M.M. van Weissenbruch

Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age.

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at <32 weeks of gestation and/or with a birth weight of <1500 g in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

Early influences on the tempo of puberty.

Fetal growth retardation appears to be associated with an increased risk of premature adrenarche, early puberty, polycystic ovary syndrome and associated fertility problems. In a rat model of intrauterine growth retardation, based on ligation of the uterine arteries, the onset of puberty was delayed in female pups, with anovulation during the first cycle. The ovaries showed a lower number of follicles. The onset of puberty was also delayed in male pups. Testosterone production was lower in these growth-retarded rats compared with controls. The relationship between birth weight and the onset of puberty and pubertal progression in different cohorts of healthy children has been examined. In girls, no differences were observed in timing and progression of puberty, including age of menarche, between groups of different birth weights. In boys, a relatively delayed onset of puberty was observed in those with low birth weight, with a normally timed progression. In children with low birth weight, particularly boys, higher dehydroepiandrosterone levels were found compared with children with a normal birth weight, indicating an overactive adrenal gland in children with low birth weight. These data indicate that impaired fetal growth may have long-lasting effects on pubertal development. The fact that results of human studies on the relationship between fetal growth and the onset of puberty are often controversial may be explained by the heterogeneity of children born small for gestational age with respect to the intrauterine insult that they experience. From rat studies, it is clear that a serious intrauterine insult associated with growth failure can lead to dysregulation of puberty and gonadal function.Fetal growth retardation appears to be associated with an increased risk of premature adrenarche, early puberty, polycystic ovary syndrome and associated fertility problems. In a rat model of intrauterine growth retardation, based on ligation of the uterine arteries, the onset of puberty was delayed in female pups, with anovulation during the first cycle. The ovaries showed a lower number of follicles. The onset of puberty was also delayed in male pups. Testosterone production was lower in these growth-retarded rats compared with controls. The relationship between birth weight and the onset of puberty and pubertal progression in different cohorts of healthy children has been examined. In girls, no differences were observed in timing and progression of puberty, including age of menarche, between groups of different birth weights. In boys, a relatively delayed onset of puberty was observed in those with low birth weight, with a normally timed progression. In children with low birth weight, particularly boys, higher dehydroepiandrosterone levels were found compared with children with a normal birth weight, indicating an overactive adrenal gland in children with low birth weight. These data indicate that impaired fetal growth may have long-lasting effects on pubertal development. The fact that results of human studies on the relationship between fetal growth and the onset of puberty are often controversial may be explained by the heterogeneity of children born small for gestational age with respect to the intrauterine insult that they experience. From rat studies, it is clear that a serious intrauterine insult associated with growth failure can lead to dysregulation of puberty and gonadal function.

Clinical pharmacokinetics of phenobarbital in neonates

Demographic and clinical pharmacokinetic data collected from term and preterm neonates who were treated with intravenous phenobarbital have been analysed to evaluate the role of patient characteristics in pharmacokinetic parameters. Significant relationships between total body weight (TBW) or body surface area (BSA) and volume of distribution (Vd) and total body clearance (CL) were found. Coefficients of determination were: 0.55 and 0.59 for Vd, and 0.76 and 0.72 for CL against TBW and BSA, respectively. In addition, significant relationships between height of the infants and volume of distribution of phenobarbital and total body clearance were observed. Coefficients of determination were 0.58 for Vd and 0.56 for CL. A weaker but significant correlation existed between gestational age and Vd or CL of phenobarbital. Coefficients of determination were 0.43 and 0.64, respectively. There was no correlation between volume of distribution per kg body weight or total body clearance per kg body weight and any patient parameter investigated. However, these latter pharmacokinetic parameters tended to decrease with increasing gestational age and height of the neonates. The results obtained were used to develop new loading and maintenance doses for phenobarbital in neonates based on total body weight and body surface area and based on height and gestational age for cases that weight is not available.

Ovarian reserve in young women with low birth weight and normal puberty: a pilot case–control study

Aim.u2003Studies indicate that women born small for gestational age (SGA) have impaired ovarian function. The origin of this ovarian dysfunction is still debatable. The aim of this study was to compare ovarian ageing between girls born appropriate for gestational age (AGA) and SGA. Therefore, we measured Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), E2, Anti-Müllerian hormone (AMH) levels and the pituitary response to endogenous Gonadotropin-releasing hormone (GnRH) in adolescent girls born SGA and AGA. Methods.u2003A case–controlled pilot study consisting of seven SGA women (birth weightu200a<10th percentile AGA) and 13 AGA women with regular menstrual cycles, age 19.9 (±0.42). Early follicular FSH, LH, Oestradiol (E2) and AMH levels were measured. After baseline samples, 100u2009μg GnRH was administered intravenously and at 30, 60 and 90u2009min blood samples were taken to measure gonadotropin levels and to compute the response to endogenous GnRH. Results.u2003Mean follicular phase LH, FSH, E2 and AMH levels did not significantly differ between young women born SGA and AGA. Furthermore, the response to endogenous GnRH showed no significant differences either. Conclusions.u2003We concluded against extension of this pilot study. Based on our observations it seems unlikely that limited ovarian reserve is a predominated problem in adolescent SGA.

Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus.

AbstractBackground and aim: A patent ductus arteriosus (PDA) may influence renal and hepatic blood flow and hence pharmacokinetics of drugs in neonates compared to neonates with a closed ductus arteriosus (CDA). A 10‐percent difference of gentamicin pharmacokinetic parameters between PDA and CDA has been reported, but its implications are unclear. The relevance of this difference relative to the variability within the neonatal population was investigated.nMethods: Twenty‐four neonates (12 with a PDA and 12 with a CDA) treated with gentamicin were retrospectively included. Before closing treatment of the PDA, serum levels were drawn and analysed for regular therapeutic drug monitoring of gentamicin. Data were analysed using the standard two‐stage approach (STS) and an iterative 2‐stage Bayesian population analysis approach (It2B).nResults: Both types of analysis showed no significant differences between both populations for gentamicin total body clearance per kg bodyweight (CL/kg). Volume of distribution per kg bodyweight (Vd/kg) tended to be larger and elimination rate (Kel) tended to be smaller in neonates with PDA. Multiple regression analysis showed for both populations highly significant correlations between total body clearance and body weight (p<0.0001) or gestational age (p<0.0001), and between volume of distribution and body weight (p<0.0001) or gestational age (p<0.0001).nConclusion: Although neonates with a PDA may have small differences in gentamicin pharmacokinetics compared to neonates with a CDA, this is not relevant for clinical practice taking the variability within that population into account.

Relation of maternal hypertension with infant growth in a prospective birth cohort: the ABCD study

The aim of this study was to investigate the assumed positive association of pre-existent and pregnancy-induced hypertension with the offsprings weight and length gain in the first 14 months of life. We studied 3994 pregnant women and their offspring in a prospective community-based cohort study, starting between 2003 and 2004 (Amsterdam Born Children and their Development, ABCD study). Questionnaires obtaining information about hypertension during pregnancy were completed, and this was complemented with additional information from the obstetric caregiver. Anthropometry of the offspring was followed during the first 14 months of life. Main outcome measures were presence or absence of growth acceleration in weight or length (normal: ΔSDS ⩽ 0.67 v. growth acceleration: ΔSDS > 0.67). The relation between hypertension during pregnancy and weight and length gain was addressed by logistic regression analyses. We found that pre-existent hypertension was related to growth acceleration in weight and length. After correction for birth weight and pregnancy duration, the effect remained significant for growth acceleration in weight (OR 1.89; 95% CI 1.21-2.97; P < 0.01). Pregnancy-induced hypertension showed similar results, although correction for birth weight and pregnancy duration rendered the associations non-significant. In conclusion, infants of women with pre-existent hypertension during pregnancy more frequently have growth acceleration in weight and length, and yet the mechanisms acting on postnatal growth appear to be different.

OC21.07: *Additional value of advanced neurosonography and magnetic resonance imaging in fetuses at risk for brain damage

(>3) sonographic findings, respectively. PPV of major or multiple minor US abnormalities in case of symptomatic congenital infection were 80,0 % in fetuses or infants with congenital infection, and 61.5% when all exposed fetuses were considered, with a specificity of 95.7% and 98.1%, respectively. Conclusions: When fetal status is unknown, any US abnormality can only predict a symptomatic congenital infection in 41.3% of cases. The classification of US semiology as major and minor infectious criteria leads to increase US prediction performance of symptomatic congenital infection when major or multiple minor criteria are found.

Neonatale pneumatosis ventriculi

SamenvattingIn de neonatale periode wordt pneumatosis intestinalis (PI) met name gezien in de acute fase van necrotiserende enterocolitis (NEC) met het terminale ileum en het proximale colon als voorkeurslocaties. Pneumatosis geïsoleerd tot de maag is zeldzaam bij neonaten. Pneumatosis van de maag (pneumatosis ventriculi) wordt soms gezien secundair aan gastro-intestinale obstructies. Daarnaast kan het gezien worden bij een fulminant verlopende NEC. De hier beschreven casus betreft een preterme neonaat met een ongecompliceerde pneumatosis ventriculi zonder gastro-intestinale obstructie en zonder fulminante NEC. Geïsoleerde pneumatosis van de maag is vooralsnog een lastig symptoom, waarvan het beloop anders kan zijn dan tot nu toe in de literatuur is beschreven.SummaryPneumatosis intestinalis (PI) is commonly observed in neonates with necrotizing enterocolitis (NEC). In NEC the distal part of the small intestine and proximal part of the colon are most often affected. PI of the stomach (pneumatosis ventriculi) is a rare phenomenon and usually a sign of fulminant NEC. Pneumatosis ventriculi can also be observed secondarily to gastric outlet obstruction usually requiring surgical intervention. We describe a preterm infant with pneumatosis isolated to the stomach without gastro-intestinal obstruction or a fulminant NEC. The outcome was good and quite different than described in the literature.

Transiënte hyperammoniëmie van de neonaat

Abstract SummaryA preterm born male infant (34 4/7 weeks, 2290 grams) with respiratory distress syndrome (irds) presented with coma caused by hyperammonemia (2180 µmol/l) at 18 hours of age. He was treated with continuous veno-venous hemodiafiltration which corrected the hyperammonemia within 60 hours. After exclusion of inborn metabolic errors a diagnosis of transient hyperammonemia of the newborn (than) was made. than affects primarily preterm born infants. Soon after birth they develop irds followed by altered consciousness and coma. Prompt diagnosis and treatment of the hyperammonemia is important because prognosis depends both on the duration and the level of the hyperammonemia. Although the pathophysiologic mechanisms leading to than are not fully understood yet, the shunting of portal blood into the systemic circulation via the patent ductus venosus Arantii may play a role.SamenvattingEen preterm geboren mannelijke neonaat (34 4/7 weken, 2290 gram) met respiratoir distress syndroom (irds) presenteerde zich 18 uur postpartum met coma veroorzaakt door hyperammoniëmie (2180 µmol/l). Hij werd behandeld met continue veno-veneuze hemodialyse, wat binnen 60 uur een normalisering van de ammoniakconcentratie bewerkstelligde. Na uitsluiting van metabole ziekten werd de diagnose transiënte hyperammoniëmie van de neonaat (than) gesteld. than kan voorkomen bij preterm geboren neonaten. Na de geboorte ontwikkelen zij ademhalingsproblemen, gevolgd door verminderd bewustzijn en coma. Snelle diagnose en behandeling van de hyperammoniëmie is belangrijk omdat de prognose niet alleen afhangt van de mate, maar ook van de duur van de hyperammoniëmie. Het pathofysiologische mechanisme van than is niet volledig bekend. Wel zijn er aanwijzingen dat shunting van bloed door de ductus venosus Arantii naar de systeemcirculatie een rol zou kunnen spelen.