Childhood outcomes after low-grade intraventricular haemorrhage: A systematic review and meta-analysis.

AIM: To undertake a systematic review and meta-analysis exploring school-age neurodevelopmental outcomes of children after low-grade intraventricular haemorrhage (IVH). METHOD: The published and grey literature was extensively searched to identify observational comparative studies exploring neurodevelopmental outcomes after IVH grades 1 and 2. Our primary outcome was neurodevelopmental impairment after 5 years of age, which included cognitive, motor, speech and language, behavioural, hearing, or visual impairments. RESULTS: This review included 12 studies and over 2036 infants born preterm with low grade IVH. Studies used 30 different neurodevelopmental tools to determine outcomes. There was conflicting evidence of the composite risk of neurodevelopmental impairment after low-grade IVH. There was evidence of an association between low-grade IVH and lower IQ at school age (-4.23, 95% confidence interval [CI] -7.53, -0.92, I2 = 0%) but impact on school performance was unclear. Studies reported an increased crude risk of cerebral palsy after low-grade IVH (odds ratio [OR] 2.92, 95% CI 1.95, 4.37, I2 = 41%). No increased risk of speech and language impairment or behavioural impairment was found. Few studies addressed hearing and visual impairment. INTERPRETATION: This systematic review presents evidence that low-grade IVH is associated with specific neurodevelopmental impairments at school age, lending support to the theory that low-grade IVH is not a benign condition. WHAT THIS PAPER ADDS: The functional impact of low-grade intraventricular haemorrhage (IVH) at school age is unknown. Low-grade IVH is associated with a lower IQ at school age. The risk of cerebral palsy is increased after low-grade IVH. Low-grade IVH is not associated with speech and language impairment.

National Trends in Preterm Infant Mortality in the United States by Race and Socioeconomic Status, 1995-2020.

Importance: Inequalities in preterm infant mortality exist between population subgroups within the United States. Objective: To characterize trends in preterm infant mortality by maternal race and socioeconomic status to assess how inequalities in preterm mortality rates have changed over time. Design, Setting, and Participants: This was a retrospective longitudinal descriptive study using the US National Center for Health Statistics birth infant/death data set for 12 256 303 preterm infant births over 26 years, between 1995 and 2020. Data were analyzed from December 2022 to March 2023. Exposures: Maternal characteristics including race, smoking status, educational attainment, antenatal care, and insurance status were used as reported on an infant's US birth certificate. Main Outcomes and Measures: Preterm infant mortality rate was calculated for each year from 1995 to 2020 for all subgroups, with a trend regression coefficient calculated to describe the rate of change in preterm mortality. Results: The average US preterm infant mortality rate (IMR) decreased from 33.71 (95% CI, 33.71 to 34.04) per 1000 preterm births per year between 1995-1997, to 23.32 (95% CI, 23.05 to 23.58) between 2018-2020. Black non-Hispanic infants were more likely to die following preterm births than White non-Hispanic infants (IMR, 31.09; 95% CI, 30.44 to 31.74, vs 21.81; 95% CI, 21.43 to 22.18, in 2018-2020); however, once born, extremely prematurely Black and Hispanic infants had a narrow survival advantage (IMR rate ratio, 0.87; 95% CI, 0.84 to 0.91, in 2018-2020). The rate of decrease in preterm IMR was higher in Black infants (-0.015) than in White (-0.013) and Hispanic infants (-0.010); however, the relative risk of preterm IMR among Black infants compared with White infants remained the same between 1995-1997 vs 2018-2020 (relative risk, 1.40; 95% CI, 1.38 to 1.44, vs 1.43; 95% CI, 1.39 to 1.46). The rate of decrease in preterm IMR was higher in nonsmokers compared with smokers (-0.015 vs -0.010, respectively), in those with high levels of education compared with those with intermediate or low (-0.016 vs - 0.010 or -0.011, respectively), and in those who had received adequate antenatal care compared with those who did not (-0.014 vs -0.012 for intermediate and -0.013 for inadequate antenatal care). Over time, the relative risk of preterm mortality widened within each of these subgroups. Conclusions and Relevance: This study found that between 1995 and 2020, US preterm infant mortality improved among all categories of prematurity. Inequalities in preterm infant mortality based on maternal race and ethnicity have remained constant while socioeconomic disparities have widened over time.

School-age outcomes of children after perinatal brain injury: a systematic review and meta-analysis.

BACKGROUND: Over 3000 children suffer a perinatal brain injury in England every year according to national surveillance. The childhood outcomes of infants with perinatal brain injury are however unknown. METHODS: A systematic review and meta-analyses were undertaken of studies published between 2000 and September 2021 exploring school-aged neurodevelopmental outcomes of children after perinatal brain injury compared with those without perinatal brain injury. The primary outcome was neurodevelopmental impairment, which included cognitive, motor, speech and language, behavioural, hearing or visual impairment after 5 years of age. RESULTS: This review included 42 studies. Preterm infants with intraventricular haemorrhage (IVH) grades 3-4 were found to have a threefold greater risk of moderate-to-severe neurodevelopmental impairment at school age OR 3.69 (95% CI 1.7 to 7.98) compared with preterm infants without IVH. Infants with perinatal stroke had an increased incidence of hemiplegia 61% (95% CI 39.2% to 82.9%) and an increased risk of cognitive impairment (difference in full scale IQ -24.2 (95% CI -30.73 to -17.67) . Perinatal stroke was also associated with poorer academic performance; and lower mean receptive -20.88 (95% CI -36.66 to -5.11) and expressive language scores -20.25 (95% CI -34.36 to -6.13) on the Clinical Evaluation of Language Fundamentals (CELF) assessment. Studies reported an increased risk of persisting neurodevelopmental impairment at school age after neonatal meningitis. Cognitive impairment and special educational needs were highlighted after moderate-to-severe hypoxic-ischaemic encephalopathy. However, there were limited comparative studies providing school-aged outcome data across neurodevelopmental domains and few provided adjusted data. Findings were further limited by the heterogeneity of studies. CONCLUSIONS: Longitudinal population studies exploring childhood outcomes after perinatal brain injury are urgently needed to better enable clinicians to prepare affected families, and to facilitate targeted developmental support to help affected children reach their full potential.

Population-based screening methods in biliary atresia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to investigate tested methods of population-based biliary atresia (BA) screening. DESIGN: We searched 11 databases between 1 January 1975 and 12 September 2022. Data extraction was independently done by two investigators. MAIN OUTCOME MEASURES: Our primary outcomes were: sensitivity and specificity of screening method in BA detection, age at Kasai, BA associated morbidity and mortality, cost-effectiveness of screening. RESULTS: Six methods of BA screening were evaluated: stool colour charts (SCCs), conjugated bilirubin measurements, stool colour saturations (SCSs), measurements of urinary sulfated bile acids (USBAs), assessments of blood spot bile acids and blood carnitine measurements.In a meta-analysis, USBA was the most sensitive and specific, with a pooled sensitivity and specificity of 100.0% (95% CI 2.5% to 100.0%) and 99.5% (95% CI 98.9% to 99.8%) (based on one study). This was followed by conjugated bilirubin measurements: 100.0% (95% CI 0.0% to 100.0%) and 99.3% (95% CI 91.9% to 99.9%), SCS: 100.0% (95% CI 0.00% to 100.0%) and 92.4% (95% CI 83.4% to 96.7%), and SCC: 87.9% (95% CI 80.4% to 92.8%) and 99.9% (95% CI 99.9% to 99.9%).SCC reduced the age of Kasai to ~60 days, compared with 36 days for conjugated bilirubin. Both SCC and conjugated bilirubin improved overall and transplant-free survival. The use of SCC was considerably more cost-effective than conjugated bilirubin measurements. CONCLUSION: Conjugated bilirubin measurements and SCC are the most researched and demonstrate improved sensitivity and specificity in detecting BA. However, their use is expensive. Further research into conjugated bilirubin measurements, as well as alternative methods of population-based BA screening, is required. PROSPERO REGISTRATION NUMBER: CRD42021235133.

Reduced Presentation of Biliary Atresia During the COVID-19 Lockdown: A Population Based Observational Study.

OBJECTIVE: The aim of this study was to assess whether there has been a change in presentations of biliary atresia (BA) in England and Wales during the first and second coronavirus disease 2019 (COVID-19) lockdowns (January-June 2020 and 2021). DESIGN: This population study assessed all confirmed cases of BA, from January 2020 to December 2021 across the 3 UK pediatric liver centers originating from England and Wales. Data was then compared to the incidence of confirmed BA cases from January to December 2017, 2018, and 2019. RESULTS: During January-June 2020 and 2021, there were only 8 and 12 presenting cases of BA in England and Wales, compared to 16, 13, and 18 for the same time periods in 2017, 2018, and 2019, respectively. This difference was significant in a two-sided t test for 2020 ( P = 0.035) but not for 2021 ( P = 0.385). There was no difference in the mean days to Kasai procedure in January-June 2020 and 2021 compared to 2017-2019; however average time to Kasai after the lockdown periods was significantly higher. CONCLUSIONS: There was a significant reduction in the presenting cases of BA during the first COVID-19 lockdown, with an increased time for BA referrals after the pandemic lockdowns were lifted in England and Wales.

Preterm Brain Injury and Neurodevelopmental Outcomes: A Meta-analysis.

CONTEXT: Preterm brain injuries are common; neurodevelopmental outcomes following contemporary neonatal care are continually evolving. OBJECTIVE: To systematically review and meta-analyze neurodevelopmental outcomes among preterm infants after intraventricular hemorrhage (IVH) and white matter injury (WMI). DATA SOURCES: Published and grey literature were searched across 10 databases between 2000 and 2021. STUDY SELECTION: Observational studies reporting 3-year neurodevelopmental outcomes for preterm infants with IVH or WMI compared with preterm infants without injury. DATA EXTRACTION: Study characteristics, population characteristics, and outcome data were extracted. RESULTS: Thirty eight studies were included. There was an increased adjusted risk of moderate-severe neurodevelopmental impairment after IVH grade 1 to 2 (adjusted odds ratio 1.35 [95% confidence interval 1.05-1.75]) and IVH grade 3 to 4 (adjusted odds ratio 4.26 [3.25-5.59]). Children with IVH grade 1 to 2 had higher risks of cerebral palsy (odds ratio [OR] 1.76 [1.39-2.24]), cognitive (OR 1.79 [1.09-2.95]), hearing (OR 1.83 [1.03-3.24]), and visual impairment (OR 1.77 [1.08-2.9]). Children with IVH grade 3 to 4 had markedly higher risks of cerebral palsy (OR 4.98 [4.13-6.00]), motor (OR 2.7 [1.52-4.8]), cognitive (OR 2.3 [1.67-3.15]), hearing (OR 2.44 [1.42-4.2]), and visual impairment (OR 5.42 [2.77-10.58]). Children with WMI had much higher risks of cerebral palsy (OR 14.91 [7.3-30.46]), motor (OR 5.3 [3-9.36]), and cognitive impairment (OR 3.48 [2.18-5.53]). LIMITATIONS: Heterogeneity of outcome data. CONCLUSIONS: Mild IVH, severe IVH, and WMI are associated with adverse neurodevelopmental outcomes. Utilization of core outcome sets and availability of open-access study data would improve our understanding of the nuances of these outcomes.

Improving quality of teaching and child development: A randomised controlled trial of the leadership for learning intervention in preschools.

Introduction: Substantial research indicates that high quality early childhood education and care (ECEC) confers a wide range of benefits for children, yet quality in ECEC remains inconsistent. Given the variability in training and qualifications, one strategy for improving ECEC quality is in-service professional development (PD). Methods: The current study evaluated an evidence-based in-service PD programme, Leadership for Learning, via a cluster randomised controlled trial involving 83 ECEC services and 1,346 children in their final year of pre-school. Results: Results indicated significant improvements in teaching quality across treatment centres and child development outcomes in language, numeracy and social-emotional development. Discussion: This study provides strong support for making evidence-informed PD routinely available for ECEC practitioners.

Cohort profile: a national, population-based cohort of children born after assisted conception in the UK (1992-2009): methodology and birthweight analysis.

PURPOSE: To generate a large cohort of children born after assisted reproductive technology (ART) in the UK between 1992 and 2009, their naturally conceived siblings (NCS) and matched naturally conceived population (NCP) controls and linking this with health outcome data to allow exploration of the effects of ART. The effects of fresh and frozen embryo transfer on birth weight (BW) were analysed to test the validity of the cohort. PARTICIPANTS: Children recorded on the Human Fertilisation and Embryology Authority (HFEA) register as being born after ART between 1992 and 2009, their NCS and matched NCP controls linked to Office for National Statistics birth registration dataset (HFEA-ONS cohort). This cohort was further linked to the UK Hospital Episode Statistics database to allow monitoring of the child's post-natal health outcomes up to 2015 (HFEA-ONS-HES subcohort). FINDINGS TO DATE: The HFEA-ONS cohort consisted of 75 348 children born after non-donor ART carried out in the UK between 1 April 1992 and 31 July 2009 and successfully linked to birth registration records, 14 763 NCS and 164 823 matched NCP controls. The HFEA-ONS-HES subcohort included 63 877 ART, 11 343 NCS and 127 544 matched NCP controls further linked to health outcome data. The exemplar analysis showed that children born after fresh embryo transfers were lighter (BW difference: -131 g, 95% CI: -140 to -123) and those born after frozen embryo transfers were heavier (BW difference: 35 g, 95% CI: 19 to 52) than the NCP controls. The within-sibling analyses were directionally consistent with the population control analyses, but attenuated markedly for the fresh versus natural conception (BW difference: -54 g; 95% CI: -72 to -36) and increased markedly for the frozen versus natural conception (BW difference: 152 g; 95% CI: 113 to 190) analyses. FUTURE PLANS: To use this cohort to explore the relationship between ART conception and short-term and long-term health outcomes in offspring.

Obesity as a driver of international differences in COVID-19 death rates.

AIM: To determine what proportion of the inter-country variation in death rates can be explained in terms of obesity rates and other known risk factors for coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: COVID-19 death rates from 30 industrialized countries were analysed using linear regression models. Covariates modelled population density, the age structure of the population, obesity, population health, per capita gross domestic product (GDP), ethnic diversity, national temperature and the delay in the government imposing virus control measures. RESULTS: The multivariable regression model explained 63% of the inter-country variation in COVID-19 death rates. The initial model was optimized using stepwise selection. In descending order of absolute size of model coefficient, the covariates in the optimized model were the obesity rate, the hypertension rate, population density, life expectancy, the percentage of the population aged older than 65 years, the percentage of the population aged younger than 15 years, the diabetes rate, the delay in imposing national COVID-19 control measures, per capita GDP and mean temperature (with a negative coefficient indicating an association between higher national temperatures and lower death rates). CONCLUSIONS: A large proportion of the inter-country variation in COVID-19 death rates can be explained by differences in obesity rates, population health, population densities, age demographics, delays in imposing national virus control measures, per capita GDP and climate. Some of the unexplained variation is probably attributable to inter-country differences in the definition of a COVID-19 death and in the completeness of the recording of COVID-19 deaths.

Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems.

As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other's limitations.

Educational Progress of Looked-After Children in England: A Study Using Group Trajectory Analysis.

BACKGROUND: Looked-after children in local authority care are among the most disadvantaged, and measures of their well-being, including educational outcomes, are poorer than other children's. METHODS: The study sample consisted of all children in England born in academic years 1993 to 1994 through 1997 to 1998 who were in local authority care at any point during the academic years 2005 to 2006 through 2012 to 2013 and for whom results of national tests in literacy and numeracy were available at ages 7, 11, and 16 (N = 47 500). RESULTS: Group trajectory analysis of children's educational progress identified 5 trajectory groups: low achievement, late improvement, late decline, predominant, and high achievement. Being looked after earlier was associated with a higher probability of following a high achievement trajectory and a lower probability of following a late decline trajectory. For children first looked after between ages 7 and 16, having a longer total time looked after by age 16 was associated with a higher probability of following a high achievement trajectory. For children with poor outcomes at ages 7 and 11, being looked after by age 16 was associated with an increased chance of educational improvement by age 16. CONCLUSIONS: This study provides evidence that early entry into care can reduce the risk of poor educational outcomes. It also establishes group trajectory analysis as an effective method for analyzing the educational progress of looked-after children, with the particular strength that it allows factors associated with a late decline or improvement in educational progress to be identified.

Self-rated health and all-cause and cause-specific mortality of older adults: Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium.

OBJECTIVES: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as "at-least-good". STUDY DESIGN: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982-2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses. MAIN OUTCOME MEASURES: All-cause, cardiovascular and cancer mortality. RESULTS: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH "fair" or "poor" vs. "at-least-good" was associated with increased mortality: HRs 1.46 (95% CI 1·23-1.74) and 2.31 (1.79-2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence). CONCLUSION: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to "feel healthy" and "be healthy".

Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study.

BACKGROUND: Nutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. OBJECTIVE: The aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations. METHODS: Men and women aged 45-69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006-2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n=4166) and follow-up (n=2739) cognitive domain-specific z-scores were estimated using multiple linear regression. RESULTS: After adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p<0.01) and immediate recall (p<0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (ß=0.12; 95% CI=0.02, 0.21). CONCLUSIONS: Folate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline.

Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data.

BACKGROUND: The free radical/oxidative stress theory of ageing has received considerable attention, but the evidence on the association of oxidative stress markers with mortality is sparse. METHODS: We measured derivatives of reactive oxygen metabolite (D-ROM) levels as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 10,622 men and women (age range, 45-85 years), from population-based cohorts from Germany, Poland, Czech Republic, and Lithuania, of whom 1,702 died during follow-up. RESULTS: Both oxidative stress markers were significantly associated with all-cause mortality independently from established risk factors (including inflammation) and from each other in all cohorts. Regarding cause-specific mortality, compared to low D-ROM levels (≤ 340 Carr U), very high D-ROM levels (>500 Carr U) were strongly associated with both cardiovascular (relative risk (RR), 5.09; 95 % CI, 2.67-9.69) and cancer mortality (RR, 4.34; 95 % CI, 2.31-8.16). TTL was only associated with CVD mortality (RR, 1.30; 95 % CI, 1.15-1.48, for one-standard-deviation-decrease). The strength of the association of TTL with CVD mortality increased with age of the participants (RR for one-standard-deviation-decrease in those aged 70-85 years was 1.65; 95 % CI, 1.22-2.24). CONCLUSIONS: In these four population-based cohort studies from Central and Eastern Europe, the oxidative stress serum markers D-ROM and TTL were independently and strongly associated with all-cause and CVD mortality. In addition, D-ROM levels were also strongly associated with cancer mortality. This study provides epidemiological evidence supporting the free radical/oxidative stress theory of ageing and suggests that d-ROMs and TTL are useful oxidative stress markers associated with premature mortality.

Paternal Age, Paternal Presence and Children's Health: An Observational Study.

In an observational study of 31,257 children we investigated the effects of paternal age at the time of the child's birth, paternal absence and non-biological fathers on children's health. Results are per 5 year change in paternal age. Older fathers were associated with lower rates of unintentional injuries, odds ratio (OR)=0.966, P=0.0027. There was a quadratic association between paternal age and risk of hospital admission, ß=0.0121, P=0.0109, with minimum risk at paternal age 37.7. Absent fathers were associated with increased risk of hospital admission, OR=1.19, P<10(-3), lower rates of complete immunizations to 9 months, OR=0.562, P<10(-3), higher Strength and Difficulties Questionnaire (SDQ) difficulties scores: ß=0.304, P=0.0024 (3 year olds), ß=0.697, P<10(-3) (5 year olds). Non-biological fathers were associated with increased risk of unintentional injury, OR=1.16, P=0.0319 and hospital admission, OR=1.26, P=0.0166; lower rates of complete immunizations to 9 months, OR=0.343, P=0.0309 and higher SDQ difficulties scores: ß=0.908, P<10(-3).

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States.

OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences. DESIGN: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US. SETTING: General population. PARTICIPANTS: 26,018 men and women aged 50-79 years. MAIN OUTCOME MEASURES: All-cause, cardiovascular, and cancer mortality. RESULTS: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses. CONCLUSIONS: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Health and development of children born after assisted reproductive technology and sub-fertility compared to naturally conceived children: data from a national study.

In a non-matched case-control study using data from two large national cohort studies, we investigated whether indicators of child health and development up to 7 years of age differ between children conceived using assisted reproductive technology (ART), children born after sub-fertility (more than 24 months of trying for conception) and other children. Information on ART use/sub-fertility was available for 23,649 children. There were 227 cases (children conceived through ART) and two control groups: 783 children born to sub-fertile couples, and 22,639 children born to couples with no fertility issues. In models adjusted for social and demographic factors there were significant differences between groups in rate of hospital admissions before the children were 9 months old (P=0.029), with the ART group showing higher rates of hospital admission than the no fertility issues control group, the sub-fertile control group being intermediate between the two. Children born after ART had comparable health and development beyond 9 months of age to their naturally conceived peers. This applied to the whole sample and to a sub-sample of children from deprived neighborhoods.

Maternal prepregnancy BMI and child cognition: a longitudinal cohort study.

OBJECTIVE: To examine the association between maternal prepregnancy BMI and cognitive performance in children at 5 and 7 years of age. METHODS: This is a secondary analysis of data from the Millennium Cohort Study, a prospective population based cohort of 19,517 children in the United Kingdom. Standardized cognitive assessments of children, involving components of the British Ability Scales, second edition and a number skills test, were performed at 5 and 7 years of age. Principal components analysis was used to identify a general cognitive ability factor (g) from individual test scores. Maternal prepregnancy BMI was retrospectively self-reported when children were 9 months old. Mixed-effects linear regression models were fitted, controlling for multiple socio-demographic factors, child's birth weight, child's BMI, maternal smoking, and maternal diabetes. Complete data were available for 11,025 children at 5 years, and 9882 children at 7 years. RESULTS: Maternal prepregnancy BMI was negatively associated with children's cognitive performance (g) at age 5 (P = .0069) and age 7 (P < .0001). The overall effect size was modest: a 10-point increase in maternal BMI was associated with a decrease in cognitive performance of ~1/10th of an SD at age 7. CONCLUSIONS: Maternal prepregnancy BMI is negatively associated with children's cognitive performance, even after adjusting for multiple socio-demographic confounders and children's BMI. The relationship appears to become stronger as children get older, although the overall effect size is modest. In utero fetal programming or residual confounding may explain these findings.

The role of care-seeking delays in intrauterine fetal deaths among 'near-miss' women in Herat, Afghanistan.

BACKGROUND: Many pregnant women in resource-poor countries seek care only after developing severe complications during childbirth at home and often reach health facilities in moribund conditions. The objectives were to (i) investigate the association between care-seeking duration and fetal survival at admission; and (ii) assess the significance of care-seeking duration in relation to other determinants. METHODS: Data were analysed for 266 women who were pregnant with a singleton and admitted in life-threatening conditions to the maternity ward of Herat Regional Hospital in Afghanistan from February 2007 to January 2008. Information about the women's care-seeking durations, social and financial resources, reproductive factors, household economic status and household types were collected during interviews with the women and their husbands. Information about fetal heartbeats at admission was extracted from the women's medical records. RESULTS: Fifty-four per cent of the women had a decision delay lasting 3 h or more; 69% had a transport delay lasting 3 h or more. Multivariable logistic regression analyses suggest that a decision delay lasting an hour or more increased the odds of fetal death by 6.6 (95% confidence interval [CI] 1.6, 26.3) compared with a delay less than 1 h. A woman's lack of financial autonomy and a distance from her natal home increased the odds of fetal death by 3.1 [95% CI 1.1, 8.4] and 2.5 [95% CI 1.0, 6.3] respectively. CONCLUSION: An integrated approach to improving fetal and maternal health from pre-pregnancy through childbirth (including increasing women's social and financial resources) is crucial particularly where senior family members act as gatekeepers to women's access to health care.