The multiple birth rate in Canada has increased by 50%, from 1.8% in 1974 to 2.7% in 2000.1,2 Twin pregnancies account for over 95% of multiple births and are associated with perinatal mortality rates that are 3–6 times higher than among singletons.3,4 Obstetric care providers consider the second twin to be particularly vulnerable to adverse perinatal outcomes related to delivery complications.5,6 However, several studies comparing perinatal morbidity and mortality rates between first and second twins have failed to demonstrate such an increased risk.7,8 More recent large, well-designed studies have confirmed that the second twin is more likely to suffer perinatal mortality and serious neonatal morbidity than the first.9–11
Mode of delivery and presentation have been implicated as the primary determinants of adverse pregnancy outcomes for the second twin.9–11 Other factors, including differential stillbirth risk, birth weight discordance, interdelivery interval, and sex, have also been evaluated as possible determinants of increased risk for the second twin.11–14 The purpose of this study was to identify potential determinants of perinatal mortality and serious neonatal morbidity among second twins relative to first twins.
MATERIALS AND METHODS
A population-based retrospective cohort study of all twin gestations in Nova Scotia from January 1, 1988, to December 31, 2002, was conducted using the Nova Scotia Atlee Perinatal Database. The provincial perinatal database contains clinical and other relevant information on all births of 500 g or more in Nova Scotia and out-of-province deliveries to Nova Scotia residents. Data abstraction is performed by trained health records personnel from standardized forms and hospital medical records. Information is collected on maternal, obstetric, and medical conditions, prenatal complications, labor and delivery events, perinatal outcomes, and maternal demographic information. Periodic abstraction and validation studies are conducted as part of an ongoing database quality assurance program and have consistently shown that information in the database is reliable.15
Twin pregnancies complicated by monoamniotic placentation, conjoined twins, lethal or major congenital anomaly (identified prenatally or during the birth admission of the newborn), prelabor fetal death, or birth weight less than 500 g for either twin were excluded from the study cohort. Potential determinants of perinatal outcome, including mode of delivery, presentation, birth weight discordance, interdelivery interval, chorionicity, and infant sex, were evaluated. Chorionicity was determined by placental examination of all twin births. The study cohort was stratified into the following gestational age categories: 37 weeks or more, 34–36 weeks, and less than 34 weeks.
The primary outcome was a composite measure of perinatal mortality and serious neonatal morbidity, which included perinatal death, birth asphyxia, respiratory distress syndrome, neonatal infection, and birth trauma. Perinatal death was defined as intrapartum fetal death or neonatal death at 28 days or less after birth. Birth asphyxia was defined as Apgar scores of 3 or less at 5 minutes, base excess of 16 mmol/L or more, or umbilical artery pH less than 7. Respiratory distress syndrome (RDS) was described as moderate-to-severe RDS based on clinical and radiologic parameters. Serious neonatal infection required culture-proven sepsis or necrotizing enterocolitis. Birth trauma included skeletal fracture, peripheral nerve injury, spinal cord injury, or traumatic intracranial hemorrhage. Clinically suspected neonatal trauma was confirmed by appropriate diagnostic imaging techniques.
A matched-pair analysis was conducted using the McNemar matched-pair test statistic to compare the relative risk of composite adverse outcome in second twins relative to first-born co-twins.16 This statistical approach recognizes that the two infants in a twin pair are closely matched and focuses on pairs in which only one infant is affected. In this way, maternal sociodemographic, medical, and obstetric factors are controlled for. Rate ratios and 95% confidence intervals were calculated for twin pairs using the same matched-pair approach. A conditional logistic regression analysis was performed to examine the effect of birth order on perinatal outcome after adjustment for birth weight, infant sex, presentation, and mode of delivery. Factors that were identical for matched twin pairs, such as maternal demographic factors and gestational age, were withheld from the model. Data analyses were performed using SAS 8.0 (SAS Institute Inc, Cary, NC). Ethical approval for this database study was obtained from the Research Ethics Board, IWK Health Centre, Halifax, Nova Scotia.
From 1988 to 2002, there were 161,931 births in Nova Scotia. The total number of twins born during this time period was 3,722 (1,861 twin pairs), for an overall incidence of 2.3%. After excluding 319 twin pairs (lethal or major congenital anomaly , birth weight less than 500 g , monoamniotic or conjoined twins , prelabor fetal deaths , or missing data  on either twin), there were 1,542 twin pairs (3,084 twins) available for analysis. In this cohort, 876 twin pairs (57%) delivered at term, 478 (31%) between 34 and 36 weeks, and 188 (12%) before 34 weeks of gestation. Maternal demographic characteristics are presented in Table 1.
As shown in Table 2, the second twin was at significantly greater risk of composite adverse outcome than the first twin. Second twins were more likely to experience perinatal adverse outcomes than first born co-twins, whether delivered at 37 weeks or more, 34–36 weeks, or less than 34 weeks of gestation. Conditional logistic regression confirmed that the second twin was more likely to suffer adverse perinatal outcome independent of birth weight, infant sex, presentation, or mode of delivery (odds ratio [OR] 3.77 95% confidence interval [CI] 2.31–6.16).
The most common presentation among all twin pairs was vertex/vertex (47.5%), followed by vertex/nonvertex (29.5%) and nonvertex/any (23%) (Table 3). Malpresentation of either twin increased with decreasing gestational age. Although the overall risk of composite adverse outcome was increased for the second twin relative to the first, independently of the presentation of either twin, rates and rate ratios varied within gestational age categories. Among term twins, rates of composite adverse outcome were generally low, and the likelihood of adverse outcome for the second twin was significantly increased when the presentation was vertex/nonvertex. There was no difference in composite adverse outcome rates between term first and second twins when the first twin was nonvertex. Among twins born preterm between 34 and 36 weeks, the second twin was more likely to suffer adverse perinatal complications than the first, independently of the presentation of either twin. For preterm twins at less than 34 weeks, composite adverse outcome rates were high, but there were no significant differences in rates between co-twins in vertex/vertex and nonvertex/any presentations. Second twins born before 34 weeks of gestation were at significant risk of composite adverse outcome when the presentation was vertex/nonvertex, however.
Table 4 presents the effects of mode of delivery on perinatal outcome of first and second twins. Approximately 20% of twin pregnancies were delivered by cesarean without labor, and 80% attempted vaginal delivery. Among those who attempted a trial of labor, 66% of twin pairs delivered vaginally, 28% underwent emergency cesarean, and 6% experienced vaginal delivery of the first twin and cesarean for the second. Cesarean without labor rates were higher, and planned vaginal delivery rates were lower with increasing gestational age. Nonvertex first twin was the indication for 63% (185 of 294) of planned caesarean births.
For nonvertex first twin pairs, the overall rate of cesarean delivery was 95.8% (340 of 355) with 52% (185 of 355) performed before labor onset. Elective cesarean for nonvertex first twin was more likely for term (67.6%) than preterm (36.9%) twins although overall cesarean rates for this indication were equally high (96.6% and 95.0%, respectively). In contrast, the overall cesarean rate for vertex first twin pairs was 26% (308 of 1,187), and the elective cesarean rate was less than 10% (109 of 1,187). Cesarean birth rates for vertex first twin pairs were similar for term (26.9%) and preterm (32.7%) twins.
Composite adverse outcome rates were significantly increased for second twins for planned vaginal delivery at 37 or more weeks, 34–36 weeks, and less than 34 weeks of gestation. Although increased composite adverse outcome rates were observed for second twins delivered vaginally or by emergency cesarean after a trial of labor, rate ratios were only significant across gestational age categories for vaginal birth of both first and second twins. Planned cesarean at 37 or more weeks and less than 34 weeks of gestation was associated with equivalent composite adverse outcome rates for first and second twins. Cesarean birth without labor between 34 and 36 weeks of gestation was associated with an increased risk of composite adverse outcome for second twins relative to first twins, however.
The risk difference of composite adverse outcome associated with elective cesarean compared with planned vaginal delivery at 37 or more weeks of gestation was 3.0% (5.19–2.19) for either twin. The number of cesarean births required to prevent one case of composite adverse outcome, assuming causality, was 33.
Second twins had significantly higher rates of composite adverse outcome than first twins, whether their birth weights differed by less than 10%, 10–19%, or 20% or more (Table 5). The risk was greatest when the birth weight of the second twin exceeded that of the first twin by 20% or more. When the second twin was smaller than the first by 10–19% or 20% or more, composite adverse outcome rates for first and second twins were similar.
After exclusion of all prelabor (294) and intrapartum (354) cesarean deliveries for twins, there were 894 twin pairs among whom the first twin delivered vaginally (Table 5). For birth intervals of less than 15 minutes, second twins had a 1.3-fold higher risk of adverse perinatal outcome than first twins. The relative risk of composite adverse outcome for the second twin was further increased when the interdelivery interval was 15–30 minutes. Urgent cesarean delivery for the second twin 15–30 minutes after vaginal delivery of the first was associated with the highest rates of composite adverse outcome for first and second twins. Interdelivery intervals of greater than 30 minutes between twins were uncommon, and the rates of composite adverse outcome for the second twin, although increased, were not significantly different from the first twin. The likelihood of cesarean delivery for the second twin after vaginal delivery of the first twin increased as the interdelivery interval increased.
As shown in Table 5, both dichorionic and monochorionic second twins were at greater risk of composite adverse outcome than first twins. Adverse perinatal outcome rates were generally higher among monochorionic than dichorionic twins. The increased risk of adverse outcome for second twins persisted across gestational age categories, independently of chorionicity.
Among twin pairs concordant for sex, second twins were at greater risk of composite adverse outcome than same-sex first twins (Table 5). When the sex of twins was discordant, male second twins were more likely to suffer composite adverse outcome than female first co-twins. Composite adverse outcome rates for female second twins were higher than those for first-born male co-twins, but the difference was not significant.
Birth asphyxia and respiratory distress syndrome were the major contributors of excess morbidity among second twins (Table 6). The excess risk of birth asphyxia (42 versus 25 cases) was significant for planned vaginal deliveries (rate ratio [RR] 1.68, 95% CI 1.09–2.59). For cesarean deliveries performed before the onset of labor, the risk of birth asphyxia of second (6 cases) compared with first twin (3 cases) was not significant (RR 2.00, 95% CI 0.59–6.79). Term second twins had a significantly higher risk of birth asphyxia compared with first twins, whereas rates of birth asphyxia for preterm first and second twins did not differ significantly. Asphyxia complicated the births of 7 first twins and 17 second twins at 37 weeks or more of gestation who were delivered after labor (RR 2.43, 95% CI 1.05–5.64). There was no excess risk of birth asphyxia for term second twins delivered by elective cesarean (asphyxia cases: first twin [T1]=0, second twin [T2]=1).
Rates of respiratory distress were higher in second than first twins in all gestational age categories. Excess morbidity from respiratory distress in second twins (104 versus 57 cases) was significant for planned vaginal deliveries (RR 1.82, 95% CI 1.48–2.25) but not for cesarean births (27 versus 18 cases) without labor (RR 1.50, 95% CI 0.98–2.30). There were no cases of respiratory distress among term twin pairs delivered by elective cesarean, whereas all but one case of RDS in term twins who attempted vaginal delivery involved the second twin (RDS cases: T1=1, T2=5). The five-fold RR of respiratory distress among term second twins was borderline significant.
Rates of birth trauma were uncommon and similar for first and second twins. Neonatal sepsis and necrotizing enterocolitis were equally likely to occur in first and second twins. Perinatal deaths for first and second twins combined was very low (7.5/1,000) and only observed in preterm twins at less than 34 weeks of gestation. Perinatal mortality rates among first and second twins were similar.
This population-based cohort study reaffirms the prevailing evidence that the second twin is at greater risk of serious perinatal morbidity than the first twin at all gestational ages,1–6,9–12 in contrast to reports of excess morbidity limited to term,9 preterm,6 or very preterm second twins.17 The effect of birth order was marked even when other factors were controlled for, such as birth weight, infant sex, presentation, and mode of delivery.
Studies on the effect of presentation on neonatal outcome in the second twin have yielded conflicting results.7,18–20 Based on our results, the second twin is at increased risk for adverse perinatal outcome, independently of presentation. Although higher rates of composite adverse outcome for vertex/nonvertex twin pairs delivered at 37 weeks or more and at less than 34 weeks may reflect increased rates of intrapartum operative intervention, the risk for vertex and nonvertex second twins relative to first-born co-twins was similar overall and within gestational age categories. The only exception to this pattern was for term twin pairs with nonvertex first twin, in which the rate of cesarean delivery was greater than 95%.
Recent evidence from large retrospective cohort studies has consistently demonstrated that planned vaginal delivery places the second twin at increased risk of perinatal mortality and neonatal morbidity relative to the first co-twin and that cesarean birth may be protective.9–11,20–23 Data from other retrospective observational studies,24 a systematic review and meta-analysis,25 and a small randomized controlled trial of vaginal delivery versus elective cesarean delivery26 have not demonstrated any benefit of planned cesarean delivery for twins. In Nova Scotia, planned vaginal delivery is the predominant practice for twin pregnancies. Cesarean delivery before the onset of labor is generally reserved for malpresentation of the first twin or evidence of maternal or fetal compromise, for which labor is considered to be contraindicated. The lowest rates of composite adverse outcome in our twin cohort were observed in twin pairs who underwent planned cesarean delivery at term. The risk of composite adverse outcome for term first and second twins delivered by elective cesarean was equivalent, whereas the risk for second twins exposed to a trial of labor was increased three-fold.
The effect of mode of delivery on outcome of preterm twins is difficult to interpret because cesarean delivery before the onset of labor is not planned but performed on a semi-urgent basis because of fetal concerns with unpredictable perinatal outcome. Interpretation of the impact of mode of delivery in preterm twins is also limited by smaller numbers within strata and higher prevalence of the composite outcome at earlier gestational ages. Planned vaginal delivery was associated with an increased risk of perinatal morbidity for the preterm second twin, irrespective of the actual mode of delivery. The excess risk of RDS for the second twin associated with cesarean delivery before the onset of labor at 34–36 weeks compared with less than 34 weeks may be related to differential exposure of first and second twins to lower uterine segment changes, contractions, or engagement. These factors may influence the risk of RDS to a greater degree in later preterm (34–36 weeks) than early preterm (less than 34 weeks) twins. The incidence of cesarean delivery for the second twin following vaginal delivery of the first was consistent with other reports, but the risk of adverse perinatal outcome for the second twin was not increased as in other studies.10,22,23 This finding may reflect a lower threshold for cesarean delivery of the second twin for nonreassuring fetal heart rate or malpresentation and the common practice of double set-up in the operating room for all twin deliveries in our setting.27
Although the RR of serious perinatal morbidity in the second twin was increased, whether the birth weights of twin pairs were concordant or discordant, rates of composite perinatal morbidity were highest in twin pairs with birth weight discordance of more than 20%, particularly when the second twin was larger than the first twin. This finding is consistent with other reports demonstrating high rates of stillbirth, neonatal death, and neonatal morbidity associated with birth weight discrepancies of more than 20–40%.13,28,29 Higher rates of fetal distress, requirement for oxygen, respiratory distress syndrome, and low 5-minute Apgars have also been observed when the second twin is larger than the first and more prone to mechanical problems with delivery and respiratory depression.30
Delivery of the second twin between 15 and 30 minutes after vaginal delivery of the first twin was associated with higher rates composite adverse outcome as in other studies.14,30 Intertwin intervals of greater than 30 minutes were uncommon and not associated with an increased risk of perinatal morbidity for the second twin. This finding may be related to the small number of twins in this category and the tendency to only permit interdelivery intervals greater than 30 minutes in second twins with a consistently reassuring fetal heart rate tracing. As in other reports, the likelihood of cesarean delivery for the second twin increased with increasing interdelivery interval.30
Chorionicity had no influence on the birth order–related risk of adverse perinatal outcome for the second twin as in the other reports.30 Likewise, infant sex of first and second twins had minimal impact on the risk of adverse outcome for the second twin. Among discordant sex twin pairs, our data suggest that male second twins may be at slightly greater risk of adverse outcome than female second twins when compared with their opposite sex co-twins. This finding is consistent with the prevailing evidence that male infants do not do as well as female infants.4 The increased rates of composite adverse outcome observed in same sex twin pairs is due to higher rates of perinatal morbidity in monozygotic twins.
The previously recorded observation that the term second twin is at particular risk for birth asphyxia when planned vaginal delivery is attempted is confirmed by our data.9–11,22,23 We also found that planned cesarean delivery at term all but eliminated the risk of this birth-related complication for the second twin.9,21 Second twins were also at significant risk for respiratory distress across all gestational age groups as previously reported.18,31 Although the pathophysiologic mechanism for the second twin’s increased vulnerability to respiratory distress is unknown, lack of exposure to the salutary effects of labor, the effects of acute uteroplacental insufficiency after delivery of the first twin, and impairment of surfactant production have been postulated.30 These factors may explain the disproportionate distribution of RDS for 34- to 36-week twins delivered by cesarean without labor. We did not observe a higher risk of intrapartum or neonatal death among second twins as reported by others,11,21 but second twins were at increased risk of neonatal morbidity, particularly asphyxia, and respiratory distress. If this excess risk of asphyxia for term second twins can be prevented by elective cesarean delivery, both short- and long-term infant morbidity may be reduced.
The results of this retrospective study must be interpreted with caution. The limitations of the cohort size, particularly within stratified subcategories, potential for selection bias among practitioners, changing obstetric and neonatal practice over a 14-year time span, and the inherent problems with multiple comparisons must be acknowledged. Nevertheless, the use of a large, well-established perinatal database and the concordance of our findings with other recent publications lend support to our conclusions. The matched-pair analysis technique allowed us to compare second twins with their first-born co-twins, obviating the need to control for maternal factors.
Our findings confirm that the second twin is at significant risk of adverse perinatal outcome, independently of presentation, chorionicity, infant sex, birth weight, and prolonged interdelivery interval. Planned cesarean delivery at term may improve the perinatal outcome for the second twin. Until the effectiveness and maternal safety of elective cesarean for term twins has been established by well-designed, randomized controlled trials, such as the ongoing Twin Birth Study, practitioners should continue to use their clinical judgement and experience to inform their decisions regarding the optimal mode of delivery for term twins (Barrett JF. Randomised controlled trial for twin delivery [letter]. BMJ 2003;326:448.).
1. Joseph KS, Marcoux S, Ohlsson A, Liu S, Allen AC, Kramer MS, et al. Changes in stillbirths and infant mortality associated with increases in preterm birth among twins. Pediatrics 2001;108:1055–61.
2. HealthCanada. Canadian Perinatal Health report, 2003. Ottawa: Minister of Public Health Works and Government Services Canada. Available at: http://www.phac-aspc.gc.ca/publicat/cphr-rspc03/pdf/cphr-rspc03_e.pdf
. Retrieved May 23, 2006.
3. Joseph KS, Liu S, Demissie K, Wen SW, Platt RW, Ananth CV, et al. A parsimonious explanation for intersecting perinatal mortality curves: understanding the effect of plurality and of parity. BMC Pregnancy Childbirth 2003;3:3.
4. Imaizumi Y. Perinatal mortality in single and multiple births in Japan, 1980–91. Paediatr Perinat Epidemiol 1994;8:205–15.
5. Wyshak G. Birth hazard of the second twin. JAMA 1963;186:869–70.
6. Prins RP. The second-born twin: can we improve outcomes? Am J Obstet Gynecol 1994;170:1649–56.
7. Usta IM, Nassar AH, Awwad JT, Nakad TI, Khalil AM, Karam KS. Comparison of the perinatal morbidity and mortality of the presenting twin and its co-twin. J Perinatol 2002;22:391–6.
8. Sibony O, Touitou S, Luton D, Oury JF, Blot PH. A comparison of the neonatal morbidity of second twins to that of a low-risk population. Eur J Obstet Gynecol Reprod Biol 2003;108:157–63.
9. Smith GCS, Pell JP, Dobbie R. Birth order, gestational age, and risk of delivery related perinatal death in twins: retrospective cohort study. BMJ 2002;325:1004–9.
10. Wen SW, Fung KF, Oppenheimer L, Demissie K, Yang Q, Walker M. Neonatal morbidity in second twin according to gestational age at birth and mode of delivery. Am J Obstet Gynecol 2004;191:773–7.
11. Wen SW, Fung KF, Oppenheimer L, Demissie K, Yang Q, Walker M. Neonatal mortality in second twin according to cause of death, gestational age, and mode of delivery. Am J Obstet Gynecol 2004;191:778–83.
12. Sheay W, Ananth CV, Kinzler WL. Perinatal mortality in first- and second-born twins in the United States. Obstet Gynecol 2004;103:63–70.
13. Kontopoulos EV, Ananth CV, Smulian JC, Vintzileos AM. The influence of mode of delivery on twin neonatal mortality in the US: variance by birth weight discordance. Am J Obstet Gynecol 2005;192:252–6.
14. Leung TY, Tam W, Leung T, Lok IH, Lau T. Effect of twin-to-twin delivery interval on umbilical cord blood gas in the second twins. BJOG 2002;109:63–7.
15. Fair M, Cyr M, Allen AC, Wen SW, Guyon G, MacDonald RC. Validation study for a record linkage of births and infant deaths in Canada. Ottawa. Statistics Canada 1999 (Catalogue No. 84 F0013X1E). Available at: http://dsp-psd.communication.gc.ca/Collection/Statcan/84F0013X/84F0013XIE.pdf
. Retrieved May 23, 2006.
16. Greenland S. Applications of stratified analysis. In: Rothman KJ, Greenland S, editors. Modern epidemiology. 2nd ed. Philadelphia (PA): Lippincott-Raven; 1998. p. 281–300.
17. Adam C, Allen AC, Baskett TF. Twin delivery: influence of the presentation and method of delivery on the second twin. Am J Obstet Gynecol 1991;165:23–7.
18. Arnold C, McLean F, Kramer M, Usher R. Respiratory distress syndrome in second-born versus first-born twins: a matched case-control analysis. N Engl J Med 1987;317:1121–5.
19. Caukwell S, Murphy DJ. The effect of mode of delivery and gestational age on neonatal outcome of the non–cephalic-presenting second twin. Am J Obstet Gynecol 2002;187:1356–61.
20. Kontopoulos EV, Ananth CV, Smulian JC, Vintzileos AM. The impact of route of delivery and presentation on twin neonatal and infant mortality: a population-based study in the USA, 1995–97. J Matern Fetal Neonatal Med 2004;15:219–24.
21. Smith GCS, Shah I, White IR, Pell JP, Dobbie R. Mode of delivery and the risk of delivery-related perinatal death among twins at term: a retrospective cohort study of 8073 births. BJOG 2005;112:1139–44.
22. Yang Q, Wen SW, Chen Y, Krewski D, Fung KF, Walker M. Neonatal death and morbidity in vertex-nonvertex second twins according to mode of delivery and birth weight. Am J Obstet Gynecol 2005;192:840–7.
23. Yang Q, Wen SW, Chen Y, Krewski D, Fung KF, Walker M. Neonatal mortality and morbidity in vertex-vertex second twins according to mode of delivery and birth weight. J Perinatol 2006;26:3–10.
24. Greig PC, Veille JC, Morgan T, Hendersen L. The effect of presentation and mode of delivery on neonatal outcome in the second twin. Am J Obstet Gynecol 1992;167:901–6.
25. Hogle KL, Hutton EK, McBrien KA, Barrett JFR, Hannah ME. Cesarean delivery for twins: a systematic review and meta-analysis. Am J Obstet Gynecol 2003;188:220–7.
26. Rabinovici J, Barkai G, Reichman B, Serr DM, Mashiach S. Randomized management of the second non-vertex twin: vaginal delivery or cesarean section. Am J Obstet Gynecol 1987;156:52–6.
27. Persad VL, Baskett TF, O’Connell CM, Scott HM. Combined vaginal-cesarean section delivery of twin pregnancies. Obstet Gynecol 2001;98:1032–7.
28. Ananth CV, Demisse K, Hanley ML. Birth weight discordancy and adverse perinatal outcomes among twin gestations in the United States: the effect of placental abruption. Am J Obstet Gynecol 2003;188:954–60.
29. Wen SW, Fung KF, Huang L, Demissie K, Joseph KS, Allen AC, et al. Fetal and neonatal mortality among twin gestations in a Canadian population: the effect of intrapair birthweight discordance. Am J Perinatol 2005;22:279–86.
30. Hartley RS, Hitti J. Birth order and delivery intervals analysis of twin pair perinatal outcomes. J Matern Fetal Neonatal Med 2005;17:375–80.
31. Hacking D, Watkins A, Fraser S, Wolfe R, Nolan T. Respiratory distress syndrome and birth order in premature twins. Arch Dis Child Fetal Neonatal Ed 2001;84:F117–21.