Placental Pathology Findings in Unexplained Pregnancy Losses.

There are approximately 5 million pregnancies per year in the USA, with 1 million ending in miscarriage (a loss occurring prior to 20 weeks of gestation) and over 20,000 ending in stillbirth at or beyond 20 weeks of gestation. As many as 50% of these losses are unexplained. Our objective was to evaluate the effect of expanding the placental pathology diagnostic categories to include the explicit categories of (1) dysmorphic chorionic villi and (2) small placenta in examining previously unexplained losses. Using a clinical database of 1256 previously unexplained losses at 6-43 weeks of gestation, the most prevalent abnormality associated with each loss was determined through examination of its placental pathology slides. Of 1256 cases analyzed from 922 patients, there were 878 (69.9%) miscarriages and 378 (30.1%) antepartum stillbirths. We determined the pathologic diagnoses for 1150/1256 (91.6%) of the entire series, 777/878 (88.5%) of the miscarriages (< 20 weeks' gestation), and 373/378 (98.7%) of the stillbirths (≥ 20 weeks' gestation). The most common pathologic feature observed in unexplained miscarriages was dysmorphic chorionic villi (757 cases; 86.2%), a marker associated with genetic abnormalities. The most common pathologic feature observed in unexplained stillbirths was a small placenta (128 cases; 33.9%). Our classification system reinforced the utility of placental examination for elucidating potential mechanisms behind pregnancy loss. The improved rate of diagnosis appeared to be the result of filling a gap in previous pregnancy loss classification systems via inclusion of the categories of dysmorphic chorionic villi and small placenta.

Trophoblast inclusions and adverse birth outcomes.

OBJECTIVE: Trophoblast inclusions-cross sections of abnormal trophoblast bilayer infoldings-have previously been associated with aneuploidy, placenta accreta, and prematurity. This study was conducted to establish the relationship between trophoblast inclusions and a range of placental, pregnancy, and birth outcomes in a patient population with high smoking and alcohol exposure. Specifically, we sought to evaluate the association between the presence of trophoblast inclusions and 1) three primary birth outcomes: full-term birth, preterm birth, and stillbirth; 2) gestational age at delivery; and 3) specific placental pathologies. METHODS: Two slides containing chorionic villi were evaluated from 589 placentas that were collected from Stellenbosch University in Cape Town, South Africa as part of the prospective, multicenter cohort Safe Passage Study of the Prenatal Alcohol and SIDS and Stillbirth Network. The subsample included 307 full-term live births, 212 preterm live births, and 70 stillbirths. RESULTS: We found that the odds of identifying at least one trophoblast inclusion across two slides of chorionic villi was significantly higher for placentas from preterm compared to term liveborn deliveries (OR = 1.74; 95% CI: 1.22, 2.49, p = 0.002), with an even greater odds ratio for placentas from stillborn compared to term liveborn deliveries (OR = 4.95; 95% CI: 2.78, 8.80, p < 0.001). Gestational age at delivery was inversely associated with trophoblast inclusion frequency. Trophoblast inclusions were significantly associated with small for gestational age birthweight, induction of labor, villous edema, placental infarction, and inflammation of the chorionic plate. CONCLUSIONS: The novel associations that we report warrant further investigation in order to understand the complex network of biological mechanisms through which the factors that lead to trophoblast inclusions may influence or reflect the trajectory and health of a pregnancy. Ultimately, this line of research may provide critical insights that could inform both clinical and research applications.

Genetics, not the uterine environment, drive the formation of trophoblast inclusions: Insights from a twin study.

INTRODUCTION: Trophoblast inclusions (TIs) are associated with aneuploidy and pregnancy loss and have thus been considered to be a marker of genetic abnormality. However, to date, no study has specifically explored whether TIs are a manifestation of fetal genetics or, rather, the result of the intrauterine environment. The goal of this study was to compare the frequency of TIs in the placentas of monozygotic (MZ) and dizygotic (DZ) twin pairs in order to determine whether the formation of TIs is genetically driven or not. METHODS: We performed a retrospective case series of placentas from 48 twin pairs. The placentas were grouped based on zygosity: MZ, DZ, or unknown (UZ). The average number of total TIs per slide was calculated for each twin individual and the mean absolute difference in the total TIs per slide between the twin pairs was calculated for each zygosity group and compared. RESULTS: The mean difference in the total TIs per slide for DZ twins was significantly greater than the mean difference in the total TIs per slide for MZ twins (p = 0.003). The mean difference in the total TIs per slide for the UZ group was also significantly greater than the mean difference in total TIs per slide between MZ twin pairs (p = 0.028). DISCUSSION: Our finding that MZ twins were significantly more concordant than DZ twins for the average number of TIs per slide supports the conclusion that TIs are intrinsic to the genetics of the fetus, not the uterine environment.

Trophoblast inclusions in the human placenta: Identification, characterization, quantification, and interrelations of subtypes.

We sought to examine placentas enriched for trophoblast inclusions (TIs) in order to characterize, quantify, and examine the interrelations between subtypes of TIs to better understand their underlying biology. We examined a cohort of 600 placentas from deliveries between 200 and 430 weeks of gestation. Forty-five percent of the placentas had at least one TI in the two slides examined. Four percent of the placentas had 10 or more TIs and two placentas had more than 70 TIs. Four distinct TI subtypes were observed: inclusionoids (early forming inclusions), inclusions, calcified inclusions, and calcified bodies. We suggest this reflects a developmental trajectory of TI maturation, the timing of which might be useful when comparing TI expression to clinical outcomes.