Publications

Abstract

Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population-based cohort of births below 32 weeks of gestation in 11 European countries in 2011-2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever-breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25-34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high-risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio-economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge.

Expert Rev Vaccines. 2018 May;17(5):383-393. doi: 10.1080/14760584.2018.1471988. Epub 2018 May 9.

INTRODUCTION:

Vaccination in pregnancy has been shown to be effective for the prevention of influenza and pertussis in infants, providing support for similar strategies to prevent group B streptococcus and respiratory syncytial virus infections that represent a large burden in pediatric population.

AREAS COVERED:

This review addresses the principle of maternal immunization, efficacy and safety of both pertussis and seasonal influenza vaccines and presents available data on group B streptococcus and respiratory syncytial virus that are in development for administration during pregnancy.

EXPERT COMMENTARY:

Complementary data is needed to help in understanding pertussis vaccine mechanisms, improving influenza vaccine efficacy and addressing the interference phenomenon which is when maternal antibodies interfere with the infant vaccine response. Several knowledge gaps need to be filled in group B streptococcus and respiratory syncytial virus vaccines research

Molecules. 2018 May 4;23(5). pii: E1085. doi: 10.3390/molecules23051085.

Abstract

Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations carrying rhodamine-labelled siRNAs were evaluated on an in vitro model, i.e., human primary villous cytotrophoblasts. siRNA internalization rate from lipoplexes were compared to the one in the presence of the lipofectamine reagent and assessed by confocal microscopy. Results showed cellular internalization of nucleic acid with all three formulations, based on two cationic lipids, either DMAPAP or CSL-3. Moreover, incubation with DMAPAP+AA provided a rate of labelled cells as high as with lipofectamine (53 _ 15% and 44 _ 12%, respectively) while being more biocompatible. The proportion of cells which internalized siRNA were similar when using DMAPAP/DDSTU (16 _ 5%) and CSL-3 (22 _ 5%). This work highlights that liposomes could be a promising approach for gene therapy dedicated to pregnant patients.

Drug Discov Today. 2018 May; 23(5):1099-1107. doi: 10.1016/j.drudis.2018.01.048. Epub 2018 Jan 31.

Abstract

Preeclampsia is a serious pregnancy disorder characterized by the onset of high blood pressure and proteinuria. Although the understanding of the disease is increasing, it remains without treatment, other than the delivery of the baby and the placenta. This review sets out to discuss some new developments and strategies in the treatment of preeclampsia. We briefly review the current knowledge on the pre-eclamptic pathophysiology. We then examine the recent trends in preeclampsia treatment and, in particular, the tracks of potential therapeutic targets. Finally, we focus on the possibilities nano-carriers could offer in the management of preeclampsia. Indeed, nano-carriers could help to prevent transplacental passage and promote placental-specific drug delivery, thereby enhancing efficacy and improving safety. Tendencies are then drawn from the available studies on the optimal characteristics of a nano-carrier to deliver drugs to the placenta.

Med Sci (Paris). 2018 Apr;34(4):331-337. doi: 10.1051/medsci/20183404014. Epub 2018 Apr 16.

Abstract

Some diseases seem to have a developmental origin. Today, the microbiota is recognized as a determinant in health and diseases and one important step is its establishment in the neonate. Some variations in its composition including an imbalance (also called dysbiosis) have been associated to several pathologies. Recent studies suggest a bacterial colonization in the non-pregnant uterus, in the amniotic fluid and in the placenta, which were previously thought sterile. So, during developmental phases, the fetus could have encounter bacteria in utero. These bacteria could contribute to its microbiota establishment before parturition and therefore before the encounter with all microorganisms from vaginal, fecal and cutaneous microbiotas according to the delivery mode. However, studies stating the existence of such in utero microbiota, characterized by a low biomass, are somewhat disputed.

Eur J Public Health. 2018 Apr 1;28(2):303-309. doi: 10.1093/eurpub/ckx131.

Background:

Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset.

Methods:

We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses.

Results:

Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset.

Conclusion:

Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.

Journal of Developmental Origins of Health and Disease. 2018; 9: 590–597. doi: 10.1017/S2040174418000119.

Abstract

The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from the conception to the 2 years of life). The process of the gut microbiota establishment is included in this time window. Various perinatal determinants, such as cesarean section delivery, type of feeding, antibiotics treatment, gestational age or environment, can affect the pattern of bacterial colonization and result in dysbiosis. The alteration of the early bacterial gut pattern can persist over several months and may have long-lasting functional effects with an impact on disease risk later in life. As for example, early gut dysbiosis has been involved in allergic diseases and obesity occurrence. Besides, while it was thought that the fetus developed under sterile conditions, recent data suggested the presence of a microbiota in utero, particularly in the placenta. Even if the origin of this microbiota and its eventual transfer to the infant are nowadays unknown, this placental microbiota could trigger immune responses in the fetus and would program the infant’s immune development during fetal life, earlier than previously considered. Moreover, several studies demonstrated a link between the composition of placental microbiota and some pathological conditions of the pregnancy. All these data show the evidence of relationships between the neonatal gut establishment and future health outcomes. Hence, the use of pre- and/or probiotics to prevent or repair any early dysbiosis is increasingly attractive to avoid long-term health consequences.

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.