Maternal biomarker patterns for metabolism and inflammation in pregnancy are influenced by multiple micronutrient supplementation and associated with child biomarker patterns and nutritional status at 9-12 years of age.

Maternal nutritional status influences fetal development and long-term risk for adult non-communicable diseases. However, the underlying mechanisms remain poorly understood. We examined whether biomarkers for metabolism and inflammation during pregnancy were associated with maternal health and with child biomarkers and health at 9-12 years of age in 44 maternal-child dyads from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, ISRCTN34151616) in Lombok, Indonesia. Archived blood for each dyad from maternal enrollment, later in pregnancy, postpartum, and from children at 9-12 years comprised 132 specimens. Multiplex microbead immunoassays were used to quantify vitamin D-binding protein (D), adiponectin (A), retinol-binding protein 4 (R), C-reactive protein (C), and leptin (L). Principal component analysis (PCA) revealed distinct variance patterns, i.e. principal components (PC), for baseline pregnancy, bp.pc1.D↓A↓R↓ and bp.pc2.C↓L↑; combined follow-up during pregnancy and postpartum, dp-pp.pc1.D↑↓A↑R↑↓L↓ and dp-pp.pc2.A↑C↑L↑; and children, ch.pc1.D↑R↑C↑ and ch.pc2.D↓A↑L↑. Maternal multiple micronutrient (MMN) supplementation led to an association of baseline maternal bp.pc2.C↓L↑ with decreased post-supplementation maternal dp-pp.pc2.A↑C↑L↑ (p = 0.022), which was in turn associated with both increased child ch.pc1.D↑R↑C↑ (p = 0.036) and decreased child BMI z-score (BMIZ) (p = 0.022). Further analyses revealed an association between maternal dp-pp.pc1.D↑↓A↑R↑↓L↓ and increased child BMIZ (p = 0.036). Child ch.pc1.D↑R↑C↑ was associated with decreased birth weight (p = 0.036) and increased child BMIZ (p = 0.002). Child ch.pc2.D↓A↑L↑ was associated with increased child BMIZ (p = 0.005), decreased maternal height (p = 0.030) and girls (p = 0.002). A pattern of elevated maternal adiponectin and leptin in pregnancy was associated with increased C-reactive protein, vitamin A, and D binding proteins pattern in children, suggesting biomarkers acting in concert may have qualitative as well as quantitative influence beyond single biomarker effects. Patterns in pregnancy proximal to birth were more associated with child status. In addition, child patterns were more associated with child status, particularly child BMI. MMN supplementation affects maternal biomarker patterns of metabolism and inflammation in pregnancy, and potentially in the child. However, child nutrition conditions after birth may have a greater impact on metabolism and inflammation.

A genetic approach to study the relationship between maternal Vitamin D status and newborn anthropometry measurements: the Vitamin D pregnant mother (VDPM) cohort study.

PURPOSE: Adverse effects of maternal vitamin D deficiency have been linked to adverse pregnancy outcomes. We investigated the relationship between maternal vitamin D status and newborn anthropometry measurements using a genetic approach and examined the interaction between genetic variations in involved in vitamin D synthesis and metabolism and maternal vitamin D concentrations on newborn anthropometry. METHODS: The study was conducted in 183 pregnant Indonesian Minangkabau women. Genetic risk scores (GRSs) were created using six vitamin D-related single nucleotide polymorphisms and their association with 25-hydroxyvitamin D [25(OH)D] levels and newborn anthropometry (183 infants) were investigated. RESULTS: There was no significant association between maternal 25(OH)D concentrations and newborn anthropometry measurements (P > 0.05, for all comparisons). After correction for multiple testing using Bonferroni correction, GRS was significantly associated with 25(OH)D in the third trimester (P = 0.004). There was no association between GRS and newborn anthropometric measurements; however, there was an interaction between GRS and 25(OH)D on head circumference (P = 0.030), where mothers of neonates with head circumference < 35 cm had significantly lower 25(OH)D if they carried ≥4 risk alleles compared to those who carried ≤3 risk alleles. CONCLUSION: Our findings demonstrate the impact of vitamin D-related GRS on 25(OH)D and provides evidence for the effect of vitamin D-related GRS on newborn anthropometry through the influence of serum 25(OH)D levels among Indonesian pregnant women. Even though our study is a prospective cohort, before the implementation of vitamin D supplementation programs in Indonesia to prevent adverse pregnancy outcomes, further large studies are required to confirm our findings.

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia.

BACKGROUND: The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood. OBJECTIVE: The aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN). METHODS: We used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models. RESULTS: In both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (ß = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (ß = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (ß = -7.39, P = 0.017). CONCLUSION: Maternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Vitamin D deficiency status and its related risk factors during early pregnancy: a cross-sectional study of pregnant Minangkabau women, Indonesia.

BACKGROUND: Vitamin D deficiency (VDD) is a common problem in reproductive-aged women and has become a major public health problem worldwide. The effect of VDD in pregnancy has been associated with several adverse pregnancy outcomes. This study aims to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) in the first trimester and its associated factors (socio-demographics, pregnancy profiles, dietary intake, and maternal anthropometry measurements) for the determination of vitamin D deficiency status in early pregnancy. METHODS: A cross-sectional study of 239 pregnant mothers in West Sumatra, Indonesia was conducted. We measured lifestyle, socio-demographics and pregnancy profile through a structured questionnaire and interview process. A semi quantitative-food frequency questionnaire (SQ-FFQ) was used to analyse the dietary intake of the pregnant women. Serum 25(OH)D concentrations were measured at < 13 weeks gestation using ELISA and logistic regression models were employed to identify the predictors of low vitamin D status. RESULTS: The prevalence of first-trimester maternal VDD and sufficiency were 82.8 and 17.2% respectively. The median 25(OH)D was 13.15 ng/mL (3.00-49.29 ng/mL). The significant independent predictors were no working status (OR: 0.029;0.001-0.708) (p = 0.030); nulliparous parity status (OR: 7.634;1.550-37.608) (p = 0.012); length of outdoor activity status of less than an hour (OR: 9.659;1.883-49.550) (p = 0.007); and no consumption of supplements before pregnancy (OR: 4.49;1.081-18.563) (p = 0.039). CONCLUSIONS: The prevalence of VDD is common in early pregnancy among Minangkabau women. Recommendations and policies to detect and prevent such insufficiency during pregnancy should be developed by considering the associated factors.