Modulating influence of maternal pre-pregnancy body weight and gestational weight gain on the relationship between biochemical markers of placentation and infant birth weight: A prospective observational study with retrospective stratification by out

Background. Intrauterine fetal growth is largely determined by the quality of placentation. However, several factors, such as pre-pregnancy body mass and gestational weight gain, can significantly modulate this effect. Objective. To evaluate the relationship between birth weight and first-trimester concentrations of pregnancy-associated plasma protein-A and free beta-human chorionic gonadotropin, while accounting for the modulating effects of pre-pregnancy body mass and gestational weight gain. Methods. This prospective observational study with retrospective stratification by outcome included 588 healthy pregnant women with singleton, full-term pregnancies residing in Smolensk and registered for outpatient care at the prenatal clinic of the Clinical Maternity Hospital. The patients were divided into three groups based on neonatal birth weight, with 4 infants classified as small-for-gestational-age, 428 as newborns with normal weight, and 156 as large-for-gestational-age. A comparative analysis of birth weights was performed based on the pre-pregnancy body mass index and gestational weight gain. The collected data included medical histories, infant birth weights, and first-trimester levels of pregnancy-associated plasma protein-A and free beta-human chorionic gonadotropin from first-trimester prenatal screening, as well as calculated pre-pregnancy body mass index and gestational weight gain. Statistical analysis was performed using methods established for biomedical data. The null hypothesis was rejected at p ≤ 0.05. Results . First-trimester pregnancy-associated plasma protein-A concentration, pre-pregnancy body mass, and gestational weight gain were found to be significant predictors of birth weight. The Spearman’s rank correlation coefficient was 0.144 for pregnancy-associated plasma protein-A (95% CI: 0.064–0.222, p < 0.001), 0.198 for body mass index (95% CI: 0.119–0.275, p < 0.001), and 0.317 for gestational weight gain (95% CI: 0.242–0.395, p < 0.001). Notably, maternal body mass index did not modify the effect of gestational weight gain on infant birth weight. The relationships between these variables are described by the following linear regression model: R 2 = 0.108, Adjusted R 2 = 0.103, F = 23.417, p < 0.001. The regression coefficient was 106.5 for pregnancy-associated plasma protein-A (95% CI: 47.67–165.43, p < 0.001); 22.8 for pre-pregnancy body mass index (95% CI: 15.222–30.379, p < 0.001); and 22.2 for gestational weight gain (95% CI: 14.893–29.619, p < 0.001). Gestational weight gain emerged as the strongest predictor in the described model. First-trimester pregnancy-associated plasma protein-A concentration (β = 106.5, 95% CI: 47.67–165.43, p < 0.001) significantly affected infant birth weight when adjusting for pre-pregnancy body mass (β = 22.8, 95% CI: 15.222–30.379, p < 0.001), and gestational weight gain (β = 22.2, 95% CI: 14.893–29.619, p < 0.001). Infant birth weight demonstrated no significant relationship with first-trimester concentration of free beta-human chorionic gonadotropin. Conclusion. Infant birth weight and its pathological deviations are associated with maternal pre-pregnancy body mass, gestational weight gain, and first-trimester pregnancy-associated plasma protein-A concentration. Maternal body mass and gestational weight gain exert a modulating influence on the relationship between pregnancy-associated plasma protein-A levels and infant birth weight. These findings can be significant in developing personalized recommendations for maternal gestational weight gain to mitigate perinatal risks.