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To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses. Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV. We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p 0.001). Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.ZIEL: Untersuchung des Effekts der antenatalen Gabe von Betamethason auf den fetalen Doppler und die Kurzzeitvariation der fetalen Herzfrequenz (CTG-STV) bei Föten mit früher Wachstumsrestriktion (FGR). Post-hoc-Analyse von Daten der TRUFFLE-Studie, einer prospektiven, multizentrischen, randomisierten Managementstudie bei schwerer, früh einsetzender FGR. Wiederholte Doppler- und CTG-STV-Messungen zwischen der letzten Aufnahme innerhalb von 48 Stunden vor der ersten Betamethason-Dosis (Ausgangswert) und über 10 Tage wurden bewertet. Eine mehrstufige Analyse erfolgte, um den longitudinalen Verlauf der umbilikal-zerebralen Ratio (UC-Ratio), des Pulsatilitätsindex des Ductus venosus (DVPIV) und der CTG-STV zu analysieren. Wir haben 115 Föten eingeschlossen. Ein signifikanter Anstieg der CTG-STV gegenüber dem Ausgangswert wurde am Tag + 1 (p = 0,019) ermittelt, danach gab es keinen Unterschied. Der DVPIV unterschied sich an keinem der 10 Tage nach erster Betamethason-Dosis signifikant vom Ausgangswert (p = 0,167). Eine mehrstufige Analyse ergab, dass die verstrichene Zeit nach der antenatalen Betamethason-Gabe über 10 Tage hinweg signifikant mit der Abnahme der CTG-STV (p = 0,045) und der Zunahme des DVPIV (p = 0,001) und der UC-Ratio (p 0,001) assoziiert war. Obwohl die Steroidverabreichung bei früher FGR eine kleine Auswirkung auf den Anstieg der CTG-STV 1 Tag darauf hatte, waren die Effekte auf die Doppler-Parameter äußerst gering mit Regressionskoeffizienten von geringer Höhe, die nicht auf klinische Signifikanz schließen lassen. Sie stehen höchstwahrscheinlich in Zusammenhang mit der Verschlechterung bei FGR im Laufe der Zeit. Daher bleibt die Beurteilung der arteriellen und venösen Doppler bezüglich des Gesundheitszustandes des Fötus aussagekräftig, nachdem diesem zur Beschleunigung der fetalen Lungenreifung antenatal Steroide verabreicht wurden.

Item does not contain fulltext OBJECTIVE: Since 2010 the guideline 'Guideline for perinatal policy in cases of extreme prematurity' has advised an active policy in infants born at 24 weeks gestation. We investigated how infants born at 24 and 25 weeks gestation in the first year following the implementation of the guideline had developed by the age of 2 years. DESIGN: Retrospective national cohort study. METHOD: The study population consisted of all surviving infants born in the Netherlands at 24 or 25 weeks gestation in the period from 1 October 2010 to 1 October 2011. At a corrected age of 2 years the children underwent a general physical and neurological examination, and their cognitive scores were determined on the 'Bayley scales of infant and toddler development' (Bayley III). Examinations took place in the 10 neonatal intensive care units (NICU's) in the Netherlands. RESULTS: Of 185 extremely premature infants, 166 were admitted to a NICU. A total of 95 survived to a corrected age of 2 years; 78 (82%) children were examined. Their average cognitive score on the Bayley III scale was 88 (SD: 16). Among the children born at 24 weeks gestation, 20% had mild disabilities and 20% had moderate to severe disabilities. Among the children born at 25 weeks gestation, 17% had mild disabilities and 12% had moderate to severe disabilities. CONCLUSION: Of the children born at 24 weeks gestation in the first year after the introduction of active policy in the Netherlands and surviving to 2 years of age (46%), more than half had developed without disabilities. This was comparable to children born at 25 weeks gestation. Of all children born at 24 weeks gestation, 25% survived to 2 years of age without disabilities.

In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR) short-term variation (STV) on cardiotocography (CTG); (2) early changes in fetal ductus venosus (DV) waveform (DV-p95); and (3) late changes in fetal DV waveform (DV-no-A). However, many infants per monitoring protocol were delivered because of safety-net criteria, for maternal or other fetal indications, or after 32 weeks of gestation when the protocol was no longer applied. The objective of the present posthoc subanalysis was to investigate the indications for delivery in relation to 2-year outcome in infants delivered before 32 weeks to further refine management proposals.We included all 310 cases of the TRUFFLE study with known outcome at 2 years' corrected age and seven fetal deaths, excluding seven cases with inevitable perinatal death. Data were analyzed according to the allocated fetal monitoring strategy in combination with the indication for delivery.Overall, only 32% of liveborn infants were delivered according to the specified monitoring parameter for indication for delivery; 38% were delivered because of safety-net criteria, 15% for other fetal reasons and 15% for maternal reasons. In the CTG-STV group, 51% of infants were delivered because of reduced STV. In the DV-p95 group, 34% of infants were delivered because of abnormal DV and, in the DV-no-A group, only 10% of infants were delivered accordingly. The majority of infants in the DV groups were delivered for the safety-net criterion of spontaneous decelerations in FHR. Two-year intact survival was highest in the DV groups combined compared with the CTG-STV group (P = 0.05 for live births only, P = 0.21 including fetal death), with no difference between DV groups. A poorer outcome in the CTG-STV group was restricted to infants delivered because of FHR decelerations in the safety-net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significantly higher intact survival.In this subanalysis of infants delivered before 32 weeks, the majority were delivered for reasons other than the allocated monitoring strategy indication. Since, in the DV group, CTG-STV criteria were used as a safety net but in the CTG-STV group, no DV safety-net criteria were applied, we speculate that the slightly poorer outcome in the CTG-STV group might be explained by the absence of DV data. The optimal timing of delivery of fetuses with early intrauterine growth restriction may therefore be best determined by monitoring them longitudinally, with both DV and CTG monitoring. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

OBJECTIVE: Since 2010 the guideline 'Guideline for perinatal policy in cases of extreme prematurity' has advised an active policy in infants born at 24 weeks gestation. We investigated how infants born at 24 and 25 weeks gestation in the first year following the implementation of the guideline had developed by the age of 2 years. DESIGN: Retrospective national cohort study. METHOD: The study population consisted of all surviving infants born in the Netherlands at 24 or 25 weeks gestation in the period from 1 October 2010 to 1 October 2011. At a corrected age of 2 years the children underwent a general physical and neurological examination, and their cognitive scores were determined on the 'Bayley scales of infant and toddler development' (Bayley III). Examinations took place in the 10 neonatal intensive care units (NICU's) in the Netherlands. RESULTS: Of 185 extremely premature infants, 166 were admitted to a NICU. A total of 95 survived to a corrected age of 2 years; 78 (82%) children were examined. Their average cognitive score on the Bayley III scale was 88 (SD: 16). Among the children born at 24 weeks gestation, 20% had mild disabilities and 20% had moderate to severe disabilities. Among the children born at 25 weeks gestation, 17% had mild disabilities and 12% had moderate to severe disabilities. CONCLUSION: Of the children born at 24 weeks gestation in the first year after the introduction of active policy in the Netherlands and surviving to 2 years of age (46%), more than half had developed without disabilities. This was comparable to children born at 25 weeks gestation. Of all children born at 24 weeks gestation, 25% survived to 2 years of age without disabilities.

Item does not contain fulltext AIM: To evaluate 10-year quality assurance of newborn hearing screening (NHS) in Dutch neonatal intensive care units (NICU). METHODS: Results of the two-stage automated auditory brainstem response (AABR) screening and diagnostic examination in NICU graduates were centrally registered between October 1998 and December 2008. This registration facilitates screening, tracking and follow-up after abnormal screening results. Outcome measures are referral rates, prevalence rate of hearing loss and (trends of) coverage rates and timeliness of follow-up. RESULTS: Thirty-two thousand one hundred and two infants have been screened. Referral rates were 9.2% at the first and 26.3% at the second stage. Hearing loss was diagnosed in 728 infants (2.2%). Coverage rates were 98.7% at the first, 92.1% at the second stage, 92.3% for the diagnostic examination and 97.9% for the complete programme. After correction for gestational age, 95.8% of the infants had their first AABR

Context: Transient hypothyroxinaemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. Objective: To examine whether there is an effect of THoP on intelligence quotient (IQ) score and motor functioning at young adult age. Design: This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth (POPS) cohort, which included infants born very preterm (i.e.

Contains fulltext : 108726.pdf (Publisher’s version ) (Open Access) BACKGROUND: Extremely preterm infants are at high risk of neonatal mortality and adverse outcome. Survival rates are slowly improving, but increased survival may come at the expense of more handicaps. METHODOLOGY/PRINCIPAL FINDINGS: Prospective population-based cohort study of all infants born at 23 to 27 weeks of gestation in the Netherlands in 2007. 276 of 345 (80%) infants were born alive. Early neonatal death occurred in 96 (34.8%) live born infants, including 61 cases of delivery room death. 29 (10.5%) infants died during the late neonatal period. Survival rates for live born infants at 23, 24, 25 and 26 weeks of gestation were 0%, 6.7%, 57.9% and 71% respectively. 43.1% of 144 surviving infants developed severe neonatal morbidity (retinopathy of prematurity grade >/=3, bronchopulmonary dysplasia and/or severe brain injury). At two years of age 70.6% of the children had no disability, 17.6% was mild disabled and 11.8% had a moderate-to-severe disability. Severe brain injury (p = 0.028), retinopathy of prematurity grade >/=3 (p = 0.024), low gestational age (p = 0.019) and non-Dutch nationality of the mother (p = 0.004) increased the risk of disability. CONCLUSIONS/SIGNIFICANCE: 52% of extremely preterm infants born in the Netherlands in 2007 survived. Surviving infants had less severe neonatal morbidity compared to previous studies. At two years of age less than 30% of the infants were disabled. Disability was associated with gestational age and neonatal morbidity.

Aim: To determine the prevalence and independent relationship between hearing loss and risk factors in a representative neonatal intensive care unit (NICU) population. Methods: Automated auditory brainstem response (AABR) hearing screening has been introduced since 1998 in the Dutch NICUs. After a second AABR failure, diagnostic ABR was used to establish diagnosis of hearing loss. Newborns who died before the age of 3 months were excluded. In the present study only the NICU infants who were born with a gestational age

Veel 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.

PCBs are known for their neurotoxic properties, especially on the developing brain. To increase insight into the neurotoxic effects of PCB exposure, the authors studied the effects of perinatal exposure to environmental levels of these compounds on different neuropsychological domains. In 9-year-old children of the Rotterdam PCB-dioxin cohort, higher prenatal PCB levels were associated with longer response times (RTs), more variation in RTs, and lower scores on the Tower of London (TOL; Shallice, 1982). A longer breast-feeding duration was associated with lower TOL scores and with better spatial organizational skills. There was some evidence of negative effects of lactational exposure to PCBs on scores on the TOL.

Aim: As part of a future national neonatal hearing screening programme in the Netherlands, automated auditory brainstem response (AABR) hearing screening was implemented in seven neonatal intensive care units (NICUs). The objective was to evaluate key outcomes of this programme: participation rate, first stage success rate, pass/referral rates, rescreening compliance, diagnostic referral rates, age of first diagnostic evaluation and prevalence of congenital hearing loss (CHL). Methods: This prospective cohort study collected data on 2513 survivors. NICU graduates with one or more risk factors according to the Joint Committee on Infant Hearing were included in a two-stage AABR hearing screening programme. Conventional ABR was used to establish a diagnosis of CHL. Results: A total of 2513 newborns enrolled in the programme with a median gestational age of 31.6 (range 24-43) wk and a median birthweight of 1450 (range 510-4820) g. In 25 (1%) cases parents refused screening. Four out of 2513 newborns were initially lost; 2484 newborns have been tested initially. A final 98% participation rate (2465/2513) was obtained for the whole programme. After a median postmenstrual age at the first test of 33.7 (range 27-54) wk, a pass rate of 2284/2484 (92%) resulted at the first stage. The rescreening compliance after the first test was 92% (184/200). A referral rate for diagnostic ABR of 3.1% (77/2484) resulted. Of the 77 referrals 14 (18.2%) had normal screening thresholds, 15 (19.5%) had unilateral CHL and 48 (62.3%) had bilateral CHL. The prevalence of unilateral CHL was 0.6% (15/2484) and of bilateral CHL 1.9% (48/2484). Conclusion: A financially supported two-stage AABR hearing screening programme can be successfully incorporated in NICU centres and detects a high prevalence of CHL in NICU graduates. Neonatal hearing screening should be part of standard clinical practice in all NICU infants.

Objective: Our purpose was to evaluate whether effects of exposure to environmental levels of PCBs and dioxins on development in the Dutch cohort persist until school age. Study design: In the Dutch PCB/dioxin study, cognitive and motor abilities were assessed with the McCarthy Scales of Children's Abilities in children at school age. During infancy, half of this population was fully breast-fed for at least ≥6 weeks and the other half formula fed. Prenatal exposure to PCBs was defined as the sum of PCB118, 138, 153, and 180 in maternal and cord plasma. In breast milk, additional measurements of 17 dioxins, 6 dioxin-like PCBs, and 20 nondioxin-like PCBs were done. Results: Negative effects of prenatal PCB and dioxin exposure on cognitive and motor abilities were seen when parental and home characteristics were less optimal. These effects were not measurable in children raised in more optimal environments. Concluslons: Neurotoxic effects of prenatal PCB and dioxin exposure may persist into school age, resulting in subtle cognitive and motor developmental delays. More optimal intellectual stimulation provided by a more advantageous parental and home environment may counteract these effects of prenatal exposure to PCBs and dioxins on cognitive and motor abilities. Chemicals/CAS: Dioxins; Environmental Pollutants; Polychlorinated Biphenyls

Department of Pediatrics, Division of Neonatology, Erasmus University and University Hospital/Sophia Children's Hospital, Rotterdam, The Netherlands. Food is the major source for polychlorinated biphenyl (PCB) and dioxin accumulation in the human body. Therefore, investigating food habits from early ages until reproductive age (25 years) is important in order to assess exposure risk for the next generation. The objective of this study was to assess the PCB/dioxin exposure and the relative contribution of different foods to total exposure during preschool age. Particularly, the importance of lactational PCB/dioxin exposure vs. dietary exposure until adulthood was investigated. A cohort of 207 children was studied from birth until preschool age. Based on 3 planar PCBs and 17 2,3,7,8-substituted dibenzo-para-dioxins (PCDDs) and dibenzofurans (PCDFs) measured in breast milk, a model was developed to calculate the cumulative toxic equivalent (TEQ) intake during breast-feeding (0-1 year). In 3. 5-year-old children, daily dietary intake of planar PCB-TEQ and dioxin-TEQ was measured with a validated food questionnaire. Cumulative TEQ intake from 1 to 5 years was estimated using the PCB- and dioxin-TEQ intake measured with the food questionnaire. Cumulative TEQ intake from 6 to 25 years was estimated using national food consumption and contamination data of PCB- and dioxin-TEQ intake. In toddlers, dairy products contributed 43% to PCB-TEQ and 50% to dioxin-TEQ intake. Meat and meat products contributed 14% and 19%, respectively, and processed foods 23% and 15%, respectively. Breast-feeding for 6 months contributed to the cumulative PCB/dioxin TEQ intake until 25 years of age, 12% in boys and 14% in girls. The daily TEQ intake per kilogram body weight is 50 times higher in breast-fed infants and three times higher in toddlers than in adults. Long-term dietary exposure to PCBs and dioxins in men and women is partly due to breast-feeding (12 and 14%, respectively). After weaning, dairy products, processed foods, and meat are major contributors of PCB and dioxin accumulation until reproductive age. Instead of discouraging breast-feeding, maternal transfer of PCBs and dioxins to the next generation must be avoided by enforcement of strict regulations for PCB and dioxin discharge and by reducing consumption of animal products and processed foods in all ages.

This study investigated the effect of early feeding mode on the neurological condition at 42 months. For this purpose, healthy pregnant women were recruited in Groningen and Rotterdam, The Netherlands. Children were healthy and born at term. At 42 months, the children were neurologically examined by means of the Touwen/Hempel technique. In addition to the clinical diagnosis, the neurological findings were interpreted in terms of optimality. Special attention was paid to the quality of movements in terms of fluency. In total, 200 (51%) exclusively breastfed (for greater than or equal to 6 weeks) and 194 (49%) formula-fed children were studied. Twelve (3%) 42-month-old children were considered to be neurologically mildly abnormal and 1 child was diagnosed as abnormal. No effect of the type of feeding was found on the clinical diagnosis or the neurological optimality. After adjustments for study centre and social, obstetric, perinatal and neonatal neurological differences, a beneficial effect of breastfeeding on the fluency of movements was found (odds ratio for non-optimal fluency 0.56; 95% confidence interval 0.37-0.85). The prolongation of full breastfeeding beyond 6 weeks did not influence the quality of movements. In conclusion, among Dutch preschool children, there was a small advantageous effect of full breastfeeding during the first 6 weeks of life on the fluency of movements.

Adverse neurological effects of exposure to PCBs have been found up to 18 months of age. Now we report on the effect of pre-and postnatal exposure to PCBs and dioxins on the neurological condition at 42 months of age. For this purpose, PCB levels were determined in cord and maternal plasma, and used as a measure of prenatal exposure. Breast milk was analyzed for PCBs and dioxins. In addition, PCBs were determined in plasma sampled from the child at 42 months of age. We evaluated the neurological condition of 394 children using the Touwen/Hempel method. After adjustment for covariates, neither prenatal PCB exposure nor postnatal exposure to PCBs and dioxins was found to be related to the neurological condition at 42 months of age. (C) 1998 Elsevier Science Ireland Ltd.