Publications

Appl Environ Microbiol. 2018 Mar 19;84(7). pii: e02428-17. doi: 10.1128/AEM.02428-17. Print 2018 Apr 1.

ABSTRACT

We aimed at identifying potential bacterial factors linking clostridia with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity, and inflammatory capabilities of the largest collection of Clostridium butyricum and Clostridium neonatale strains isolated from fecal samples of NEC preterm neonates (PN) and control PNs. When strain characteristics were used as explanatory variables, a statistical discriminant analysis allowed the separation of NEC and control strains into separate groups. Strains isolated from NEC PN were characterized by a higher viability at 30°C (P  0.03) and higher aerotolerance (P 0.01), suggesting that NEC strains may have a competitive and/or survival advantage in the environmental gastrointestinal tract conditions of NEC PN. Heat-treated NEC bacteria induced higher production of interleukin-8 in Caco-2 cells (P  0.03), suggesting proinflammatory activity. In vitro, bacteria, bacterial components, and fecal filtrates showed variable cytotoxic effects affecting the cellular network and/or cell viability, without specific association with NEC or control samples. Altogether, our data support the existence of a specific clostridial strain signature associated with NEC.

IMPORTANCE

Clostridia are part of the commensal microbiota in preterm neonates (PN). However, microbiota analyses by culture and metagenomics have linked necrotizing enterocolitis (NEC) and intestinal colonization with clostridial species. Nevertheless, little is known about the specific characteristics that may be shared by clostridia associated with NEC compared to commensal clostridia. Therefore, our goal was to identify specific bacterial factors linking clostridial strains with NEC. We report the existence of a specific bacterial signature associated with NEC and propose that activation of the innate immune response may be a unifying causative mechanism for the development of NEC independent of a specific pathogenic organism. The present study provides new insights into NEC pathophysiology that are needed for better diagnostics and strategies for implementing prevention of the disease.

BMJ Open. 2018 Jan 24;8(1):e018745. doi: 10.1136/bmjopen-2017-018745.

OBJECTIVES

To investigate whether risk factors for preterm (<37 weeks gestation) and early-term birth (37 and 38 weeks gestation) are similar.

DESIGN

Nationally representative cross-sectional study of births.

SETTING

France in 2010.

PARTICIPANTS

Live singleton births (n=14 326).

PRIMARY AND SECONDARY OUTCOME MEASURES

Preterm and early-term birth rates overall and by mode of delivery (spontaneous and indicated). Risk factors were maternal sociodemographic characteristics, previous preterm birth, height, prepregnancy body mass index (BMI) and smoking, assessed using multinomial regression models with full-term births 39 weeks and over as the reference group.

RESULTS

There were 5.5% preterm and 22.5% early-term births. Common risk factors were: a previous preterm delivery (adjusted relative risk ratio (aRRR) 8.2 (95% CI 6.2 to 10.7) and aRRR 2.4 (95% CI 2.0 to 3.0), respectively), short stature, underweight (overall and in spontaneous deliveries), obesity (in indicated deliveries only), a low educational level and Sub-Saharan African origin. In contrast, primiparity was a risk factor only for preterm birth, aRRR 1.8 (95% CI 1.5 to 2.2), while higher parity was associated with greater risk of early-term birth.

CONCLUSIONS

Most population-level risk factors were common to both preterm and early-term birth with the exception of primiparity, and BMI which differed by mode of onset of delivery. Our results suggest that preterm and early-term birth share similar aetiologies and thus potentially common strategies for prevention.

BMJ Open.2018 Jan8;8(1):e019014. doi: 10.1136/bmjopen-2017-019014

PURPOSE:

REtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus.

PARTICIPANTS:

For this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment.

FINDINGS TO DATE:

Pregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively.

FUTURE PLANS:

REtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future.

BMJ . 2017 Aug 16;358:j3448. doi: 10.1136/bmj.j3448.

Abstract

Objectives: To describe neurodevelopmental outcomes at 2 years corrected age for children born alive at 22-26, 27-31, and 32-34 weeks’ gestation in 2011, and to evaluate changes since 1997.

Design: Population based cohort studies, EPIPAGE and EPIPAGE-2.

Setting: France.

Participants: 5567 neonates born alive in 2011 at 22-34 completed weeks’ gestation, with 4199 survivors at 2 years corrected age included in follow-up. Comparison of outcomes reported for 3334 (1997) and 2418 (2011) neonates born alive in the nine regions participating in both studies.

Main outcome measures: Survival; cerebral palsy (2000 European consensus definition); scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ; at least one of five domains below threshold) if completed between 22 and 26 months corrected age, in children without cerebral palsy, blindness, or deafness; and survival without severe or moderate neuromotor or sensory disabilities (cerebral palsy with Gross Motor Function Classification System levels 2-5, unilateral or bilateral blindness or deafness). Results are given as percentage of outcome measures with 95% confidence intervals.

Results: Among 5170 liveborn neonates with parental consent, survival at 2 years corrected age was 51.7% (95% confidence interval 48.6% to 54.7%) at 22-26 weeks’ gestation, 93.1% (92.1% to 94.0%) at 27-31 weeks’ gestation, and 98.6% (97.8% to 99.2%) at 32-34 weeks’ gestation. Only one infant born at 22-23 weeks survived. Data on cerebral palsy were available for 3599 infants (81.0% of the eligible population). The overall rate of cerebral palsy at 24-26, 27-31, and 32-34 weeks’ gestation was 6.9% (4.7% to 9.6%), 4.3% (3.5% to 5.2%), and 1.0% (0.5% to 1.9%), respectively. Responses to the ASQ were analysed for 2506 children (56.4% of the eligible population). The proportion of children with an ASQ result below threshold at 24-26, 27-31, and 32-34 weeks’ gestation were 50.2% (44.5% to 55.8%), 40.7% (38.3% to 43.2%), and 36.2% (32.4% to 40.1%), respectively. Survival without severe or moderate neuromotor or sensory disabilities among live births increased between 1997 and 2011, from 45.5% (39.2% to 51.8%) to 62.3% (57.1% to 67.5%) at 25-26 weeks’ gestation, but no change was observed at 22-24 weeks’ gestation. At 32-34 weeks’ gestation, there was a non-statistically significant increase in survival without severe or moderate neuromotor or sensory disabilities (P=0.61), but the proportion of survivors with cerebral palsy declined (P=0.01).

Conclusions: In this large cohort of preterm infants, rates of survival and survival without severe or moderate neuromotor or sensory disabilities have increased during the past two decades, but these children remain at high risk of developmental delay.