Publications

Abstract

Background: An increased risk of severe maternal morbidity and mortality has been described in migrant women, particularly in those born in sub-Saharan Africa. The mechanisms in question are poorly identified and rarely studied specifically.

Objective: To compare changes in maternal and perinatal morbidity inequalities among migrant and native women over time, between 2008 and 2014.

Material and method: A retrospective, single-centre study carried out at the Maternity Unit of the University of Caen Hospital in France. All women who gave birth in 2008 or 2014 were included. Twin pregnancies and delivery before reaching 22 weeks of pregnancy were excluded. Pre-pregnancy characteristics and maternal and perinatal morbidities were collected from the university hospital’s medical and administrative database. We compared the maternal and perinatal morbidity in 2008 and 2014 of women born in France to the morbidity of women born abroad. Secondly, we compared these migrant women between 2008 and 2014 to see if changes in the characteristics of migrant women were associated with a change in the type of maternal and perinatal complications.

Results: Of the 3,038 and 3,001 women included in 2008 and 2014, respectively, 272 (9.0 %) and 385 (12.8 %) women were migrants. Compared to women born in France, we found two times more severe postpartum hemorrhages in women born in sub-Saharan Africa (aOR = 2.1[1.1-3.9]) and a significant increase in the risk of gestational diabetes in women born in North Africa (aOR = 1.9[1.2-2.9]). We found a significant increase in the risk of severe postpartum hemorrhage (aOR = 2.1[1.5-3.0]) and gestational diabetes (aOR = 3.0[2.5-3.7]) in 2014 compared to 2008. We did not find a significant difference in perinatal morbidity between 2008 and 2014.

Conclusion: We noted a significant increase in the risk of severe postpartum hemorrhage in women born in sub-Saharan Africa and gestational diabetes in women born in North Africa compared to those born in France, and these risks increase in 2014 relative to 2008.

Abstract

Study question: Is there a difference in the risk of serious maternal complications during pregnancy and the postpartum in twin pregnancies according to mode of conception: natural conception, non-IVF fertility treatment, IVF, ICSI or oocyte donation?

Summary answer: Women with twin pregnancies after medically assisted reproduction (MAR) had an overall risk of serious maternal complications 30% higher compared with women with natural twin pregnancies, and this association varied according to the MAR procedure; the risk was increased by 50% with IVF using autologous oocytes and by 270% with oocyte donation.

What is known already: IVF has been reported as a risk factor for serious maternal complications in several concordant studies of singleton pregnancies. For twin pregnancies, this association is less well documented with imprecise categorisation of the mode of conception, and results are contradictory.

Study design, size, duration: This is a secondary analysis of the national, observational, prospective, population-based cohort study of twin pregnancies (JUmeaux Mode d’Accouchement), which took place in France from 10 February 2014 through 1 March 2015. All French maternity units performing more than 1500 annual deliveries were invited to participate, regardless of their academic, public or private status or level of care. Of the 191 eligible units, 176 (92%) participated.

Participants/materials, setting, methods: Women with a twin pregnancy who gave birth at or after 22 weeks of gestation were eligible (N = 8823 women included). We excluded women whose mode of conception was unknown (n = 75). Serious maternal complications were regrouped within the recently emerged concept of severe acute maternal morbidity (SAMM), as a binary composite outcome. The exposure of interest was the mode of conception, studied in five classes: natural conception (reference group), non-IVF fertility treatment including insemination and ovarian stimulation, IVF with autologous oocyte, ICSI with autologous oocyte and oocyte donation. To assess the association between the mode of conception and SAMM, we used multivariate logistic regression to adjust for confounders. Structural equation modelling (SEM) was used to explore the contribution to this association of potential intermediate factors, i.e. factors possibly caused by the mode of conception and responsible for SAMM: non-severe pre-eclampsia, placenta praevia and planned mode of delivery.

Main results and the role of chance: Among the 8748 women of the study population, 5890 (67.3%) conceived naturally, 854 (9.8%) had non-IVF fertility treatment, 1307 (14.9%) had IVF with autologous oocytes, 368 (4.2%) had ICSI with autologous oocytes and 329 (3.8%) used oocyte donation. Overall, 538 (6.1%) developed SAMM. Women with twin pregnancy after any type of MAR had a higher risk of SAMM than those with a natural twin pregnancy, after adjustment for confounders (7.9% (227/2858) compared to 5.3% (311/5890), adjusted odds ratio (aOR) 1.3, 95% CI 1.1-1.6). This association varied according to the MAR procedure. The risk of SAMM was higher among women with IVF using either autologous oocytes (8.3%; 108/1307) or oocyte donation (14.0%; 46/329) compared with the reference group (respectively aOR 1.5, 95% CI 1.1-1.9 and aOR 2.7, 95% CI 1.8-4.1) and higher after oocyte donation compared with autologous oocytes (aOR 1.7, 95% CI 1.1-2.6). Conversely, the risk of SAMM for women with non-IVF fertility treatment (6.2%; 53/854) and with ICSI using autologous oocytes (5.4%; 20/368) did not differ from that of the reference group (5.3%; 311/5890) (respectively aOR 1.1, 95% CI 0.8-1.5 and aOR 0.9, 95% CI 0.6-1.5). The tested intermediate factors poorly explained these increased risks.

Limitations, reasons for caution: Beyond the confounders and intermediate factors considered in our analysis, specific causes of infertility and specific aspects of infertility treatments may explain the differences in the risk of SAMM by mode of conception. However, these data were not available.

Wider implications of the findings: Our study showed an increased risk of SAMM in women with twin pregnancies after MAR, notably after IVF using autologous oocytes and particularly after oocyte donation. To avoid unnecessary exposure to the high-risk combination of MAR and multiple pregnancies, transfer of a single embryo should be encouraged whenever possible. Knowledge of these differential risks may inform discussions between clinicians and women about the mode of conception and help to optimise obstetric care for women in subgroups at higher risk.

Study funding/competing interest(s): This work was supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique, AOM2012). There are no competing interests.

The Journal of Pediatrics. 2020 Jul 22;S0022-3476(20)30959-8., doi: https://doi.org/10.1016/j.jpeds.2020.07.060.

Letter to the Editor:

We read with great interest the report by Li et al [1] that compared the incidence of necrotizing enterocolitis (NEC) in very low birth weight infants according to early antibiotic treatment. We would like to raise the question: association of early antibiotic exposure and NEC: causality or confounding bias?

Refers to:

Yanqi Li, René Liang Shen, Adejumoke I. Ayede, & al.
Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: The NEOMUNE-NeoNutriNet Cohort Study
The Journal of Pediatrics, Available online 14 June 2020, Pages

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Acta Obstet Gynecol Scand. 2020 Dec;99(12):1682-1690. doi: 10.1111/aogs.13939.Epub 2020 Jul 13.

Abstract

Introduction: The objective of this study was to investigate the association between planned mode of delivery and neonatal outcomes with spontaneous very preterm birth among singletons in cephalic presentation.

Material and methods: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national, prospective, population-based cohort study of preterm infants. For this study, we included women with a singleton cephalic pregnancy and spontaneous preterm labor or preterm premature rupture of membranes at 24-31 weeks’ gestation. The main exposure was the planned mode of delivery (ie planned vaginal delivery or planned cesarean delivery at the initiation of labor). The primary outcome was survival at discharge and secondary outcome survival at discharge without severe morbidity. Propensity scores were used to minimize indication bias in estimating the association.

Results: The study population consisted of 1008 women: 206 (20.4%) had planned cesarean delivery and 802 (79.6%) planned vaginal delivery. In all, 723 (90.2%) finally had a vaginal delivery. Overall, 187 (92.0%) and 681 (87.0%) neonates in the planned cesarean delivery and planned vaginal delivery groups were discharged alive, and 156 (77.6%) and 590 (76.3%) were discharged alive without severe morbidity. After matching on propensity score, planned cesarean delivery was not associated with survival (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 0.48-2.28) or survival without severe morbidity (aOR 0.64, 95% CI 0.36-1.16).

Conclusions: Planned cesarean delivery for cephalic presentation at 24-31 weeks’ gestation after preterm labor or preterm premature rupture of membranes does not improve neonatal outcomes.

Nanomaterials (Basel). 2020 Jul 3;10(7):1309. doi: 10.3390/nano10071309. PMID: 32635405

Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta – PubMed

Abstract

The human placenta is at the interface between maternal and fetal circulations, and is crucial for fetal development. The nanoparticles of cerium dioxide (CeO₂ NPs) from air pollution are an unevaluated risk during pregnancy. Assessing the consequences of placenta exposure to CeO₂ NPs could contribute to a better understanding of NPs’ effect on the development and functions of the placenta and pregnancy outcome. We used primary villous cytotrophoblasts purified from term human placenta, with a wide range of CeO₂ NPs concentrations (0.1-101 μg/cm²) and exposure time (24-72 h), to assess trophoblast uptake, toxicity and impact on trophoblast differentiation and endocrine function. We have shown the capacity of both cytotrophoblasts and syncytiotrophoblasts to internalize CeO₂ NPs. CeO₂ NPs affected trophoblast metabolic activity in a dose and time dependency, induced caspase activation and a LDH release in the absence of oxidative stress. CeO₂ NPs decreased the fusion capacity of cytotrophoblasts to form a syncytiotrophoblast and disturbed secretion of the pregnancy hormones hCG, hPL, PlGF, P4 and E2, in accordance with NPs concentration. This is the first study on the impact of CeO₂ NPs using human primary trophoblasts that decrypts their toxicity and impact on placental formation and functions.

Abstract

Background: Monitoring severe acute maternal morbidity (SAMM) appears essential for optimising care and informing health care policies, especially given changes in obstetric practices and mother profiles. International comparisons can identify areas where improvement is needed, but the comparability of indicators must be evaluated.

Objective: To assess the feasibility of monitoring SAMM using common definitions from hospital discharge databases across Europe.

Methods: We used hospital discharge data in eight countries (2 826 868 deliveries) to identify women with SAMM among all hospitalisations of women of reproductive age admitted for antenatal or delivery care. Five SAMM indicators were investigated: eclampsia, septicaemia, hysterectomy, hysterectomy associated with a diagnosis of obstetric haemorrhage, and red blood cell (RBC) transfusion associated with a diagnosis of obstetric haemorrhage. Between-country variation was described, by the ratio of the highest to lowest rates, while external validation was assessed by comparing with population-based studies on maternal morbidity.

Results: Ratios for hysterectomy and red blood cell (RBC) transfusion in the context of obstetric haemorrhage were 1:2.1 and 1:3.5, respectively. High values of hysterectomy and low values of transfusion were both consistent with high maternal mortality from haemorrhage (France, Italy, Portugal). Ratios across countries were relatively low for eclampsia (1:3.4) but very high for septicaemia (1:22.5). Compared to population-based morbidity estimates, eclampsia was over-reported in hospital databases whereas the two indicators of severe haemorrhage had good external validity.

Conclusions: In association with diagnosis codes indicating obstetric haemorrhage, hysterectomy and RBC transfusion appear to be good candidates for surveillance of maternal morbidity in Europe.

J Pediatr. 2020 Jul;222:71-78.e6. doi: 10.1016/j.jpeds.2020.03.021.

Abstract

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 24^0/7 to 31^6/7 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.

Abstract

Objectives: To describe patterns of care for very preterm (VP) babies across neonatal intensive care units (NICUs) and associations with outcomes.

Design: Prospective cohort study, EPIPAGE-2.

Setting: France, 2011.

Participants: 53 (NICUs); 2135 VP neonates born at 27 to 31 weeks.

Outcome measures: Clusters of units, defined by the association of practices in five neonatal care domains – respiratory, cardiovascular, nutrition, pain management and neurodevelopmental care. Mortality at 2 years corrected age (CA) or severe/moderate neuro-motor or sensory disabilities and proportion of children with scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ).

Methods: Hierarchical cluster analysis to identify clusters of units. Comparison of outcomes between clusters, after adjustment for potential cofounders.

Results: Three clusters were identified: Cluster 1 with higher proportions of neonates free of mechanical ventilation at 24 hours of life, receiving early enteral feeding, and neurodevelopmental care practices (26 units; n=1118 babies); Cluster 2 with higher levels of patent ductus arteriosus and pain screening (11 units; n=398 babies); Cluster 3 with higher use of respiratory, cardiovascular and pain treatments (16 units; n=619 babies). No difference was observed between clusters for the baseline maternal and babies’ characteristics. No differences in outcomes were observed between Clusters 1 and 3. Compared with Cluster 1, mortality at 2 years CA or severe/moderate neuro-motor or sensory disabilities was lower in Cluster 2 (adjusted OR 0.46, 95% CI 0.25 to 0.84) but with higher proportion of children with an ASQ below threshold (adjusted OR 1.49, 95% CI 1.07 to 2.08).

Conclusion: In French NICUs, care practices for VP babies were non-randomly associated. Differences between clusters were poorly explained by unit or population differences, but were associated with mortality and development at 2 years. Better understanding these variations may help to improve outcomes for VPT babies, as it is likely that some of these discrepancies are unwarranted.

Obstet Gynecol. 2020 Jun;135(6):1435-1443. doi: 10.1097/AOG.0000000000003862.

Abstract

Objective: To assess neonatal morbidity and mortality according to whether cephalic second twins were born after internal version followed by total breech extraction or after instructions to push. We hypothesized that interval version would result in shorter intertwin delivery intervals and lower cesarean delivery rates for the second twin and therefore better neonatal outcomes.

Methods: These planned analyses of the JUMODA (JUmeaux MODe d’Accouchement) cohort, a national prospective population-based study of twin deliveries, examined births of cephalic second twins after vaginal birth of the first twin at or after 32 weeks of gestation. The internal version group of second twins born in breech presentation after obstetric maneuvers was compared with the pushing group, comprising those born in cephalic presentation. The primary outcome was a composite of neonatal morbidity and mortality. Multivariate modified Poisson regression models were used to control for potential confounders.

Results: Of 2,256 cephalic second twins, 487 (21.6%) were born in breech presentation after internal version and total breech extraction and 1,769 (78.4%) in cephalic presentation after pushing. Composite neonatal morbidity and mortality was not lower in the internal version (17/487 [3.5%]) compared with the pushing group (38/1,769 [2.1%]; adjusted relative risk [aRR] 1.73 [95% CI 0.98-3.05]), although median [quartile 1-quartile 3] intertwin delivery intervals were shorter (5 [4-8] vs 8 [5-12] minutes, P<.001) and the cesarean delivery rate for the second twin lower (5/487 [1.0%] vs 66/1,769 [3.7%], P=.002). Subgroup analyses showed no difference between groups at or after 37 weeks of gestation but higher composite neonatal morbidity and mortality after internal version before 37 weeks (14/215 [6.5%] vs 26/841 [3.1%]; aRR 2.18 [95% CI 1.15-4.13]). Secondary analyses according to center expertise in the overall population and stratified by gestational age yielded concordant results.

Conclusion: Although our sample size precluded a robust assessment for small differences in outcomes between groups, internal version followed by total breech extraction of cephalic second twins was not associated with better neonatal outcomes than pushing.

J Cell Mol Med Actions. 2020 Jun 9;24(13):7660-7669. doi: 10.1111/jcmm.15401. Online ahead of print.

Abstract

The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is essential for placental development, and alterations in its expression and/or activity are associated with human placental pathologies such as pre-eclampsia or IUGR. However, the molecular regulation of PPARG in cytotrophoblast differentiation and in the underlying mesenchyme remains poorly understood. Our main goal was to study the impact of mutations in the ligand-binding domain (LBD) of the PPARG gene on cytotrophoblast fusion (PPARG^E352Q ) and on fibroblast cell migration (PPARG^R262G /PPARG^L319X ). Our results showed that, compared to cells with reconstituted PPARG^WT , transfection with PPARG^E352Q led to significantly lower PPARG activity and lower restoration of trophoblast fusion. Likewise, compared to PPARG^WT fibroblasts, PPARG^R262G /PPARG^L319X fibroblasts demonstrated significantly inhibited cell migration. In conclusion, we report that single missense or nonsense mutations in the LBD of PPARG significantly inhibit cell fusion and migration processes.