Publications

Abstract

Introduction: Pre-viable premature rupture of membranes (pre-viable PROM) is a rare event occurring in less than 1% of pregnancies. Nevertheless, it can be responsible for severe maternal complications, the risk of which needs to be balanced with the possibility to prolong the pregnancy up to viable gestational age. Maternal sepsis was reported in 1%-5% of women who received conservative management and prophylactic antibiotics, but information on maternal mortality is lacking. Our objective was to identify maternal deaths in women who had pre-viable PROM, describe the characteristics of the women, explore preventability factors within the care they received, and estimate the lethality of pre-viable PROM.

Material and methods: We identified all maternal deaths associated with pre-viable PROM from the 2001-2015 French National Confidential Enquiry into Maternal Deaths (NCMM). Data on women’s characteristics and the care they received were extracted from the ENCMM database. The lethality was determined after estimating the total number of pregnant women with pre-viable PROM from the national hospital discharge database.

Results: Between 2001 and 2015, we identified seven maternal deaths associated with pre-viable PROM, representing 0.6% of all maternal deaths over this period (ie, maternal mortality ratio 0.06/100 000 live births). Six maternal deaths were attributed to sepsis after genital infection by Gram-negative bacilli and one to postpartum hemorrhage due to placenta accreta. Four of these seven cases were considered preventable. The main preventability factors were delayed diagnosis, delayed fetal extraction, and inappropriate antibiotic treatment. The estimated lethality was 4.5/10 000 women with pre-viable PROM.

Conclusions: Maternal death associated with pre-viable PROM is rare but possible. Most of these deaths seem preventable, with areas for improvement related to earlier diagnosis and better treatment of uterine infections, which can evolve rapidly.

No abstract available

Abstract

The impact of the COVID-19 pandemic on bloodstream infections (BSIs) due to Streptococcus pneumoniae and Streptococcus pyogenes was assessed in 25 university hospitals of Paris. Monthly BSIs incidence rates that appeared stable in 2018 and 2019, decreased for the 2 pathogens during the 2 COVID-19 lockdown periods of 2020. Containment policies, including social distancing, masking and hand hygiene strengthening in both community and hospital settings are likely to reduce BSIs due to these pathogens.

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.

No abstract available

Abstract

Background and objectives: Despite the potentially devastating effects of pregnancy-related stroke, few studies have examined its incidence by type of stroke. We aimed to study the nationwide incidence rates and recent temporal trends for all types of pregnancy-related stroke and to compare these incidences with stroke incidence in nonpregnant women.

Methods: We conducted a study of 6,297,698 women aged 15-49 years who gave birth in France between 2010 and 2018 with no history of stroke before pregnancy by collecting data from the French National Health Insurance Information System database. Poisson regression was used to estimate the incidence by types of strokes for the different pregnancy periods and the incidence rate ratio of stroke in pregnant vs nonpregnant French women.

Results: Among the 6,297,698 women, 1,261 (24.0 per 100,000 person-years) experienced a first ever stroke during, antepartum peripartum, or the first 6 weeks of postpartum. Of the pregnancy-related strokes, 42.9% were ischemic (IS), 41.9% were hemorrhagic (with similar proportion of intracerebral and subarachnoid hemorrhage), and 17.4% were cerebral venous thrombosis (CVT). Compared with nonpregnant women, incidence rates of stroke were similar during pregnancy for IS (adjusted incidence risk ratio [IRR] 0.9 [0.8-1.1]), slightly higher for all hemorrhagic strokes (IRR 1.4 [1.2-1.8]), and considerably increased for CVT (IRR 8.1 [6.5-10.1]). Pregnancy-related stroke incidence rose between 2010 and 2018 for IS and HS but was stable for CVT.

Discussion: The risk of pregnancy-related CVT was more than 8-fold higher than that observed in nonpregnant women. The incidence of pregnancy-related IS and HS is increasing over time, and efforts should be made for prevention considering treatable cardiovascular risk factors and hypertensive disorders in pregnant women.

Abstract

Background: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome.

Methods: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks’ gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076.

Findings: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia.

Interpretation: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction.

Abstract

Purpose: This study aims to (1) describe the health-related quality of life (HRQoL) outcomes experienced by children born very preterm (28-31 weeks’ gestation) and extremely preterm (< 28 weeks’ gestation) at five years of age and (2) explore the mediation effects of bronchopulmonary dysplasia (BPD) and severe non-respiratory neonatal morbidity on those outcomes.

Methods: This investigation was based on data for 3687 children born at < 32 weeks’ gestation that contributed to the EPICE and SHIPS studies conducted in 19 regions across 11 European countries. Descriptive statistics and multi-level ordinary linear squares (OLS) regression were used to explore the association between perinatal and sociodemographic characteristics and PedsQL^™ GCS scores. A mediation analysis that applied generalised structural equation modelling explored the association between potential mediators and PedsQL^™ GCS scores.

Results: The multi-level OLS regression (fully adjusted model) revealed that birth at < 26 weeks’ gestation, BPD status and experience of severe non-respiratory morbidity were associated with mean decrements in the total PedsQL^™ GCS score of 0.35, 3.71 and 5.87, respectively. The mediation analysis revealed that the indirect effects of BPD and severe non-respiratory morbidity on the total PedsQL^™ GCS score translated into decrements of 1.73 and 17.56, respectively, at < 26 weeks’ gestation; 0.99 and 10.95, respectively, at 26-27 weeks’ gestation; and 0.34 and 4.80, respectively, at 28-29 weeks’ gestation (referent: birth at 30-31 weeks’ gestation).

Conclusion: The findings suggest that HRQoL is particularly impaired by extremely preterm birth and the concomitant complications of preterm birth such as BPD and severe non-respiratory morbidity.

Abstract

Objectives: Recent studies suggest an association between COVID-19 infection during pregnancy and preeclampsia. Nonetheless, these studies are subject to numerous biases. We compared the onset of preeclampsia in a group with symptomatic COVID-19 during pregnancy to that in a group whose non-exposure to the virus was certain, in a center where pregnancy management was identical in both groups.

Study design: This was a single-center study comparing exposed and unexposed patients. The exposed group included pregnant women with symptomatic COVID-19 infection (diagnosed by RT-PCR or CT scan), who gave birth between March and December, 2020. The unexposed group included pregnant women who gave birth between March and December, 2019. Only cases of preeclampsia that occurred after COVID-19 infection were considered. A multivariate analysis was performed to study the existence of an association between COVID-19 and preeclampsia. A sensitivity analysis was performed among nulliparous patients.

Results: The frequency of preeclampsia was 3.2% (3/93) in the exposed group, versus 2.2% (4/186) in the unexposed group (P = 0.58). Among the nulliparous patients, the frequency of preeclampsia was 4.9% (2/41) in the exposed group versus 0.9% (1/106) in the unexposed group (P = 0.13). The association between COVID-19 and preeclampsia was not significant after multivariate analysis (OR 3.12, 95% CI 0.39-24.6).

Conclusion: Symptomatic COVID-19 infection during pregnancy does not appear to increase the risk of preeclampsia strongly, although the size of our sample prevents us from reaching a conclusion about a low or moderate risk. It therefore does not appear necessary to reinforce preeclampsia screening in patients with symptomatic COVID-19 infection during pregnancy.

Abstract

Objective: To evaluate the use of cervical dilators concurrently with misoprostol to shorten labor in second-trimester medical termination of pregnancy.

Methods: This multicenter randomized controlled trial compared the efficacy of cervical dilators inserted concurrently with misoprostol with that of misoprostol, alone, to shorten labor for women undergoing termination of pregnancy between 15 0/7 and 27 6/7 weeks of gestation. The primary outcome was the proportion of women with a duration of labor exceeding 12 hours. Secondary outcomes included median duration of labor, time to amniotomy, side effects, complications, NPRS (Numeric Pain Rating Scale) score, and women’s distress as measured by the IES-R (Impact of Event Scale-Revised). These outcomes also were studied separately in the nulliparous subgroup. To demonstrate a reduction of 50% of the proportion of women with a duration of labor exceeding 12 hours in the dilator group, with a power of 80% and a 2-sided 0.05 significance level, a sample of 268 women (134 in each group) was required.

Results: Between December 2017 and September 2019, this study enrolled and analyzed 347 women: 174 in the dilator group and 173 in the control group, including 87 and 93 nulliparous patients, respectively. Sociodemographic and obstetric characteristics were similar between groups. The proportion of women with labor exceeding 12 hours was not different between groups (49/174 [28.2%] in the dilator group vs 53/173 [30.6%] in the control group [P=.61] for the whole population, and 37/87 [42.5%] vs 42/93 [45.2%] [P=.72], respectively, among nulliparous patients). Median duration of labor was 8.5 hours in the dilator group compared with 9.2 hours in the control group (P=.65) for the whole population, and 10.5 hours compared with 11.8 hours, respectively, among nulliparous patients (P=.33). Median time to amniotomy was 3.6 hours in the dilator group compared with 5.0 hours in the control group (P=.08) for the whole population, and 3.5 hours compared with 6.7 hours, respectively, among nulliparous patients (P=.003). Side effects, complications, NPRS score, and IES-R score were similar between groups.

Conclusion: Cervical dilators inserted concurrently with misoprostol did not reduce the proportion of women whose labor exceeded 12 hours compared with misoprostol alone.