Publications

Abstract

Maternal 25-hydroxyvitamin D (25-OHD) deficiency during pregnancy may increase the risk of preterm and small-for-gestational age (SGA) birth, but studies report conflicting results. We used a multicenter prospective cohort of 2813 pregnant women assessed for 25-OHD levels in the first trimester of pregnancy to investigate the association between maternal 25-OHD concentrations and risks of preterm birth (<37 weeks) and SGA (birthweight <10th percentile). Odds ratios were adjusted (aOR) for potential cofounders overall and among women with light and dark skin separately, based on the Fitzpatrick scale. 25-OHD concentrations were <20 ng/mL for 45.1% of the cohort. A total of 6.7% of women had a preterm birth. The aOR for preterm birth associated with the 1st quartile of 25-OHD concentrations compared to the 4th quartile was 1.53 (95% confidence interval (CI): 0.97-2.43). In stratified analyses, an association was observed for women with darker skin (aOR = 2.89 (95% CI: 1.02-8.18)), and no association with lighter skin. A total of 11.9% of births were SGA and there was no association overall or by skin color. Our results do not provide support for an association between maternal first trimester 25-OHD deficiency and risk of preterm or SGA birth overall; the association with preterm birth risk among women with darker skin requires further investigation.

eLife 2019;8:e48772

Le streptocoque du groupe B (Streptococcus agalactiaeou «SGB») est la principale cause d’infection néonatale bactérienne invasive. Un clone hypervirulent spécifique au nouveau-né, le clone CC17, est responsable à lui seul de près de 80% des cas de méningites et de la quasi-totalité des infections tardives qui surviennent au-delà d’une semaine de vie et majoritairement entre trois semaines et deux mois. La voie d’invasion et les facteurs impliqués dans la physiopathologie de l’infection à SGB CC17 sont encore mal connus.

Dans ces travaux publiés au sein dela revue eLIFE, c’est l’impact des hormones maternelles que sont l’estradiol (E2) et la progestérone (P4) qui imprègnent le fœtus tout au long de la grossesse et les premiers mois de la vie du nouveau-né qui a été étudié. Grâce à des approches expérimentales multiples reproduisant l’infection néonatale humaine, les chercheurs ont montré dans un modèle murin que les concentrations élevées d’estradiol (E2) et de progestérone (P4) retrouvées au-delà de 7 jours après la naissance favorisaient spécifiquement la sévérité de la méningite à SGB CC17 après une infection orale. Ces travaux démontrent que le SGB CC17 franchit la barrière intestinale via les cellules M (cellules épithéliales spécialisées permettant le passage des bactéries ou d’antigènes) dans un processus dépendant dela protéine de surface Srr2 spécifique du clone hypervirulent CC17.

Enfin, ils montrent que les concentrations d’estradiol (E2) et de progestérone (P4) retrouvées chez le nouveau-né au-delà de 7 jours de vie favorisent la différenciation des cellules M etle franchissement de la barrière intestinale par ce streptocoque, ce qui apporte pour la première fois une explication à la susceptibilité très particulière des nouveau-nés vis à vis de cette bactérie.

Ces résultats constituent une avancée majeure dans lacompréhension de la physiopathologie des infections néonatales tardives à streptocoque du groupe B et ouvrent la voie aux recherches futures portant sur la physiopathologie des infections néonatales dues à d’autres pathogènes.

Abstract

Background: Delayed interval delivery is a rare practice aiming at prolonging gestation for the second twin in case of pre-viable birth of twin one. Our objective was to identify factors related to successful delayed delivery of the second twin, among cases in which the interval after delivery of the first twin was above 24h.

Method: A descriptive, retrospective and multicenter study of all delayed interval deliveries in dichorionic twins in 4 perinatal centers in Paris over a 14-year period.

Results: In 13 cases of delayed interval delivery, delivery of twin 1 was at a median of 18 weeks’ gestation (range 14WG+2days to 24WG), and none survived. Delivery of the second twin occurred at a median of 25 weeks’ gestation +3 days, 51 days after twin 1 (range 13-138 days). Seven of the 13s twins (54 %) survived. There were 5 cases of chorioamnionitis and 1 case of maternal disseminated intravascular coagulation. Poor outcome was not significantly associated with the gestational age, presentation for PPROM or inflammatory markers (C-reactive protein and white blood cell count) at the time of delivery of twin 1.

Conclusion: Delayed-interval delivery of the second twin may prolong pregnancy and lead the second twin child to a viable term of birth; but carries a risk of maternal complications.

Abstract

Objective: To estimate the prevalence of severe maternal morbidity among very preterm births and determine its association with very preterm infant mortality and morbidity.

Study design: This study used New York City Vital Statistics birth and death records linked with maternal and newborn discharge abstract data for live births between 2010 and 2014. We included 6901 infants without congenital anomalies born between 24^0/7 and 32^6/7 weeks of gestation. Severe maternal morbidity was identified as life-threatening conditions or life-saving procedures. Outcomes were first-year infant mortality, severe neonatal morbidity (bronchopulmonary dysplasia, severe necrotizing enterocolitis, stage 3-5 retinopathy of prematurity, and intraventricular hemorrhage grades 3-4), and a combined outcome of death or morbidity.

Results: Twelve percent of very preterm live-born infants had a mother with severe maternal morbidity. Maternal and pregnancy characteristics associated with occurrence of severe maternal morbidity were multiparity, being non-Hispanic black, and preexisting health conditions, but gestational age and the percentage small for gestational age did not differ. Infants whose mothers experienced severe maternal morbidity had higher first-year mortality, 11.2% vs 7.7% without severe maternal morbidity, yielding a relative risk of 1.39 (95% CI: 1.14-1.70) after adjustment for maternal characteristics, preexisting comorbidities, pregnancy complications, and hospital factors. Severe neonatal morbidity was not associated with severe maternal morbidity.

Conclusions: Severe maternal morbidity is an independent risk factor for mortality in the first year of life among very preterm infants after consideration of other maternal and pregnancy risk factors.

J Pers. 2019 Nov 30. doi: 10.1111/jopy.12528.

OBJECTIVE

Assuming personality to be a system of intra-individual processes emerging over time in interaction with the environment, we propose an idiographic approach to investigate potential changes of intra-individual dynamics in the perception of situations and emotions of individuals varying in personality traits. We compared the semiparametric time-varying autoregressive model (TV-AR) that takes into account the non-stationarity of psychological processes at the individual level, with the standard AR model.

METHOD

We conducted analyses of individual time series to assess intra-individual changes in mean levels and inertia on data from two adolescents who completed measures of personality and indicated their situation perceptions and emotions five times a day for 19 days.

RESULTS

For the less honest, emotional, extraverted, and more agreeable adolescent, the TV-AR model detected reliable changes in the intra-individual dynamics of situation perceptions and emotions whereas, for the other individual, the standard AR model was more preferred, given the lack of changes in the intra-individual dynamics.

CONCLUSIONS

Psychological processes dynamics in situation perception and emotions may vary from person to person depending on their personality. This work constitutes a first step in demonstrating that an idiographic approach has advantages in identifying changes in individuals’ perceptions and reactions to situations.

Assessing the risk of early unplanned rehospitalisation in preterm babies: EPIPAGE 2 study – PubMed

Abstract

Background: Gaining a better understanding of the probability, timing and prediction of rehospitalisation amongst preterm babies could help improve outcomes. There is limited research addressing these topics amongst extremely and very preterm babies. In this context, unplanned rehospitalisations constitute an important, potentially modifiable adverse event. We aimed to establish the probability, time-distribution and predictability of unplanned rehospitalisation within 30 days of discharge in a population of French preterm babies.

Methods: This study used data from EPIPAGE 2, a population-based prospective study of French preterm babies. Only those babies discharged home alive and whose parents responded to the one-year survey were eligible for inclusion in our study. For Kaplan-Meier analysis, the outcome was unplanned rehospitalisation censored at 30 days. For predictive modelling, the outcome was binary, recording unplanned rehospitalisation within 30 days of discharge. Predictors included routine clinical variables selected based on expert opinion.

Results: Of 3841 eligible babies, 350 (9.1, 95% CI 8.2-10.1) experienced an unplanned rehospitalisation within 30 days. The probability of rehospitalisation progressed at a consistent rate over the 30 days. There were significant differences in rehospitalisation probability by gestational age. The cross-validated performance of a ten predictor model demonstrated low discrimination and calibration. The area under the receiver operating characteristic curve was 0.62 (95% CI 0.59-0.65).

Conclusions: Unplanned rehospitalisation within 30 days of discharge was infrequent and the probability of rehospitalisation progressed at a consistent rate. Lower gestational age increased the probability of rehospitalisation. Predictive models comprised of clinically important variables had limited predictive ability.

Abstract

Objective: To determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 years of age.

Design: Prospective standardised cohort study.

Setting: 15 regions in 10 European countries.

Patients: VPT births: 22⁺⁰-31⁺⁶ weeks of gestation.

Data collection: Standardised data collection tools relating to pregnancy, birth and neonatal care and developmental outcomes at 2 years corrected age using a validated parent completed questionnaire.

Main outcome measures: Crude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models.

Results: Parent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2%-26.1% between regions grouped by country) with crude standardised prevalence ratios ranging from 0.60 to 1.53. Adjustment for population, maternal and infant factors resulted in a small reduction in the overall variation (ranging from 0.65 to 1.30).

Conclusion: There is wide variation in the rates of moderate to severe neurodevelopmental impairment for VPT cohorts across Europe, much of which persists following adjustment for known population, maternal and infant factors. Further work is needed to investigate whether other factors including quality of care and evidence-based practice have an effect on neurodevelopmental outcomes for these children.

Nephrol Dial Transplant. 2019 Nov 1;34(11):1819-1826. doi: 10.1093/ndt/gfy328.

Abstract

Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.

Clin Infect Dis. 2019 Oct 30;69(10):1740-1748. doi: 10.1093/cid/ciz033.

BACKGROUND:

In infants, the mode of acquisition of CC17 group B Streptococcus (GBS), the hypervirulent clone responsible for late-onset disease (LOD), remains elusive.

METHODS:

In a prospective multicenter study in France, we evaluated GBS colonization in mother-baby pairs with 2 months of follow-up between 2012 and 2015. Criteria included positivity for GBS colonization at antenatal screening or at delivery. Maternal vaginal samples and infant oral cavity and stool samples were analyzed at delivery, 21 ± 7 days (D21), and 60 ± 7 days (D60) post-delivery.

RESULTS:

A total of 890 mother-baby pairs were analyzed. GBS colonized 7%, 21%, and 23% of the infants at birth, D21, and D60, respectively, of which 10%, 11%, and 13% were identified as CC17 GBS. Concordance between maternal and infant GBS type was 96%. At D21, the main risk factors for infant colonization by GBS were simultaneous maternal colonization of the vagina (odds ratio [OR], 4.50; 95% confidence interval [CI], 1.69-15.61) and breast milk (OR, 7.93; 95% CI, 3.81-17.14). Importantly, 38% (95% CI, 23%-56%) of infants colonized by CC17 GBS appeared colonized for the first time at D60 vs 18% (95% CI, 14%-24%; P < .049) of infants colonized by non-CC17 GBS. Multivariate analysis showed a higher risk for de novo infant colonization by CC17 at D60 than by other GBS (OR, 2.45; 95% CI, 1.02-5.88).

CONCLUSIONS:

The high incidence of CC17 GBS in LOD is likely due to an enhanced post-delivery mother-to-infant transmission.

Emerg Infect Dis. 2019 Oct;25(10):1851-1860. doi: 10.3201/eid2510.181177.

Abstract

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of <2 years. Seroprevalence against these peptides reflected declines and rebounds of transmission in southern Mozambique during 2004-2012, reduced exposure associated with use of preventive measures during pregnancy, and local clusters of transmission that were missed by detection of P. falciparum infections. These data suggest that VAR2CSA serology can provide a useful adjunct for the fine-scale estimation of the malaria burden among pregnant women over time and space.