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Objective: To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small‐for‐gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. Design: Multicentre cohort study with nested randomised controlled trial (RCT). Setting: Nineteen secondary and tertiary care centres. Population: Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. Methods: Women were classified: (1) RCT‐eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below 35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT‐eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. Main outcome measures: A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. Results: The cohort consisted of 690 women. The study was halted prematurely for low RCT‐inclusion rates (n = 40). In the RCT‐eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59–0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near‐significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre‐eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67–0.76). Conclusions: Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34–36 weeks should only be performed in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). Methods: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks' postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. Results: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57–0.95; aOR 0.70, 95% CI 0.54–0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09–9.61; aOR 5.44, 95% CI 1.62–18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11–5.57). Conclusion: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI. [ABSTRACT FROM AUTHOR]

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]

Over 90% of preterm neonates are, often empirically, exposed to antibiotics as a potentially life-saving measure against sepsis. Long-term outcome in association with antibiotic exposure (NABE) has insufficiently been studied after preterm birth. We investigated the association of NABE-duration with early-childhood developmental and health outcomes in preterm-born children and additionally assessed the impact of GA on outcomes. Preterm children (GA < 30 weeks) participating in a multicenter cohort study were approached for follow-up. General expert-reviewed health questionnaires on respiratory, atopic and gastrointestinal symptoms were sent to parents of children > 24 months' corrected age (CA). Growth and developmental assessments (Bayley Scales of Infant and Toddler Development (BSID) III) were part of standard care assessment at 24 months' CA. Uni- and multivariate regressions were performed with NABE (per 5 days) and GA (per week) as independent variables. Odds ratios (OR) for health outcomes were adjusted (aOR) for confounders, where appropriate. Of 1079 infants whose parents were approached, 347 (32%) responded at a mean age of 4.6 years (SD 0.9). In children with NABE (97%), NABE duration decreased by 1.6 days (p < 0.001) per week of gestation. Below-average gross-motor development (BSID-III gross-motor score < 8) was associated with duration of NABE (aOR = 1.28; p = 0.04). The aOR for constipation was 0.81 (p = 0.04) per gestational week. Growth was inversely correlated with GA. Respiratory and atopic symptoms were not associated with NABE, nor GA. We observed that prolonged NABE after preterm birth was associated with below-average gross-motor development at 24 months' CA, while a low GA was associated with lower weight and stature Z-scores and higher odds for constipation. [ABSTRACT FROM AUTHOR]

Objective: In 2010, the Dutch practice regarding initiation of active treatment in extremely preterm infants was lowered from 25 completed weeks' to 24 completed weeks' gestation. The nationwide Extremely Preterm Infants - Dutch Analysis on Follow-up Study was set up to provide up-to-date data on neurodevelopmental outcome at 2 years' corrected age (CA) after this guideline change. Design: National cohort study.Patients: All live born infants between 240/7 weeks' and 266/7 weeks' gestational age who were 2 years' CA in 2018-2020.Main Outcome Measure: Impairment at 2 years' CA, based on cognitive score (Bayley-III-NL), neurological examination and neurosensory function.Results: 651 of 991 live born infants (66%) survived to 2 years' CA, with data available for 554 (85%). Overall, 62% had no impairment, 29% mild impairment and 9% moderate-to-severe impairment (further defined as neurodevelopmental impairment, NDI). The percentage of survivors with NDI was comparable for infants born at 24 weeks', 25 weeks' and 26 weeks' gestation. After multivariable analysis, severe brain injury and low maternal education were associated with higher odds on NDI. NDI-free survival was 48%, 67% and 75% in neonatal intensive care unit (NICU)-admitted infants at 24, 25 and 26 weeks' gestation, respectively.Conclusions: Lowering the threshold has not been accompanied by a large increase in moderate-to-severely impaired infants. Among live-born and NICU-admitted infants, an increase in NDI-free survival was observed from 24 weeks' to 26 weeks' gestation. This description of a national cohort with high follow-up rates gives an accurate description of the range of outcomes that may occur after extremely preterm birth. [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]

Aim: This study determined possible discrepancies between verbal IQ and performance IQ in 8-year-old very preterm (VPT) and extremely preterm (EPT) children, and examined associations between verbal IQ and performance IQ, and sociodemographic factors, perinatal factors, early cognitive outcomes and also with school achievement scores.Methods: This prospective cohort study included 120 eight-year-old VPT/EPT children. Cognitive development was assessed at the ages of 2, 5 and 8 years. Eight years' school achievement results in arithmetic, reading and spelling were collected. Multiple regression analyses were performed to determine predictors of verbal IQ and performance IQ at the age of 8 years and to determine associations with school achievement scores.Results: Mean performance IQ (89.8) was significantly lower than mean verbal IQ (99.4; Cohen's d = 0.59) at the age of 8 years. Gestational age (GA), small for GA status, and cognitive scores at the ages of 2 and 5 years significantly predicted verbal IQ and performance IQ at the age of 8 years. Performance IQ at age 8 years was an important predictor for arithmetic scores (β = 0.42).Conclusion: Performance IQ was more strongly affected than verbal IQ in 8-year-old VPT/EPT children and was strongly related to mathematical difficulties. [ABSTRACT FROM AUTHOR]

Introduction: Severe early-onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long-term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live-born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity.Material and Methods: A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument.Results: Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well-designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live-born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live-born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy.Conclusions: When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups. [ABSTRACT FROM AUTHOR]

Copyright of Infant Mental Health Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The ProTWIN trial previously showed no beneficial effect of treatment with a cervical pessary vs usual care to prevent preterm birth in women with a multiple pregnancy. However, in women with a midtrimester short cervix (<38 mm), pessary did reduce the composite outcome of neonatal morbidity and mortality. This follow-up study evaluates the long-term outcomes of all children born to mothers who participated in the ProTWIN trial at 4 years of age.Material and Methods: Parents received the Ages and Stages Questionnaire, Strength and Difficulties Questionnaire and a health questionnaire. All questionnaires were reported separately and as a combined outcome (abnormal child outcome). A linear mixed effects model was used to adjust for correlated data in twins and correction for confounders was performed. In exploratory analysis, a composite outcome of death or survival with abnormal child outcome was used by combining extrapolated data on child outcome with survival data. All data were analyzed for the total group and the subgroup of women with midtrimester short cervix.Results: Of the original 813 women of the ProTWIN trial, we approached 579, of whom 258 participated (45%) in follow-up. We received questionnaires of 514 children (281 pessary vs 233 control), with 119 children in the subgroup of women with midtrimester short cervix. An abnormal child outcome was found in 23% in the pessary group vs 16% in the control group (odds ratio 1.58; 95% confidence interval 0.94-2.65). In exploratory analysis with extrapolated data on child outcome (n = 815), no difference in abnormal child outcome was seen between the pessary and control group. In the subgroup of women with a short cervix (n = 268), this composite outcome indicated a favorable outcome for children born to mothers with pessary.Conclusions: In women with a multiple pregnancy, the use of a cervical pessary did not improve development, behavior or physical outcomes of the surviving children at age 4. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Background: Compared to their term-born peers, children born very preterm are at risk for poorer cognitive, academic and behavioral outcomes, however this finding may have been confounded by lower parental education level in the very preterm children. Studies that compare very preterm and term-born children with comparable (high) parental education level are needed to assess the true effect of very preterm birth on outcomes.Aims: To compare cognitive, academic and behavioral functioning in very preterm and term-born children of highly educated parents. To examine whether outcomes differ for children of whom one or both parents are highly educated.Study Design: Cross-sectional study with a term-born comparison group.Subjects: 113 very preterm children and 38 term-born children aged 8-12 years old, with highly educated parents.Measures: Cognitive functioning (Intelligence Quotient), academic functioning (arithmetic facts and reading) and parent and teacher rated behavioral functioning (attention, executive function, hyperactivity, and emotional, conduct and peer problems). Parental education was considered high when children had two highly educated parents or one highly- and one middle educated parent.Results: Very preterm children had significantly poorer cognitive (difference of 10 IQ points) and behavioral functioning than their term-born peers, but did not differ on academic functioning. Children with one highly educated parent performed poorer than children with two highly educated parents on most outcome measures.Conclusions: Performance of very preterm children should be compared to term-born peers with parents having comparable educational levels for accurate assessment of outcomes. The number of highly educated parents also impacts outcomes. [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]

Background: Already in preschool, very preterm (VP) children perform worse than term born-children on preschool mathematical skills tests. Strong associations have been found between preschool mathematical skills, cognition and visual-motor integration.Aims: To compare VP children and their term-born peers on preschool mathematical achievement at the corrected age of five years, and determine whether cognitive, visual-perceptive, visual-motor, and motor-coordination skills, account for any significant differences observed.Study Design: Single-center, consecutive cohort study with a term-born comparison group.Subjects: 54 five-year-old VP children and 28 term-born comparison children.Outcome Measures: Standardized test for preschool mathematical skills (Dutch pupil monitoring system), cognitive skills (Wechsler Preschool and Primary Scale for Intelligence - third edition), visual-perception, visual-motor integration, and motor-coordination (Beery Visual-Motor Integration test - sixth edition). Group differences were analyzed with ANCOVAs, adjusting for maternal education, preschool grade, and time of assessment. Sobel's mediation analyses tested for possible mediation effects.Results: Preschool mathematical skills and visual perceptive skills were significantly lower in VP children than in term-born children (Cohen's d = 0.63, p = 0.01; Cohen's d = 0.84, p < 0.01, respectively). Sobel's test indicated a significant mediating effect of visual perceptive skills on the association between VP birth and preschool mathematical skills.Conclusions: At preschool age, VP children have poorer preschool mathematical skills compared to term-born peers; deficits that were fully accounted for by poor visual perceptive skills. Our findings indicate the relevance of screening visual perceptive skills at preschool age, enabling timely identification of children at risk for mathematical difficulties. [ABSTRACT FROM AUTHOR]