Effects of calcium supplementation during pregnancy on maternal, fetal and birth outcomes

Gestational hypertensive disorders are the second leading cause of maternal death worldwide. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal morbidity and mortality. A literature search was carried out on PubMed, WHOLIS, PAHO and Cochrane Library. Only randomised trials were included in the review. Data were extracted into a standardised Excel sheet. Primary outcomes were pre-eclampsia, preterm birth and birthweight. Other neonatal outcomes such as neonatal mortality, small-for-gestational age and low birthweight were also evaluated. A total of 15 randomised controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy reduced risk of pre-eclampsia by 52% [relative risk (RR) 0.48; 95% confidence interval (CI) 0.34, 0.67] and that of severe pre-eclampsia by 25% (RR 0.75 [95% CI 0.57, 0.98]). There was no effect on incidence of eclampsia (RR 0.73 [95% CI 0.41, 1.27]). There was a significant reduction for risk of maternal mortality/severe morbidity (RR 0.80 [95% CI 0.65, 0.97]). Calcium supplementation during pregnancy was also associated with a significant reduction in risk of pre-term birth (RR 0.76 [95% CI 0.60, 0.97]). There was an extra gain of 85 g in the intervention group compared with control (mean difference 85 g [95% CI 37, 133]). There was no effect of calcium supplementation on perinatal mortality (RR 0.90 [95% CI 0.74, 1.09]). There was a statistically non-significant increased risk of urolithiasis in the intervention group compared with control (RR 1.52 [95% CI 0.06, 40.67]). In conclusion, calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertensive disorders and pre-term birth and an increase in birthweight. There is no increased risk of kidney stones.     

Routine iron/folate supplementation during pregnancy: effect on maternal anaemia and birth outcomes

Iron deficiency is the most common nutritional deficiency globally. Children and women of reproductive age are at a particular risk of iron deficiency. Anaemia during pregnancy is a specific risk factor for adverse maternal and perinatal outcomes. The objective of this review was to assess the impact of routine iron supplementation on maternal anaemia and perinatal outcomes. A literature search was conducted for published randomised and quasi-randomised trials on PubMed and the Cochrane Library. Only those studies were included in the review that assessed the preventive effect of iron supplementation during pregnancy. Data from selected studies were double abstracted in a standardised excel sheet. The studies were graded according to study design, limitations, intervention specifics and outcome effects. Meta-analyses were conducted where data were available from more than one study for an outcome. After screening 5209 titles, 30 studies were selected for inclusion in this review. Daily iron supplementation resulted in 69% reduction in incidence of anaemia at term in the intervention group compared with control [relative risk (RR) 0.31 [95% confidence interval (CI) 0.22, 0.44]] and 66% reduction in iron deficiency anaemia at term (RR 0.44 [95% CI 0.28, 0.68]; random model) compared with no intervention/placebo. The quality grade for these outcomes was that of 'moderate' level. Routine daily iron supplementation during pregnancy resulted in a significant reduction of 20% in incidence of low birthweight in the intervention group compared with control (RR 0.80 [95% CI 0.71, 0.90]). Preventive iron supplementation during pregnancy has a significant benefit in reducing incidence of anaemia in mothers and low birthweight in neonates.     

Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review

Supplementation with multiple micronutrients (MM) during pregnancy may result in improved pregnancy and infant outcomes. We conducted meta-analyses of randomised controlled trials that evaluated the effects of prenatal supplementation with MM (defined as containing at least five micronutrients and typically included iron or iron and folic acid). The outcomes of interest were low birthweight (<2500 g), birthweight, small-for-gestational age (SGA), gestational age, preterm birth (<37 weeks' gestation), stillbirth and neonatal death, maternal morbidity and mortality. We identified eligible studies through PubMed and EMBASE database searches. Meta-analyses were performed by pooling results for outcomes that were reported from more than one trial and sub-analyses were conducted to evaluate the effect of timing of intervention and amount of iron. We included published results from 16 trials in this review. Compared with control supplementation that was usually iron plus folic acid in most studies, MM supplementation resulted in a significant reduction in the incidence of low birthweight [pooled risk ratio (RR) 0.86; 95% confidence interval (CI) 0.81, 0.91] and SGA (pooled RR 0.83 [95% CI 0.73, 0.95]) and an increase in mean birthweight (weighted mean difference (WMD) 52.6 g [95% CI 43.2 g, 62.0 g]). There was no significant difference in the overall risk of preterm birth, stillbirth, and maternal or neonatal mortality, but we found an increased risk of neonatal death for the MM group compared with iron-folate in the subgroup of five trials that began the intervention after the first trimester (RR 1.38 [95% CI 1.05, 1.81]). None of the studies evaluated maternal morbidity. Compared with iron plus folic acid supplementation alone, prenatal maternal supplementation with MM resulted in a reduction in the incidence of low birthweight and SGA but increased risk of neonatal death in the subgroup of studies that began the intervention after the first trimester.     

Is conception delay a risk factor for reduced gestation or birthweight?

Previous studies have suggested an association between delays in conception and adverse perinatal outcomes, specifically, low birthweight and preterm birth. We investigated the relationship between conception delay (defined as >6 months to become pregnant) and three perinatal outcomes: low birthweight (LBW; <2500 g), preterm birth (PTB; <37 weeks), and small-for-gestational-age (SGA; <10th percentile weight for given gestational age) using data from the Collaborative Perinatal Project. The study cohort was limited to pregnancies with a known time-to-pregnancy (n = 8465; 15%). Generalised estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals [CI] for risk of adverse perinatal outcomes accounting for the clustering of pregnancy outcomes for women with more than one pregnancy. After adjusting for confounders, all ORs were close to the null (LBW, OR = 1.01; 95% CI = 0.86, 1.20), (PTB, OR = 1.10; 95% CI = 0.95, 1.27), (SGA, OR = 1.06; 95% CI = 0.91, 1.25). Thus, we found no evidence to support an adverse relationship between conception delay and decrements in gestation or birthweight among this select sample of fertile women, even after varying the cut-point for defining conception delay.     

Evidence for an association between environmental tobacco smoke exposure and birthweight: a meta-analysis and new data

Because of the strong association of active smoking with fetal growth retardation, increasing interest has focused on whether there is also an association with exposure to environmental tobacco smoke (ETS). We examined this issue in a retrospective study and by conducting a review of the literature and data pooling. In our study, nonsmoking women with singleton livebirths born in 1986–87 ( n  = 992) provided information on exposure to ETS for 1 h or more per day and paternal smoking. The risk of low birthweight (LBW, < 2500 g) was not increased in infants of ETS-exposed women, but there was a somewhat increased risk for LBW at term (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.6, 4.8) and small-for-gestational-age (< 10th percentile of weight; OR = 1.4, 95% CI = 0.8, 2.5). These results were in the range of 16 other studies in the literature that had odds ratios from 1.0 to 2.2. A weighted average of the results of all studies on LBW at term or small-for-gestational-age yielded a pooled estimate of 1.2 [95% CI = 1.1, 1.3] in nonsmoking women. The pooled estimate of mean birthweight indicated a decrement of 28 g with ETS exposure of nonsmoking women [95% CI = −41, −16], with a greater decrement (about 40 g) seen among more homogeneous studies.     

Effect of n-3 long-chain polyunsaturated fatty acid intake during pregnancy on maternal, infant, and child health outcomes: a systematic review

Evidence from observational studies and randomised trials has suggested a potential association between intake of n-3 long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy and certain pregnancy and birth outcomes. Marine foods (e.g. fatty sea fish, algae) and select freshwater fish contain pre-formed n-3 LCPUFA, which serve as precursors for bioactive molecules (e.g. prostaglandins) that influence a variety of biological processes. The main objective of this analysis was to summarise evidence of the effect of n-3 LCPUFA intake during pregnancy on select maternal and child health outcomes. Searches were performed in PubMed, EMBASE, and other electronic databases to identify trials where n-3 LCPUFA were provided to pregnant women for at least one trimester of pregnancy. Data were extracted into a standardised abstraction table and pooled analyses were conducted using RevMan software. Fifteen randomised controlled trials were eligible for inclusion in the meta-analysis, and 14 observational studies were included in the general review. n-3 LCPUFA supplementation during pregnancy resulted in a modest increase in birthweight (mean difference = 42.2 g; [95% CI 14.8, 69.7]) and no significant differences in birth length or head circumference. Women receiving n-3 LCPUFA had a 26% lower risk of early preterm delivery (<34 weeks) (RR = 0.74; [95% CI 0.58, 0.94]) and there was a suggestion of decreased risk of preterm delivery (RR = 0.91; [95% CI 0.82, 1.01]) and low birthweight (RR = 0.92; [95% CI 0.83, 1.02]). n-3 LCPUFA in pregnancy did not influence the occurrence of pre-eclampsia, high blood pressure, infant death, or stillbirth. Our review of observational studies revealed mixed findings, with several large studies reporting positive associations between fish intake and birthweight and several reporting no associations. In conclusion, n-3 LCPUFA supplementation during pregnancy resulted in a decreased risk of early preterm delivery and a modest increase in birthweight. More studies in low- and middle-income countries are needed to determine any effect of n-3 LCPUFA supplementation in resource-poor settings, where n-3 PUFA intake is likely low.     

Birth outcomes associated with prenatal participation in a government support programme for mothers with low incomes

Background Women with low incomes are at higher risk to have low‐birthweight (LBW) babies and less likely to participate in prenatal support programmes than women with higher incomes. This study examined birth outcomes among participants in the Newfoundland and Labrador Mother‐Baby Nutrition Supplement (MBNS), a prenatal programme for women with low incomes that provides a monthly financial supplement and printed information on infant health and development, along with a referral to public health nursing services. Methods Application data (e.g. mother's age, education) for those who applied between August 2002 and December 2004 were obtained from the Provincial Government. Birth outcomes (e.g. birthweight, weeks of gestation) were available for 1599 women. Of these, 862 were parity zero and subsequently delivered full‐term infants. Comparisons were made on demographics, timeliness of enrolment and rates of full‐term LBW. Results Participants were more often single, younger and less educated than the average woman who gave birth in the Province or Canada in 2004. Women enrolled early were less likely to have a full‐term LBW baby than those enrolled late (χ²₍₁₎= 4.03, P= 0.045). Mothers enrolled late had a higher rate of full‐term LBW than was the case in the Province [risk ratio (RR) = 2.76, 95% confidence interval (CI) = 1.61?4.74] and Canada (RR = 2.53, 95% CI = 1.55?4.21) whereas those enrolled earlier, despite increased risk due to low income, age and education, single status and zero parity, had rates of full‐term LBW on par with the Province (RR = 1.29, 95% CI = 0.71?2.32) and Canada (RR = 1.19, 95% CI = 0.68?2.08). Conclusion The MBNS is an effective intervention for improving birth outcomes in women considered at risk. The challenge is to enrol pregnant women as early as possible. Future research will examine what programme component or combination of components (e.g. financial, information, referral) affects birth outcomes.     

Maternal night blindness during pregnancy is associated with low birthweight, morbidity, and poor growth in South India

Maternal night blindness is common during pregnancy in many developing countries. Previous studies have demonstrated important consequences of maternal night blindness during pregnancy on the health of the mother and newborn infant. We compared birthweight, 6-mo infant mortality, morbidity, and growth among infants of women who did and did not report a history of night blindness from a community-based, randomized trial of newborn vitamin A supplementation in south India. Birthweight was measured within 72 h of delivery. Infants were followed until 6 mo of age for mortality and morbidity was assessed at household visits every 2 wk. Anthropometry was assessed at 6 mo of age. A total of 12,829 live-born infants were included, 680 of whom were infants of mothers with night blindness during the index pregnancy. Maternal night blindness was associated with an increased risk of low birthweight in a dose-dependent fashion based on birthweight cut-offs: <2500 g, adjusted relative risk (RR) = 1.13 (95% CI = 1.01, 1.26); <2000 g, adjusted RR = 1.70 (95% CI = 1.27, 2.26); <1500 g, adjusted RR = 3.38 (95% CI = 1.18, 6.33); with an increased risk of diarrhea (adjusted RR = 1.16, 95% CI = 1.03, 1.30), dysentery (adjusted RR = 1.25, 95% CI = 1.03, 1.53), acute respiratory illness (adjusted RR = 1.32, 95% CI = 1.21, 1.44), and poor growth at 6 mo; underweight (adjusted RR = 1.14, 95% CI = 1.02, 1.26), stunting (adjusted RR = 1.19, 95% CI = 1.05, 1.34). Maternal night blindness was not associated with 6-mo infant mortality or wasting at 6 mo. This study demonstrates that there are important consequences to the infant of maternal vitamin A deficiency during pregnancy.     

Antihelminthics in pregnancy and maternal, newborn and child health

Soil-transmitted helminths (STHs), primarily Ascaris, Trichuris and hookworm, inflict a substantial morbidity burden on poor populations living in tropical and subtropical regions. Chronic STH infections can cause intestinal blood loss and nutrient loss and/or malabsorption, which can result in or exacerbate iron deficiency, anaemia and other nutritional deficiencies. More than 1 billion people are infected with at least one STH, and at least 44 million pregnant women are infected with hookworm alone. Pregnant women are especially vulnerable to the harmful consequences of these parasitic infections due to increased nutritional demands during pregnancy. We aimed to determine the effect of antihelminthics in pregnancy on maternal, newborn and child health (MNCH) outcomes. A systematic review was conducted using online databases, and relevant articles were hand searched. We included four observational studies in the general review and four randomised controlled trials (RCTs) in the meta-analysis (total n = 3777 for the meta-analysis). Antihelminthics in pregnancy had no overall benefit on maternal anaemia [risk ratio (RR) = 0.93 [95% confidence interval (CI) 0.79, 1.10]], low birthweight (RR = 0.96 [95% CI 0.72, 1.29]) or perinatal mortality (RR = 0.98 [95% CI 0.58, 1.68]). The risk of very low birthweight was lower in the antihelminthics group (RR = 0.21 [95% CI 0.05, 0.83]); however, this estimate included data from only two trials (total n = 1936). In all four trials, antihelminthics in pregnancy significantly decreased the prevalence of STH infection. Three observational studies showed that antihelminthics in pregnancy improved maternal iron status, two studies reported beneficial effects on birthweight, and two studies found a beneficial effect on infant survival. Although few RCTs to date have failed to collectively demonstrate a clear beneficial impact of antihelminthics in pregnancy on maternal, newborn and child health outcomes, findings from observational studies suggest a potential benefit on maternal anaemia, birthweight and infant mortality. This meta-analysis was limited by a dearth of evidence from RCTs, and further trials examining the effect of antihelminthics starting in the second trimester of pregnancy in poor, STH-endemic regions with high rates of anaemia are needed.     

Preconception hemoglobin and ferritin concentrations are associated with pregnancy outcome in a prospective cohort of Chinese women

Prenatal anemia and iron deficiency are associated with adverse birth outcomes, but no previous studies have examined the relation between preconception anemia, iron deficiency, and pregnancy outcome in healthy women. We measured hemoglobin (Hb), ferritin, transferrin receptor (TfR), and vitamins B-6, B-12, and folate concentrations before pregnancy in 405 Chinese women (median time from sample collection to gestation end = 316 d). Both mild (95 /=60 microg/L) ferritin were also significantly associated with lower birthweight (106 and 123 g, respectively). The risks of low birthweight (LBW) and fetal growth restriction (FGR) were significantly greater among women with moderate anemia compared with nonanemic controls [odds ratio (OR): 6.5; 95% CI: 1.6, 26.7; P = 0.009 and OR: 4.6; 95% CI: 1.5, 13.5; P = 0.006, respectively]. TfR and low ferritin were not associated with adverse birth outcome, but elevated ferritin, which could be a marker of inflammation, was associated with increased risk of LBW (OR: 2.2; 95% CI: 0.9, 5.7; P = 0.09) and FGR (OR: 2.7; 95% CI: 1.3, 5.6; P = 0.008). Preconception anemia, particularly iron-deficiency anemia, was associated with reduced infant growth and increased risk of adverse pregnancy outcome in Chinese women.     

Weight loss during pregnancy is associated with adverse pregnancy outcomes among HIV-1 infected women

In a prospective study of 1002 pregnant, HIV-1 infected Tanzanian women, we examined the incidence of fetal death, preterm delivery, low birth weight (LBW), and small for gestational age (SGA) births in relation to maternal anthropometry at the first prenatal visit, weight loss, and low weight gain during pregnancy. Anthropometric measurements were obtained monthly during the 2nd and 3rd trimesters. Low maternal height and weight at the first visit were significantly related to lower mean birth weight and increased risk of SGA, but not to preterm delivery. Maternal stature < 150 cm was significantly related to fetal death. Weight loss during pregnancy, defined as a negative slope of the regression of weight measurements on the week of gestation, occurred in 10% of the women. It was related to increased relative risk (RR) of fetal death (RR = 1.83, 95% CI = 0.93, 3.57), preterm delivery (RR = 1.85, 95% CI = 1.40, 2.44), and LBW (RR = 2.85, 95% CI = 1.69, 4.79) after adjusting for multivitamin supplementation, height, primiparity, baseline weight, malaria, CD4 cell count, HIV disease stage, and intestinal parasitoses. The significant association with fetal death was stronger for weight loss during the 2nd trimester, whereas increased risks of preterm delivery and LBW were higher for weight loss during the 3rd. Similar but weaker associations were found with low weight gain during pregnancy (slope < 25th percentile). We conclude that poor anthropometric status at the first prenatal visit and weight loss during pregnancy among HIV-1 infected women are strong risk factors for adverse pregnancy outcomes.     

Population‐attributable risk of low birthweight related to PM10 pollution in seven Korean cities

Seo J‐H, Leem J‐H, Ha E‐H, Kim O‐J, Kim B‐M, Lee J‐Y, Park H‐S, Kim H‐C, Hong Y‐C, Kim Y‐J. Population‐attributable risk of low birthweight related to PM₁₀ pollution in seven Korean cities. Paediatric and Perinatal Epidemiology 2010; 24: 140–148. To understand the preventable fraction of low birthweight (LBW) deliveries due to maternal exposure to air pollution during pregnancy in Korea, it is important to quantify the population‐attributable risk (PAR). Thus, we investigated the association between maternal exposure to air pollution during pregnancy and LBW, and calculated the PAR for air pollution and LBW in seven Korean cities. We used birth records from the Korean National Birth Register for 2004. A geographic information system and kriging methods were used to construct exposure models. Associations between air pollution and LBW were evaluated using univariable and multivariable logistic regression, and the PAR for LBW due to air pollution was calculated. Of 177 660 full‐term singleton births, 1.4% were LBW. When only spatial variation of air pollution was considered in each city, the adjusted odds ratios unit of particulate matter <10 µm in diameter (PM₁₀) for LBW were 1.08 [95% confidence interval [CI] 0.99, 1.18] in Seoul, 1.24 [95% CI 1.02, 1.52] in Pusan, 1.19 [95% CI 1.04, 1.37] in Daegu, 1.12 [95% CI 0.98, 1.28] in Incheon, 1.22 [95% CI 0.98, 1.52] in Kwangju, 1.05 [95% CI 1.00, 1.11] in Daejeon and 1.19 [95% CI 1.03, 1.38] in Ulsan. The PARs for LBW attributable to maternal PM₁₀ exposure during pregnancy were 7%, 19%, 16%, 11%, 18%, 5% and 16% respectively. Because a large proportion of pregnant women in Korea are exposed to PM₁₀– which is associated with LBW – a substantial proportion of LBW could be prevented in Korea if air pollution was reduced.     

Incidence of and socio-demographic risk factors for stillbirth, preterm birth and low birthweight among Zimbabwean women

Data on birth outcomes are important for planning maternal and child health care services in developing countries. Only a few studies have examined frequency of birth outcomes in Zimbabwe, none of which has jointly examined the spectrum of poor birth outcomes across important demographic subgroups. We assessed delivery patterns and birth outcomes in 17 174 births over a one-year period from October 1997 to September 1998 at Harare Hospital, Zimbabwe. The annual rate of stillbirth was 61 per 1000 live births, rate of preterm birth (<37 weeks) was 168 per 1000, and low birthweight (LBW) (<2500 g) was 199 per 1000. Not attending antenatal care (prenatal care) was associated with increased risks of stillbirth [relative risk (RR) = 2.54, 95% CI 2.21, 2.92], preterm delivery [RR = 2.43, 95% CI 2.26, 2.61] and LBW births [RR = 2.16, 95% CI 2.02, 2.31]. Preterm births and LBW births were more likely to be stillborn [RR = 7.26, 95% CI 6.28, 8.39 and RR = 6.85, 95% CI 5.94, 7.91]. In conclusion, the rate of stillbirth is high and is predominantly associated with preterm births and to a lesser extent LBW. Reducing the frequency of stillbirth will require a better understanding of the determinants of preterm births and strategies for addressing this particular subset of high-risk births.     

Risks of induction of labour in uncomplicated term pregnancies

Our objective was to evaluate the risks of maternal and perinatal morbidity associated with induction of labour in uncomplicated term pregnancies. We conducted a retrospective cohort study including 7,430 women, not referred from another institution, with a single baby in vertex presentation, and delivering between 38 and 40 weeks of pregnancy. Among these women, 3,546 were excluded for prelabour pregnancy complications. Relative risks (RR), adjusted for parity, were computed to compare 3,353 women who went into labour spontaneously with 531 women whose labour was induced. Induction of labour was found to be associated with a higher risk of caesarean section [RR = 2.4, 95% CI 1.8, 3.4]. Use of non-epidural [RR = 1.5, 95% CI 1.2, 1.8] and of epidural analgesia [RR = 1.4, 95% CI 1.1, 1.7] was more frequent after labour induction. Resuscitation [RR = 1.2, 95% CI 1.0, 1.5], admission to the intensive care unit [RR = 1.6, 95% CI 1.0, 2.4] and phototherapy [RR = 1.3, 95% CI 1.0, 1.6] were more frequent after induction of labour. Results were similar when controlling simultaneously for parity, maternal age, gestational age, year of delivery, birthweight and the physician in charge of delivery in a logistic regression analysis. The results of this study suggests that induction of labour is associated with a higher risk of caesarean section and of some perinatal adverse outcomes. Induction of labour should be reserved for cases where maternal and perinatal benefits outweigh the risk of these complications.     

Chloroquine prophylaxis, iron-folic acid supplementation or case management of malaria attacks in primigravidae in western Uganda: effects on maternal parasitaemia and haemoglobin levels and on birthweight

The effects of weekly chloroquine prophylaxis, daily iron-weekly folic acid supplementation or passive case management on maternal haemoglobin and parasitaemia and on birthweight were examined in primigravidae in a randomized, double-blind placebo-controlled intervention trial in 1996-98 in Hoima District, western Uganda. Iron-folic acid supplementation significantly increased mean birthweight as compared to case management (P = 0.03). Low birthweight (< 2.5 kg) occurred in 2% of babies of women receiving chloroquine prophylaxis for > or = 8 weeks and in 9% in the case management group (RR = 0.36, 95% CI 0.13-1.00, P = 0.009). Parasitaemia at enrolment significantly correlated with low birthweight in the case management group as compared to the intervention groups (P = 0.02). Women in the case management group who were parasitaemia and had haemoglobin levels < 100 g/L at delivery had babies with lower mean birthweight as compared to babies in the other groups (P = 0.04). Low haemoglobin level at enrolment, irrespective of parasitaemia status, was a predictor of low birthweight in the case management group only (P = 0.04). Chloroquine prophylaxis and iron-folic acid supplementation significantly increased maternal haemoglobin levels during pregnancy as compared to case management (P = 0.01 and 0.007, respectively) and the increase correlated to the duration of the intervention.     

Vitamin A and carotenoids during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis

Vitamin A (VA) deficiency during pregnancy is common in low-income countries and a growing number of intervention trials have examined the effects of supplementation during pregnancy on maternal, perinatal and infant health outcomes. We systematically reviewed the literature to identify trials isolating the effects of VA or carotenoid supplementation during pregnancy on maternal, fetal, neonatal and early infant health outcomes. Meta-analysis was used to pool effect estimates for outcomes with more than one comparable study. We used GRADE criteria to assess the quality of individual studies and the level of evidence available for each outcome. We identified 23 eligible trials of which 17 had suitable quality for inclusion in meta-analyses. VA or beta-carotene (βC) supplementation during pregnancy did not have a significant overall effect on birthweight indicators, preterm birth, stillbirth, miscarriage or fetal loss. Among HIV-positive women, supplementation was protective against low birthweight (<2.5 kg) [risk ratio (RR) = 0.79 [95% confidence interval (CI) 0.64, 0.99]], but no significant effects on preterm delivery or small-for-gestational age were observed. Pooled analysis of the results of three large randomised trials found no effects of VA supplementation on neonatal/infant mortality, or pregnancy-related maternal mortality (random-effects RR = 0.86 [0.60, 1.24]) although high heterogeneity was observed in the maternal mortality estimate (I(2) = 74%, P = 0.02). VA supplementation during pregnancy was found to improve haemoglobin levels and reduce anaemia risk (<11.0 g/dL) during pregnancy (random-effects RR = 0.81 [0.69, 0.94]), also with high heterogeneity (I(2) = 52%, P = 0.04). We found no effect of VA/βC supplementation on mother-to-child HIV transmission in pooled analysis, although some evidence suggests that it may increase transmission. There is little consistent evidence of benefit of maternal supplementation with VA or βC during pregnancy on maternal or infant mortality. While there may be beneficial effects for certain outcomes, there may also be potential for harm through increased HIV transmission in some populations.     

A population-based cohort study of the relation between maternal birthweight and risk of gestational diabetes mellitus in four racial/ethnic groups

Intrauterine growth retardation and low birthweight have been associated with an increased risk of insulin resistance and type II diabetes later in life. We hypothesised that maternal low birthweight is associated with an increased risk of gestational diabetes mellitus (GDM). Study subjects comprised women giving birth in Washington State between 1987 and 1995. Information for 21,528 births to non-Hispanic white women, 6359 to African-American women, 7456 to Native American women and 6496 to Hispanic women was available for analysis. All information was derived from statewide computerised vital records and hospital discharge summaries of obstetric and neonatal admissions with linkage to birth certificates of mothers. Maternal birthweight was collected from subjects' birth certificates. Information from both the birth certificates and the obstetric and neonatal admissions database was used to determine whether subjects developed GDM. Poisson regression models were estimated to calculate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for GDM by categories of maternal birthweight. The cumulative incidence of GDM among non-Hispanic white, African-American, Native American and Hispanic women was 2.8, 2.6, 2.7 and 3.0% respectively. After adjusting for maternal age, parity, cigarette smoking, history of chronic hypertension and participation in the Medicaid programme, non-Hispanic white women with a birthweight < 2000 g were 1.7 times more likely to have had their pregnancy complicated by GDM (RR = 1.7; 95% CI 0.8, 3.3) than those with a birthweight 3000-3999 g. The corresponding adjusted RRs for African-American, Native American, and Hispanic women were 2.8 [95% CI 1.2, 6.1], 3.1 [95% CI 1.2, 8.2] and 2.4 [95% CI 0.9, 6.0] respectively. Among African-American women, those with a birthweight > or = 4000 g also experienced a twofold increased risk of GDM (RR = 2.1; 95% CI 1.0, 4.1). This association of high birthweight and increased GDM risk was not found among women in the other three racial/ethnic groups. These findings suggest that individuals with low birthweight constitute a group at increased risk for GDM.     

Preconception Hemoglobin Concentration and Risk of Low Birth Weight and Small-for-Gestational-Age: A Large Prospective Cohort Study in China

Less is known about the impact of maternal preconception anemia on birth outcomes. We aimed to examine associations between preconception hemoglobin (Hb) concentrations with risk of low birth weight (LBW) and small-for-gestational-age (SGA). This study was from a large population-based prospective cohort in China and included 124,725 women with singleton live births delivered at gestational ages of 28–45 weeks who were registered before pregnancy. Maternal Hb concentrations were measured during registration, and other health-related information was recorded prospectively. Logistic regression was used to evaluate the associations between preconception Hb concentrations with risk of LBW and SGA, adjusting for potential confounders. The results showed women with preconception anemia accounted for 22.28%. The incidences of LBW/SGA were 2.37%/6.30% among anemic women, and 2.01%/5.48% among non-anemic women, respectively. Preconception mild anemia increased by 17% (95% confidence interval (CI): 1.06, 1.28) and 14% (95% CI: 1.07, 1.21) the risk for LBW and SGA, while moderate-to-severe anemia had no significant association with LBW and SGA. Compared with the 120–129 g/L group, a U-shaped association was observed between preconception Hb concentrations with LBW and SGA. In conclusion, not only maternal anemia but also elevated Hb concentrations before pregnancy contribute to an increased risk of LBW and SGA.     

Interventions with vitamins B6, B12 and C in pregnancy

The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health and nutrition outcomes. Relevant publications were identified by searching PubMed, Popline and Web of Science databases. Meta-analyses were conducted for outcomes where results from at least three controlled trials were available. Potential benefits of vitamin B6 supplementation were reduction in nausea and vomiting, improvement in dental health, and treatment of some cases of anaemia. In meta-analysis based on three small studies, vitamin B6 supplementation had a significant positive effect on birthweight (d = 217 g [95% confidence interval (CI) 130, 304]). Interventions with vitamin C alone or combined with vitamin E did not systematically reduce the incidence of pre-eclampsia, premature rupture of membranes, or other adverse pregnancy outcomes. In meta-analyses, vitamins C and E increased the risk of pregnancy-related hypertension (relative risk 1.10 [95% CI 1.02, 1.19]). Effects of vitamin B6 or C intervention on other neonatal outcomes, including preterm birth, low birthweight, and perinatal morbidity and mortality, were not significant. Data on child health outcomes were lacking. Despite the prevalence of vitamin B12 deficiency amongst populations with limited intake of animal source foods, no intervention trials have evaluated vitamin B12 supplementation before or during pregnancy. In conclusion, existing evidence does not justify vitamin C supplementation during pregnancy. Additional studies are needed to confirm positive effects of vitamin B6 supplementation on infant birthweight and other outcomes. While vitamin B12 supplementation may reduce the incidence of neural tube defects in the offspring based on theoretical considerations, research is needed to support this hypothesis.     

Association between low gynaecological age and preterm birth

Low gynaecological age, defined as conception within 2 completed years of menarche, was examined for its association with preterm birth, using data from a geographically based cohort of over 1700 young primigravidae aged 18 or younger at start of prenatal care. After stratifying by chronological age and controlling for confounding variables, low gynaecological age was associated with almost double the risk of preterm delivery whether estimated from the mother's last menstrual period (adjusted odds ratio (AOR) = 1.77, 95% CI 1.19-2.64) or using the obstetric estimate of gestation (AOR = 2.10, 95% CI 1.36-3.25). Low gynaecological age was also associated with an increase in risk of low birthweight (LBW) (AOR = 1.70, 95% CI 1.01-2.88), but not of small-for-gestational-age babies (AOR = 0.94, 95% CI 0.49-1.81). Thus low gynaecological age may be an important addition to assessment systems to detect women at risk of preterm labour and delivery.