Publications

Abstract

Introduction: Postnatal corticosteroids (PNC) are effective for reducing bronchopulmonary dysplasia (BPD) in very preterm neonates but are associated with adverse effects including an increased risk of cerebral palsy. PNC use in Europe is heterogeneous across regions. This study aimed to assess whether European neonatal intensive care units (NICUs) with a low use of PNC or an explicit policy to reduce PNC use had higher risks of mortality or BPD.

Methods: We included 3,126 infants in 105 NICUs born between 24 + 0 and 29 + 6 weeks’ gestational age in 19 regions in 11 countries in the EPICE cohort. First, we identified clusters of NICUs using hierarchical clustering based on PNC use and BPD prevalence and compared case mix and mortality between the clusters. Second, a multilevel analysis was performed to evaluate the association between a restrictive PNC policy and BPD occurrence.

Results: There were 3 clusters of NICUs: 52 with low PNC use and a low BPD rate, 37 with low PNC use and a high BPD rate, and 16 with high PNC use and a medium BPD rate. Neonatal mortality did not differ between clusters (p = 0.88). A unit policy of restricted PNC use was not associated with a higher risk of BPD (odds ratio 0.68; 95% confidence interval: 0.45-1.03) after adjustment.

Conclusion: Up to 49% of NICUs had low PNC use and low BPD rates, without a difference in mortality. Infants hospitalized in NICUs with a stated policy of low PNC use did not have an increased risk of BPD.

Abstract

STOX1 is a transcription factor involved in preeclampsia and Alzheimer disease. We show that the knock-down of the gene induces rather mild effect on gene expression in trophoblast cell lines (BeWo). We identified binding sites of STOX1 shared by the two major isoforms, STOX1A and STOX1B. Profiling gene expression of cells overexpressing either STOX1A or STOX1B, we identified genes downregulated by both isoforms, with a STOX1 binding site in their promoters. Among those, STOX1-induced Annexin A1 downregulation led to abolished membrane repair in BeWo cells. By contrast, overexpression of STOX1A or B has opposite effects on trophoblast fusion (acceleration and inhibition, respectively) accompanied by syncytin genes deregulation. Also, STOX1A overexpression led to abnormal regulation of oxidative and nitrosative stress. In sum, our work shows that STOX1 isoform imbalance is a cause of gene expression deregulation in the trophoblast, possibly leading to placental dysfunction and preeclampsia.

PLoS One. 2019 Feb 20;14(2):e0212568. doi: 10.1371/journal.pone.0212568. eCollection 2019.

Background

Premature neonates (PN) present multiple risk factors for high frequencies and high levels of colonization by C. difficile, yet data is missing about this specific pediatric population. Here, we investigated PN C. difficile carriage and colonization dynamics, analyzed the impact of perinatal determinants on colonization, and characterized the isolates.

Methods

A one year longitudinal monocentric prospective cohort study was performed on 121 PN. C. difficile strains isolated from fecal samples on selective medium were identified and characterized by PCR (tpi housekeeping gene; tcdA and tcdB, and binary toxin genes), capillary gel-based electrophoresis PCR-ribotyping, and Multi-Locus Variable-number tandemrepeat Analysis (MLVA).

Results

Of the 379 samples analyzed, 199 (52%) were C. difficile culture positive with the mean levels of C. difficile colonization decreasing significantly (P = .027) over time. During hospitalization, C. difficile colonization frequency increased up to 61% with 95% of the strains belonging to both non-toxigenic PCR-ribotypes (RTs) FR082 (35%) and 032 (60%). After hospital discharge, if a higher diversity in RTs was observed, RTs FR082 and 032 remained predominant (respectively 40% and 28%). MLVA showed clonal relationship within each FR082 and 032 RTs. Ten toxigenic strains (5%) were isolated, all tcdA+/tcdB+ except for one tcdA-/tcdB+, and all being acquired after hospitalization. At 1 week, the only factors found to be linked with a higher frequency of C. difficile colonization were a higher gestational age (P = 0.006) and a higher birth weight (P = 0.016).

Conclusion

The dynamics of C. difficile colonization in PN followed a specific pattern. C. difficile colonization rapidly occurred after birth with a low diversity of non-toxigenic RTs. After hospitalization, non-toxigenic RTs diversity increased. Sporadic carriage of toxigenic strains was observed after hospitalization.

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.