Publications

Abstract

Preeclampsia, a hypertensive disorder occurring during pregnancy, is characterized by excessive oxidative stress and trophoblast dysfunction with dysregulation of soluble Fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) production. Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase (Nox) is the major source of placental superoxide in early pregnancy and its activation with the subsequent formation of superoxide has been demonstrated for various agents including Transforming Growth Factor beta-1 (TGF-β1), a well-known p38 MAPK pathway activator. However, the bridge between Nox and sFlt-1 remains unknown. The purpose of this study was to explore the possible signaling pathway of TGF-β1/Nox/p38 induced sFlt-1 production in human chorionic villi (CV).

Methods: Human chorionic villi from first trimester placenta (7-9 Gestational Weeks (GW)) were treated with TGF-β1 or preincubated with p38 inhibitor, SB203580. For NADPH oxidase inhibition, CV were treated with diphenyleneiodonium (DPI). The protein levels of phospho-p38, p38, phospho-Mothers Against Decapentaplegic homolog 2 (SMAD2), and SMAD2 were detected by Western blot. The secretion of sFlt-1 and PlGF by chorionic villi were measured with Electrochemiluminescence Immunologic Assays, and NADPH oxidase activity was monitored by lucigenin method.

Results: We demonstrate for the first time that NADPH oxidase is involved in sFlt-1 and PlGF secretion in first trimester chorionic villi. Indeed, the inhibition of Nox by DPI decreases sFlt-1, and increases PlGF secretions. We also demonstrate the involvement of p38 MAPK in sFlt-1 secretion and Nox activation as blocking the p38 MAPK phosphorylation decreases both sFlt-1 secretion and superoxide production. Nevertheless, TGF-β1-mediated p38 activation do not seem to be involved in regulation of the first trimester placental angiogenic balance and no crosstalk was found between SMAD2 and p38 MAPK pathways.

Conclusions: Thus, the placental NADPH oxidase play a major role in mediating the signal transduction cascade of sFlt-1 production. Furthermore, we highlight for the first time the involvement of p38 activation in first trimester placental Nox activity.

Abstract

Introduction: Retinopathy of prematurity (ROP) is a blinding disease that requires screening by retinal examination. Screening practices are rarely evaluated. We aimed to determine the prevalence of ROP screening in very preterm infants and individual- and center-related factors associated with ROP screening.

Methods: Data were extracted from the EPIPAGE-2 cohort, a French prospective population-based study of premature births in 2011. Children born before 32 weeks’ gestation (WG) without severe malformation and alive at the recommended time for ROP screening were included. Outcome measures were achievement of ROP screening and compliance with recommended screening timeline. Individual- and center-related factors associated with both measures were studied using mixed models.

Results: Among 3,077 eligible infants, 2,169 (70.5%) had a ROP screening, ranging from 96% at 24 WG to 50% at 31 WG. Large variability among units was observed. Individual characteristics associated with screening were low gestational age, low birth weight, severe bronchopulmonary dysplasia or neurological lesions, and transfer between neonatal units during the screening period. Odds of screening were higher in neonatal units using wide-angle imaging (odds ratio 2.65 [95% confidence interval 1.17-6.01]) but decreased in units without a local protocol for ROP screening (0.03 [0.01-0.09]). Among screened children, 1,641/2,169 (75.7%) were screened according to recommended timeline. Delayed screening was associated with low gestational age, severe bronchopulmonary dysplasia or necrotizing enterocolitis, and absence of local protocol for ROP screening.

Discussion/conclusions: In this large cohort study of infants born very preterm, almost one-third were not screened for ROP. Children most at risk for ROP were the best screened but often with delay. The higher compliance of neonatal units using wide-angle imaging systems supports its use.

Abstract

Introduction: While use of augmentation of labor (AL) is appropriate for labor dystocia, it is frequently used inadequately and unnecessarily. The objective was to assess at a national level, the frequency and determinants of misuse of augmentation of labor (AL).

Material and methods: Women of the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. « Misuse of AL » was defined by artificial rupture of the membranes (ROM) and/or oxytocin within one hour of admission and/or duration between ROM and oxytocin of less than one hour. Women, labor and maternity unit’s characteristics were compared between the « misuse of AL » and « no misuse of AL » groups by bivariate analysis. To identify the determinants of misuse of AL, a multivariable multilevel logistic regression was performed taking into account the data’s hierarchical structure (first level: women, second level: maternity units).

Results: Among the 7196 women included, 1524 (21.2%) had a misuse of AL. The determinants of misuse of AL were middle school educational level (reference high school), aOR = 1.21; 95%CI[1.01-1.45], gestational age at delivery ≥41weeks (reference 39-40 weeks), aOR = 1.19; 95%CI[1.00-1.42], cervical dilation ≥6cm at admission (reference <3cm), aOR = 1.39; 95%CI[1.10-1.76], epidural analgesia aOR = 1.63; 95%CI[1.35-1.96], delivery in a private hospital (reference public teaching hospital), aOR = 2.25; 95%CI[1.57-3.23]; and maternity units with <1000 deliveries/year and 1000-1999 deliveries/year (reference ≥3000 deliveries/year), respectively aOR = 1.52; 95%CI[1.11-2.08] and aOR = 1.42; 95%CI[1.05-1.92]. Less than 3% of the variance was explained by women characteristics, and 24.17% by the maternity units’ characteristics.

Conclusions: In France, one spontaneous laboring woman among five is subject to misuse of AL. The misuse is mostly explained by maternity unit’s characteristics. The determinants identified in this study can be used to implement targeted actions in small and private maternity units.

[Maternal mortality in France 2013-2015: An evolving profile].

Editorial: No abstract available

Editorial : No abstract available

Abstract

Objectives: Following an alert on neural tube defects and dolutegravir, we sought to evaluate if the exposure integrase strand transfer inhibitors (INSTIs) at conception was associated with birth defects or other adverse pregnancy outcomes.

Methods: In the prospective national French Perinatal Cohort (EPF), we studied birth defects and other perinatal outcomes by matching each pregnant woman exposed to INSTIs with a pregnant woman exposed to darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors and matched for other characteristics such as age, geographic origin, centre and year of delivery.

Results: Among 808 women exposed to INSTIs during pregnancy (raltegravir = 703, dolutegravir = 57 and elvitegravir = 48), we reported a slightly higher rate of birth defects in infants exposed at conception to raltegravir (6.7%) vs. infants exposed to raltegravir later in pregnancy: 2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment, P =0.04. When compared with matched controls, raltegravir exposure at conception was not significantly associated with birth defects: 6.4 vs. 2.3%, P = 0.08. There was no cluster of birth defect type and no neural tube defects were observed. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched counterparts. No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir.

Conclusion: We found a nonsignificant trend for an association between exposure to raltegravir at conception and birth defects, which needs to be evaluated by larger prospective surveillance data, as these drugs are increasingly prescribed in women living with HIV.

[Systemic racism and health inequalities, a sanitary emergency revealed by the COVID-19 pandemic]

Editorial

Abstract

Introduction: Preterm babies are a vulnerable population that experience significant short and long-term morbidity. Rehospitalisations constitute an important, potentially modifiable adverse event in this population. Improving the ability of clinicians to identify those patients at the greatest risk of rehospitalisation has the potential to improve outcomes and reduce costs. Machine-learning algorithms can provide potentially advantageous methods of prediction compared to conventional approaches like logistic regression. 

Objective: To compare two machine-learning methods (least absolute shrinkage and selection operator (LASSO) and random forest) to expert-opinion driven logistic regression modelling for predicting unplanned rehospitalisation within 30 days in a large French cohort of preterm babies. 

Design, Setting and Participants: This study used data derived exclusively from the population-based prospective cohort study of French preterm babies, EPIPAGE 2. Only those babies discharged home alive and whose parents completed the 1-year survey were eligible for inclusion in our study. All predictive models used a binary outcome, denoting a baby’s status for an unplanned rehospitalisation within 30 days of discharge. Predictors included those quantifying clinical, treatment, maternal and socio-demographic factors. The predictive abilities of models constructed using LASSO and random forest algorithms were compared with a traditional logistic regression model. The logistic regression model comprised 10 predictors, selected by expert clinicians, while the LASSO and random forest included 75 predictors. Performance measures were derived using 10-fold cross-validation. Performance was quantified using area under the receiver operator characteristic curve, sensitivity, specificity, Tjur’s coefficient of determination and calibration measures. 

Results: The rate of 30-day unplanned rehospitalisation in the eligible population used to construct the models was 9.1% (95% CI 8.2-10.1) (350/3,841). The random forest model demonstrated both an improved AUROC (0.65; 95% CI 0.59-0.7; p = 0.03) and specificity vs. logistic regression (AUROC 0.57; 95% CI 0.51-0.62, p = 0.04). The LASSO performed similarly (AUROC 0.59; 95% CI 0.53-0.65; p = 0.68) to logistic regression. 

Conclusions: Compared to an expert-specified logistic regression model, random forest offered improved prediction of 30-day unplanned rehospitalisation in preterm babies. However, all models offered relatively low levels of predictive ability, regardless of modelling method.

Abstract

In high-income countries, breastfeeding has been shown to be positively associated with socioeconomic position. However, less is known about breastfeeding practices and their associated factors among extremely disadvantaged populations. We aimed to assess the associations of cultural origins and socioeconomic factors with any breastfeeding initiation and duration in homeless families. We analyzed data from 456 children aged 6 months to 5 years from the cross-sectional ENFAMS survey, conducted in 2013 among a random sample of homeless families in shelters in the Greater Paris area. Data were collected by bilingual interviewers in 17 languages. Four nested multivariable robust Poisson regression models were run in a hierarchical framework to determine the factors associated with breastfeeding initiation and with any breastfeeding for 6 months or more. Most of the children (86.0%) had previously been or were currently being breastfed at the time of the survey; 58.9% were fed with breast milk ≥6 months. A higher maternal age and African origin were positively associated with breastfeeding ≥6 months, although the relation to the region of origin was moderated by education level. Migration to escape war, unrest or other violence and the child’s birth in France were inversely associated with breastfeeding ≥6 months. Any breastfeeding by these homeless mothers seems influenced predominantly by their cultural origin and complicated by a difficult migration trajectory. The possible influence of poor material circumstances and cumulative hardship should encourage interventions targeted at homeless mothers that emphasize social/family support with a commitment to improving the family’s living conditions.

Abstract

Objective: To assess twins’ perinatal outcomes after planned vaginal delivery according to chorionicity.

Methods: JUMODA (JUmeaux MOde D’Accouchement) was a national prospective population-based cohort study of twin deliveries performed in 176 maternity units in France from 02/2014 to 03/2015. In this planned secondary analysis, we compared perinatal outcomes of twins born at or after 32 weeks of gestation after planned vaginal delivery when the first twin was in cephalic presentation according to chorionicity. To select a population with well recognized indications of planned vaginal delivery, we applied the same exclusion criteria as in the international randomized trial, the Twin Birth Study. Finally, twin-to-twin transfusion syndromes and twin anemia-polycythemia sequences defined complicated monochorionic twin pregnancies and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. We used multivariable logistic regression models to control for potential confounders. We conducted subgroup analyses according to birth order, first or second twin, and gestational age at delivery, before or after 37 weeks of gestation.

Results: Among 3873 women at or after 32 weeks with a cephalic first twin and a planned vaginal delivery according to the Twin Birth Study criteria, 729 (18.8%) were uncomplicated monochorionic and 3144 (81.2%) dichorionic twin pregnancies. Composite intrapartum mortality and neonatal morbidity and mortality did not differ between uncomplicated monochorionic (27/1458 (1.9%)) and dichorionic (107/6288 (1.7%)) twin pregnancies (aRR 1.07, 95% CI 0.66-1.75). No significant difference between groups was shown in subgroup analyses according to birth order and gestational age at delivery.

Conclusions: In case of planned vaginal delivery at or after 32 weeks of gestation when the first twin is in cephalic presentation, uncomplicated monochorionic twin pregnancies are not associated with higher composite intrapartum mortality and neonatal morbidity and mortality than dichorionic twin pregnancies. This article is protected by copyright. All rights reserved.