Correction to: Predictors of survival of very preterm births (born between 23 and 29 weeks' gestation) at a tertiary care center in Karachi, Pakistan: additional multivariate analyses on data from primary cohort.

For better clarity, the author would like to amend the title of the original article [1].

High proportion of overt diabetes mellitus in pregnancy and missed opportunity for early detection of diabetes at a tertiary care centre in Pakistan.

OBJECTIVES: To determine the frequency of diabetes in pregnancy (DIP), namely pre-gestational, gestational (GDM) and overt diabetes mellitus (DM) in women registered for delivery. METHODS: A retrospective chart review of antenatal women registered between January 01 to August 31, 2017 was performed. Gestational age, diagnosis of DIP, glucose levels at diagnosis and other relevant data was extracted. The effect of various fasting blood glucose (FBG) thresholds for diagnosis of DIP was assessed. RESULTS: DIP was diagnosed in 21.8% women (pre-gestational: 2%, GDM: 81.2%, overt: DM: 16.8%). In early registrants, 30.2% were detected through screening. However, 55.3% of women registered late. Women with pre-gestational DM were older, had more miscarriages, and greater personal and family history of diabetes versus GDM and overt DM. Raising the diagnostic threshold of FBG from 92 mg/dl to 95 mg/dl missed three women (0.1%) and to 105 mg/dl, missed six women (0.2%). CONCLUSION: We observed a high proportion of overt DM. In early registrants, almost one third of DIP was diagnosed in the first half of pregnancy, an opportunity missed in late registrants. Altering diagnostic thresholds of DIP affected only a small proportion of women.

Predictors of survival of very preterm births (born between 23 and 29 weeks' gestation) at a tertiary care center in Karachi, Pakistan: additional multivariate analyses on data from primary cohort.

OBJECTIVE: Previously, we have published univariate analyses on a cohort of all singleton, very preterm infants (N = 101) born between 23 and 29 weeks of gestation during January 01, 1998 to June 30, 2003 at The Aga Khan University Hospital in Karachi, Pakistan. Our main objective was to extend these analyses to multivariate logistic regression models and report odds ratios (ORs) for univariate and multivariate analyses. All variables in univariate were included in multivariate models. RESULTS: The survival incidences were 0% at 23, 16.7% at 24, 40.0% at 25, 30.0% at 26, 33.3% at 27, 68.8% at 28 and 83.9% at 29 weeks of gestation. In univariate analyses, gestational age, birth-weight and mode of delivery (cesarean-section had higher survival compared to vaginal) were statistically significant predictors of survival (P ≤ 0.001 each). Other variables that also included antenatal steroids did not achieve significance. However, in complete-case multivariate analyses, only gestational age (per week) was associated with survival (OR = 2.5, 95% CI 1.1-5.5, P = 0.03); birth-weight (per 100 g) and C-section were not associated-1.2, 0.88-1.6, P = 0.26 and 2.4, 0.48-12.2, P = 0.28. Antenatal steroid use, maternal age, year of birth, parity, history of preterm delivery, hemoglobin levels, complications and time of birth remained not associated.

Promising Biomarkers of Environmental Enteric Dysfunction: A Prospective Cohort study in Pakistani Children.

Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkers associated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months. Fecal myeloperoxidase (neutrophil activation marker) at 6 months [ß = -0.207, p = 0.005], and serum GLP 2 (enterocyte proliferation marker) at 6 and 9 months [6M: ß = -0.271, p = 0.035; 9M: ß = -0.267, p = 0.045] were associated with decreasing LAZ score. Ferritin at 6 and 9 months was associated with decreasing LAZ score [6M: ß = -0.882, p < 0.0001; 9M: ß = -0.714, p < 0.0001] and so was CRP [ß = -0.451, p = 0.039] and AGP [ß = -0.443, p = 0.012] at 9 months. Both gut specific and systemic biomarkers correlated negatively with IGF-1, but only weakly correlated, if at all with each other. We therefore conclude that EED may be contributing directly towards growth faltering, and this pathway is not entirely through the pathway of systemic inflammation.

Vitamin A Supplementation for Prevention and Treatment of Malaria during Pregnancy and Childhood: A Systematic Review and Meta-analysis.

Animal studies have shown that vitamin A plays a role in immunity and protection against infectious diseases. Its role reducing incidence of diarrhea and measles, and childhood mortality is known, but its role in relation to malaria is unclear. Thus, a comprehensive, systematic literature search was conducted on PubMed and Cochrane Library to identify randomized controlled trials (RCTs) on the role of vitamin A during pregnancy and childhood for prevention and treatment of malaria. A total of 107 titles/abstracts were identified, of which 15 articles (11 studies) were selected for final inclusion. Based on the meta-analysis, vitamin A supplementation during pregnancy had no benefit for placental infection (relative risk = 1.09; 95% confidence interval (CI), 0.95-1.25; fixed effects, I2 = 0; 2 RCTs). Similarly, there was no effect on peripheral parasitemia or episodes of new clinical malaria. Preventive vitamin A supplementation in children younger than 5 years did not reduce the incidence of peripheral parasitemia or malaria mortality (latter rate ratio = 0.49; 95% CI, 0.07-3.26; random effects, I2 = 72%, 2 RCTs). Vitamin A as an adjunct treatment for cerebral or severe malaria in children did not have benefit on survival, fever resolution time, parasite clearance time, or incidence of neurological or other complications. Vitamin A has no benefit for malarial infection either as prevention or treatment in pregnancy or childhood based on RCT evidence.

Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.

BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke. METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses' Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis. RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results. CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.

Nutrition (Micronutrients) in Child Growth and Development: A Systematic Review on Current Evidence, Recommendations and Opportunities for Further Research.

OBJECTIVE: An important aspect of malnutrition is deficiency of different micronutrients during pregnancy or early childhood. We systematically reviewed the role of nutrition in child growth (weight or height gain) and development. METHODS: A comprehensive literature search was done on PubMed/Cochrane Library browsing through 38,795 abstracts until December 31, 2016 to select systematic reviews/meta-analyses and individual randomized controlled trials (RCTs) of micronutrient supplementation. RESULTS: Micronutrients studied included iron, iodine, folate, zinc, calcium, magnesium, selenium, vitamin D, vitamin A, vitamin B complex, and multiple micronutrients. We summarize evidence with details and results of RCTs, highlight strengths/weaknesses, and critically interpret findings. Effects of breastfeeding-promotion, food-supplementation (complementary and school feeding), conditional-cash-transfers, and integrated nutrition/psychosocial interventions are discussed. CONCLUSION: Based on this evidence we make policy and programmatic recommendations for supplementation to mothers and children at high-risk of deficiency.

Associations of Cigarette Smoking With Subclinical Inflammation and Atherosclerosis: ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health).

BACKGROUND: There is a need to identify sensitive biomarkers of early tobacco-related cardiovascular disease. We examined the association of smoking status, burden, time since quitting, and intensity, with markers of inflammation and subclinical atherosclerosis. METHODS AND RESULTS: We studied 14 103 participants without clinical cardiovascular disease in ELSA-Brasil (Brazilian Longitudinal Study of Adult Health). We evaluated baseline cross-sectional associations between smoking parameters and inflammation (high-sensitivity C-reactive protein [hsCRP]) and measures of subclinical atherosclerosis (carotid intima-media thickness, ankle-brachial index, and coronary artery calcium [CAC]). The cohort included 1844 current smokers, 4121 former smokers, and 8138 never smokers. Mean age was 51.7±8.9 years; 44.8% were male. After multivariable adjustment, compared with never smokers, current smokers had significantly higher levels of hsCRP (ß=0.24, 0.19-0.29 mg/L; P<0.001) and carotid intima-media thickness (ß=0.03, 0.02-0.04 mm; P<0.001) and odds of ankle-brachial index ≤1.0 (odds ratio: 2.52; 95% confidence interval, 2.06-3.08; P<0.001) and CAC >0 (odds ratio: 1.83; 95% confidence interval, 1.46-2.30; P<0.001). Among former and current smokers, pack-years of smoking (burden) were significantly associated with hsCRP (P<0.001 and P=0.006, respectively) and CAC (P<0.001 and P=0.002, respectively). Among former smokers, hsCRP and carotid intima-media thickness levels and odds of ankle-brachial index ≤1.0 and CAC >0 were lower with increasing time since quitting (P<0.01). Among current smokers, number of cigarettes per day (intensity) was positively associated with hsCRP (P<0.001) and CAC >0 (P=0.03) after adjusting for duration of smoking. CONCLUSIONS: Strong associations were observed between smoking status, burden, and intensity with inflammation (hsCRP) and subclinical atherosclerosis (carotid intima-media thickness, ankle-brachial index, CAC). These markers of early cardiovascular disease injury may be used for the further study and regulation of traditional and novel tobacco products.

Impact of Nonoptimal Intakes of Saturated, Polyunsaturated, and Trans Fat on Global Burdens of Coronary Heart Disease.

BACKGROUND: Saturated fat (SFA), ω-6 (n-6) polyunsaturated fat (PUFA), and trans fat (TFA) influence risk of coronary heart disease (CHD), but attributable CHD mortalities by country, age, sex, and time are unclear. METHODS AND RESULTS: National intakes of SFA, n-6 PUFA, and TFA were estimated using a Bayesian hierarchical model based on country-specific dietary surveys; food availability data; and, for TFA, industry reports on fats/oils and packaged foods. Etiologic effects of dietary fats on CHD mortality were derived from meta-analyses of prospective cohorts and CHD mortality rates from the 2010 Global Burden of Diseases study. Absolute and proportional attributable CHD mortality were computed using a comparative risk assessment framework. In 2010, nonoptimal intakes of n-6 PUFA, SFA, and TFA were estimated to result in 711 800 (95% uncertainty interval [UI] 680 700-745 000), 250 900 (95% UI 236 900-265 800), and 537 200 (95% UI 517 600-557 000) CHD deaths per year worldwide, accounting for 10.3% (95% UI 9.9%-10.6%), 3.6%, (95% UI 3.5%-3.6%) and 7.7% (95% UI 7.6%-7.9%) of global CHD mortality. Tropical oil-consuming countries were estimated to have the highest proportional n-6 PUFA- and SFA-attributable CHD mortality, whereas Egypt, Pakistan, and Canada were estimated to have the highest proportional TFA-attributable CHD mortality. From 1990 to 2010 globally, the estimated proportional CHD mortality decreased by 9% for insufficient n-6 PUFA and by 21% for higher SFA, whereas it increased by 4% for higher TFA, with the latter driven by increases in low- and middle-income countries. CONCLUSIONS: Nonoptimal intakes of n-6 PUFA, TFA, and SFA each contribute to significant estimated CHD mortality, with important heterogeneity across countries that informs nation-specific clinical, public health, and policy priorities.

The impact of dietary habits and metabolic risk factors on cardiovascular and diabetes mortality in countries of the Middle East and North Africa in 2010: a comparative risk assessment analysis.

OBJECTIVE/DESIGN: We conducted a comparative risk assessment analysis to estimate the cardiometabolic disease (CMD) mortality attributable to 11 dietary and 4 metabolic risk factors in 20 countries of the Middle East by age, sex and time. The national exposure distributions were obtained from a systematic search of multiple databases. Missing exposure data were estimated using a multilevel Bayesian hierarchical model. The aetiological effect of each risk factor on disease-specific mortality was obtained from clinical trials and observational studies. The number of disease-specific deaths was obtained from the 2010 Global Burden of Disease mortality database. Mortality due to each risk factor was determined using the population attributable fraction and total number of disease-specific deaths. SETTING/POPULATION: Adult population in the Middle East by age, sex, country and time. RESULTS: Suboptimal diet was the leading risk factor for CMD mortality in 11 countries accounting for 48% (in Morocco) to 72% (in the United Arab Emirates) of CMD deaths. Non-optimal systolic blood pressure was the leading risk factor for CMD deaths in eight countries causing 45% (in Bahrain) to 68% (in Libya) of CMD deaths. Non-optimal body mass index and fasting plasma glucose were the third and fourth leading risk factors for CMD mortality in most countries. Among individual dietary factors, low intake of fruits accounted for 8% (in Jordan) to 21% (in Palestine) of CMD deaths and low intake of whole grains was responsible for 7% (in Palestine) to 22% (in the United Arab Emirates) of CMD deaths. Between 1990 and 2010, the CMD mortality attributable to most risk factors had decreased except for body mass index and trans-fatty acids. CONCLUSIONS: Our findings highlight key similarities and differences in the impact of the dietary and metabolic risk factors on CMD mortality in the countries of the Middle East and inform priorities for policy measures to prevent CMD.

The interconnections between maternal and newborn health--evidence and implications for policy.

The past decade has witnessed increasing global attention and political support for maternal, newborn and child health. Despite this increased attention, actual progress has been slow and sporadic: coverage of key maternal and newborn health interventions remains low and there are wide disparities in access to care, within and across countries. Strategies for improving maternal and newborn health are closely linked, and can be delivered most effectively through a continuum of care approach. While these interventions are largely known, there is little information on which interventions have a positive health impact for both women and newborns. This supplement identifies the interventions during the preconception, pregnancy, intrapartum and postnatal periods found to have a positive, synergistic effect on maternal and neonatal outcomes. These interventions are then grouped into packages of care for delivery at the community, health center or hospital levels.

Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis.

OBJECTIVE: To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. DESIGN: Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or ß carotene were excluded. RESULTS: 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). CONCLUSIONS: Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.

Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths.

BACKGROUND: There is a strong association between stillbirth and fetal growth restriction. Early detection and management of IUGR can lead to reduce related morbidity and mortality. In this paper we have reviewed effectiveness of fetal movement monitoring and Doppler velocimetry for the detection and surveillance of high risk pregnancies and the effect of this on prevention of stillbirths. We have also reviewed effect of maternal body mass index (BMI) screening, symphysial-fundal height measurement and targeted ultrasound in detection and triage of IUGR in the community. METHODS: We systematically reviewed all published literature to identify studies related to our interventions. We searched PubMed, Cochrane Library, and all World Health Organization Regional Databases and included publications in any language. Quality of available evidence was assessed using GRADE criteria. Recommendations were made for the Lives Saved Tool (LiST) based on rules developed by the Child Health Epidemiology Group. Given the paucity of evidence related to the effect of detection and management of IUGR on stillbirths, we undertook Delphi based evaluation from experts in the field. RESULTS: There was insufficient evidence to recommend against or in favor of routine use of fetal movement monitoring for fetal well being. (1) Detection and triage of IUGR with the help of (1a) maternal BMI screening, (1b) symphysial-fundal height measurement and (1c) targeted ultrasound can be an effective method of reducing IUGR related perinatal morbidity and mortality. Pooled results from sixteen studies shows that Doppler velocimetry of umbilical and fetal arteries in 'high risk' pregnancies, coupled with the appropriate intervention, can reduce perinatal mortality by 29 % [RR 0.71, 95 % CI 0.52-0.98]. Pooled results for impact on stillbirth showed a reduction of 35 % [RR 0.65, 95 % CI 0.41-1.04]; however, the results did not reach the conventional limits of statistical significance. This intervention could be potentially recommended for high income settings or middle income countries with improving rates and standards of facility based care. Based on the Delphi, a combination of screening with maternal BMI, Symphysis fundal height and targeted ultrasound followed by the appropriate management could potentially reduce antepartum and intrapartum stillbirth by 20% respectively. This estimate is presently being recommended for inclusion in the LiST. CONCLUSION: There is insufficient evidence to recommend in favor or against fetal movement counting for routine use for testing fetal well being. Doppler velocimetry of umbilical and fetal arteries and appropriate intervention is associated with 29 % (95 % CI 2% to 48 %) reduction in perinatal mortality. Expert opinion suggests that detection and management of IUGR with the help of maternal BMI, symphysial-fundal height measurement and targeted ultrasound could be effective in reducing IUGR related stillbirths by 20%.

Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes.

OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ≥ 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ≥ 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.

Effect of screening and management of diabetes during pregnancy on stillbirths.

BACKGROUND: Diabetes during pregnancy is associated with significant risk of complications to the mother, fetus and newborn. We reviewed the potential impact of early detection and control of diabetes mellitus during pregnancy on stillbirths for possible inclusion in the Lives Saved Tool (LiST). METHODS: A systematic literature search up to July 2010 was done to identify all published randomized controlled trials and observational studies. A standardized data abstraction sheet was employed and data were abstracted by two independent authors. Meta-analyses were performed with different sub-group analyses. The analyses were graded according to the CHERG rules using the adapted GRADE criteria and recommendations made after assessing the overall quality of the studies included in the meta-analyses. RESULTS: A total of 70 studies were selected for data extraction including fourteen intervention studies and fifty six observational studies. No randomized controlled trials were identified evaluating early detection of diabetes mellitus in pregnancy versus standard screening (glucose challenge test between 24th to 28th week of gestation) in pregnancy. Intensive management of gestational diabetes (including specialized dietary advice, increased monitoring and tailored dietary therapy) during pregnancy (3 studies: 3791 participants) versus conventional management (dietary advice and insulin as required) was associated with a non-significant reduction in the risk of stillbirths (RR 0.20; 95% CI: 0.03-1.10) ('moderate' quality evidence). Optimal control of serum blood glucose versus sub-optimal control was associated with a significant reduction in the risk of perinatal mortality (2 studies, 5286 participants: RR = 0.40, 95% CI 0.25- 0.63), but not stillbirths (3 studies, 2469 participants: RR = 0.51, 95% CI 0.14-1.88). Preconception care of diabetes (information about need for optimization of glycemic control before pregnancy, assessment of diabetes complications, review of dietary habits, intensification of capillary blood glucose self-monitoring and optimization of insulin therapy) versus none (3 studies: 910 participants) was associated with a reduction in perinatal mortality (RR = 0.29, 95% CI 0.14 -0.60). Using the Delphi process for estimating effect size of optimal diabetes recognition and management yielded a median effect size of 10% reduction in stillbirths. CONCLUSIONS: Diabetes, especially pre-gestational diabetes with its attendant vascular complications, is a significant risk factor for stillbirth and perinatal death. Our review highlights the fact that very few studies of adequate quality are available that can provide estimates of the effect of screening for aid management of diabetes in pregnancy on stillbirth risk. Using the Delphi process we recommend a conservative 10% reduction in the risk of stillbirths, as a point estimate for inclusion in the LiST.

Impact of vitamin A supplementation on infant and childhood mortality.

INTRODUCTION: Vitamin A is important for the integrity and regeneration of respiratory and gastrointestinal epithelia and is involved in regulating human immune function. It has been shown previously that vitamin A has a preventive effect on all-cause and disease specific mortality in children under five. The purpose of this paper was to get a point estimate of efficacy of vitamin A supplementation in reducing cause specific mortality by using Child Health Epidemiology Reference Group (CHERG) guidelines. METHODS: A literature search was done on PubMed, Cochrane Library and WHO regional data bases using various free and Mesh terms for vitamin A and mortality. Data were abstracted into standardized forms and quality of studies was assessed according to standardized guidelines. Pooled estimates were generated for preventive effect of vitamin A supplementation on all-cause and disease specific mortality of diarrhea, measles, pneumonia, meningitis and sepsis. We did a subgroup analysis for vitamin A supplementation in neonates, infants 1-6 months and children aged 6-59 months. In this paper we have focused on estimation of efficacy of vitamin A supplementation in children 6-59 months of age. Results for neonatal vitamin A supplementation have been presented, however no recommendations are made as more evidence on it would be available soon. RESULTS: There were 21 studies evaluating preventive effect of vitamin A supplementation in community settings which reported all-cause mortality. Twelve of these also reported cause specific mortality for diarrhea and pneumonia and six reported measles specific mortality. Combined results from six studies showed that neonatal vitamin A supplementation reduced all-cause mortality by 12 % [Relative risk (RR) 0.88; 95 % confidence interval (CI) 0.79-0.98]. There was no effect of vitamin A supplementation in reducing all-cause mortality in infants 1-6 months of age [RR 1.05; 95 % CI 0.88-1.26]. Pooled results for preventive vitamin A supplementation showed that it reduced all-cause mortality by 25% [RR 0.75; 95 % CI 0.64-0.88] in children 6-59 months of age. Vitamin A supplementation also reduced diarrhea specific mortality by 30% [RR 0.70; 95 % CI 0.58-0.86] in children 6-59 months. This effect has been recommended for inclusion in the Lives Saved Tool. Vitamin A supplementation had no effect on measles [RR 0.71, 95% CI: 0.43-1.16], meningitis [RR 0.73, 95% CI: 0.22-2.48] and pneumonia [RR 0.94, 95% CI: 0.67-1.30] specific mortality. CONCLUSION: Preventive vitamin A supplementation reduces all-cause and diarrhea specific mortality in children 6-59 months of age in community settings in developing countries.