well as to overview the most recent knowledge of the impact of CeO₂ NPs on human health, and more specifically during the sensitive window of pregnancy. Further research is needed to highlight the relationship between environmental exposure to CeO₂ and placental dysfunction with its implications for pregnancy outcome.

Abstract

Background: This study aims to estimate the economic costs of care provided to children born very preterm and extremely preterm across 11 European countries, and to understand what perinatal and socioeconomic factors contribute to higher costs.

Methods: Generalised linear modelling was used to explore the association between perinatal and sociodemographic characteristics and total economic costs (€, 2016 prices) during the fifth year of life.

Results: Lower gestational age was associated with increased mean societal costs of €2755 (p < 0.001), €752 (p < 0.01) and €657 (p < 0.01) for children born at < 26, 26-27 and 28-29 weeks, respectively, in comparison to the reference group born at 30-31 weeks. A sensitivity analyses that excluded variables (BPD, any neonatal morbidity and presence of congenital anomaly) plausibly lying on the causal pathway between gestational age at birth and economic outcomes elevated incremental societal costs by €1482, €763 and €144 at < 26, 26-27 and 28-29 weeks, respectively, in comparison to the baseline model.

Conclusion: This study provides new evidence about the main cost drivers associated with preterm birth in European countries. Evidence identified by this study can act as inputs within cost-effectiveness models for preventive or treatment interventions for preterm birth.

Impact: What is the key message of your article? This study provides new evidence about the magnitude and drivers of economic costs associated with preterm birth in European countries. What does it add to the existing literature? Lower gestational age is associated with increased mean societal costs during mid-childhood with indirect costs representing a key driver of increased costs. What is the impact? For policy makers, this study adds to sparse evidence about the main cost drivers associated with preterm birth in European countries beyond the first 2 years of life.

Abstract

Introduction: In case of term prelabor rupture of membranes (PROM), expectant management is a reasonable option. We aimed at assessing the frequency of spontaneous onset of labor after two days of term PROM and its associated factors.

Material and methods: Women delivering at a tertiary center of a singleton in cephalic presentation, after a term PROM with an unfavorable cervix and with an expectant management period of at least two days were included during a 2-year period. Women were excluded in case of induction of labor before or at day 2(D2) or of spontaneous labor before D2. The frequency of spontaneous labor was assessed, then maternal characteristics at admission and at D2 were compared between women with a spontaneous onset of labor before D3, and women with an induced labor at D3. The maternal and neonatal outcomes were compared between the two groups. The factors associated with spontaneous labor in univariate analysis were tested in multivariable analysis.

Results: Among the 11 608 women delivering at term, 933(8.4%) had a term PROM. Among them, 191 had an unfavorable cervix after D2 including 86(45%) women with a spontaneous labor onset between D2 and D3 and 105(55%) induced at D3. Maternal age below 35 years (reference ≥35years) and Bishop score of 3-4 and 5-6 at D2 (reference score 0-2) were significantly associated with spontaneous onset of labor, respectively aOR 2.62; 95%CI[1.26-5.45], aOR 2.38; 95%CI[1.18-4.78] and aOR 10.16; 95%CI[3.67-28.15].

Discussion: In women with a term PROM and an unfavorable cervix, spontaneous labor still occurs in nearly half of women undelivered after two days of expectant management.

Abstract

The survival rate of infants born before 25 weeks of gestational age in France is extremely low compared with that of many other countries: 0%, 1%, and 31% at 22, 23, and 24 weeks’ in the last national cohort study. A non-optimal regionalization and variations in practice are prevalent. Some parents in social media and support groups have reported feeling lost and confused with mixed messages leading to lack of trust. These data kindled a major debate in France around perinatal management leading to an investigation exploring neonatologists’ perspectives and ways to improve care. The majority (81%) of the responding neonatologists reported more active care and higher survival rates than in 2011, although others continued preferring delivery room comfort care and limited NICU treatment at or before 24 weeks. The desire to improve was an overarching theme in all the respondents’ answers to open-ended questions. Barriers to active care included an absence of expertise and of benchmarking to guide optimal care, and limited resources in the NICU and during follow-up – all leading to self-fulfilling prophecies of poor prognosis. Optimization of regionalization, perinatal teamwork and parental involvement, fostering experience by creating specific perinatal centers, stimulating benchmarking, and working with policy makers to allow better long-term outcomes could enable higher survival.

Abstract

Objective: In the context of a medical termination of pregnancy, prolonged labor may accentuate the difficulty of women’s experience and increase the risk of associated complications. The factors associated with prolonged labor are not known. Reducing the duration of labor could limit these complications.Determining the relevant factors associated with prolonged labor defined as a delay between the onset of induction and delivery greater than or equal to 12 hours and comparing the complications rates between the two groups.

Method: We conducted a retrospective study at Port Royal Maternity Hospital from 2017 to 2019, including medical terminations of pregnancy by vaginal delivery in the 2nd and 3rd trimesters for fetal or maternal reasons.

Results: Two hundred twenty-seven patients were included and divided into two comparative groups based on the duration of labor: labor <12h (N= 173) and labor ≥12h (N=54). The mean maternal age was 33.7 years. Forty-four percent of patients were nulliparous, 15.8% had a history of cesarean section. The average gestational age was 20+2 weeks of gestation. The average duration of labor was 9.7 hours. The duration of labor was greater than 24 hours in 3% of cases (7/227). Advanced gestational age (22+3 vs 20+5 p=0,04) and nulliparity (p=0.01) were associated with prolonged labor. Two other intermediate factors, not independent of the duration of labor, were significant: long time to rupture of membranes (239 min vs 427 min p<0,01) and an unfavorable Bishop score at rupture (p=0,003). In both groups, the complications were placental retention and the occurrence of fever during labor.

Conclusion: Two main factors affecting labor duration were identified in this study (term and nulliparity). This knowledge could allow women to be better informed about the expected time of labor and the potential associated risks.

Abstract

Background: In contrast with birthweight or other growth charts, a feature of most intrauterine charts is that they are not differentiated by sex. Differences in weight by sex during pregnancy are considered to be relatively minor, however, small systematic differences may affect the sensitivity and specificity of screening for fetuses with growth restriction.

Objective: To assess differences between unisex and sex-specific estimated fetal weight (EFW) charts at the third trimester ultrasound on the sex ratio of fetuses detected with an EFW <10^th percentile and subsequent detection of small for gestational age (SGA) newborns with morbidity at birth.

Study design: The study included 9940 singleton live births from a French population-based study in 2016. Main outcomes were an EFW <10^th percentile at the routine third trimester ultrasound between 30 and 35 weeks of gestation, and SGA (birthweight <10^th percentile) with neonatal morbidity (Apgar score <7 at 5 minutes and/or resuscitation in delivery room and/or admission to a neonatal unit). We used two charts with unisex and sex-specific options: the World Health Organization (WHO) international standard chart and a customized chart for fetal sex based on Gardosi’s GROW model adapted to the French population (Epopé). Hadlock’s unisex chart, commonly used in clinical care and research, was also included to provide an external reference. We compared the proportions of female and male fetuses with an EFW <10^th percentile and the sensitivity and specificity of an EFW <10^th percentile for predicting SGA newborns with morbidity when using unisex versus sex-specific charts, overall and by sex.

Results: Among all singleton births, there were 51.6% males and 48.4% females. Males faced higher risks of SGA with morbidity at birth (2.4% vs 1.8%, P=.031). Using the WHO unisex chart, 6.9% of males and 9.9% of females had an EFW <10^th percentile versus 9.9% of males and 7.1% of females with the sex-specific chart; these proportions were 3.5% and 4.6% and, 4.3% and 2.7% respectively for Epopé. Proportions of EFW <10^th percentile using Hadlock were slightly higher compared with the unisex WHO chart (7.5% of males and 10.6% of females), but the difference of about 3% was the same. The sensitivity of an EFW <10^th percentile for identifying SGA newborns with morbidity differed for males and females by type of chart; unisex charts detected more SGA females with morbidity and sex-specific charts detected more SGA males with morbidity, but the overall sensitivity was the same (49.1% for WHO and Hadlock and 34.9% for Epopé).

Conclusion: This study suggests that use of sex-specific charts instead of unisex charts would avert sex-bias in intrauterine growth screening during the third trimester of pregnancy. Prospective studies are needed to assess the effects of using sex-specific charts compared to unisex charts on obstetrical management and outcomes.