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Maternal experiences before pregnancy predict birth outcomes, a key indicator of health trajectories, but the timing and pathways for these effects are poorly understood. Here we test the hypothesis that maternal pre‐adult growth patterns predict pregnancy glucose and offspring fetal growth in Cebu, Philippines.

Using multiple regression and path analysis, gestational age‐adjusted birthweight and variables reflecting infancy, childhood, and post‐childhood/adolescent weight gain (conditional weights) were used to predict pregnancy HbA1c and offspring birth outcomes among participants in the Cebu Longitudinal Health and Nutrition Survey.

Maternal early/mid‐childhood weight gain predicted birth weight, length, and head circumference in female offspring. Late‐childhood/adolescent weight gain predicted birth length, birth weight, skinfold thickness, and head circumference in female offspring, and head circumference in male offspring. Pregnancy HbA1c did not mediate relationships between maternal growth and birth size parameters.

In Cebu, maternal growth patterns throughout infancy, childhood, and adolescence predict fetal growth via a pathway independent of circulating glucose, with stronger impacts on female than male offspring, consistent with a role of developmental nutrition on offspring fetal growth. Notably, the strength of relationships followed a pattern opposite to what occurs in response to acute pregnancy stress, with strongest effects on head circumference and birth length and weakest on skinfolds. We speculate that developmental sensitivities are reversed for stable, long‐term nutritional cues that reflect average local environments. These findings are relevant to public health and life‐history theory as further evidence of developmental influences on health and resource allocation across the life course.

Consistent with evolutionarily theorized costs of reproduction (CoR), reproductive history in women is associated with life expectancy and susceptibility to certain cancers, autoimmune disorders and metabolic disease. Immunological changes originating during reproduction may help explain some of these relationships.

To explore the potential role of the immune system in female CoR, we characterized leukocyte composition and regulatory processes using DNA methylation (DNAm) in a cross-sectional cohort of young (20–22 years old) women differing in reproductive status.

Compared to nulliparity, pregnancy was characterized by differential methylation at 828 sites, 96% of which were hypomethylated and enriched for genes associated with T-cell activation, innate immunity, pre-eclampsia and neoplasia. Breastfeeding was associated with differential methylation at 1107 sites (71% hypermethylated), enriched for genes involved in metabolism, immune self-recognition and neurogenesis. There were no significant differences in DNAm between nulliparous and parous women. However, compared to nullipara, pregnant women had lower proportions of B, CD4T, CD8T and natural killer (NK) cells, and higher proportions of granulocytes and monocytes. Monocyte counts were lower and NK counts higher among breastfeeding women, and remained so among parous women.

Our findings point to widespread differences in DNAm during pregnancy and lactation. These effects appear largely transient, but may accumulate with gravidity become detectable as women age. Nulliparous and parous women differed in leukocyte composition, consistent with more persistent effects of reproduction on cell type. These findings support transient (leukocyte DNAm) and persistent (cell composition) changes associated with reproduction in women, illuminating potential pathways contributing to CoR.

Lay Summary: Evolutionary theory and epidemiology support costs of reproduction (CoR) to women’s health that may involve changes in immune function. We report differences in immune cell composition and gene regulation during pregnancy and breastfeeding. While many of these differences appear transient, immune cell composition may remain, suggesting mechanisms for female CoR.

Microchimerism is the presence of a small quantity of cells or DNA from a genetically distinct individual. This phenomenon occurs with bidirectional maternal‐fetal exchange during pregnancy. Microchimerism can persist for decades after delivery and have long‐term health implications. However, little is known about why microchimerism is detectable at varying levels in different individuals. We examine the variability and the following potential determinants of maternal‐origin microchimerism (MMc) in young women in the Philippines: gestational duration (in utero exposure to MMc), history of being breastfed (postpartum exposure to MMc), maternal telomere length (maternal cells' ability to replicate and persist), and participant's pregnancies in young adulthood (effect of adding fetal‐origin microchimerism to preexisting MMc).

Data are from the Cebu Longitudinal Health and Nutrition Survey, a population‐based study of infant feeding practices and long‐term health outcomes. We quantified MMc using quantitative PCR (qPCR) in 89 female participants, ages 20–22, and analyzed these data using negative binomial regression.

In a multivariate model including all predictors, being breastfed substantially predicted decreased MMc (detection rate ratio = 0.15,p= 0.007), and there was a trend of decreasing MMc in participants who had experienced more pregnancies (detection rate ratio = 0.55,p= 0.057).

These results might be explained by breastfeeding having lasting impact on immune regulatory networks, thus reducing MMc persistence. MMc may also decrease in response to the introduction of fetal‐origin microchimerism with pregnancies experienced in adulthood.

We investigated the relationship between early life growth patterns and blood telomere length (TL) in adulthood using conditional measures of lean and fat mass growth to evaluate potentially sensitive periods of early life growth.

This study included data from 1562 individuals (53% male; age 20‐22 years) participating in the Cebu Longitudinal Health and Nutrition Survey, located in metropolitan Cebu, Philippines. Primary exposures included length‐for‐agez‐score (HAZ) and weight‐for‐agez‐score (WAZ) at birth and conditional measures of linear growth and weight gain during four postnatal periods: 0‐6, 6‐12, and 12‐24 months, and 24 months to 8.5 years. TL was measured at ~21 years of age. We estimated associations using linear regression.

The study sample had an average gestational age (38.5 ± 2 weeks) and birth size (HAZ = –0.2 ± 1.1, WAZ = –0.7 ± 1.0), but by age 8.5 years had stunted linear growth (HAZ = –2.1 ± 0.9) and borderline low weight (WAZ = –1.9 ± 1.0) relative to World Health Organization references. Heavier birth weight was associated with longer TL in early adulthood (P= .03), but this association was attenuated when maternal age at birth was included in the model (P= .07). Accelerated linear growth between 6 and 12 months was associated with longer TL in adulthood (P= .006), whereas weight gain between 12 and 24 months was associated with shorter TL in adulthood (P= .047).

In Cebu, individuals who were born heavier have longer TL in early adulthood, but that birthweight itself may not explain the association. Findings suggest that childhood growth is associated with the cellular senescence process in adulthood, implying early life well‐being may be linked to adult health.