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ORIGINAL RESEARCH |
From the Division of Epidemiology, University of Medicine and Dentistry of New Jersey—School of Public Health, Piscataway; Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway; and Division of Maternal–Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School/Saint Peter’s University Hospital, New Brunswick, New Jersey.
Address reprint requests to: Kitaw Demissie, MD, PhD, University of Medicine and Dentistry of New Jersey, School of Public Health, Division of Epidemiology, 675 Hoes Lane, Piscataway, NJ 08854; E-mail: demisski{at}umdnj.edu.
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ABSTRACT |
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METHODS: The 1995–1997 Centers for Disease Control and Prevention’s Matched Multiple Birth file was used for this analysis. Birth weight discordance was calculated as the difference in birth weight between the largest and the smallest triplet’s weight and expressed as percentage of the largest triplet’s weight. For the middle-weight triplet, we also used the largest triplet’s weight as a reference in calculating percentage birth weight discordance, which was then grouped into quintiles.
RESULTS: Among 15,511 triplet live births and fetal deaths (at least 20 weeks’ gestation), 35% had less than 10% birth weight discordance, 19.3% had 10–15%, 16.4% had 15–21%, 15.2% had 21–29%, and 14.1% had 29% or more. After controlling for confounders, the risk of fetal death associated with quintile V was significantly higher than that associated with quintile I for smallest (odds ratio [OR] 10.88; 95% confidence interval [CI] 4.87, 26.56), middle (OR 22.6; 95% CI 11.05, 46.3), and largest (OR 2.41; 95% CI 1.01, 5.89) triplets. Smallest and middle triplets in quintile V were more likely than quintile I triplets to be born small for gestational age (OR 26.0; 95% CI 17.1, 39.9 for smallest, and OR 13.4; 95% CI 8.01, 22.3 for middle). Birth weight discordance quintile was not associated with smallness for geatational age among largest triplets nor consistently with neonatal mortality among smallest, middle, or largest triplets.
CONCLUSION: Increasing birth weight discordance was associated with increased risk of fetal death and smallness for gestational age. A birth weight discordance threshold of at least 29% should alert obstetricians for appropriate decision making.
There has been an increase in the incidence of multiple births in the United States over the last 2 decades. The rate of triplet and higher order births increased almost 166% between 1990 (73 per 100,000 live births) and 1998 (194 per 100,000 live births).1 Triplets are becoming more common because of the frequent use of assisted reproductive technology for the treatment of infertility, especially among older women.2 In 1997, 43.3% of triplet births were due to assisted reproductive technology, in comparison with 22% in 1990 and 1991.2
Perinatal mortality in triplets is significantly greater than in twin and singleton births.3 In 1997, the infant mortality rate for triplet and higher order births was more than double the rate for twin births and ten times the rate for singleton births.4 The increased risk of perinatal mortality among triplets is mainly due to preterm birth and smallness for gestational age. Smallness for gestational age among triplets may increase birth weight discordance, which is likely to increase the risk of perinatal mortality. Very little is known about the occurrence and associated adverse perinatal outcomes of birth weight discordance among triplet births. Our objective was to describe the extent of birth weight discordance among triplets, and to identify a birth weight discordance threshold that is associated with an increased risk of neonatal and fetal death as well as smallness for gestational age.
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MATERIALS AND METHODS |
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The principal outcomes were fetal (20 weeks or more) and neonatal (0–27 days) death, with small for gestational age (SGA) births examined as the secondary outcome. Gestational age information on the file was derived from 1) computation using dates of birth and last menstrual period (LMP), 2) from the clinical estimate, and 3) imputation for missing days of LMP. In more than 95% of the pregnancies, gestational age was based on LMP. Smallness for gestational age was defined as birth weight below the tenth percentile for gestational age. For this purpose, we used the 1995–1997 triplet birth normogram derived on the basis of all triplet births delivered during that period. Because of substantial differences among the states in reporting live births and fetal deaths, live births that were less than 20 weeks of gestation or had birth weight less than 400 g were excluded. Similarly, fetal deaths of less than 20 weeks’ gestation or involving weights less than 100 g were also excluded.
Birth weight discordance was the independent variable and calculated as the difference in birth weight between the largest triplet’s weight and the smallest triplet’s weight and expressed as percentage of the largest triplet. For the middle-weight triplet, we calculated the difference in birth weight between the largest triplet’s weight and the middle triplet’s weight and expressed it as percentage of the largest triplet’s weight. As there was no standard to categorize percentage birth weight discordance into groups, the cutoff values were based on quintiles. Less than 10% birth weight difference formed quintile I, 10–15% formed quintile II, 15–21% discordance formed quintile III, 21–29% constituted quintile IV, and 29% or more represented quintile V. Factors considered as potential confounders included maternal age (younger than 20, 20–24, 25–29, 30–34, and 35 years or older), maternal race (white, black, or other), maternal education in completed years of schooling (less than 12, 12, 13–15, 16, and 17 or more), marital status, trimester of prenatal care initiation, and live birth parity (0, 1, 2, or 3 or more). Disorders complicating pregnancy included diabetes (includes pregestational and gestational), chronic hypertension, pregnancy-induced hypertension (including eclampsia), placental abruption, placenta previa, and anemia. Data on characteristics of labor and delivery included delivery method (cesarean delivery, forceps, or vacuum), premature rupture of membranes, and prolonged labor. Prolonged labor was defined as abnormally slow progress of labor lasting more than 20 hours due to either weak or inadequate contraction or abnormal presentation; the information was obtained from the mother’s birth record or from her attendant.
We examined the distribution of potential confounding factors according to birth weight discordance categories. We then calculated the fetal and neonatal mortality and SGA rates for birth weight discordance groups. Finally, we estimated the risk associated with birth weight discordance groups for the above outcomes using logistic regression models before and after accounting for important confounding variables. Birth weight discordance quintile I served as a reference. Potential confounders were evaluated in logistic regression models, and variables that changed the unadjusted association (odds ratio) by at least 10% were retained in final models.
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RESULTS |
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The distribution of selected variables by birth weight discordance quintile is provided in Table 1
. There was no clear association between maternal age and birth weight discordance quintile. The highest proportion of triplet births occurred among women 30 years and older in each quintile. The proportion of nulliparous women was lowest among quintile I, and progressively increased with increasing quintile. In general, the proportion of mothers with diabetes, chronic hypertension, pregnancy-induced hypertension, and anemia increased with increasing birth weight discordance quintile. About 90% of triplets were delivered by cesarean. There was no relationship between placental abruption, placenta previa, and birth weight discordance.
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. After accounting for confounders, the risk of fetal death associated with quintile V was significantly higher than that associated with quintile I for smallest, middle, and largest triplets. The percentage birth weight discordance that was associated with significant fetal death was at least 29%.
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Data for SGA births by percentage birth weight discordance quintile are shown in Table 3. After accounting for the effects of important confounding variables, the risk of smallness for gestational age progressively increased from quintile I to quintile V in smallest and middle triplets. The risk associated with quintile V discordance was almost double among smallest triplets in comparison with the middle triplets. There was no association between smallness for gestational age and birth weight discordance quintile among largest triplets.
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DISCUSSION |
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Although numerous authors have addressed the issue of birth weight discordance among twin deliveries,6–10 very little is known about birth weight discordance in triplets. Mordel and his colleagues11 studied 114 triplets during a period of 11 years and reported a 15% or more and greater than 25% discordance in 58% and 25% of triplets, respectively. In that study the authors concluded that discordance per se was not associated with adverse perinatal outcomes. Our results agree with those of Mordel et al11 with regard to the distribution of birth weight discordance among triplets, but are at variance with respect to adverse perinatal outcomes. The reason for this inconsistency could be the small number of triplets studied by Mordel et al,11 which limited their study power to detect statistically important differences.
Various birth weight discordance thresholds that correlate with perinatal mortality among twins have been identified.7,12–14 More recently, Demissie et al6 studied almost 300,000 twin births and found a 20% or larger discordance to be a clinically significant cutoff associated with adverse perinatal outcomes. In contrast to twin births, in triplets we found a 29% or larger discordance to be significantly associated with fetal death.
The finding that birth weight discordance is associated with the risk of fetal death but not with smallness for gestational age among largest triplets suggests that the excess stillborn fetus rate observed among largest triplets may not be mediated through smallness for gestational age. Part of the association between fetal death and weight difference may be due to a common cause for both.
The results of the present study were based on a large population and include all triplet births in the United States between 1995 and 1997 (adding power and generalizability). Our analysis estimated risk separately for smallest, middle, and largest triplets and at the same time established a clinically important threshold at which obstetricians should be alerted. Unfortunately, birth weight is not a parameter that is available to the clinician prenatally. Instead, sonographic estimated fetal weights must be interpreted. Ultrasound evaluation not only provides a reasonable estimation of fetal weight, but also allows for determination of interval growth. In fact, predicted fetal weights fall within 15–18% of actual weights in 95% of cases.15 Ultrasound can also provide information on amniotic fluid volume, which improves the positive predictive value of antenatal detection of fetal growth restriction from 45% with the use of biometry alone to 55%. Sensitivity and specificity are 82–89% and 88–94%, respectively.16 Once a fetal growth abnormality is diagnosed, increased fetal surveillance with the use of biophysical profiles, nonstress tests, and Doppler velocimetry can be employed to assess fetal well-being and appropriate timing of obstetric intervention. Doppler velocimetry of the umbilical artery has been particularly useful. As placental blood flow resistance increases, diastolic flow in the umbilical artery decreases.17,18 The highest perinatal mortality rates are found with absent or reversed end diastolic flow.19,20 When used with other types of surveillance, a reduction in perinatal deaths has been demonstrated.21 Therefore, when fetal growth abnormalities and increased weight discordance are detected, heightened antepartum fetal surveillance is warranted.
Our finding on the association between birth weight discordance and fetal death should be interpreted with caution. This is because of the problematic association between intrauterine fetal death and weight of the fetus at delivery. The use of birth weight as a surrogate for fetal weight may not always be accurate. A study that estimated fetal weight during the 15 days before delivery and compared it with values of the actual birth weight did not find a significant difference between the mean fetal weight and birth weight.22 If the time elapsed between the death of one triplet and the delivery of the other triplets is long, the birth weight of the dead triplet may not be reliable. However, in multiple pregnancies with a single fetal death, mothers usually start labor soon after the diagnosis of fetal death.23 Another study limitation is the accuracy and completeness of gestational age based on the LMP date reported on the birth certificate. This measure is subject to error but has been demonstrated to be the most accurate available on a population-wide basis.24 Similarly, under-reporting of fetal deaths and pregnancy complications is likely to occur in birth certificate and fetal death data.25 Potential bias may also have been introduced in the definition of discordance among triplets with transfusion syndrome, as the largest triplet may not be an appropriate standard for judging the extent of discordance (eg, fetal hydrops).
In conclusion, increasing birth weight discordance was associated with increased risk of fetal death and smallness for gestational age. A birth weight discordance of 29% or larger should alert obstetricians for appropriate decision making.
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Footnotes |
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Received May 7, 2002. Received in revised form October 9, 2002. Accepted November 21, 2002.
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REFERENCES |
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2. Facts about triplet and higher-order births. Atlanta: Centers for Disease Control and Prevention, Office of Communication, Division of Media Relations, 2000. Available at: http://www.cdc.gov/od/oc/media/pressrel/r2k0623.htm. Accessed 2002 Dec 16.
3. Imaizumi Y, Inouye E, Asaka A. Mortality rate of Japanese twins and triplets III. Infant deaths of triplets after birth to one year of age. Acta Genet Med Gemellol (Roma) 1981; 30:281–4.[Medline]
4. MacDorman MF, Atkinson JO. Infant mortality statistics from the 1997 period linked birth/infant death data set. Natl Vital Stat Rep 1999;47(23):1–23.[Medline]
5. National Center for Health Statistics. 1995–97 Matched Multiple Birth data set. NCHS CD-ROM series 21, no. 12. Hyattsville, Maryland: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2000.
6. Demissie K, Ananth CV, Martin J, Hanley ML, MacDorman MF, Rhoads GG. Fetal and neonatal mortality among twin gestations in the United States: The role of intrapair birth weight discordance. Obstet Gynecol 2002;100: 474–80.
7. Hollier LM, McIntire DD, Leveno KJ. Outcome of twin pregnancies according to intrapair birthweight differences. Obstet Gynecol 1999;94:1006–10.
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18. Divon MY, Hsu HW. Maternal and fetal blood flow velocity waveforms in intrauterine growth retardation. Clin Obstet Gynecol 1992;35:156–71.[Medline]
19. Brar HS, Platt LD. Reverse end-diastolic flow velocity on umbilical artery velocimetry in high-risk pregnancies: An ominous finding with adverse pregnancy outcome. Am J Obstet Gynecol 1988;159:559–61.[Medline]
20. Battaglia C, Artini PG, Galli PA, D’Ambrogia G, Droghini F, Genazzani AR. Absent or reversed end-diastolic flow in umbilical artery and severe intrauterine growth retardation. An ominous association. Acta Obstet Gynecol Scand 1993;72:167–71.[Medline]
21. Alfirivec Z, Neilson JP. Doppler ultrasonography in high risk pregnancies: Systematic review with meta-analysis. Am J Obstet Gynecol 1995;172:1379–87.[Medline]
22. Mzeh DA, Rimmer S, Moore WMO, Hunt L. Prediction of birth weight by fetal ultrasound biometry. Br J Radiol 1992;66:987–9.
23. Santema JG, Swaak AM, Wallenburg HCS. Expectant management of twin pregnancy with single fetal death. Br J Obstet Gynaecol 1995;102:26–30.[Medline]
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25. Gaudino JA, Blackmore-Prince C, Yip R, Rochat RW. Quality assessment of fetal death records in Georgia: A method for improvement. Am J Public Health 1997;87: 1323–7.
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