Publications

Abstract

Context: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1. The uncertainty of pathogenicity of MEN1 variants complexifies the selection of the patients likely to benefit from specific care.

bjective: MEN1-mutated patients should be offered tailored tumor screening and genetic counseling. We present a patient with hyperparathyroidism for whom genetic analysis identified a variant of uncertain significance in the MEN1 gene (NM_130799.2): c.654G > T p.(Arg218=). Additional functional genetic tests were performed to classify the variant as pathogenic and allowed prenatal testing.

Design: Targeted next generation sequencing identified a synonymous variant in the MEN1 gene in a 26-year-old male with symptomatic primary hyperparathyroidism. In silico and in vitro genetic tests were performed to assess variant pathogenicity.

Results: Genetic testing of the proband’s unaffected parents showed the variant occurred de novo. Transcript study showed a splicing defect leading to an in-frame deletion. The classification of the MEN1 variant as pathogenic confirmed the diagnosis of MEN1 and recommended an adapted medical care and follow-up. Pathogenic classification also allowed to propose a genetic counseling to the proband and his wife. Noninvasive prenatal diagnosis was performed with a personalized medicine-based protocol by detection of the paternally inherited variant in maternal plasmatic cell free DNA, using digital PCR.

Conclusion: We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counseling decisions.

Abstract

Background: Inadequate or excessive gestational weight gain (GWG) is associated with adverse maternal and neonatal outcomes. Little is known on adequacy of GWG in migrant women. This study investigates whether migrant women in France are at higher risk of inadequate or excessive GWG, and what characteristics are associated with GWG in migrant and non-migrant groups.

Methods: We used data from the PreCARE multicentric prospective cohort (N=10 419). The study includes 5403 women with singleton deliveries, with non-migrant (n=2656) and migrant (n=2747) status. We used multinomial logistic regression, adjusting for maternal age and parity, to investigate the association of migrant status, socioeconomic status-related variables and GWG. In stratified analyses, we identified factors associated with GWG in both groups.

Results: Compared with non-migrant women, migrant women had increased risk of inadequate GWG (adjusted odds ratio (aOR) 1.18; 95% CI 1.03 to 1.34). Non-migrant women with foreign origins had increased risk of excessive GWG (aOR 1.58; 95% CI 1.30 to 1.92). Women born in Sub-Saharan Africa had increased risk of both inadequate and excessive GWG. Regardless of migration status, women with lower education and women who did not start pregnancy with a normal weight were less likely to gain adequately. Inadequate prenatal care was associated with inadequate GWG only among non-migrant women.

Conclusion: Migrant women are at higher risk of inadequate GWG.

Abstract

Abstract

Aim: Neonatal unit design may affect the neurodevelopment of hospitalised neonates and the well-being of parents and healthcare staff (HCS). We aimed to provide recommendations regarding the minimum area required for a hospital room for a single neonate and their family.

Methods: We searched PubMed and Web of Science for relevant articles published from 1 January 2011 to 1 May 2021 by using the keywords NICU and facility design. Recommendations were developed after internal and external review by a multidisciplinary group including 15 professionals and parent representatives.

Results: We identified 314 studies and developed six recommendations from four eligible studies. Recommendations for room size were developed according to three perspectives: opinions of users, who emphasised the need for a spacious room; proposals of organisations by HCS, which advocated for a minimum floor area of 11.2-18 m² in a single non-family room and 15.3-24 m² in a single-family room; and simulation methods indicating that the minimum floor area in the neonatal unit should be 18.5-24 m² .

Conclusion: Units need to provide a minimum room size to allow for optimal newborn development and a better experience for parents and caregivers.

Abstract

Objective: To compare the ability of six scoring systems to predict successful labor induction with cervical ripening among women with a Bishop score <3.

Methods: Secondary analysis of data from a prospective, multicenter observational Methods of Induction of Labor and Perinatal Outcomes (MEDIP) cohort study in 94 obstetrical French units. We included women with a Bishop score <3 before cervical ripening. We compared six scores: Bishop, simplified Bishop, modified Bishop, simplified Bishop including parity, Hughey, and Levine scores. Vaginal delivery defined successful labor induction. The ability of each score to predict successful labor induction was evaluated by comparing their area under the curve (AUC).

Results: Among the 600 eligible women in this study, 408 (68%) delivered vaginally. Body mass index (calculated as weight in kilograms divided by the square of height in meters; mean ± standard deviation [SD]: 24.7 ± 5.5 vs 26.0 ± 5.7; P = 0.01) and nulliparity (48.8% vs 85.4%; P < 0.001) were lower in the successful induction group, whereas height was higher (mean ± SD: 165.3 ± 6.0 cm vs 163.7 ± 6.0 cm; P = 0.002). The simplified Bishop including parity, Hughey, and Levine scores had the highest AUC (0.70, 95% confidence interval [CI] 0.65-0.73; 0.68, 95% CI 0.64-0.74; and 0.69, 95% CI 0.65-0.74, respectively).

Conclusion: In women with a very unfavorable cervix, scores that include parity predict successful labor induction more accurately, such as simplified Bishop including parity, Hughey, or Levine scores.

Abstract

Objective

Objective : To assess the risk of severe maternal outcomes among migrant women, considering both their legal status and birthplace; in Europe, migrant women, especially from sub-Saharan Africa, have higher risks of adverse maternal outcomes compared with non-migrants and legal status, a component of migrant condition, may be an important, and potentially actionable, risk factor.

Design : Prospective cohort study.

Setting : Four maternity units around Paris in 2010–12

Sample : A total of 9599 women with singleton pregnancies

Methods : Legal status was categorised in four groups: reference group of non-migrant native Frenchwomen, legal migrants with French or European citizenship, other legal migrants with non-European citizenship, and undocumented migrants. The risk of severe maternal morbidity was assessed with multivariable logistic regression models according to women’s legal status and birthplace.

Main outcome measure: Binary composite criterion of severe maternal morbidity.

Results : Undocumented migrants had resided for less time in France, experienced social isolation, linguistic barriers and poor housing conditions more frequently and had a pre-pregnancy medical history at lower risk than other migrants. The multivariable analysis showed that they had a higher risk of severe maternal morbidity than non-migrants (33/715 [4.6%] versus 129/4523 [2.9%]; adjusted odds ratio [aOR] 1.68, 95% CI 1.12–2.53). This increased risk was significant for undocumented women from sub-Saharan Africa (18/308 [5.8%] versus 129/4523 [2.9%]; aOR 2.26, 95% CI 1.30–3.91), and not for those born elsewhere (15/407 [3.7%] versus 129/4523 [2.9%]; aOR 1.44, 95% CI 0.82–2.53).

Conclusion: Undocumented migrants are the migrant subgroup at highest risk of severe maternal morbidity, whereas the prevalence of risk factors does not appear to be higher in this subgroup. This finding suggests that their interaction with maternity care services may be sub-optimal.

Abstract

Background: The infant mortality rate (IMR) serves as a key indicator of population health.

Methods: We used data from the French National Institute of Statistics and Economic Studies on births and deaths during the first year of life from 2001 to 2019 to calculate IMR aggregated by month. We ran joinpoint regressions to identify inflection points and assess the linear trend of each segment. Exploratory analyses were performed for overall IMR, as well as by age at death subgroups (early neonatal [D0-D6], late neonatal [D7-27], and post-neonatal [D28-364]), and by sex. We performed sensitivity analyses by excluding deaths at D0 and using other time-series modeling strategies.

Results: Over the 19-year study period, 53,077 infant deaths occurred, for an average IMR of 3·63/1000 (4·00 in male, 3·25 in female); 24·4% of these deaths occurred during the first day of life and 47·8% during the early neonatal period. Joinpoint analysis identified two inflection points in 2005 and 2012. The IMR decreased sharply from 2001 to 2005 (slope: -0·0167 deaths/1000 live births/month; 95%CI: -0·0219 to -0·0116) and then decreased slowly between 2005 and 2012 (slope: -0·0041; 95%CI: -0·0065 to -0·0016). From 2012 onwards, a significant increase in IMR was observed (slope: 0·0033; 95%CI: 0·0011 to 0·0056). Subgroup analyses indicated that these trends were driven notably by an increase in the early neonatal period. Sensitivity analyses provided consistent results.

Interpretation: The recent historic increase in IMR since 2012 in France should prompt urgent in-depth investigation to understand the causes and prepare corrective actions.

Funding: No financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Abstract

Background: The mechanisms of disparities in maternal and perinatal health between migrant and native women are multiple and remain poorly understood. Access to and quality of care are likely to participate in these mechanisms, and one hypothesis is the existence of implicit biases among caregivers through which ethno-racial belonging can influence medical decisions and consequently engender healthcare disparities. Their existence and their role in the generation of non-medically justified differential care have been documented in the United States apart from perinatal care, but remain largely unexplored in Europe. In this article, we present the study protocol and theoretical framework of a study that aims to test and quantify the existence of implicit bias toward African Sub-Saharan migrant women among caregivers working in the perinatal field, and to explore the association between implicit bias and differential care.

Material and methods: This study is based on an online survey to which French obstetricians, midwives, and anesthetists were invited to take part. The potential existence of implicit biases toward African Sub-Saharan migrant will be quantified through a validated tool, the Implicit Association Test. Then we will assess how implicit biases are likely to influence clinical decisions and lead to differential care using clinical vignettes designed by an experts group.

Discussion: Implicit bias and differential care are concept that are tricky to capture and interpret. This research program opens up in France a field of research on certain forms of health discriminations and sheds new light on the issue of social inequalities in perinatal health.

Abstract

Introduction: Pregnant women are at increased risk for COVID-19, and COVID-19 vaccine is the most promising solution to overcome the current pandemic. This study was conducted to evaluate pregnant women’s perceptions and acceptance of COVID-19 vaccination.

Materials & methods: A cross-sectional study was conducted from February 18 to April 5 2021. An anonymous survey was distributed in 7 French obstetrics departments to all pregnant women before a prenatal visit. All pregnant women attending a follow-up consultation were asked to participate in the study. An anonymous web survey was available through a QR code and participants were asked whether or not they would agree to be vaccinated against SARS-CoV-2, and why. The questionnaire included questions on the patients’ demographics and their knowledge of COVID-19 vaccines.

Results: Of the 664 pregnant women who completed the questionnaire, 29.5% (95% CI 27.7; 31.3) indicated they would agree to be vaccinated against COVID-19. The main reason for not agreeing was being more afraid of potential side effects of the SARS-CoV-2 vaccine on the fetus than of COVID-19. Factors influencing acceptance of vaccination were: being slightly older, multiparity, having discussed it with a caregiver and acceptance of the influenza vaccine.

Discussion: Nearly one-third of pregnant women in this population would be willing to be vaccinated. In addition to studies establishing fetal safety, public health agencies and healthcare professionals should provide accurate information about the safety of COVID-19 vaccines

Abstract

Background: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial.

Objective: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix.

Study design: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks’ gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects.

Results: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use.

Conclusion: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.