Publications

Abstract

Objective: Herpes simplex virus (HSV) infection during pregnancy can cause severe neonatal infections. It is also a rare cause of congenital infections. We aimed to describe fetal and neonatal abnormalities of congenital HSV infection in order to define the features that are accessible to prenatal diagnosis during ultrasound screening and/or during a work-up for congenital malformations.

Methods: We analysed all cases of congenital HSV infection (CHI) described before and/or after birth and identified in Pubed and classified the findings as accessible or not to prenatal diagnosis.

Results: Thirty-six cases of congenital herpes infection were reported, of which 15 were described prenatally and 21 postnatally. The most frequently reported malformations accessible to prenatal diagnosis were cerebral anomalies. The most common abnormalities described after birth were skin lesions and keratitis, which are not considered amenable to prenatal ultrasound detection. CHI can due to either HSV1 or HSV2 infection, whether primary or non-primary infection, with or without the presence of maternal symptoms.

Conclusion: Prenatal ultrasound abnormalities due to CHI are rare, varied and non-specific. There is no clear role for fetal ultrasound in the routine management of women with primary or non-primary HSV infection in pregnancy. However, in fetuses with ultrasound abnormalities suggestive of congenital infection, HSV should still be considered as a differential diagnosis after the more common in utero infections, such as cytomegalovirus, are excluded.

No abstract available.

Abstract

Background: Socioeconomic factors influence language development in the general population, but the association remains poorly documented in children born very preterm (VPT). We assessed the impact of maternal education on language development in children born VPT and effect modification by perinatal risk.

Methods: Data were from the Effective Perinatal Intensive Care in Europe (EPICE) population-based cohort of children born <32 weeks’ gestational age (GA) in 2011/2012. Regions from six countries (Estonia, France, Germany, Italy, Sweden and UK) used a validated short form MacArthur Developmental Communicative Inventories Checklist to assess language at 2 years corrected age. Perinatal variables were collected from clinical records. We assessed expressive language delay (ELD), defined as (a) not combining words; and (b) expressive vocabulary <10th percentile of norms for age and sex. Perinatal risk (low, moderate and high) was determined using GA, small for GA and neonatal morbidities. We estimated adjusted risk ratios (aRR) of ELD by maternal education with inverse weighting to account for non-response bias.

Results: Of 2741 children, 24.6% were not combining words and 39.7% had a low expressive vocabulary. Low maternal education (lower secondary or less compared with a bachelor’s degree or more) increased risks of ELD: not combining words: aRR=1.52 (95% CI 1.36 to 1.69); low expressive vocabulary: aRR=1.25 (1.04 to 1.51). For children with low perinatal risk, the aRR were 1.88 (1.26 to 2.80) and 1.44 (1.06 to 1.95), respectively, compared with those with high perinatal risks: 1.36 (1.10 to 1.67) and 1.11 (0.97 to 1.27), respectively.

Conclusion: Low maternal education affects ELD for children born VPT, although the association appears attenuated among those with highest perinatal risk.

Abstract

The etiologies of undifferentiated fever in pregnant women have not been studied thoroughly. Because of its non-specific presentation but severe prognosis, listeriosis is often suspected in this setting, but in most cases not confirmed. We studied the causes of undifferentiated fever in pregnant women who received preemptive listeriosis treatment. We conducted from November 1, 2011, to June 30, 2013, a prospective multicentric observational cohort study of pregnant women referred to obstetrical wards with undifferentiated fever and who received listeriosis preemptive treatment. Clinical and biological features, treatment, outcome, and final diagnosis were collected. We enrolled 103 febrile pregnant women. A cause was identified in 77/103 (75%): viral infection in 52/103 (50%, influenza in 21 (20%)), bacterial infection in 22 (21%, including 16 pyelonephritis (16%) and 3 pneumonias (3%)), and TORCH infection in 3 (3%, varicella, toxoplasmosis, and cytomegalovirus primo-infections, n=1, each). Viral infections collected during influenza outbreaks (December-March) accounted for 43/57 (75%) cases. Two fetal losses were reported in the context of febrile pneumonia. Final diagnoses required adapting medical care in 46/77 (60%) of cases, for bacterial, influenza, or TORCH infections. A large array of benign to potentially severe infections manifests as acute undifferentiated fever in pregnant women, requiring careful repeated evaluation.

Arch Dis Child Fetal Neonatal. 2020 Feb 6;fetalneonatal-2019-317991. doi: 10.1136/archdischild-2019-317991.

Abstract

Objectives

To develop research priorities on the consequences of very preterm (VPT) birth for the RECAP Preterm platform which brings together data from 23 European VPT birth cohorts.

Design and setting

This study used a two-round modified Delphi consensus process. Round 1 was based on 28 research themes related to childhood outcomes (<12 years) derived from consultations with cohort researchers. An external panel of multidisciplinary stakeholders then ranked their top 10 themes and provided comments. In round 2, panel members provided feedback on rankings and on new themes suggested in round 1.

Results

Of 71 individuals contacted, 64 (90%) participated as panel members comprising obstetricians, neonatologists, nurses, general and specialist paediatricians, psychologists, physiotherapists, parents, adults born preterm, policy makers and epidemiologists from 17 countries. All 28 initial themes were ranked in the top 10 by at least six panel members. Highest ranking themes were: education (73% of panel members’ top 10 choices); care and outcomes of extremely preterm births, including ethical decisions (63%); growth and nutrition (60%); emotional well-being and social inclusion (55%); parental stress (55%) and impact of social circumstances on outcomes (52%). Highest ranking themes were robust across panel members classified by background. 15 new themes had at least 6 top 10 endorsements in round 2.

Conclusions

This study elicited a broad range of research priorities on the consequences of VPT birth, with good consensus on highest ranks between stakeholder groups. Several highly ranked themes focused on the socioemotional needs of children and parents, which have been less studied.

BMC Pediatr. 2020 Jan 7;20(1):8. doi: 10.1186/s12887-019-1856-1.

Background

Perinatal decision-making affects outcomes for extremely preterm babies (22-26 weeks’ gestational age (GA)): more active units have improved survival without increased morbidity. We hypothesised such units may gain skills and expertise meaning babies at higher gestational ages have better outcomes than if they were born elsewhere. We examined mortality and morbidity outcomes at age two for babies born at 27-28 weeks’ GA in relation to the intensity of perinatal care provided to extremely preterm babies.

Methods

Fetuses from the 2011 French national prospective EPIPAGE-2 cohort, alive at maternal admission to a level 3 hospital and delivered at 27-28 weeks’ GA, were included. Morbidity-free survival (survival without sensorimotor (blindness, deafness or cerebral palsy) disability) and overall survival at age two were examined. Sensorimotor disability and Ages and Stages Questionnaire (ASQ) result below threshold among survivors were secondary outcomes. Perinatal care intensity level was based on birth hospital, grouped using the ratio of 24-25 weeks’ GA babies admitted to neonatal intensive care to fetuses of the same gestation alive at maternal admission. Sensitivity analyses used ratios based upon antenatal steroids, Caesarean section, and newborn resuscitation. Multiple imputation was used for missing data; hierarchical logistic regression accounted for births nested within centres.

Results

633 of 747 fetuses (84.7%) born at 27-28 weeks’ GA survived to age two. There were no differences in survival or morbidity-free survival: respectively, fully adjusted odds ratios were 0.96 (95% CI: 0.54 to 1.71) and 1.09 (95% CI: 0.59 to 2.01) in medium and 1.12 (95% CI: 0.63 to 2.00) and 1.16 (95% CI: 0.62 to 2.16) in high compared to low-intensity hospitals. Among survivors, there were no differences in sensorimotor disability or ASQ below threshold. Sensitivity analyses were consistent with the main results.

Conclusions

No difference was seen in survival or morbidity-free survival at two years of age among fetuses alive at maternal hospital admission born at 27-28 weeks’ GA, or in sensorimotor disability or presence of an ASQ below threshold among survivors. There is no evidence for an impact of intensity of perinatal care for extremely preterm babies on births at a higher gestational age.

J Infect Dis. 2020 Jan 2;221(2):293-303. doi: 10.1093/infdis/jiz451. PubMed PMID: 31677349.

Background

Innovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions.

Methods

Plasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women.

Results

In HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes.

Conclusions

Selection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.

Mol Cell Endocrinol. 2020 Jan 1;499:110586. doi: 10.1016/j.mce.2019.110586. Epub 2019 Sep 17. PMID: 31539598.

Abstract

Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.

Abstract

Objective: To evaluate whether a history of spontaneous early-term birth (37⁺⁰ -38⁺⁶ weeks of gestation) in the previous singleton pregnancy is a risk factor for preterm birth (PTB) in a subsequent twin pregnancy.
Design: Retrospective cohort study.
Settings: Two French university hospitals (2006-2016).
Population: All women who delivered twins from 24⁺⁰ weeks after a preceding singleton pregnancy birth at 37⁺⁰ to 41⁺⁶weeks.
Methods: Multivariate logistic regression analysis of association between twin PTB and a previous spontaneous singleton early-term birth.
Main outcome measures: Twin PTB rate before 37, 34 and 32 weeks of gestation.
Results: Among 618 twin pregnancies, 270 were born preterm, 92 of them with a preceding spontaneous singleton early-term birth. The univariate analysis showed a significantly higher risk of twin PTB before 37, 34 and 32 weeks among those 92 women compared with those with a full- or late-term birth in their previous singleton pregnancy. This association remained significant after logistic regression (odds ratio [OR] between 2.42 and 3.88). The secondary analysis, restricted to the twin pregnancies with spontaneous PTB found similar results, with a risk of PTB before 37, 34 and 32 weeks significantly higher among women with a previous spontaneous singleton early-term birth, including after logistic regression analysis (OR between 3.51 and 3.56).
Conclusion: A preceding spontaneous singleton early-term birth is a strong and easily identified risk factor for PTB in twin pregnancies.

Sci Rep. 2019 Dec 13;9(1):19034. doi: 10.1038/s41598-019-55046-5.

Abstract

Despite the clinically proven advantages of intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), utilisation has been low in many African countries. To increase uptake and achieve the desired effect, the World Health Organization revised the policy to a monthly administration. Assessing the coverage and impact of the revised policy on pregnancy and neonatal outcomes is, therefore, a necessity. A 2-parallel cross-sectional hospital-based study was carried out among pregnant women attending first antenatal care (ANC) and delivery. Maternal and cord blood samples were assayed for malaria parasites by quantitative PCR targeting both the 18S rDNA and the acidic terminal segment of Plasmodium falciparum var genes, and plasma SP levels were measured by liquid chromatography coupled to tandem mass spectrometry. Parasite prevalence was similar between the two study sites but decreased significantly between the first ANC (9% or 43%) and delivery (4% or 11%) based on the qPCR target. At delivery, 64.5% of women received ≥3 IPTp-SP dose, 15.5% received 2 doses and 6% had 1 dose. Taking ≥3 IPTp-SP doses was associated with an average birth weight increase of more than 0.165 kg. IPTp-SP uptake was associated with plasma SP level at delivery (OR = 32.3, p ≤ 0.005, 95% CI (13.3;78.4) for those that reported ≥3 IPTp-SP doses) while the same trend of improved birth weight was observed with high plasma SP levels. The new IPTp policy is well implemented and well utilised by women in the sites considered in this study and translates to the improved birth weight observed. This study confirms the interest and the clinical benefit expected from this policy change.