skip to main content


Title: Evidence that highly canalized fetal traits are sensitive to intergenerational effects of maternal developmental nutrition
Abstract Objectives

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.

Methods

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.

Results

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.

Discussion

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.

 
more » « less
NSF-PAR ID:
10476712
Author(s) / Creator(s):
 ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
American Journal of Biological Anthropology
Volume:
183
Issue:
4
ISSN:
2692-7691
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Objectives

    The maternal environment during gestation influences offspring health at birth and throughout the life course. Recent research has demonstrated that endogenous immune processes such as dysregulated inflammation adversely impact birth outcomes, increasing the risk for preterm birth and restricted fetal growth. Prior analyses examining this association suggest a relationship between maternal C‐reactive protein (CRP), a summary measure of inflammation, and offspring anthropometric outcomes. This study investigates pro‐ and anti‐inflammatory cytokines, and their ratio, to gain deeper insight into the regulation of inflammation during pregnancy.

    Methods

    IL6, IL10, TNFɑ, and CRP were quantified in dried blood spots collected in the early third trimester (mean = 29.9 weeks) of 407 pregnancies in Metropolitan Cebu, Philippines. Relationships between these immune markers and offspring anthropometrics (birth weight, length, head circumference, and sum of skinfold thicknesses) were evaluated using multivariate regression analyses. Ratios of pro‐ to anti‐inflammatory cytokines were generated.

    Results

    Higher maternal IL6 relative to IL10 was associated with reduced offspring weight and length at birth. Individual cytokines did not predict birth outcomes.

    Conclusions

    Consistent with the idea that the relative balance of cytokines with pro‐ and anti‐inflammatory effects is a key regulator of inflammation in pregnancy, the IL6:IL10 ratio, but neither cytokine on its own, predicted offspring birth outcomes. Our findings suggest that prior reports of association between CRP and fetal growth may reflect, in part, the balance between pro‐ and anti‐inflammatory cytokines, and that the gestational environment is significantly shaped by cytokine imbalance.

     
    more » « less
  2. Abstract Objective

    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.

    Methods

    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.

    Results

    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).

    Conclusions

    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.

     
    more » « less
  3. Abstract Objectives

    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).

    Materials and Methods

    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.

    Results

    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).

    Discussion

    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.

     
    more » « less
  4. Abstract Objectives

    Lactational programming, through which milk‐borne bioactives influence both neonatal and long‐term biological development, is well established. However, almost no research has investigated how developmental stimuli during a mother's early life may influence her milk bioactives in adulthood. Here, we investigated the association between maternal birth weight and milk epidermal growth factor (EGF) and epidermal growth factor receptor (EGF‐R) in later life. We predicted there would be a decrease in both milk EGF and EGF‐R in the milk produced by mothers who were themselves born low birth weight.

    Methods

    Study participants are from the Cebu Longitudinal Health and Nutrition Survey. Mothers (n= 69) were followed longitudinally since birth with prospective data collection. Anthropometrics, health, and dietary recalls were collected with early morning milk samples when mothers were 24 to 25 years of age. Milk samples were analyzed for EGF and its receptor (EGF‐R). Analysis of variance was used to test for differences in milk EGF and EGF‐R between low and average birthweight mothers after adjustment for parity, age, and maternal dietary energy intake.

    Results

    Mothers who were low birth weight produced milk with significantly less EGF and more EGF‐R which resulted in a lower ratio of EGF to EGF‐R. These associations persisted after adjustment for infant age, maternal adiposity, and dietary energy.

    Conclusions

    While this is a small sample size, these preliminary findings suggest that maternal early life characteristics, such as birth weight, may be important contributors to variation in milk bioactives. Future work is necessary to understand how variation in maternal early life may influence milk composition in adulthood.

     
    more » « less
  5. Abstract Objective

    A mother–child dyad trajectory model of weight and body composition spanning from conception to adolescence was developed to understand how early life exposures shape childhood body composition.

    Methods

    African American (49.3%) and Dominican (50.7%) pregnant mothers (n= 337) were enrolled during pregnancy, and their children (47.5% female) were followed from ages 5 to 14. Gestational weight gain (GWG) was abstracted from medical records. Child weight, height, percentage body fat, and waist circumference were measured. GWG and child body composition trajectories were jointly modeled with a flexible latent class model with a class membership component that included prepregnancy BMI.

    Results

    Four prenatal and child body composition trajectory patterns were identified, and sex‐specific patterns were observed for the joint GWG–postnatal body composition trajectories with more distinct patterns among girls but not boys. Girls of mothers with high GWG across gestation had the highest BMIzscore, waist circumference, and percentage body fat trajectories from ages 5 to 14; however, boys in this high GWG group did not show similar growth patterns.

    Conclusions

    Jointly modeled prenatal weight and child body composition trajectories showed sex‐specific patterns. Growth patterns from childhood though early adolescence appeared to be more profoundly affected by higher GWG patterns in females, suggesting sex differences in developmental programming.

     
    more » « less