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ORIGINAL RESEARCH |
From the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, and Department of Epidemiology, and Department of Pediatrics, Columbia Presbyterian Medical Center, New York, New York; and the Department of Obstetrics and Gynecology, University of Colorado, Denver, Colorado.
Address reprint requests to: Julian N. Robinson, MD, College of Physicians and Surgeons, Columbia University, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, 620 West 168th Street, PH 16, New York, NY 10032; E-mail: JR1017{at}columbia.edu.
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ABSTRACT |
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METHODS: We analyzed 11,061,599 singleton, 297,622 twin, and 15,375 triplet gestations drawn from the 1995–1998 National Center for Health Statistics linked birth and death files. Prospective risk of fetal death was expressed as a proportion of all fetuses still at risk at a given gestational age and compared with fetal death rate. Fetal death risk and neonatal death rates were represented graphically for singletons, twins, and triplets.
RESULTS: The prospective risk of fetal death at 24 weeks was 0.28 per 1000, 0.92 per 1000, and 1.30 per 1000 for singletons, twins, and triplets, respectively. At 40 weeks, the corresponding risk was 0.57 per 1000 and 3.09 per 1000 for singletons and twins, respectively and, at 38 or more weeks, 13.18 per 1000 for triplets. Plots of gestation-specific prospective risk of fetal death and neonatal mortality converged for singletons and twins at term but crossed for triplets at approximately 36 weeks’ gestation.
CONCLUSION: Prospective risk of fetal death is greater for triplets and twins than for singletons and greater for triplets than for twins during the third trimester. The pattern corroborates with uteroplacental insufficiency as a suspected underlying mechanism. When prospective risk of fetal death exceeds neonatal mortality risk, delivery might be indicated. When this model is used, this data set suggests that it might be reasonable to consider delivery of twins by 39 weeks and triplets by 36 weeks to improve perinatal outcome.
The prevalence of multiple gestations is increasing owing to delayed childbearing and increased use of assisted reproductive technology.1 Twin and higher-order multiples are at considerably greater risk for adverse outcomes than are singleton pregnancies. Multiple gestations are prone to preterm delivery, growth disturbances, and umbilical cord insertion abnormalities, among other complications, which can lead to increased perinatal morbidity and mortality.1–4
By the classic definition, fetal death rate is calculated from the number of fetal deaths at a particular gestational age divided by the number of live births and fetal deaths during the same period.5 This statistic is not informative for risk of fetal death for women who have not yet delivered and is therefore of limited value to clinicians who must anticipate a problem and effect delivery before intrauterine fetal death occurs. Fetal mortality rates are high at the threshold of viability, whereas the incidence of delivery at extreme prematurity is low. Low fetal mortality rates at later gestational ages might provide false reassurance. The lower rates are a function of the greater number of deliveries that occur closer to term, which serve to inflate the denominator. In contrast, the denominator for prospective risk of fetal death is the population of fetuses still at risk. For singletons, the number of fetuses still at risk is equivalent to the number of ongoing pregnancies.6 A more accurate impression of fetal risk for intrauterine fetal death might be obtained with this statistic.
We hypothesized that prospective fetal risk might be greater in multiple pregnancies, based on an increased theoretic risk of uteroplacental insufficiency at advanced gestational ages. To test our hypothesis, we performed a retrospective cohort study that compared twin and triplet mortality statistics with those of singletons. A MEDLINE search from 1966 to the present indicated that this is the first study to separately analyze prospective risk for twin and triplet pregnancies.
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MATERIALS AND METHODS |
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The National Center for Health Statistics data set included month and year of birth, gestational age at delivery, birth weight, delivery method, and plurality. Fetal, neonatal, and infant outcomes were recorded. If death occurred, age at death was recorded. Gestational age was calculated according to delivery date and last menstrual period. If that information was unavailable, the clinical statement of gestational age on the birth certificate was used (the standard technique for data presentation in National Center for Health Statistics publications). Fetal death was defined as death before expulsion from the mother, excluding cases of voluntary termination. Neonatal death was defined as death occurring in the period from the day of delivery to before the 28th day of age. Postneonatal death was defined as death between 28 days and 1 year of age.5
A problem reported in the use of large, vital-record databases is that bivariate analyses reveal implausible birth weight–gestational age combinations in singletons.7–10 We used previously published methodology to trim the singletons in our database to reduce this inaccuracy.7 Assuming birth weights were recorded with more reliability than were gestational ages, we examined gestational age distributions within 250-g birth weight intervals and trimmed the extreme top and bottom 1% (Table 1
). There was no trimming for multiple gestations. Finally, all deliveries before 24 weeks were excluded (Table 1). Gestational age groups were collapsed when individual weeks contained less than 5% of all gestations (ie, 43 or more weeks for singletons, 41 or more weeks for twins, and 38 or more weeks for triplets).
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RESULTS |
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). Maternal age and race are presented in Table 2. Fetal death rate and prospective risk of fetal death are presented for singletons, twins, and triplets in Tables 3, 4, and 5, respectively. Rates for quadruplets and above are not presented because there were only 30 fetal deaths and 59 neonatal deaths in these groups combined.
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When presented graphically, the prospective risk of fetal death was U-shaped for singletons, twins, and triplets, with the risk at the third trimester greater than at the limits of viability. Prospective risk of fetal death and neonatal mortality intersected at approximately 36 weeks for triplets, approximately 39 weeks for twins, and approximately 43 weeks for singletons.
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DISCUSSION |
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Conversely, the prospective risk for fetal death is lower at early gestational ages and rises as pregnancy progresses. Our results were similar to those from the recent study by Sairam et al,14 which demonstrated that the prospective risk of fetal death in multiple gestations at 37 to 38 weeks was equivalent to that of postterm singletons. However, Sairam et al did not report risk for twins and triplets separately. They reported that 99.8% of their multiples were twins, which suggests that their data is applicable to twins only.14
Prior publications have compared the prospective risk of fetal death at given gestational ages with that of singletons at term.11,14 When the prospective risk of fetal death is calculated for twin and triplet gestations separately, the risk for twins and triplets is greater than for singletons, and, at later gestations, the risk for triplets is greater than for twins. In our data set, the prospective risk of fetal death for twins equaled the prospective risk of fetal death for postterm singletons by approximately 36 to 37 weeks’ gestation. The upswing in fetal death risk for triplets began at an earlier gestational age and was steeper than for singletons and twins. The prospective risk for triplets equaled that of postterm singletons by approximately 28–30 weeks. These findings are consistent with the hypothesis that placental insufficiency increases in the third trimester for twins and even more so for triplets.
We think it is more useful clinically to compare gestation-specific prospective risk of fetal death with gestation-specific neonatal death rate. If the rate of neonatal death at a given gestational age is less than that of the prospective risk of fetal death if the pregnancy continues, delivery should be considered. Therefore, we have combined neonatal mortality and prospective risk of fetal death on the same graph (Figures 1, 2, 3). This is the first study of prospective risk to use this form of data presentation. It is our belief that the intersection of these two graphs marks the point at which it is logical to consider elective delivery. The prospective risk of fetal death for twins intersects with neonatal death rates at approximately 39 weeks. It seems reasonable to consider delivery of twins by 39 weeks, depending on the clinical situation. The data regarding triplets are more thought-provoking. Prospective risk of fetal death and the neonatal death rate intersect at approximately 36 weeks for triplets. Although the majority of triplets are delivered before 36 weeks for various obstetric reasons, in this data set of all fetuses attaining at least 24 weeks’ gestation, 15.8% of triplets remained undelivered at 36 weeks. Although this is a small proportion of triplets, delivery at this point might still result in decreased perinatal mortality for these pregnancies.
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A unique feature of our study is that prospective risk analysis commenced at 24 weeks for all pregnancies. The only other study with early-calculated prospective risk analysis was carried out by Feldman,6 who calculated risk in singletons starting at 26 weeks. Meanwhile, the study by Sairam et al,14 the only other study on multiples, started prospective risk analysis at 28 weeks. There was a difference between these studies, which started prospective risk analysis at later gestational ages, and our own that is interesting to explore. Studies beginning analysis at later gestational ages suggested that prospective risk of fetal death started low and increased steadily with advancing gestational age. In our study, the prospective risk was U-shaped in singletons, twins, and triplets. Prospective risk of fetal death at early gestational ages was higher than in the early third trimester, increasing thereafter to levels higher than at the limits of viability. Irregularities in the triplet graph are presumably due to instability caused by smaller sample sizes. Whereas prior studies suggested that there was less fetal death at early gestational ages, extending the analysis to the threshold of viability indicates that there are actually higher rates of fetal death at earlier gestational ages. Notably, this heightened risk at early gestation is not as dramatic as the heightened risk in the third trimester.
Although this study has many important findings, there are limitations that should be acknowledged. Dating was not as precise as possible because it was based on last menstrual period and gestational age recorded from birth certificates. It is well known that first-trimester ultrasound is the most accurate method of determining dates.17 Data regarding chorionicity and fetal anatomic and chromosomal abnormalities were not available. Chorionicity affects outcomes; monochorionic gestations are at increased risk for adverse outcomes.18,19 Similarly, fetal anatomic and chromosomal abnormalities can influence gestational age of delivery and can result in intrauterine fetal death.20 Presence of maternal disease, such as hypertension and diabetes, and adverse obstetric outcomes, such as preeclampsia and placental abruption, were not known and could have affected rates of intrauterine fetal death and gestational age of delivery.21 In addition, we made the assumption that fetuses with indications for delivery were delivered, whereas fetuses without indication for delivery were not electively delivered. If fetuses with serious identifiable risk of fetal death are undelivered, the prospective risk of fetal death will be greater than if these babies are delivered. However, because complications of pregnancy that lead to fetal death are rare and, if of significant severity to cause fetal death, often have noticeable clinical signs, such conditions are not likely to be missed.
An important confounding factor was that the exact time of intrauterine fetal death was not known. Intrauterine fetal death could have occurred days or weeks before diagnosis. As a result, the rise in prospective risk of fetal death might actually have occurred earlier. The most significant finding in this study was the increased risk of fetal death in multiple gestations at advanced gestational ages. The majority of women with multiple pregnancy have frequent office checkups (during which fetal heart rate tones are documented), lessening the chance of delayed diagnosis and making prolonged undiagnosed intrauterine fetal death less likely.22
The finding of greater prospective risk of fetal death in twins and triplets is potentially of considerable clinical importance. Prospective risk of fetal death rather than fetal death rate should be forefront in the minds of all practitioners managing twins and higher-order multiples for the purpose of preventing fetal death. In practice, there is a temptation to be reassured by increasing gestational age in multiples in the third trimester as the potential complications of prematurity recede. According to this data set, it seems reasonable to consider delivery of twins by 39 weeks to optimize perinatal outcomes. However, regarding triplets, consideration should be given to delivery at 36 weeks because at that time the prospective risk of fetal death seems to equal the neonatal death rate. Conversely, for this data set, survival for twins and triplets is better if they remain in utero up until these gestational ages, and this should also be considered when making clinical decisions about delivery.
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Footnotes |
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doi:10.1016/S0029-7844(03)00616-1
Received January 2, 2003. Received in revised form April 22, 2003. Accepted May 2, 2003.
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REFERENCES |
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2. Malone FD, D’Alton ME. Anomalies peculiar to multiple gestations. Clin Perinatol 2000;27:1033–46.[Medline]
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18. Dube J, Dodds L, Armson BA. Does chorionicity or zygosity predict adverse perinatal outcomes in twins? Am J Obstet Gynecol 2002;186:579–83.[Medline]
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21. Simpson L. Maternal medical disease: Risk of antepartum fetal death. Semin Perinatol 2002;26:42–50.[Medline]
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This article has been cited by other articles:
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  Y. M. Lee, B. J. Wylie, L. L. Simpson, and M. E. D'Alton Twin Chorionicity and the Risk of Stillbirth Obstet. Gynecol., February 1, 2008; 111(2): 301 - 308. [Abstract] [Full Text] [PDF]
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