Self-regulation and executive functioning are known key predictors of future cognitive development and mental health. We examined the effect of early life neonatal stress, maternal perinatal stress, kangaroo care, maternal parenting behavior and secure child attachment on executive function at 2 years corrected age (CA) in children born preterm (i.e. < 34 weeks of gestation and/or < 1500 g birth weight). Neonatal child characteristics were recorded at the Neonatal Intensive Care Unit (NICU). We examined self-reported perinatal maternal stress during NICU stay, maternal emotional availability at 4 months CA, and child attachment security at 14 months CA. The executive function battery at 2 years CA was completed by 97 children. Low birth weight, a high number of skin breaking procedures and high level of maternal stress predicted lower executive function scores. Kangaroo care, non-intrusive maternal parenting behavior and secure attachment were associated with higher executive function scores. Even after controlling for background factors, modifiable factors such as neonatal child and mother stress, kangaroo care, parenting style, and child attachment style uniquely predict later executive functioning development, indicating that preventive interventions need to integrate multiple aspects of neuroprotective care, including supporting the child-parent bond, both at the NICU and beyond.

Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of these neonates are lacking. The aim was to retrospectively describe all neonates admitted to the University Hospitals Leuven after in utero exposure to lithium (January 2010 to April 2020), and to propose a postnatal care protocol. Descriptive statistics were performed. For continuous parameters with serial measurements, median population values were calculated. In total, 10 mother-neonate pairs were included. The median gestational age was 37 (interquartile range, IQR, 36–39) weeks. Neonatal plasma lithium concentration at birth was 0.65 (IQR 0.56–0.83) mmol/L with a median neonate/mother ratio of 1.02 (IQR 0.87–1.08). Three neonates needed respiratory support, 7/10 started full enteral (formula) feeding on day 1. The median length of neonatal stay was 8.5 (IQR 8–12) days. One neonate developed nephrogenic diabetes insipidus. This study reported in detail the postnatal characteristics and short-term neonatal outcomes. A postnatal care protocol was proposed, to enhance the quality of care for future neonates, and to guide parental counselling. Future prospective protocol evaluation is needed.

Receptor–Blocking Autoantibodies During Pregnancy Background: Graves disease is an autoimmune disease caused by thyroid-stimulating hormone receptor antibodies (TSH-R-Ab), which can be stimulating (TSAb), neutral, or blocking (TBAb). The net antibody activity determines the clinical phenotype. Typically, TSAbs dominate, resulting in hyperthyroidism. Rarely, TBAbs prevail, resulting in hypothyroidism (1). The conventional TSH-R-Ab binding assay used in clinical practice does not differentiate among antibody types.

Abstract Background For several decades, transient hypothyroxinemia of prematurity (THOP) has been a topic of debate. The pathophysiology is incompletely understood and consensus on the therapeutic approach is lacking. This study aimed at gaining a better insight into the pathogenesis by studying the trends in thyroid hormone (TH) levels during the first week of life. Methods This single-center prospective observational study analyzed the plasma levels of total thyroxine (T4) and free thyroxine (fT4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH) and T4-binding globulin (TBG) in cord blood and at the end of the first week of life in 120 preterm infants (gestational age [GA] <37 weeks). The change over time was calculated (delta, ∆). The impact of perinatal and subsequently postnatal variables on ∆ was studied by hierarchical multiple regression. The impact of ∆ on the neurodevelopmental outcome at the corrected ages of 9 and 24 months, measured by the Bayley Scales of Infant Development (BSID)-II, was assessed by logistic regression. Results ∆fT4 levels were negatively affected by GA and use of dopamine, whereas only GA was associated with low ∆T3 levels. Negative ∆fT4 levels were present in 75% of the extremely low-for-gestational-age infants, whereas 23.5% had a negative ∆T3 level. There was an increased risk for an abnormal mental developmental score (<85) with decreasing ∆T3 at 9 months, corrected age, but not at 24 months. Conclusions A negative evolution in circulating TH levels is principally an immaturity phenomenon, whereas dopamine can further suppress the hypothalamic-pituitary-thyroid axis. There is at least a temporary negative effect of this evolution on the infants’ neurodevelopment.

Aim Thyroid hormones are crucial for foetal and neonatal brain development. This paper provides an overview of the normal role of thyroid hormones in foetal brain development and the pathophysiology of transient hypothyroxinaemia of prematurity (THOP). It also discusses the diagnostic and therapeutic controversies around THOP and looks at directions for future research. Methods We used the PubMed and Embase databases to identify papers published in English from 1969 to June 2018. This identified 20 papers about the impact of THOP on neurodevelopment and seven randomised controlled trials about therapeutic approaches from 1981-2016. Results THOP has been researched for more than three decades. The impact of temporarily low thyroxine levels, without any increase in pituitary-secreted thyroid-stimulating hormone at a critical timeframe in an infant's brain development, is still debated. Heterogeneity in THOP definitions, difficulties with thyroid hormone assessment, identifying patients at risk and a clear lack of sufficiently powered studies add to the current controversy. There are indications that thyroid hormone substitution might be useful in extremely low gestational age neonates with THOP. Conclusion Some preterm infants could benefit from THOP treatment, but more studies are needed to clarify further treatment strategies, including the optimal timing of initiation and duration.

Thyroid hormones are crucial for foetal and neonatal brain development. This paper provides an overview of the normal role of thyroid hormones in foetal brain development and the pathophysiology of transient hypothyroxinaemia of prematurity (THOP). It also discusses the diagnostic and therapeutic controversies around THOP and looks at directions for future research. We used the PubMed and Embase databases to identify papers published in English from 1969 to June 2018. This identified 20 papers about the impact of THOP on neurodevelopment and seven randomised controlled trials about therapeutic approaches from 1981–2016. THOP has been researched for more than three decades. The impact of temporarily low thyroxine levels, without any increase in pituitary-secreted thyroid-stimulating hormone at a critical timeframe in an infant's brain development, is still debated. Heterogeneity in THOP definitions, difficulties with thyroid hormone assessment, identifying patients at risk and a clear lack of sufficiently powered studies add to the current controversy. There are indications that thyroid hormone substitution might be useful in extremely low gestational age neonates with THOP. Some preterm infants could benefit from THOP treatment, but more studies are needed to clarify further treatment strategies, including the optimal timing of initiation and duration.

Context: Thyroid hormones are indispensable for normal fetal development.Since the fetus depends to a large extent on maternal thyroid hormone supply through the placenta, this challenges maternal thyroid economy.Several molecular mechanisms are involved in placental thyroid hormone transport and metabolism.Chronic pregnancy complications, associated with utero-placental hypoxia, trigger the development of accelerated placental maturation in order to improve fetal-placental exchange to strengthen the offspring's chance of survival.This review provides an overview of normal maternal-fetal thyroid hormone supply and explores the presence of placental adaptive mechanisms in complicated pregnancies with chronical utero-placental hypoxia to improve the thyroid hormone supply to the fetus under pressure, to end with reflections about the long term health consequences.Evidence acquisition: This work is based on a comprehensive literature review of the Pubmed and Embase database, including relevant articles from 1969 to June 2018.Conclusions:The placenta is actively involved in fetal thyroid hormone delivery through a combination of stimulatory and inhibitory mechanisms.Parallel with histological adaptations to improve trans-placental fetal-maternal exchange, there are indications of placental adaptive mechanisms in thyroid hormone transport and metabolism in case of complicated pregnancies, from animal models and in-vitro experiments.Evidence from human in-vivo studies is limited due to heterogeneity in study populations, small study samples and technical limitations.Further research is necessary to reveal the role of the placenta in pathological circumstances.The placenta might thus be considered as the infants' black box of pregnancy.Results will contribute to more insights in the concept of fetal programming, which lays the foundations of optimum health, growth, and neurodevelopment across the lifespan.

Background: During pregnancy, maternal thyroid hormone supply is crucial for fetal development. Preterm infants often present with hypothyroxinemia. Preterm birth, either spontaneous or medically indicated, is always the result of a complicated pregnancy. We hypothesized that in preterm birth, the maternal transplacental thyroid hormone supply is influenced by the pregnancy complication and we questioned whether maternal and placental compensatory mechanisms are activated to increase thyroid hormone transfer. Methods: Observational case-control study in mother-infant-dyads with complicated pregnancies ending in spontaneous preterm birth (n = 31) or indicated preterm birth due to vascular complications (n = 45) and normal pregnancies (healthy term controls; n = 41). At delivery, maternal and cord blood and placenta samples were collected. Cord and maternal plasma concentrations of thyroid stimulating hormone (TSH), total T4, fT4/FTI, total T3, and T4 binding globulin (TBG), and maternal serum concentrations of thyroid peroxidase (TPO)-antibodies were measured. Placental maturity was evaluated histologically and mRNA and/or protein levels of thyroid hormone deiodinases (DiO) 1, 2 and 3, and transporters (MCT8, MCT10, and OATP1c1) were quantified. Results: In indicated and spontaneous preterm births, cord plasma T4 concentrations were lower than in healthy term controls (p <= .001), whereas T3 was only decreased in spontaneous preterm birth (p <= .001). Compared with spontaneous preterm births and healthy term controls, indicated preterm birth was characterized by higher maternal plasma TSH (p <= .05), earlier placental maturation, higher placental DiO2 gene and MCT10 protein levels and lower DiO3 gene levels (all p <= .01). Conclusions: Low T4 was observed in preterm infants irrespective of the cause of preterm birth, while maternal (TSH) and placental (DiO2, DiO3, and MCT10) compensatory responses were only activated in indicated preterm birth due to vascular complications. This may have mediated the normal fetal T3 availability in preterm infants born after indicated preterm birth but not after spontaneous preterm birth.

The rate of neonatal overweight remains generally high in type 1 diabetes (T1DM). Since glycemic control has improved over time other contributors need to be identified. Our aim is to evaluate the risk factors for large-for-gestational age infants (LGA) in women with T1DM and to evaluate whether the rate of LGA decreased over time.

Background and aims: Serum creatinine is traditionally used as a marker of renal function in neonates and relates to gestational age and disease severity in extremely low birth weight (ELBW) infants. Creatinine is commonly used as a biomarker for early morbidity, but we aim to compare postnatal creatinemia trends as a biomarker for subsequent cognitive outcome. We hypothesize that impaired microcirculation not only in the kidney, but also in general (i.e. brain development) can explain this possible link.Study design and outcome measures: A cohort of ELBW infants was analyzed by Bayley Scales of Infant Development (BSID-II) at the corrected age of 2 years old. Besides other perinatal indicators, neonatal creatinemia trends of survivors (n = 140) and BSID scores (n = 96) are compared and analyzed using optimal matching analysis. Hierarchical clustering analysis is applied to identify createnimia trends.Results: Four different creatinemia trends were identified (persistently high, normal, low, high but normalizing). A low creatinemia trend is significantly associated with the lowest percentages of postnatal corticosteroids, NSAIDS and intraventricular hemorrhage (p = 0.005, p = 0.013 and p = 0.041 respectively) compared to a normal or persistently high creatinemia trend and associated with the best cognitive outcome (+13 points compared to the mean creatinemia trend and +23 points compared to a persistently high creatinemia trend).Conclusions: Creatinemia trends after birth are not only useful to predict renal function, but are also associated with cognitive outcome in extremely low birth weight infants. Neonates who have low creatinemia trends after birth, have the highest BSID scores at the age of two years old. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Objectives Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth.Study design Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g).Results Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 mu g/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02).Conclusions Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

PurposeRetinopathy of prematurity (ROP) is a leading cause of preventable blindness throughout the world. Several risk factors have been studied, but most studies remain inconclusive. Evidence is accumulating that one of the strongest predictors of ROP, in addition to oxygen use and low gestational age, is poor weight gain during the first postnatal weeks. MethodsIn a prospective study, we sought to determine the importance of serial weight measurements to help predict neovascularization (NV). In a first stage, a summary of the response in each case is identified and calculated as area under the curve (AUC). In a second stage, these different AUCs are analyzed by nonparametric Mann-Whitney U test. For the murine study, pups were redistributed in smaller and larger litters. On postnatal day (P)7–12, the oxygen-induced retinopathy (OIR) model was applied. Body weight was measured on P7, P14, and P17. Retinal NV was assessed on P17. For the human study, the subjects were part of the control arm of the NIRTURE trial. Ophthalmologists screened for ROP. Birthweight was recorded. Weekly weight measurements were performed for the first 4 weeks. ResultsThe AUC of serial weight (gain) measurements was significantly lower in murine (14 vs 17 g; p = 0.01) and human (140 g/wk vs 240 g/wk; p = 0.0001) newborns developing retinal NV. ConclusionsThis prospective study supports previous findings, using a new way of statistical analysis, that early postnatal weight gain is an important indicator in the development of neovascular disease.

Purpose To use the continuous glucose monitoring system (CGMS) in very low birthweight (VLBW) infants to further explore the association between elevated glucose levels and retinopathy of prematurity (ROP) and to find new preventive strategies for ROP. Methods A secondary analysis of risk factors for ROP in VLBW infants was performed in the neonatal intensive care units of University Hospital Leuven and ZOL Genk, Belgium. The subjects were part of the NIRTURE trial (ISRCTN78428828). Only control subjects with conclusive ROP assessments who received standard clinical care were included in this analysis. A total of 100 VLBW infants (birthweight ≤ 1500 g) were included. Twenty-three (23%) infants developed ROP; 77 (77%) did not. Results Development of ROP was linked to the known classic risk factors. In addition, ROP was associated with higher glycemia levels across the first week (p between 0.01 and <0.0001). Across the first week, glycemia predicted ROP with receiver operating characteristic (ROC) scores between 0.67 and 0.80, and with a median glycemia cutoff of 6.7 mmol/L. Comparison of ROC curves revealed first-week glycemia as an important variable in the development of ROP with a predictive power as high as the classic risk factors. Conclusions Moderately elevated glucose levels in the first week of life are associated with the development of ROP. They contribute to this multifactorial disease in a way equal to the known classical risk factors for ROP. Therefore, careful monitoring of glucose levels by CGMS can be helpful in the prevention of ROP.