Lower Socioeconomic Status Predicts Increased Proinflammatory Signaling in Late Pregnancy: Evidence From a Filipino Cohort.

OBJECTIVES: Maternal socioeconomic status (SES) is an important predictor of adverse birth outcomes and postnatal health across global populations. Chronic inflammation is implicated in cardiometabolic disease risk in high-income contexts and is a potential pathway linking maternal adversity to offspring health trajectories. To clarify how socioeconomic inequality shapes pregnancy inflammation in middle-income settings, we investigated SES as a predictor of inflammatory cytokines in late gestation in a sample from the Cebu Longitudinal Health Nutrition Survey in Cebu, Philippines. METHODS: We used multiple regression to evaluate maternal SES, reflected in household assets, as a predictor of general inflammation (C-reactive protein), inflammatory cytokines (interleukin-6, interleukin-10), and inflammatory balance (n = 407). Inflammatory markers were measured at 29.9 weeks gestation in dried blood spots, and a measure reflecting relative balance of IL6 and IL10 was calculated to capture pro- versus anti-inflammatory skewed immune profiles. RESULTS: Greater household assets significantly predicted lower IL6 concentration (p <  0.001), with a trend toward lower IL6 relative to IL10 (p = 0.084). C-reactive protein and IL10 were not individually related to SES. CONCLUSIONS: The inverse relationship between SES and pregnancy inflammation in Cebu is consistent with results from high-income settings. These findings further highlight the influence of socioeconomic conditions on immune regulation during pregnancy. Given the evidence that gestational inflammation impacts offspring fetal growth, our results suggest that social and economic effects on immune function may be an important pathway for the intergenerational transmission of health disparities.

Regulation of inflammation during gestation and birth outcomes: Inflammatory cytokine balance predicts birth weight and length.

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.

Evidence that highly canalized fetal traits are sensitive to intergenerational effects of maternal developmental nutrition.

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.

Investigating the IGF axis as a pathway for intergenerational effects.

Early nutritional and growth experiences can impact development, metabolic function, and reproductive outcomes in adulthood, influencing health trajectories in the next generation. The insulin-like growth factor (IGF) axis regulates growth, metabolism, and energetic investment, but whether it plays a role in the pathway linking maternal experience with offspring prenatal development is unclear. To test this, we investigated patterns of maternal developmental weight gain (a proxy of early nutrition), young adult energy stores, age, and parity as predictors of biomarkers of the pregnancy IGF axis (n = 36) using data from the Cebu Longitudinal Health and Nutrition Survey in Metro Cebu, Philippines. We analyzed maternal conditional weight measures at 2, 8, and 22 years of age and leptin at age 22 (a marker of body fat/energy stores) in relation to free IGF-1 and IGFBP-3 in mid/late pregnancy (mean age = 27). Maternal IGF axis measures were also assessed as predictors of offspring fetal growth. Maternal age, parity, and age 22 leptin were associated with pregnancy free IGF-1, offspring birth weight, and offspring skinfold thickness. We find that free IGF-1 levels in pregnancy are more closely related to nutritional status in early adulthood than to preadult developmental nutrition and demonstrate significant effects of young adult leptin on offspring fetal fat mass deposition. We suggest that the previously documented finding that maternal developmental nutrition predicts offspring birth size likely operates through pathways other than the maternal IGF axis, which reflects more recent energy status.

Global population variation in placental size and structure: Evidence from Cebu, Philippines.

INTRODUCTION: Placental morphology influences the intrauterine environment and fetal growth, which help set life-course health trajectories across generations. Little is known about placental characteristics in populations with chronic nutritional insufficiency where birth weights tend to be lower, and how these relationships between birth and placental weights vary across populations. METHODS: We collected weights and stereologically-determined villous mass and surface area of 21 placentas from offspring of women enrolled in a birth cohort study in metropolitan Cebu, Philippines, a low-income population. We identified 15 samples from other global populations ranging from low to high income that had similar data to ours to assess patterns of variation between birth and placental weights and microscopic characteristics. We ranked the population samples in order for each characteristic. RESULTS: Mean birth weight in Cebu was 3162 ±â€¯80 g (ranked 9/16) and placental weight was 454 ±â€¯32 g (ranked 12/16). Birth:placental weight ratio was 7.0 (ranked 3/16). Average villous surface area for Cebu placentas was 6.5 m2 (ranked 9/12); Birth weight:villous surface area was 0.048 g/m2 (ranked 4/12). DISCUSSION: Placentas from Cebu produced heavier neonates per units of placental weight and villous surface area than most other populations, despite lower villous surface areas and less complex surface-to-volume topography. This range of placental efficiency spurs questions about the mechanisms by which placental morphology optimizes efficiency in different environmental contexts during gestation. Placental variation both within and across populations is likely due to many intersecting environmental, metabolic, and (epi)genetic factors that will require additional research to clarify.