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Background: Early childhood education offers opportunities for stimulation in multiple developmental domains and its positive impact on long-term outcomes and wellbeing for children is well documented. Few studies have explored early education in children born very preterm (VPT; <32 weeks of gestation) who are at higher risk of neurodevelopmental disorders and poor educational outcomes than their term-born peers. The purpose of the study is to describe and compare the educational environment of children born VPT in European countries at 5 years of age according to the degree of perinatal risk. Methods: Data originated from the population-based Screening to Improve Health In very Preterm infants (SHIPS) cohort of children born VPT in 2011/2012 in 19 regions from 11 European countries. Perinatal data were collected from medical records and the 5-year follow-up was conducted using parental questionnaires. Outcomes at 5 years were participation in early education (any, type, intensity of participation) and receipt of special educational support, which were harmonized across countries. Results: Out of 6,759 eligible children, 3,687 (54.6%) were followed up at 5 years (mean gestational age 29.3 weeks). At 5 years, almost all children (98.6%) were in an educational program, but type (preschool/primary), attendance (full-time/part-time) and use and type of school support/services differed by country. In some countries, children with high perinatal risk were more likely to be in full-time education than those with low risk (e.g. Estonia: 97.9% vs. 87.1%), while the inverse pattern was observed elsewhere (e.g. Poland: 78.5% vs. 92.8%). Overall, 22.8% of children received special educational support (country range: 12.4–34.4%) with more support received by children with higher perinatal risk. Large variations between countries remained after adjustment for socio-demographic characteristics. Conclusions: There are marked variations in approaches to early education for children born VPT in Europe, raising opportunities to explore its impact on their neurodevelopment and well-being. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up is a major challenge for very preterm (VPT) cohorts; attrition is associated with social disadvantage and parents with impaired children may participate less in research. We investigated the impact of loss to follow-up on the estimated prevalence of neurodevelopmental impairment in a VPT cohort using different methodological approaches.Methods: This study includes births < 32 weeks of gestational age (GA) from 4 regions in the UK and Portugal participating in a European birth cohort (N = 1737 survivors). Data on maternal characteristics, pregnancy complications, neonatal outcomes and neighborhood deprivation were collected at baseline. Neurodevelopment was assessed at 2 years of corrected age (CA) using standardized parent-report measures. We applied (1) multiple imputation (MI) and (2) inverse probability weighting (IPW) to estimate the impact of non-response on the prevalence of moderate to severe neurodevelopmental impairment and assessed violations of the missing at random (MAR) assumption using the delta method.Results: 54.2% of children were followed-up. Follow-up was less likely when mothers were younger, multiparous, foreign-born, did not breastfeed and came from deprived areas. The prevalence of neurodevelopmental impairment was 18.4% (95% confidence interval (CI):15.9-21.1) and increased to 20.4% (95%CI: 17.3-23.4) and 20.0% (95%CI:16.9-23.1) for MI and IPW models, respectively. Simulating strong violations of MAR (children with impairments being 50% less likely to be followed-up) raised estimates to 23.6 (95%CI:20.1-27.1) CONCLUSIONS: In a VPT cohort with high loss to follow-up, correcting for attrition yielded modest increased estimates of neurodevelopmental impairment at 2 years CA; estimates were relatively robust to violations of the MAR assumption. [ABSTRACT FROM AUTHOR]

Background: Ordinary meta-analyses indicate that magnesium sulphate (MgSO4 ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g. by trial sequential analysis (TSA), for which there are previously insufficient samples to draw a firm conclusion. Recently, a randomised controlled trial (RCT) provided additional data that potentially increased the sample size such that a new TSA might detect a statistically significant effect.Objectives: To assess the possible fetal neuroprotective effect of MgSO4 for women at imminent risk for preterm delivery in an updated systematic review with meta-analysis and TSA.Search Strategy: We searched MEDLINE, Embase, Cochrane and ClinicalTrials.gov on 8 October 2019. The search strategy clustered terms describing the MgSO4 intervention and preterm delivery.Selection Criteria: RCTs.Data Collection and Analysis: Two reviewers extracted the data. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models. A TSA was applied to the primary outcome, CP. The quality of the evidence was assessed using GRADE. The protocol was registered in PROSPERO (registration: CRD42019151441).Main Results: We identified six eligible trials (5917 women). MgSO4 intervention in women at imminent risk for preterm birth decreased the offspring's CP risk (meta-analysis RR 0.68, 95% CI 0.54-0.85; TSA RR 0.69, 95% CI 0.48-0.97).Conclusions: This systematic review with meta-analysis and TSA shows conclusively that MgSO4 , when given to women at imminent risk for preterm delivery, decreases the offspring's CP risk.Tweetable Abstract: Antenatal magnesium sulphate decreases the risk of cerebral palsy in children born preterm. [ABSTRACT FROM AUTHOR]

After preterm premature rupture of membranes (PPROM), antibiotics and antenatal steroids are effective evidence-based interventions, but the use of tocolysis is controversial. We investigated whether a unit policy of tocolysis use after PPROM is associated with prolonged gestation and improved outcomes for very preterm infants in units that systematically use these other evidence-based treatments. From the prospective, observational, population-based EPICE cohort study (all very preterm births in 19 regions from 11 European countries, 2011–2012), we included 607 women with a singleton pregnancy and PPROM at 24–29 weeks' gestation, of whom 101, 195 and 311 were respectively managed in 17, 32 and 45 units with no-use, restricted and liberal tocolysis policies for PPROM. The association between unit policies and outcomes (early-onset sepsis, survival at discharge, survival at discharge without severe morbidity and survival at two years without gross motor impairment) was investigated using three-level random-intercept logistic regression models, showing no differences in neonatal or two-year outcomes by unit policy. Moreover, there was no association between unit policies and prolongation of gestation in a multilevel survival analysis. Compared to a unit policy of no-use of tocolysis after PPROM, a liberal or restricted policy is not associated with improved obstetric, neonatal or two-year outcomes. [ABSTRACT FROM AUTHOR]

Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population‐based cohort of births below 32 weeks of gestation in 11 European countries in 2011–2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever‐breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25–34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high‐risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio‐economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge. [ABSTRACT FROM AUTHOR]

Background: Ordinary meta-analyses indicate that magnesium sulphate (MgSO 4 ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g. by trial sequential analysis (TSA), for which there are previously insufficient samples to draw a firm conclusion. Recently, a randomised controlled trial (RCT) provided additional data that potentially increased the sample size such that a new TSA might detect a statistically significant effect., Objectives: To assess the possible fetal neuroprotective effect of MgSO 4 for women at imminent risk for preterm delivery in an updated systematic review with meta-analysis and TSA., Search Strategy: We searched MEDLINE, Embase, Cochrane and ClinicalTrials.gov on 8 October 2019. The search strategy clustered terms describing the MgSO 4 intervention and preterm delivery., Selection Criteria: RCTs., Data Collection and Analysis: Two reviewers extracted the data. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models. A TSA was applied to the primary outcome, CP. The quality of the evidence was assessed using GRADE. The protocol was registered in PROSPERO (registration: CRD42019151441)., Main Results: We identified six eligible trials (5917 women). MgSO 4 intervention in women at imminent risk for preterm birth decreased the offspring's CP risk (meta-analysis RR 0.68, 95% CI 0.54-0.85; TSA RR 0.69, 95% CI 0.48-0.97)., Conclusions: This systematic review with meta-analysis and TSA shows conclusively that MgSO 4 , when given to women at imminent risk for preterm delivery, decreases the offspring's CP risk., Tweetable Abstract: Antenatal magnesium sulphate decreases the risk of cerebral palsy in children born preterm., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Objective: To study the effect of antenatal magnesium sulphate (MgSO 4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis., Design: Double-blind, randomised, placebo-controlled, multi-centre trial., Setting: Fourteen Danish obstetric departments., Population: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children., Methods: Women were randomised to receive either a loading dose of 5 g MgSO 4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire., Main Outcome Measure: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP., Results: The crude rates of moderate to severe CP in the MgSO 4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO 4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65)., Conclusions: Antenatal MgSO 4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis., Tweetable Abstract: Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Objective: The objective of this study was to examine the association between multivitamin use in the periconceptional period and the risk of preeclampsia., Study Design: The association was investigated in a prospective cohort study. 15,154 deliveries in women followed at a large university hospital in Denmark were included between 16 September 2012 and 31 October 2016. Pregnant women were sent a questionnaire containing items related to socio-demographic-, lifestyle- and health factors. The responses on multivitamin use were merged with the preeclampsia diagnosis from the Danish Medical Birth Registry. We used multiple logistic regression analyses to assess the association and to adjust for potential confounders., Main Outcome Measures: The outcome of interest, preeclampsia, included the preeclampsia subtypes eclampsia and HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome., Results: In total 12,954 women (85%) reported multivitamin use. A diagnosis of preeclampsia was found in 397 women (2.6%). We found a similar risk of preeclampsia in multivitamin user and non-users, adjusted odds ratio (AOR) for periconceptional multivitamin use = 0.97 (95% CI: 0.70 to 1.36) and AOR for early pregnancy multivitamin use = 0.97 (95% CI: 0.71 to 1.32). Subgroup analyses stratified on body mass index showed that among women with overweight, both periconceptional and early pregnancy multivitamin use were associated with a statistically significant lower risk of preeclampsia (AOR = 0.49, 95% CI: 0.24 to 0.99 and AOR = 0.35, 95% CI: 0.18 to 0.69, respectively)., Conclusion: Periconceptional- and early pregnancy multivitamin use was found to be associated with a similar risk of preeclampsia compared to non-users., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives:  To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity., Design:  Prospective multinational population based observational study., Setting:  19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project., Participants:  7336 infants born between 24+0 and 31+6 weeks' gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission., Main Outcome Measures:  Combined use of four evidence based practices for infants born before 28 weeks' gestation using an "all or none" approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital., Results:  Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants., Conclusions:  More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Rickets due to malnutrition is rare in Denmark. The Danish Board of Health recommend that: pregnant women are treated with a daily dose of vitamin D daily (10 micrograms); emigrants with coloured skin have their vitamin D level assessed during pregnancy; all children receive a daily dose of vitamin D (10 micrograms) until two years old. Despite of these recommendations two cases of severe nutritional rickets among children of emigrants were discovered upon hospital admission. The symptoms were heterogeneous: delayed walking skills and convulsions. We conclude that nutritional rickets is a tricky diagnosis, but is preventable.

Preterm birth increases the child's risk of cerebral palsy. Observational studies as well as randomized studies find that magnesium sulphate given to women in preterm birth decreases such risk. A Cochrane meta-analysis of the randomized studies shows no change in mortality, whereas some observational studies find a mortality decrease. It is important to identify the neuroprotective mechanism and to decide whether these results are relevant in the current Danish obstetrical practice. Should we use magnesium sulphate now or should questions about doses, time of administration and maternal side effects be answered first?