In this cohort study, we observed an increased risk of miscarriage associated with first-trimester subchorionic hematoma in singleton pregnancies. Further analysis showed that among women with SCH, the volume of SCH is positively, while the earlier onset of SCH is negatively, associated with the occurrence of miscarriage. We observed no statistically significant associations between SCH and neonatal and other maternal outcomes.
The exact pathological mechanism of SCH is unknown, although the asynchronous development of the decidua and trophoblast and the impaired function of trophoblastic capillaries are suspected. When the impaired capillaries are located in the margin of trophoblast or closed in cervix, bleeding could flow through the cervix and could not form a hematoma, but when the impaired capillaries are located in the inner interface of the chorionic and uterine wall, the collected blood could result in partial detachment of the trophoblasts from the uterine wall. Theoretically, it is possible that the hematoma changes the local microenvironment of chorionic and might have an impact on function of trophoblast. Our results suggest that SCH occurring in the first trimester might increase the risk of miscarriage. This result is consistent with three previous studies[4, 5, 15], but inconsistent with the study of Mackenzie et al. In their study, the rate of pregnancy loss before 20 weeks of gestation was 7.5% and 4.9% in women with and without SCH, respectively, which was substantially lower than the rates (15%-25%) observed in other populations[17, 18]. The higher percentage of vaginal bleeding we observed in the women with SCH is not surprising, as it has been suggested that both SCH and vaginal bleeding are very likely to concur following the bleeding in the area of the trophoblast site.
Prior studies concerning the effect of hematoma size on the pregnancy loss reported inconsistent findings[4, 16, 20, 21]. These studies were subject to a smaller sample size and lack of consistent methods used to assess bleeding volume. For example, Bennett et al. and Heller et al. evaluated the hematoma size using the percentage of hematoma area to gestational sac[20, 21], Naert et al. and Maso et al. in volumes[4, 16], and Lulu et al. in median centimeters. The cut-off value of hematoma size also varied across studies. Our results suggest that the risk of miscarriage might be proportional to the volume of the hematoma, which however deserves a more detailed study where more women with higher volume of bleeding are included.
The present study supports the existing evidence that earlier onset of SCH is particularly dangerous to maintenance of pregnancy. The study of Maso et al. showed that the risk of pregnancy loss was nearly 15 times higher for SCH diagnosed before 9 weeks of gestation than for those diagnosed after 9 weeks. Likewise, Howard et al. observed that compared with women diagnosed with SCH after 8 weeks of gestation, SCH diagnosed before 8 weeks was associated with a significantly higher risk of miscarriage. It is well known that over half of the early miscarriages are caused by chromosomal abnormalities such as aneuploidy[3, 23]. However, it is unclear whether women with aneuploidy pregnancies are more prone to subchorionic hematoma because of the embryonic origin of the trophoblast cells. It is suggested that presence of SCH in the early stage of pregnancy affects the normal process of trophoblast invasion, which is vital for a successful pregnancy[19, 24]. However, as the pregnancy proceeds, it is possible that the fetus would become less vulnerable to and the resulting trophoblast impairment.
Our data demonstrated no statistically significant associations between first-trimester SCH and maternal complications other than miscarriage, not fully in line with the two prior studies [9, 25], where SCH was also associated with increased risks of stillbirth and placental abruption. Of note, the two prior studies detected SCH at, on average, 18 and 10 gestational weeks, respectively, considerably later than the present study (around 7 gestational weeks), suggesting that SCH at the early stage of pregnancy has chance to dissolve spontaneously and eventually causes less harm, while persisting SCH might be more concerning and indicative of multiple maternal complications. In addition, our results also suggest that the risks of neonatal outcomes were not increased in pregnant women with SCH in first trimester. Three recent studies also found no relationship between birth weight and SCH [8, 10, 26], but two early studies reported lower birth weight in women with SCH than in those without[9, 15]. Oxidative stress impairment and mechanical effects of the hematoma are two supposed mechanisms underlying the positive associations between SCH and adverse pregnancy outcomes [5, 27] All the cases included in our study were women with SCH detected in first trimester. If the pregnancy continued, the hematoma would probably be absorbed after several months and the mechanical effects of the hematoma in the third trimester would diminish. Prospective studies should be designed to continuously observe the hematoma during the pregnancy in order to analyze persistent hematoma compared with those absorbed over time to clarify the potentially differed associations with perinatal outcomes.
Our study has several limitations. Firstly, the data of the study were collected retrospectively. Secondly, we were unable to confirm the potential impact of the localization of the hematoma on pregnancy outcomes since the location data of SCH were not routinely collected in our institute. However, several studies have consistently shown that retroplacental hematomas are significantly associated with an increased risk of averse maternal and neonatal outcomes.[9, 10] Lastly, our study did not include information on previous miscarriage, previous premature birth, and use of in vitro fertilization for the index pregnancy, as data on these variables were largely missing.
In conclusion, SCH during the first trimester might significantly increase the risk of miscarriage in women with singleton pregnancy, particularly the one that occurs early and the one with large size. However, a diagnosed of SCH is not associated with adverse maternal complications and neonatal outcomes. Our study provides new evidence for the clinical consultant of those expected patients.