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Khatry S.K.,Nepal Nutrition Intervention Project Sarlahi | StewartParul C.P.,University of California at Davis
Nutrients | Year: 2014

Little attention has been given to the association of plasma homocysteine (Hcy) and metabolic syndrome (MetS) in children. We have evaluated the risk of MetS with plasma Hcy in a cohort of 6 to 8 year old rural Nepalese children, born to mothers who had participated in an antenatal micronutrient supplementation trial. We assessed Hcy in plasma from a random selection of n = 1000 children and determined the relationship of elevated Hcy (>12.0 μmol/L) to MetS (defined as the presence of any three of the following: abdominal adiposity (waist circumference ≥ 85th percentile of the study population), high plasma glucose (≥85th percentile), high systolic or diastolic blood pressure (≥90th percentile of reference population), triglyceride ≥ 1.7 mmol/L and high density lipoprotein < 0.9 mmol/L.) and its components. There was an increased risk of low high-density lipoproteins (HDL), [odds ratios (OR) = 1.77, 95% confidence intervals (CI) = 1.08-2.88; p = 0.020], high blood pressure [OR = 1.60, 95% CI = 1.10-2.46; p = 0.015] and high body mass index (BMI) [OR = 1.98, 95% CI = 1.33-2.96; p = 0.001] with elevated Hcy. We observed an increased risk of MetS (OR = 1.75, 95% CI = 1.06-2.90; p = 0.029) with elevated Hcy in age and gender-adjusted logistic regression models. High plasma Hcy is associated with increased risk of MetS and may have implications for chronic disease later in life. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Stewart C.P.,University of California at Davis | Christian P.,Center for Human Nutrition | Schulze K.J.,Center for Human Nutrition | Arguello M.,Center for Human Nutrition | And 3 more authors.
Journal of Nutrition | Year: 2011

Questions have been raised about potentially negative effects of antenatal folic acid use in populations with a high prevalence of vitamin B-12 deficiency. Our objective was to examine the association between maternal folate and vitamin B-12 status in pregnancy on offspring insulin resistance and examine whether the effects of maternal micronutrient supplementation varied by baseline maternal folate and/or vitamin B-12 status. Pregnant women were cluster randomized to receive daily supplements containing vitamin A alone or with folic acid, folic acid+iron, folic acid+iron+zinc, or a multiple micronutrient. In a subsample (n = 1132), micronutrient status biomarkers were analyzed at baseline and late pregnancy. Children born to the women who participated in the trial were visited at 6-8 y of age. Fasting plasma glucose and insulin were used to estimate insulin resistance using the homeostasis model assessment (HOMA-IR). Children whose mothers were deficient in vitamin B-12 (<148 pmol/L, 27%) during early pregnancy had a 26.7% increase in HOMA-IR (P = 0.02), but there was no association with maternal folate status. Among children born to women who were vitamin B-12 deficient at baseline, the percent difference in HOMA-IR compared to the control group was 15.1% (95% CI: 235.9, 106.4), 4.9% (-41.6, 88.5), 3.3% (238.4, 73.5), and 18.1% (-29.0, 96.7) in the folic acid, folic acid-iron, folic acid-iron-zinc, and multiple micronutrient supplementation groups, respectively, none of which were significant. Maternal vitamin B-12 deficiency is associated with an elevated risk of insulin resistance, but supplementation with folic acid or other micronutrients led to no significant change in insulin resistance in school-aged offspring. © 2011 American Society for Nutrition.


Stewart C.P.,University of California at Davis | Christian P.,Center for Human Nutrition | Wu L.S.F.,Center for Human Nutrition | Leclerq S.C.,Center for Human Nutrition | And 2 more authors.
Metabolic Syndrome and Related Disorders | Year: 2013

Background: Chronic disease begins early in life, yet population data are sparse on potential causal factors in children and young adults in South Asia. Methods: We assessed risk factors for chronic disease in two population cohorts, aged 9-23 years, in rural Nepal. Assessed variables included short height (less than -2 z), high body mass index (BMI) (z>0.42), waist circumference (WC) >90 cm (male) or 80 cm (female) or age-adjusted child cutoff], high blood pressure (>120/80 mmHg), fasting glucose (≥100 mg/dL), glycosylated hemoglobin (HbA1c) (>7%), blood lipids [triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol], diet, smoking, alcohol, and socioeconomic status (SES) factors. Results: The population was stunted (46%) and few were overweight (∼2%-4% with high BMI or WC). Twelve percent had high blood pressure. Plasma hypertriglyceridemia (≥150 mg/dL) affected ∼8.5%, and 78% had low HDL-C concentrations <40 mg/dL (male) or <50 mg/dL (female)], while few (≤3%) had elevated total cholesterol (≥180 mg/dL), glucose, and HbA1c. Females were at higher risk than males for high blood pressure [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.6-2.3] and overweight (4.2; 3.0-5.8), but had lower risk of dyslipidemia (0.7; 0.6-0.9). Ethnic plains Madheshi were less likely to be overweight (0.3; 0.2-0.4), but had greater risk of dyslipidemia (1.4; 1.1-1.7) versus those of Hill origin. Some dietary factors were significantly associated with high blood pressure or dyslipidemia, but not overweight. Conclusions: Dyslipidemia and high blood pressure are emerging health concerns among young adults in rural Nepal. © Mary Ann Liebert, Inc.


PubMed | George Washington University and Nepal Nutrition Intervention Project Sarlahi
Type: Journal Article | Journal: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics | Year: 2016

To assess levels of awareness and use of obstetric ultrasonography in rural Nepal.Between March 2014 and March 2015, a cross-sectional survey was conducted among married women aged 15-40years residing in rural Sarlahi District, Nepal, regarding their knowledge and use of obstetric ultrasonography during their most recent pregnancy. Regression analyses were conducted to identify reproductive health, socioeconomic, and other characteristics that increased the likelihood of undergoing an obstetric ultrasonographic examination.Among 6182 women, 1630 (26.4%) had undergone obstetric ultrasonography during their most recent pregnancy, of whom 1011 (62.0%) received only one examination. Odds of receiving an ultrasonographic examination were higher among women with post-secondary education than among those with none (11years education: adjusted odds ratio [aOR] 10.28, 95% confidence interval [CI] 5.55-19.04), and among women whose husbands had post-secondary education than among those with husbands with none (11years education: aOR 1.99, 95% CI 1.47-2.69). Odds were lower among women younger than 18years than among those aged 18-34years (aOR 0.72, 95% confidence interval 0.59-0.90).Utilization of obstetric ultrasonography in rural Nepal was very limited. Further research is necessary to assess the potential health impact of obstetric ultrasonography in low-resource settings, while addressing limitations such as cost and misuse.


PubMed | Cincinnati Childrens Hospital and Medical Center, Tribhuvan University, University of Washington, Nepal Nutrition Intervention Project Sarlahi and George Washington University
Type: Journal Article | Journal: Vaccine | Year: 2016

Immunization programs currently measure coverage by assessing the proportion of children 12-24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited.To estimate the time to Bacillus Calmette-Gurin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants <6 months of age in a district in southern Nepal where traditional coverage metrics are high.Infants enrolled in a randomized controlled trial of maternal influenza vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan-Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine.The median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months.A significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health.


Katz J.,Johns Hopkins University | Khatry S.K.,Nepal Nutrition Intervention Project Sarlahi | LeClerq S.C.,Johns Hopkins University | Mullany L.C.,Johns Hopkins University | And 4 more authors.
Journal of Nutrition | Year: 2010

A community-based, cluster-randomized, placebo-controlled trial of daily zinc and/or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1-36 mo of age between 2001 and 2006. Treatment groups included placebo, zinc (10 mg), iron+folic acid (12.5 mg iron + 50 mg folic acid), and zinc +iron+folic acid (10 mg zinc + 12.5 mg iron + 50 μg folic acid). Infants received half of these doses. The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board; zinc and placebo continued until January 2006. A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo. Mean age at first walking unassisted did not differ among groups and was 444 ± 81 d (mean ± SD) in the placebo group, 444 ± 81 d in the zinc group, 464 ± 85 d in the iron+folic acid group, and 446 ± 87 d in the iron+folic acid+zinc group. Results were similar after adjustment for age at enrollment, asset ownership, maternal literacy, and prior child deaths in the household and in children who consumed at least 60 tablets. Compared with placebo, iron+folic acid was associated with an adjusted mean delay of 28.0 d (95% CI: 11.3, 44.7) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference (MUAC) < 9.5 cm [60.6 d, (95% CI: 28.5, 92.6)]. Risks and benefits of universal iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration. © 2010 American Society for Nutrition.


Lee A.C.C.,Johns Hopkins University | Lee A.C.C.,Brigham and Women's Hospital | Mullany L.C.,Johns Hopkins University | Tielsch J.M.,Johns Hopkins University | And 5 more authors.
Pediatrics | Year: 2011

OBJECTIVES: To characterize the incidence of, risk factors for, and neonatal morbidity and mortality associated with respiratory depression at birth and neonatal encephalopathy (NE) among term infants in a developing country. METHODS: Data were collected prospectively in 2002-2006 during a community-based trial that enrolled 23 662 newborns in rural Nepal and evaluated the impact of umbilical-cord and skin cleansing on neonatal morbidity and mortality rates. Respiratory depression at birth and NE were defined on the basis of symptoms from maternal reports and study-worker observations during home visits. RESULTS: Respiratory depression at birth was reported for 19.7% of live births, and 79% of cases involved term infants without congenital anomalies. Among newborns with probable intrapartum-related respiratory depression (N = 3465), 112 (3%) died before their first home visit (presumed severe NE), and 178 (5%) eventually developed symptoms of NE. Overall, 629 term infants developed NE (28.1 cases per 1000 live births); 2% of cases were associated with congenital anomalies, 25% with infections, and 28% with a potential intrapartum event. The incidence of intrapartum-related NE was 13.0 cases per 1000 live births; the neonatal case fatality rate was 46%. Infants with NE more frequently experienced birth complications and were male, of multiple gestation, or born to nulliparous mothers. CONCLUSIONS: In Sarlahi, the incidence of neonatal respiratory depression and NE, associated neonatal case fatality, and morbidity prevalence are high. Action is required to increase coverage of skilled obstetric/neonatal care in this setting and to evaluate long-term impairments. Copyright © 2011 by the American Academy of Pediatrics.


Hughes M.M.,Johns Hopkins University | Katz J.,Johns Hopkins University | Mullany L.C.,Johns Hopkins University | Khatry S.K.,Nepal Nutrition Intervention Project Sarlahi | And 3 more authors.
BMC Pregnancy and Childbirth | Year: 2014

Background: While seasonality of birth outcomes has been documented in a variety of settings, data from rural South Asia are lacking. We report a descriptive study of the seasonality of prematurity, low birth weight, small for gestational age, neonatal deaths, and stillbirths in the plains of Nepal.Methods: Using data collected prospectively during a randomized controlled trial of neonatal skin and umbilical cord cleansing with chlorhexidine, we analyzed a cohort of 23,662 babies born between September 2002 and January 2006. Project workers collected data on birth outcomes at the infant's household. Supplemental data from other studies conducted at the same field site are presented to provide context. 95% confidence intervals were constructed around monthly estimates to examine statistical significance of findings.Results: Month of birth was associated with higher risk for adverse outcomes (neonatal mortality, low birthweight, preterm, and small for gestational age), even when controlling for maternal characteristics. Infants had 87% (95% CI: 27 - 176%) increased risk of neonatal mortality when born in August, the high point, versus March, the low point.Conclusion: Seasonality of neonatal deaths, stillbirths, birth weight, gestational age, and small for gestational age were found in Nepal. Maternal factors, meteorological conditions, infectious diseases, and nutritional status may be associated with these adverse birth outcomes. Further research is needed to understand the causal mechanisms that explain the seasonality of adverse birth outcomes. © 2014 Hughes et al.; licensee BioMed Central Ltd.


Checkley W.,Johns Hopkins University | West Jr. K.P.,Johns Hopkins University | Wise R.A.,Johns Hopkins University | Baldwin M.R.,Johns Hopkins University | And 7 more authors.
New England Journal of Medicine | Year: 2010

Background: Vitamin A is important in regulating early lung development and alveolar formation. Maternal vitamin A status may be an important determinant of embryonic alveolar formation, and vitamin A deficiency in a mother during pregnancy could have lasting adverse effects on the lung health of her offspring. We tested this hypothesis by examining the long-term effects of supplementation with vitamin A or beta carotene in women before, during, and after pregnancy on the lung function of their offspring, in a population with chronic vitamin A deficiency. Methods: We examined a cohort of rural Nepali children 9 to 13 years of age whose mothers had participated in a placebo-controlled, double-blind, cluster-randomized trial of vitamin A or beta-carotene supplementation between 1994 and 1997. Results: Of 1894 children who were alive at the end of the original trial, 1658 (88%) were eligible to participate in the follow-up trial. We performed spirometry in 1371 of the children (83% of those eligible) between October 2006 and March 2008. Children whose mothers had received vitamin A had a forced expiratory volume in 1 second (FEV1) and a forced vital capacity (FVC) that were significantly higher than those of children whose mothers had received placebo (FEV1, 46 ml higher with vitamin A; 95% confidence interval [CI], 6 to 86; FVC, 46 ml higher with vitamin A; 95% CI, 8 to 84), after adjustment for height, age, sex, body-mass index, calendar month, caste, and individual spirometer used. Children whose mothers had received beta carotene had adjusted FEV1 and FVC values that were similar to those of children whose mothers had received placebo (FEV1, 14 ml higher with beta carotene; 95% CI, -24 to 54; FVC, 17 ml higher with beta carotene, 95% CI, -21 to 55). Conclusions: In a chronically undernourished population, maternal repletion with vitamin A at recommended dietary levels before, during, and after pregnancy improved lung function in offspring. This public health benefit was apparent in the preadolescent years. Copyright © 2010 Massachusetts Medical Society. All rights reserved.


Mullany L.C.,Johns Hopkins University | Katz J.,Johns Hopkins University | Khatry S.K.,Nepal Nutrition Intervention Project Sarlahi | LeClerq S.C.,Johns Hopkins University | And 2 more authors.
Archives of Pediatrics and Adolescent Medicine | Year: 2010

Objective: To quantify incidence, age distribution, and seasonality of neonatal hypothermia among a large population cohort. Design: Longitudinal cohort study. Setting: Sarlahi, Nepal. Participants: A total of 23 240 newborns born between September 2, 2002, and February 1, 2006. Main Exposures: Community-based workers recorded axillary temperature on days 1 through 4, 6, 8, 10, 12, 14, 21, and 28 (213 636 total measurements). Main Outcome Measures: Regression smoothing was used to describe axillary temperature patterns during the newborn period. Hypothermia incidence in the first day, week, and month were estimated using standard cutoffs. Ambient temperatures allowed comparison of mild hypothermia (36.0° C to <36.5° C) and moderate or severe hypothermia (<36.0° C) incidence over mean ambient temperature quintiles. Results: Measurements lower than 36.5° C were observed in 21 459 babies (92.3%); half (48.6%) had moderate or severe hypothermia, and risk peaked in the first 24 to 72 hours of life. Risk of moderate or severe hypothermia increased by 41.3% (95% confidence interval, 40.0%-42.7%) for every 5° C decrease in average ambient temperature. Relative to the highest quintile, risk was 4.03 (95% confidence interval, 3.77-4.30) times higher among babies exposed to the lowest quintile of average ambient temperature. In the hot season, one-fifth of the babies (18.2%) were observed below the moderate hypothermia cutoff. Conclusions: Mild or moderate hypothermia was nearly universal, with substantially higher risk in the cold season. However, incidence in the hot season was also high; thus, year-round thermal care promotion is required. Research on community, household, and caretaker practices associated with hypothermia can guide behavioral interventions to reduce risk. ©2010 American Medical Association. All rights reserved.

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