Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients.

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium.

Hair as an alternative matrix to assess exposure of premature neonates to phthalate and alternative plasticizers in the neonatal intensive care unit.

Due to adverse health effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted, and gradually replaced by alternative plasticizers (APs). Up to this date, urine was the sole matrix studied for plasticizer exposure in neonates hospitalized in the neonatal intensive care unit (NICU), a population highly vulnerable to toxic effects of plasticizers. The primary aim of this study was to assess simultaneous measurement of phthalate and AP metabolites in neonatal scalp hair.

Development of a neonatal Göttingen Minipig model for dose precision in perinatal asphyxia: technical opportunities, challenges, and potential further steps.

Animal models provide useful information on mechanisms in human disease conditions, but also on exploring (patho)physiological factors affecting pharmacokinetics, safety, and efficacy of drugs in development. Also, in pediatric patients, nonclinical data can be critical for better understanding the disease conditions and developing new drug therapies in this age category. For perinatal asphyxia (PA), a condition defined by oxygen deprivation in the perinatal period and possibly resulting in hypoxic ischemic encephalopathy (HIE) or even death, therapeutic hypothermia (TH) together with symptomatic drug therapy, is the standard approach to reduce death and permanent brain damage in these patients.

Neonatal exposure to phthalate and alternative plasticizers via parenteral nutrition.

Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted in PMDs due to adverse health effects, being gradually replaced by alternative plasticizers (APs). Parenteral nutrition (PN), essential in the care for premature neonates in the neonatal intensive care unit, is stored in plastic storage bags and administered intravenously through plastic infusion circuits. We investigated to which extent PN contributes to current phthalate and AP exposure in premature neonates.

Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus.

Background: Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.

Methods: In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks' gestational age) to receive either expectant management or early ibuprofen treatment.

Multi-centre, randomised non-inferiority trial of early treatment versus expectant management of patent ductus arteriosus in preterm infants (the BeNeDuctus trial): statistical analysis plan.

Background: Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome.

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development.

Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point.

Machine Learning to Support Hemodynamic Intervention in the Neonatal Intensive Care Unit.

Hemodynamic support in neonatal intensive care is directed at maintaining cardiovascular wellbeing. At present, monitoring of vital signs plays an essential role in augmenting care in a reactive manner. By applying machine learning techniques, a model can be trained to learn patterns in time series data, allowing the detection of adverse outcomes before they become clinically apparent.

Amnioinfusion Compared With No Intervention in Women With Second-Trimester Rupture of Membranes: A Randomized Controlled Trial.

Objective: To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes.

Methods: We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a one-to-one ratio by a web-based system.

External Validation Study of First Trimester Obstetric Prediction Models (Expect Study I): Research Protocol and Population Characteristics.

Background: A number of first-trimester prediction models addressing important obstetric outcomes have been published. However, most models have not been externally validated. External validation is essential before implementing a prediction model in clinical practice.

Growth and endothelial function in the first 2 years of life.

Objective: To test the hypothesis that the inverse association between infant growth and endothelial function at 6 months would persist to 24 months and that accelerated growth would lead to an increased percent body fat, which would, in turn, impact negatively on endothelial function.

Study Design: In a prospective observational study, 104 healthy term newborns underwent anthropometry and measurements of vascular vasodilation at 0, 6, 12, and 24 months. We recorded maximum vasodilation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) by use of laser-Doppler vascular perfusion monitoring of the forearm skin vasculature.

Can neonatal sepsis be predicted in late preterm premature rupture of membranes? Development of a prediction model.

Objective: Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women.

Study Design: We used multivariable logistic regression to develop a prediction model.

Economic analysis comparing induction of labor and expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks (PPROMEXIL trial).

Objective: To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM).

Design: Economic analysis based on a randomized clinical trial.

Setting: Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands.

Genetic, maternal and placental factors in the association between birth weight and physical fitness: a longitudinal twin study.

Background: Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design: Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10-18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study.

Genetic and environmental factors in associations between infant growth and adult cardiometabolic risk profile in twins.

Background: Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear.

Objective: The objective was to examine the importance of genetic and environmental factors in the associations between infant growth and adult cardiometabolic risk factors (anthropometric characteristics, lipids, insulin sensitivity, leptin, blood pressure, and fibrinogen) in twins.

Influence of growth during infancy on endothelium-dependent vasodilatation at the age of 6 months.

Low birth weight and accelerated infant growth are associated with cardiovascular disease in adulthood. Endothelial dysfunction is regarded as a precursor of atherosclerosis and is also related to infant growth. We aimed to examine whether an association between infant growth and endothelial function is already present during discrete periods of growth during the first 6 months of life in healthy term infants.

Management of late-preterm premature rupture of membranes: the PPROMEXIL-2 trial.

Objective: The evidence for the management of near term prelabor rupture of membranes is poor. From January 2007 until September 2009, we performed the PPROM Expectant Management versus Induction of Labor (PPROMEXIL) trial. In this trial, we showed that in women with preterm prelabor rupture of membranes (PPROM), the incidence of neonatal sepsis was low, and the induction of labor (IoL) did not reduce this risk.

Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial.

Background: At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term.

Methods And Findings: We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34(+0) and 37(+0) wk of gestation. Participants were randomly allocated in a 1:1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization.

Changes in genetic and environmental effects on growth during infancy.

Background: Accelerated infant growth is a possible explanation for the relation between birth weight and adult diseases.

Objective: The aim of this study was to estimate the heritability of infant growth and to examine whether the genetic contribution changes with increasing or decreasing birth weight and gestational age.

Design: Growth (change in weight z score) was analyzed in 522 infants from the East Flanders Prospective Twin Survey for age windows of 0-1, 1-6, 6-12, and 12-24 mo.

Endothelial vasodilatation in newborns is related to body size and maternal hypertension.

Objective: The fetal response to an adverse intrauterine environment - reflected in low birth weight - is thought to cause an increased risk for adult hypertension. A possible mechanism by which fetal adaptive responses contribute to hypertension is an adverse effect on endothelial function. Identifying individuals with endothelial dysfunction as early as possible may assist in understanding the inverse association between birth weight and hypertension.

Determinants of infant growth in four age windows: a twin study.

Objective: To identify determinants of growth during infancy.

Study Design: The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated.