Background Marked differences in birth weight (BW) between South Asian and White European-origin populations are well-documented and pose public health concerns.

Methods We analyzed fetal BW, the fat mass (FM), and fat-free mass (FFM) components in South Asian (n=938) and White European (n=3,044 and 804) newborns from three Canadian birth cohorts, examining the contribution of 16 maternal factors to observed BW differences using epidemiological and Mendelian randomization analyses.

Findings South Asian newborns had on average, a significantly lower BW (3.3±0.4kg) than White Europeans (3.5±0.5kg), even after accounting for birth length (p<0.001). FFM was the primary driver of this difference, contributing to 0.22kg lower BW (p<2.2E-16), while FM had a significant but weaker counteracting effect of 0.01kg higher BW in South Asians (p=0.006). Five maternal factors demonstrated a direct maternal genetic influence: pre-pregnancy weight primarily increased BW via FFM, it also had a non-negligible increasing effect on FM. On the other hand, maternal glucose and gestational diabetes mellitus (GDM) causally increased BW through FM accumulation. Maternal height had a minimal effect only on FFM. After adjusting for these 5 maternal predictors, roughly 50% of the ethnic difference in BW (0.1kg; 95% CI: 0.067–0.13kg) was accounted for.

Interpretation Different maternal factors influence specific components of BW. Targeting body fat reduction and maternal glucose regulation in South Asian mothers may help reduce the intergenerational transmission of increased FM and its associated adverse health outcomes.

Funding This study was funded by the Canadian Institutes of Health Research DOHaD Team Grant: MWG-146332.

Evidence before this study Ethnic difference in birth weight between South Asian (and other non-White European populations) and White European-origin populations are well-documented in cohort studies such as in Born in Bradford and nation-wide estimates, but not well understood. Previous studies have looked at different body compositions, maternal environment, or genetics, but no study has integrated all of these to determine the causal drivers of differences in BW, and their impact on body composition, between South Asians and White Europeans.

Added value of this study The present study adds evidence that difference in birth weight is not a unitary concept but rather the balance of both fat and lean mass. Importantly, these components are strongly driven by a set of maternal factors, and accounting for these factors, we were able to level the difference in birth weight by up to 50%.

Implications of all the available evidence Together with other emerging research on the causal determinants of birth weight, these findings suggest a potential set of maternal intrauterine factors that can be targeted to optimize early-life and long-term cardiometabolic health—particularly in high-risk populations such as South Asians. These results also emphasize the need to go beyond birth weight alone and consider neonatal body composition and its maternal drivers when evaluating and addressing health disparities.

The authors have declared no competing interest.

This study was funded by the Canadian Institutes of Health Research DOHaD Team Grant: MWG-146332.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval was obtained independently from the Hamilton Integrated Research Ethics Board (HiREB): CHILD (REB 07-2929) and START (REB 10-640). CHILD was additionally approved by the respective Human Research Ethics Boards at McMaster University, the Universities of Manitoba, Alberta, and British Columbia, and the Hospital for Sick Children. Legal guardians of each participant provided written informed consent. Written informed consent was obtained from the parent/guardian (participating mother) for each study separately. We also have now obtained additional ethics board approval from HiREB (REB 16592) for using the data from the two cohorts together without additional consent from the participants.

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The PGS data used to derive the PGS are available from the PGS catalog with reference number shown in Table S3. Data collected for this study, including individual participant data and data dictionary defining each field in the dataset, are available to researchers who provide a proposal detailing intended analyses, pending access approval by the NutriGen Alliance Team. CHILD study data can be separately requested from the CHILDdb database. Access can be initiated through https://childstudy.ca/childdb/.

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