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Moderately preterm infants (32-36 weeks of gestational age) have an increased risk of worse health and developmental outcomes compared to infants born at term. Optimal nutrition may alter this risk. The aim of this study was to investigate the neurological, growth, and health outcomes up to six years of age in children born moderately preterm who receive either exclusive or fortified breast milk and/or formula in the neonatal unit. In this longitudinal cohort study, data were collected for 142 children. Data were collected up to six years of age via several questionnaires containing questions about demographics, growth, child health status, health care visits, and the Five to Fifteen Questionnaire. Data on the intake of breast milk, human milk fortification, formula, and growth during hospitalization were collected from the children's medical records. No statistically significant differences in neurological outcomes, growth, or health at six years of age were found between the two groups (exclusive breast milk, n = 43 vs. fortified breast milk and/or formula, n = 99). There is a need for research in larger populations to further assess potential effects on health and developmental outcomes when comparing the use of exclusive versus fortified breast milk for moderately preterm infants during neonatal hospitalization.

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(1) Background: Mothers of very preterm (VPT) infants may experience psychological symptoms compromising long-term emotional wellbeing. This study describes the emotional wellbeing of mothers of five-year-old children born VPT. We assess the association between sociodemographic, perinatal and neonatal characteristics, and the child's health and development at five years old and maternal emotional wellbeing. (2) Methods: Data are from the prospective European "Effective Perinatal Intensive Care in Europe" (EPICE) and subsequent "Screening for Health In very Preterm infantS in Europe" (SHIPS) projects including births <32 weeks' gestational age in 11 countries in 2011/12. Data were abstracted from obstetric and neonatal records. At five years old, 2605 mothers answered a parental questionnaire including the Mental Health Inventory-5 (MHI-5). Associations between sociodemographic and health characteristics and the mother's MHI-5 score were investigated using multilevel multivariate linear regression analysis with the country modelled as a random effect and inverse probability weighting to correct for attrition bias. (3) Results: The mean MHI-5 score was 71.3 (SD 16.7) out of 100 (highest emotional wellbeing) with a variation among countries from 63.5 (SD 16.8; Poland) to 82.3 (SD 15.8; the Netherlands). MHI-5 scores were significantly lower for mothers whose child had a severe health problem, developmental, or speech delay, for multiparous and single mothers, and when at least one of the parents was unemployed. (4) Conclusions: The emotional wellbeing of mothers of VPT infants differs between European countries. Identifying sociodemographic characteristics and child's health and developmental conditions that affect maternal emotional wellbeing may help to identify groups of mothers who need special assistance to cope with consequences of the delivery of a VPT child.

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In a cohort of children born very preterm (VPT), we investigated the association between breast milk feeding (BMF) initiation and its duration on cognitive development at 2 years of corrected age. Data were obtained from the Effective Perinatal Intensive Care in Europe population-based prospective cohort of children born <32 weeks of gestation, in 11 European countries, in 2011-2012. The study sample included 4323 children. Nonverbal cognitive ability was measured applying the Parental Report of Children's Abilities, except for France where the problem-solving domain of the Ages & Stages Questionnaire was used. Verbal cognition was based on the number of words the child could say. To determine the association between BMF (mother's own milk) and nonverbal and verbal cognition (outcome categorized as optimal and suboptimal), adjusted risk ratios (aRRs) were estimated fitting Poisson regression models, with inverse probability weights to account for nonresponse bias. Overall, 16% and 11% of the children presented suboptimal nonverbal and verbal cognition, respectively. Never BMF was associated with a significantly increased risk for suboptimal nonverbal (aRR = 1.29, 95% confidence interval [CI] = 1.09-1.53) and verbal (aRR = 1.45, 95% CI = 1.09-1.92) cognitive development compared with those ever breastfed, after adjustment for perinatal and sociodemographic characteristics. Compared with children breastfed 6 months or more, children with shorter BMF duration exhibited a statistically nonsignificant elevated aRR. VPT children fed with breast milk had both improved nonverbal and verbal cognitive development at 2 years in comparison with never breastfed, independently of perinatal and sociodemographic characteristics. This study encourages targeted interventions to promote BMF among these vulnerable children.

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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.

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OBJECTIVE: The documented benefits of maternal milk for very preterm infants have raised interest in hospital policies that promote breastfeeding. We investigated the hypothesis that more liberal parental policies are associated with increased breastfeeding at discharge from the neonatal unit. DESIGN: Prospective area-based cohort study. SETTING: Neonatal intensive care units (NICUs) in 19 regions of 11 European countries. PATIENTS: All very preterm infants discharged alive in participating regions in 2011-2012 after spending >70% of their hospital stay in the same NICU (n=4407). MAIN OUTCOME MEASURES: We assessed four feeding outcomes at hospital discharge: any and exclusive maternal milk feeding, independent of feeding method; any and exclusive direct breastfeeding, defined as sucking at the breast. We computed a neonatal unit Parental Presence Score (PPS) based on policies regarding parental visiting in the intensive care area (range 1-10, with higher values indicating more liberal policies), and we used multivariable multilevel modified Poisson regression analysis to assess the relation between unit PPS and outcomes. RESULTS: Policies regarding visiting hours, duration of visits and possibility for parents to stay during medical rounds and spend the night in unit differed within and across countries. After adjustment for potential confounders, infants cared for in units with liberal parental policies (PPS≥7) were about twofold significantly more likely to be discharged with exclusive maternal milk feeding and exclusive direct breastfeeding. CONCLUSION: Unit policies promoting parental presence and involvement in care may increase the likelihood of successful breastfeeding at discharge for very preterm infants.

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AIM: This study investigated the different strategies used in 11 European countries to prevent hypothermia, which continues to affect a large proportion of preterm births in the region. METHODS: We examined the association between the reported use of hypothermia prevention strategies in delivery rooms and body temperatures on admission to neonatal intensive care units (NICUs) in 5861 infants born at 22 + 0 to 31 +6 weeks of gestation. The use of plastic bags, wraps, caps, exothermic heat and mattresses was investigated. RESULTS: The proportion of infants born in units that systematically used one or more hypothermia prevention strategies was 88.2% and 50.9% of those infants were hypothermic on admission to NICUs. Of the 9.6% born in units without systematic hypothermia prevention, 73.2% were hypothermic. Only 2.2% of infants were born in units with no reported prevention strategies. Lower gestational age increased the probability of hypothermia. No significant differences were found between the various hypothermia prevention strategies. Hyperthermia was seen in 4.8% of all admitted infants. CONCLUSION: Very preterm infants had lower risks of hypothermia on NICU admission if the unit used systematic prevention strategies. All the strategies had similar effects, possibly due to implementation rather than a strategy's specific efficacy.

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Breast milk feeding (BMF) is associated with lower neonatal morbidity in the very preterm infant (<32 weeks gestation) and breastfeeding is beneficial for maternal health. Previous studies show large variations in BMF after very preterm birth and recognize the need for targeted breastfeeding support in the neonatal intensive care units (NICU). In a European collaboration project about evidence-based practices after very preterm birth, we examined the association between maternal, obstetric, and infant clinical factors; neonatal and maternal care unit policies; and BMF at discharge from the NICU. In multivariable analyses, covariates associated with feeding at discharge were first investigated as predictors of any BMF and in further analysis as predictors of exclusive or partial BMF. Overall, 58% (3,826/6,592) of the infants received any BMF at discharge, but there were large variations between regions (range 36-80%). Primiparity, administration of antenatal corticosteroids, first enteral feed <24 hr after birth, and mother's own milk at first enteral feed were predictors positively associated with any BMF at discharge. Vaginal delivery, singleton birth, and receiving mother's own milk at first enteral feed were associated with exclusive BMF at discharge. Units with a Baby Friendly Hospital accreditation improved any BMF at discharge; units with protocols for BMF and units using donor milk had higher rates of exclusive BMF at discharge. This study suggests that there is a high potential for improving BMF through policies and support in the NICU.

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Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective: To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.

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OBJECTIVE: To investigate the association between body temperature at admission to neonatal intensive care and in-hospital mortality in very preterm infants, stratified by postnatal age of death. Moreover, we assessed the association between admission temperature and neonatal morbidity. STUDY DESIGN: In this cohort study from 19 regions in 11 European countries, we measured body temperature at admission for infants admitted for neonatal care after very preterm birth (<32 weeks of gestation; n = 5697) who were followed to discharge or death. Associations between body temperature at admission and in-hospital mortality and neonatal morbidity were analyzed by the use of mixed effects generalized linear models. The final model adjusted for pregnancy complications, singleton or multiple pregnancy, antenatal corticosteroids, mode of delivery, gestational age, infant size and sex, and Apgar score <7 at 5 minutes. RESULTS: A total of 53.4% of the cohort had a body temperature at admission less than 36.5°C, and 12.9% below 35.5°C. In the adjusted model, an admission temperature <35.5°C was associated with increased mortality at postnatal ages 1-6 days, (risk ratio 2.41; 95% CI 1.45-4.00), and 7-28 days (risk ratio 1.79; 1.15-2.78) but not after 28 days of age. We found no associations between admission temperature and neonatal morbidity. CONCLUSION: Admission hypothermia after very preterm birth is a significant problem in Europe, associated with an increased risk of early and late neonatal death.

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BACKGROUND: Breast milk is associated with a lower risk of neonatal morbidity in very preterm infants. Despite the benefits, the duration of breastfeeding is shorter in very preterm infants than in term infants. OBJECTIVE: This study aimed to investigate how early provision of mother's own milk (MOM) and maternal and infant characteristics are related to breast milk feeding (BMF) between 36 and 40 weeks postmenstrual age (PMA) after very preterm birth. METHODS: A regional observational study of 138 singleton infants born at < 32 weeks of gestation in Stockholm, Sweden, was conducted. Data were derived from medical charts to investigate the association between early provision of MOM; maternal and infant characteristics; and exclusive, partial, or no BMF at 36 weeks PMA. Moreover, changes in BMF between 36 and 40 weeks PMA were studied. RESULTS: Most infants (80%) received MOM at 36 weeks PMA (55% exclusively, 25% partial). High provision of MOM at postnatal day 7 was associated with exclusive BMF at 36 weeks PMA, odds ratio (OR) 1.18 per 10 mL/kg MOM (95% confidence interval [CI], 1.06-1.32). Mothers born in non-Nordic countries provided MOM exclusively less often, adjusted OR 0.27 (95% CI, 0.10-0.69), compared to Nordic mothers. Between 36 and 40 weeks PMA, BMF decreased overall. This change was not associated with investigated predictors. CONCLUSION: It is possible to achieve high rates of BMF in very preterm infants. High intake of MOM early in the postnatal period is strongly related to exclusive BMF at 36 weeks PMA.

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