Publications

BMC Pediatr. 2020 Jan 7;20(1):8. doi: 10.1186/s12887-019-1856-1.

Background

Perinatal decision-making affects outcomes for extremely preterm babies (22-26 weeks’ gestational age (GA)): more active units have improved survival without increased morbidity. We hypothesised such units may gain skills and expertise meaning babies at higher gestational ages have better outcomes than if they were born elsewhere. We examined mortality and morbidity outcomes at age two for babies born at 27-28 weeks’ GA in relation to the intensity of perinatal care provided to extremely preterm babies.

Methods

Fetuses from the 2011 French national prospective EPIPAGE-2 cohort, alive at maternal admission to a level 3 hospital and delivered at 27-28 weeks’ GA, were included. Morbidity-free survival (survival without sensorimotor (blindness, deafness or cerebral palsy) disability) and overall survival at age two were examined. Sensorimotor disability and Ages and Stages Questionnaire (ASQ) result below threshold among survivors were secondary outcomes. Perinatal care intensity level was based on birth hospital, grouped using the ratio of 24-25 weeks’ GA babies admitted to neonatal intensive care to fetuses of the same gestation alive at maternal admission. Sensitivity analyses used ratios based upon antenatal steroids, Caesarean section, and newborn resuscitation. Multiple imputation was used for missing data; hierarchical logistic regression accounted for births nested within centres.

Results

633 of 747 fetuses (84.7%) born at 27-28 weeks’ GA survived to age two. There were no differences in survival or morbidity-free survival: respectively, fully adjusted odds ratios were 0.96 (95% CI: 0.54 to 1.71) and 1.09 (95% CI: 0.59 to 2.01) in medium and 1.12 (95% CI: 0.63 to 2.00) and 1.16 (95% CI: 0.62 to 2.16) in high compared to low-intensity hospitals. Among survivors, there were no differences in sensorimotor disability or ASQ below threshold. Sensitivity analyses were consistent with the main results.

Conclusions

No difference was seen in survival or morbidity-free survival at two years of age among fetuses alive at maternal hospital admission born at 27-28 weeks’ GA, or in sensorimotor disability or presence of an ASQ below threshold among survivors. There is no evidence for an impact of intensity of perinatal care for extremely preterm babies on births at a higher gestational age.

J Infect Dis. 2020 Jan 2;221(2):293-303. doi: 10.1093/infdis/jiz451. PubMed PMID: 31677349.

Background

Innovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions.

Methods

Plasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women.

Results

In HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes.

Conclusions

Selection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.

Mol Cell Endocrinol. 2020 Jan 1;499:110586. doi: 10.1016/j.mce.2019.110586. Epub 2019 Sep 17. PMID: 31539598.

Abstract

Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.

Abstract

Objective: To evaluate whether a history of spontaneous early-term birth (37⁺⁰ -38⁺⁶ weeks of gestation) in the previous singleton pregnancy is a risk factor for preterm birth (PTB) in a subsequent twin pregnancy.
Design: Retrospective cohort study.
Settings: Two French university hospitals (2006-2016).
Population: All women who delivered twins from 24⁺⁰ weeks after a preceding singleton pregnancy birth at 37⁺⁰ to 41⁺⁶weeks.
Methods: Multivariate logistic regression analysis of association between twin PTB and a previous spontaneous singleton early-term birth.
Main outcome measures: Twin PTB rate before 37, 34 and 32 weeks of gestation.
Results: Among 618 twin pregnancies, 270 were born preterm, 92 of them with a preceding spontaneous singleton early-term birth. The univariate analysis showed a significantly higher risk of twin PTB before 37, 34 and 32 weeks among those 92 women compared with those with a full- or late-term birth in their previous singleton pregnancy. This association remained significant after logistic regression (odds ratio [OR] between 2.42 and 3.88). The secondary analysis, restricted to the twin pregnancies with spontaneous PTB found similar results, with a risk of PTB before 37, 34 and 32 weeks significantly higher among women with a previous spontaneous singleton early-term birth, including after logistic regression analysis (OR between 3.51 and 3.56).
Conclusion: A preceding spontaneous singleton early-term birth is a strong and easily identified risk factor for PTB in twin pregnancies.

Sci Rep. 2019 Dec 13;9(1):19034. doi: 10.1038/s41598-019-55046-5.

Abstract

Despite the clinically proven advantages of intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), utilisation has been low in many African countries. To increase uptake and achieve the desired effect, the World Health Organization revised the policy to a monthly administration. Assessing the coverage and impact of the revised policy on pregnancy and neonatal outcomes is, therefore, a necessity. A 2-parallel cross-sectional hospital-based study was carried out among pregnant women attending first antenatal care (ANC) and delivery. Maternal and cord blood samples were assayed for malaria parasites by quantitative PCR targeting both the 18S rDNA and the acidic terminal segment of Plasmodium falciparum var genes, and plasma SP levels were measured by liquid chromatography coupled to tandem mass spectrometry. Parasite prevalence was similar between the two study sites but decreased significantly between the first ANC (9% or 43%) and delivery (4% or 11%) based on the qPCR target. At delivery, 64.5% of women received ≥3 IPTp-SP dose, 15.5% received 2 doses and 6% had 1 dose. Taking ≥3 IPTp-SP doses was associated with an average birth weight increase of more than 0.165 kg. IPTp-SP uptake was associated with plasma SP level at delivery (OR = 32.3, p ≤ 0.005, 95% CI (13.3;78.4) for those that reported ≥3 IPTp-SP doses) while the same trend of improved birth weight was observed with high plasma SP levels. The new IPTp policy is well implemented and well utilised by women in the sites considered in this study and translates to the improved birth weight observed. This study confirms the interest and the clinical benefit expected from this policy change.

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.