**Background:** Pregnancy induces significant metabolic and physiological changes, and inadequate adaptation can lead to cardiometabolic alterations such as maternal obesity, elevated fasting glucose, insulin resistance, dyslipidemia, and elevated blood pressure, which increase the risk of complications like gestational diabetes, pre-eclampsia, and excessive gestational weight gain. While individual lifestyle factors (diet, physical activity, smoking, alcohol) have been studied, few investigations have used a clustered cardiometabolic risk (CCR) score combining multiple biological markers, and even fewer have focused on Mediterranean populations where lifestyle traits may be protective. This study aimed to investigate associations between prenatal sociodemographic, lifestyle, and clinical characteristics and CCR (and its individual components) in the first and third trimesters of pregnancy.
**Methods:** This was a prospective cohort study of 265 healthy pregnant women (≤12 weeks gestation at enrollment) from the ECLIPSES study in northern Spain. Data were collected at 12 weeks (first trimester) and 36 weeks (third trimester). Sociodemographic data included age, education (low/medium/high), and social class (low/medium/high per Catalan classification). Lifestyle factors included physical activity (IPAQ-S, divided into tertiles: T1 <1070, T2 1070–3336, T3 ≥3336 METs-min/week), smoking status (never, former, current), alcohol consumption (yes/no), and diet quality (relative Mediterranean diet score, range 0–18, divided into tertiles: T1 <9, T2 9–12, T3 ≥12). Clinical measures included BMI (normal weight 18.5–24.9, overweight 25.0–29.9, obesity ≥30 kg/m²) and gestational weight gain (categorized as insufficient, adequate, or excessive per 2009 IOM recommendations). Fasting blood samples were analyzed for glucose, insulin, total cholesterol, HDL-c, LDL-c (Friedewald formula), and triglycerides. HOMA-IR was calculated. Blood pressure was measured with an automatic digital monitor. A CCR score was created by summing standardized z-scores of seven markers: BMI, SBP, glucose, log HOMA-IR, log TG, LDL-c, and HDL-c (multiplied by −1). Multivariable linear regression was used, adjusting for all listed characteristics. Statistical significance was set at p < 0.05.
**Key Results:** The mean age was 29.6 (SD 4.7) years; 36% were overweight/obese (BMI ≥25); mean GWG was 10.4 (3.6) kg; 45% had insufficient, 37% adequate, and 18% excessive GWG; 32% had university education; 19% were high social class; 31% were former/current smokers; 13% consumed alcohol; mean PA was 475.8 (701.9) METs-min/week; mean rMedDiet score was 9.4 (2.4). All cardiometabolic markers increased from first to third trimester except fasting glucose, which decreased (all p < 0.05). In cross-sectional first-trimester analyses: age ≥30 was associated with higher HDL-c (β 6.93, p = 0.007); university education with lower BMI (β −0.68, p = 0.030) and lower SBP (β −4.12, p = 0.017); higher PA (T3 vs T1) with lower LDL-c (β −9.83, p = 0.023); overweight/obesity with higher BMI (β 5.83, p < 0.001), SBP (β 5.42, p = 0.001), DBP (β 3.64, p < 0.001), insulin (β 0.30, p < 0.001), HOMA-IR (β 0.33, p < 0.001), and LDL-c (β 6.80, p = 0.045). In prospective third-trimester analyses: overweight/obesity remained associated with higher BMI (β 4.14, p < 0.001) and lower HDL-c (β −5.10, p = 0.039); excessive GWG was associated with higher BMI (β 2.15, p < 0.001), higher SBP (β 5.76, p = 0.017), and higher HDL-c (β 8.02, p = 0.012); insufficient GWG was associated with lower BMI (β −1.32, p < 0.001), lower SBP (β −4.07, p = 0.018), lower DBP (β −3.45, p = 0.008), and lower glucose (β −3.38, p = 0.036); smoking was associated with higher TG (β 0.18, p = 0.016) and higher LDL-c (β 1.19, p = 0.034); alcohol consumption was associated with higher SBP (β 4.74, p = 0.032), higher DBP (β 3.57, p = 0.034), and higher LDL-c (β 1.57, p = 0.032); high social class was associated with lower glucose (β −5.87, p = 0.008), lower insulin (β −0.40, p = 0.002), and lower HOMA-IR (β −0.49, p < 0.001). For the CCR score: in the first trimester, overweight/obesity was positively associated (p < 0.05), while university education and higher PA were negatively associated (p < 0.05). In the third trimester, overweight/obesity remained positively associated, while insufficient GWG and high social class were negatively associated (p < 0.05). The first-trimester CCR score significantly predicted the third-trimester CCR score (β 0.31, 95% CI 0.19–0.43, p < 0.001).
**Clinical Implications:** This study demonstrates that modifiable prenatal factors—particularly normal pre-pregnancy weight, higher education and social class, regular physical activity, and avoidance of smoking and alcohol—are independently associated with lower clustered cardiometabolic risk during pregnancy. Overweight/obesity in early pregnancy was the strongest and most consistent predictor of adverse cardiometabolic profile across both trimesters. The finding that first-trimester CCR independently predicts third-trimester CCR suggests that risk tracks across gestation, highlighting early pregnancy as a critical window for intervention. These results support preconception and early-pregnancy lifestyle interventions targeting weight normalization, physical activity, and smoking/alcohol cessation to improve maternal cardiometabolic health and potentially reduce obstetric complications. The use of a composite CCR score (rather than individual markers) may better identify high-risk women. Limitations include potential misclassification of GWG (using weight at ~36 weeks), a CCR score specific to this sample, and equal weighting of components. Further research is needed to determine whether the CCR approach predicts adverse maternal and child outcomes better than individual risk factors.