Publications

J Clin Virol. 2020 Jul;128:104447. doi: 10.1016/j.jcv.2020.104447. Epub 2020 May 18.

Abstract

While SARS-CoV-2 infection has spread rapidly worldwide, data remains scarce about the natural history of infection in pregnant women and the risk of mother-to-fetal transmission. Current data indicates that viral RNA levels in maternal blood are low and there is no evidence of placental infection with SARS-CoV-2. Published reports to date suggest that perinatal transmission of SARSCoV- 2 can occur but is rare. Among 179 newborns tested for SARS-CoV2 at birth from mothers with COVID-19, transmission was suspected in 8 cases, 5 with positive nasopharyngeal SARS-CoV-2 RT-PCR and 3 with SARS-CoV-2 IgM. However, these cases arise from maternal infection close to childbirth and there are no information about exposition during first or second trimester of pregnancy. Welldesigned prospective cohort studies with rigorous judgement criteria are needed to determine the incidence and risk factors for perinatal transmission of SARS-CoV-2.

 Pharmacol Ther. 2020 Nov;108(5):1026-1035. doi: 10.1002/cpt.1887. Epub 2020 Jun 4.

Abstract

Despite antenatal corticosteroids therapy, Respiratory Distress Syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date the relationship between in utero fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS. Pregnant women more than 27 weeks’ gestation and who received at least a single dose of betamethasone for prevention of RDS were enrolled. Maternal, cord blood and amniotic fluid betamethasone time-courses were analyzed using the Monolix software. A total of 220 maternal blood, 56 cord blood and 26 amniotic fluid samples were described by a two-compartment model with two effect compartments linked by rate transfer constants. Apparent clearances and volumes of distribution parameters were allometrically scaled for a 70kg third trimester pregnant woman. The impact of a twin pregnancy was found to increase maternal clearance by 28%. Using a fetal-to-mother exposure ratio, the median [95%CI] transplacental transfer of betamethasone was estimated to 35% [0.11 – 0.67]. After adjustment for gestational age and twin pregnancy, RDS was found to be associated to the time spent in utero below quantifiable concentrations (i.e. < 1 ng/mL): OR [95%CI] of 1.10 [1.01 – 1.19] per day increase (p<0.05). Trying to take into account both efficacy and safety, we simulated different dosing schemes in order to maintain a maximum of fetuses above 1 ng/mL without exceeding the total standard dose.

Abstract

Few data are available on invasive group A Streptococcus (GAS) infections (IGASIs) in infants. We described initial clinical and laboratory features and outcomes of <3-month-old infants hospitalized for an IGASI between 2007 and 2016 in France. Patients were identified from the French National Reference Centre for streptococci. IGASI was defined by the isolation of GAS from blood cultures or from other usually sterile sites. Data collection was performed by assessing the patients’ hospitalization reports. Twenty-six patients (15 males; 57.7%) were included. Among 19 cases with available data, 14 (73.7%) were household contacts of a GAS infection, reaching 8/9 (88.9%) in neonates. The diagnoses were bacteremia (n = 18; 69.2%), pleural effusion or pneumonia (n = 6; 23.1%), meningitis with brain abscess (n = 1; 3.8%), and septic arthritis (n = 1; 3.8%). Fever (n = 10; 38.5%), hemodynamic disorders (n = 11; 42.3%), respiratory disorders (n= 7; 26.9%), thrombocytopenia (n = 7; 26.9%), and neutropenia (n = 5; 19.2%) were frequently observed. The main emm-genotype was emm-1 (n = 8; 30.8%). Thirteen (50.0%) infants have been admitted to the intensive care unit, and two (7.7%) died. Respiratory disorders, high C-reactive protein level, and the need for transfusion were significantly associated with severity. IGASI remains uncommon in <3-month-old children but leads to a high morbidity. Whether an antibiotic prophylaxis for contact neonates of a patient with GAS infection decreases the risk of infection remains to be determined.

Abstract

Pregnant women and infants are at high risk for severe influenza and many countries, including France, recommend annual influenza immunization during pregnancy. We aimed to estimate influenza vaccination and refusal rates and assess associated factors among pregnant women during the 2015-16 season in France. We used data from a national representative sample of women who gave birth in March 2016 and were interviewed before hospital discharge (N = 11,752). In the multivariable analysis, robust Poisson regression models were used to study associations with maternal characteristics and prenatal care characteristics. Influenza vaccine coverage among pregnant women was 7.4% (95% confidence interval [CI]: 6.9-7.9). Only 24.9% (95% CI: 24.2-25.7) of women said that they received a care provider proposal for vaccination and 70.4% (95% CI: 68.7-72.0) of these declined it. Vaccine uptake was associated with low parity (prevalence ratio [PR] = 2.1; 95% CI: 1.4-3.2 for parity 0 vs ≥ 3), high educational level (PR = 2.5; 95% CI: 2.0-3.2), healthcare occupation during pregnancy (PR = 1.8; 95% CI: 1.5-2.1) and preexisting conditions at risk for influenza (PR = 1.7; 95% CI: 1.3-2.2). Women were more frequently vaccinated when their main care provider was a general practitioner. Multiparae women and those with medium or low educational level were significantly more likely than others to decline influenza vaccine after a provider proposal. Influenza vaccine coverage is very low in France, mainly because of infrequent care provider proposals and also frequent women’s refusals. Effective interventions should be designed to promote vaccination among medical professionals and reduce vaccine hesitancy among pregnant women.

Obstet Gynecol. 2020 May;135(5):1015-1023.doi: 10.1097/AOG.0000000000003785.

Abstract

Objective: To compare neonatal mortality and morbidity of first twins according to the planned mode of delivery when the first twin is in breech presentation, in a country where planned vaginal delivery is an option.

Methods: This is a planned secondary analysis of the JUMODA (JUmeaux MODe d’Accouchement) cohort, a national prospective population-based study of twin deliveries conducted in 176 French hospitals. We analyzed pregnancies with first twins in breech presentation and applied the inclusion criteria of the Twin Birth Study (except the criterion for first-twin presentation): both fetuses alive, with a birth weight between 1,500 g and 4,000 g, at or after 32 0/7 weeks of gestation. The primary outcome was a composite of neonatal mortality and morbidity. We used multivariate Poisson regression models to control for potential confounders and propensity score analyses, that is, matching and inverse probability of treatment weighting to control for indication bias.

Results: Among the 1,467 women with a breech-presenting first twin included in this analysis, 1,169 (79.7%) had planned cesarean and 298 (20.3%) planned vaginal births, of whom 185 (62.1%) delivered both twins vaginally. The neonatal mortality and severe morbidity rate for first twins was 1.7% (5/298) in the planned vaginal and 1.9% (22/1,169) in the planned cesarean delivery groups (crude relative risk [RR] 0.90, 95% CI 0.34-2.34). Planned vaginal delivery was not associated with higher neonatal mortality and morbidity than planned cesarean delivery, regardless of the statistical method used: adjusted RR 0.71, 95% CI 0.27-1.86; RR 0.61, 95% CI 0.20-1.83 after matching for propensity score; RR 0.63, 95% CI 0.23-1.74 with inverse probability of treatment weighting. Analyses of neonatal mortality and morbidity of second twins yielded similar results.

Conclusion: Although our sample size precluded a robust assessment for small differences in outcomes between planned cesarean and planned vaginal delivery in twin pregnancies in which the first twin was in breech presentation, in our cohort planned vaginal delivery was not associated with higher neonatal mortality and morbidity for either twin.

Abstract

Background: The rate of premature births in France is 6% and is increasing, as is the rate of extremely premature births. Morbidity and mortality rates in this population remain high despite significant medical progress. We aimed to evaluate the morbidity and mortality rate in preterm neonates weighing<750g and to evaluate their outcome at 2 years’ corrected age (CA).

Methods: This was a retrospective monocentric study including babies born between May 2011 and April 2013 who were preterm and weighed<750g. We evaluated mortality and morbidity in the neonatal period. At 2 years’ CA, we focused on developmental quotient (DQ) with the Brunet-Lézine test, on neurosensory assessment (sleeping/behavior), and growth evaluation.

Results: Among the 107 infants included, 29 (27%) died in the neonatal period. Mean gestational age was 25.6 weeks’ gestation. Female sex and higher birth weight were independent predictors of survival. A total of 61 (78.2%) infants showed extra-uterine growth retardation at 36 weeks’ postmenstrual age. At 2 years’ CA, 57 children were followed up; 38 were evaluated using the Brunet-Lézine test, 20 (52.6%) had a DQc<85, and none had a severe developmental delay (DQc<50). Six (10%) children had cerebral palsy and 22 of 56 (39.2%) showed language delay. Growth retardation persisted in 15 of 52 (28.8%) children.

Conclusion: Our results confirm the acute fragility of extremely low-birth-weight babies with a high rate of morbidity and mortality. At 2 years’ CA, this population still shows a considerable rate of mild difficulties, whose long-term evolution needs to be followed.

Abstract

Background: Neonatal morbidity is associated with lifelong impairments, but the absence of a consensual definition and the need for large data sets limit research.

Objectives: To inform initiatives to define standard outcomes for research, we reviewed composite neonatal morbidity indicators derived from routine hospital discharge data.

Data sources: PubMed (updated on October 12, 2018). The search algorithm was based on three components: « morbidity, » « neonatal, » and « hospital discharge data. »

Study selection and data extraction: Studies investigating neonatal morbidity using a composite indicator based on hospital discharge data were included. Indicators defined for specific conditions (eg congenital anomalies, maternal addictions) were excluded. The target population, objectives, component morbidities, diagnosis and procedure codes, validation methods, and prevalence of morbidity were extracted.

Synthesis: For each study, we assessed construct validity by describing the methods used to select the indicator components and evaluated whether the authors assessed internal and external validity. We also calculated confidence intervals for the prevalence of the morbidity composite.

Results: Seventeen studies fulfilled inclusion criteria. Indicators targeted all (n = 4), low-/moderate-risk (n = 9), and very preterm (VPT, n = 4) infants. Components were similar for VPT infants, but domains and diagnosis codes within domains varied widely for all and low-/moderate-risk infants. Component selection was described for 8/17 indicators and some form of validation reported for 12/17. Neonatal morbidity prevalence ranged from 4.6% to 9.0% of all infants, 0.4% to 8.0% of low-/moderate-risk infants, and 17.8% to 61.0% of VPT infants.

Conclusions: Multiple neonatal morbidity indicators based on hospital discharge data have been used for research, but their heterogeneity limits comparisons between studies. Standard neonatal outcome measures are needed for benchmarking and synthesis of research results.

Abstract

Background: Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.

Objectives: To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.

Methods: In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010-18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.

Results: Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.

Conclusions: In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes.

Hum Reprod Update. 2020 Apr 29:dmaa014. doi: 10.1093/humupd/dmaa014. Epub ahead of print. PMID: 32347305.

Abstract

Background

Haem oxygenases (HO) catabolise haem, which is the prosthetic group of numerous haemoproteins. Thus, multiple primary cellular pathways and functions rely on haem availability. HO exists in two isoforms, both expressed in the placenta, namely HO-1 and HO-2, the first being inducible. Haem oxygenases, particularly HO-1, have garnered specific interest in the field of physiological and pathological placental function. These enzymes mediate haem degradation by cleaving the alpha methene bridge to produce biliverdin, which is subsequently converted to bilirubin, carbon monoxide and iron. HO-1 has anti-inflammatory and antioxidant activities.

Search methods

An initial literature analysis was performed using PubMed on 3 October 2018 using key terms such as ‘haem oxygenase and pregnancy’, ‘haem oxygenase and placenta’, ‘HO-1 and pregnancy’, ‘HO-1 and placenta’, ‘HO and placenta’, ‘HO and pregnancy’, ‘genetic variant and HO’, ‘CO and pregnancy’, ‘CO and placenta’, ‘Bilirubin and pregnancy’, ‘Iron and pregnancy’ and ‘PPAR and Haem’, selecting consensus conferences, recommendations, meta-analyses, practical recommendations and reviews. A second literature analysis was performed, including notable miscarriages, foetal loss and diabetes mellitus, on 20 December 2019. The three authors studied the publications independently to decipher whether they should be included in the manuscript.

Objective and rationale

This review aimed to summarise current pieces of knowledge of haem oxygenase location, function and regulation in the placenta, either in healthy pregnancies or those associated with miscarriages and foetal loss, pre-eclampsia, foetal growth restriction and diabetes mellitus.

Outcomes

HO-1 exerts some protective effects on the placentation, probably by a combination of factors, including its interrelation with the PGC-1α/PPAR pathway and the sFlt1/PlGF balance, and through its primary metabolites, notably carbon monoxide and bilirubin. Its protective role has been highlighted in numerous pregnancy conditions, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus and miscarriages.

Wider implications

HO-1 is a crucial enzyme in physiological and pathological placentation. This protective enzyme is currently considered a potential therapeutic target in various pregnancy diseases.

Seminars in Fetal and Neonatal Medicine. 2020 Jun;25(3):101109. doi: 10.1016/j.siny.2020.101109. Epub 2020 Apr 8.

Abstract

We summarise rates of survival and neurodevelopmental impairment in very (<32 weeks’ gestation) and extremely (<28 weeks’ gestation) preterm infants using data from recent meta-analyses. Methodological issues that require consideration when comparing international data are highlighted using examples of population-based or multi-centre cohorts of children born extremely preterm. The impact of baseline population, outcome definition, gestational age assessment, age at neurodevelopmental assessment, year of birth and follow-up rates are discussed. The impact of the intensity of perinatal care and of post-discharge management on survival and neurodevelopmental outcomes is also discussed. There is a future need for harmonisation of data collection and for more accurate and standardised reporting of neurodevelopmental outcomes in very preterm children.