Advertisement

The risk of stillbirth and infant death by each additional week of expectant management in twin pregnancies

Published:March 21, 2015DOI:https://doi.org/10.1016/j.ajog.2015.03.033

      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.

      Key words

      Twin pregnancies are at an increased risk of stillbirth, antenatal morbidity, and infant death compared with singleton gestations.
      • Mathews T.J.
      • MacDorman M.F.
      Infant mortality statistics from the 2008 period linked birth/infant death data set. National vital statistics reports. Vol. 60, no 5.
      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.
      • Fretts R.C.
      • Schmittdiel J.
      • McLean F.H.
      • Usher R.H.
      • Goldman M.B.
      Increased maternal age and the risk of fetal death.
      • Reddy U.M.
      • Laughon S.K.
      • Sun L.
      • Troendle J.
      • Willinger M.
      • Zhang J.
      Prepregnancy risk factors for antepartum stillbirth in the United States.
      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.
      • Burgess J.L.
      • Unal E.R.
      • Nietert P.J.
      • et al.
      Risk of late-preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins.
      • Hack K.
      • Derks J.
      • Elias S.
      • et al.
      Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study.
      • Wood S.
      • Tang S.
      • Ross S.
      • Sauve R.
      Stillbith in twins, exploring the optimal gestational age for delivery: a retrospective cohort study.
      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.
      • Barigye O.
      • Pasquini L.
      • Galea P.
      • Chambers H.
      • Chappell L.
      • Fisk N.M.
      High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study.
      • Lee Y.M.
      • Wylie B.J.
      • Simpson L.L.
      • D’Alton M.E.
      Twin chorionicity and the risk 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.
      • Burgess J.L.
      • Unal E.R.
      • Nietert P.J.
      • et al.
      Risk of late-preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins.
      • Breathnach F.M.
      • McAuliffe F.M.
      • Geary M.
      • et al.
      Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies.
      • Domingues A.P.
      • Fonseca E.
      • Vasco E.
      • Moura P.
      • et al.
      Should apparently uncomplicated monochorionic twins be delivered electively at 32 weeks?.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      • Smith N.A.
      • Wilkins-Haug L.
      • Santolaya-Forgas J.
      • et al.
      Contemporary management of monochorionic diamniotic twins: outcomes and delivery recommendations revisited.
      • Sullivan A.E.
      • Hopkins P.N.
      • Weng H.-Y.
      • et al.
      Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs.
      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.
      • Mathews T.J.
      • MacDorman M.F.
      Infant mortality statistics from the 2008 period linked birth/infant death data set. National vital statistics reports. Vol. 60, no 5.
      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.
      • Halloran D.R.
      • Alexander G.R.
      Preterm delivery and age of SIDS death.
      • Reddy U.M.
      • Bettegowda V.R.
      • Dias T.
      • Yamada-Kushnir T.
      • Ko C.W.
      • Willinger M.
      Term pregnancy: a period of heterogeneous risk for infant mortality.
      • Rosenstein M.G.
      • Cheng Y.W.
      • Snowden J.M.
      • Nicholson J.M.
      • Caughey A.B.
      Risk of stillbirth and infant death stratified by gestational age.
      • Smith G.C.
      • Pell J.P.
      • Dobbie R.
      Risk of sudden infant death syndrome and week of gestation of term birth.
      • Zhang X.
      • Kramer M.S.
      Variations in mortality and morbidity by gestational age among infants born at term.
      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.
      • Burgess J.L.
      • Unal E.R.
      • Nietert P.J.
      • et al.
      Risk of late-preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins.
      • Hack K.
      • Derks J.
      • Elias S.
      • et al.
      Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study.
      • Wood S.
      • Tang S.
      • Ross S.
      • Sauve R.
      Stillbith in twins, exploring the optimal gestational age for delivery: a retrospective cohort study.
      • Breathnach F.M.
      • McAuliffe F.M.
      • Geary M.
      • et al.
      Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies.
      • Sullivan A.E.
      • Hopkins P.N.
      • Weng H.-Y.
      • et al.
      Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs.
      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.
      • Dodd J.M.
      • Deussen A.R.
      • Grivell R.M.
      • Crother C.A.
      Elective birth at 37 weeks’ gestation for women with an uncomplicated twin pregnancy.
      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.
      • Caughey A.B.
      • Musci T.J.
      Complications of term pregnancies beyond 37 weeks of gestation.
      • Caughey A.B.
      • Washington A.E.
      • Laros Jr., R.K.
      Neonatal complications of term pregnancy: rates by gestational age increase in a continuous, not threshold, fashion.
      • Cheng Y.W.
      • Kaimal A.
      • Bruckner T.
      • Halloran D.
      • Caughey A.
      Perinatal morbidity associated with late preterm deliveries compared with deliveries between 37 and 40 weeks of gestation.
      • Cheng Y.W.
      • Nicholson J.M.
      • Nakagawa S.
      • Bruckner T.A.
      • Washington A.E.
      • Caughey A.B.
      Perinatal outcomes in low-risk term pregnancies: do they differ by week of gestation?.
      • Clark S.L.
      • Miller D.D.
      • Belfort M.A.
      • et al.
      Neonatal and maternal outcomes associated with elective term delivery.
      • Hibbard J.U.
      • Wilkins I.
      • et al.
      Consortium on Safe Labor
      Respiratory morbidity in late preterm births.
      • Oshiro B.T.
      • Henry E.
      • Wilson J.
      • Branch D.W.
      • Varner M.W.
      Decreasing elective deliveries before 39 weeks of gestation in an integrated health care system.
      • Reddy U.M.
      • Ko C.W.
      • Raju T.N.
      • Willinger M.
      Delivery indications at late-preterm gestations and infant mortality rates in the United States.
      • Tita A.T.
      • Landon M.B.
      • Spong C.Y.
      • et al.
      Timing of elective repeat cesarean delivery at term and neonatal outcomes.
      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.
      • Mathews T.J.
      • MacDorman M.F.
      Infant mortality statistics from the 2008 period linked birth/infant death data set. National vital statistics reports. Vol. 60, no 5.
      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.
      National Center for Health Statistics
      Guide to completing the facility worksheets for the certificate of live birth and report of fetal death (2003 revision).
      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.
      • Smith G.
      Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies.
      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).
      Figure thumbnail gr1
      Figure 1Stillbirth, infant death, and expectant management risk calculations
      Equation 1 describes the stillbirth risk calculation, which takes into account fetuses at risk by dividing the number of stillbirths by all ongoing fetuses minus half the deliveries occurring at the gestational age week studied. Equation 2 displays the infant death calculation with the number of infant deaths divided by the total number of live births at that gestational age. Equation 3 shows the composite risk associated with expectant management with the stillbirth risk during the additional week of expectant management added to the infant death risk following delivery at the subsequent week.
      GA, gestational age.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      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 χ2 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).
      Table 1Risk of fetal/infant death per 10,000 twins
      GAIUFD per 10,000 fetuses (95% CI)Infant death per 10,000 births (95% CI)Fetal/infant death per additional week expectant management (95% CI)
      326.2(2.8–9.5)133.2(117.7–148.8)101.2(92.4–110.0)
      335.0(2.4–7.6)95.0(83.8–106.3)80.3(74.0–86.6)
      347.1(4.7–9.4)75.3(67.6–83.0)58.8(54.4–63.2)
      357.0(5.1–9.0)51.7(46.4–57.1)49.3(45.9–52.7)
      369.8(7.8–11.8)42.2(38.1–46.4)47.8(44.7–50.8)
      3712.5(10.3–14.7)37.9(34.2–41.7)43.9(40.7–47.0)
      3822.5(18.9–26.0)31.4(27.2–35.6)59.2(54.0–64.3)
      3923.4(16.2–30.6)36.7(27.7–45.7)75.4(64.2–86.5)
      4069.2(47.9–90.6)52.0(33.4–70.5)190.9(157.1–224.7)
      CI, confidence interval; GA, gestational age; IUFD, intrauterine fetal death.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      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.
      Figure thumbnail gr2
      Figure 2Risk of fetal/infant death per week of expectant management vs delivery in 10,000 twins
      The risk of infant death following delivery and composite fetal/infant mortality risk with expectant management are shown by gestational age in twin pregnancies from 32 through 40 weeks’ gestation.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      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.
      Table 2Relative risk of fetal/infant mortality with each additional week of expectant management vs delivery
      GARR95% CI
      341.28(1.15–1.44)
      351.05(0.94–1.18)
      360.88(0.79–1.00)
      370.87(0.77–0.99)
      380.53(0.45–0.63)
      390.49(0.36–0.67)
      400.27(0.18–0.43)
      CI, confidence interval; GA, gestational age; RR, relative risk.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      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.
      Table 3Number needed to deliver to prevent 1 fetal/infant death in the additional week of expectant management
      GANNT
      34−606
      35−4071
      361811
      371689
      38360
      39259
      4072
      GA, gestational age; NNT, number needed to treat.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      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.
      Table 4Risk of fetal/infant death per 10,000 twins excluding those complicated by GDM, HTN, and IUGR
      GAIUFD per 10,000 fetuses (95% CI)Infant death per 10,000 births (95% CI)Fetal/infant death per additional week expectant management (95% CI)
      325.1(1.6–8.5)102.1(86.6–117.6)81.8(72.0–91.6)
      333.9(1.2–6.5)76.8(65.0–88.5)64.3(56.7–71.9)
      345.0(2.7–7.4)60.4(52.3–68.6)43.6(38.7–48.5)
      354.4(2.5–6.3)38.5(32.9–44.2)38.2(34.2–42.1)
      367.5(5.3–9.6)33.8(29.2–38.4)35.4(32.1–38.7)
      376.7(4.7–8.7)27.9(23.9–32.0)25.8(23.0–28.5)
      3817.3(13.0–21.5)19.0(14.6–23.5)47.0(42.0–51.9)
      3914.0(5.5–22.6)29.7(17.3–42.1)46.8(35.8–57.8)
      4046.6(15.5–77.7)32.7(6.6–58.9)193.7(149.1–238.2)
      CI, confidence interval; GA, gestational age; GDM, gestational diabetes; HTN, hypertensive disorders; IUFD, intrauterine fetal death; IUGR, intrauterine growth restriction.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      Figure thumbnail gr3
      Figure 3Risk of fetal/infant death excluding GDM, HTN, and IUGR
      The risk of infant death following delivery and composite fetal/infant mortality risk with expectant management are shown by gestational age in twin pregnancies from 32 through 40 weeks’ gestation excluding those complicated by gestational diabetes, hypertensive disorders, and intrauterine growth restriction.
      GDM, gestational diabetes; HTN, hypertensive disorders; IUGR, intrauterine growth restriction.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.
      Analysis of neonatal complications by gestational age at delivery is shown in Table 5. The NICU admission rate was lowest following delivery at 38 weeks’ gestation, and the NICU admission rate decreased significantly with each additional week of pregnancy from 32 through 38 weeks’ gestational age. Additional outcomes studied included neonatal seizures and a need for mechanical ventilation. Because of the low incidence of seizures, there were no significant differences found by gestational age at delivery. The need for ventilation for greater than 6 hours of time was used as a marker for neonatal respiratory complications. Significantly fewer cases of mechanical ventilation were found with advancing gestational age from 32 through 38 weeks.
      Table 5Neonatal complications by week of delivery per 10,000 live births
      GANICU admission (95% CI)Neonatal seizures (95% CI)Need for ventilation >6 h (95% CI)
      328211.9(8136.6–8287.3)5.0(0.6–9.4)1323.2(1256.6–1389.8)
      337913.2(7845.6–7980.7)2.9(0.1–5.7)1020.1(969.8–1070.4)
      346744.6(6684.1–6805.2)3.0(0.8–5.3)623.4(592.2–654.7)
      353811.6(3759.2–3864.0)3.0(1.2–4.9)339.9(320.4–359.5)
      361752.1(1717.2–1787.0)2.0(0.7–3.3)149.0(137.9–160.1)
      37766.7(743.1–790.2)1.6(0.5–2.8)64.4(57.3–71.5)
      38484.0(460.4–507.6)1.9(0.4–3.4)39.7(32.8–46.6)
      39596.9(546.4–647.4)2.4(–0.9 to 5.6)35.5(22.8–48.1)
      40739.4(635.1–843.6)8.3(–3.2 to 19.7)41.3(15.8–66.9)
      CI, confidence interval; GA, gestational age; NICU, neonatal intensive care unit.
      Page. Fetal/infant mortality risk in twin pregnancies by gestational age at delivery. Am J Obstet Gynecol 2015.

      Comment

      Our work demonstrates that the risk of immediate delivery is lower than expectant management at 37 weeks’ gestation for unselected twin pregnancies in the absence of fetal anomalies. This corresponds with prior studies that have also recommended this timing of delivery for uncomplicated dichorionic pregnancies.
      • Burgess J.L.
      • Unal E.R.
      • Nietert P.J.
      • et al.
      Risk of late-preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins.
      • Breathnach F.M.
      • McAuliffe F.M.
      • Geary M.
      • et al.
      Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies.
      • Sullivan A.E.
      • Hopkins P.N.
      • Weng H.-Y.
      • et al.
      Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs.
      When limited to the lower-risk twin pregnancies, excluding gestational diabetes, hypertension, and small-for-gestational-age (SGA)/IUGR pregnancies, 38 weeks became the threshold above which mortality only increased. Although this analysis suggests 38 weeks in the lowest-risk group because SGA/IUGR is so poorly identified, the 37 vs 38 week issue is not fully answered by this analysis in which most SGA/IUGR was identified by birthweight.
      Even with these analyses, the decision between delivery at 37 vs 38 weeks is unclear. Although the risk of stillbirth would be reduced by delivery at 37 weeks, the risk of complications of prematurity with subsequent increased likelihood of infant death at this gestational age is higher as compared with 38 weeks. However, common obstetric practice entails individualized counseling regarding risk factors, circumstances, and patient preferences, and this increased risk of stillbirth is often unacceptable to a patient in comparison with the risk of possible infant mortality and neonatal complications.
      Given that our analysis was conducted with fetus level data as opposed to pregnancy level data, the risk of both stillbirth and of infant death is essentially double the risks we have estimated in Table 1 because the event could occur to 1 twin or the other. This fact is relevant in patient counseling because the expectant mother is carrying 2 fetuses at risk.
      Whereas this study is the first to compare the long-term impact of immediate delivery, infant death, with expectant management in twins, it is not without limitations. This work is based on birth certificate data and as such is limited by the coding and accuracy of data available. Because of these date, detailed information regarding chorionicity is not available, which would be an important analysis to perform.
      Several studies have examined the effect of chorionicity on the prospective risk of stillbirth in uncomplicated monochorionic vs dichorionic pregnancies. Although some have found an increased risk of stillbirth independent of typical risk factors associated with monochorionicity such as twin-twin transfusion, others have not reproduced this risk.
      • Barigye O.
      • Pasquini L.
      • Galea P.
      • Chambers H.
      • Chappell L.
      • Fisk N.M.
      High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study.
      • Lee Y.M.
      • Wylie B.J.
      • Simpson L.L.
      • D’Alton M.E.
      Twin chorionicity and the risk of stillbirth.
      We did not have information on the complication of twin-to-twin transfusion syndrome. This complication would bias the results toward higher rates of stillbirth. However, given the low incidence of this disorder in the late preterm and term periods, this would likely be only a very small source of bias in the study.
      Several studies have estimated a similar risk of stillbirth at gestational ages longer than 32 weeks between uncomplicated monochorionic and dichorionic pregnancies.
      • Domingues A.P.
      • Fonseca E.
      • Vasco E.
      • Moura P.
      • et al.
      Should apparently uncomplicated monochorionic twins be delivered electively at 32 weeks?.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      • Smith N.A.
      • Wilkins-Haug L.
      • Santolaya-Forgas J.
      • et al.
      Contemporary management of monochorionic diamniotic twins: outcomes and delivery recommendations revisited.
      • Sullivan A.E.
      • Hopkins P.N.
      • Weng H.-Y.
      • et al.
      Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs.
      Given the variation in the recommended timing of delivery and stillbirth risk for monochorionic and dichorionic pregnancies, this represents a considerable limitation in our work and an important area of future research.
      To estimate how the combination of monochorionic and dichorionic twins would have an impact on the mortality risks near and at term, one needs to be able to estimate the prevalence of monochorionic twins toward the end of the third trimester and the relative risk of stillbirth between the 2 subgroups of twins. Among twins beyond 34 weeks’ gestation, approximately 10% are monochorionic and the relative risk of stillbirth is 1.69 (95% CI, 1.04–2.75).
      • Hack K.
      • Derks J.
      • Elias S.
      • et al.
      Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study.
      • McPherson J.A.
      • Odibo A.O.
      • Shanks A.L.
      • et al.
      Impact of chorionicity on risk and timing of intrauterine fetal demise in twin pregnancies.
      Given these estimates, this suggests that our estimate of fetal death for twins is approximately 7% above the actual risk for dichorionic twins.
      Additionally, with such administrative data, there is often a concern of undercoding of outcomes. However, because these data are generated by linking birth and death certificates, the chances of undercoding of mortality are relatively small. We chose to study stillbirth and infant death as our primary outcomes, given that they are well coded in administrative data (death certificates), of clinical importance, and are rare occurrences that are best studied using large databases such as that utilized here.
      Our composite risk of expectant management is intended to be an estimate of overall mortality risk by week of gestation, which is multifactorial and influenced by maternal and neonatal factors. Some of these factors are independent of gestational age, but others have been shown to vary by gestational age.
      • Caughey A.B.
      • Musci T.J.
      Complications of term pregnancies beyond 37 weeks of gestation.
      • Caughey A.B.
      • Stotland N.E.
      • Escobar G.
      What is the best measure of maternal complications of term pregnancy: ongoing pregnancies or pregnancies delivered?.
      Given the lack of detail regarding chorionicity in our work, it is difficult to make specific conclusions regarding the ideal gestational age for delivery. However, our work does seem to correlate with prior recommendations with decreasing mortality risk around 37 weeks’ gestation for both monochorionic and dichorionic pregnancies. These guidelines include consideration of expectant management for monochorionic pregnancies through 37 6/7 weeks’ gestation and dichorionic pregnancies through 38 6/7 weeks.
      American College of Obstetricians and Gynecologists
      Medically indicated late-preterm and early-term deliveries. ACOG Committee opinion no. 560.
      • Spong C.Y.
      • Mercer B.M.
      • D’Alton M.
      • Kilpatrick S.
      • Blackwell S.
      • Saade G.
      Timing of indicated late-preterm and early-term birth.
      Given that most pregnancies continuing to 38 weeks and beyond are likely dichorionic, this may reflect an increased rate of stillbirth warranting delivery by 38 weeks’ gestation for dichorionic pregnancies. However, because we cannot examine dichorionic pregnancies specifically in this study, further work is needed to better clarify this potential risk. It is also notable that we did not have information on whether the twin gestation was a product of assisted reproductive technology and as such cannot ascertain risk differences between spontaneous and conception-assisted pregnancies.
      Additionally, these calculations done per week allow for baseline information for counseling women with twin gestations. The reported risk here is intended as a baseline estimation; if maternal or fetal complications arose during the course of the pregnancy, these would likely increase the potential stillbirth risk above what we have estimated. We hope that these data provide information to assist providers in determining an appropriate gestational age for delivery of twin pregnancies in the absence of additional complications that may indicate earlier delivery.

      References

        • Mathews T.J.
        • MacDorman M.F.
        Infant mortality statistics from the 2008 period linked birth/infant death data set. National vital statistics reports. Vol. 60, no 5.
        National Center for Health Statistics, Hyattsville, MD2012
        • Fretts R.C.
        • Schmittdiel J.
        • McLean F.H.
        • Usher R.H.
        • Goldman M.B.
        Increased maternal age and the risk of fetal death.
        N Engl J Med. 1995; 333: 953-957
        • Reddy U.M.
        • Laughon S.K.
        • Sun L.
        • Troendle J.
        • Willinger M.
        • Zhang J.
        Prepregnancy risk factors for antepartum stillbirth in the United States.
        Obstet Gynecol. 2010; 116: 1119-1126
        • Burgess J.L.
        • Unal E.R.
        • Nietert P.J.
        • et al.
        Risk of late-preterm stillbirth and neonatal morbidity for monochorionic and dichorionic twins.
        Am J Obstet Gynecol. 2014; 210: 578.e1-578.e9
        • Hack K.
        • Derks J.
        • Elias S.
        • et al.
        Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study.
        BJOG. 2008; 115: 58-67
        • Wood S.
        • Tang S.
        • Ross S.
        • Sauve R.
        Stillbith in twins, exploring the optimal gestational age for delivery: a retrospective cohort study.
        BJOG. 2014; 121: 1284-1293
        • Barigye O.
        • Pasquini L.
        • Galea P.
        • Chambers H.
        • Chappell L.
        • Fisk N.M.
        High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study.
        PLoS Med. 2005; 2: e172
        • Lee Y.M.
        • Wylie B.J.
        • Simpson L.L.
        • D’Alton M.E.
        Twin chorionicity and the risk of stillbirth.
        Obstet Gynecol. 2008; 111: 301-308
        • Breathnach F.M.
        • McAuliffe F.M.
        • Geary M.
        • et al.
        Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies.
        Obstet Gynecol. 2012; 119: 50-59
        • Domingues A.P.
        • Fonseca E.
        • Vasco E.
        • Moura P.
        • et al.
        Should apparently uncomplicated monochorionic twins be delivered electively at 32 weeks?.
        J Matern Fetal Neonatal Med. 2009; 22: 1077-1080
        • Lewi L.
        • Jani J.
        • Blickstein I.
        • et al.
        The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
        Am J Obstet Gynecol. 2008; 199: 514.e1-514.e8
        • Smith N.A.
        • Wilkins-Haug L.
        • Santolaya-Forgas J.
        • et al.
        Contemporary management of monochorionic diamniotic twins: outcomes and delivery recommendations revisited.
        Am J Obstet Gynecol. 2010; 203: 133.e1-133.e6
        • Sullivan A.E.
        • Hopkins P.N.
        • Weng H.-Y.
        • et al.
        Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs.
        Am J Obstet Gynecol. 2012; 206: 257.e1-257.e7
        • Halloran D.R.
        • Alexander G.R.
        Preterm delivery and age of SIDS death.
        Ann Epidemiol. 2006; 16: 600-606
        • Reddy U.M.
        • Bettegowda V.R.
        • Dias T.
        • Yamada-Kushnir T.
        • Ko C.W.
        • Willinger M.
        Term pregnancy: a period of heterogeneous risk for infant mortality.
        Obstet Gynecol. 2011; 117: 1279-1287
        • Rosenstein M.G.
        • Cheng Y.W.
        • Snowden J.M.
        • Nicholson J.M.
        • Caughey A.B.
        Risk of stillbirth and infant death stratified by gestational age.
        Obstet Gynecol. 2012; 120: 76-82
        • Smith G.C.
        • Pell J.P.
        • Dobbie R.
        Risk of sudden infant death syndrome and week of gestation of term birth.
        Pediatrics. 2003; 111: 1367-1371
        • Zhang X.
        • Kramer M.S.
        Variations in mortality and morbidity by gestational age among infants born at term.
        J Pediatr. 2009; 154: 358-362
        • Dodd J.M.
        • Deussen A.R.
        • Grivell R.M.
        • Crother C.A.
        Elective birth at 37 weeks’ gestation for women with an uncomplicated twin pregnancy.
        Cochrane Database of Systematic Reviews. 2014; : CD003582
        • Caughey A.B.
        • Musci T.J.
        Complications of term pregnancies beyond 37 weeks of gestation.
        Obstet Gynecol. 2004; 103: 57-62
        • Caughey A.B.
        • Washington A.E.
        • Laros Jr., R.K.
        Neonatal complications of term pregnancy: rates by gestational age increase in a continuous, not threshold, fashion.
        Am J Obstet Gynecol. 2005; 192: 185-190
        • Cheng Y.W.
        • Kaimal A.
        • Bruckner T.
        • Halloran D.
        • Caughey A.
        Perinatal morbidity associated with late preterm deliveries compared with deliveries between 37 and 40 weeks of gestation.
        BJOG. 2011; 118: 1446-1454
        • Cheng Y.W.
        • Nicholson J.M.
        • Nakagawa S.
        • Bruckner T.A.
        • Washington A.E.
        • Caughey A.B.
        Perinatal outcomes in low-risk term pregnancies: do they differ by week of gestation?.
        Am J Obstet Gynecol. 2008; 199: 370.e1
        • Clark S.L.
        • Miller D.D.
        • Belfort M.A.
        • et al.
        Neonatal and maternal outcomes associated with elective term delivery.
        Am J Obstet Gynecol. 2009; 200: 156.e1-156.e4
        • Hibbard J.U.
        • Wilkins I.
        • et al.
        • Consortium on Safe Labor
        Respiratory morbidity in late preterm births.
        JAMA. 2010; 304: 419-425
        • Oshiro B.T.
        • Henry E.
        • Wilson J.
        • Branch D.W.
        • Varner M.W.
        Decreasing elective deliveries before 39 weeks of gestation in an integrated health care system.
        Obstet Gynecol. 2009; 113: 804-811
        • Reddy U.M.
        • Ko C.W.
        • Raju T.N.
        • Willinger M.
        Delivery indications at late-preterm gestations and infant mortality rates in the United States.
        Pediatrics. 2009; 124: 234-240
        • Tita A.T.
        • Landon M.B.
        • Spong C.Y.
        • et al.
        Timing of elective repeat cesarean delivery at term and neonatal outcomes.
        N Engl J Med. 2009; 360: 111-120
        • National Center for Health Statistics
        Guide to completing the facility worksheets for the certificate of live birth and report of fetal death (2003 revision).
        US Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville, MD2003 (updated May 2006. Available at:) (Accessed Jan. 30, 2015)
        • Smith G.
        Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies.
        Am J Obstet Gynecol. 2001; 184: 489-496
        • McPherson J.A.
        • Odibo A.O.
        • Shanks A.L.
        • et al.
        Impact of chorionicity on risk and timing of intrauterine fetal demise in twin pregnancies.
        Am J Obstet Gynecol. 2012; 207: 190.e1-190.e6
        • Caughey A.B.
        • Stotland N.E.
        • Escobar G.
        What is the best measure of maternal complications of term pregnancy: ongoing pregnancies or pregnancies delivered?.
        Am J Obstet Gynecol. 2003; 189: 1047-1052
        • American College of Obstetricians and Gynecologists
        Medically indicated late-preterm and early-term deliveries. ACOG Committee opinion no. 560.
        Obstet Gynecol. 2013; 121: 908-910
        • Spong C.Y.
        • Mercer B.M.
        • D’Alton M.
        • Kilpatrick S.
        • Blackwell S.
        • Saade G.
        Timing of indicated late-preterm and early-term birth.
        Obstet Gynecol. 2011; 118: 323-333

      Linked Article