OBJECTIVE: A significant increase in the triplet birth rate has occurred recently. This rise is of concern, as these infants are historically reported to be at risk of adverse outcome. Thus, we examined the outcome of triplet births in a large contemporary case series.
STUDY DESIGN: Since 1993, detailed clinical data have been collected on all patients admitted to our Neonatal Intensive Care Unit. We retrospectively analyzed this database to examine triplet outcome.
RESULTS: A total of 51 consecutive sets of triplets were born over a 9-year period. The mean birth weight for triplets was 1789±505 g, mean gestational age was 32.6±2.7 weeks, with discordancy present in 17.6% of neonates. Complications of prematurity were infrequent. Triplet survival to discharge was 96%.
CONCLUSIONS:This large contemporary case series of triplets demonstrates excellent survival with low associated morbidity. These data suggest that there may no longer be medical justification for offering selective fetal reduction to parents with triplet pregnancies.
Over the last 20 years, there has been a 400% rise in the rate of higher-order multiple births. Over the same time period, the singleton birth rate rose by only 6%, and the twin birth rate by 52%.1 According to the most recent national vital statistics, triplet births comprise the overwhelming majority of higher-order multiples, accounting for 91% of all higher-order multiple births.2 The increase in the triplet birth rate has been most marked in women aged 40 years and over, with an increase of over 1000%. Conversely, in women aged 30 to 40 years the multiple birth rate increased by 30%, and increased by only 13% in women less than 20 years. There are two main reasons for this exponential rise in the multiple birth rate. Firstly, the recent trend for childbearing at an older age—which in itself is associated with increased risk of multiple births—accounts for an estimated one-third of the rise in multiple birth rates. However, the majority of the increase in multiple births is attributable to the increasing availability and use of fertility-enhancing medications and procedures (assisted reproduction).
The rise in triplet births is of concern, as these infants are historically reported to be at risk of adverse outcomes.3,4,5 The mean gestational age for triplets is reported to be 32 weeks and for twins 35 weeks, resulting in 91.6% of triplets and 47% of twins being born preterm (<37 weeks) compared to only 9.8% of singletons.6,7 In keeping with shorter gestations, many triplets are born low birth weight. Overall, 92% of triplets are born with low birth weight (<2500 g) compared to 53% of twins and only 6% of singletons. The shorter gestational age and lower birth weights, typically seen in triplets, both contribute to a reported 11-fold increase in infant mortality rate when compared with singletons and 2.2 when compared with twins.7
Selective fetal reduction is a procedure that has been widely employed over the last 15-years to reduce the risk of complications related to multiple gestation, and correspondingly improve pregnancy outcome.8 Many investigators have compared the outcome of triplets with reduced and nonreduced twins with conflicting results. Studies in the early 1990s suggested that reduction of triplet pregnancies improved outcome. However, more recent studies have failed to demonstrate adverse outcome in triplet births when compared with reduced and even nonreduced twins.9,10,11 We propose that recent advances in both neonatal and obstetric care have greatly improved outcome for younger and lighter neonates, and thus the perceived benefits of performing fetal reduction in order to improve neonatal outcome may no longer exist.
We describe an up-to-date case series of 51 consecutive sets of triplets, and report survival rates comparable to that of twins.
We retrospectively reviewed data from the obstetric and neonatal patient databases at Georgetown University Hospital (GUH). Baseline demographics and in-hospital complications were confirmed by independent hospital chart review, and data entered into the database by experienced medical secretaries. The records of all triplets born between July 1993 and May 2002 were analyzed. All infants were inborn at GUH and, because of their perceived high-risk status all were admitted to the neonatal intensive care nursery. GUH is a regional perinatal referral center for high-risk pregnancies, with 1800 mostly high-risk deliveries a year and 525 infants admitted to the neonatal intensive care nursery per year.
Data extracted from the database included birth weight, gestational age and Apgar scores. The percentage of infants who were discordant in weight (defined as >20% difference) was calculated. Neonatal outcomes recorded were as follows: (1) chronic lung disease defined as oxygen or ventilator dependency at 28 days of age; (2) necrotizing enterocolitis stage II or greater, as defined by the Bell classification;12 (3) grade III and IV intraventricular hemorrhage documented by cranial ultrasound performed within the first week of life;13 (4) periventricular leukomalacia detected by cranial ultrasound performed at 4 to 6 weeks of life, as diagnosed by a pediatric radiologist;14 and (5) retinopathy of prematurity greater than stage I diagnosed by a pediatric ophthalmologist performing routine eye examinations according to the American Academy of Pediatrics guidelines.15 Length of stay in days for survivors and survival to hospital discharge were also recorded. Descriptive statistics were used to characterize the population and outcomes.
Between July 1993 and May 2002, 51 sets of triplets (153 infants) were born at GUH. Complete data were available for all births. Data are presented as mean ±SD or median (range) in Table 1.
The mean birth weight for triplets was 1789 ±505 g, and the mean gestational age was 32.6±2.7 weeks. In all, 37.3% of the triplets were born between 34 and 36 weeks of gestation. Gestational age by 1-week categories is displayed in Figure 1. Apgar scores were 7 (1 to 9) and 9 (1 to 9) at 1 and 5 minutes, respectively. Discordancy was present in 17.6% of triplets. Three of the triplet infants had congenital abnormalities—two with hypospadias, and one with a ventricular septal defect.
Complications of prematurity in triplets were seen infrequently. Chronic lung disease was diagnosed in 3% of cases, necrotizing enterocolitis in 3%, and there were no cases of intraventricular hemorrhage and periventricular leukomalacia, or advanced retinopathy of prematurity. The mean length of hospital stay was 23 days, with a median of 19 days. Triplet survival to hospital discharge was 96%.
According to the recently published National Vital Statistics for triplets, the national average gestational age for triplets is 32. 2 weeks, with 34.6% of births occurring between 34 and 36 weeks gestation.7 The national average birth weight for triplets is 1698 g. The present study demonstrated comparable results.
Previous studies suggest that higher-order multiples are more likely to have discordant birth weights than twins and singletons.9,16 These earlier studies reported discordancy rates of 48 and 54% for triplets, compared to 13 and 15% for twins. Discordancy rates were 17% in the current series, a rate similar to those seen in twins in previous studies. Improved obstetric management of triplet pregnancies may be one factor contributing to the observed decrease in discordancy. Congenital abnormalities occurred in 1.9% of triplets in this series—two neonates had hypospadias and one had a ventricular septal defect. This rate compares favorably with a 4.8% rate of major abnormalities reported in 1998 and adds further weight to the supposition that triplets are not at risk of adverse outcomes.17
This series demonstrates very low rates of morbidity associated with triplet birth. There were no reports of intraventricular hemorrhage or retinopathy of prematurity, and rates of only 3% for chronic lung disease and necrotizing enterocolitis. Previous work has reported similar frequencies of bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage and periventricular leukomalacia between twins and triplets, but suggested that triplets had a statistically significant increased risk of retinopathy of prematurity.17 Increased clinical surveillance and heightened awareness may have contributed to the lack of an excess of retinopathy in this current series. Length of hospital stay is reported to be longer for triplets, with one paper describing a mean stay of 51 days for triplets born at 31 weeks.18 The current study shows a much shorter hospital stay of 23 days, albeit in a cohort that was 1-week more mature. Such a profound difference is surprising and potential explanations include varying institutional discharge policy, variation in discharge policy over time, as well as improvements in neonatal care.
In the current series, 96% of triplets survived to discharge. Over the last 20 years, survival in higher-order multiple birth has gradually improved. For example, survival rates in the late 1980s were reported to be 79.0%,3 and the most recent National Statistics including births up to 1994 report 90.6% of triplets surviving.6 This improvement is also confirmed in other cohort studies quoting survival rates of 94 to 97%.18,19,20
During the early 1990s, studies suggested a benefit in neonatal outcome and survival if triplet pregnancies were reduced to twins. For example, one series demonstrated that neonatal survival improved from 79 to 97% if triplet pregnancies were reduced to twins.3 However, this perceived benefit in neonatal survival has not been maintained in studies published more recently. In a study reported in 2000, there was no difference in neonatal survival when 81 sets of triplets were compared with 46 sets of triplets reduced to twins.19 In addition, a 1999 study comparing 25 sets of triplets with 19 sets of reduced twins reported no difference in overall neonatal survival.9
Consistent with more recent data, our triplet survival is comparable to a large cohort (n=319 sets) of nonreduced twins born over the same period at our institution. Twin survival was 94%, which was not statistically different from that of the triplets. Additionally, triplet morbidity was comparable to that seen in our twin cohort. However, there may have been selection bias in our twin cohort as our institution is a regional referral center, and as such these twins may be higher risk. Therefore, a more definitive comparison would be between outcome in triplets and twins reduced within our institution. However, as our institution is a Catholic hospital, fetal reduction is not practiced, and thus this comparison cannot be made. Nevertheless, our findings are consistent with the most recently published literature, comparing outcome in triplet and twin cohorts.
This large contemporary case series of triplet pregnancies demonstrates excellent survival rates with very low associated morbidity. Given our data and several other reports of such improvements, the need to offer selective fetal reduction to parents expecting triplets should be re-examined.
Centers for Disease Control and Prevention. Contribution of assisted reproduction technology and ovulation- inducing drugs to triplet and higher-order multiple births—United States, 1980–1997. JAMA 2000;284:299–300.
Martin JA, Park MM . Trends in Twin and Triplet Births: 1980–97. National Vital Statistics Reports 1999;47(24):2.
Macones GA, Shemmer G, Pritts E, et al. Multifetal reduction of triplets to twins improves perinatal outcome. Am J Obstet Gynecol 1993;169:982–986.
Yaron Y, Bryant-Greenwood PK, Dave N, et al. Multifetal pregnancy reduction of triplets to twins: Comparison with non-reduced triplets and twins. Am J Obstet Gynecol 1999;180:1268–1271.
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Angel JL, Kalter CS, Morales WJ, et al. Aggressive perinatal care for the high-order multiple gestations: Does good perinatal outcome justify aggressive assisted reproductive techniques. Am J Obstet Gynecol 1999;181:253–259.
Evans MI, Berkowitz RL, Wapner RJ, et al. Improvement in outcomes of multifetal pregnancy reduction with increased experience. Am J Obstet Gynecol 2001;184:97–103.
Anstaklis AJ, Drakakis P, Vlazakis GP, et al. Reduction of multifetal pregnancies to wins does not increase obstetric or perinatal risks. Hum Reprod 1999;14:1338–1340.
Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978;187:1–7.
Papile LA, Burstein J, Burstein R, et al. Incidence and evolution of sub-ependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 g. J Pediatr 1978;92:529–534.
Volpe JJ . Hypoxic–ischemic encephalopathy: neuropathology and pathogenesis. In: Neurology of the Newborn. 3rd ed. Philadelphia, PA: WB Saunders; 1987.
Anonymous. An international classification for retinopathy of prematurity. The Committee for the Classification of Retinopathy of Prematurity. Arch Ophthalmol 1994;102:1130.
Smith-Levitin M, Kowalik A, Birnholz J, et al. Selective reduction of multifetal pregnancies to twins improves outcome over non-reduced triplet gestations. Am J Obstet Gynecol 1996;175:878–882.
Kaufman GE, Malone FD, Harvey-Wilkes KB, et al. Neonatal morbidity and mortality associated with triplet pregnancy. Obstet Gynecol 1998;91:342–348.
Suri K, Bhandari V, Lerer T, et al. Morbidity and mortality of preterm twins and higher-order multiple births. J Perinatol 2001;21:293–299.
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This case series of 51 consecutive sets of triplets demonstrates low morbidity rates and excellent survival rates with contemporary neonatal care.
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Barr, S., Poggi, S. & Keszler, M. Triplet Morbidity and Mortality in a Large Case Series. J Perinatol 23, 368–371 (2003). https://doi.org/10.1038/sj.jp.7210950
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