Background Many maternal traits are associated with a neonate’s gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. Methods and findings Based on 10,734 mother–infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration ( p = 2.2 × 10 −4 ). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length ( p < 1 × 10 −17 ). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect ( p = 1.6 × 10 −4 ). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect ( p = 9.4 × 10 −3 ), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects ( p = 3.3 × 10 −2 and p = 4.5 × 10 −3 , respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight ( p = 4.7 × 10 −6 ); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect ( p = 2.2 × 10 −3 ). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect ( p = 6.4 × 10 −3 ) and a stronger fetal effect ( p = 1.3 × 10 −5 ). The paternal transmitted birth weight score was significantly associated with reduced gestational duration ( p = 1.8 × 10 −4 ) and increased maternal systolic BP during pregnancy ( ...

Low cobalamin intake and status during pregnancy or lactation have been linked to adverse maternal and perinatal health outcomes, whereas low cobalamin status during early childhood is associated with impaired development in children. Women who begin pregnancy with depleted stores (low or very low plasma cobalamin) will give birth to depleted infants who are likely to develop deficiency symptoms during the first few weeks or months postpartum. Newly ingested cobalamin during pregnancy and lactation (from diet or supplements) is transferred to the child and is not likely to correct cobalamin status in depleted women. The prevalence of low cobalamin status is high especially in low-income settings or in populations with a low intake of animal products. Folate and cobalamin play interdependent roles in one-carbon metabolism. Although folic acid supplementation during early pregnancy is widely recommended and practiced, cobalamin supplementation during pregnancy and lactation has received little attention. Furthermore, the intake recommendations for pregnant and lactating women and in early life need reevaluation in the light of newly available evidence in the field.

Early childhood obesity is a growing global concern, however the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood BMI at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform GWAS across 12 time points from birth to eight years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are enriched near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1, and KLF14 point toward a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profile through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth. ResultsBMI from 28,681 children was measured at birth,

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.