Maternal Vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years

Sara Neelon, A. J. White, A. C. Vidal, J. M. Schildkraut, A. P. Murtha, S. K. Murphy, S. W. Kullman, C. Hoyo

Research output: Contribution to journalArticle

Abstract

Background/Objective:Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how Vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring.SubjectS/Methods:We conducted linear regressions to assess maternal plasma 25-hydroxyVitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10.Results:Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l â 'm at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (â '0.43 units; CI: â '0.79, â '0.07; P=0.02 for Q1 and â '0.56 units; CI: â '0.89, â '0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing.Conclusions:Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.

Original languageEnglish (US)
Pages (from-to)587-593
Number of pages7
JournalInternational Journal of Obesity
Volume42
Issue number4
DOIs
StatePublished - Apr 1 2018

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Nucleic Acid Regulatory Sequences
DNA Methylation
Birth Weight
Vitamin D
Mothers
Gestational Age
Weights and Measures
Body Mass Index
Pregnancy
Vitamin D Deficiency
Fetal Development
Methylation
Genes
Linear Models
Parturition
Growth

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Maternal Vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years. / Neelon, Sara; White, A. J.; Vidal, A. C.; Schildkraut, J. M.; Murtha, A. P.; Murphy, S. K.; Kullman, S. W.; Hoyo, C.

In: International Journal of Obesity, Vol. 42, No. 4, 01.04.2018, p. 587-593.

Research output: Contribution to journalArticle

Neelon, S, White, AJ, Vidal, AC, Schildkraut, JM, Murtha, AP, Murphy, SK, Kullman, SW & Hoyo, C 2018, 'Maternal Vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years', International Journal of Obesity, vol. 42, no. 4, pp. 587-593. https://doi.org/10.1038/ijo.2017.160
Neelon, Sara ; White, A. J. ; Vidal, A. C. ; Schildkraut, J. M. ; Murtha, A. P. ; Murphy, S. K. ; Kullman, S. W. ; Hoyo, C. / Maternal Vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years. In: International Journal of Obesity. 2018 ; Vol. 42, No. 4. pp. 587-593.
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title = "Maternal Vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years",
abstract = "Background/Objective:Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how Vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring.SubjectS/Methods:We conducted linear regressions to assess maternal plasma 25-hydroxyVitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10.Results:Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l {\^a} 'm at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores ({\^a} '0.43 units; CI: {\^a} '0.79, {\^a} '0.07; P=0.02 for Q1 and {\^a} '0.56 units; CI: {\^a} '0.89, {\^a} '0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing.Conclusions:Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.",
author = "Sara Neelon and White, {A. J.} and Vidal, {A. C.} and Schildkraut, {J. M.} and Murtha, {A. P.} and Murphy, {S. K.} and Kullman, {S. W.} and C. Hoyo",
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T1 - Maternal Vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years

AU - Neelon, Sara

AU - White, A. J.

AU - Vidal, A. C.

AU - Schildkraut, J. M.

AU - Murtha, A. P.

AU - Murphy, S. K.

AU - Kullman, S. W.

AU - Hoyo, C.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background/Objective:Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how Vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring.SubjectS/Methods:We conducted linear regressions to assess maternal plasma 25-hydroxyVitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10.Results:Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l â 'm at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (â '0.43 units; CI: â '0.79, â '0.07; P=0.02 for Q1 and â '0.56 units; CI: â '0.89, â '0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing.Conclusions:Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.

AB - Background/Objective:Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how Vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring.SubjectS/Methods:We conducted linear regressions to assess maternal plasma 25-hydroxyVitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10.Results:Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l â 'm at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (â '0.43 units; CI: â '0.79, â '0.07; P=0.02 for Q1 and â '0.56 units; CI: â '0.89, â '0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing.Conclusions:Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.

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