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.

Biological mechanisms for nutritional regulation of maternal health and fetal development.

This review paper highlights mechanisms for nutritional regulation of maternal health and fetal development. Malnutrition (nutrient deficiencies or obesity) in pregnant women adversely affects their health by causing or exacerbating a plethora of problems, such as anaemia, maternal haemorrhage, insulin resistance, and hypertensive disorders (e.g. pre-eclampsia/eclampsia). Maternal malnutrition during gestation also impairs embryonic and fetal growth and development, resulting in deleterious outcomes, including intrauterine growth restriction (IUGR), low birthweight, preterm birth, and birth defects (e.g. neural tube defects and iodine deficiency disorders). IUGR and preterm birth contribute to high rates of neonatal morbidity and mortality. Major common mechanisms responsible for malnutrition-induced IUGR and preterm birth include: (i) abnormal growth and development of the placenta; (ii) impaired placental transfer of nutrients from mother to fetus; (iii) endocrine disorders; and (iv) disturbances in normal metabolic processes. Activation of a series of physiological responses leading to premature and sustained contraction of the uterine myometrium also results in preterm birth. Recent epidemiologic studies have suggested a link between IUGR and chronic metabolic disease in children and adults, and the effects of IUGR may be carried forward to subsequent generations through epigenetics. While advanced medical therapies, which are generally unavailable in low-income countries, are required to support preterm and IUGR infants, optimal nutrition during pregnancy may help ameliorate many of these problems. Future studies are necessary to develop effective nutritional interventions to enhance fetal growth and development and alleviate the burden of maternal morbidity and mortality in low- and middle-income countries.

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.

Measurement of food consumption to inform food fortification and other nutrition programs: an introduction to methods and their application.

BACKGROUND: Information on dietary intake is essential for the assessment, planning, monitoring, and evaluation of nutritional interventions. A number of methods are available, each with unique strengths and weaknesses. Dietary intake records, 24-hour recalls, and Food Frequency Questionnaires (FFQs) determine food consumption and nutrient intakes of populations based on individual assessment; few countries have such data at national or regional levels. Food and Agriculture Organization (FAO) Food Balance Sheets (FBS) and food industry data, available in most countries, permit calculations of per capita food consumption but do not provide data on individual consumption. Household Consumption and Expenditures Surveys (HCES) are available for most countries and provide data that can be used to calculate consumption of fortification vehicles and to estimate additional intakes of micronutrients delivered through them to specific population groups. OBJECTIVE: To introduce the reader to the set of papers included in this Supplement reviewing methods and experience with HCES to inform nutrition, and specifically food fortification programs. METHODS: The Monitoring, Assessment, and Data (MAD) working group and colleagues critically reviewed experiences in estimating dietary intakes,focusing on the use of secondary analysis of HCES. RESULTS: HCES predict coverage of the population that consumes a fortification vehicle and consumed amounts of fortification vehicles. HCES allow comparisons of different population strata and may also approximate micronutrient adequacy, based on nutrient density, at the household level. CONCLUSIONS: HCES are useful to inform food fortification and other nutrition programs for planning interventions, but further work is necessary. Currently, combined use of traditional dietary surveys is needed for assessment and for program monitoring and evaluation.

Methods of using household consumption and expenditures survey (HCES) data to estimate the potential nutritional impact of fortified staple foods.

BACKGROUND: Micronutrient malnutrition, caused largely by inadequate dietary intake, is a global public health problem that adversely affects health, child growth and development, work capacity, and quality of life. Mass fortification of widely consumed edible products has the potential to increase micronutrient intakes and thus alleviate some nutritional deficiencies. Although individual-level data about food consumption patterns are ideal for informing the design of food fortification programs, they are often unavailable. Household Consumption and Expenditures Surveys (HCES) are nationally representative cross-sectional surveys conducted over a 12-month period every 2 to 5 years, primarily to characterize household expenditures. OBJECTIVE: We describe how expenditure data from HCES can serve as a proxy for household food consumption and thus aid in choosing which foods to fortify and in determining how much of a micronutrient to add to that food. METHODS: We describe methods of using HCES data to characterize apparent food consumption patterns among different strata within a population. RESULTS: There are several limitations of using HCES data to describe apparent food consumption. HCES do not directly capture information about true food intake, but rather describe food expenditures. We assume that purchased foods are not shared with guests, wasted, fed to animals, gifted, or stockpiled for later use. We also assume that foods are allocated within each household based on energy needs. CONCLUSIONS: Despite the limitations of using HCES data to estimate apparent food consumption, the dearth of individual-level data about food intake renders HCES data useful in designing food fortification programs.

Docosahexaenoic acid supplementation from mid-pregnancy to parturition influenced breast milk fatty acid concentrations at 1 month postpartum in Mexican women.

(n-3) PUFA, including DHA, are essential for neural development and accumulate extensively in the fetal and infant brain. (n-3) PUFA concentrations in breast milk, which are largely dependent on maternal diet and tissue stores, are correlated with infant PUFA status. We investigated the effect of prenatal DHA supplementation on PUFA concentrations in breast milk at 1 mo postpartum. In a double-blind, randomized, controlled trial conducted in Mexico, pregnant women were supplemented daily with 400 mg DHA or placebo from 18-22 wk gestation to parturition. Fatty acid concentrations in breast milk obtained from 174 women at 1 mo postpartum were determined using GLC and were expressed as % by weight of total detected fatty acids. Breast milk DHA concentrations in the DHA and placebo groups were (mean ± SD) 0.20 ± 0.06 and 0.17 ± 0.07 (P < 0.01), respectively, and those of α-linolenic acid (ALA) were 1.38 ± 0.47 and 1.24 ± 0.46 (P = 0.01), respectively. Concentrations of EPA and arachidonic acid did not differ between groups (P > 0.05). Maternal plasma DHA concentrations at 1 mo postpartum correlated positively with breast milk DHA at 1 mo postpartum in both the placebo and DHA groups (r = 0.4; P < 0.01 for both treatment groups). Prenatal DHA supplementation from 18-22 wk gestation to parturition increased concentrations of DHA and ALA in breast milk at 1 mo postpartum, providing a mechanism through which breast-fed infants could benefit.

Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico.

BACKGROUND: The need for omega-3 fatty acids, especially docosahexaenoic acid (DHA), during pregnancy has received much attention, but evidence of effects on birth outcomes is limited. OBJECTIVE: To evaluate whether prenatal DHA supplementation increases gestational age and birth size. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in Cuernavaca, Mexico. We randomly assigned 1,094 pregnant women (18 to 35 years of age; median DHA dietary intake, 55 mg/day) to 400 mg/day of algal DHA or placebo from 18 to 22 weeks of gestation through delivery. Birth outcomes (968 live births and 5 stillbirths) were ascertained from hospital records within 24 hours of delivery. RESULTS: Intention-to-treat analysis showed no differences between the control and DHA group (all p > .05) in mean gestational age (39.1 + 1.7 and 39.0 +/- 1.9 weeks, respectively), weight (3.20 + 0.47 and 3.21 +/- 0.45 kg, respectively), length (50.3 +/- 2.7 and 50.3 +/- 2.3 cm, respectively) and head circumference (34.3 +/- 1.8 and 34.3 +/- 1.5 cm, respectively) at birth. Offspring of supplemented primigravidae (n = 370) were heavier (difference, 99.4 g; 95% CI, 5.5 to 193.4) and had larger head circumferences (difference, 0.5 cm; 95% CI, 0.1 to 0.9) than controls; the differences in multigravidae (n = 603) were -53.3 g (95% CI, -126.8 to 20.2) and -0.2 cm (95% CI, -0.4 to 0.1), respectively (p < .05 for heterogeneity). CONCLUSIONS: Prenatal DHA supplementation of primigravid women may result in increased birth size in a population where dietary DHA intakes are very low. Benefits of the intervention on infant health and neurodevelopment are under study.

Potential Dietary Contributions From Rice and Wheat Flour Fortification in the Solomon Islands: Results From the 2012-2013 Household Income and Expenditure Survey.

BACKGROUND: Solomon Islands (SI) mandated wheat flour fortification in 2010. Rice is a key staple food in SI, and its fortification may provide an opportunity to deliver additional micronutrients to the population. OBJECTIVE: To determine whether fortified rice (proposed) and fortified wheat flour potentially benefit women of reproductive age (WRA). METHODS: We analyzed data from the 2012-2013 Household Income and Expenditure Survey to quantify food purchases, which served as a proxy for food consumption. We accounted for varied household composition by using adult male equivalent (AME) adjustments. RESULTS: Among 4478 households, 95.6% purchased rice and 86.6% purchased at least 1 food containing fortified wheat flour in the previous 14 days. Median apparent intake of rice among WRA was 205 g/d/AME. If fortified according to proposed standards, this apparent intake could result in the consumption of 12.3 mg iron/d, fulfilling 44% of the estimated average requirement (EAR), and 226 µg folic acid/d, satisfying 57% of World Health Organization's recommended intake of 400 µg/d. Overall, apparent rice consumption could fulfill 113%, 114%, and 131% of the EAR for WRA for zinc, thiamin, and niacin, respectively. Fortified wheat flour was consumed in much lower quantities, with an estimated apparent median intake of 22 g/d/AME among WRA and 78 g/d/AME among women in urban populations. CONCLUSIONS: The potential benefit of fortified wheat flour in SI is likely limited to urban populations. Apparent consumption of fortified rice in SI could contribute considerably to daily intake of iron, B vitamins including folic acid, and zinc among WRA.

Maternal nutrition interventions to improve maternal, newborn, and child health outcomes.

Maternal undernutrition affects a large proportion of women in many developing countries, but has received little attention as an important determinant of poor maternal, newborn, and child health (MNCH) outcomes such as intrauterine growth restriction, preterm birth (PTB), and maternal and infant morbidity and mortality. We recently evaluated the scientific evidence on the effects of maternal nutrition interventions on MNCH outcomes as part of a project funded by the Gates Foundation to identify critical knowledge gaps and priority research needs. A standardized tool was used for study data abstraction, and the effect of nutrition interventions during pregnancy or of factors such as interpregnancy interval on MNCH outcomes was assessed by meta-analysis, when possible. Several nutrient interventions provided during pregnancy have beneficial effects on MNCH outcomes, but are not widely adopted. For example, prenatal calcium supplementation decreases the risk of PTB and increases birthweight; prenatal zinc, omega-3 fatty acids and multiple micronutrient supplements reduce the risk of PTB (<37 weeks), early PTB (<34 weeks) and low birthweight (LBW), respectively. Among currently implemented interventions, balanced protein-energy and iron-folic acid supplementation during pregnancy significantly reduce the risk of LBW by 20-30% in controlled settings, but variable programmatic experiences have led to questionable effectiveness. Early age at pregnancy and short interpregnancy intervals were also associated with increased risk of PTB, LBW and neonatal death, but major gaps remain on the role of women's nutrition before and during early pregnancy and nutrition education and counseling. These findings emphasize the need to examine the benefits of improving maternal nutrition before and during pregnancy both in research and program delivery.

Prenatal docosahexaenoic acid supplementation and infant morbidity: randomized controlled trial.

OBJECTIVE: Long-chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) influence immune function and inflammation; however, the influence of maternal DHA supplementation on infant morbidity is unknown. We investigated the effects of prenatal DHA supplementation on infant morbidity. METHODS: In a double-blind randomized controlled trial conducted in Mexico, pregnant women received daily supplementation with 400 mg of DHA or placebo from 18 to 22 weeks' gestation through parturition. In infants aged 1, 3, and 6 months, caregivers reported the occurrence of common illness symptoms in the preceding 15 days. RESULTS: Data were available at 1, 3, and 6 months for 849, 834, and 834 infants, respectively. The occurrence of specific illness symptoms did not differ between groups; however, the occurrence of a combined measure of cold symptoms was lower in the DHA group at 1 month (OR: 0.76; 95% CI: 0.58-1.00). At 1 month, the DHA group experienced 26%, 15%, and 30% shorter duration of cough, phlegm, and wheezing, respectively, but 22% longer duration of rash (all P ≤ .01). At 3 months, infants in the DHA group spent 14% less time ill (P < .0001). At 6 months, infants in the DHA group experienced 20%, 13%, 54%, 23%, and 25% shorter duration of fever, nasal secretion, difficulty breathing, rash, and "other illness," respectively, but 74% longer duration of vomiting (all P < .05). CONCLUSIONS: DHA supplementation during pregnancy decreased the occurrence of colds in children at 1 month and influenced illness symptom duration at 1, 3, and 6 months.

Role of docosahexaenoic acid in maternal and child mental health.

Mental health problems in women and children represent a significant public health problem worldwide, especially in developing countries. The role of nutrition as a cost-effective approach in the prevention and management of these conditions has received recent attention, particularly nutrients such as iron, zinc, and n-3 (omega-3) fatty acids, which play a role in brain structure and function. The objective of this article was to review current evidence on the relation between n-3 fatty acids, especially docosahexaenoic acid (DHA), and maternal and child mental health disorders. Human studies published in English were identified from Medline databases (1966 to June 2008) by using key search terms and review articles. A summary of the role of DHA in the human brain is followed by a review of human studies, both observational and intervention trials, that examine the relation between n-3 fatty acids such as DHA and depression and child mental health disorders. Observational studies support a direct association between poor n-3 fatty acid status and increased risk of maternal depression and childhood behavioral disorders such as attention-deficit hyperactivity disorder (ADHD). However, evidence from intervention trials is weak. Most of the studies reviewed had small sample sizes and were conducted in clinically diagnosed samples, with no placebo-controlled groups. Little is known about the benefits of DHA in the prevention of maternal depression and ADHD. Large, well-designed, community-based prevention trials are needed.

Wheat flour fortification is unlikely to benefit the neediest in Guatemala.

The potential impact of wheat flour fortification with iron and folic acid was assessed using data about food purchases from the nationally representative 2000 Guatemalan Living Standards Measurement Survey. Of 7265 households, 35% were indigenous and 57% rural; 11% were extremely poor, 35% were poor, and 54% were nonpoor. The percentage of households that purchased wheat flour, sweet bread, French rolls, and sliced bread in the previous 15 d was 10, 88, 59, and 11%, respectively. The median amount of fortified wheat flour equivalents in purchased foods was 50 g/d per adult equivalent; fortified wheat flour equivalents were 7, 25, and 110 g/d for the poverty groups, 16 g/d in indigenous households and 24 g/d in rural households. Wheat flour fortification contributed 2.3 mg/d of iron and 90 microg/d of folic acid per adult equivalent. Assuming 5% bioavailability, wheat flour fortification provided 2% of the recommended dietary allowance (RDA) and 6% of estimated average requirement (EAR) iron levels for women of reproductive age; values were 1, 3, and 12% of EAR levels for the poverty groups, respectively. Wheat flour fortification met 26% of folic acid RDA and 33% of EAR levels for women; values were 5, 16, and 71% of EAR levels for the poverty groups, respectively. In conclusion, the impact of fortification is likely to be substantial for folate status in nonpoor and urban women but limited in the case of iron status among all social groups. The poorest, rural, indigenous populations who suffer the highest burden of nutritional deficiencies likely benefit least from wheat flour fortification.