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Independent and Joint Effects of Prenatal Zinc and Vitamin A Deficiencies on Birthweight in Rural Sidama, Southern Ethiopia: Prospective Cohort Study

1 , * , 2 , 3


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      The effects of prenatal Zinc Deficiency (ZD) and Vitamin A Deficiency (VAD) on birthweight are controversial and their interaction has not been investigated.


      To assess the independent and interaction effects of prenatal zinc and vitamin A deficiencies on birthweight in rural Sidama, Southern Ethiopia.


      A community-based prospective cohort study design was employed. Six hundred fifty pregnant women in their second or third trimester were randomly selected and their serum zinc and retinol concentrations were determined. About 575 subjects were successfully followed until delivery and birthweight was measured within 72 hours after delivery. The association between the exposures and birthweight was examined using log-binomial and liner regression analyses. Potential interaction between ZD and VAD was examined using Synergy Index (SI).


      The mean birthweight (± standard deviation) was 2896 g (±423). About 16.5% (95% CI: 13.5–19.6%) of the babies had Low Birthweight (LBW). Prenatal ZD and VAD were not significantly associated to LBW with Adjusted Relative Risk (ARR) of 1.25 (95 CI: 0.86–1.82) and 1.27 (95% CI: 0.86–1.87), respectively. Stratified analysis on the basis of gestational trimester showed that the occurrence of the deficiencies neither in the second nor third trimester were associated to LBW. The deficiencies did not show synergetic interaction in causing LBW [SI = 1.04 (95% CI: 0.17–6.28)]. Important risk factors of LBW were maternal illiteracy [RR = 1.80 (95% CI: 1.11–2.93)], female sex of the newborn [RR = 1.79 (95% CI: 1.19–2.67)], primiparity [RR = 1.16 (95% CI: 1.02–1.35)], short maternal stature [RR = 1.63 (95% CI: 1.06–2.51)] and maternal thinness [RR = 1.52 (95% CI: 1.03–2.25)]. In the linear regression model, elevated CRP was also negatively associated to birthweight.


      LBW is of public health significance in the locality. The study did not witness any independent or interaction effect of prenatal ZD and VAD on birthweight.

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      Most cited references 24

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      Calculating measures of biological interaction.

      An editorial in this issue explains that the degree of biological interaction between risk factors is measured as the deviation from additivity by the corresponding disease rates and not for example as deviation from multiplicativity. It is the purpose of this article to describe how a logistic regression model, or a Cox regression model, can be defined in order to produce the output that is needed for assessment of biological interaction. We will also demonstrate how common software can be programmed to deliver this output. Finally, we show how this output can be used as input in an Excel sheet that is set up to calculate the measures of biological interaction to be used for the assessment.
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        Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study.

        To examine the association between birth weight and cognitive function in the normal population. A longitudinal, population based, birth cohort study. 3900 males and females born in 1946. Cognitive function from childhood to middle life (measured at ages 8, 11, 15, 26, and 43 years). Birth weight was significantly and positively associated with cognitive ability at age 8 (with an estimated standard deviation score of 0.44 (95% confidence interval 0.28 to 0.59)) between the lowest and highest birthweight categories after sex, father's social class, mother's education, and birth order were controlled for. This association was evident across the normal birthweight range (>2.5 kg) and so was not accounted for exclusively by low birth weight. The association was also observed at ages 11, 15, and 26, and weakly at age 43, although these associations were dependent on the association at age 8. Birth weight was also associated with education, with those of higher birth weight more likely to have achieved higher qualifications, and this effect was accounted for partly by cognitive function at age 8. Birth weight was associated with cognitive ability at age 8 in the general population, and in the normal birthweight range. The effect at this age largely explains associations between birth weight and cognitive function at subsequent ages. Similarly, the association between birth weight and education was accounted for partly by earlier cognitive scores.
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          Interaction: A word with two meanings creates confusion.


            Author and article information

            [1 ]College of Agriculture, Hawassa University, Hawassa, Ethiopia
            [2 ]School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia
            [3 ]School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
            Aga Khan University, Pakistan
            Author notes

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

            Conceived and designed the experiments: SG FE MU. Analyzed the data: SG FE MU. Wrote the paper: SG FE MU.

            Role: Editor
            PLoS One
            PLoS ONE
            PLoS ONE
            Public Library of Science (San Francisco, USA )
            13 December 2012
            : 7
            : 12
            23272058 3521768 PONE-D-12-17799 10.1371/journal.pone.0050213

            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.

            Pages: 8
            The study was funded by Addis Ababa University, School of Public Health. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Research Article
            Clinical Research Design
            Cohort Studies
            Observational Studies
            Epidemiological Methods
            Pediatric Epidemiology
            Non-Clinical Medicine
            Health Care Policy
            Child and Adolescent Health Policy
            Health Risk Analysis
            Micronutrient Deficiencies
            Obstetrics and Gynecology
            Child Development
            Public Health
            Child Health
            Preventive Medicine
            Women's Health



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