Publications

Abstract

Background: Placental passage of drugs in twins is poorly understood, and is unknown regarding antiretrovirals (ARVs). In the event of large differences in the exposure of 2 twins to the same maternal therapy, this could have a clinical impact in terms of prevention of perinatal HIV transmission or adverse effects.

Objective: To describe the frequency of differential transplacental passage of antiretrovirals between twins.

Study design: The study was performed retrospectively, on data from women included in a multicenter perinatal HIV cohort study. All twin pairs for which the mother received antiretroviral therapy and for which drug concentrations in both of the umbilical cords after cord clamping at delivery were studied. We considered that a difference in concentrations of more than 50 % between twins was a substantial difference (ratios below 0.67 or above 1.50).

Results: We analyzed 29 twin pairs, 27 dichorionic and 2 monochorionic diamniotic. Cord blood concentrations differed between the 2 twins by more than 50 % for at least one ARV in 9 twin pairs, 8 dichorionic and 1 monochorionic. Discordant concentrations were observed in one or more cases for several nucleoside reverse transcriptase inhibitors (tenofovir, emtricitabine, lamivudine, zidovudine) and protease inhibitors (atazanavir, lopinavir, saquinavir et ritonavir); within individual twin pairs placental transfer was discordant for one or more ARVs, but identical for others.

Conclusion: Concentrations differed in nearly one third of twin pairs. This may be due to interindividual genetic variability of placental transporters between dizygotic twins as well as physiological differences between twins.

Abstract

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA. This approach takes into account the timing of TMA in pregnancy or postpartum, coexisting symptoms, first-line laboratory workup, and probability-based assessment of possible causes of pregnancy-associated TMA. Its aims are: to rule thrombotic thrombocytopenic purpura (TTP) in or out, with urgency, using ADAMTS13 activity testing; to consider alternative disorders with features of TMA (preeclampsia/eclampsia; hemolysis elevated liver enzymes low platelets syndrome; antiphospholipid syndrome); or, ultimately, to diagnose complement-mediated atypical hemolytic uremic syndrome (aHUS; a diagnosis of exclusion). Although they are rare, diagnosing TTP and aHUS associated with pregnancy, and postpartum, is paramount as both require urgent specific treatment.

Abstract

Endometriosis is a frequent, chronic, inflammatory gynecological disease characterized by the presence of ectopic endometrial tissue causing pain and infertility. Macrophages have a central role in lesion establishment and maintenance by driving chronic inflammation and tissue remodeling. Macrophages can be reprogrammed to acquire memory-like characteristics after antigenic challenge to reinforce or inhibit a subsequent immune response, a phenomenon termed « trained immunity. » Here, whereas bacille Calmette-Guérin (BCG) training enhances the lesion growth in a mice model of endometriosis, tolerization with repeated low doses of lipopolysaccharide (LPS^low) or adoptive transfer of LPS^low-tolerized macrophages elicits a suppressor effect. LPS^low-tolerized human macrophages mitigate the fibro-inflammatory phenotype of endometriotic cells in an interleukin-10 (IL-10)-dependent manner. A history of severe Gram-negative infection is associated with reduced infertility duration and alleviated symptoms, in contrast to patients with Gram-positive infection history. Thus, the manipulation of innate immune memory may be effective in dampening hyper-inflammatory conditions, opening the way to promising therapeutic approaches.

Abstract

We analyzed group B Streptococcus (GBS) neonatal invasive infections reported during 2007-2019 in France. The hypervirulent clonal complex (CC) 17 GBS was responsible for 66% (827/1,262) of cases. The role of CC17 GBS increased over time (p for trend = 0.0001), together with the emergence of a multidrug-resistant CC17 GBS sublineage.

J Gynecol Obstet Hum Reprod. 2020 Oct 31;101964. doi: 10.1016/j.jogoh.2020.101964.Online ahead of print.

Abstract

Objective: Assess the discordance between scalp pH and lactates performed from the same sample during labor.

Method: This single-center retrospective study included all women with a singleton fetus who had at least one fetal blood sample taken during labor. Some of them had up to seven samples. Scalp pH was the reference parameter for obstetric decision-making. The correlation between the pH and lactates was studied using Pearson coefficient. By categorizing the values as normal, pre-acidosis and acidosis, we were able to estimate agreement with Cohen’s kappa coefficient. The frequency of discordance in the categorization and the factors related to it were studied with univariate and multivariable analyses. Cases of severe acidosis at birth (cord pH < 7.00) and cases with acidosis scalp lactates but normal scalp pH were analyzed.

Results: We analyzed 480 samples from 268 fetuses among the 2644 deliveries during the study periode. Fetal blood sampling represented 10 % of deliveries. The scalp pH and lactates results were strongly correlated (r=-0.83), but their agreement was only fair (K = 0.36). In 29.4 % of cases, pH and lactates were discordant. Factors related to discordance were meconium-stained fluid, sampling at full dilation and multiple sampling. Six infants (2.2 %) had severe acidosis at birth. Cases’ analyses did not allow to conclude severe acidosis could have been avoided using scalp lactates for obstetric decision-making.

Conclusion: For more than a quarter of the samples, results were discordant between scalp pH and lactates, especially when cervix was full dilated and when the amniotic fluid was meconium-stained. A randomized controlled trial comparing the relevance of each parameter according to the obstetrical situation would be necessary.

Abstract

Background: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries.

Main body: The term « PREPARE » designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls).

Short conclusion: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease.

Bull Epidémiol Hebd. 2020;(28):562-70. http://beh.santepubliquefrance.fr/beh/2020/28/2020_28_2.html

Résumé

Contexte : Malgré les bénéfices reconnus du lait maternel, les taux d’allaitement chez les enfants nés prématurément sont variables selon les pays et les unités néonatales. Les caractéristiques maternelles et néonatales associées à l’allaitement d’un enfant né prématurément ont largement été étudiées et n’expliquent pas l’ensemble de cette variabilité.

Objectifs : Décrire et analyser les facteurs associés à l’allaitement à la sortie d’hospitalisation chez les enfants nés prématurément, avec un intérêt particulier pour les politiques d’unités soutenant l’allaitement.

Méthodes : La cohorte Epipage-2 (Étude épidémiologique sur les petits âges gestationnels-2) est une étude nationale prospective en population ayant inclus les naissances survenues en 2011 entre 22 et 34 semaines d’aménorrhée (SA) dans toutes les unités néonatales de 25 régions françaises. Les déterminants de l’allaitement ont été analysés par régression logistique multivariée dans deux populations distinctes : 3 108 enfants nés avant 32 SA et 883 enfants nés entre 32 et 34 SA.

Résultats : Au total, 47% des enfants nés avant 32 SA et 59% des enfants nés entre 32 et 34 SA recevaient du lait maternel à la sortie d’hospitalisation, avec une variabilité inter-unités respective de 21% à 84% et de 27% à 87%. Les politiques d’unités soutenant l’allaitement, en particulier le peau-à-peau précoce, la participation des parents à l’alimentation de leur enfant, étaient en partie associées à cette variabilité. Des taux élevés d’initiation de l’allaitement dans la population générale n’étaient associés à l’allaitement à la sortie que chez les enfants nés entre 32 et 34 SA.

Conclusion : L’adoption des politiques de soutien des unités les plus performantes pourrait permettre de réduire la variabilité des taux d’allaitement à la sortie dans cette population à risque des enfants nés prématurément.

Abstract

Objective: To evaluate whether caesarean delivery before 26 weeks of gestation was associated with symptoms of depression and anxiety in mothers in comparison with deliveries between 26 and 34 weeks.

Design: Prospective national population-based EPIPAGE-2 cohort study.

Setting: 268 neonatology departments in France, March to December 2011.

Population: Mothers who delivered between 22 and 34 weeks and whose self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (State-Trait Anxiety Inventory: STAI) were assessed at the moment of neonatal discharge.

Methods: The association of caesarean delivery before 26 weeks with severe symptoms of depression (CES-D ≥16) and anxiety (STAI ≥45) was assessed by weighted and design-based log-linear regression model.

Main outcome measures: Severe symptoms of depression and anxiety in mothers of preterm infants.

Results: Among the 2270 women completing CES-D and STAI questionnaires at the time of neonatal discharge, severe symptoms of depression occurred in 25 (65.8%) women having a caesarean before 26 weeks versus in 748 (50.6%) women having a caesarean after 26 weeks. Caesarean delivery before 26 weeks was associated with severe symptoms of depression compared with caesarean delivery after 26 weeks (adjusted relative risk [aRR] 1.42, 95% CI 1.12-1.81) adjusted to neonatal birthweight and severe neonatal morbidity among other factors. There was no evidence of an association between mode of delivery and symptoms of anxiety.

Conclusions: Mothers having a caesarean delivery before 26 weeks’ gestation are at high risk of symptoms of depression and may benefit from specific preventive care.

Abstract

Background: The association between prolonged non-nutritive sucking habits (NNSHs, ie, sucking pacifiers or fingers) and maxillofacial growth anomalies in the general population has been widely described. Because maturation of sucking abilities is not fully achieved in very preterm infants (<32 weeks’ gestation), neonatal services worldwide rely on the use of pacifiers to promote the development of adequate sucking reflexes, possibly prolonging NNSHs during infancy.

Objective: We aimed to describe the frequency and to identify factors associated with NNSHs at age 2 years in very preterm children.

Methods: The study was based on data from EPIPAGE-2, a French national prospective cohort study of preterm births during 2011 that included 2593 children born between 24 and 31 weeks’ gestation. The primary outcome was NNSHs at 2 years. Multivariable log-linear regression models with generalized estimation equations were used to study the association between the characteristics studied and NNSHs. Multiple imputations were used to take into account missing data.

Results: The frequency of NNSHs was 69% in the overall sample but higher among girls (adjusted risk ratio [RR] 1.12, 95% confidence interval [CI] 1.05, 1.17), children born from multiple pregnancies (eg, twins/triplets) (RR 1.07, 95% CI 1.00, 1.11), children who were fed by nasogastric tube (RR 1.07, 95% CI 1.01, 1.13), or those who benefitted from developmental care programmes (RR 1.10, 95% CI 1.02, 1.19). The NNSHs frequency was lower if mothers were not born in France (RR 0.70, 95% CI 0.64, 0.77), children had 2 or more older siblings (RR 0.88, 95% CI 0.82, 0.96), or children were breast-fed at discharge (RR 0.90, 95% CI 0.85, 0.95).

Conclusions: NNSHs at 2 years seemed associated with cultural background, development care programmes, and breast feeding. Whether NNSHs at 2 years among very preterm children are associated with future maxillofacial growth anomalies deserves further attention.

Gynecol Obstet Fertil Senol. 2020 Dec;48(12):850-857. French. doi: 10.1016/j.gofs.2020.09.021. Epub 2020 Oct 3. PMID: 33022445.

Abstract

Objectives: International literature suggests that active perinatal management at extremely low gestational ages improves survival without increasing the risk of impairment in survivors, compared to less active management. Although these results are limited to a small number of countries, they question current practices in France. New propositions on perinatal management of extremely preterm infants have carried out by the French Society of Perinatal Medicine, the French Society of Neonatology and the National College of French Obstetricians and Gynecologists.

Methods: This group was set up in 2015 on the initiative of the professional societies and in collaboration with parents’ and users’ associations. The work was based on a review of the literature on the prognosis of extremely preterm children, as well as on recommendations by European societies. Based on this information, a text was produced, submitted to all members of the working group and definitively validated in April 2019.

Results: This text offers a decision-making guideline for the management at extremely low gestational ages. Its principles are: the administration of steroids independently of management (resuscitation or comfort care); a prognostic evaluation and a collegial decision, outside the context of the emergency; a consensus on the information to be given to parents before going to inform them and gather their opinion.

Conclusions: These new propositions will contribute to modifying perinatal care at extremely low gestational ages in France.