Long-Term Neurodevelopmental and Functional Outcomes of Infants Born Very Preterm and/or with a Very Low Birth Weight

Background: Birth weight (BW) is often used as a proxy for gestational age (GA) in studies on preterm birth. Recent findings indicate that, in addition to perinatal outcomes, subjects born very preterm (VP; GA <32 weeks) differ from those with a very low birth weight (VLBW; BW <1,500 g) in postnatal growth up to their final height. Objective: To study whether neurodevelopmental and functional outcomes at the age of 19 years differ in VP and/or VLBW subjects. Methods: 705 19-year-old subjects from the Project on Preterm and Small-for-Gestational-Age Infants (POPS) cohort were classified as (1) VP+/VLBW+ (n = 354), (2) VP+/VLBW– (n = 144), or (3) VP–/VLBW+ (n = 207), and compared with regard to IQ as assessed with the Multicultural Capacity Test-intermediate level; neuromotor function using Touwen’s examination of mild neurologic dysfunction; hearing loss; self- and parent-reported behavioral and emotional functioning; educational achievement and occupation; and self-assessed health using the Health Utilities Index and the London Handicap Scale. Results: VP+/VLBW– infants, on average, had 3.8-point higher IQ scores (95% confidence interval [CI] 0.5– 7.1), a trend towards higher educational achievement, 3.3- dB better hearing (95% CI 1.2–5.4), and less anxious behavior, attention problems, and internalizing behavior than to VP+/VLBW+ subjects. VP–/VLBW+ infants reported 1.8 increased odds (95% CI 1.2–2.6) of poor health compared to VP+/VLBW+ subjects. Conclusions: At the age of 19 years, subjects born VP+/VLBW+, VP+/VLBW–, and VP-/VLBW+ have different neurodevelopmental and functional outcomes, although effect sizes are small. Hence, the terms VP and VLBW are not interchangeable. We recommend, at least for industrialized countries, to base inclusion in future studies on preterm populations on GA instead of on B

Diurnal rhythmicity in breast-milk glucocorticoids, and infant behavior and sleep at age 3 months

Purpose: In previous studies, associations between breast-milk cortisol levels obtained on one occasion and infant neurodevelopment were demonstrated. However, more recent evidence indicates that breast-milk cortisol and cortisone concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis, peaking in the early morning and with a nadir at midnight. We studied associations between breast-milk glucocorticoid (GC) rhythmicity, and infant behavior and sleep. Methods: We included 59 mothers, and their infants, of whom 17 had consulted an expert center during pregnancy for an increased risk of psychological distress. At 1 month postpartum, breast milk was sampled (on averag

Interpretation of glucocorticoids in neonatal hair: A reflection of intrauterine glucocorticoid regulation?

Background: Glucocorticoids (GCs) measured in neonatal hair might reflect intrauterine as well as postpartum GC regulation. We aimed to identify factors associated with neonatal hair GC levels in early life, and their correlation with maternal hair GCs. Methods: In a single-center observational study, mother-infant pairs (n = 107) admitted for >72 h at the maternity ward of a general hospital were included. At birth and an outpatient visit (OPV, n = 72, 44 ± 11 days postpartum), maternal and neonatal hair was analyzed for cortisol and cortisone levels by LC-MS/MS. Data were analyzed regarding: (1) neonatal GC levels postpartum and at the OPV, (2) associations of neonatal GC levels with maternal GC levels and (3) with other perinatal factors. Results: (1) Neonatal GC levels were >5 times higher than maternal levels, with a decrease in ±50% between birth and the OPV for cortisol. (2) Maternal and neonatal cortisol, but not cortisone, levels were correlated both at postpartum and at the OPV. (3) Gestational age was associated with neonatal GC postpartum (log-transformed β (95% CI): cortisol 0.07 (0.04-0.10); cortisone 0.04 (0.01-0.06)) and at the OPV (cortisol 0.08 (0.04-0.12); cortisone 0.00 (-0.04 to 0.04)), while weaker associations were found between neonatal GCs and other perinatal and maternal factors. Conclusions: Neonatal hair GCs mainly reflect the third trimester increase in cortisol, which might be caused by the positive feedback loop, a placenta-driven phenomenon, represented by the positive association with GA. Between birth and 1.5 months postpartum, neonatal hair cortisol concentrations decrease sharply, but still appear to reflect both intra- and extrauterine periods

Gender differences in respiratory symptoms in 19-year-old adults born preterm

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Bloom syndrome in short children born small for gestational age: A challenging diagnosis

Background: GH treatment has become a frequently applied growth-promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is contraindicated, eg, chromosomal breakage syndromes. Bloom syndrome is a rare chromosomal breakage syndrome characterized by severe pre- and postnatal growth deficiency, a photosensitive facial erythema, immunodeficiency, mental retardation or learning disabilities, endocrinopathies, and a predisposition to develop a wide variety of cancers. Objective: We report 2 patients with Bloom syndrome illustrating the variety in clinical manifes-tations. They were initially diagnosed with shortstature after SGA birth and Silver Russell syndrome and treated with GH. Cases: Both patients presented with pre- and postnatal growth failure but no clear other characteristic features associated with Bloom syndrome. Photosensitive skin lesions developed only at a pubertal age and were minimal. Also, both children showed normal immunoglobulin levels, normal development, and no signs of endocrino pathiesat start of GH. Dysmorphic features resembling Silver Russell syndrome were observed in both patients. Remarkably, during GH treatment IGF-1 levels increased to values greater than 3.5 SD score, with normal IGF binding protein-3 levels. Conclusion: Short children born SGA comprise a heterogeneous group. Bloom syndrome should be tested for in children with consanguineous parents, dysmorphic features (particularly resembling Silver Russell syndrome), skin abnormalities, and/or IGF-1 levels greater than 2.5 SD score during standard GH treatment with normal IGF binding protein-3 levels. Copyrigh

Is there an association between cortisol and hypertension in overweight or obese children?

Objective: The precise mechanisms behind the development of hypertension in overweight or obese children are not yet completely understood. Alterations in hypothalamic-pituitary-adrenal axis activity may play a role. We aimed to investigate the association between cortisol parameters and hypertension in overweight or obese children. Methods: Random urine (n=180) and early-morning saliva samples (n=126) for assessment of cortisol and cortisone were collected from 1) hypertensive overweight children (n=50), 2) normotensive overweight children (n=145), and 3) normotensive non-overweight children (n=75). Results: The age of participants was 10.4±3.3 years and 53% were boys. The urinary cortisol-to-cortisone ratio [β 1.11, 95% confidence interval (CI) 1.05-1.19] as well as urinary cortisol/creatinine (β 1.38, 95% CI 1.09-1.54), and cortisone/creatinine ratios (β 1.26, 95% CI 1.17-1.36) were significantly higher in overweight or obese than in non-overweight children. After adjusting for body mass index-standard deviation score and urinary cortisone/creatinine ratio, but not cortisol/creatinine ratio, was significantly associated with presence of hypertension (β 1.12, 95% CI 1.02-1.23). Salivary cortisol and cortisone levels were significantly lower in overweight or obese than in non-overweight children (β -4.67, 95% CI -8.19- -1.15, and β 0.89, 95% CI 0.80-0.97 respectively). There were no significant differences in cortisol parameters between hypertensive and normotensive overweight or obese children. Conclusion: This study provided further evidence for an increased cortisol production rate with decreased renal 11β-hydroxysteroid dehydrogenase 2 activity and flattening of early-morning peak cortisol and cortisone in overweight or obese children. However, there were no significant differences in cortisol parameters between hypertensive and normotensive overweight and obese children

Sexual dimorphism in cortisol metabolism throughout pubertal development: A longitudinal study

Objective: Sex differences in disease susceptibility might be explained by sexual dimorphism in hypothalamic-pituitary-adrenal axis activity, which has been postulated to emerge during puberty. However, studies conducted thus far lacked an assessment of Tanner pubertal stage. This study aimed to assess the contribution of pubertal development to sexual dimorphism in cortisol production and metabolism. Methods: Participants (n = 218) were enrolle

Vroeggeboorte, intra-uteriene groeiachterstand en lichamelijke ziehten op de volwassen leeftijd; resultaten van 19 jaar POPS-follow-up

Infants born very prematurely are at greater risk of neurosensory handicaps and developmental problems than are term born children. Premature birth, intrauterine growth retardation, and the combination of both, may also be risk factors for physical disease in adulthood. As this aspect has been little studied so far, we looked into its first signs in the pops-cohort (Project On Preterm and Small for gestational age infants). Prematurity seems to be a risk factor for the development of insulin resistance. The risk is extra high for individuals showing disposition to obesity at later age. Having experienced intrauterine growth retardation even increases the risk. Former premature infants on average show higher mean systolic blood pressure, yet unrelated to degree of intrauterine growth retardation. Renal function (clearance and protein excretion) in young adulthood is less favorable for prematurely born individuals who also experienced intrauterine growth retardation. Prematurely born children show more airway symptoms and poorer lung function in young adulthood. We conclude that neonatal follow up is not only indicated for very premature infants but also for children who experienced severe intrauterine or neonatal growth retardation. Pediatricians ought to inform parents and children as well as the family doctor that prematurity or intrauterine growth retardation may be risk factors for chronic disease at adult age. Active prevention of obesity from an early age onwards is indicated for prematurely born children who experienced intrauterine growth retardation. Family doctors should be extra alert to the development of particularly hypertension and microalbuminuria when these children reach young adult age; a regular check-up for example every two years is recommended. Awareness of their medical history may stimulate the children themselves to prevent obesity, take up sports, and never start smoking