Gestational diabetes mellitus (GDM), a glucose intolerance condition developing during pregnancy, affects 4–9% of pregnancies and carries short- and long-term risks for both mother and offspring, including cardiovascular disease, pre-eclampsia, type 2 diabetes, and increased offspring obesity and diabetes risk. Risk factors for GDM include advanced maternal age, obesity, family history of diabetes, high-fat/carbohydrate diet, micronutrient deficiencies, and oxidative stress. Diets rich in fruits and vegetables, providing antioxidants, have shown potential in preventing chronic diseases, including GDM. Several components in these foods decrease inflammation and oxidative stress. While research has examined individual antioxidants, dietary total antioxidant capacity (DTAC) provides a more comprehensive assessment of a diet's antioxidant potential, reflecting the synergistic effects of various antioxidants. This study aims to investigate the previously unstudied association between DTAC during early pregnancy and the risk of GDM using data from the Mothers and their Children's Health (MATCH) cohort study, employing propensity score-based inverse probability weighting (IPW) to account for potential confounders.

Existing literature highlights the link between high fruit and vegetable intake and reduced risk of GDM. Studies have shown associations between individual antioxidants like vitamin C and lower GDM risk. However, considering the synergistic effects of multiple dietary antioxidants is crucial. DTAC, as a measure of the overall antioxidant capacity of the diet, has been linked to various health benefits, but its association with GDM remains unexplored. This gap in knowledge prompted this study to investigate the relationship using DTAC as a comprehensive measure of dietary antioxidant potential. The use of propensity score matching was a key methodological component to adjust for differences in the baseline characteristics of women in the different quartiles of DTAC.

This prospective cohort study utilized data from the Mothers and their Children's Health (MATCH) study, enrolling 2103 pregnant women aged 18–45. After exclusions (due to planned delivery elsewhere, gestational age <12 weeks, multiple pregnancies, metabolic or chronic diseases, specific diets or supplements, and declination), 1856 women with complete data were included. Data were collected at four time points. Baseline data (before 12 weeks of pregnancy) included demographics, lifestyle, medical history, and dietary intake assessed via a validated 168-item semi-quantitative food frequency questionnaire (FFQ). DTAC was calculated using the ferric reducing ability of plasma (FRAP) method from a food antioxidant database. Anthropometric measurements (height, weight, waist and hip circumferences) were taken. GDM was diagnosed based on American Diabetes Association (ADA) criteria using oral glucose tolerance test results. Propensity score-based inverse probability weighting (IPW) using a generalized boosted model (GBM) adjusted for potential confounders (age, education, BMI, pre-existing diabetes, smoking, etc.) identified via directed acyclic graphs (DAGs). Statistical analysis included descriptive statistics, multiple imputations for missing data, and modified Poisson regression with IPTW to estimate risk ratios (RRs) and 95% confidence intervals.

A total of 369 (19.9%) participants developed GDM. The mean DTAC score was 2.82 ± 2.56 mmol/100 g. In the crude model, compared with the lowest quartile, the RRs for GDM were 0.83 (95% CI: 0.65, 1.05), 0.72 (95% CI: 0.56, 0.92), and 0.61 (95% CI: 0.46, 0.78) for successive quartiles of DTAC score, respectively. After adjustment for potential confounders using propensity score matching, the adjusted RRs (95% CIs) for GDM from the lowest to highest quartiles of the DTAC score were 1 (reference), 0.32 (95% CI: 0.14, 0.73), 0.26 (95% CI: 0.11, 0.60), and 0.29 (95% CI: 0.12, 0.68), respectively (*p* for trend < 0.001). When DTAC was modeled as a continuous variable, a significant inverse association with GDM risk was observed (aRR: 0.66; 95% CI: 0.48, 0.90). Women with higher DTAC scores had a significantly lower risk of GDM even after adjusting for confounders such as BMI, age, education, smoking, and pre-existing diabetes.

This study's findings strongly support the hypothesis that higher DTAC during early pregnancy is associated with a reduced risk of GDM. The significant inverse association remained robust even after adjusting for multiple potential confounders, suggesting a potentially independent protective effect of DTAC. This is consistent with other research linking higher antioxidant intake to a decreased GDM risk, but this study is strengthened by its use of a comprehensive measure like DTAC and a prospective cohort design with extensive adjustment for confounders. The prospective nature allows for a more definitive assessment of the temporal relationship between DTAC and GDM development, reducing reverse causality concerns. Compared to a previous case-control study, this larger prospective cohort study provides more robust evidence due to its ability to directly calculate risk ratios and control for multiple confounding variables. The protective effect may be mediated through improved glucose control and reduced oxidative stress, thereby protecting pancreatic beta cells and improving insulin sensitivity. Further research is needed to explore potential mediating mechanisms.

This prospective cohort study demonstrates a significant association between higher dietary total antioxidant capacity (DTAC) in early pregnancy and a reduced risk of gestational diabetes mellitus (GDM). These findings suggest that promoting a diet rich in antioxidants may be a beneficial strategy for GDM prevention. Larger studies are needed to confirm these findings and elucidate the underlying mechanisms. Future research should focus on exploring the role of specific antioxidant compounds and their interactions within the context of overall dietary patterns, and investigating the relationship between DTAC, insulin resistance, and other metabolic factors.

The study's limitations include potential selection bias due to recruitment from a specialized gynecological hospital, which may limit the generalizability of findings to other populations. The absence of data on insulin resistance indices prevents a complete understanding of how DTAC impacts glucose metabolism and insulin action. Further research incorporating data from diverse settings and including insulin resistance markers would strengthen the evidence and enhance understanding of the mechanisms involved.