Clinical Research Directory

The Developmental Origins of Obesity

Pregestational obesity (PGO, BMI ≥30) is a significant independent risk factor for the development of obesity in childhood and adolescence. Notably, elevated levels of IL-6 and leptin have been found in the cord blood of offspring born to women with PGO, along with increased body fat. Both our research and that of others have shown an upregulation of pro-inflammatory genes in cord blood monocytes and alterations in innate immune function, including a blunted response to pro-inflammatory stimuli. However, it remains unclear whether these effects are due to an altered immune response in differentiated immune cells or if they are programmed earlier in gestation, during the progenitor cell stage. Long-chain polyunsaturated fatty acids (LCPUFAs) are crucial for cellular function, acting as precursors to membrane components and signaling molecules involved in cardiovascular, metabolic, and immune processes. Modern dietary patterns have led to a relative deficiency in n-3 LCPUFAs, such as Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA). As a result, international health guidelines recommend LCPUFA supplementation during pregnancy. Studies have shown that increased intake of n-3 LCPUFAs during pregnancy exerts effective anti-inflammatory effects in the maternal circulation, adipose tissue, and placenta. The recently completed MIGHT study (NCT02574767), which involved 1005 women with overweight or PGO, investigated the effects of DHA supplementation during pregnancy (200 mg vs. 800 mg/day). A subgroup of the newborns from this cohort also participated in the EpiFat study (NCT04249635), conducted by our team (2017-2021). The findings demonstrated that maternal DHA supplementation (800 mg/day) significantly reduced body fat and improved adipose metabolic markers in offspring at birth, with these effects persisting until 4 months of age. Additionally, the cord blood monocytes of PGO offspring exhibited increased expression of pro-inflammatory genes (IL-6, MCP-1, TNF-α, IL-8), but these effects were completely reversed in the offspring of DHA-supplemented women. These results provide strong evidence of pro-inflammatory programming in innate immune cells and adiposity in offspring of women with PGO, and show that maternal PUFA supplementation during pregnancy can reverse these early obesity biomarkers. However, it remains unclear whether these effects persist into early childhood (5 years of age), particularly in high-risk populations such as those born to women with PGO. Moreover, we hypothesize that maternal obesogenic signals during early embryonic development may affect the progenitor cells of adipocytes (mesenchymal stem cells, MSC) and monocytes (hematopoietic stem cells, HSC), potentially leading to long-term effects on the offspring. This study hypothesizes that: "Maternal obesity increases the risk of childhood obesity by programming adipose and immune progenitor cells, an effect that may be mitigated by maternal supplementation with polyunsaturated fatty acids during pregnancy." To test this hypothesis, we propose: A pilot clinical study to examine whether maternal PGO affects the lineage commitment, number, TLR4 signaling, and epigenetic markers (ChIP-seq) of monocyte (HSC) and adipocyte (MSC) progenitor cells, and whether maternal supplementation with PUFAs during pregnancy can modify these effects. The OMEGA Stem study will invite 160 healthy women (80 with normal weight and 80 with pregestational obesity) with singleton pregnancies to participate. Participants will receive either 600 mg/day of EPA/DHA (1 capsule) or standard antenatal care. A trained midwife will enroll the women \<16 weeks of pregnancy, with data collection (sociodemographic information, clinical data and blood samples) at study initiation, 26-28 weeks, and at delivery. Neonatal body composition will be assessed by a trained midwife (24-48 hours after delivery) through anthropometric measurements and skinfold thickness, calculated using Catalano's formula.

Impact of Maternal Body Mass Index on Infant Hypoxic Events at Time of Delivery ,Cross-sectional Study.

Offspring from overweight or obese mothers appear to be at up to 38% increased risk of being admitted to the neonatal intensive care unit than the offspring of mothers with a normal BMI. In terms of Apgar scores at birth, babies of obese mothers have been reported to have a 31% excess risk of having a low Apgar score (defined at \<7 at 1 minute) . Infants born to obese mothers demonstrate a spectrum of outcomes, suggesting that there is a complex interplay of factors that defines the precise altered metabolic environment to which the fetus is exposed and that determines the risk of complications

Healthy Early Life Moments in Singapore

This study aims to assess whether an integrated continuum of care from the preconception period, across maternity until the first 18 months of life, can promote maternal metabolic and mental health, as well as offspring health, among overweight and obese women.

Early Life Feeding Exposure and Infant Immune and Health Status.

Background: Although breastfeeding has known protective effects, such as preventing childhood obesity, the specific mechanisms remain unclear. Idaho has a high breastfeeding initiation rate (92%) but a significant prevalence of childhood obesity (30.5% overweight/obese). Limited research exists on the impact of maternal inflammation, maternal body mass index (BMI), C-reactive protein (CRP), and interleukin-6 (IL-6) concentrations in breastmilk on infant health outcomes, especially in healthy full-term infants. Objective: This study aims to expand understanding of the role of maternal inflammation on breastmilk composition and its effect on infant immune development. The investigators seek to investigate the relationship between maternal health status, breastmilk inflammatory concentrations, and balanced immune development in infants. Additionally, the investigators aim to explore the potential influence of early diet exposure, including maternal inflammatory status, on the risk of obesity and other inflammatory conditions. Methods: Healthy full-term infants (breastfed/formula-fed) and their mothers will be recruited. Maternal inflammation markers (BMI, CRP, IL-6) and immune markers in infants will be analyzed. Flow cytometry will assess immune populations. Correlations between maternal systemic inflammation, infant inflammation, and breastmilk inflammatory markers will be examined for breastfeeding mothers. Outcomes: The investigators hypothesize breastfed infants will display a more favorable anti-inflammatory profile. This study will identify factors influencing immune development and potential pathways linking early-life exposures to long-term health outcomes. Findings will inform strategies for promoting balanced immune development and elucidate the role of early diet exposure, including maternal inflammation, as a protective or risk factor for obesity and inflammatory conditions.