Early Pregnancy Losses: Review of Nomenclature, Histopathology, and Possible Etiologies.

Miscarriage is a frequent complication of human pregnancy: ∼50% to 70% of spontaneous conceptions are lost prior to the second trimester. Etiology of miscarriage includes genetic abnormalities, infections, immunological and implantation disorders, uterine and endocrine abnormalities, and lifestyle factors. Given such variability, knowledge regarding causes, pathophysiological mechanisms, and morphologies of primary early pregnancy loss has significant gaps; often, pregnancy losses remain unexplained. Pathologic evaluation of miscarriage tissue is an untapped source of knowledge. Although miscarriage specimens comprise a significant part of pathologists' workload, information reported from these specimens is typically of minimal clinical utility for delineating etiology or predicting recurrence risk. Standardized terminology is available, though not universally used. We reintroduce the terminology and review new information about early pregnancy losses and their morphologies. Current clinical terminology is inconsistent, hampering research progress. This review is a resource for diagnostic pathologists studying this complex problem.

Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network.

BACKGROUND: Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. OBJECTIVE: This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. STUDY DESIGN: White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. RESULTS: A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 + ). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 103 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). CONCLUSION: Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.