Publications

Abstract

Objectives: To describe experiences including interviews with bereaved women in a clinical audit.

Design: The data come from an audit of all stillbirths and neonatal deaths at ≥22 weeks of gestation in Seine-Saint-Denis, a disadvantaged French district in 2014. We included bereaved women using a questionnaire that also contained open-ended questions administered in an interview format by a midwife-investigator several weeks after the death. The study included a referral protocol for bereaved women with unmet needs revealed during the interviews. A psychological support for the three midwife-investigators was set-up, in the form of a support group.

Setting: The 11 maternity hospitals in the district.

Participants: 218 women (227 deaths).

Analyses: Data come from medical records, maternal interviews, the reviews of the audit’s expert panel and written narratives of their experiences provided by the midwife-investigators. Quantitative data were analysed statistically, and qualitative data thematically.

Results: One-third (75) of the women agreed to an interview, but acceptance ranged from 6% to 60% by maternity unit. Characteristics of respondents and non-respondents were similar. Members of the audit’s expert panel reported that 41% of the interviews contained new information relevant to their assessment. Of the women interviewed, 35% were referred to a medical professional, psychologist or social worker. Midwife-investigators’ experiences illustrated the benefits of a support group with three main themes identified: improving their interactions with bereaved women as well as medical teams and protecting their psychological well-being.

Conclusion: These results showed that including interviews with bereaved women in audit designs was feasible and provided valuable information on women’s care and social circumstances that were not available in medical records. They also highlight the importance of implementing referral protocols for the bereaved women, used in over one-third of cases, as well as providing support for study investigators.

J Gynecol Obstet Hum Reprod. 2020 Sep 22;101920. doi: 10.1016/j.jogoh.2020.101920.Online ahead of print.

Abstract

Introduction: Recent studies have shown that the cause of very preterm births may be related to neonatal morbidity and mortality. Even though these risks are lower among late preterm births, this group accounts for the vast majority of all preterm births. The objective of this study was to evaluate the relation of neonatal morbidity and mortality to the cause of late preterm birth.

Materials and methods: This retrospective observational cohort study included all women who gave birth to liveborn singletons from 34 to 36 weeks+6 days of gestation in a French level III maternity hospital in the 5-year period 2013-2017. The causes of preterm delivery were divided into 6 mutually exclusive groups. The main outcome was a composite neonatal morbidity criterion, defined by at least one among the following criteria: neonatal respiratory distress, neurological complications, neonatal sepsis, severe necrotizing enterocolitis, and neonatal hypoglycemia. We analyzed the association between cause of preterm delivery and neonatal morbidity after adjustment for gestational age and antenatal corticosteroid therapy. The reference group was preterm labor, defined by spontaneous preterm labor with intact membranes.

Results: During the study period, there were a total of 27 110 births, including 1114 singleton births at 34 to 36 weeks of gestation + 6 days (4.1%). Among the 968 late preterm births included, the risk of neonatal morbidity in the group with preterm premature rupture of membranes (PPROM) was similar to that in the preterm labor (reference) group: adjusted odds ratio (aOR) 1.2 (95% CI, 0.8-1.8). All the other causes of late preterm birth were associated with a higher risk of neonatal morbidity than the reference group: aOR 2.0 [95% CI, 1.1-3.5] for hypertensive disorders without suspected fetal growth restriction (FGR) (9.1% of cases), aOR 2.4 [95% CI, 1.4-4.2] for hypertensive disorders with suspected FGR (8.9%), aOR 4.2 [95% CI, 2.2-8.0] for suspected FGR without hypertensive disorders (5.8%), and aOR 4.4 [95% CI, 2.2-8.8] for vaginal bleeding related to abnormal placental insertion (4.7%).

Conclusion: Among infants born from 34 to 36 weeks + 6 days of gestation, PPROM and preterm labor had similar risks of neonatal morbidity, while the other causes were associated with a risk of neonatal morbidity at least twice that with preterm labor.

Abstract

Background: Preeclampsia (PE) is a frequently occurring multisystemic disease affecting ~5% of pregnancies. PE patients may develop HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet), a mother and foetus life-threatening condition. Research into HELLP’s genetic origin has been relatively unsuccessful, mainly because normal placental function and blood pressure regulation involve the fine-regulation of hundreds of genes.

Objective: To identify new genes and mutations constituting potential biomarkers for HELLP syndrome.

Study design: The present case-control study involved whole-exome sequencing of 79 unrelated HELLP women. Candidate variants were screened in a control population constituted by 176 individuals. Stringent bioinformatics filters were used for selecting potentially etiological sequence variants in a subset of 487 genes. We used robust in silico mutation modelling for predicting the potential effect on protein structure.

Results: We identified numerous sequence variants in genes related to angiogenesis/coagulation/blood pressure regulation, cell differentiation/communication/adhesion, cell cycle and transcriptional gene regulation, extracellular matrix biology, lipid metabolism and immunological response. Five sequence variants generated premature stop codons in genes playing an essential role in placental physiology (STOX1, PDGFD, IGF2, MMP1 and DNAH11). Six variants (ERAP1- p.Ile915Thr, ERAP2- p.Leu837Ser, COMT-p.His192Gln, CSAD-p.Pro418Ser, CDH1- p.Ala298Thr and CCR2-p.Met249Lys) led to destabilisation of protein structure as they had significant energy and residue interaction-related changes. We identified at least two mutations in 57% of patients, arguing in favour of a polygenic origin for the HELLP syndrome.

Conclusion: Our results provide novel evidence regarding PE/HELLP’s genetic origin, leading to new biomarkers, having potential clinical usefulness, being proposed.

Abstract

Background: Follow-up of very preterm infants is essential for reducing risks of health and developmental problems and relies on parental engagement. We investigated parents’ perceptions of post-discharge healthcare for their children born very preterm in a European multi-country cohort study.

Methods: Data come from a 5-year follow-up of an area-based cohort of births <32 weeks’ gestation in 19 regions from 11 European countries. Perinatal data were collected from medical records and 5-year data from parent-report questionnaires. Parents rated post-discharge care related to their children’s preterm birth (poor/fair/good/excellent) and provided free-text suggestions for improvements. We analyzed sociodemographic and medical factors associated with poor/fair ratings, using inverse probability weights to adjust for attrition bias, and assessed free-text responses using thematic analysis.

Results: Questionnaires were returned for 3635 children (53.8% response rate). Care was rated as poor/fair for 14.2% [from 6.1% (France) to 31.6% (Denmark)]; rates were higher when children had health or developmental problems (e.g. cerebral palsy (34.4%) or epilepsy (36.9%)). From 971 responses, 4 themes and 25 subthemes concerning care improvement were identified.

Conclusions: Parents’ experiences provide guidance for improving very preterm children’s post-discharge care; this is a priority for children with health and developmental problems as parental dissatisfaction was high.

Impact: In a European population-based very preterm birth cohort, parents rated post-discharge healthcare as poor or fair for 14.2% of children, with a wide variation (6.1-31.6%) between countries. Dissatisfaction was reported in over one-third of cases when children had health or developmental difficulties, such as epilepsy or cerebral palsy. Parents’ free-text suggestions for improving preterm-related post-discharge healthcare were similar across countries; these focused primarily on better communication with parents and better coordination of care. Parents’ lived experiences are a valuable resource for understanding where care improvements are needed and should be included in future research.

Abstract

In this study, for the first time we report on a comprehensive overview of different strategies to hyphenate droplet-based sample handling and preparation with electrophoretic separation in different formats (i.e. microchip and capillary electrophoresis). Droplet-interfaced electrophoresis is an emerging technique in which micro/nanometric droplets are used as a bridge and carrier of target analytes between sample treatment and electrokinetic separation steps, thus being expected to overcome the challenges of working dimension mismatch and low degree of module integration. This review covers all works on this topic from 2006 (the year of the first communication) up to 2020, with focus being given to three principal interfacing strategies, including droplets in immiscible phases, digital microfluidics with electrowetting-on-dielectric principle and inkjet droplet generation. Different instrumental developments for such purpose, the viewpoints on pros and cons of these designs as well as application demonstrations of droplet-interfaced electrokinetic strategies are discussed.

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.