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Effects of micronutrients on placental function: evidence from clinical studies to animal models.

Abstract

Micronutrient deficiencies are common in pregnant women due to low dietary intake and increased requirements for fetal development. Low maternal micronutrient status is associated with a range of pregnancy pathologies involving placental dysfunction, including fetal growth restriction (FGR), small-for-gestational age (SGA), pre-eclampsia and preterm birth. However, clinical trials commonly fail to convincingly demonstrate beneficial effects of supplementation of individual micronutrients, attributed to heterogeneity and insufficient power, potential interactions and lack of mechanistic knowledge of effects on the placenta. We aimed to provide current evidence of relationships between selected micronutrients (vitamin D, vitamin A, iron, folate, vitamin B12) and adverse pregnancy outcomes, combined with understanding of actions on the placenta. Following a systematic literature search, we reviewed data from clinical, in vitro and in vivo studies of micronutrient deficiency and supplementation. Key findings are potential effects of micronutrient deficiencies on placental development and function, leading to impaired fetal growth. Studies in human trophoblast cells and rodent models provide insights into underpinning mechanisms. Interestingly, there is emerging evidence that deficiencies in all micronutrients examined induce a pro-inflammatory state in the placenta, drawing parallels with the inflammation detected in FGR, pre-eclampsia, stillbirth and preterm birth. Beneficial effects of supplementation are apparent in vitro and in animal models and for combined micronutrients in clinical studies. However, greater understanding of the roles of these micronutrients, and insight into their involvement in placental dysfunction, combined with more robust clinical studies, is needed to fully ascertain the potential benefits of supplementation in pregnancy.

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  • Authors+Show Affiliations

    ,

    Maternal and Fetal Health Research CentreDivision of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

    ,

    Maternal and Fetal Health Research CentreDivision of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

    Maternal and Fetal Health Research CentreDivision of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Rebecca.Lee.Jones@manchester.ac.uk.

    Source

    Reproduction (Cambridge, England) 156:3 2018 09 pg R69-R82

    MeSH

    Animals
    Dietary Supplements
    Female
    Fetal Development
    Folic Acid
    Folic Acid Deficiency
    Humans
    Infant, Newborn
    Iron
    Iron, Dietary
    Micronutrients
    Models, Animal
    Placenta
    Pregnancy
    Pregnancy Complications
    Pregnancy Outcome
    Randomized Controlled Trials as Topic
    Trophoblasts
    Vitamin A
    Vitamin A Deficiency
    Vitamin B 12
    Vitamin B 12 Deficiency
    Vitamin D
    Vitamin D Deficiency

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    29844225

    Citation

    Baker, Bernadette C., et al. "Effects of Micronutrients On Placental Function: Evidence From Clinical Studies to Animal Models." Reproduction (Cambridge, England), vol. 156, no. 3, 2018, pp. R69-R82.
    Baker BC, Hayes DJ, Jones RL. Effects of micronutrients on placental function: evidence from clinical studies to animal models. Reproduction. 2018;156(3):R69-R82.
    Baker, B. C., Hayes, D. J., & Jones, R. L. (2018). Effects of micronutrients on placental function: evidence from clinical studies to animal models. Reproduction (Cambridge, England), 156(3), pp. R69-R82. doi:10.1530/REP-18-0130.
    Baker BC, Hayes DJ, Jones RL. Effects of Micronutrients On Placental Function: Evidence From Clinical Studies to Animal Models. Reproduction. 2018;156(3):R69-R82. PubMed PMID: 29844225.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of micronutrients on placental function: evidence from clinical studies to animal models. AU - Baker,Bernadette C, AU - Hayes,Dexter Jl, AU - Jones,Rebecca L, Y1 - 2018/05/29/ PY - 2018/03/12/received PY - 2018/05/29/accepted PY - 2018/5/31/pubmed PY - 2018/11/28/medline PY - 2018/5/31/entrez SP - R69 EP - R82 JF - Reproduction (Cambridge, England) JO - Reproduction VL - 156 IS - 3 N2 - Micronutrient deficiencies are common in pregnant women due to low dietary intake and increased requirements for fetal development. Low maternal micronutrient status is associated with a range of pregnancy pathologies involving placental dysfunction, including fetal growth restriction (FGR), small-for-gestational age (SGA), pre-eclampsia and preterm birth. However, clinical trials commonly fail to convincingly demonstrate beneficial effects of supplementation of individual micronutrients, attributed to heterogeneity and insufficient power, potential interactions and lack of mechanistic knowledge of effects on the placenta. We aimed to provide current evidence of relationships between selected micronutrients (vitamin D, vitamin A, iron, folate, vitamin B12) and adverse pregnancy outcomes, combined with understanding of actions on the placenta. Following a systematic literature search, we reviewed data from clinical, in vitro and in vivo studies of micronutrient deficiency and supplementation. Key findings are potential effects of micronutrient deficiencies on placental development and function, leading to impaired fetal growth. Studies in human trophoblast cells and rodent models provide insights into underpinning mechanisms. Interestingly, there is emerging evidence that deficiencies in all micronutrients examined induce a pro-inflammatory state in the placenta, drawing parallels with the inflammation detected in FGR, pre-eclampsia, stillbirth and preterm birth. Beneficial effects of supplementation are apparent in vitro and in animal models and for combined micronutrients in clinical studies. However, greater understanding of the roles of these micronutrients, and insight into their involvement in placental dysfunction, combined with more robust clinical studies, is needed to fully ascertain the potential benefits of supplementation in pregnancy. SN - 1741-7899 UR - https://www.unboundmedicine.com/medline/citation/29844225/Effects_of_micronutrients_on_placental_function:_evidence_from_clinical_studies_to_animal_models_ L2 - https://rep.bioscientifica.com/doi/10.1530/REP-18-0130 DB - PRIME DP - Unbound Medicine ER -