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Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue. To investigate the association of maternal hyperglycemia exposure during pregnancy with obesity and abnormal glucose tolerance in offspring, and the age at occurrence. We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04-0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13-0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18-0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2-5 years old to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23-30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse. Only observational studies were included, with a few adequately adjusted for covariables. Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only.

Vitamin A (VA) supplementation reduces the risk of developing bronchopulmonary dysplasia (BPD). However, a previous meta-analysis showed that VA had minimal efficacy for preventing BPD in very low birth weight infants (VLBWIs). To elucidate the effects of VA supplementation for BPD prevention in extremely low birth weight infants (ELBWIs). This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We registered the protocol on PROSPERO, the international prospective registry of systematic reviews (registration number: CRD42016050887). We searched the following five databases: CINAHL, CENTRAL, EMBASE, MEDLINE, and PubMed; screened the reference lists of retrieved articles to identify randomized controlled trials (RCTs); and assessed the Cochrane Risk of Bias for each study. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Four studies (total, 1,011 infants) were included. VA was administered intramuscularly in 3 studies and orally in 1 study. VA supplementation for ELBWIs had benefited oxygen dependency at the postmenstrual age of 36 weeks in survivors (pooled risk ratio, 0.88; 95% confidence intervals (CI), 0.77-0.99; 4 trials, 841 infants, moderate certainty of evidence), which is similar to the meta-analysis in VLBWIs. Length of hospital stay was reduced in the VA group (mean difference, -49.9; 95% CI, -88.78 to -11.02; 1 trial, 20 infants, low certainty of evidence). The meta-analysis showed no reduction in the risk of neonatal death, oxygen use at 28 days in survivors, duration of mechanical ventilation, intraventricular hemorrhage, retinopathy in prematurity, and necrotizing enterocolitis. VA supplementation for ELBWIs is potentially effective in decreasing oxygen dependency at the postmenstrual age of 36 weeks.

The poor coverage of essential maternal services, such as antenatal care (ANC) and skilled delivery care utilization, accounts for higher maternal and infant mortality in low- and middle-income countries (LMICs). Although mobile health (mHealth) interventions could potentially improve the service utilization in resource-limited settings, their effectiveness remains unclear. This review aimed to summarize the effect of mHealth interventions on improving the uptake of ANC visits, skilled birth attendance at the time of delivery, and facility delivery among pregnant women in LMICs. We conducted a comprehensive search on 9 electronic databases and other resources from inception to October 2020. We included individual randomized controlled trials and cluster randomized controlled trials that assessed the effectiveness of mHealth interventions for improving perinatal health care utilization among healthy pregnant women in LMICs. We performed a random-effects meta-analysis and estimated the pooled effect size by using risk ratios (RRs) with 95% CIs. In addition, 2 reviewers independently assessed the risk of bias of the included studies by using the Cochrane risk of bias tool and the certainty of the evidence by using the Grading of Recommendation, Assessment, Development and Evaluation approach. A total of 9 studies (10 articles) that randomized 10,348 pregnant women (n=6254, 60.44% in the intervention group; n=4094, 39.56% in the control group) were included in this synthesis. The pooled estimates showed a positive effect of mHealth interventions on improving 4 or more ANC visit utilizations among pregnant women in LMICs, irrespective of the direction of interventions (1-way communications: RR 2.14, 95% CI 1.76-2.60, I =36%, 2 studies, moderate certainty; 2-way communications: RR 1.17, 95% CI 1.08-1.27, I =59%, 3 studies, low certainty). Only 2-way mHealth interventions were effective in improving the use of skilled birth attendance during delivery (RR 1.23, 95% CI 1.14-1.33, I =0%, 2 studies, moderate certainty), but the effects were unclear for 1-way mHealth interventions (RR 1.04, 95% CI 0.97-1.10, I =73%, 3 studies, very low certainty) when compared with standard care. For facility delivery, the interventions were effective in settings where fewer pregnant women used facility delivery (RR 1.68, 95% CI 1.30-2.19, I =36%, 2 studies, moderate certainty); however, the effects were unclear in settings where most pregnant women already used facility delivery (RR 1.01, 95% CI 0.97-1.04, I =0%, 1 study, low certainty). mHealth interventions may contribute to improving ANC and skilled delivery care utilization among pregnant women in LMICs. However, more studies are required to improve their reproducibility and efficiency or strengthen the evidence of different forms of mHealth interventions because of the considerable heterogeneity observed in the meta-analyses. PROSPERO CRD42020210813; https://tinyurl.com/2n7ny9a7.

Pre-eclampsia has an immense adverse impact on maternal and perinatal health especially in low- and middle-income settings. We aimed to estimate the associations between pre-eclampsia/eclampsia and its risk factors, and adverse maternal and perinatal outcomes. We performed a secondary analysis of the WHO Global Survey on Maternal and Perinatal Health. The survey was a multi-country, facility-based cross-sectional study. A global sample consisting of 24 countries from three regions and 373 health facilities was obtained via a stratified multi-stage cluster sampling design. Maternal and offspring data were extracted from records using standardized questionnaires. Multi-level logistic regression modelling was conducted with random effects at the individual, facility and country levels. Data for 276,388 mothers and their infants was analysed. The prevalence of pre-eclampsia/eclampsia in the study population was 10,754 (4%). At the individual level, sociodemographic characteristics of maternal age ≥30 years and low educational attainment were significantly associated with higher risk of pre-eclampsia/eclampsia. As for clinical and obstetric variables, high body mass index (BMI), nulliparity (AOR: 2.04; 95%CI 1.92-2.16), absence of antenatal care (AOR: 1.41; 95%CI 1.26-1.57), chronic hypertension (AOR: 7.75; 95%CI 6.77-8.87), gestational diabetes (AOR: 2.00; 95%CI 1.63-2.45), cardiac or renal disease (AOR: 2.38; 95%CI 1.86-3.05), pyelonephritis or urinary tract infection (AOR: 1.13; 95%CI 1.03-1.24) and severe anemia (AOR: 2.98; 95%CI 2.47-3.61) were found to be significant risk factors, while having >8 visits of antenatal care was protective (AOR: 0.90; 95%CI 0.83-0.98). Pre-eclampsia/eclampsia was found to be a significant risk factor for maternal death, perinatal death, preterm birth and low birthweight. Chronic hypertension, obesity and severe anemia were the highest risk factors of preeclampsia/eclampsia. Implementation of effective interventions prioritizing risk factors, provision of quality health services during pre-pregnancy and during pregnancy for joint efforts in the areas of maternal health are recommended.

Background\\nOptimum timing of umbilical cord clamping has not been established in preterm infants.\\nObjectives\\nWe compared the short- and long-term effects of umbilical cord milking (UCM) versus delayed cord clamping (DCC) on infants born at less than 37 weeks of gestation.\\nSearch methods\\nA systematic review and meta-analysis was conducted according to the \"Preferred Reporting Items for Systematic Reviews and Meta-Analyses\" statement. We searched CINAHL, CENTRAL, EMBASE, MEDLINE, PubMed and ClinicalTrials.gov for relevant randomized controlled trials (RCTs).\\nSelection criteria\\nWe included individual and clustered RCTs comparing UCM to DCC for infants born before 37 weeks of gestation.\\nData collection and analysis\\nFour reviewers independently assessed trial quality and eligibility for inclusion.\\nMain results\\nTwo trials (255 preterm infants, 23 0/7 to 32 6/7 weeks of gestation) were included in the analysis. UCM was associated with fewer intraventricular hemorrhages (IVHs) (two trials, 255 infants; relative risk [RR] 0.45, 95% confidence interval [CI] 0.20 to 0.98, low quality of evidence) and UCM was an increased proportion of infants with a Bayley score at 2 years of age (two trials, 174 infants; Cognitive: RR 1.14, 95% CI 1.03 to 1.26, Language: RR 1.24, 95% CI 1.03 to 1.49, low quality of evidence) compared to DCC.\\nConclusions\\nUCM wasn't reduced in-hospital mortality and need for transfusion compared to DCC. But our study suggests that UCM may lower the risk of IVH and improve certain neurodevelopmental outcomes compared to DCC in preterm infants.

There has an increasing number of published trials on psychosocial intervention programmes for pre-school children with autism spectrum disorder (ASD). To achieve better quality of unbiased evidence for the effectiveness of ASD interventions, it is necessary to conduct a comprehensive review that covers studies with adequate quality standards, such as randomised controlled trials (RCTs), and different types of intervention In this study, we categorize interventions for ASD as behavioural, social-communication focused, and multimodal developmental based on Howlin's classification of early interventions for children with ASD. The aim of this study was to compare these three models and investigate the strengths and weaknesses of each type of intervention and to identify the approaches that contribute to a successful outcome for children with autism. We performed a systematic review and meta-analysis. We included RCTs targeting children with ASD 6 years old or younger. A random effects model was used to present the effect estimate for the outcomes. This study also performed combined meta-analyses of all the three models to investigate the overall effectiveness of the intervention programmes. 32 randomized controlled studies were found to be eligible for inclusion. The synthesized data included 594 children from 14 RCTs. There was no statistically significant difference in the effects on autism general symptoms between the social-communication-focused model and the multimodal developmental model (p = 0.83). The results suggest that there is evidence of an effect on 'reciprocity of social interaction towards others' (standard mean difference [95% confidential interval] = 0.53[0.29,0.78], p<0.01) and 'parental synchrony' (SMD = 0.99[0.70,1.29], p<0.01). The small number of studies included in the present study limited the ability to make inferences when comparing the three models and investigating the strengths and weaknesses of each type of intervention with respect to important outcomes. Since the outcome of 'reciprocity of social interaction towards others' could be a dependent variable that might be context-bound to interactions with the child's parent, we cannot conclude the interventions for pre-school children with ASD have significant effects on a generalized skill to engage in reciprocal interactions with others. However, the outcomes of 'reciprocity of social interaction towards others' and 'parental synchrony' may be promising targets for interventions involving pre-school children with ASD. Prospero CRD42011001349.

Early initiation of breastfeeding (EIBF) within 1 hour of birth can decrease neonatal death. However, the prevalence of EIBF is approximately 50% in many developing countries, and data remains unavailable for some countries. We conducted a secondary analysis using the WHO Global Survey on Maternal and Perinatal Health to identify factors hampering EIBF. We described the coverage of EIBF among 373 health facilities for singleton neonates for whom breastfeeding was initiated after birth. Maternal and facility characteristics of EIBF were compared to those of breastfeeding >1 hour after birth, and multiple logistic regression analysis was performed. In total, 244,569 singleton live births without severe adverse outcomes were analysed. The EIBF prevalence varied widely among countries and ranged from 17.7% to 98.4% (average, 57.6%). There was less intra-country variation for BFI <24 hours. After adjustment, EIBF was significantly lower among women with complications during pregnancy and caesarean delivery. Globally, EIBF varied considerably across countries. Maternal complications during pregnancy, caesarean delivery and absence of postnatal/neonatal care guidelines at hospitals may affect EIBF. Our findings suggest that to better promote EIBF, special support for breastfeeding promotion is needed for women with complications during pregnancy and those who deliver by caesarean section.

To study supplementation effect of vitamin K (VK) alone or combined with other nutrients administered to pregnant women, we searched Cochrane Pregnancy and Childbirth Group’s Trials Register (till 22 January 2016, updated on 28 February 2018) including other resources. Two review authors independently assessed randomised or quasi-randomised controlled trials for inclusion, data extraction, accuracy, and risk of bias. We included older trials from high-income countries (six; 21,493 women-newborns), judged mostly as high or unclear bias risk. We could not assess high-risk e.g. epileptic women, but healthy women (different gestational ages) received varying VK dosages and duration. We meta-analysed neonatal bleeding (RR 1.16, 95% CI 0.59 to 2.29; P  = 0.67) and maternal plasma VK1 (MD 2.46, 95% CI 0.98 to 3.93; P  = 0.001). We found many outcomes were un-assessed e.g. perinatal death, maternal bleeding, healthcare utilization. Mostly newborns were included where VK found significantly effective for e.g. serum VK (mother-newborn), maternal breast milk VK. Few trials reported neonatal adverse side effects. The GRADE evidence quality was very low i.e. neonatal bleeding, neonatal jaundice, maternal plasma VK1. The intervention was favourable for maternal sera VK1 but remained uncertain for neonatal bleeding and other outcomes. The existing literature gaps warrant future investigations on un-assessed or inadequately reported outcomes.

Japan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level. We used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations. Life expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from −32·4% (−34·8 to −30·0) to −22·0% (−20·4 to −20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015. Japan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment. Bill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund.

Since low birthweight has been correlated with both neonatal and long-term health, we performed this epidemiological study to evaluate the Japanese secular trends in mean birthweight and the prevalence of preterm/term low birthweight infants during the last three decades. We used population-based birth certificate data from January 1979 to December 2010. Time trends were analysed using a linear regression model. During the study period, we observed a significant decrease in the mean birthweight for singleton live births (3,152 ± 436 g in 1979 and 3,018 ± 421 g in 2010 p < 0.001) and an increase in the prevalence of preterm/term low birthweight infants. A 96.3% increase in the proportion of term low birthweight infants was observed during the study period (2.7% in 1979 and 5.3% in 2010). In addition, an increased proportion of preterm/low birthweight infants born to younger women was observed (<35 years vs. ≥35 years). These trends may be related to changing patterns in Japanese women’s nutritional status and the relatively strict recommended limit on weight gain during pregnancy. Understanding the long-term trends for singleton births may allow us to identify the associated risk factors and reduce the future socioeconomic burden that is associated with low birthweight infants.