Publications

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.

Research Letter

No abstract available

Abstract

Objectives: This study measured the impact of the first wave of COVID-19 pandemic (COVID-19) (March-April 2020) on the incidence of bloodstream infections (BSIs) at Assistance Publique – Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France.

Methods: The number of patient admission blood cultures (BCs) collected, number of positive BCs, and antibiotic resistance and consumption were analysed retrospectively for the first quarter of 2020, and also for the first quarter of 2019 for comparison, in 25 APHP hospitals (ca. 14 000 beds).

Results: Up to a fourth of patients admitted in March-April 2020 in these hospitals had COVID-19. The BSI rate per 100 admissions increased overall by 24% in March 2020 and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to third-generation cephalosporins (3GC) was also observed in March-April 2020, particularly in K. pneumoniae, enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae…), and P. aeruginosa. A concomitant increase in 3GC consumption occurred.

Conclusions: The COVID-19 pandemic had a strong impact on hospital management and also unfavourable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.

Abstract

Aims : Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and foetal morbidity and mortality. We aimed to estimate the impact of HDP on the onset of chronic hypertension in primiparous women in the first years following childbirth.

Methods and results : This nationwide cohort study used data from the French National Health Data System (SNDS). All eligible primiparous women without pre-existing chronic hypertension who delivered between 2010 and 2018 were included. Women were followed up from six weeks post-partum until onset of hypertension, a cardiovascular event, death, or the study end date (31 December 2018). The main outcome was a diagnosis of chronic hypertension. We used Cox models to estimate hazard ratios (HRs) of chronic hypertension for all types of HDP. Overall, 2 663 573 women were included with a mean follow-up time of 3.0 years. Among them, 180 063 (6.73%) had an HDP. Specifically 66 260 (2.16%) had pre-eclampsia (PE) and 113 803 (4.27%) had gestational hypertension (GH). Compared with women who had no HDP, the fully adjusted HRs of chronic hypertension were 6.03 [95% confidence interval (CI) 5.89-6.17] for GH, 8.10 (95% CI 7.88-8.33) for PE (all sorts), 12.95 (95% CI 12.29-13.65) for early PE, 9.90 (95% CI 9.53-10.28) for severe PE, and 13.17 (95% CI 12.74-13.60) for PE following GH. Hypertensive disorders of pregnancy exposure duration was an additional risk factor of chronic hypertension for all PE subgroups. Women with HDP consulted a general practitioner or cardiologist more frequently and earlier.

Conclusion : Hypertensive disorders of pregnancy exposure greatly increased the risk of chronic hypertension in the first years following delivery.

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is essential for placental development, whose SNPs have shown increased susceptibility to pregnancy-related diseases, such as preeclampsia. Our aim was to investigate the association between preeclampsia and three PPARγ SNPs (Pro12Ala, C1431T, and C681G), which together with nine clinical factors were used to build a pragmatic model for preeclampsia prediction. Data were collected from 1648 women from the EDEN cohort, of which 35 women had preeclamptic pregnancies, and the remaining 1613 women had normal pregnancies. Univariate analysis comparing preeclamptic patients to the control resulted in the SNP C1431T being the only factor significantly associated with preeclampsia (p < 0.05), with a confidence interval of 95% and odds ratio ranging from 4.90 to 8.75. On the other hand, three methods of multivariate feature selection highlighted seven features that could be potential predictors of preeclampsia: maternal C1431T and C681G variants, obesity, body mass index, number of pregnancies, primiparity, cigarette use, and education. These seven features were further used as input into eight different machine-learning algorithms to create predictive models, whose performances were evaluated based on metrics of accuracy and the area under the receiver operating characteristic curve (AUC). The boost tree-based model performed the best, with respective accuracy and AUC values of 0.971 ± 0.002 and 0.991 ± 0.001 in the training set and 0.951 and 0.701 in the testing set. A flowchart based on the boost tree model was constructed to depict the procedure for preeclampsia prediction. This final decision tree showed that the C1431T variant of PPARγ is significantly associated with susceptibility to preeclampsia. We believe that this final decision tree could be applied in the clinical prediction of preeclampsia in the very early stages of pregnancy.