Mandy G. Keijzer-Veen

Microalbuminuria and Lower Glomerular Filtration Rate at Young Adult Age in Subjects Born Very Premature and after Intrauterine Growth Retardation

This prospective follow-up study of 422 19-yr-old subjects born very preterm in The Netherlands was performed to determine whether intrauterine growth retardation (IUGR) predisposes to abnormal GFR and microalbuminuria in adolescents. GFR (ml/min per 1.73 m2) was estimated using the Cockcroft-Gault equation, and albumin-creatinine ratio (mg/mmol) was calculated in a cohort of 19-yr-old subjects born very preterm (gestational age <32 wk) in 1983. Birth weights were adjusted for gestational age and expressed as standard deviation scores (sds) as a measure of IUGR. All subjects had normal renal function. Birth weight (sds) was associated negatively with serum creatinine concentration (micromol/L) (beta = -1.0 micromol/L, 95% confidence interval [CI]: -1.9 to -0.2), positively with GFR (beta = 3.0, 95% CI: 1.7 to 4.2), and negatively with the logarithm of albumin-creatinine ratio (beta = -0.05, 95% CI: -0.09 to -0.01) in young adults born very preterm. IUGR is associated with unfavorable renal functions at young adult age in subjects born very premature. These data suggest that intrauterine growth-retarded subjects born very premature have an increased risk to develop progressive renal failure in later life.

Is Blood Pressure Increased 19 Years After Intrauterine Growth Restriction and Preterm Birth? A Prospective Follow-up Study in the Netherlands

Objective. To determine whether intrauterine growth restriction (IUGR) is a predisposing factor for high blood pressure (BP) in 19-year-olds who were born (very) preterm. Methods. A prospective follow-up study was conducted at age 19 in individuals who born preterm in the Netherlands in 1983. Systolic, diastolic, and mean BP values and plasma renin activity concentration were obtained in 422 young adults who were born with a gestational age (GA) <32 weeks. BP values were also measured in 174 individuals who born with a GA of ≥32 weeks and a birth weight of <1500 g. Results. An increased prevalence of hypertension and probably also of prehypertensive stage was found. IUGR, birth weight, GA, and plasma renin activity were not associated with BP. Current weight and BMI were the best predicting factors for systolic BP at the age of 19 years. Conclusions. The prevalence of hypertension is high in individuals who were born preterm when compared with the general population. In the individuals who were born very preterm, no support to the hypothesis that low birth weight is associated with increased BP at young adult age can be given.

Lipid profile and carotid intima-media thickness in a prospective cohort of very preterm subjects at age 19 years: effects of early growth and current body composition

Cardiovascular disease (CVD) risk is associated with prenatal and infancy growth. However, the relative importance of these time periods for the CVD risk is uncertain. To elucidate this, we tested in a very preterm cohort the effects of birth weight for gestational age and weight gain between birth and 3 mo post-term (early postnatal weight gain) and between 3 mo and 1 y post-term (late infancy weight gain) on the lipid profile and carotid intima-media thickness (CIMT) at age 19 y. A less favorable lipid profile was strongly associated with higher current body mass index (BMI), greater waist circumference, and greater absolute fat mass. CIMT was positively associated with current height, and with low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) levels, and LDL/high-density lipoprotein (HDL) cholesterol and ApoB/apolipoprotein AI (ApoAI) ratios. Lipid profile and CIMT were unrelated to gestational age, birth weight standard deviation score (SDS) and early postnatal weight gain. CIMT was positively associated with late infancy weight gain, but the relationship disappeared after correction for current height. Our findings in 19 y olds born very preterm argue for an effect of current body composition, rather than of early growth, on the CVD risk. Attempts to reduce the CVD risk in this specific population should focus on weight reduction in young adulthood rather than on optimizing the early growth pattern.

Antenatal glucocorticoid treatment is not associated with long-term metabolic risks in individuals born before 32 weeks of gestation

Background: A single course of maternal glucocorticoid treatment is effective in reducing neonatal mortality after preterm birth. However, in animals, maternal glucocorticoid treatment is associated with lifelong hyperglycaemia and hypertension, and impaired nephrogenesis in offspring. Findings from studies in humans on this topic are highly contradictory due to a number of methodological flaws, and renal function after glucocorticoid exposure has never been assessed. Objectives: To assess in individuals born <32 gestational weeks whether antenatal glucocorticoid treatment for preterm birth is associated with long-term metabolical risks, including renal function, in adulthood. Design: Birth cohort study. Setting: Multicentre study. Patients: 412 19 year olds born <32 gestational weeks from the Project On Preterm and Small-for-gestational-age infants (POPS) cohort. Interventions: Maternal betamethasone 12 mg administered twice with a 24 h interval. Main outcome measures: Body composition, insulin resistance, the serum lipid profile, blood pressure and estimated renal function. Results: We did not find any long-term adverse effects of antenatal betamethasone, with the exception of an effect on glomerular filtration rate (GFR). In 19-year-old survivors, GFR was lower after betamethasone: −5.2 ml/min (95% CI −8.9 to −1.4) per 1.73 m2. Conclusions: The reduction in neonatal mortality associated with a single course of maternal betamethasone is not accompanied by long-term metabolical risks in survivors of preterm birth. The only adverse effect found was lower GFR. Although this difference was not clinically relevant at 19 years, it might predict an increased risk of chronic renal failure in prematurely born individuals who were exposed antenatally to betamethasone.

The Effect of Preterm Birth on Kidney Development and Kidney Function over Time

In the last decades the survival of (extremely) preterm born and small for gestational age individuals has improved significantly.(Faranoff 2003; EXPRESS 2009) Many articles have been published showing a relation between unfavourable perinatal factors (eg growth restriction, maternal factors, maternal and postnatal medication use such as antenatal steroids and nephrotoxic agents) and increased risk for diseases in later life, like cardiovascular disease, diabetes mellitus, unfavourable lipid profile (together: the metabolic syndrome) and renal impairment. Recently, an increasing amount of studies have been published concerning the effects of preterm birth and these adult diseases as well. This chapter discusses the normal kidney development and the effect of premature and small for gestational age birth on kidney development and kidney function over time.

Rituximab for patients with nephrotic syndrome

We read with interest the trial by Kazumoto Iijima and colleagues (Oct 4, p 1273); however, the results raised some questions. Is rituximab better than conventional treatment (calcineurin inhibitors or mycophenolate mofetil) because a third of patients received concomitant ciclosporin? After, all participants relapsed by 19 months, what can be expected in a few years? We did a propensity-matched analysis in an observational cohort of 339 children between 1993 and 2012. We assessed the efficacy of rituximab in 11 children who repeatedly relapsed on second-line drugs or had toxic eff ects from steroids (table). We compared the outcomes with 53 participants who are propensity-matched controls based on conditional probability with the last drug (cyclophosphamide, calcineurin inhibitors, and mycophenolic acid) as a comparator. Nine patients relapsed (median relapse-free period was 370 days), of which two had sustained remissions at days 355 and 688, and four reported severe side-effects. The duration between relapses improved from a median of 60 days (interquartile range [IQR] 35–101 days) to 334 days (IQR 206–463 days) with rituximab and from 78 days (IQR 64–103 days) to 321 days (IQR 81–868 days) with conventional therapy (p<0·01). Relapse rates improved from 4·7 per year to 0·9 per year with rituximab (p=0·005) and from 5·2 per year to 1·0 per year with conventional therapy (p<0·001), but no diff erences in relapse rates were noted between treatments. The relapse-free period was similar for both treatments at up to 3 years (relative hazard ratio 0·7; 95% CI 0·3–1·5). Rituximab might provide a time off of steroids or low cumulative steroid dose to minimise toxic eff ects; however, it does not significantly improve relapse-free periods during years of treatment and is associated with possible adverse risks. Trials comparing second-line drugs and different doses of rituximab with longer follow-ups and safety profi les are needed. A propensity-matched analysis provides data to design and power an appropriate trial for this drug.

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

SamenvattingInfants 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.SamenvattingVeel te vroeg geboren kinderen lopen een groter risico op neurosensorische handicaps en ontwikkelingsproblemen dan op tijd geboren kinderen. Vroeggeboorte, intra-uteriene groeiachterstand, en de combinatie hiervan, zijn ook mogelijke risicofactoren voor lichamelijke ziekten op de volwassen leeftijd. Omdat hier tot nu toe weinig onderzoek naar is verricht, zijn in de pops-cohort (Project On Preterm and Small for gestational age infants) de eerste tekenen hiervan bekeken. Vroeggeboorte lijkt een risicofactor te zijn voor het ontwikkelen van insulineresistentie. Bij een latere neiging tot vetzucht is dat risico extra groot. Nog groter wordt dat als hieraan een intra-uteriene groeiachterstand voorafging. De systolische bloeddruk is gemiddeld hoger bij ex-prematuren maar is niet gerelateerd aan de mate van intra-uteriene groeiretardatie. De nierfunctie (klaring en eiwituitscheiding) is op de jongvolwassen leeftijd minder gunstig voor die individuen die naast de vroeggeboorte ook zijn blootgesteld aan intra-uteriene groeiretardatie. Te vroeg geboren kinderen hebben als jongvolwassenen meer luchtwegklachten en een minder goede longfunctie. De conclusie is dat neonatale follow-up niet alleen noodzakelijk is voor veel te vroeg geboren kinderen maar ook voor kinderen met een ernstige intra-uteriene groeiachterstand. De kinderarts moet in het contact met zowel ouders en kind als met de huisarts benoemen dat een voorgeschiedenis van vroeggeboorte of groeiachterstand ook een mogelijke risicofactor is voor chronische ziekten op de volwassen leeftijd. Bij te vroeg geboren kinderen met intra-uteriene groeiachterstand is actieve preventie van obesitas vanaf jonge leeftijd geïndiceerd. Vanaf jongvolwassen leeftijd zal de huisarts extra alert moeten zijn op het ontstaan van met name hypertensie en microalbuminurie door dit bijvoorbeeld tweejaarlijks te controleren. Voor het kind zelf kan de voorgeschiedenis een extra reden zijn om overgewicht te vermijden, om aan sport te doen en om niet te beginnen met roken.

Influenza bij kinderen.

SummaryIn this article influenzavirus infection in children is reviewed. Young children often present a influenzavirus infection with atypical symptoms, which complicates recognizing the diagnosis. In risk groups, influenzavirus infection can have a serious course. Young children play an important part in the spread of influenza among adults and other children. There also is an association between influenzavirus infections and other diseases in childhood, like otitis media acuta, and febrile convulsions.Recently, many articles concerning the high morbidity and mortality in young infants are published. Development of influenza medication and vaccines opens possibilities to reduce the morbidity and mortality in young infants. Introduction of new intranasal influenzavirus vaccines will make vaccinating children at a larger scale, as in National Health Programmes, a realistic and feasible option.SamenvattingIn dit artikel wordt een overzicht gegeven van influenza bij kinderen. Jonge kinderen met een influenzavirusinfectie presenteren zich vaak met een atypisch beloop, waardoor het stellen van de diagnose moeilijk kan zijn. Influenzavirusinfectie kan een ernstig beloop hebben, vooral in risicogroepen. Kinderen spelen ook een belangrijke rol in de verspreiding van influenza onder de bevolking. Tevens bestaat een relatie tussen influenzavirusinfecties en andere ziekten bij kinderen, zoals acute otitis media en koortsconvulsies.Recent is de aandacht gevestigd op de hoge morbiditeit en mortaliteit bij jonge zuigelingen. De ontwikkeling van influenzavaccins en medicatie maakt het mogelijk ook bij hen de morbiditeit en mortaliteit te verlagen. Door introductie van intranasale vaccins zal de drempel tot vaccineren dalen en zal opname van een influenzavirusvaccin in nationale en wereldwijde vaccinatieprogrammas, zoals het Rijksvaccinatieprogramma, denkbaar worden.