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      Maternal vitamin B 12 deficiency and perinatal outcomes in southern India

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          Abstract

          Background

          Vitamin B 12 deficiency during pregnancy has been associated with adverse maternal and infant health outcomes. Few prospective studies have investigated vitamin B 12 status early in pregnancy, and its links to infant vitamin B 12 status, particularly in India where the burden of vitamin B 12 deficiency is estimated to be the highest globally. The objective of this study was to examine the associations of maternal vitamin B 12 biomarkers with neonatal vitamin B 12 status.

          Methods

          Pregnant women (~12 weeks’ gestation) were enrolled in a perinatal cohort study in Bangalore, India. Total vitamin B 12, methylmalonic acid (MMA), and homocysteine concentrations were evaluated in maternal samples at enrollment and in neonates at birth using cord blood. Linear and binomial regression models were used to evaluate the associations of maternal vitamin B 12 biomarkers with neonatal vitamin B 12 status and perinatal outcomes.

          Results

          A total of 63.2% of women had vitamin B 12 deficiency (<148 pmol/L), 87.2% had vitamin B 12 insufficiency (<221 pmol/L), and 47.3% had impaired vitamin B 12 status (vitamin B 12<148 pmol/L and MMA>0.26μmol/L) at enrollment; 40.8% of neonates had vitamin B 12 deficiency, 65.6% were insufficiency, and 38.1% had impaired vitamin B 12 status at birth. Higher maternal vitamin B 12 concentrations at enrollment were associated with increased neonatal vitamin B 12 concentrations (β(SE): 0.40 (0.05); p<0.0001) and lower risk of neonatal vitamin B 12 deficiency (Risk Ratio [RR]: 0.53; 95% CI: [0.43, 0.65]; p<0.0001). Maternal vitamin B 12 deficiency (RR: 1.97 [1.43, 2.71]; p<0.001), insufficiency (RR: 2.18 [1.23, 3.85]; p = 0.007), and impaired vitamin B 12 status (RR: 1.49 [1.13, 1.97]; p = 0.005) predicted a two-fold increase in the risk of neonatal vitamin B 12 deficiency at birth.

          Conclusions

          The prevalence of vitamin B 12 deficiency was high early in pregnancy and predicted neonatal vitamin B 12 status. Future research is needed to determine the role of vitamin B 12 in the development of pregnancy and infant outcomes, and to inform screening and interventions to improve maternal and child health.

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          Most cited references103

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          A WHO expert consultation addressed the debate about interpretation of recommended body-mass index (BMI) cut-off points for determining overweight and obesity in Asian populations, and considered whether population-specific cut-off points for BMI are necessary. They reviewed scientific evidence that suggests that Asian populations have different associations between BMI, percentage of body fat, and health risks than do European populations. The consultation concluded that the proportion of Asian people with a high risk of type 2 diabetes and cardiovascular disease is substantial at BMIs lower than the existing WHO cut-off point for overweight (> or =25 kg/m2). However, available data do not necessarily indicate a clear BMI cut-off point for all Asians for overweight or obesity. The cut-off point for observed risk varies from 22 kg/m2 to 25 kg/m2 in different Asian populations; for high risk it varies from 26 kg/m2 to 31 kg/m2. No attempt was made, therefore, to redefine cut-off points for each population separately. The consultation also agreed that the WHO BMI cut-off points should be retained as international classifications. The consultation identified further potential public health action points (23.0, 27.5, 32.5, and 37.5 kg/m2) along the continuum of BMI, and proposed methods by which countries could make decisions about the definitions of increased risk for their population.
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            Relative risk is usually the parameter of interest in epidemiologic and medical studies. In this paper, the author proposes a modified Poisson regression approach (i.e., Poisson regression with a robust error variance) to estimate this effect measure directly. A simple 2-by-2 table is used to justify the validity of this approach. Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100. The method is illustrated with two data sets.
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              In 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21(st) Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants. INTERGROWTH-21(st) is a population-based project that assessed fetal growth and newborn size in eight geographically defined urban populations. These groups were selected because most of the health and nutrition needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21(st) Project, we measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound estimate of gestational age using crown-rump length before 14 weeks of gestation or biparietal diameter if antenatal care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional polynomials assuming a skewed t distribution were used to estimate the fitted centiles. We identified 20,486 (35%) eligible women from the 59,137 pregnant women enrolled in NCSS between May 14, 2009, and Aug 2, 2013. We calculated sex-specific observed and smoothed centiles for weight, length, and head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex. We have developed, for routine clinical practice, international anthropometric standards to assess newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across multiethnic populations. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Formal analysis
                Role: Project administration
                Role: ConceptualizationRole: Funding acquisitionRole: Project administration
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 April 2021
                2021
                : 16
                : 4
                : e0248145
                Affiliations
                [1 ] Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States of America
                [2 ] St. John’s Research Institute, Bangalore, Karnataka, India
                Holbaek Sygehus, DENMARK
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-7976-1096
                https://orcid.org/0000-0002-3190-6126
                Article
                PONE-D-20-30201
                10.1371/journal.pone.0248145
                8023483
                33822790
                c61b63bd-386a-47f2-8863-3170c79af93c
                © 2021 Finkelstein et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 October 2020
                : 19 February 2021
                Page count
                Figures: 1, Tables: 7, Pages: 23
                Funding
                Funded by: Division of Nutritional Sciences, Cornell University
                Award Recipient :
                Funded by: St. John's Research Institute, India
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5 T32 HD087137
                Award Recipient :
                Funded by: International Life Sciences Institute Future Leader Award
                Award Recipient :
                This research was funded by the Division of Nutrition, St. John’s Research Institute and the Division of Nutritional Sciences, Cornell University. J.L.F. was supported by the ILSI North America Future Leader Award. A.F. was supported by the National Institutes of Health under award 5 T32 HD087137. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Vitamins
                B Vitamins
                Cobalamins
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Vitamins
                B Vitamins
                Cobalamins
                Biology and Life Sciences
                Developmental Biology
                Neonates
                Medicine and health sciences
                Hematology
                Anemia
                Megaloblastic anemia
                Vitamin B12 deficiency
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Birth Weight
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Birth
                Labor and Delivery
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Birth
                Labor and Delivery
                People and Places
                Population Groupings
                Age Groups
                Children
                Infants
                People and Places
                Population Groupings
                Families
                Children
                Infants
                Custom metadata
                The data is publicly available at: https://doi.org/10.7910/DVN/HIOUQN (Contact Dr. Pratibha Dwarkanath at: Pratibha@ 123456sjri.res.in ).

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