Norman, Shayna M. MD; Odibo, Anthony O. MD, MSCE; Macones, George A. MD, MSCE; Dicke, Jeffrey M. MD; Crane, James P. MD; Cahill, Alison G. MD, MSCI
OBJECTIVE: To estimate the association between the ultrasonographic diagnosis of subchorionic hemorrhage and adverse pregnancy outcomes.
METHODS: This was a retrospective cohort study of all consecutive women undergoing routine ultrasonography before 22 weeks with a singleton gestation at one institution from 1994 to 2008. Presence or absence of subchorionic hemorrhage defined the two study groups. The primary outcomes were abruption, intrauterine growth restriction defined as birth weight less than the 10th percentile, and nonanomalous intrauterine fetal demise after 20 weeks. Secondary outcomes included preeclampsia, preterm premature rupture of membranes, and preterm delivery before 37 weeks and before 34 weeks of gestation. Univariable, bivariate, and multiple logistic regression analyses were performed.
RESULTS: Of the 63,966 women in the patient population, 1,081 had subchorionic hemorrhage (1.7%). Women with a subchorionic hemorrhage were at increased risk of abruption (n=432, 3.6% compared with 0.6%, adjusted odds ratio 2.6, 95% confidence interval 1.8–3.7) and of preterm delivery (n=6,601, 15.5% compared with 10.5%, adjusted odds ratio 1.3, 95% confidence interval 1.1–1.5), even after adjusting for bleeding during pregnancy, chronic hypertension, body mass index, race, diabetes mellitus, tobacco use, and previous preterm delivery.
CONCLUSION: Women with ultrasound-detected subchorionic hemorrhage before 22 weeks of gestation are at increased risk of placental abruption and preterm delivery but are not at increased risk of other adverse pregnancy outcomes.
LEVEL OF EVIDENCE: II
The detection of subchorionic hemorrhage is a relatively common finding on ultrasound examinations. The two largest studies to date report an incidence of subchorionic hemorrhage of 1.3% to 3.1%.1,2 However, the clinical outcomes associated with sonographically detected subchorionic hemorrhage are not well-established.
In the past, studies have found opposing results. Some investigators have reported an association between subchorionic hemorrhage and abruption, preterm delivery, intrauterine growth restriction (IUGR), or intrauterine fetal death, whereas others have found no association between subchorionic hemorrhage and these outcomes.1–3 These studies have mainly focused on the finding of subchorionic hemorrhage in the first trimester, making their findings only generalizable to patients who undergo a first-trimester ultrasound examination and are potentially biased by the indication for ultrasonography in the first place, such as bleeding. Conflicting data and small sample sizes have ultimately left clinicians unable to confidently counsel patients when subchorionic hemorrhage is detected on routine ultrasound examination.
This study aims to estimate the association between the ultrasonographic diagnosis of subchorionic hemorrhage and adverse pregnancy outcomes, including placental abruption, IUGR, and intrauterine fetal death.
MATERIALS AND METHODS
We conducted a retrospective cohort study of all viable, singleton pregnancies undergoing routine ultrasound anatomic survey between 17 and 22 weeks of gestation during the 14-year study period from 1994 to 2008 at Washington University in St. Louis Medical Center. Before initiation of the study, approval was obtained from the Washington University human research protection board. The Washington University prenatal diagnosis database was created in 1990 and has gathered extensive information on all women who have undergone ultrasound evaluation (including demographics, medical, obstetric, and social history, indication for examination, and ultrasound findings). Dedicated pregnancy outcome coordinators obtained complete pregnancy outcome data for women undergoing ultrasound evaluation in an ongoing, prospective manner, contemporaneously with delivery admission, and by record acquisition and physician contact in the rare event of delivery at an out-of-network hospital or if delivery admission was missed. Included in this analysis are only those patients with complete follow-up data.
Pregnancies were dated by a woman's last menstrual period if that date was within 7 days of a first-trimester ultrasound examination or within 10 days of a second-trimester ultrasound examination. Pregnancies were dated by ultrasonography if the last menstrual period was unknown or if the ultrasound dating was outside the aforementioned parameters. At the time of anatomic survey, placentas were evaluated as a routine part of the study using the American Institute of Ultrasound in Medicine guidelines.4 All ultrasound examinations were performed by full-time registry of diagnostic medical ultrasonographers credentialed in obstetrics and gynecology. Final diagnostic interpretations were made by maternal–fetal medicine attending physicians. Presence of subchorionic hemorrhage, defined as a retroplacental, hypoechoic region, of any size and any location was included in the study (Fig. 1).5
Presence or absence of subchorionic hemorrhage, determined dichotomously by the attending physician performing the final ultrasound interpretation, identified the two study groups. The primary outcomes of the study were placental abruption defined clinically by the attending physician at the time of delivery, IUGR defined as birth weight less than the 10th percentile based on the Alexander growth standard,6 and intrauterine fetal death after 20 weeks of gestation. Fetuses with major congenital anomalies were excluded from the analysis of intrauterine fetal death.5 Secondary outcomes studied were preeclampsia, defined using American College of Obstetricians and Gynecologists criteria (the College), for which both mild and severe preeclampsia were included, preterm premature rupture of membranes (PROM), also defined using the College criteria, and preterm delivery before 37 weeks of gestation as well as before 34 weeks of gestation.7,8 Only patients who delivered after 20 weeks of gestation were included in our analysis. Baseline characteristics were compared between the two study groups (women with subchorionic hemorrhage and those without). Continuous variables were compared using the Student t and Mann-Whitney U tests, and categorical variables were compared using the χ2 and Fisher exact test as appropriate. Stratified analyses were used to identify potentially confounding factors. Incidence, relative risks and 95% confidence intervals (CI) were calculated for each of the primary and secondary outcomes. Bleeding during the first trimester or any time before the anatomy scan was considered in subgroup analyses to distinguish between a symptomatic patient and one in whom the finding of subchorionic hemorrhage was incidental. Additionally, analyses of the preterm delivery outcomes were further explored, excluding cases of placental abruption. The results of the univariable and stratified analyses were used to select factors for our final multivariable models for the outcomes. Backward step-wise selection was used to reduce the number of variables in the model by assessing the magnitude of change in the effect size of subchorionic hemorrhage and other risk covariates. Differences in the explanatory models were tested using the likelihood ratio test or Wald test.9 Only variables that were statistically significant were included in the final models. All statistical analyses were completed using STATA software package, version 10, special edition (College Station, TX).
Of 72,373 women, 63,966 had complete follow-up data and therefore were available for this analysis. Subchorionic hemorrhage was identified in 1,081 (1.7%) women.
Baseline characteristics of the two study groups are provided in Table 1. Women with subchorionic hemorrhage are more likely to be advanced maternal age, with higher gravidity and parity, lower body mass index, and of non–African-American race. Women with subchorionic hemorrhage also were more likely to have a history of previous preterm birth and were more likely to have reported bleeding during the pregnancy before their ultrasound evaluation. Women with subchorionic hemorrhage also underwent ultrasound examinations at an earlier gestational age, on average, compared with those without subchorionic hemorrhage (17.7 weeks compared with 18.4 weeks).
Women with subchorionic hemorrhage were found to have a statistically significant increased risk of abruption (n=432, 3.6% compared with 0.6%, adjusted odds ratio [aOR] 2.6, 95% CI 1.8–3.7, P<.01), even after adjusting for bleeding, chronic hypertension, pregestational diabetes, tobacco use, and previous preterm birth (Table 2). Additionally, presence of a subchorionic hemorrhage was associated with an increased risk of abruption regardless of whether there had been bleeding before the ultrasound examination (ie, symptomatic; aOR 1.6, 95% CI 1.0 – 2.7), or if subchorionic hemorrhage was an incidental finding (aOR 5.0, 95% CI 3.0–8.3).
The risks of preterm delivery before 37 weeks of gestation (n=6601, 15.5% compared with 10.5%, aOR 1.3, 95% CI 1.1–1.5, P<.01) and before 34 weeks of gestation (n=1774, 5.3% compared with 2.8%, aOR 1.5, 95% CI 1.1–2.0, P<.01) were significantly higher in women with subchorionic hemorrhage after adjusting for previous preterm birth, bleeding, and tobacco use (Table 3). Chronic hypertension, body mass index, race, and diabetes mellitus did not remain significant in the final models. Additionally, the association between subchorionic hemorrhage and risk of preterm delivery before 37 and 34 weeks of gestation remained even after excluding cases of abruption (preterm delivery less than 37 weeks: 14.5% compared with 10.4%, aOR 1.5, 95% CI 1.2–1.8, P<.01; preterm delivery less than 34 weeks: 4.2% compared with 2.7%, aOR 1.7, 95% CI 1.3–2.4, P<.01). Symptomatic bleeding did not have an impact on the risk of preterm delivery or any of the other outcomes of interest. There was no statistically significant association between presence of subchorionic hemorrhage and preterm PROM (n=1,484, 4.1% compared with 2.3%, aOR 1.3, 95% CI 1.0–1.8, P=.07), IUGR (n=8,159, 13.0% compared with 13.1%, aOR 1.1, 95% CI 0.9–1.4, P=.59), intrauterine fetal death (n=445, 1.3% compared with 0.8%, aOR 1.4, 95% CI 0.8–3.1, P=.21), or preeclampsia (n=4,683, 6.4% compared with 7.5%, aOR 0.8, 95% CI 0.6–1.1, P=.18).
We found that the detection of a subchorionic hemorrhage during routine second-trimester ultrasonography was associated with a more than twofold increased risk of placental abruption, regardless of whether the woman reported bleeding in the early half of pregnancy. We also identified that women with subchorionic hemorrhage are at increased risk of preterm delivery. In contrast, we did not find evidence for an increased risk of IUGR, intrauterine fetal death, preterm PROM, or preeclampsia in women with subchorionic hemorrhage compared with those without. Our findings represent new, more robust information regarding the risks associated with the common clinical entity, subchorionic hemorrhage, compared with the existing data in the published literature.
After a few early observational reports,10,11 Ball et al1 conducted a case–control study that examined pregnancy outcomes in 238 individuals found to have subchorionic hemorrhage on first-trimester scan. This study found ultrasonically detected subchorionic hemorrhage to be associated with an increased risk of subsequent placental abruption and preterm labor. The study by Ball et al1 found no increased risk of IUGR in those with subchorionic hemorrhage, but it did find a statistically significant association with intrauterine fetal death that was related to increasing size of the hemorrhage. Later, among more observational studies,3,12–15 Nagy et al2 studied 187 individuals with subchorionic hemorrhage compared with 6,488 women in the control group and found an increased risk of abruption, IUGR, and preterm delivery, but the study did not demonstrate an association with intrauterine fetal death. Size and location of hematoma did not correlate with any adverse pregnancy outcomes.
By studying a cohort of unselected patients undergoing routine, standard-of-care, second-trimester anatomic survey, we were able to more accurately assess the incidence of subchorionic hemorrhage. Our larger sample also allowed us to estimate the associated risk of many less-frequent adverse pregnancy outcomes with the detection of subchorionic hemorrhage. The detailed information available for the patients in our cohort, including demographics, history, and pregnancy outcomes, allowed us to identify many associated outcomes and adjust for potential confounders. Finally, by identifying our cohort by those undergoing a routine second-trimester anatomic survey, we are able to avoid the selection bias inherent in selecting based on first-trimester ultrasound examinations, allowing our results to be applied to the general obstetric population. Despite the strengths of our study, there are some limitations that must be considered as well. Previous studies have attempted to adjust for size or location of subchorionic hemorrhage, but we were unable to do so because only the presence or absence of subchorionic hemorrhage was most frequently recorded.1,5,11 However, although we did not evaluate or adjust for these features, it is worth noting that the size of the hemorrhage was large enough to be clinically observed, further improving our generalizability. Additionally, approximately 11% of the potential cohort lacked outcome data and could not be included in this analysis, creating the potential for selection bias. However, patients who lacked follow-up information did not differ from those analyzed on baseline or exposure characteristics, making the potential impact of this on the result minimal. Last, as is the case with all retrospective and many prospective studies that investigate preterm PROM as an outcome, there may be some misclassification with regard to concomitant preterm labor that cannot be accounted for with statistics.
We found that patients with an ultrasound-detected subchorionic hemorrhage at the time of routine anatomic survey have an increased risk of placental abruption and preterm birth, corroborating earlier findings in smaller studies with selected patient populations. Although there is currently no prevention or treatment for either of these outcomes, patients with an identified subchorionic hemorrhage could be counseled to report early with any bleeding or signs or symptoms of preterm labor because of their increased risk. Conversely, patients can be reassured based on our findings that the identification of subchorionic hemorrhage does not confer an increased risk of IUGR, intrauterine fetal death, preeclampsia, or preterm PROM.
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