Objective
We sought to determine the perinatal risks associated with growth discordance in appropriately grown twin gestations.
Study Design
We conducted a retrospective cohort study of all twin gestations excluding those complicated by monoamnionicity, twin-twin transfusion syndrome, structural anomalies, selective reduction, or a birthweight <10th percentile. Growth discordance was defined as ≥20%. Outcomes considered were stillbirth, preterm delivery <34 weeks and <28 weeks, and admission to the neonatal intensive care unit. Analyses were stratified by chorionicity.
Results
Of 895 included dichorionic pregnancies, 63 (7.0%) were discordant. Discordant dichorionic twins were not at increased risk of preterm delivery <34 weeks (34.9% vs 25.6%; relative risk [RR], 1.4; 95% confidence interval [CI], 1.0−1.9), preterm delivery <28 weeks (3.2% vs 2.8%; RR, 1.1; 95% CI, 0.3−4.8), or admission to intensive care (26.9% vs 23.5%; RR, 1.5; 95% CI, 1.0−2.3). We had >90% power to detect a 2.5-fold increase in preterm delivery and admission to the neonatal intensive care unit in dichorionic twins. Of 250 monochorionic pregnancies, 23 (9.2%) were discordant. Monochorionic twin pregnancies were at increased risk of preterm delivery <34 weeks (65.2% vs 26.4%; RR, 2.5; 95% CI, 1.7−3.6), preterm delivery <28 weeks (34.8% vs 4.0%; RR, 8.8; 95% CI, 3.7−20.5), and admission to intensive care (68.2% vs 23.3%; RR, 2.9; 95% CI, 2.0−4.3).
Conclusion
In appropriately grown twins, growth discordance is a risk factor for adverse perinatal outcomes in monochorionic, but not dichorionic, twins. Discordant monochorionic twins may benefit from increased antenatal surveillance.
Compared to singleton gestations, twin gestations are at higher risk of fetal growth restriction and stillbirth. Consequently, twin pregnancies are typically monitored with serial ultrasounds for fetal growth, as the presence of growth restriction may alter plans for antenatal testing and timing of delivery. Several studies suggest that growth discordance, typically defined as a difference in birthweights of 10-20%, between the 2 fetuses is a marker of adverse outcomes, such as stillbirth, perinatal morbidity, and preterm delivery. Growth discordance may suggest that the smaller twin is not meeting its growth potential, implying a pathologic condition such as placental insufficiency. However, frequently when significant growth discordance exists, the smaller twin is actually growth restricted (≤10th percentile for gestational age), which may account for the increased morbidity experienced in these pregnancies. The clinical significance of growth discordance in normally grown fetuses (>10th percentile for gestational age) is not clear from reviewing the literature.
Therefore, we sought to assess the association of growth discordance and adverse pregnancy outcomes in twins appropriately grown for gestational age.
Materials and Methods
This was a retrospective cohort study of all patients with a twin gestation who underwent routine second-trimester (15-22 weeks) ultrasound for anatomic survey at a single, tertiary care center. Institutional review board approval was obtained from Washington University in St. Louis, MO. Data were collected prospectively by dedicated nurses from 1990 through 2008. Each patient undergoing ultrasound in our center received a standardized handout requesting information regarding pregnancy complications (eg, date of delivery, diabetes, preeclampsia), delivery complications (eg, mode of delivery, need for transfusion), and neonatal outcomes (eg, birthweight, admission to intensive care unit, infant date of discharge), to be filled out and returned after delivery. The coordinator called the patient, and in cases where the patient could not be reached, the physician, if the form was not returned within 4 weeks of the delivery date. These data have been validated with selected chart review and have been found to be >90% accurate.
Patients were included in this study if they carried a viable twin gestation; singleton gestations, intrauterine fetal demise of either twin at the second-trimester ultrasound, and higher-order multiple gestations were excluded. Twin pregnancies complicated by monoamnionicity (due to its rarity), twin-twin transfusion syndrome, structural anomalies in either, and pregnancies resulting in selective reduction were also excluded. Pregnancies where the birthweight of either twin was <10th percentile for gestational age by the Alexander growth standard were excluded. Gestational age was determined by last menstrual period if known and concordant with ultrasound (within 7 days of first-trimester ultrasound or 14 days of second-trimester ultrasound) or by the earliest ultrasound when the last menstrual period was unknown or discordant. Chorionicity was determined at the earliest ultrasound available. First-trimester diagnosis of chorionicity was based on the number of gestational sacs, amnions, and yolk sacs present or the presence of a lambda sign. Second-trimester determination of chorionicity was based on gender discordance, presence of 2 placental masses, and characteristics of the intertwin dividing membrane (twin peak sign, T-sign, thickness of membrane). Final assignment of chorionicity was determined by an attending physician dedicated to obstetric ultrasound.
Birthweight discordance was calculated as the difference between birthweights divided by the birthweight of the larger twin ([larger birthweight – smaller birthweight]/larger birthweight × 100%). Discordance was defined a priori as ≥20%, based on the findings of prior studies.
Pregnancy outcomes of concordant twin pairs and discordant twin pairs were compared. The outcomes considered were stillbirth of one or both twins, preterm delivery <34 weeks, preterm delivery <28 weeks, and admission of one or both twins to the neonatal intensive care unit (NICU). Because chorionicity may identify unique twin populations, the analysis was stratified by chorionicity.
In a subset of twins, detailed delivery records were available, including Apgar scores, cord gases, and discharge summaries. In these twins, the incidence of 5-minute Apgar scores ≤3, umbilical cord pH ≤7.1, neonatal death, need for ventilator support, and intraventricular hemorrhage in either one or both twins were compared between groups. These outcomes were considered as a composite and individually.
Concordant and discordant twins were compared using descriptive and univariate statistics using unpaired Student t test or Mann-Whitney U test, as appropriate, for continuous variables and χ 2 test or Fisher exact test, as appropriate, for dichotomous variables. Continuous variables were tested for normality visually and with the Kolmogorov-Smirnov test. All analyses were stratified by chorionicity. Because the outcomes considered were pregnancy-level outcomes (eg, preterm delivery, stillbirth of one or both twins), the analyses were not paired. Adjusted analyses were not performed due to the rarity of both the exposure and outcome. The statistical analysis was performed using software (STATA, version 11, Special Edition; StataCorp, College Station, TX).
Results
Of 2445 twin pairs undergoing routine second-trimester ultrasound at our institution, 1145 (46.8%) were included (190 excluded for anomalies, 24 for suspected twin-twin transfusion, 3 for conjoined, 125 for monoamniotic or uncertain chorionicity, 784 for growth restriction of one or both twins, 51 for delivery <24 weeks, 123 for incomplete outcome information) ( Figure ). Twins with ≥20% discordance in birthweight were similar to concordant twins with respect to maternal age, race, history of stillbirth, hypertension, diabetes, preeclampsia, and chorionicity ( Table 1 ).
| Demographic | Concordant (n = 1059) | Discordant (20%) (n = 86) | P value |
|---|---|---|---|
| Age, y | 31.0 ± 6.0 | 31.4 ±5.7 | .70 |
| Race | .90 | ||
| White | 502 (62.3%) | 42 (64.6%) | |
| Black | 149 (18.5%) | 12 (18.5%) | |
| Other | 155 (19.2%) | 11 (16.9%) | |
| History of IUFD | 28 (2.6%) | 0 | .17 |
| Hypertension | 30 (2.8%) | 1 (1.2%) | .50 |
| Diabetes | 79 (7.5%) | 6 (7.0%) | .85 |
| Preeclampsia | 212 (20.2%) | 12 (14.0%) | .16 |
| Type of twins | .25 | ||
| Dichorionic | 832 (78.6%) | 63 (73.3%) | |
| Monochorionic | 227 (21.4%) | 23 (26.7%) |
No stillbirths occurred in the dichorionic twins discordant for birthweight ( Table 2 ). Discordant dichorionic twins were not at an increased risk of delivery <34 weeks (34.9% vs 25.6%; relative risk [RR], 1.4; 95% confidence interval [CI], 1.0−1.9) or <28 weeks (3.2% vs 2.8%; RR, 1.1; 95% CI, 0.3−4.8). The risk of either twin being admitted to the NICU was not increased in the discordant dichorionic twins (26.9% vs 23.5%; RR, 1.5; 95% CI, 1.0−2.3).
| Variable | Concordant | Discordant | RR (95% CI) | P value |
|---|---|---|---|---|
| Dichorionic | n = 832 | n = 63 | ||
| IUFD, either twin | 1 (0.12%) | 0 | — | .78 |
| PTD, <34 wk | 213 (25.6%) | 22 (34.9%) | 1.4 (1.0–1.9) | .11 |
| PTD, <28 wk | 23 (2.8%) | 2 (3.2%) | 1.1 (0.3–4.8) | .85 |
| NICU, either twin | 189 (23.5%) | 17 (26.9%) | 1.5 (1.0–2.3) | .05 |
| Monochorionic | n = 227 | n = 23 | ||
| IUFD, either twin | 2 (0.9%) | 1 (4.6%) | 4.9 (0.5–52.4) | .15 |
| PTD, <34 wk | 60 (26.4%) | 15 (65.2%) | 2.5 (1.7–3.6) | < .01 |
| PTD, <28 wk | 9 (4.0%) | 8 (34.8%) | 8.8 (3.7–20.5) | < .01 |
| NICU, either twin | 51 (23.3%) | 15 (68.2%) | 2.9 (2.0–4.3) | < .01 |
In monochorionic twins, discordant twins were at an increased risk of preterm delivery <34 weeks (65.2% vs 26.4%; RR, 2.5; 95% CI, 1.7−3.6) and <28 weeks (34.8% vs 4.0%; RR, 8.8; 95% CI, 3.7−20.5). Discordant twins were at greater risk of requiring admission to the NICU (68.2% vs 23.3%; RR, 2.9; 95% CI, 2.0−4.3). Of note, this risk was not confined to the smaller twin. In this cohort the risk of stillbirth was not increased among monochorionic, discordant twins compared to concordant twins (4.6% vs 0.9%; RR, 5.2; 95% CI, 0.5−54.7), although due to the rarity of the outcome we have only 60% power to detect a 5-fold difference between groups.
We examined the indications for delivery among the subset of patients for whom detailed delivery records were available ( Table 3 ). Among both dichorionic and monochorionic twins, the most common indication for delivery <34 weeks’ gestation was spontaneous labor and/or spontaneous rupture of membranes. Discordant twins were more likely to be delivered for an indication of nonreassuring fetal status or chorioamnionitis compared to concordant twins. One set of monochorionic twins was delivered <34 weeks for the indication of growth discordance. Of the 138 twin pairs delivered <34 weeks with detailed delivery records available, only 3 (2.1%) did not have a clearly documented indication for delivery.
| Variable | Concordant | Discordant |
|---|---|---|
| Dichorionic | n = 103 | n = 9 |
| Spontaneous labor/SROM | 75 (72.8%) | 7 (77.8%) |
| Preeclampsia | 17 (16.5%) | 0 |
| Nonreassuring fetal status | 4 (3.9%) | 1 (11.1%) |
| Chorioamnionitis | 4 (3.9%) | 1 (11.1%) |
| Suspected growth discordance | 0 | 0 |
| Unknown | 3 (2.9%) | 0 |
| Monochorionic | n = 22 | n = 4 |
| Spontaneous labor/SROM | 9 (40.9%) | 2 (50.0%) |
| Preeclampsia | 5 (22.7%) | 1 (25.0%) |
| Nonreassuring fetal status | 2 (9.1%) | 0 |
| Chorioamnionitis | 4 (18.2%) | 0 |
| Suspected growth discordance | 2 (9.1%) | 1 (25.0%) |
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