Pre-Conception Physical Activity and the Risk of Gestational Diabetes Mellitus: Findings from the BORN 2020 Study

<b>Background/Objectives</b>: Pre-conception health behaviors may influence the risk of gestational diabetes mellitus (GDM), but evidence on the joint effects of physical activity (PA) and dietary patterns remains limited. This study investigated the associations between pre-conception PA and GDM risk and explored their interaction with adherence to a Mediterranean diet (MD). <b>Methods</b>: This analysis used data from the BORN2020 cohort, which included pregnant women in Greece (2020-2022). Pre-conception PA was assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), expressed as the metabolic equivalent of task (MET)-min/week and categorized into quartiles. Adherence to the MD was assessed via the Trichopoulou score and then grouped into tertiles. Multivariable logistic regression models were computed, accounting for sociodemographic and clinical covariates, including sedentary time and post-lunch nap frequency. <b>Results</b>: In total, 524 women were included and 13.9% (<i>n</i> = 73) were diagnosed with GDM. Women who developed GDM were significantly older (mean age 34.41 vs. 31.98 years, <i>p</i> < 0.0001), were more likely to be >35 years old (46.6% vs. 26.6%, <i>p</i> < 0.001), had higher pre-pregnancy BMI (median 24.6 vs. 22.7 kg/m², <i>p</i> = 0.014), and were more likely to be obese (23.3% vs. 11.8%, <i>p</i> = 0.012). No significant association was observed between total pre-conception PA and GDM risk. Compared to the lowest PA quartile, women in the medium (aOR = 0.80, 95% CI: 0.45-1.40), high (aOR = 1.12, 95% CI: 0.52-2.39), and very high (aOR = 1.10, 95% CI: 0.50-2.38) PA quartiles showed no significant differences in GDM risk. PA, when modeled as a continuous variable, showed no significant trend (aOR = 0.99, 95% CI: 0.99-1.00; <i>p</i>-trend = 0.61). A joint analysis of PA and MD adherence also yielded no significant associations overall. However, in very small BMI-stratified subgroups, a low level of PA combined with very high MD adherence in normal-weight women was associated with increased GDM risk (aOR = 14.06, 95% CI: 1.55-165.54, <i>p</i> = 0.022), while in obese women, very high levels of PA and medium MD adherence showed a potentially protective effect (aOR = 0.006, 95% CI: 8.43 × 10^-6-0.42, <i>p</i> = 0.048). These subgroup findings require cautious interpretation, due to the limited size of the sample set and wide confidence intervals. <b>Conclusions</b>: In this cohort, pre-conception PA, either alone or in combination with MD adherence, was not a reliable predictor of GDM. While our subgroup signals are hypothesis-generating, they do not yet support changes to clinical risk stratification. Future large-scale and interventional studies should investigate combined lifestyle interventions before conception to clarify the potential synergistic effects on GDM prevention.