Association of Maternal Prepregnancy Body Mass Index With Placental Histopathological Characteristics in Uncomplicated Term Pregnancies.

INTRODUCTION: Prepregnancy obesity is a growing global health problem and has several risks for mother and child. The aim of this study was to systematically examine the effect of increased maternal body mass index (BMI) on placental pathology in otherwise uneventful term pregnancies. METHODS: In this analysis, we studied data of the Netherlands Amniotic Fluid study, a prospective study of women delivering in Utrecht, the Netherlands, between 2006 and 2007. We included women with uncomplicated pregnancies, vaginal delivery, and data on prepregnancy weight and height (n = 382). Placental histopathology was compared between women of normal BMI (≤24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2). RESULTS: Increasing prepregnancy BMI was associated with heavier placentas and higher mean infant's birth weight. In addition, obesity was positively associated with high-grade chronic villitis (odds ratio [OR]: 18.1, 95% confidence interval [CI]: 1.6-205.2), accelerated villous maturation (OR: 1.1, 95% CI: 1.0-1.2), and lower incidence of placental weight below the 10th percentile for gestational age (OR: 0.5, 95% CI: 0.3-1.0). There was a substantial effect of parity on maternal, placental, and neonatal weights. CONCLUSIONS: Even in uncomplicated pregnancies, maternal obesity is associated with characteristic changes in placental pathology. Further research is needed to evaluate these changes in view of later-life health of infants born to obese mothers.

Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels.

OBJECTIVE: The primary aim of this study was to investigate the correlation between pregnancy outcome and bile acid (BA) levels in pregnancies that were affected by intrahepatic cholestasis of pregnancy (ICP). In addition, correlations between maternal and fetal BA levels were explored. STUDY DESIGN: We conducted a retrospective study that included women with pruritus and BA levels ≥10 µmol/L between January 2005 and August 2012 in 3 large hospitals in the Netherlands. The study group was divided in mild (10-39 µmol/L), moderate (40-99 µmol/L), and severe (≥100 µmol/L) ICP. Main outcome measures were spontaneous preterm birth, meconium-stained amniotic fluid, asphyxia, and perinatal death. Univariate and multivariate logistic regression analysis was used to study associations between BA levels and adverse outcome. RESULTS: A total of 215 women were included. Gestational age at diagnosis and gestational age at delivery were significantly lower in the severe, as compared with the mild, ICP group (P < .001). Spontaneous preterm birth (19.0%), meconium-stained fluid (47.6%), and perinatal death (9.5%) occurred significantly more often in cases with severe ICP. Higher BA levels were associated significantly with spontaneous preterm birth (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 1.03-1.28), meconium-stained amniotic fluid (aOR, 1.15; 95% CI, 1.06-1.25), and perinatal death (aOR, 1.26; 95% CI, 1.01-1.57). Maternal BA levels at diagnosis and at delivery were correlated positively with umbilical cord blood BA levels (P = .006 and .012, respectively). CONCLUSION: Severe ICP is associated with adverse pregnancy outcome. Levels of BA correlate between mother and fetus.

Human Tregs at the materno-fetal interface show site-specific adaptation reminiscent of tumor Tregs.

Tregs are crucial for maintaining maternal immunotolerance against the semiallogeneic fetus. We investigated the elusive transcriptional profile and functional adaptation of human uterine Tregs (uTregs) during pregnancy. Uterine biopsies, from placental bed (materno-fetal interface) and incision site (control) and blood were obtained from women with uncomplicated pregnancies undergoing cesarean section. Tregs and CD4+ non-Tregs were isolated for transcriptomic profiling by Cel-Seq2. Results were validated on protein and single cell levels by flow cytometry. Placental bed uTregs showed elevated expression of Treg signature markers, including FOXP3, CTLA-4, and TIGIT. Their transcriptional profile was indicative of late-stage effector Treg differentiation and chronic activation, with increased expression of immune checkpoints GITR, TNFR2, OX-40, and 4-1BB; genes associated with suppressive capacity (HAVCR2, IL10, LAYN, and PDCD1); and transcription factors MAF, PRDM1, BATF, and VDR. uTregs mirrored non-Treg Th1 polarization and tissue residency. The particular transcriptional signature of placental bed uTregs overlapped strongly with that of tumor-infiltrating Tregs and was remarkably pronounced at the placental bed compared with uterine control site. In conclusion, human uTregs acquire a differentiated effector Treg profile similar to tumor-infiltrating Tregs, specifically at the materno-fetal interface. This introduces the concept of site-specific transcriptional adaptation of Tregs within 1 organ.

Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia.

BACKGROUND: Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated. METHODS: We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies. RESULTS: Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia. CONCLUSIONS: Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.

Spiral artery remodeling and maternal cardiovascular risk: the spiral artery remodeling (SPAR) study.

BACKGROUND: Women with a history of placental bed disorders, including preeclampsia and intrauterine growth restriction have an increased long-term risk of cardiovascular disease (CVD). Further, similarities exist between atherosclerosis and abnormalities observed in placental bed spiral arteries in pregnancies affected by preeclampsia and intrauterine growth restriction, such as acute atherosis and defective remodeling. This suggests a common pathophysiological pathway underlying both disorders. OBJECTIVES: The aim of this study was to investigate vascular and inflammatory lesions in the placental bed of women with preeclampsia and normal pregnancy using a systematic approach to characterize lesions of the placental bed, and relate spiral artery pathology to postpartum CVD risk assessment. METHODS: Placental bed punch biopsies were performed following caesarean section and systematically studied to assess vascular pathology, arterial remodeling, and the presence of CD3, CD56, and CD68 cells. In addition, levels of modifiable CVD risk factors were assessed immediately postpartum. RESULTS: We found fewer spiral arteries with complete remodeling in women with preeclampsia than in the control group (21 vs. 68%; P = 0.008). Further, women with preeclampsia showed less presence of CD3 cells in both the decidua and the myometrium. Preliminary findings of CVD risk factor assessment postpartum suggest a correlation between acute atherosis and higher triglyceride and low-density lipoprotein cholesterol levels. CONCLUSION: Systematic study of vascular pathology in uterine spiral artery biopsy samples in relation to CVD risk factors provides valuable insight into the link between cardiovascular health and placental bed disorders.