Publications

Abstract

Objective: To re-visit short-term outcomes and associated risk factors of newborns with hypoxic-ischemic encephalopathy (HIE) in an era where hypothermia treatment (HT) is widespread.

Methods: This is a prospective population-based cohort in French neonatal intensive care units (NICU). Neonates born at or after 34 weeks of gestational age with HIE were included; main outcomes were in-hospital death and discharge with abnormal or normal MRI. Associations of early perinatal risk factors, present at birth or at admission to NICU, with these outcomes were studied.

Results: A total of 794 newborns were included and HT was administered to 670 (84.4%); 18.3% died and 28.5% and 53.2% survived with abnormal and normal MRI, respectively. Severe neurological status, Apgar score at 5 mn ≤5, lactate at birth ≥11 mMoles/l, and glycemia ≥100 mg/dL at admission were associated with an increased risk of death (relative risk ratios (aRRR) (95% CI) 19.93 (10.00-39.70), 2.89 (1.22-1.62), 3.06 (1.60-5.83), and 2.55 (1.38-4.71), respectively). Neurological status only was associated with survival with abnormal MRI (aRRR (95% CI) 1.76 (1.15-2.68)).

Conclusion: Despite high use of HT in this cohort, 46.8% died or presented brain lesions. Early neurological and biological examinations were associated with unfavorable outcomes and these criteria could be used to target children who warrant further neuroprotective treatment.

Trial registration: Clinical trial registry, NCT02676063, ClinicalTrials.gov.

Impact: In this population-based cohort of newborns with HIE where 84% received hypothermia, 46.8% still had an unfavorable evolution (death or survival with abnormal MRI). Risk factors for death were high lactate, low Apgar score, severe early neurological examination, and high glycaemia. While studies have established risk factors for HIE, few have focused on early perinatal factors associated with short-term prognosis. This French population-based cohort updates knowledge about early risk factors for adverse outcomes in the era of widespread cooling. In the future, criteria associated with an unfavorable evolution could be used to target children who would benefit from another neuroprotective strategy with hypothermia.

Abstract

Background: Cardiovascular diseases, including acute coronary syndromes, are the leading cause of maternal death in many developed countries.

Objective: We assessed acute coronary syndrome incidences during pregnancy, peripartum, and postpartum periods. We also compared overall pregnancy (ie, covering all 3 periods) incidence with that found in nonpregnant women of childbearing age.

Study design: All women aged between 15 and 49 years without ischemic heart disease who delivered between 2010 and 2018 in France were included in the CONCEPTION cohort. Data were extracted from the French National Health Insurance Information System database. Acute coronary syndromes were defined according to the International Classification of Diseases, Tenth Revision codes recorded in the principal hospital diagnosis. We used Poisson regression to estimate crude acute coronary syndrome incidences, and tested age-adjusted Poisson models to compare the incidence risk ratio of acute coronary syndrome between pregnant and nonpregnant women, with 95% confidence intervals.

Results: Among 6,298,967 deliveries in France, we observed 225 first-time acute coronary syndrome diagnoses during overall pregnancy (overall pregnancy-related acute coronary syndrome incidence, 4.34/100,000 person-years; 1 case/23,000 pregnancies). In multivariate analysis, independent factors associated with acute coronary syndrome were age, social deprivation, obesity, tobacco use, chronic hypertension, and hypertensive disorders of pregnancy (all P<.05). Among the nonpregnant women aged 15 to 49 years in the general French population, 18,247 cases of acute coronary syndrome (incidence, 16.5/100,000 person-years) occurred throughout the whole study period (>100 million person-years). Compared with the acute coronary syndrome incidence in nonpregnant women, age-adjusted overall pregnancy-related acute coronary syndrome incidence was lower (incidence rate ratio, 0.76; 95% confidence interval, 0.57-0.98; P<.05). Although compared with nonpregnant women, age-adjusted incidence rates were lower during pregnancy, risk was increased during peripartum and postpartum periods.

Conclusion: With an incidence of 4.34 per 100,000 person-years, acute coronary syndrome still accounts for a significant proportion of maternal mortality. The peripartum and postpartum periods remain high-risk periods, and greater efforts should be made in terms of acute coronary syndrome prevention, especially because several cardiovascular risk factors are treatable, such as tobacco use and hypertensive disorders of pregnancy.

Abstract

Background: In early terminations of pregnancy for fetal anomaly (TOPFA) without identified cytogenetic abnormality, a fetal autopsy is recommended for diagnostic purposes, to guide genetic counseling. Medical induction, which allows analysis of a complete fetus, is generally preferred over surgical vacuum aspiration. Our objective was to assess the diagnostic value of fetal autopsies in these early terminations, relative to the first-trimester ultrasound, overall and by termination method.

Materials: For this retrospective study at the Port Royal Maternity Hospital, we identified all TOPFA performed from 11 weeks to 16 weeks diagnosed at the first-trimester ultrasound in cases with a normal karyotype. The principal endpoint was the additional value of the autopsy over /compared to the ultrasound and its impact on genetic counseling, globally and by termination method. The secondary objective was to compare the complication rate by method of termination.

Results: The study included 79 women during period of 2013-2017: 42 with terminations by medical induction and 37 by aspiration. Fetal autopsy found additional abnormalities in 54.4% of cases, more frequently after medical induction (77.5%) than after aspiration (21.4%, p < .01). Genetic counseling was modified in 20.6% of cases, more often after induction (32.5% vs 3.6%, p < .01). The length of stay was significantly longer and a secondary aspiration was required in 16,7% of case in the medical induction group (p < .01).

Conclusion: Medically induced vaginal expulsion appears preferable and can change genetic counseling for subsequent pregnancies.

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.