International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Neonatal morbidities and postnatal growth failure in very low birth weight, very preterm infants.

AIM: To assess postnatal growth in infants with and without major neonatal morbidities. METHODS: This study is based on analysis of data collected by the Israel Neonatal Network on VLBW infants (≤1500 g) born in Israel from 2009 to 2018. Postnatal growth was assessed in two 5 years epochs: 2009-2013 (n = 4583) and 2014-2018 (n = 4558). Outcome was considered as severe, mild and no postnatal growth failure (PNGF). Morbidities included respiratory distress syndrome, bronchopulmonary dysplasia, necrotising enterocolitis, patent ductus arteriosus and grades 3-4 intraventricular haemorrhage. Multinomial logistic regression analyses with the generalised estimating equation approach were applied. RESULTS: The study population composed 9141 infants. Of them, 2089 had at least one major morbidity and 7052 infants had none. In infants with no morbidities, 2.1% had severe PNGF, 23.7% mild PNGF and 74.2% had no PNGF, as compared to 13.6%, 43.9% and 42.5%, respectively, in infants with any major neonatal morbidity (p < 0.0001). CONCLUSION: Despite enormous advances in neonatal care, postnatal growth remains a challenge in VLBW infants, particularly in infants with major neonatal morbidities. Along with efforts to decrease morbidity, a more personalised plan and follow-up may be required in infants with major morbidities, given their high risk for diminished growth and potentially, adverse neurodevelopmental outcomes.

Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study.

OBJECTIVE: The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. STUDY DESIGN: This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March - 5th May 2020) compared with rates before (January 1st 2020 - March 10th 2020), and after the lockdown (May 6th 2020-June 30th 2020) and to the corresponding periods in 2017to 2019. RESULTS: During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of -0.52% (95% confidence interval -0.89%; -0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). CONCLUSION: The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. KEY POINTS: · A 10% decline in all preterm deliveries was observed during the COVID-19 pandemic national lock-down period.. · The lock-down might influence environmental changes which contribute to the decrease in preterm deliveries.. · Changes in lifestyle, and societal behavior might contribute to the decrease in preterm deliveries..

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Antenatal corticosteroid therapy is associated with a lower risk of cystic periventricular leukomalacia.

AIM: To evaluate the association of antenatal corticosteroids (ACS) therapy on the risk for cystic periventricular leukomalacia (c-PVL) in very low birth weight (VLBW), very preterm infants, whilst accounting for the occurrence of major neonatal morbidities; sepsis, necrotising enterocolitis, intraventricular haemorrhage and bronchopulmonary dysplasia. METHODS: Population-based observational cohort study applying data collected by the Israel national VLBW infant database from 1995-2016. RESULTS: Cystic PVL was diagnosed in 692 (6.8%) of the 10,170 study infants. Among 7522 infants exposed to ACS, the rate of c-PVL was 5.4%, compared to 10.7% among those not exposed (p < 0.0001). ACS was associated with significantly lower odds for c-PVL (Odds Ratio [OR] 0.69, 95% confidence interval [CI] 0.57-0.84). In subgroup analyses, excluding infants with one or more morbidities the rates of c-PVL ranged from 2.7% to 5.4% among infants exposed to ACS compared to 5.6% to 10.7% in those not exposed (all p < 0.0001). ACS was associated with significantly lower OR's for c-PVL in all subgroups, ranging from 0.52 (95% CI 0.40-0.66) to 0.62 (95% CI 0.50-0.77). CONCLUSION: Infants exposed to ACS had a significantly lower risk of c-PVL. Subgroup analyses excluding infants with major neonatal comorbidities showed a consistent reduction of 40%-50% in the risk for c-PVL following ACS therapy.

Antepartum Hemorrhage and Outcome of Very Low Birth Weight, Very Preterm Infants: A Population-Based Study.

OBJECTIVE: We aimed to determine the independent effect of maternal antepartum hemorrhage (APH) on mortality and major neonatal morbidities among very low birth weight (VLBW), very preterm infants. STUDY DESIGN: A population-based cohort study of VLBW singleton infants born at 24 to 31 weeks of gestation between 1995 and 2016 was performed. Infants born with the following pregnancy associated complications were excluded: maternal hypertensive disorders, prolonged rupture of membranes, amnionitis, maternal diabetes, and small for gestational age. APH included hemorrhage due to either placenta previa or placental abruption. Univariate and multivariable logistic regression analyses were performed to assess the effect of maternal APH on mortality and major neonatal morbidities. RESULTS: The initial cohort included 33,627 VLBW infants. Following exclusions, the final study population comprised 6,235 infants of whom 2,006 (32.2%) were born following APH and 4,229 (67.8%) without APH. In the APH versus no APH group, there were higher rates of extreme prematurity (24-27 weeks of gestation; 51.6% vs. 45.3%, p < 0.0001), mortality (20.2 vs. 18.5%, p = 0.011), bronchopulmonary dysplasia (BPD, 16.1 vs. 13.0%, p = 0.004) and death or adverse neurologic outcome (37.4 vs. 34.5%, p = 0.03). In the multivariable analyses, APH was associated with significantly increased odds ratio (OR) for BPD in the extremely preterm infants (OR: 1.31, 95% confidence interval: 1.05-1.65). The OR's for mortality, adverse neurological outcomes, and death or adverse neurological outcome were not significantly increased in the APH group. CONCLUSION: Among singleton, very preterm VLBW infants, maternal APH was associated with increased odds for BPD only in extremely premature infants, but was not associated with excess mortality or adverse neonatal neurological outcomes. KEY POINTS: · Outcome of very low birth weight infants born after antepartum hemorrhage (APH) was assessed.. · APH was not associated with higher infant mortality.. · APH was not associated with adverse neurological outcome.. · APH was associated with increased bronchopulmonary dysplasia in extremely preterm infants..

Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Family Rooms in Neonatal Intensive Care Units and Neonatal Outcomes: An International Survey and Linked Cohort Study.

OBJECTIVES: To evaluate the proportion of neonatal intensive care units with facilities supporting parental presence in their infants' rooms throughout the 24-hour day (ie, infant-parent rooms) in high-income countries and to analyze the association of this with outcomes of extremely preterm infants. STUDY DESIGN: In this survey and linked cohort study, we analyzed unit design and facilities for parents in 10 neonatal networks of 11 countries. We compared the composite outcome of mortality or major morbidity, length of stay, and individual morbidities between neonates admitted to units with and without infant-parent rooms by linking survey responses to patient data from 2015 for neonates of less than 29 weeks of gestation. RESULTS: Of 331 units, 13.3% (44/331) provided infant-parent rooms. Patient-level data were available for 4662 infants admitted to 159 units in 7 networks; 28% of the infants were cared for in units with infant-parent rooms. Neonates from units with infant-parent rooms had lower odds of mortality or major morbidity (aOR, 0.76; 95% CI, 0.64-0.89), including lower odds of sepsis and bronchopulmonary dysplasia, than those from units without infant-parent rooms. The adjusted mean length of stay was 3.4 days shorter (95%, CI -4.7 to -3.1) in the units with infant-parent rooms. CONCLUSIONS: The majority of units in high-income countries lack facilities to support parents' presence in their infants' rooms 24 hours per day. The availability vs absence of infant-parent rooms was associated with lower odds of composite outcome of mortality or major morbidity and a shorter length of stay.

Postnatal steroid therapy is associated with autism spectrum disorder in children and adolescents of very low birth weight infants.

BACKGROUND: This study evaluates the association between major neonatal morbidities and autism spectrum disorder (ASD) in children and adolescents born of very low birth weight (VLBW). METHODS: Historical cohort study using the Israel national VLBW infant database linked with the Maccabi Healthcare Services (MHS) medical records. The study cohort comprised 4963 VLBW subjects born from 1999 to 2012, >1 year of age. Multivariable logistic regression analyses were used to assess factors associated with ASD. RESULTS: The diagnosis of ASD was confirmed in 113 children (2.3%). Infants with major neonatal morbidities had higher rates of ASD; however, in the multivariable analyses these were not significantly associated with ASD: severe intraventricular hemorrhage (OR 1.21 [95% CI 0.60-2.45]), post-hemorrhagic hydrocephalus (OR 1.77 [0.73-4.29]), periventricular leukomalacia (OR 1.02 [0.42-2.51]), severe retinopathy of prematurity (OR 1.91 [0.995-3.67]), and bronchopulmonary dysplasia (OR 1.44 [0.84-2.45]). Postnatal steroid therapy when included separately was associated with an OR of 1.97 [1.18-3.29] for ASD. This association remained significant when postnatal steroid therapy was included with each of the neonatal morbidities (ORs ranging from 1.91 to 2.11). CONCLUSIONS: This study suggests a significant association between postnatal steroid therapy and ASD in VLBW infants. This possible association should be considered in future studies evaluating potential risk factors for ASD in preterm infants.

Survey shows marked variations in approaches to redirection of care for critically ill very preterm infants in 11 countries.

AIM: We surveyed care practices for critically ill very preterm infants admitted to neonatal intensive care units (NICUs) in the International Network for Evaluating Outcomes in Neonates (iNeo) to identify differences relevant to outcome comparisons. METHODS: We conducted an online survey on care practices for critically ill very preterm infants and infants with severe intracranial haemorrhage (ICH). The survey was distributed in 2015 to representatives of 390 NICUs in 11 countries. Survey replies were compared with network incidence of death and severe ICH for infants born between 230/7 and 286/7  weeks of gestation from January 1, 2015, to December 31, 2015. RESULTS: Most units in Israel, Japan and Tuscany, Italy, favoured withholding care when care was considered futile, whereas most units in other networks favoured redirection of care. For infants with bilateral grade 4 ICH, redirection of care was very frequently (≥90% of cases) offered in the majority of units in Australia and New Zealand and Switzerland, but rarely in other networks. Networks where redirection of care was frequently offered for severe ICH had lower rates of survivors with severe ICH. CONCLUSION: We identified marked inter-network differences in care approaches that need to be considered when comparing outcomes.

The association between obesity and secular trend of stature: a nationwide study of 2.8 million adolescents over five decades.

BACKGROUND/OBJECTIVES: It is unclear whether adolescent obesity is associated with limited linear growth. We assessed this association in a nationwide sample of adolescents. METHODS: We conducted a population-based, study of 2,785,227 Israeli adolescents (60% males) who were examined before military service since 1967 through 2015. Height and weight were measured along with assessment of medical status at age 17.4 ± 0.4 years. The secular trend of height was plotted using United States Center for Disease Control (US CDC) age- and sex-adjusted BMI percentile groups. We accounted for health status at enrollment and computed the expected height based on parental data that was available for 512,978 examinees. RESULTS: Over five decades, the mean height increased by 3.1 cm among males, but remained unchanged among females. Among males, gain in height was attained predominantly during the first 25 years and has stabilized since. Males with obesity were taller than their normal-weight and underweight counterparts. Underweight girls had a prominent increase in mean height during the first two decades, exceeding the mean height of their counterparts with obesity by over 2 cm. There was a gradual decrease in the difference between measured and expected height in males and females regardless of BMI status, with the exception of the underweight females who achieved consistently higher stature than expected (≥3 cm). CONCLUSIONS: During five decades, excessive BMI was not a limiting factor in growth potential compared with normal BMI in both sexes. The only group that exceeded its growth potential, when accounting for expected mid-parental height, were underweight females with unimpaired health.

Severe obesity and cardio-metabolic comorbidities: a nationwide study of 2.8 million adolescents.

BACKGROUND: Severe obesity is rising among adolescents, but data on the prevalence of metabolic abnormalities among this group are limited. We assessed the secular trend of severe obesity and its association with major cardio-metabolic morbidities. METHODS: A total of 2,785,227 Israeli adolescents (aged 17.2 ± 0.5 years) who underwent a pre-recruitment medical examination including routine measurements of weight, height and blood pressure between 1967 and 2015 were included. In all, 230,639 adolescents with abnormally excessive BMI were classified into overweight, classes I, II, and III (severe) obesity. Logistic regression was applied to determine the association between BMI groups and prehypertension, high blood pressure and type 2 diabetes (T2DM). RESULTS: There was 45-fold increase in the prevalence of class III obesity during study period. Severe obesity was recorded in 2060 males and 1149 females, in whom nearly 35 and 43% had prehypertension or high blood pressure, respectively. Compared with adolescents with overweight, the odds ratios (ORs) for high blood pressure in classes II and III obesity groups, respectively, were 2.13 (95% CI, 2.04-2.23) and 2.86 (2.60-3.15) in males, and 2.59 (2.43-2.76) and 3.44 (3.04-3.90) in females, whereas the ORs for T2DM were 19.1 (12.3-29.6) and 38.0 (22.6-64.0) in males, and 15.1 (11.4-20.0) and 24.8 (17.2-35.7) in females. Results persisted in extensive sensitivity analyses including a longitudinal follow-up (median: males, 3.4 years; females, 4.9 years). CONCLUSIONS: Severe obesity showed a marked secular increase and was associated with significantly higher risk for abnormal blood pressure and T2DM than lower degrees of obesity, in both males and females.

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries.

OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 240/7 to 316/7 weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm.

Rehospitalization Through Childhood and Adolescence: Association with Neonatal Morbidities in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the impact of major neonatal morbidities on the risks for rehospitalization in children and adolescents born of very low birth weight. STUDY DESIGN: An observational study was performed on data of the Israel Neonatal Network linked together with the Maccabi Healthcare Services medical records. After discharge from the neonatal intensive care unit, 6385 infants of very low birth weight born from 1995 to 2012 were registered with Maccabi Healthcare Services and formed the study cohort. Multivariable negative binomial regression models were calculated to estimate the adjusted relative risk (aRR) and 95% CI for hospitalization. RESULTS: Up to 18 years following discharge, 3956 infants were hospitalized at least once. The median age of follow-up was 10.7 years with total of follow-up of 67 454 patient years and 10 895 hospitalizations. The risks for rehospitalization were increased significantly for each of the neonatal morbidities: surgical necrotizing enterocolitis (NEC), aRR 2.71 (95% CI 2.08-3.53), intraventricular hemorrhage grades 3-4, 2.13 (1.85-2.46), periventricular leukomalacia (PVL), 1.83 (1.58-2.13), bronchopulmonary dysplasia, 1.94 (1.72-2.17), and retinopathy of prematurity stages 3-4, 1.59 (1.36-1.85). During the first 4 years, children with surgically treated NEC, intraventricular hemorrhage, PVL, or bronchopulmonary dysplasia had 1.5- to 2.5-fold greater risks for hospitalization compared with those without the specific morbidity. In the 11th-14th and 15th-18th years, respectively, surgically treated NEC was associated with a 3.05 (1.32-7.04) and 3.26 (0.99-10.7) aRR for hospitalization, and PVL was associated with a 2.67 (1.79-3.97) and 3.47 (2.03-5.92) aRR for hospitalization. CONCLUSIONS: Specific major neonatal morbidities as well as the number of morbidities were associated with excess risks of rehospitalization through childhood and adolescence.

Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus.

The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria. CONCLUSION: A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.

Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates: An International Comparison.

OBJECTIVE: To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN: We included 58 004 infants born weighing <1500 g at 24(0)-31(6) weeks' gestation from databases in Australia/New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the United Kingdom. We compared a composite outcome (mortality or any of grade ≥3 peri-intraventricular hemorrhage, periventricular echodensity/echolucency, bronchopulmonary dysplasia, or treated retinopathy of prematurity) between each country and all others by using standardized ratios and pairwise using logistic regression analyses. RESULTS: Despite differences in population coverage, included neonates were similar at baseline. Composite outcome rates varied from 26% to 42%. The overall mortality rate before discharge was 10% (range: 5% [Japan]-17% [Spain]). The standardized ratio (99% CIs) estimates for the composite outcome were significantly greater for Spain 1.09 (1.04-1.14) and the United Kingdom 1.16 (1.11-1.21), lower for Australia/New Zealand 0.93 (0.89-0.97), Japan 0.89 (0.86-0.93), Sweden 0.81 (0.73-0.90), and Switzerland 0.77 (0.69-0.87), and nonsignificant for Canada 1.04 (0.99-1.09) and Israel 1.00 (0.93-1.07). The adjusted odds of the composite outcome varied significantly in pairwise comparisons. CONCLUSIONS: We identified marked variations in neonatal outcomes between countries. Further collaboration and exploration is needed to reduce variations in population coverage, data collection, and case definitions. The goal would be to identify care practices and health care organizational factors, which has the potential to improve neonatal outcomes.

Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: An International Study.

BACKGROUND: Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS: Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS: The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION: Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable.

Association between neonatal morbidities and head growth from birth until discharge in very-low-birthweight infants born preterm: a population-based study.

AIM: To evaluate the possible association between major neonatal morbidities and poor head growth from birth to discharge home in very-low-birthweight (VLBW) infants born preterm. METHOD: Population-based observational study comprising 12 992 infants (6340 male, 6652 female) of 24 to 32 weeks' gestation, and birthweight ≤1500g. Severe head growth failure (HGF) was defined as a decrease in head circumference z-score >2 z-scores, and moderate HGF as a decrease of 1 to 2 z-scores. Multinomial logistic regression analysis was applied to determine morbidities associated with HGF. RESULTS: Severe HGF occurred in 4.5% and moderate HGF in 20.9% of infants. Each unit increase in head circumference z-score at birth was associated with increased odds for severe and moderate HGF (odds ratios [OR] 5.29, 95% confidence intervals [CI] 4.67-6.00, and OR 2.38, 95% CI 2.23-2.54 respectively). Both severe and moderate HGF were associated with respiratory distress syndrome (OR 2.03, 95% CI 1.58-2.62, and OR 1.66, 95% CI 1.48-1.85 respectively); bronchopulmonary dysplasia (OR 3.38, 95% CI 2.33-4.91, and OR 1.87, 95% CI 1.52-2.30 respectively); necrotizing enterocolitis (OR 2.89, 95% CI 2.04-4.09, and OR 1.72, 95% CI 1.38-2.16 respectively), and sepsis (OR 2.06, 95% CI 1.69-2.50, and OR 1.38, 95% CI 1.24-1.53 respectively). INTERPRETATION: Major neonatal morbidities were associated with HGF in VLBW infants born preterm. Identification of whether this is a direct effect of these morbidities or mediated through nutritional or growth factors may enable interventions to improve postnatal head growth of infants born preterm.

[THE ISRAEL NATIONAL VERY LOW BIRTH WEIGHT INFANT DATABASE].

BACKGROUND: Very low birth weight (VLBW ≤ 1,500g] infants represent approximately 1% of all live births in Israel but are responsible for about 45% of all infant deaths and account for 45% of all hospitalization days in the neonatal special and intensive care units (NICU's). AIM: To identify perinatal and neonatal factors associated with mortality, morbidity and handicap among VLBW infants. METHODS: Since 1995 data for > 99% of VLBW infants were received from all 27 NICU's in Israel. The data includes maternal obstetric history, infant's status at birth, deaths, major neonatal morbidities and treatments during the infant's hospitalization. The data are analyzed, collated and annual national and departmental reports prepared. RESULTS: The database comprises information on 25,800 VLBW infants born from 1995-2011. Approximately 20% of VLBW infants were conceived by in-vitro fertilization, one-third of the births were multiple births and 60% of multiple births were the result of infertility treatments. Mortality declined significantly from 23.7% in 1995-1997 to 16.8% in 2010-2011. During this period significant decreases in major neonatal morbidities were documented: Late onset sepsis (> 3 days) decreased from 29.9% to 23.2% in 2010-2011; severe retinopathy of prematurity from 7.6% to 3.8% and periventricular leukomalacia from 8.3% to 5.0%. The rate of bronchopulmonary dysplasia increased from 9.5% in 1995-1997 to 13% in the period 2001-2006, subsequently declining to 10.8% in the last years. CONCLUSION: Since 1995 the Israel national VLBW infant database has provided information at both national and hospital levels, documenting the improving care and outcomes for VLBW infants. The significant decline in VLBW infant mortality has been associated with a parallel decrease in major neonatal morbidities.

An intervention for improving the lifestyle habits of kindergarten children in Israel: a cluster-randomised controlled trial investigation.

OBJECTIVE: To assess the effectiveness of an intervention programme to improve kindergarten children's eating and leisure habits in Israel. DESIGN: A cluster-randomised controlled trial. SETTING: Six full-day kindergartens in Israel were randomly divided into three groups. Group A received the full intervention programme, which included lessons on good eating habits and daily physical exercise. Group B received a partial intervention of lessons only. Group C, the reference group, did not receive any intervention. SUBJECTS: Children aged 4-6 years (n 204) were recruited for the study. METHODS: Objective data for weight and height were collected to calculate BMI Z-scores. Activity, sedentary time, sleeping hours and daily energy intake were assessed via a parental questionnaire. Nutritional knowledge was assessed by a single dietitian using a questionnaire addressed to the children. Assessments were done at baseline and at the end of the intervention. RESULTS: After adjustment for baseline levels we observed a significant reduction in daily energy intake for the full intervention group A (P = 0.03). A positive intervention effect was demonstrated on nutritional knowledge in the partial intervention group B (P = 0.03), although no significant change was demonstrated for BMI Z-score. CONCLUSIONS: The study supports the incorporation of education on healthy lifestyle habits and physical activity into the curricula of kindergartens.