Marked Third-Trimester Placental Thickening Is Associated with Maternal Infectious, Hormonal, and Metabolic Burden: A...

Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study aimed to compare maternal characteristics, comorbidities, medication exposure, infection history, and fetal findings between pregnancies with marked placental thickening, defined as placental thickness ≥70 mm, and gestational-age-matched control pregnancies with a placental thickness <70 mm and no documented maternal or fetal abnormalities. Methods: This retrospective matched case-control study included singleton pregnancies referred for fetal echocardiography to a tertiary referral center in Łódź, Poland, between 1 January 2022 and 14 March 2025. Placental thickness was measured sonographically in a perpendicular plane from the chorionic plate to the basal plate, excluding the umbilical cord insertion site. Only anterior and/or fundal placentas assessed at ≥28 weeks of gestation were included. Among pregnancies with recorded third-trimester placental thickness measurements, 99 cases with placental thickness ≥70 mm were identified as the thick-placenta group. A control group of 99 pregnancies with placental thickness <70 mm was selected and matched for gestational age. Control pregnancies had no documented maternal disease, no fetal structural or functional abnormalities, and no exposure to the medications analyzed in this study. Maternal demographic characteristics, body mass index, comorbidities, infection history, obstetric history, and medication use were compared between groups. Continuous variables were compared using Welch's t-test and the Mann-Whitney U test, and categorical variables were compared using Fisher's exact test. Results: The study included 99 pregnancies with marked placental thickening and 99 control pregnancies with normal placental thickness. Gestational age at examination was comparable between groups, with a mean of 35.5 weeks in controls and 35.0 weeks in the thick-placenta group (p = 0.662, Welch's t-test). Median gestational age was also not significantly different between groups (35.4 vs. 36.43 weeks; p = 0.340, Mann-Whitney U test). Mean placental thickness was significantly greater in the thick-placenta group than in controls (81.4 mm vs. 46.9 mm; p < 0.0001). Maternal age and anthropometric characteristics were comparable between groups, whereas BMI > 25 kg/m² was more common in the thick-placenta group. In contrast to the clinically healthy control group, maternal infection was documented in 100.0% of thick-placenta cases, hormonal treatment in 97.0%, history of COVID-19 in 52.5%, hypothyroidism in 44.4%, prior miscarriage in 37.4%, aspirin or anticoagulant use in 32.3%, gestational diabetes mellitus in 25.3%, and pregnancy-induced hypertension in 7.1%. All evaluated maternal clinical factors were significantly more common in the thick-placenta group than in controls. Fetal cardiac or extracardiac dysfunction was present in 68.7% of thick-placenta pregnancies. Conclusions: In this gestational-age-matched case-control study, pregnancies with marked third-trimester placental thickening showed a distinct maternal profile compared with healthy controls with normal placental thickness. Despite comparable gestational age, maternal age, and maternal anthropometric characteristics, the thick-placenta group demonstrated a significantly higher infectious, hormonal, metabolic, and endocrine burden. These findings indicate that, in this selected tertiary referral cohort, placental thickness ≥70 mm was associated with a higher burden of maternal clinical abnormalities and fetal functional findings. Rather than representing an independent marker of placental maladaptation or maternal-fetal risk, marked placental thickening should be interpreted as a clinically relevant ultrasound finding that may prompt careful review of maternal history and targeted fetal assessment. Prospective studies are needed to determine which maternal factors are independently associated with placental thickening and to clarify their relationship with fetal function and perinatal outcomes.