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UNLABELLED Infants suffering from neonatal sepsis face an increased risk of early death and long-term neurodevelopmental delay. This paper analyses and summarises the existing data on short-term and long-term outcomes of neonatal sepsis, based on 12 studies published between January 2000 and 1 April 2012 and covering 3669 neonates with sepsis. CONCLUSION Infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications such as brain damage and, or, neurodevelopmental delay.

Background: In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of\ud preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis.\ud The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial\ud protocol.\ud \ud Methods/Design: The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction)\ud Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with\ud meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015. The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound\ud abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate\ud performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score\ud and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of\ud the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor,\ud absent/reversed umbilical arterial end diastolic flow at commencement of treatment, and other patient characteristics\ud available at baseline such as gestational age and estimated fetal weight. The secondary outcomes for mothers include\ud co-incidence and severity of the maternal syndrome of pre-eclampsia, mortality, and other serious adverse events.\ud \ud Discussion: Trials are expected to start in 2013–2014 and end in 2016–2017. Data analyses of individual trials are\ud expected to finish in 2019. Given the pre-planned and agreed IPD protocol, these results should be available in 2020

Aim: To examine visual sensory and perceptive functions, study their interrelations, and explore associations between visual dysfunctions and intelligence in very preterm/very-low-birthweight (VP/VLBW) children. Method: One-hundred and sixteen VP/VLBW children (57 males, 59 females; mean gestational age 30.1wks, SD 2.3; mean corrected age 5y 6mo, SD 1mo) and 73 term-born children (40 males, 33 females; mean gestational age 39.9wks, SD 1.3; mean age 5y 6mo, SD 3mo) completed visual sensory (acuity, visual field, contrast-, color-, and stereovision), perceptive (visual coherence, and Developmental Test of Visual Perception non-motor scale), and intelligence assessments. Results: Compared with term-born children, VP/VLBW children had reduced acuity (d=0.70, p

Aim To elucidate the relation between motor impairment and other developmental deficits in very preterm-born children without disabling cerebral palsy and term-born comparison children at 5 years of (corrected) age. Method In a prospective cohort study, 165 children (81 very preterm-born and 84 term-born) were assessed with the Movement Assessment Battery for Children - 2nd edition, Touwen's neurological examination, the Wechsler Preschool and Primary Scale of Intelligence, processing speed and visuomotor coordination tasks of the Amsterdam Neuropsychological Tasks, and the Strengths and Difficulties Questionnaire. Results Motor impairment (≤15th centile) occurred in 32% of the very preterm-born children compared with 11% of their term-born peers (p=0.001). Of the very preterm-born children with motor impairment, 58% had complex minor neurological dysfunctions, 54% had low IQ, 69% had slow processing speed, 58% had visuomotor coordination problems, and 27%, 50%, and 46% had conduct, emotional, and hyperactivity problems respectively. Neurological outcome (odds ratio [OR]=41.7, 95% confidence intervals [CI] 7.5–232.5) and Full-scale IQ (OR=7.3, 95% CI 1.9–27.3) were significantly and independently associated with motor impairment. Processing speed (OR=4.6, 95% CI 1.8–11.6) and attention (OR=3.2, 95% CI 1.3–7.9) were additional variables associated with impaired manual dexterity. These four developmental deficits mediated the relation between preterm birth and motor impairment. Interpretation Complex minor neurological dysfunctions, low IQ, slow processing speed, and hyperactivity/inattention should be taken into account when very preterm-born children are referred for motor impairment.

Onderzoeken van het effect van het Infant Behavioral Assessment and Intervention Program© (IBAIP) op de ontwikkeling van zeer vroeg geboren kinderen, het welbevinden van de ouder en de ouder-kindinteractie. In een multicenter gerandomiseerde gecontroleerde studie kregen 86 te vroeg geboren kinderen (zwangerschapsduur < 32 weken en/of een geboortegewicht < 1500 g) thuisbegeleiding tot de gecorrigeerde leeftijd van 6 maanden en 90 kinderen kregen standaardzorg. Op de gecorrigeerde leeftijd van 6, 12, 18 en 24 maanden en 3,7 en 5,5 jaar werden de ontwikkeling van het kind en/of het welbevinden van de ouder en de ouder-kindinteractie onderzocht. De interventiegroep had significant betere scores op cognitie op 6 maanden en 5,5 jaar, op motoriek op 6, 12 en 24 maanden, 3,7 en 5,5 jaar en op gedrag op 6 en 12 maanden. De moeders in de interventiegroep waren sensitiever op 6 maanden en hadden minder opvoedkundige stress op 24 maanden. Er was geen interventie-effect op het psychisch welbevinden van de moeder, maar het welbevinden verbeterde wel over de tijd. Het IBAIP leidt tot meer sensitieve moeder-kindinteracties en heeft een positief effect op de ontwikkeling van het kind. Verbetering van de motorische ontwikkeling hield aan en 5 jaar na de interventie was er opnieuw verbetering van de cognitieve ontwikkeling, vooral van de performale vaardigheden. De ervaringen uit deze studie hebben geleid tot implementatie van een preventief interventieprogramma voor vroeg geboren kinderen in Nederland, het ToP-programma (Transmurale Ontwikkelingsondersteuning voor Prematuur geboren kinderen en hun ouders).

Objectives: Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery. Methods: We report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26-32 weeks of gestation, with abdominal circumference < 10th percentile and umbilical artery Doppler pulsatility index > 95th percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis. Results: Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were significantly related to gestational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome. Conclusions: Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions.

Background Infants with very low birth weight (VLBW) are at increased risk for motor deficits, which may be reduced by early intervention programs. For detection of motor deficits and to monitor intervention, different assessment tools are available. It is important to choose tools that are sensitive to evaluate the efficacy of intervention on motor outcome. Objective The purpose of this study was to compare the Alberta Infant Motor Scale (AIMS) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development–Dutch Second Edition (BSID-II-NL) in their ability to evaluate effects of an early intervention, provided by pediatric physical therapists, on motor development in infants with VLBW at 12 months corrected age (CA). Design This was a secondary study in which data collected from a randomized controlled trial (RCT) were used. Methods At 12 months CA, 116 of 176 infants with VLBW participating in an RCT on the effect of the Infant Behavioral Assessment and Intervention Program were assessed with both the AIMS and the PDI. Intervention effects on the AIMS and PDI were compared. Results Corrected for baseline differences, significant intervention effects were found for AIMS and PDI scores. The highest effect size was for the AIMS subscale sit. A significant reduction of abnormal motor development in the intervention group was found only with the AIMS. Limitations No Dutch norms are available for the AIMS. Conclusions The responsiveness of the AIMS to detect intervention effects was better than that of the PDI. Therefore, caution is recommended in monitoring infants with VLBW only with the PDI, and the use of both the AIMS and the Bayley Scales of Infant Development is advised when evaluating intervention effects on motor development at 12 months CA.

Aim This study aimed to compare a broad array of neurocognitive functions (processing speed, aspects of attention, executive functioning, visual–motor coordination, and both face and emotion recognition) in very preterm and term-born children and to identify perinatal risk factors for neurocognitive dysfunctions. Method Children who were born very preterm (n=102; 46 males, 56 females), defined as a gestational age of less than 30 weeks and/or birthweight under 1000g, and a comparison group of term-born children (n=95; 40 males, 55 females) were assessed at age 5 with the Wechsler Preschool and Primary Scale of Intelligence, Stop Signal Task, several tasks of the Amsterdam Neuropsychological Tasks, and a Digit Span task. Results When sociodemographic characteristics were taken into account, very preterm children scored worse than term-born children on all neurocognitive functions, except on tasks measuring inhibition and sustained attention, for which results were inconclusive. Effect sizes for group effects were small to medium (r2 varying between 0.02 and 0.07). Principal component isolated four factors: visual–motor coordination, face/emotion recognition, reaction time/attention, and accuracy/attention. When sociodemographic and child characteristics at birth were accounted for, bronchopulmonary dysplasia was significantly negatively associated with all four components and also with working memory. Interpretation Very preterm children are at risk for problems on a broad array of neurocognitive functions. Bronchopulmonary dysplasia is an independent risk factor for impaired neurocognitive functioning.

OBJECTIVES: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis.METHODS: Historical cohort study in a population of infants born at RESULTS: Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4-4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5-15.9] and 3.2 [0.7-14.7], respectively.CONCLUSIONS: We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram-negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period.

To evaluate the effect of the Infant Behavioral Assessment and Intervention Program (IBAIP) in very low birth weight (VLBW) infants on cognitive, neuromotor, and behavioral development at 5.5 years corrected age (CA). In a randomized controlled trial, 86 VLBW infants received post discharge IBAIP intervention until 6 months CA, and 90 VLBW infants received standard care. At 5.5 years CA, cognitive and motor development, and visual-motor integration were assessed with the Wechsler Preschool and Primary Scale of Intelligence, third Dutch version, the Movement Assessment Battery for Children, second edition, and the Developmental Test of Visual Motor Integration. Neurologic conditions were assessed with the neurologic examination according to Touwen, and behavior with the Strengths and Difficulties Questionnaire. At 5.5 years CA, 69 children in the intervention and 67 children in the control group participated (response rate 77.3%). Verbal and performance IQ-scores

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

Background and aims The study aimed to assess the psychosocial developmental trajectory of young adults who were born preterm, by comparing their trajectory with that of peers who receive disability benefits and of peers from the general population. Methods Young adults from the POPS (Project On Preterm and Small for gestational age infants) cohort study, born in 1983 in the Netherlands, completed online the Course of Life Questionnaire (CoLQ - achievement of psychosocial developmental milestones) at 28 years of age (n = 300). Their scores were compared to the scores of 134 young adults who receive disability benefits (EMWAjong-group), and 211 age-matched peers from the general population (Ref-group), using analysis of variance and logistic regression analysis. Results The POPS-group scored significantly lower than the Ref-group on Psychosexual Development (effect size -0.26, p Conclusions Young adults born preterm showed some psychosocial developmental trajectory delays and might benefit from support at teenage age, especially those receiving disability benefits. Because of non-response bias in the POPS-group the results might be an underrepresentation of the psychosocial developmental problems of young adults born preterm.

Background Cross-sectional analyses at 6, 12, 24 months and 5.5 years, revealed positive intervention effects on child development in VLBW infants who were supported by the Infant Behavioural Assessment and Intervention Program© (IBAIP) as comparing to standard follow-up care. Longitudinal effects were not analysed yet. AIM To investigate the longitudinal effects of the IBAIP in VLBW infants on cognitive and motor development. Methods In a RCT, 86 VLBW infants received the IBAIP until 6 months CA, 90 VLBW infants received standard care. At 6, 12, and 24 months CA, cognitive and motor development were assessed with the Bayley Scales of Infant Development. At 5.5 years CA the Wechsler Preschool and Primary Scale of Intelligence and the Movement Assessment Battery for Children were used. Longitudinal data were analysed with linear mixed models in total group and three subgroups, using Z-scores generated from raw cognitive and motor scores. Results A significant intervention effect (0.4SD) on motor development was found (p = 0.006). On cognitive development, a non-significant intervention effect over time was found (p = 0.063). In children with bronchopulmonary dysplasia (BPD) significant intervention effects were found for both cognitive (effect=0.7SD; p = 0.019) and motor (effect=0.9SD; p = 0.026) outcome. Maternal education hardly influenced intervention effects over time, but in children with combined biological and social risks a longitudinal intervention effect of 0.8SD was found on cognitive development (p = 0.044). Conclusion The IBAIP leads to improved motor development in VLBW infants, and in infants with BPD also to improved cognitive development, over a five years period after the intervention.