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We sought to estimate whether the presence of a maternal uterine anomaly is associated with adverse pregnancy outcomes.
This retrospective cohort study included singleton pregnancies undergoing routine anatomic survey from 1990 through 2008 at a major tertiary care medical center. Pregnancies with a diagnosis of uterine anomaly (uterine septum, unicornuate uterus, bicornuate uterus, uterine didelphys) were compared to those with normal anatomy. Primary outcomes of interest were spontaneous preterm birth (PTB), breech presentation, and cesarean delivery.
The presence of an anomaly was associated with PTB <34 weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI], 4.8–11.4; P < .01), PTB <37 weeks (aOR, 5.9, 95% CI, 4.3–8.1; P < .01), primary nonbreech cesarean delivery (aOR, 2.6; 95% CI, 1.7–4.0; P < .01), preterm premature rupture of membranes (aOR, 3.2; 95% CI, 1.8–5.6; P < .01), and breech presentation (aOR, 8.6; 95% CI, 6.2–12.0; P < .01).
Women with a uterine anomaly are at risk for PTB, highlighting an at-risk population that needs additional study for possible interventions for PTB prevention.
The most common müllerian anomalies include uterine septum, unicornuate uterus, bicornuate uterus, and uterine didelphys. Although it has been established that congenital uterine anomalies lead to infertility and recurrent first-trimester pregnancy loss,
the relationship between uterine anomalies and adverse pregnancy outcomes in the third trimester is less well studied. Some who have found an association between uterine anomalies and preterm birth (PTB) theorize that diminished muscle mass, particularly in a unicornuate uterus, plays an important role in the mechanism of preterm delivery.
The existing data linking the presence of uterine anomalies to outcomes such as PTB, preterm premature rupture of membranes (PPROM), breech presentation, and cesarean section are mostly derived from small case-control studies or case reports.
We aimed to improve upon the existing published data regarding congenital uterine anomalies and adverse pregnancy outcomes. We hypothesized that the presence of a uterine anomaly at routine ultrasound is associated with PTB, preterm rupture of membranes, and cesarean delivery.
Materials and Methods
We performed a retrospective cohort study to estimate the relationship between congenital uterine anomalies and adverse pregnancy outcomes. Our cohort was comprised of all consecutive singleton pregnancies undergoing routine anatomic survey from 1990 through 2008 at our tertiary care center. The study was conducted using the institutional perinatal database. Before study initiation, approval by our institutional human studies review board was obtained.
Women participating in the study had their demographic information, history, and pregnancy outcomes entered into a prenatal database. Since creation of the prenatal database in 1988, all of the patients seen in the prenatal diagnosis center have been followed by dedicated pregnancy outcome coordinators. To achieve complete follow-up information on pregnancy outcome, each patient was given a standardized form at the first visit to be completed after delivery, which detailed pregnancy outcome. The database included follow-up sheet also included details about pregnancy complications, delivery indications, and neonatal outcomes, including chromosomal and structural abnormalities. If the form was not returned within 4 weeks of expected date of delivery, the patient received a telephone call from an outcome coordinator. If the patient could not be reached after delivery, the referring physician was then contacted. For patients delivering within network, outcome information was extracted from the electronic medical record. Gestational age was determined by the first day of the woman's last menstrual period (LMP). If the LMP-estimated due date was consistent (±5 days in the first trimester, ±14 days in the second trimester, and ±21 days in the third trimester) with the due date obtained from growth measurements at the first ultrasound then the due date was not changed. If the due dates by LMP and first ultrasound were not consistent, then the ultrasound-obtained due date was used to define gestational age. Maternal demographics, obstetric history, indications for the ultrasound visit, findings from the ultrasound examination or any testing performed, and outcome of the pregnancy were all collected and stored in the database. Patients with incomplete follow-up data were excluded from this study.
Evaluation of maternal uterine anatomy was performed as part of every routine anatomic survey. We defined the primary exposure as the presence of a uterine anomaly diagnosed prior to pregnancy or identified at that survey. We compared the incidence of adverse pregnancy outcomes in our 2 study populations: those with a congenital uterine anomaly vs those with normal uterine anatomy. Our primary outcomes were spontaneous PTB (both <34 weeks and <37 weeks), PPROM (defined as rupture of membranes <37 weeks), breech presentation, and cesarean delivery. Intrauterine growth restriction (IUGR) was defined as <10th percentile for gestational age.
The incidence of müllerian anomalies in our study population was estimated. Descriptive statistics were used to describe and compared the baseline characteristics of the 2 study groups. To compare baseline features between groups, Student t test was used for continuous variables, χ2 for categorical variables, or Fisher exact test for rare categorical variables. Univariable analysis was used to estimate the relative risk (RR) of each outcome of interest (PTB, PPROM, breech, and cesarean delivery). We performed stratified analyses to identify potentially confounding factors. Logistic regression analyses were used to better estimate the relationship between uterine anomalies and our defined outcomes while adjusting for potentially confounding effects. Factors identified by the stratified analyses, as well as those with biological plausibility or historically reported to be associated with the outcomes of interest, were considered in the logistic regression analysis. Year of examination was considered categorically in increments of 4 years, to account for the long duration of the study period. Backward selection was used to reduce the number of variables in the model by assessing the magnitude of change in the effect size of the other covariates. Differences in the explanatory models were tested using the likelihood ratio test or Wald test.
All variables that were statistically significant were included in the final models. A subgroup analysis of risk of PTB before both 34 and 37 weeks in women with a uterine anomaly compared to women with normal anatomy by parity (nulliparas vs multiparas) was performed. Descriptive analysis was used to estimate the incidence of various types of uterine anomalies within the primary exposure group and subgroup analysis to estimate the association between specific müllerian anomalies and risk of spontaneous PTB was also performed. All statistical analyses were performed using software (STATA 10.0, special edition; StataCorp, College Station, TX).
Of 72,373 singleton pregnancies, 66,956 (93%) had complete pregnancy outcome information and were used in this analysis. A total of 203 (0.3%) pregnancies complicated by maternal uterine anomaly were identified at anatomic survey.
When comparing women with a uterine anomaly to those with normal uterine anatomy, the groups were statistically similar with respect to mean maternal age and gravidity. The incidence of preeclampsia and gestational diabetes was also statistically similar between the 2 groups. However, there were some differences. Women with a uterine anomaly were more likely to have a history of PTB or stillbirth. Women with normal uterine anatomy were more likely to have higher parity and to be African American (Table 1).
TABLE 1Maternal and pregnancy characteristics of patients with a congenital uterine anomaly compared to those without
Abnormal uterine morphology (n = 203)
Normal uterine morphology (n = 66,753)
Mean maternal age, y
29.3 ± 0.4
30.1 ± 0.02
Median age, y (IQR)
2.4 ± 1.5
2.7 ± 1.6
Median gravidity (IQR)
0.7 ± 0.9
1.0 ± 1.2
Median parity (IQR)
Mean maternal BMI
23.7 ± 7.8
25.0 ± 9.4
Median maternal BMI (IQR)
Gestational age at examination, wk
18.9 ± 1.7
19.2 ± 1.7
Prior preterm birth
African American race
Maternal renal disease
BMI, body mass index; IQR, interquartile range.
Hua. Pregnancy complications associated with müllerian anomalies. Am J Obstet Gynecol 2011.
Within our exposure population, bicornuate uterus represented >50% of the uterine anomalies, while unicornuate uterus was the least common. While women with uterine didelphys accounted for only 13% of the uterine anomalies, they had a higher proportion of PTB <34 weeks and <37 weeks than any other subgroup (Figure).
The presence of a uterine anomaly was associated with a 7-fold increased risk in PTB <34 weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI], 4.8–11.4; P < .01) and a nearly 6-fold increased risk in PTB <37 weeks (aOR, 5.9; 95% CI, 4.3–8.1; P < .01) compared to those pregnancies in women with normal uterine anatomy after excluding those with a history of PTB, and adjusting for prior African American race, and preeclampsia. Uterine anomalies were associated with a 3-fold increased risk of PPROM (RR, 3.0; 95% CI, 1.8–5.0) after adjusting for preeclampsia and African American race (aOR, 3.2; 95% CI, 1.8–5.6; P < .01) when compared with normal uterine anatomy (Table 2). Examination year did not influence the results and therefore did not remain in the models. The presence of a uterine anomaly also confers an increased risk of breech presentation (aOR, 8.6; 95% CI, 6.2–12.0; P < .01) and primary cesarean delivery of a nonbreech fetus (aOR, 2.6; 95% CI, 1.7–4.0; P < .01). Increased rates of placenta previa (odds ratio, 5.8; 95% CI, 2.2–15.3; P < .01) and placental abruption (aOR, 3.1; 95% CI, 1.1–8.3; P < .01) were also seen (Table 3). Primiparous patients with a uterine anomaly, compared to multiparas, were shown to have a higher magnitude of risk of PTB before both 34 and 37 weeks (Table 4).
TABLE 2Outcomes of interest: congenital uterine anomalies vs normal uterine morphology
Finally, to better estimate the relationship between the presence of a uterine anomaly and stillbirth, we excluded all pregnancies in women with a history of stillbirth. There were 3 cases of antepartum stillbirth in the uterine anomaly group and 668 in the normal uterine morphology group (1.6% vs 1.0%; RR, 1.5; 95% CI, 0.5–5.0; P = .40).
We found that the presence of a maternal uterine anomaly detected at the time of anatomic survey is associated with an increased risk of PTB, PPROM, breech presentation, and cesarean section. We also found an increased risk for placenta previa, placental abruption, and IUGR in women with a uterine anomaly. These findings support much of what has been previously described by small, published reports.
compared 176 patients with known uterine malformations to 28 women with other genital and/or urinary anomalies but a normal uterus. The study confirmed higher rates of preterm delivery and breech presentation in the uterine anomaly group. However, the central conclusions that can be drawn from this study are limited due to its observational nature and the inability to adjust for confounding factors, such as history of PTB. Additionally, only 53% of the pregnancies in women with uterine malformations ended with a child surviving >7 days, suggesting that many of the PTBs occurred before or near viability. This makes it difficult to draw meaningful conclusions from this study regarding the risk of PTB in the viability period.
performed a prospective cohort study in which women considered to be at low risk for uterine anomalies provided their obstetrical histories prior to being screened for uterine anomalies via transvaginal ultrasound. They reported a higher incidence of preterm labor in their arcuate uterus cohort than the normal uterine anatomy group (12.5% vs 6.2%, P < .01). Their study did not comment on the incidence of preterm delivery, nor did it find an increased incidence of PPROM. The interpretation of their study results may be limited, due to analytical limitations with no adjustment for possible confounding factors, as well as examination of surrogate rather than desired outcomes.
With respect to IUGR, our study found an increased risk of growth restriction even after adjusting for confounding factors. Some have hypothesized that abnormal uterine blood flow and decreased muscle mass may be the culprits behind growth restriction related to uterine anomalies.
of 20 studies examining the impact of a unicornuate uterus on pregnancy outcomes likewise found an association between uterine anomalies and growth restriction. Based on the current American Congress of Obstetrics and Gynecology guidelines for management of IUGR,
reported among fertile women. Although other texts have cited septate uterus as the most common anomaly in the general population, our study population is of women who present at anatomic survey in the midtrimester, which reflects the risk of early pregnancy loss published for women with a uterine septum.
We attempted to estimate the risk of intrauterine fetal demise (IUFD) in the uterine anomaly population. However, given the low incidence of cases (n = 3) of IUFD in the uterine anomaly population, we were underpowered to report reliably on the risk estimate of IUFD and uterine anomaly.
Our study offered several strengths. Our large sample size allowed us to study a relatively rare diagnosis and its association with rare but clinically important outcomes. Additionally, the comprehensive database allowed us to access complete pregnancy follow-up information that was obtained in a prospective manner, as well as data on patient demographics and history. This allowed us to estimate the relationship between uterine anomalies and multiple outcomes of interest, while adjusting for known confounders. However, our study was not without weaknesses. One potential weakness was that we used ultrasound diagnosis of uterine anomaly at midtrimester screening rather than the gold standard of magnetic resonance imaging.
However, we would argue that the most likely consequence of this was that uterine anomalies were likely underdiagnosed in our control population, and this misclassification bias would bias our results toward the null hypothesis. A second weakness, inherent to retrospective cohort studies, is the potential for missing data. While our database was complete with respect to potentially confounding variables, we were lacking follow-up information on 7.0% of our patients. However, sensitivity analyses revealed that the patients with missing outcome data who were excluded from this study were not significantly different from those included with respect to baseline and exposure data, making this potential source of selection bias less likely (data not shown, but available on request). Lastly, while our cohort is, to our knowledge, the largest used to study congenital uterine anomalies and pregnancy outcomes, we were still limited in our ability to refine the relationship estimates between specific subtypes of uterine anomalies and adverse pregnancy outcomes due to the rare occurrence of those outcomes in our cohort.
In conclusion, our study found a significant increase in the risk of PTB, breech, cesarean delivery, and IUGR in pregnancies complicated by a uterine anomaly detected at routine ultrasound compared to those with normal uterine morphology. These findings can be used to counsel women whose pregnancies are complicated by a müllerian anomaly, and to help guide appropriate antenatal surveillance. Specifically, it seems reasonable to screen these pregnancies for the development of IUGR with serial ultrasound assessments of estimated fetal weight. Although there are limited data regarding PTB prevention in this particular cohort, we have identified an at-risk population that deserves future study.
Obstetric outcome of women with uterine anomalies in China.
We read with great interest the article titled “Congenital uterine anomalies and adverse pregnancy outcomes” by Meiling Hua et al1 (2011). However, the article contains a section that may not be correct regarding the incidence of preterm births <37 weeks by uterine anomalies, which requires the authors' attention. And the article also has some confusing presentation in the “Materials and Methods,” “Results,” and “Comment” sections concerning the diagnosis of uterine anomalies.