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Background: Gestational age is positively associated with cognitive development, but socio‐demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio‐economic status (SES) at increased risk of the negative effects of prematurity. Objectives: To investigate the association between gestational age in weeks, socio‐demographic characteristics, and school performance at the age of 12 years among children in regular primary education. Methods: Population‐based cohort study among liveborn singletons (N = 860,332) born in the Netherlands in 1999–2006 at 25–42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction. Results: School performance increased with gestational age up to 40 weeks. This pattern was evident across socio‐demographic strata. Children born at 25 weeks had −0.57 SD (95% confidence interval −0.79, −0.35) lower school performance z‐scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non‐European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25–29 years, with intermediate SES or first borns (evidence of interaction). Conclusions: Higher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut‐off of preterm birth and across socio‐demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow‐up. [ABSTRACT FROM AUTHOR]

Introduction: There is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management.Material and Methods: This Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27+5 and 33+5 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome. In participants allocated to receive immediate delivery, either induction of labor or cesarean section was initiated at least 48 hours after admission. Primary outcomes were adverse perinatal outcome, defined as a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, culture proven sepsis, intraventricular hemorrhage grade 3 or worse, periventricular leukomalacia grade 2 or worse, necrotizing enterocolitis stage 2 or worse, and perinatal death. Major maternal complications were secondary outcomes. It was estimated 1130 women needed to be enrolled. Analysis was by intention-to-treat.Results: The trial was halted after 35 months because of slow recruitment. Between February 2011 and December 2013, a total of 56 women were randomized to immediate delivery (n = 26) or temporizing management (n = 30). Median gestational age at randomization was 30 weeks. Median prolongation of pregnancy was 2 days (interquartile range 1-3 days) in the temporizing management group. Mean birthweight was 1435 g after immediate delivery vs 1294 g after temporizing management (P = .14). The adverse perinatal outcome rate was 55% in the immediate delivery group vs 52% in the temporizing management group (relative risk 1.06; 95% confidence interval 0.67-1.70). In both groups there was one neonatal death and no maternal deaths. In the temporizing treatment group, one woman experienced pulmonary edema and one placental abruption. Analyses of only the singleton pregnancies did not result in other outcomes.Conclusions: Early termination of the trial precluded any conclusions for the main outcomes. We observed that temporizing management resulted in a modest prolongation of pregnancy without changes in perinatal and maternal outcome. Conducting a randomized study for this important research question did not prove feasible. [ABSTRACT FROM AUTHOR]

Objective of the current study was to assess whether game-formatted executive function (EF) training, is effective in improving attention, EF and academic performance in very preterm and/or extremely low birthweight children aged 8–12 years. A multi-center, double-blind, placebo- and waitlist controlled randomized trial (NTR5365) in two academic hospitals in The Netherlands was performed. Eighty-five very preterm children with parent-rated attention problems on the Child Behavior Checklist were randomized to one of three treatment conditions: EF training, placebo training or waitlist condition. EF or placebo training was completed at home (6 weeks, 25 sessions of 30–45 min each). At baseline, 2 weeks after training or being on the waitlist, and five months after first follow-up visit, children underwent assessments of primary outcomes (parent and teacher ratings of attention) and secondary outcomes (parent and teacher ratings of daily-life EF, computerized EF tasks and academic performance). Linear mixed model analyses were performed for all outcome measures. There were no significant differences in improvement over time on parent- and teacher ratings of attention, parent- and teacher ratings of daily-life EF, computerized EF tasks, and academic performance (arithmetic and reading) between the EF training, placebo training and waitlist condition. In conclusion, game-formatted EF training does not improve attention, EF or academic performance in very preterm children with parent-rated attention problems. [ABSTRACT FROM AUTHOR]

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Objective: Very preterm children have poorer attentional, behavioral and emotional functioning than term-born children. Problems on these domains have been linked to poorer executive function (EF). This study examined effects of a game-formatted, comprehensive EF training on attentional, behavioral and emotional functioning and self-perceived competence in very preterm children. Study Design: Eighty-five children participated in a multi-center, double-blind, placebo and waitlist-controlled randomized trial. Children were recruited from neonatal follow-up units of two academic medical centers in The Netherlands. Eligible for inclusion were 8–12 year old children born very preterm (<30 weeks of gestation) and/or with extremely low birthweight (<1000 g) with parent reported attention problems. Children were randomly assigned to one of three treatment arms: EF training, placebo training or waitlist. The EF and placebo training involved a 6 weeks, 25 (30–45 min) sessions training program. Attentional functioning (Attention Network Test), behavioral and emotional functioning (parent and teacher Strengths and Difficulties questionnaire) and self-perceived competence (Self-Perception Profile for Children) were assessed at baseline, at the end of the training program and 5 months after the training was finished. Data analyses involved linear mixed model analyses. Results: Children in the EF training arm significantly improved on all training tasks over the course of the EF training program. Despite these improvements on the EF training tasks, there were no significant differences over time on any of the outcome measures between the three treatment arms, indicating that this computerized EF training program had no beneficial effects. Conclusion: Although there were significant improvements in the EF training tasks, there was no generalization of these improvements to any of the outcome measures. Thus, our findings do not support the use of computerized EF training programs. Future research should investigate effectivity of more ecologically valid, real-world like EF training programs. [ABSTRACT FROM AUTHOR]

Aim: We examined the association between early maternal psychological distress after severe hypertensive disorders of pregnancy (HDP) and behavioural issues in their 12‐year‐old offspring. Methods: This secondary analyses of a prospective mother–child birth cohort focused on 95 women with severe HDP and their singleton offspring. The mothers were recruited during pregnancy from 2000 to 2003 in Amsterdam, the Netherlands. Maternal distress at child term age and three months post‐term was measured using the Symptom Checklist‐90. The Child Behaviour Checklist for six years to 18 years was used to quantify social and attention problems in their offspring at 12 years of age. Perinatal and neonatal risk factors were also analysed. Results: The children were born at a mean age of just under 32 weeks and 90% weighed below the 10th percentile. High psychological distress (score ≥133) affected 45% of the mothers at term age and 44% three months post‐term. Child social problems were significantly associated with maternal distress at three months and were highest in cases of high maternal distress in combination with major neonatal morbidity. Child attention problems were associated with maternal anxiety at three months post‐term. Conclusion: Early maternal psychological distress after severe maternal HDP was associated with childhood behavioural issues at the age of 12. [ABSTRACT FROM AUTHOR]

Objective: Many studies that examine growth in growth-restricted children at birth do not discriminate between fetal growth restriction (FGR) and small for gestational age (SGA). These terms however are not synonymous. In SGA, stunting and increased weight gain have been reported. We do not know if this holds true for FGR. Our aim was to study postnatal growth until age 12.5 years in a cohort of children born FGR due to early onset placental insufficiency, and its relation to FGR severity.Design: Prospective cohort study, follow-up of an antenatal randomised controlled trial in two tertiary centres.Patients: Children aged 12.5 years born after FGR, with mothers who had severe early onset hypertensive pregnancy disorders (N=96).Main Outcome Measures: Anthropometry at age 12.5 years in SD scores (SDS).Results: Mean height SDS (SD) corrected for target height was -0.09 (0.94), mean body mass index (BMI) SDS was 0.00 (1.16) and mean head circumference SDS was -0.37 (1.11). Catch-up growth was at fastest rate between term age and 3 months and similar for height (0.55 SDS/months) and weight (0.49 SDS/months). Neither FGR severity nor gestational age was related to height and BMI at age 12.5 years.Conclusions: Children born growth restricted due to early onset placental insufficiency have height and BMI scores comparable to their age-matched peers at age 12.5 years. FGR severity was not related to height and BMI at age 12.5 years. These reassuring results differ from most studies that examine SGA children. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the predictive capacity of mid-trimester cervical length (CL) measurement for spontaneous and iatrogenic preterm birth.Material and Methods: We performed a prospective observational cohort study in nulliparous women and low-risk multiparous women with a singleton pregnancy between 16(+0) and 21(+6) weeks of gestation. We assessed the prognostic capacity of transvaginally measured mid-trimester CL for spontaneous and iatrogenic preterm birth (<37 weeks) using likelihood ratios (LR) and receiver-operating-characteristic analysis. We calculated numbers needed to screen to prevent one preterm birth assuming different treatment effects. Main outcome measures were preterm birth <32, <34 and <37 weeks.Results: We studied 11,943 women, of whom 666 (5.6%) delivered preterm: 464 (3.9%) spontaneous and 202 (1.7%) iatrogenic. Mean CL was 44.1 mm (SD 7.8 mm). In nulliparous women, the LRs for spontaneous preterm birth varied between 27 (95% CI 7.7-95) for a CL ≤ 20 mm, and 2.0 (95% CI 1.6-2.5) for a CL between 30 and 35 mm. For low-risk multiparous women, these LRs were 37 (95% CI 7.5-182) and 1.5 (95% CI 0.97-2.2), respectively. Using a cut-off for CL ≤ 30 mm, 28 (6.0%) of 464 women with spontaneous preterm birth were identified. The number needed to screen to prevent one case of preterm birth was 618 in nulliparous women and 1417 for low-risk multiparous women (40% treatment effect, cut-off 30 mm).Conclusion: In women at low risk of preterm birth, CL predicts spontaneous preterm birth. However, its isolated use as a screening tool has limited value due to low sensitivity. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in lowrisk pregnant women with a short cervical length (CL). Study Design Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat. Results Between 2009 and 2013, 20,234 women were screened. A CL of 30 mmor less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5). Conclusion In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB. [ABSTRACT FROM AUTHOR]

Preterm born children have more behaviour problems than term born children. Perinatal risks, current child functioning, sociodemographic characteristics, parental psychological distress and parental perceptions of child vulnerability (PCV) have been shown to be risk factors for behaviour problems. However, the role of maternal and paternal PCV is unclear, as these have not been investigated as a risk factor for behaviour problems, with all other risk factors taken into account. Aim of this study is to investigate whether maternal and paternal PCV are independent risk factors for behaviour problems in very preterm (VP) and term born children. The present study is a single centre prospective cohort study. Preterm children ( n = 104), born at <30 weeks' gestation and/or birth weight <1000 g, and term children ( n = 95) were assessed at age 5. Results showed that risk factors for parent-rated behaviour problems were low/middle parental education, VP birth, parental stress and, in VP children, maternal PCV. Risk factors for teacher-rated behaviour problems were low/middle parental education, foreign parental country of birth, intrauterine growth restriction and objective child vulnerabilities. It can be concluded that maternal PCV is a risk factor for parent-rated behaviour problems in VP children. When VP children are presented with behavioural problems, clinicians ought to be aware of the possibility that parents might still perceive their child as vulnerable. The neonatal history of the child, the way parents experienced that period, their perceptions of the child and possible consequences of these perceptions could be subjects for conversation during visits at follow-up clinics. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The achievement of age-specific developmental milestones in youth is of great importance to the adjustment in adult life. Young adults who were born preterm, might go through a different developmental trajectory and transition into adulthood than their peers. This study aimed to compare the psychosocial developmental trajectory of young adults who were born preterm with peers from the general population. 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. Analysis of variance by group, age and gender was performed to test differences on the CoLQ scale scores between the POPS-group and 211 peers (25–30 years) from the general population (Ref-group). Differences on item level, representing the achievement of individual milestones, were analyzed with logistic regression analyses by group, age and gender. Results: The POPS-group (n = 300, 32,3% biased response) scored significantly lower than the Ref-group on the scales Psychosexual Development (effect size − 0.26, p < 0.01), Antisocial Behavior (ES − 0.44, p < 0.001) and Substance Use & Gambling (ES − 0.35, p <.001). A further exploration on item-level revealed, among others, that the POPS-group had their first boyfriend/girlfriend at later age, were more often single, misbehaved less at school and smoked, drank and gambled less than the Ref-group. On the scales Autonomy Development and Social Development no differences were found between the POPS-group and the Ref-group. Conclusions: A relatively less vulnerable respondent group of young adults born preterm showed some psychosocial developmental trajectory delays and might benefit from support at teenage age. Because of the non-response bias, we hypothesize that the total group of young adults born preterm will show more severe psychosocial developmental problems. [ABSTRACT FROM AUTHOR]

Objective: Perinatal mortality after previable prelabor rupture of membranes (previable PROM) might be underestimated as most studies exclude patients with poor prognosis, or solely include patients in tertiary-care centers. We aimed to report perinatal, neonatal and long-term outcomes in a consecutive series of women with pregnancies complicated by previable PROM.Study Design: We conducted a prospective cohort study including women with singleton pregnancies and previable PROM ≤ 23+6 weeks gestational age (GA) from one tertiary hospital and eight affiliated secondary hospitals in the region of Amsterdam, the Netherlands (June 2012 until January 2016, PPROMEXIL-III cohort). Exclusion criteria were signs of active labor before onset of PROM or fetal structural anomalies visible at ultrasound. We assessed perinatal mortality. Furthermore, outcomes were maternal, perinatal, neonatal and long-term child characteristics.Results: We included 98 pregnancies with previable PROM. Twelve women (12.2%) opted for termination of pregnancy, resulting in 86 pregnancies included in further analyses. Median GA at PROM was 20+2 weeks (interquartile range (IQR) 17+6-22+0). Median GA at delivery was 22+6 weeks (IQR 20+1-26+4). Delivery within 1 week occurred in 38.4% of women and 60.4% delivered before 24 weeks GA (viability). Perinatal mortality occurred in 73.3% of pregnancies. 23/33 (69.7%) live-born neonates survived to discharge, representing 26.7% of total. None of the children died after discharge. Developmental data at two and/or five years of age was available for 13/23 children (i.e. all children born before 32 weeks of gestation), with 69.2% of children reporting a normal neurodevelopment. However, more than half of children reported respiratory problems.Conclusion: In women with previable PROM perinatal mortality was 73.3%, with a normal neurodevelopment in 69.2% of surviving children with follow-up data. Due to broad inclusion criteria, this cohort represents a population more generalizable to daily practice as compared to previous studies. [ABSTRACT FROM AUTHOR]

Background: Perinatally chikungunya infected neonates have been reported to have high rates of post-infection neurologic sequelae, mainly cognitive problems. In older children and adults chikungunya does not appear to have sequelae, but data on postnatally infected infants are lacking., Methods: We performed a prospective, non-controlled, observational study of infants infected before the age of 6 months with a severe chikungunya infection during the 2014-2015 epidemic in Curaçao, Dutch Antilles. Two years post-infection cognitive and motor - (BSID-III) and social emotional assessments (ITSEA) were performed., Results: Of twenty-two infected infants, two died and two were lost to follow up. Eighteen children were seen at follow-up and included in the current study. Of these, 13 (72%) had abnormal scores on the BSID-III (cognitive/motor) or ITSEA., Conclusion: In the first study aimed at postnatally infected infants, using an uncontrolled design, we observed a very high percentage of developmental problems. Further studies are needed to assess causality, however until these data are available preventive measure during outbreaks should also include young infants. Those that have been infected in early infancy should receive follow up.

Objective: To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes., Methods: We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a one-to-one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (β error 0.20, two-sided α error 0.05)., Results: Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.60-1.22, P=.39)., Conclusion: In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion., Clinical Trial Registration: NTR Dutch Trial Register, NTR3492.

Introduction: This study aimed to establish visual search performance and attention functioning in very preterm/very low birth weight (VP/VLBW) children using novel and well established measures, and to study their contribution to intellectual functioning., Methods: Visual search and attention network efficiency were assessed in 108 VP/VLBW children and 72 age matched term controls at 5.5 years corrected age. Visual search performance was investigated with a newly developed paradigm manipulating stimulus density and stimulus organization. Attention functioning was studied using the Attention Network Test (ANT). Intellectual functioning was measured by a short form of the Wechsler Preschool and Primary Scale of Intelligence. Data were analyzed using ANOVAs and multiple regression analyses., Results: Visual search was less efficient in VP/VLBW children as compared to term controls, as indicated by increased search time (0.31 SD, p = .04) and increased error rate (0.36 SD, p = .02). In addition, VP/VLBW children demonstrated poorer executive attention as indicated by lower accuracy for the executive attention measure of the ANT (0.61 SD, p < .001). No differences were found for the alerting (0.06 SD, p = .68) and orienting attention measures (0.13 SD, p = .42). Visual search time and error rate, and executive attention, collectively, accounted for 14% explained variance in full scale IQ (R(2) = .14, p < .001)., Discussion: VP/VLBW children were characterized by less efficient visual search ability and reduced executive attention. Visual attention dysfunctions contributed to intelligence, suggesting the opportunity to improve intellectual functioning by using interventions programs that may enhance attention capacities., (© 2013.)

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 <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997-2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley-test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis., 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.