Publications

Abstract

Background: Harmful maternal and neonatal health outcomes result from malaria in pregnancy, the prevention of which primarily relies on intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). WHO recommends IPTp-SP in sub-Saharan Africa, but implementation is highly heterogeneous and often sub-optimal in terms of the number of doses and their timing. In this study, we assessed the impact of this heterogeneity on malaria in pregnancy, mainly with respect to submicroscopic Plasmodium falciparum infections.

Methods: We used data from 273 Beninese women followed throughout pregnancy. Screening for P. falciparum infections, using both microscopy- and polymerase chain reaction (PCR) -based methods, was performed monthly, and information on IPTp-SP dose was collected. Gestational age was estimated by repeated ultrasound scans. Using a negative binomial model, we investigated the effect of IPTp-SP doses and timing, after 17 weeks of gestation, on the number of P. falciparum infections, focusing on submicroscopic infections detectable only by PCR.

Results: At least two IPTp-SP doses were taken by 77.3% of the women. The median gestational age at first IPTp-SP dose was 22 weeks. A late first IPTp-SP dose (>21.2 weeks) was marginally associated with an increased number of P. falciparum infections (adjusted incidence rate ratio [aIRR] =1.3; p=0.098). The number of IPTp-SP doses was not associated with the number of submicroscopic infections (aIRR=1.2, p=0.543).

Conclusion: A late first IPTp-SP dose fail to provide optimal protection against P. falciparum, especially submicroscopic infections. This highlights the need for a new antimalarial drug for IPTp that could be taken early in pregnancy.

Abstract

Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants, and accurate genotyping of this complex structural variation remains a challenge. Here, we use a polymerase chain reaction-based strategy to genotype structural variation at the human glycophorin gene cluster, including the alleles responsible for the U- blood group. We validate our approach, based on a triplex paralogue ratio test, on publically available samples from the 1000 Genomes project. We then genotype 574 individuals from a longitudinal birth cohort (Tori-Bossito cohort) using small amounts of DNA at low cost. Our approach readily identifies known deletions and duplications, and can potentially identify novel variants for further analysis. It will allow exploration of genetic variation at the glycophorin locus, and investigation of its relationship with malaria, in large sample sets at minimal cost, using standard molecular biology equipment.

Abstract

Importance: In very preterm newborns, gut microbiota is highly variable with major dysbiosis. Its association with short-term health is widely studied, but the association with long-term outcomes remains unknown.

Objective: To investigate in preterm newborns the associations among practice strategies in neonatal intensive care units (NICUs), gut microbiota, and outcomes at 2 years.

Design, setting, and participants: EPIFLORE is a prospective observational cohort study that includes a stool sample collection during the fourth week after birth. Preterm newborns of less than 32 weeks of gestational age (GA) born in 2011 were included from 24 NICUs as part of the French nationwide population-based cohort, EPIPAGE 2. Data were collected from May 2011 to December 2011 and analyzed from September 2016 to December 2018.

Exposures: Eight NICU strategies concerning sedation, ventilation, skin-to-skin practice, antibiotherapy, ductus arteriosus, and breastfeeding were assessed. A NICU was considered favorable to a practice if the percentage of that practice in the NICU was more than the expected percentage.

Main outcomes and measures: Gut microbiota was analyzed by 16S ribosomal RNA gene sequencing and characterized by a clustering-based method. The 2-year outcome was defined by death or neurodevelopmental delay using a Global Ages and Stages questionnaire score.

Results: Of 577 newborns included in the study, the mean (SD) GA was 28.3 (2.0) weeks, and 303 (52.5%) were male. Collected gut microbiota was grouped into 5 discrete clusters. A sixth cluster included nonamplifiable samples owing to low bacterial load. Cluster 4 (driven by Enterococcus [n = 63]), cluster 5 (driven by Staphylococcus [n = 52]), and cluster 6 (n = 93) were significantly associated with lower mean (SD) GA (26.7 [1.8] weeks and 26.8 [1.9] weeks, respectively) and cluster 3 (driven by Escherichia/Shigella [n = 61]) with higher mean (SD) GA (29.4 [1.6] weeks; P = .001). Cluster 3 was considered the reference. After adjustment for confounders, no assisted ventilation at day 1 was associated with a decreased risk of belonging to cluster 5 or cluster 6 (adjusted odds ratio [AOR], 0.21 [95% CI, 0.06-0.78] and 0.19 [95% CI, 0.06-0.62], respectively) when sedation (AOR, 10.55 [95% CI, 2.28-48.87] and 4.62 [1.32-16.18], respectively) and low volume of enteral nutrition (AOR, 10.48 [95% CI, 2.48-44.29] and 7.28 [95% CI, 2.03-26.18], respectively) was associated with an increased risk. Skin-to-skin practice was associated with a decreased risk of being in cluster 5 (AOR, 0.14 [95% CI, 0.04-0.48]). Moreover, clusters 4, 5, 6 were significantly associated with 2-year nonoptimal outcome (AOR, 6.17 [95% CI, 1.46-26.0]; AOR, 4.53 [95% CI, 1.02-20.1]; and AOR, 5.42 [95% CI, 1.36-21.6], respectively).

Conclusions and relevance: Gut microbiota of very preterm newborns at week 4 is associated with NICU practices and 2-year outcomes. Microbiota could be a noninvasive biomarker of immaturity.

Abstract

Racial/ethnic disparities persist in obstetrical outcomes. In this paper, we ask how research in obstetrical quality can go beyond a purely quantitative approach to tackle the challenge of health inequity in quality and safety. This overview debriefs the use of positive deviance and mixed methods in others areas of medicine, describes the shortcomings of quantitative methods in obstetrics and presents qualitative studies carried out in obstetrics as well as the insights provided by this method. The article concludes by proposing positive deviance as a mixed methods approach to generate new knowledge for addressing racial and ethnic disparities in maternal outcomes.

Eur J Clin Microbiol Infect Dis. 2020 Aug 18. doi: 10.1007/s10096-020-04011-6. Epub ahead of print. PMID: 32812077.

Abstract

To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.

Abstract

Research question: What are the perinatal outcomes and especially the risk of small for gestational age (SGA) babies born after frozen versus fresh embryo transfer in mothers affected by endometriosis undergoing treatment with assisted reproductive technology (ART)?

Design: A cohort study conducted between November 2012 and October 2017, in which infertile women with endometriosis undergoing ART and achieving singleton pregnancies that lasted beyond 12 weeks of gestation were included. Pregnancies obtained after a frozen embryo transfer (FET) were compared with those obtained after a fresh embryo transfer. A total of 339 pregnant women were included: 112 patients in the fresh embryo transfer group and 227 in the FET group. The main outcome was the rate of SGA. Secondary analyses were performed for adverse pregnancy outcomes and perinatal complications.

Results: Of the included women, 109/112 (97.3%) and 222/227 (97.8%) delivered a live child after at least 24 weeks of gestation in the fresh and in the frozen embryo transfer groups, respectively (P = 0.53). The risk of SGA decreased after a FET compared with a fresh embryo transfer (odds ratio [OR] 0.49 [0.25-0.98], P = 0.04) after multivariable analysis. The mean birthweight and the gestational age at delivery were not significantly different between the two study groups. Other pregnancy and perinatal complications were not statistically different between the two study populations.

Conclusions: The present study of endometriosis-affected women found a significantly lower risk of SGA in patients undergoing frozen, mainly blastocyst, embryo transfer compared with patients undergoing fresh, mainly cleavage stage, embryo transfer.

PLoS One. 2020 Aug 10;15(8):e0237232. doi: 10.1371/journal.pone.0237232. eCollection 2020. PMID: 32776951

Evidence for contamination as the origin for bacteria found in human placenta rather than a microbiota – PubMed

Abstract

Until recently the in utero environment of pregnant women was considered sterile. Recent high-sensitivity molecular techniques and high-throughput sequencing lead to some evidence for a low-biomass microbiome associated with the healthy placenta. Other studies failed to reveal evidence for a consistent presence of bacteria using either culture or molecular based techniques. Comparing conflicting « placental microbiome » studies is complicated by the use of varied and inconsistent protocols. Given this situation, we undertook an evaluation of the in utero environment sterility using several controlled methods, in the same study, to evaluate the presence or absence of bacteria and to explain contradictions present in the literature. Healthy pregnant women (n = 38) were recruited in three maternity wards. Placenta were collected after cesarean section with or without Alexis® and vaginal delivery births. For this study we sampled fetal membranes, umbilical cord and chorionic villi. Bacterial presence was analyzed using bacterial culture and qPCR on 34 fetal membranes, umbilical cord and chorionic villi samples. Shotgun metagenomics was performed on seven chorionic villi samples. We showed that the isolation of meaningful quantities of viable bacteria or bacterial DNA was possible only outside the placenta (fetal membranes and umbilical cords) highlighting the importance of sampling methods in studying the in utero environment. Bacterial communities described by metagenomics analysis were similar in chorionic villi samples and in negative controls and were dependent on the database chosen for the analysis. We conclude that the placenta does not harbor a specific, consistent and functional microbiota.

Abstract

A 33-year-old pregnant woman was hospitalised with fever, cough, myalgia and dyspnoea at 23.5 weeks of gestation (WG). Development of acute respiratory distress syndrome (ARDS) mandated invasive mechanical ventilation. A nasopharyngeal swab proved positive for severe acute respiratory syndrome coronavirus 2 by reverse transcription-PCR. The patient developed hypertension and biological disorders suggesting pre-eclampsia and HELLP (haemolysis, elevated liver enzyme levels and low platelet levels) syndrome. Pre-eclampsia was subsequently ruled out by a low ratio of serum soluble fms-like tyrosine kinase-1 to placental growth factor. Given the severity of ARDS, delivery by caesarean section was contemplated. Because the ratio was normal and the patient’s respiratory condition stabilised, delivery was postponed. She recovered after 10 days of mechanical ventilation. She spontaneously delivered a healthy boy at 33.4 WG. Clinical and laboratory manifestations of COVID-19 infection can mimic HELLP syndrome. Fetal extraction should not be systematic in the absence of fetal distress or intractable maternal disease. Successful evolution was the result of a multidisciplinary teamwork.

Feeding with human milk has been recognised as an essential component of newborn care and is especially important for infants born very preterm (VPT, below 32 weeks of gestation) who face higher risks of adverse outcomes. WHO recommends that infants who cannot be fed mother’s own milk (MOM) should receive donor human milk. Direct feeding at the breast takes time to establish after VPT birth and procedures are required for expressing, collecting, storing and administering breast milk that respect microbiological safety rules and ensure nutritional and immunological quality. However, as recommendations are scarce, these procedures appear to be dependent on organisational structures and policies of the units. […]

Placenta. 2020 Aug 4;99:157-165. doi: 10.1016/j.placenta.2020.07.024. Online ahead of print. PMID: 32805615

Abstract

Introduction: To date, we have only an incomplete understanding of how gene expression in the human placenta changes at the genome-wide scale from very early in gestation to term. Our aim was to investigate the dynamic changes in gene expression throughout placentation.

Methods: In our study, gene expression profiles were collected of human placentas from 4 to 40 gestational weeks of age. Simple linear regression and weighted correlation network analysis were applied to identify genes of interest. Analyses of gene enrichment, including gene ontology and pathways from the Kyoto Encyclopedia of Genes and Genomes, were performed using clusterProfiler. Finally, dynamic changes in the expression of individual genes were represented using line graphs of scaled and adjusted gene expression.

Results: Our results highlighted a total of 5173 genes that are involved in different periods of placentation. Downstream annotation of these genes revealed the biological processes and pathways involved, from which we chose to further investigate the PPAR signaling pathway. We were able to detect changes over time in many genes involved in lipid storage/metabolism, including members of the FABP family and LPL. These patterns were corroborated by lipid staining of placental sections, which revealed a significant decrease in lipid droplet content in placentas from early in the first trimester to term.

Conclusion: Our study provides detailed information on the dynamics of biological processes and pathways across human placentation. These findings give us new clues for deciphering the normal functions of placentation and the ways in which the mis-regulation of these pathways may be linked to pregnancy-related diseases. As an example, our results show that the PPAR signaling pathway mediates a constant decrease in placental lipid content over the course of pregnancy.