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"Zupan, Veronique"
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Transplacental transmission of SARS-CoV-2 infection
2020
SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.
Congenital infection of SARS-CoV-2 has been described, but the transmission routes remain unclear. Here, the authors report evidence of transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise.
Journal Article
Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial
by
El Moussawi, Fatima
,
Baud, Olivier
,
Andrini, Pierre
in
Anti-Inflammatory Agents - administration & dosage
,
Bronchopulmonary Dysplasia - prevention & control
,
Clinical trials
2016
Bronchopulmonary dysplasia, a major complication of extreme prematurity, has few treatment options. Postnatal steroid use is controversial, but low-dose hydrocortisone might prevent the harmful effects of inflammation on the developing lung. In this study, we aimed to assess whether low-dose hydrocortisone improved survival without bronchopulmonary dysplasia in extremely preterm infants.
In this double-blind, placebo-controlled, randomised trial done at 21 French tertiary-care neonatal intensive care units (NICUs), we randomly assigned (1:1), via a secure study website, extremely preterm infants inborn (born in a maternity ward at the same site as the NICU) at less than 28 weeks of gestation to receive either intravenous low-dose hydrocortisone or placebo during the first 10 postnatal days. Infants randomly assigned to the hydrocortisone group received 1 mg/kg of hydrocortisone hemisuccinate per day divided into two doses per day for 7 days, followed by one dose of 0·5 mg/kg per day for 3 days. Randomisation was stratified by gestational age and all infants were enrolled by 24 h after birth. Study investigators, parents, and patients were masked to treatment allocation. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. We used a sequential analytical design, based on intention to treat, to avoid prolonging the trial after either efficacy or futility had been established. This trial is registered with ClinicalTrial.gov, number NCT00623740.
1072 neonates were screened between May 25, 2008, and Jan 31, 2014, of which 523 were randomly assigned (256 hydrocortisone, 267 placebo). 255 infants on hydrocortisone and 266 on placebo were included in analyses after parents withdrew consent for one child in each group. Of the 255 infants assigned to hydrocortisone, 153 (60%) survived without bronchopulmonary dysplasia, compared with 136 (51%) of 266 infants assigned to placebo (odds ratio [OR] adjusted for gestational age group and interim analyses 1·48, 95% CI 1·02–2·16, p=0·04). The number of patients needed to treat to gain one bronchopulmonary dysplasia-free survival was 12 (95% CI 6–200). Sepsis rate was not significantly different in the study population as a whole, but subgroup analyses showed a higher rate only in infants born at 24–25 weeks gestational age who were treated with hydrocortisone (30 [40%] of 83 vs 21 [23%] of 90 infants; sub-hazard ratio 1·87, 95% CI 1·09–3·21, p=0·02). Other potential adverse events, including notably gastrointestinal perforation, did not differ significantly between groups.
In extremely preterm infants, the rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was significantly increased by prophylactic low-dose hydrocortisone. This strategy, based on a physiological rationale, could lead to substantial improvements in the management of the most premature neonates.
Assistance Publique-Hôpitaux de Paris.
Journal Article
Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population‐based cohort study
by
ZUPAN‐SIMUNEK, VÉRONIQUE
,
FRESSON, JEANNE
,
BURGUET, ANTOINE
in
At Risk Persons
,
Brain
,
Brain Diseases - epidemiology
2010
Aim The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population‐based cohort of very preterm infants. Method As part of EPIPAGE, a population‐based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. Results The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1367g (SD 393g; range 450–2645g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7–10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1305g (SD 386g; range 500–2480g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03–2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95–3.14) were predictors of the development of CP in very preterm infants. Interpretation Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.
Journal Article
Natural evolution of patent ductus arteriosus in the extremely preterm infant
2015
Objective The persistence of the patent ductus arteriosus (PDA) is frequently encountered in very preterm infants. Neither preventive nor curative treatments of PDA have been shown to improve the outcome of these infants. Since no consensus on optimal treatment of PDA is established, we evaluated the rate of spontaneous PDA closure in infants born before 28 weeks of gestation. Patients and methods We studied a retrospective cohort of 103 infants (gestational age 24–27 weeks) admitted to our neonatal intensive care unit from 1 June 2008 to 31 July 2010. Maternal and neonatal characteristics were collected. The PDA was defined by the persistence of ductal patency after 72 h and was followed up by regular echocardiography. Results Twelve infants died within the first 72 h and were excluded from the analysis. Among 91 infants analysed, 8 (9%) closed their ductus arteriosus before 72 h and the ductus could not be determined patent in 13. Of the 70 infants with a PDA still persistent, one underwent surgical ligation and echocardiography showed spontaneous closure in 51 (73%) of them. In the remaining 18 infants, the date of PDA closure could not be determined either because of their death (n=11) or due to discharge (n=7). Overall, a spontaneous closure of the ductus arteriosus was observed in 59 of the 91 infants. Conclusions We have to question whether exposure to the risks of therapeutic interventions targeted for ductal closure is warranted since a PDA closes spontaneously in at least 73% of infants born before 28 weeks.
Journal Article
Premedication practices for neonatal tracheal intubation: Results from the EPIPPAIN 2 prospective cohort study and comparison with EPIPPAIN 1
2021
To describe the frequency and nature of premedication practices for neonatal tracheal intubation (TI) in 2011; to identify independent risk factors for the absence of premedication; to compare data with those from 2005 and to confront observed practices with current recommendations. Data concerning TI performed in neonates during the first 14 days of their admission to participating neonatal/pediatric intensive care units were prospectively collected at the bedside. This study was part of the Epidemiology of Procedural Pain in Neonates study (EPIPPAIN 2) conducted in 16 tertiary care units in the region of Paris, France, in 2011. Multivariate analysis was used to identify factors associated with premedication use and multilevel analysis to identify center effect. Results were compared with those of the EPIPPAIN 1 study, conducted in 2005 with a similar design, and to a current guidance for the clinician for this procedure. One hundred and twenty‐one intubations carried out in 121 patients were analyzed. The specific premedication rate was 47% and drugs used included mainly propofol (26%), sufentanil (24%), and ketamine (12%). Three factors were associated with the use of a specific premedication: nonemergent TI (Odds ratio (OR) [95% CI]: 5.3 [1.49‐20.80]), existence of a specific written protocol in the ward (OR [95% CI]:4.80 [2.12‐11.57]), and the absence of a nonspecific concurrent analgesia infusion before TI (OR [95% CI]: 3.41 [1.46‐8.45]). No center effect was observed. The specific premedication rate was lower than the 56% rate observed in 2005. The drugs used were more homogenous and consistent with the current recommendations than in 2005, especially in centers with a specific written protocol. Premedication use prior to neonatal TI was low, even for nonemergent procedures. Scientific consensus, implementation of international or national recommendations, and local written protocols are urgently needed to improve premedication practices for neonatal intubation.
Journal Article
Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period
by
Demoulin, Silvia
,
Zupan, Veronique
,
Bonabel, Claude
in
Analysis
,
Asthma
,
Bronchopulmonary dysplasia
2023
This study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA). A repeated instillation of 200 mg/kg poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but the SURF infants needed less re-hospitalization than the controls for respiratory problems at 1- and 2-year PNA. There was no growth difference at 7.1 ± 0.3 years between 41 SURF infants and 36 controls (80% of the eligible children), and 7.9% SURF infants vs. 28.6% controls presented asthma (p = 0.021). The children underwent cognitive assessment (WISC IV) and pulmonary function testing (PFT), measuring their spirometry, lung volume, and airway resistance. The spirometry measures showed differences (p < 0.05) between the SURF infants and the controls (mean ± standard deviation (median z-score)) for FEV1 (L/s) (1.188 ± 0.690(−0.803) vs. 1.080 ± 0.243 (−1.446)); FEV1 after betamimetics (1.244 ± 0.183(−0.525) vs. 1.091 ± 0.20(−1.342)); FVC (L) (1.402 ± 0.217 (−0.406) vs. 1.265 ± 0.267 (−1.141)), and FVC after betamimetics (1.452 ± 0.237 (−0.241) vs. 1.279 ± 0.264 (−1.020)). PFT showed no differences in the volumes or airway resistance. The global IQ median (interquartile range) was 89 (82:99) vs. 89 (76:98), with 61% of the children >85 in both groups. Repeated surfactant treatment in VPNs presenting severe RDS led to the attenuation of early lung injuries, with an impact on long-term pulmonary sequelae, without differences in neurodevelopmental outcomes.
Journal Article
Longitudinal study of infants born preterm
2025
Purpose The SEV-IDF programme aims to track infants born before 33 weeks of gestation, with very low birth weight (VLBW), neonatal encephalopathy or severe birth anomalies and perinatal disease. It employs an open, prospective, multicentric, population-based cohort approach. This report aims to describe the methodology employed to establish and manage the programme, details regarding follow-up procedures, baseline characteristics of the included infants, and highlights new research opportunities emerging from the 'Suivi des Enfants Vulnérables d'Ile-de-France' (SEV-IDF) programme.Participants The programme aims to (1) detect developmental anomalies early, (2) improve prevention using standardised data, (3) optimise follow-up care and (4) support multidisciplinary research.Eligible participants are infants alive at discharge from the 59 maternities with a neonatal unit of the Île-de-France (IDF) region (France). A network of 567 trained physicians monitors the children’s development at 4 months, 1 and 2 years of corrected age, and 3, 4, 5, 6 and 7 years of age. Collected data include sociodemographic, pregnancy and neonatal characteristics, and standardised child development scores.Findings to date The programme enrolled 21 175 participants between 2016 and 2023, with 16 461 (77.7%) having a gestational age less than 33 weeks, 1916 (9.0%) others having VLBW, 1525 (7.2%) having encephalopathy and 1273 (6.0%) having another severe birth anomaly.Future plans The collected data will enable the SEV-IDF scientific committee to describe high-risk infants in the IDF region, design evidence-based campaigns to improve the quality and effectiveness of the follow-up as well as conduct research on developmental anomalies in these high-risk infants. Ongoing research currently focuses on anticipating loss to follow-up and early detection of developmental anomalies.
Journal Article
The Assessment of IgG Avidity in the Evaluation of Perinatal Herpes Simplex Virus Infection
by
Cointe, Denis
,
Odièvre, Marie-Hélène
,
Lacaze-Masmonteil, Thierry
in
Antibody Affinity - physiology
,
Avidity
,
Female
2002
Classical serologic assays are not useful for the diagnosis of perinatal herpes simplex virus (HSV) infection during the acute phase of the disease. We report two cases of neonatal HSV infection that highlight the diagnostic value of HSV-specific IgG avidity and its contribution for further characterization of neonatal HSV infection.
Journal Article
Longitudinal study of infants born preterm (<33 weeks) or with a very low birth weight in the Ile de France region of France (SEV-IDF programme): cohort profile
2025
PurposeThe SEV-IDF programme aims to track infants born before 33 weeks of gestation, with very low birth weight (VLBW), neonatal encephalopathy or severe birth anomalies and perinatal disease. It employs an open, prospective, multicentric, population-based cohort approach. This report aims to describe the methodology employed to establish and manage the programme, details regarding follow-up procedures, baseline characteristics of the included infants, and highlights new research opportunities emerging from the \"Suivi des Enfants Vulnérables d'Ile-de-France\" (SEV-IDF) programme.ParticipantsThe programme aims to (1) detect developmental anomalies early, (2) improve prevention using standardised data, (3) optimise follow-up care and (4) support multidisciplinary research.Eligible participants are infants alive at discharge from the 59 maternities with a neonatal unit of the Île-de-France (IDF) region (France). A network of 567 trained physicians monitors the children’s development at 4 months, 1 and 2 years of corrected age, and 3, 4, 5, 6 and 7 years of age. Collected data include sociodemographic, pregnancy and neonatal characteristics, and standardised child development scores.Findings to dateThe programme enrolled 21 175 participants between 2016 and 2023, with 16 461 (77.7%) having a gestational age less than 33 weeks, 1916 (9.0%) others having VLBW, 1525 (7.2%) having encephalopathy and 1273 (6.0%) having another severe birth anomaly.Future plansThe collected data will enable the SEV-IDF scientific committee to describe high-risk infants in the IDF region, design evidence-based campaigns to improve the quality and effectiveness of the follow-up as well as conduct research on developmental anomalies in these high-risk infants. Ongoing research currently focuses on anticipating loss to follow-up and early detection of developmental anomalies.
Journal Article