Publications

Abstract

Aim: Children born very preterm require additional specialist care because of the health and developmental risks associated with preterm birth, but information on their health service use is sparse. We sought to describe the use of specialist services by children born very preterm in Europe.

Method: We analysed data from the multi-regional, population-based Effective Perinatal Intensive Care in Europe (EPICE) cohort of births before 32 weeks’ gestation in 11 European countries. Perinatal data were abstracted from medical records and parents completed a questionnaire at 2 years corrected age (4322 children; 2026 females, 2296 males; median gestational age 29wks, interquartile range [IQR] 27-31wks; median birthweight 1230g, IQR 970-1511g). We compared parent-reported use of specialist services by country, perinatal risk (based on gestational age, small for gestational age, and neonatal morbidities), maternal education, and birthplace.

Results: Seventy-six per cent of the children had consulted at least one specialist, ranging across countries from 53.7% to 100%. Ophthalmologists (53.4%) and physiotherapists (48.0%) were most frequently consulted, but individual specialists varied greatly by country. Perinatal risk was associated with specialist use, but the gradient differed across countries. Children with more educated mothers had higher proportions of specialist use in three countries.

Interpretation: Large variations in the use of specialist services across Europe were not explained by perinatal risk and raise questions about the strengths and limits of existing models of care.

What this paper adds: Use of specialist services by children born very preterm varied across Europe. This variation was observed for types and number of specialists consulted. Perinatal risk was associated with specialist care, but did not explain country-level differences. In some countries, mothers’ educational level affected use of specialist services.

J Pediatr. 2018 Dec;203:150-155. doi: 10.1016/j.jpeds.2018.07.072. Epub 2018 Sep 27.

OBJECTIVE:

To evaluate the association between active antenatal management and neonatal outcomes in extremely preterm newborns admitted to a neonatal intensive care unit (NICU).

STUDY DESIGN:

This population-based cohort study was conducted in 25 regions of France. Infants born in 2011 between 22^0/7 and 26^6/7 weeks of gestation and admitted to a NICU were included. Infants with lethal congenital malformations or death in the delivery room were excluded. A multilevel multivariable analysis was performed, accounting for clustering by mother (multiple pregnancies) and hospital plus individual characteristics, to estimate the association between the main exposure of no active antenatal management (not receiving antenatal corticosteroids, magnesium sulfate, or cesarean delivery for fetal indications) and a composite outcome of death or severe neonatal morbidity (including severe forms of brain or lung injury, retinopathy of prematurity, and necrotizing enterocolitis).

RESULTS:

Among 3046 extremely preterm births, 783 infants were admitted to a NICU. Of these, 138 (18%) did not receive active antenatal management. The risk of death or severe morbidity was significantly higher for infants without active antenatal management (crude OR, 2.60; 95% CI, 1.44-4.66). This finding persisted after adjustment for gestational age (OR, 2.08; 95% CI, 1.19-3.62) and all confounding factors (OR, 1.86; 95% CI, 1.09-3.20).

CONCLUSIONS:

The increased risk of severe neonatal outcomes for extremely preterm babies admitted to a NICU without optimal antenatal management should be considered in individual-level decision making and in the development of professional guidelines for the management of extremely preterm births.

PLoS One.2018 Sep 24;13(9):e0204498. doi:10.1371/journal.pone.0204498. eCollection 2018

BACKGROUND AND OBJECTIVES:

Small for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population.

METHODS:

Retrospective single-center cohort study including 141 neonates born between 24 and 30 weeks’ gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks’ postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS:

Bronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2-15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9-11.3]).

CONCLUSIONS:

Small for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia.

Erratum in

• Risk of Severe Acute Maternal Morbidity According to Planned Mode of Delivery in Twin Pregnancies: Correction.[No authors listed]Obstet Gynecol. 2018 Dec;132(6):1507. doi: 10.1097/AOG.0000000000002998.PMID: 30461682 No abstract available.

Abstract

Objective: To evaluate the association between the planned mode of delivery and severe acute maternal morbidity in women with twin pregnancies.

Methods: In this planned secondary analysis of the JUmeaux MODe d’Accouchement cohort, a national prospective population-based study of twin deliveries conducted from February 2014 to March 2015 in 176 hospitals performing more than 1,500 annual deliveries in France, we included women with twin pregnancies at 24 weeks of gestation or greater with two live fetuses. Women delivering before 24 weeks of gestation, those with recognized indications for cesarean delivery, and those with severe acute maternal morbidity symptomatic before labor were excluded to limit confounding by indication. The primary outcome was a composite measure of intra- or postpartum severe acute maternal morbidity. Multivariate Poisson regression models and propensity score matching were used to control for potential confounding by indication. Analyses were conducted for the overall study cohort as well as stratified by maternal age in years (younger than 30, 30-34, 35 years or older). No adjustments were made for multiple comparisons.

Results: Among the 8,124 women included in this analysis, 3,062 (37.7%) had planned cesarean deliveries and 5,062 (62.3%) had planned vaginal deliveries, of whom 4,015 (79.3%) delivered both twins vaginally. No significant overall association was found between the planned mode of delivery and severe acute maternal morbidity (6.1% in the planned cesarean delivery group and 5.4% in the planned vaginal group; adjusted relative risk 1.00, 95% CI 0.81-1.24). In women 35 years or older, the risk of severe acute maternal morbidity was significantly higher for those with planned cesarean delivery than planned vaginal delivery (7.8% vs 4.6%, adjusted relative risk 1.44, 95% CI 1.02-2.06). Propensity score and secondary analyses yielded similar results.

Conclusion: In twin pregnancies, there is no overall association between planned mode of delivery and severe acute maternal morbidity. Women older than 35 years may be at higher risk of severe acute maternal morbidity after planned cesarean delivery.

Abstract

Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population-based cohort of births below 32 weeks of gestation in 11 European countries in 2011-2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever-breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25-34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high-risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio-economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge.

Expert Rev Vaccines. 2018 May;17(5):383-393. doi: 10.1080/14760584.2018.1471988. Epub 2018 May 9.

INTRODUCTION:

Vaccination in pregnancy has been shown to be effective for the prevention of influenza and pertussis in infants, providing support for similar strategies to prevent group B streptococcus and respiratory syncytial virus infections that represent a large burden in pediatric population.

AREAS COVERED:

This review addresses the principle of maternal immunization, efficacy and safety of both pertussis and seasonal influenza vaccines and presents available data on group B streptococcus and respiratory syncytial virus that are in development for administration during pregnancy.

EXPERT COMMENTARY:

Complementary data is needed to help in understanding pertussis vaccine mechanisms, improving influenza vaccine efficacy and addressing the interference phenomenon which is when maternal antibodies interfere with the infant vaccine response. Several knowledge gaps need to be filled in group B streptococcus and respiratory syncytial virus vaccines research

Molecules. 2018 May 4;23(5). pii: E1085. doi: 10.3390/molecules23051085.

Abstract

Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations carrying rhodamine-labelled siRNAs were evaluated on an in vitro model, i.e., human primary villous cytotrophoblasts. siRNA internalization rate from lipoplexes were compared to the one in the presence of the lipofectamine reagent and assessed by confocal microscopy. Results showed cellular internalization of nucleic acid with all three formulations, based on two cationic lipids, either DMAPAP or CSL-3. Moreover, incubation with DMAPAP+AA provided a rate of labelled cells as high as with lipofectamine (53 _ 15% and 44 _ 12%, respectively) while being more biocompatible. The proportion of cells which internalized siRNA were similar when using DMAPAP/DDSTU (16 _ 5%) and CSL-3 (22 _ 5%). This work highlights that liposomes could be a promising approach for gene therapy dedicated to pregnant patients.

Drug Discov Today. 2018 May; 23(5):1099-1107. doi: 10.1016/j.drudis.2018.01.048. Epub 2018 Jan 31.

Abstract

Preeclampsia is a serious pregnancy disorder characterized by the onset of high blood pressure and proteinuria. Although the understanding of the disease is increasing, it remains without treatment, other than the delivery of the baby and the placenta. This review sets out to discuss some new developments and strategies in the treatment of preeclampsia. We briefly review the current knowledge on the pre-eclamptic pathophysiology. We then examine the recent trends in preeclampsia treatment and, in particular, the tracks of potential therapeutic targets. Finally, we focus on the possibilities nano-carriers could offer in the management of preeclampsia. Indeed, nano-carriers could help to prevent transplacental passage and promote placental-specific drug delivery, thereby enhancing efficacy and improving safety. Tendencies are then drawn from the available studies on the optimal characteristics of a nano-carrier to deliver drugs to the placenta.

Med Sci (Paris). 2018 Apr;34(4):331-337. doi: 10.1051/medsci/20183404014. Epub 2018 Apr 16.

Abstract

Some diseases seem to have a developmental origin. Today, the microbiota is recognized as a determinant in health and diseases and one important step is its establishment in the neonate. Some variations in its composition including an imbalance (also called dysbiosis) have been associated to several pathologies. Recent studies suggest a bacterial colonization in the non-pregnant uterus, in the amniotic fluid and in the placenta, which were previously thought sterile. So, during developmental phases, the fetus could have encounter bacteria in utero. These bacteria could contribute to its microbiota establishment before parturition and therefore before the encounter with all microorganisms from vaginal, fecal and cutaneous microbiotas according to the delivery mode. However, studies stating the existence of such in utero microbiota, characterized by a low biomass, are somewhat disputed.

Eur J Public Health. 2018 Apr 1;28(2):303-309. doi: 10.1093/eurpub/ckx131.

Background:

Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset.

Methods:

We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses.

Results:

Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset.

Conclusion:

Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.