Objective
We sought to estimate the association between chorionicity and intrauterine fetal demise (IUFD) of one or both fetuses in twin pregnancies.
Study Design
In a retrospective cohort of twins undergoing anatomic survey, risk of IUFD in monochorionic and dichorionic twins was compared. The primary outcome was IUFD of one or both fetuses; secondary outcomes included nonanomalous fetal deaths.
Results
Of 2161 twin pregnancies meeting inclusion criteria, 86 had at least 1 IUFD and 32 experienced a double fetal loss. Monochorionic pregnancies had an increased risk of a single demise (adjusted odds ratio, 1.69; 95% confidence interval, 1.04–2.75) and a double demise (adjusted odds ratio, 2.11; 95% confidence interval, 1.02–4.37). Of all double demises, 70% occurred <24 weeks.
Conclusion
Monochorionic twins carry an increased risk of fetal death compared to dichorionic twins. Double demise occurs primarily <24 weeks, regardless of chorionicity.
Since 1980, there has been a 70% increase in the number of twin pregnancies, attributable to delayed childbearing and use of assisted-reproductive therapies. It is known that twins carry a high burden of morbidity and mortality, with the published risk of intrauterine fetal demise (IUFD) ranging from 2.6–5.8%. Available data on the comparative rates of demise by chorionicity are limited, predominantly by sample size and assessment of chorionicity. The largest published studies have approximately 1000 twin pregnancies and assessment of chorionicity is often incomplete, or a surrogate such as gender is used.
Additionally, there is little evidence available to manage women after a twin pregnancy is complicated by the death of 1 fetus, limiting much of counseling and management to expert opinion. The recent systematic review and metaanalysis by Hillman et al confirms the need for additional data on the risk of IUFD of one or both fetuses in twin pregnancies.
The aims of our study were to estimate the association between chorionicity and the risk of IUFD of one or both fetuses and, further, to describe the effect of chorionicity on the risk and timing of the second twin death, in those pregnancies complicated by a double fetal loss.
Materials and Methods
We performed a retrospective cohort study of all consecutive twin pregnancies undergoing routine sonographic anatomic survey at 17-22 weeks from 1990 through 2008 at Washington University Medical Center. The Washington University School of Medicine Human Studies Review Board approved the study prior to initiation. Obstetric sonographers performed all standardized examinations with review and final interpretation by maternal–fetal medicine physicians.
Dedicated research nurses collected the data prospectively. The data were primarily extracted from medical records, and then secondarily by the patient. Each patient provided detailed information regarding medical history, obstetrical history, and social history at the time of the second-trimester ultrasound. Each patient was also given a form to be completed after delivery reflecting pregnancy outcomes including antenatal complications, delivery complications, and neonatal outcomes. If the form was not completed and received within 4 weeks of the expected date of delivery, a research coordinator called the patient to obtain the information. The majority of patients (92%) delivered at our institution; if the patient could not be reached and delivered at an outside facility, the coordinator contacted the referring physician to obtain outcome data. For twin pregnancies discordant for outcomes, the details and outcomes regarding each twin were obtained. Only twin pregnancies with complete outcome information were included in this study.
Study groups were defined by chorionicity, which is a standard component of twin pregnancy sonographic examinations. Final chorionicity designation was made by the earliest available ultrasound and confirmed by pathology specimens in 71% of the pregnancies. Gestational age was assigned based on the first day of a woman’s last menstrual period. If this dating was not consistent with dating based on the earliest ultrasound (±7 days in the first trimester or ±10 days in the second trimester), the gestational age was reassigned. In twin pairs that were discordant in size at the time of a dating ultrasound, the biometry of the larger twin was used to date the pregnancy as to err on the side of safety by maximizing sensitivity for abnormal growth. At the discretion of the providers but in accordance with typical practice at our institution, ultrasounds were performed every 2 weeks for monochorionic twins to assess for evidence of twin-to-twin transfusion syndrome (TTTS), and every 3-4 weeks for all twins to assess growth. Antenatal testing with twice-weekly nonstress tests or biophysical profiles was initiated at 32 weeks unless there was a clinical indication for earlier testing.
Dichorionic diamniotic pregnancies were compared to monochorionic diamniotic pregnancies. Monoamniotic pregnancies, pregnancies affected by TTTS, singleton gestations, and higher-order multiple gestations were excluded from the study. The primary outcome was IUFD of one or both fetuses defined as fetal death ≥20 weeks and confirmed by ultrasound examination at our institution. If a fetal death occurred <20 weeks, the pregnancy was not included in the analysis. Risk of IUFD of either twin was estimated, as well as the risk of IUFD of either twin by week of continuing gestation. In the subanalysis of women who experienced an IUFD of at least 1 fetus, the effect of chorionicity on timing of IUFD of the second twin was described.
Baseline characteristics of women by chorionicity were compared. The Student t test or Mann-Whitney U test was used for continuous variables and the χ 2 or Fisher exact test was used for categorical variables as appropriate. The relative risk of IUFD within the pregnancy and the 95% confidence interval (CI) were estimated and compared by chorionicity. Stratified analyses were performed to identify potentially confounding factors. Logistic regression analyses were used to refine the risk estimate by chorionicity for any IUFD in the pregnancy by adjusting for confounding factors that were identified by unadjusted and stratified analyses, as well as those factors historically reported to be associated with IUFD. Backward stepwise selection was used to reduce the number of variables in the model by assessing the magnitude of change in the effect size of remaining covariates. Differences in the explanatory model were tested using the likelihood ratio test or Wald test. Statistically significant variables were included in the final models. To estimate the risk of stillbirth of either twin by chorionicity, conditional logistic regression adjusting for twin clusters was used to account for nonindependence of twin pairs and adjust for prior fetal death. A subanalysis excluding pregnancies affected by known major congenital anomalies and known chromosomal abnormalities was performed.
Next, the prospective risk of any IUFD by chorionicity was calculated for each week of continuing gestation using the number of ongoing pregnancies as the denominator. In a subanalysis of women who experienced IUFD of both twins, gestational age at loss of the second twin was described by chorionicity. Presence of intrauterine growth restriction (IUGR), defined as birthweight <10th percentile by the Alexander growth standard, was described within pregnancies experiencing single or double fetal loss. Finally, women who experienced a double fetal demise were compared to those who lost 1 twin to identify possible factors, besides chorionicity, associated with risk of a second twin loss. Statistical analyses were performed using STATA 10.0, special edition (StataCorp, College Station, TX).
Results
Of 2445 twin intrauterine pregnancies, 2333 met inclusion criteria. Of those, 2161 (92.6%) had complete outcome data and were included in the analysis; 496 (23%) were monochorionic and 1665 (77%) were dichorionic pregnancies ( Figure ).
The 2 groups were similar in terms of gravidity, nulliparity, rates of preeclampsia, pregestational diabetes, gestational diabetes, history of preterm delivery including spontaneous preterm delivery, IUGR, and having any major congenital anomaly diagnosed during the pregnancy ( Table 1 ). Women carrying monochorionic twins on average were younger, delivered at an earlier gestational age, were more likely to be smokers, and were more likely to report alcohol exposure during the pregnancy. Women carrying dichorionic twins were more likely to have a body mass index >30 kg/m 2 , be of African American race, have chronic hypertension, and have a history of an IUFD. Women excluded for lack of follow-up were generally statistically similar, although less advanced maternal age, and they were more likely to be African American, be obese, and use tobacco.
| Characteristics | Monochorionic n = 496 | Dichorionic n = 1665 | P value a | No outcome n = 172 |
|---|---|---|---|---|
| Age, y | 29.8 ± 6.2 | 31.4 ± 5.9 | < .01 | 29.1 ± 6.0 |
| Age ≥35 y | 23.2 | 29.3 | < .01 | 6.3 |
| Gravidity | 2.6 ± 1.5 | 2.6 ± 1.6 | .78 | 3.1 ± 2.2 |
| Nulliparity | 27.0 | 27.3 | .91 | 27.8 |
| Gestational age at delivery, wk | 33.9 ± 4.8 | 34.8 ± 4.2 | < .01 | N/A |
| BMI, kg/m 2 | 25.1 ± 6.4 | 26.0 ± 7.0 | < .01 | 27.04 ± 7.5 |
| BMI ≥30 kg/m 2 | 16.6 | 22.0 | .01 | 22.8 |
| African American | 17.1 | 21.7 | .03 | 46.2 |
| Tobacco use | 13.1 | 9.1 | .01 | 14.6 |
| Alcohol use | 16.2 | 11.7 | < .01 | 10.3 |
| Chronic hypertension | 1.4 | 3.3 | .03 | 2.1 |
| Preeclampsia | 17.9 | 20.9 | .13 | 10.8 |
| Pregestational diabetes | 0.6 | 1.2 | .26 | 1.9 |
| Gestational diabetes | 6.5 | 6.2 | .82 | 8.1 |
| History of IUFD | 1.8 | 3.0 | .15 | 1.9 |
| History of preterm delivery | 5.2 | 6.7 | .25 | 7.1 |
| Birthweight <10th percentile b | 25.1 | 21.0 | .32 | N/A |
| Any anomaly c | 1.6 | 2.3 | .33 | 2.5 |
a Comparing monochorionic and dichorionic groups only;
b Based on Alexander birth standard;
c Includes any major congenital anomaly identified in either twin.
Monochorionic pregnancies were at increased risk of at least 1 fetal demise (adjusted odds ratio [OR], 1.69; 95% CI, 1.04–2.75) as well as an increased risk of a double fetal demise (adjusted OR, 2.11; 95% CI, 1.02–4.37) when compared to dichorionic pregnancies ( Table 2 ). Risk of IUFD of either twin within a monochorionic compared to a dichorionic pregnancy was also significantly increased and remained increased after adjusting for fetal demise in a prior pregnancy (adjusted OR, 1.74; 95% CI, 1.10–2.78). When excluding pregnancies complicated by any major congenital anomaly, monochorionic pregnancies remained at increased risk of a single IUFD; the increased risk of a double fetal demise did not reach statistical significance. The prospective risk of IUFD within the pregnancy for ongoing pregnancies by week of gestation starting at 20 weeks is presented in Table 3 . A greater risk for any IUFD was observed in women with monochorionic compared to dichorionic twins throughout gestation, particularly in the second trimester. The risk for any IUFD decreased as pregnancy progressed.
| Outcome | Monochorionic n = 496 | Dichorionic n = 1665 | Unadjusted RR (95% CI) | Adjusted OR (95% CI) | P value |
|---|---|---|---|---|---|
| Any IUFD (n = 86) | 6.0% (n = 30) | 3.4% (n = 56) | 1.76 (1.15–2.72) | 1.69 a (1.04–2.75) | .03 |
| IUFD of both (n = 32) | 2.4% (n = 12) | 1.2% (n = 20) | 1.65 (1.05–2.60) | 2.11 b (1.02–4.37) | .04 |
| Any nonanomalous IUFD (n = 77) | 5.7% (n = 28) | 3.0% (n = 49) | 1.61 (1.19–2.19) | 1.87 a (1.12–3.10) | .02 |
| Nonanomalous IUFD of both (n = 30) | 2.3% (n = 11) | 1.2% (n = 19) | 1.60 (0.99–2.58) | 2.02 b (0.95–4.30) | .07 |
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