Uterine fibroid tumors have been associated with adverse outcomes in singleton pregnancies. We aimed to estimate risk for adverse obstetric outcomes that are associated with fibroid tumors in twin pregnancies.
A retrospective cohort study of twin pregnancies with ≥1 fibroid tumor on second trimester ultrasound examination. Outcomes included small-for-gestational-age fetal growth, preterm delivery, preterm rupture of membranes, abruption, preeclampsia, and intrauterine fetal death. Univariable and multivariable analyses were used to evaluate the impact of fibroid tumors on outcomes in twin pregnancies compared with twin pregnancies without fibroid tumors.
Of 2378 nonanomalous twin pregnancies, 2.3% had fibroid tumors. Twin pregnancies with fibroid tumors were no more likely to have small-for-gestational-age growth (40.0% vs 36.0%; adjusted odds ratio, 1.1; 95% confidence interval, 0.7–2.0) or preterm delivery at <34 weeks’ gestation (25.0% vs 24.0%; adjusted odds ratio, 1.0; 95% confidence interval, 0.5–1.9) than twin pregnancies without fibroid tumors. Other adverse outcomes were no more likely to occur in twin pregnancies with fibroid tumors than in twin pregnancies without fibroid tumors. Post hoc power calculations suggested >97% power to detect 2-fold differences in small for gestational age and preterm delivery at <34 weeks’ gestation.
In contrast to data that suggest an increased risk for adverse outcomes in singleton pregnancies with fibroid tumors, twin pregnancies with fibroid tumors do not appear to be at increased risk for complications compared with those pregnancies without fibroid tumors.
Uterine fibroid tumors are the most common benign tumor of the female reproductive tract and occur in 20-50% of reproductive age women. As women age, fibroid tumors become increasingly common, and by menopause the incidence of fibroid tumors may be as high as 70-80%. Fibroid tumors may influence the entire spectrum of reproductive function from alterations in fertility, conception, and implantation events to later pregnancy outcomes, such as preterm birth or need for cesarean delivery. Several observational studies have investigated the impact of fibroid tumors on obstetric outcomes in singleton pregnancies with conflicting results. In a cohort of women with singleton pregnancies from our institution, we found a positive association between fibroid tumors and multiple adverse obstetric outcomes that included malpresentation, placenta previa, preterm birth, and intrauterine fetal death.
Given the trend for women to delay childbearing and the high prevalence of fibroid tumors in reproductive age women, the question of whether fibroid tumors influence obstetric outcomes is not infrequent for obstetric providers. In addition, the incidence of twin pregnancies has risen 47% since 1990 and currently accounts for approximately 32 per 1000 births in 2009. All previous investigations, which include the one from our institution, estimated the risk for adverse outcomes only among singleton gestations, which left obstetric providers to extrapolate the impact of fibroid tumors in twin pregnancies from singleton studies. Thus, we aimed to investigate whether women with twin pregnancies and fibroid tumors are also at increased risk for adverse obstetric outcomes.
Materials and Methods
This is a retrospective cohort study of all consecutive viable twin gestations who presented for routine second-trimester anatomic ultrasound examination between 1990 and 2007 at Washington University Medical Center. This analysis was performed with the large institutional perinatal database and was approved by the Washington University School of Medicine human studies review board.
Ultrasound examinations were performed by dedicated obstetric and gynecologic sonographers with final interpretation and diagnoses made by Maternal Fetal Medicine attending physicians. Fetal number, chorionicity, placental location, fetal anatomy, and maternal anatomy are recorded routinely as part of second-trimester anatomic surveys. Gestational age was determined by the best data available from the last menstrual period that was consistent with ultrasound dating (±5 days in the first trimester or ±14 days in the second trimester). If last menstrual period was unknown or inconsistent with ultrasound dating, the pregnancy was dated according to the earliest ultrasound data available. Chorionicity is assigned on the basis of the evaluation of fetal genders, placental masses, visualization of the intersection of fetal membranes with placental masses (“lambda sign”), and thickness of fetal membranes. If chorionicity was determined at an earlier ultrasound examination, repeat examination of the routine markers of chorionicity, as appropriate for gestational age, was performed to confirm that the findings were consistent with previous documentation. Maternal anatomy, which included presence, location, and sizes of the 6 largest or most clinically relevant fibroid tumors were documented according to recommendations of the American Institute of Ultrasound in Medicine. Fibroid size routinely is measured in 3 dimensions. In addition, fibroid location within the uterus and relative to placental location is documented routinely.
Twin pregnancies with ≥1 fibroid tumors were compared with twin pregnancies without fibroid tumors. Obstetric outcomes were collected prospectively as the pregnancies continued through the study period and were entered into the perinatal database by trained obstetric research coordinators. Primary outcomes included preterm delivery and small-for-gestational-age (SGA) infants in 1 or both twins (defined as birthweight <10th percentile for gestational age according to the Alexander growth standard ). Other outcomes that were evaluated included placenta previa, placental abruption (defined clinically by the obstetric provider and documented in the medical record), preeclampsia (defined according to criteria established by the American College of Obstetricians and Gynecologists ), and intrauterine fetal death at >20 weeks of gestation. Pregnancies that were complicated by major fetal anomalies in either fetus were excluded.
Descriptive statistics were used to calculate the incidence of fibroid tumors in the cohort of twin pregnancies. Baseline maternal characteristics were compared between women with and without fibroid tumors with chi-square or Fisher Exact tests, as appropriate. Univariable analysis was performed for obstetric outcomes of interest to obtain relative risks with 95% confidence intervals. Backward stepwise logistic regression was used to control for pertinent confounding variables. The likelihood ratio test was used to assess the impact of removal of covariates from the model. If there were <10 observations for any cell, multivariable logistic regression was not performed to avoid the potential for misleading estimates of risk. Stratified analysis according to chorionicity and fibroid size was also performed. All outcomes were considered at the level of the pregnancy (not at the level of each individual fetus); therefore, paired analysis was not used. All statistical analyses were performed using STATA software (version 10, Special Edition; StataCorp, College Station, TX).
There were a total of 2445 women with twin pregnancies in the cohort. Of those, 67 women (2.7%) were excluded because of major fetal anomalies, which left 2378 women in the final nonanomalous cohort that was examined for obstetric outcomes. Of 2378 women with nonanomalous twin pregnancies, 55 women (2.3%) had fibroid tumors, and 2323 women (97.7%) did not. Of the 55 pregnancies with fibroid tumors, 51 of the fibroid tumors (92.7%) were <6 cm in greatest dimension, and 4 fibroid tumors (7.3%) were >6 cm.
Women with twin pregnancies that were complicated by fibroid tumors were, on average, more likely to be of advanced maternal age, have gestational diabetes mellitus, report alcohol use, have had a previous cesarean delivery, have lower parity, and have fewer living children compared with women with twin pregnancies without fibroid tumors ( Table 1 ). However, twin pregnancies with fibroid tumors had similar prevalence of black women compared with twin pregnancies without fibroid tumors. In addition, smoking during pregnancy, gestational age at study ultrasound examination, monochorionicity, previous birth of a neonate who weighed <5 pounds, and previous preterm birth did not differ between twin pregnancies with fibroid tumors and twin pregnancies without fibroid tumors.
|Characteristic||Fibroid tumor (n = 55)||No fibroid tumor (n = 2323)||P value|
|Advanced maternal age: >35 y, %||60.0||24.7||< .01|
|Black race, %||29.1||23.0||.33|
|Gravidity, n a||2.4 ± 1.5||2.6 ± 1.6||.14|
|Parity, n a||0.6 ± 1.0||1.0 ± 1.2||< .01|
|Body mass index >30 kg/m 2 , %||27.1||20.9||.30|
|Current smoker, %||7.3||10.6||.4|
|Alcohol use during pregnancy, %||21.8||12.3||.03|
|Current diagnosis of gestational diabetes mellitus, %||17.6||6.1||< .01|
|Preexisting diabetes mellitus, %||1.8||1.2||.65|
|Current diagnosis of chronic hypertension, %||5.5||2.8||.28|
|Gestational age at study ultrasound examination, wk a||19.8 ± 1.7||19.7 ± 1.6||.6|
|Monochorionic gestation, %||19.6||23.0||.56|
|Previous preterm birth, %||1.8||6.6||.14|
|Spontaneous abortions, n a||0.3 ± 0.6||0.4 ± 0.7||.58|
|Living children, n a||0.6 ± 1.0||1.0 ± 1.2||.03|
|Previous cesarean delivery, %||1.8||1.4||< .01|
|Previous birth of neonate weighing <5 lbs, %||7.3||7.3||.98|
Pregnancy outcomes are shown in Table 2 . Women with twin pregnancies and fibroid tumors were no more likely to deliver preterm at <37 weeks’ gestation (71.4% vs 62.3%; adjusted odds ratio [OR], 1.2; 95% confidence interval [CI], 0.7–2.3), <34 weeks’ gestation (25.0% vs 24.0%; adjusted OR, 1.0; 95% CI, 0.5–1.9), <28 weeks’ gestation (7.1% vs 6.7%; relative risk [RR], 1.0; 95% CI, 0.4–2.9), or <24 weeks’ gestation (3.8% vs 3.4%; RR, 1.0; 95% CI, 0.3–4.1) compared with twin pregnancies without fibroid tumors. Similarly, twin pregnancies with and without fibroid tumors had statistically similar risk for preterm premature rupture of membranes (5.7% vs 11.6%; RR, 0.5; 95% CI, 0.2–1.5). There was no difference in risk for placental abruption or preeclampsia in twin pregnancies with or without fibroid tumors. There were no cases of twin pregnancies with placenta previa; therefore, no meaningful comparisons can be made regarding the impact of fibroid tumors on this outcome.
|Outcome||Fibroid tumor, %||No fibroid tumor, %||Unadjusted relative risk (95% CI)||Adjusted odds ratio (95% CI)||P value|
|Delivery at <37 wk gestation||71.4||62.3||1.1 (1.0–1.4)||1.2 (0.7–2.3) a||.17|
|Delivery at <34 wk gestation||25.0||24.0||1.0 (0.7–1.6)||1.0 (0.5–1.9) b||.80|
|Delivery at <28 wk gestation||7.1||6.7||1.0 (0.4–2.7)||NA||.9|
|Delivery at <24 wk gestation||3.8||3.4||1.0 (0.3–4.1)||NA||.9|
|Preterm premature rupture of membranes||5.7||11.6||0.5 (0.2–1.5)||NA||.2|
|Preeclampsia||19.2||20.0||1.0 (0.5–1.7)||0.9 (0.4–1.9) c||.69|