Objective
The objective of the study was to compare the fetal/infant mortality risk associated with each additional week of expectant management with the mortality risk of immediate delivery in women with twin gestations.
Study Design
A retrospective cohort study was performed utilizing 2006–2008 National linked birth certificate and death certificate data. The incidence of stillbirth and infant death were determined for each week of pregnancy from 32 0/7 weeks’ through 40 6/7 weeks’ gestation. Pregnancies complicated by fetal anomalies were excluded. These measures were combined to estimate the theoretic risk of remaining pregnant an additional week by adding the risk of stillbirth during the extra week of pregnancy with the risk of infant death encountered with delivery during the following week. This composite fetal/infant mortality risk was compared with the risk of infant death associated with delivery at the corresponding gestational age.
Results
The risk of stillbirth increased with increasing gestational age, for example, between 37 and 38 weeks’ gestation (12.5 per 10,000 vs 22.5 per 10,000; P < .05). As expected, the risk of infant death following delivery gradually decreased as pregnancies approached term gestation. Week-by-week differences were statistically significant ( P < .05) between 32 and 36 weeks with decreasing risk of infant death at advancing gestational ages. The composite risk of stillbirth and infant death associated with an additional week of pregnancy had a significant increase from 37 to 38 weeks’ gestation (43.9 per 10,000 vs 59.2 per 10,000; P < .05). At 37 weeks’ gestation, the relative risk of mortality was statistically significantly lower with immediate delivery as compared with expectant management (relative risk, 0.87; 95% confidence interval, 0.77–0.99).
Conclusion
Our results suggest that fetal/infant death risk is minimized at 37 weeks’ gestation; however, individual maternal and fetal characteristics must also be taken into account when determining the optimal timing of delivery for twin pregnancies.
Twin pregnancies are at an increased risk of stillbirth, antenatal morbidity, and infant death compared with singleton gestations. This is largely due to uteroplacental insufficiency, preterm delivery, and maternal antenatal complications. Maternal comorbidities such as advanced maternal age, gestational diabetes, and hypertensive disorders are also more common in twin gestations and impart an elevated stillbirth risk.
The risk of stillbirth has also been shown to vary with gestational age at delivery in twin pregnancies with an increasing risk at later gestational ages. There has been considerable debate regarding the contribution of chorionicity to stillbirth risk in uncomplicated twin gestations. Several studies have concluded that even in the absence of monochorionic-specific risks such as twin-twin transfusion syndrome, monochorionic pregnancies experience an increased rate of stillbirth. Subsequent work has not demonstrated this phenomenon, finding more equivalent risks of stillbirth in monochorionic and dichorionic pregnancies during the late preterm period.
Infant death rates are 5 times higher overall following twin gestations as compared with singleton pregnancies. Complications of prematurity, congenital anomalies, and low birthweight are the primary risk factors for infant mortality in these cases. The risk of infant death varies by gestational age at delivery. Infant death risk is highest in preterm deliveries with decreasing incidence as pregnancy approaches term gestation. The primary causes of death in these cases have been shown to be sudden infant death syndrome, asphyxia, and sepsis.
The increased risk of both stillbirth and complications of iatrogenic prematurity create a challenging situation when determining the appropriate gestational age for delivery, requiring careful consideration of tradeoffs. Prior research has suggested that for uncomplicated monochorionic and dichorionic pregnancies, delivery between 36 and 38 weeks’ gestational age minimizes fetal and infant mortality. Additionally, a recent Cochrane review concluded that for uncomplicated twin pregnancies elective delivery at 37 weeks did not impart an increased risk of neonatal/infant complications. However, the known complications of late preterm and early term delivery including respiratory distress syndrome and neonatal intensive care unit (NICU) admission must be taken into account when determining the appropriate gestational age for delivery.
Given this delicate balance of stillbirth risk and complications of iatrogenic prematurity, the decision regarding delivery timing for otherwise uncomplicated twin pregnancies is challenging. Using a previously devised composite measure, we sought to determine the risk of stillbirth and infant death by week of gestation in twin pregnancies and to quantify the risk of expectant management vs delivery during the late third trimester.
Materials and Methods
A retrospective cohort study was conducted utilizing 2006-2008 national linked birth certificate and death certificate data. The National Center for Health Statistics links live birth cohort data with infant and fetal death information.
We utilized stillbirth data at each gestational age week and infant death data following live births at each gestational age week. Data were investigated for twin pregnancies from 20 weeks’ through 42 weeks’ gestational age. Comparisons were made by the individual fetus or infant as opposed to the pair present in each pregnancy. Exclusion criteria included pregnancies complicated by fetal anomalies.
Additional characteristics of our study population were also determined including gestational diabetes, hypertensive disorders, and intrauterine growth retardation (IUGR). To eliminate the potential confounding effect these factors may have on our results we conducted a secondary analysis excluding gestational diabetes, hypertensive disorders and IUGR. To better characterize the morbidity associated with late preterm and early term deliveries, neonatal outcomes by gestational age including NICU admission, neonatal seizures, and a need for ventilation for greater than 6 hours were determined.
Our study population included fetal deaths and live births following delivery from 32 0/7 through 40 6/7 weeks’ gestational age. Pregnancy dating was determined using the best obstetric estimate. This most often refers to the last menstrual period with an allowance of the correction of gestational age if the estimated age based on the last menstrual period is significantly different from that estimated by ultrasound. Stillbirth was designated as fetal death following 20 weeks’ gestational age. Infant death was designated as death occurring within the first year of life.
This study was approved by the Institutional Review Board at Oregon Health and Science University.
Stillbirth risk was determined using a fetuses at-risk life table method. This method accounts for all ongoing fetuses in the denominator with exclusion of half the deliveries occurring during the gestational age week. This technique is used to reflect the fact that a portion of pregnancies will have delivered at any given time during the gestational age week being studied and stillbirths occur in an even distribution throughout the week of gestation. The calculation includes the number of stillbirths occurring at a given gestational age in the numerator divided by the fetuses at-risk as described above ( Figure 1 , equation 1).
Infant death risk was calculated by dividing the number of infant deaths by the number of live births at the corresponding gestational age ( Figure 1 , equation 2). To estimate the risk of fetal/infant mortality associated with each additional week of pregnancy, a composite risk was calculated. This calculation included the risk of stillbirth associated with the additional week of pregnancy in addition to the risk of infant death following the gestational age at delivery ( Figure 1 , equation 3).
Stillbirth, infant death, and composite fetal/infant mortality risks were determined for each week of gestation in twin pregnancies from 32 0/7 through 40 6/7 weeks’ gestational age. This period was chosen because of the prevalence of preterm and early term delivery in this population with rare occurrence of delivery past 40 weeks’ gestation. Stata software (version 11; Stata Corp, College Station, TX) was used to perform the χ 2 analysis of fetal infant mortality at each gestational age.
To determine the optimal gestational age for delivery, the composite risk of expectant management for an additional week of pregnancy was compared with the risk of infant death for each gestational age week during this period. This method accounts for the infant mortality associated with earlier delivery vs the additional risk of stillbirth during the extra week of pregnancy and the corresponding infant death risk following delivery at the next week of gestation.
Fetal/infant mortality risk was calculated per 10,000 fetuses at risk/live births. Stillbirth, infant death, and composite fetal/infant mortality data are displayed in table format to facilitate comparison of each value by gestational age. The risks of infant death and composite mortality were graphed to display the gestational age at which overall fetal/infant mortality risk is minimized.
We calculated the relative risk of stillbirth and infant death incurred by an additional week of pregnancy compared with the risk of infant death following delivery at the gestational age in question. The 95% confidence interval for the relative risks were calculated and deemed to be statistically significant if they did not contain 1.
A number needed to treat analysis was also performed to determine the number needed to deliver by a given gestational age to avoid 1 fetal/infant death during the additional week of pregnancy. This calculation was performed by determining the inverse of the difference between the mortality probability of the expectant management and infant death at each gestational age week.
Results
A total of 454,626 twins was included in our analysis of twin gestations with stillbirth or live birth occurring from 32 0/7 through 40 6/7 weeks’ gestational age. Stillbirth was observed in 1585 fetuses (0.35%) and infant death following 2357 live births (0.52%) overall. The risk of stillbirth increased with each additional week of pregnancy ( Table 1 ). However, this increase was statistically significant only between 37 and 38 weeks’ gestation (12.5 per 10,000 vs 22.5 per 10,000) and between 39 and 40 weeks’ gestation (23.4 per 10,000 vs 69.2 per 10,000). Infant death risk was highest at early gestational ages, decreasing as gestational age approached term ( Table 1 ). The infant death risk nadir was found at 38 weeks’ gestation (31.4 per 10,000).
| GA | IUFD per 10,000 fetuses (95% CI) | Infant death per 10,000 births (95% CI) | Fetal/infant death per additional week expectant management (95% CI) | |||
|---|---|---|---|---|---|---|
| 32 | 6.2 | (2.8–9.5) | 133.2 | (117.7–148.8) | 101.2 | (92.4–110.0) |
| 33 | 5.0 | (2.4–7.6) | 95.0 | (83.8–106.3) | 80.3 | (74.0–86.6) |
| 34 | 7.1 | (4.7–9.4) | 75.3 | (67.6–83.0) | 58.8 | (54.4–63.2) |
| 35 | 7.0 | (5.1–9.0) | 51.7 | (46.4–57.1) | 49.3 | (45.9–52.7) |
| 36 | 9.8 | (7.8–11.8) | 42.2 | (38.1–46.4) | 47.8 | (44.7–50.8) |
| 37 | 12.5 | (10.3–14.7) | 37.9 | (34.2–41.7) | 43.9 | (40.7–47.0) |
| 38 | 22.5 | (18.9–26.0) | 31.4 | (27.2–35.6) | 59.2 | (54.0–64.3) |
| 39 | 23.4 | (16.2–30.6) | 36.7 | (27.7–45.7) | 75.4 | (64.2–86.5) |
| 40 | 69.2 | (47.9–90.6) | 52.0 | (33.4–70.5) | 190.9 | (157.1–224.7) |
The composite fetal/infant death risk from expectant management for 1 week was minimized at 37 weeks’ gestation ( Table 1 ). Risks were highest at the extremes of the gestational ages studied. Increased infant death risk imparted higher mortality rates in early gestational ages; conversely, elevated stillbirth risk was reflected at later gestational ages. The highest fetal/infant mortality risk from expectant management was observed at 40 weeks’ gestation (190.9 per 10,000). When comparing the rate of mortality from immediate delivery (infant death) with that of expectant management for 1 week, the rate was statistically significantly higher for immediate delivery from 32 to 34 weeks’ gestation ( Figure 2 ). From 35 to 36 weeks’ gestation, there was no statistically significant difference ( Table 1 ). From 37 weeks’ gestation and onward, the mortality risk was greater with expectant management.
The relative risk of fetal/infant mortality of delivery vs expectant management was calculated for gestational ages from 32 through 40 weeks’ gestation ( Table 2 ). We found an increased risk of mortality associated with delivery at 34 weeks’ compared with expectant management, with a statistically significant relative risk 1.28 (95% confidence interval [CI], 1.15–1.44). The relative risks at 35 and 36 weeks’ gestation were not statistically significant. At 37 weeks’, the risk profile favored delivery as opposed to continued expectant management with a relative risk 0.87 (95% CI, 0.77–0.99). Delivery continued to be the preferred management at advancing gestational ages with decreasing relative risks associated with delivery as displayed in Table 2 .
| GA | RR | 95% CI |
|---|---|---|
| 34 | 1.28 | (1.15–1.44) |
| 35 | 1.05 | (0.94–1.18) |
| 36 | 0.88 | (0.79–1.00) |
| 37 | 0.87 | (0.77–0.99) |
| 38 | 0.53 | (0.45–0.63) |
| 39 | 0.49 | (0.36–0.67) |
| 40 | 0.27 | (0.18–0.43) |
A number needed to deliver to avoid 1 fetal/infant death by gestational age was also determined ( Table 3 ). With advancing gestational age, the number needed to deliver decreased, reflecting the increased stillbirth risk at later gestational ages. For example, there would be 1689 deliveries needed at 37 weeks’ gestation to prevent 1 death as compared with 360 deliveries needed at 38 weeks’ gestation to prevent 1 death.
| GA | NNT |
|---|---|
| 34 | −606 |
| 35 | −4071 |
| 36 | 1811 |
| 37 | 1689 |
| 38 | 360 |
| 39 | 259 |
| 40 | 72 |
An additional analysis of our data excluding those pregnancies complicated by gestational diabetes, hypertensive disorders, and IUGR was performed to ascertain the comparison in a low-risk twin cohort. Table 4 displays the ratio of stillbirths, rate of infant death, and composite risk estimate by gestational age in this group. Figure 3 displays the rate of infant death vs mortality risk of expectant management. This compares the mortality risk of immediate delivery vs continued pregnancy for 1 additional week. The result was similar with that found in our primary study group, but now 38 weeks’ gestation is when a statistically significantly lower mortality rate is produced by delivery as compared with expectant management.
| GA | IUFD per 10,000 fetuses (95% CI) | Infant death per 10,000 births (95% CI) | Fetal/infant death per additional week expectant management (95% CI) | |||
|---|---|---|---|---|---|---|
| 32 | 5.1 | (1.6–8.5) | 102.1 | (86.6–117.6) | 81.8 | (72.0–91.6) |
| 33 | 3.9 | (1.2–6.5) | 76.8 | (65.0–88.5) | 64.3 | (56.7–71.9) |
| 34 | 5.0 | (2.7–7.4) | 60.4 | (52.3–68.6) | 43.6 | (38.7–48.5) |
| 35 | 4.4 | (2.5–6.3) | 38.5 | (32.9–44.2) | 38.2 | (34.2–42.1) |
| 36 | 7.5 | (5.3–9.6) | 33.8 | (29.2–38.4) | 35.4 | (32.1–38.7) |
| 37 | 6.7 | (4.7–8.7) | 27.9 | (23.9–32.0) | 25.8 | (23.0–28.5) |
| 38 | 17.3 | (13.0–21.5) | 19.0 | (14.6–23.5) | 47.0 | (42.0–51.9) |
| 39 | 14.0 | (5.5–22.6) | 29.7 | (17.3–42.1) | 46.8 | (35.8–57.8) |
| 40 | 46.6 | (15.5–77.7) | 32.7 | (6.6–58.9) | 193.7 | (149.1–238.2) |
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