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  • 1.
    Ekström, Eva-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Lindström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Raqib, Rubhana
    El Arifeen, Shams
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Brismar, Kerstin
    Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.2016In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 45, no 5, p. 1656-1667Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.

    METHODS: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.

    RESULTS: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.

    CONCLUSIONS: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.

  • 2.
    Kallioinen, Maija
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Khan, Ashraful Islam
    Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh.
    Lindström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Rahman, Anisur
    Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 12, p. 1979-1986Article in journal (Refereed)
    Abstract [en]

    AIM: A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity.

    METHODS: This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 μg folic acid, 30 mg iron with 400 μg folic acid or MMS. Quasi-Poisson regression was used to analyse morbidity.

    RESULTS: There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person-year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months.

    CONCLUSION: Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.

  • 3.
    Lindström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Nutrition and Oxidative Parameters in Pregnancy, Size at Birth and Metabolic Status of the Offspring at 4.5 Years: The MINIMat Trial in Rural Bangladesh2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Undernutrition and oxidative stress in fetal life and infancy may lead to adverse health outcomes in the offspring. We studied nutrition and oxidative parameters in pregnancy and their associations with birth anthropometry and metabolic status in the children.

    In Matlab in rural Bangladesh, women were randomized to either early (Early) invitation to food supplementation or to start at their own liking (Usual). Women were also allocated to either; 1) 60 mg iron and 400 µg folic acid (Fe60F), 2) multiple micronutrients including 30 mg iron and folic acid (MMS), or 3) 30 mg iron and folic acid (Fe30F). Micronutrients (hemoglobin, iron, zinc, folic acid, vitamin B-12) were assessed in pregnancy week 14, lipid peroxidation in week 14 and 30, and DNA oxidation in week 19. The offspring were assessed for anthropometric measurements at birth and metabolic status at 4.5 years.

    Micronutrient deficiencies were common with zinc and vitamin B-12 deficiency being most prevalent. Anemia was present in approximately one third of women, however, iron deficiency was uncommon seen in only 2%.

    Maternal Early food supplementation group resulted in an improved lipid status in the children at 4.5 years compared to Usual food group. Prenatal use of MMS lowered the children’s glucose, insulin, HOMA-IR, and growth factors compared to Fe60F.  

    Lipid peroxidation in early pregnancy was associated with size at birth and insulin and HOMA-IR levels in the children. Lipid peroxidation in late pregnancy, however, was associated with the children’s lipid status. Both increasing lipid peroxidation and increasing DNA oxidation was associated with decreasing IGF-1 levels. 

    The beneficial effects of an Early start of food supplementation show that an improved prenatal nutrition may have lasting effects in the offspring and highlights the importance of early timing food supplementation. Use of MMS, however, resulted in lower insulin levels, which, considering the already low level of insulin in these children, may be a cause of concern. MMS also resulted in growth factors indicative of slower growth and further research appears to be needed before scaling up the use of MMS. Oxidative parameters in pregnancy were associated with longer-term outcomes in the offspring, suggesting that oxidative stress may be involved in the development of later metabolic disease.

  • 4.
    Lindström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hossain, Mohammad B.
    International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Lönnerdal, Bo
    Department of Nutrition, University of California Davis, California, USA.
    Raqib, Rubhana
    International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    El Arifeen, Shams
    International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Prevalence of anemia and micronutrient deficiencies in early pregnancy in rural Bangladesh, the MINIMat trial2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 1, p. 47-56Article in journal (Refereed)
    Abstract [en]

    Objective. To describe the prevalence of anemia and micronutrient deficiencies as well as their determinants in early pregnancy. Design. Baseline data from a population-based randomized intervention trial. Setting. The study was conducted in Mat lab, a sub-district in rural Bangladesh from 1 January to 31 December 2002. Population. Pregnant women (n = 740) were enrolled in approximately week 14 in pregnancy. Methods. Data were collected using questionnaires, physical examinations and laboratory analyses of blood samples for concentrations of hemoglobin, ferritin, zinc, folate and vitamin B-12. Main Outcome Measures. Covariates associated with anemia and micronutrient deficiencies in bivariate analyses were evaluated in multivariate logistic regression models adjusting for potential confounders. Results. Anemia was present in 28% of the women, 55% were zinc deficient, 46% were vitamin B-12 deficient and 18% were folate deficient. Anemia was not associated with iron deficiency but rather with vitamin B-12 deficiency. Infestation with Ascaris was highly prevalent (67%) and associated with both folate and vitamin B-12 deficiency. Anemia and micronutrient deficiencies all varied significantly with season. Conclusions. The high prevalences of zinc and vitamin B-12 deficiencies in early pregnancy are a concern, as it could lead to adverse pregnancy outcomes and increased health risks for both mother and child. The prevalence of iron deficiency was low, but as this was during early pregnancy, the women might develop iron deficiency and consequently iron deficiency anemia as the pregnancy progresses.

  • 5.
    Lindström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Raqib, Rubhana
    El Arifeen, Shams
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Associations between oxidative parameters in pregnancy and birth anthropometry in a cohort of women and children in rural Bangladesh: The MINIMat-cohort2012In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 46, no 3, p. 253-264Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Maternal and Infant Nutrition Interventions, Matlab) in rural Bangladesh, free 8-iso-prostaglandin P-2 alpha (lipid peroxidation) was analysed in pregnancy week 14 and 30 and 8-Hydroxy-2 '-Deoxyguanosine (DNA oxidation) in week 19. We found that higher levels of lipid peroxidation in early pregnancy were associated with larger infant size (birth length and chest circumference). In late pregnancy, no clear pattern of associations was found. Increasing level of DNA oxidation was associated with lower birth length in girls but no other associations were found. In conclusion, a higher level of lipid peroxidation in early (but not late) pregnancy was associated with a favourable larger birth size suggesting that timing of lipid peroxidation is of importance.

  • 6.
    Svefors, Pernilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rahman, Anisur
    International Centre for Diarrhoeal Disease Research, Bangladesh (iccdr,b), Dhaka, Bangladesh.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Khan, Ashraful Islam
    International Centre for Diarrhoeal Disease Research, Bangladesh (iccdr,b), Dhaka, Bangladesh.
    Lindström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Persson, Lars Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekholm Selling, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stunted at 10 Years. Linear Growth Trajectories and Stunting from Birth to Pre-Adolescence in a Rural Bangladeshi Cohort.2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0149700Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Few studies in low-income settings analyse linear growth trajectories from foetal life to pre-adolescence. The aim of this study is to describe linear growth and stunting from birth to 10 years in rural Bangladesh and to analyse whether maternal and environmental determinants at conception are associated with linear growth throughout childhood and stunting at 10 years.

    METHODS AND FINDINGS: Pregnant women participating in the MINIMat trial were identified in early pregnancy and a birth cohort (n = 1054) was followed with 19 growth measurements from birth to 10 years. Analyses of baseline predictors and mean height-for-age Z-scores (HAZ) over time were modelled using GLMM. Logistic regression analysis was used to investigate the associations between baseline predictors and stunting (HAZ<-2) at 10 years. HAZ decreased to 2 years, followed by an increase up to 10 years, while the average height-for-age difference in cm (HAD) to the WHO reference median continued to increase up to 10 years. Prevalence of stunting was highest at 2 years (50%) decreasing to 29% at 10 years. Maternal height, maternal educational level and season of conception were all independent predictors of HAZ from birth to pre-adolescence (p<0.001) and stunting at 10 years. The highest probability to be stunted at 10 years was for children born by short mothers (<147.5 cm) (ORadj 2.93, 95% CI: 2.06-4.20), mothers with no education (ORadj 1.74, 95% CI 1.17-2.81) or those conceived in the pre-monsoon season (ORadj 1.94, 95% CI 1.37-2.77).

    CONCLUSIONS: Height growth trajectories and prevalence of stunting in pre-adolescence showed strong intergenerational associations, social differentials, and environmental influence from foetal life. Targeting women before and during pregnancy is needed for the prevention of impaired child growth.

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