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Risk for One or Two Very Low Birth Weight Twins: A Population Study

From the Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel (affiliated with the Hadassah-Hebrew University School of Medicine, Jerusalem); and the Department of Pediatrics, Sheba Medical Center, Tel Hashomer, Israel (affiliated with the Sackler Faculty of Medicine, Tel Aviv University).

Address reprint requests to: Isaac Blickstein, MD Department of Obstetrics and Gynecology Kaplan Medical Center Rehovot, 76100 Israel E-mail: blick{at}netvision.net.il

	Abstract

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Objective: To calculate the frequencies of very low birth weight (VLBW) neonates among twins in a large population database.

Methods: The database comprised 12,567 live-born twin pairs delivered from 1993 to 1998 in Israel. Low birth weight (LBW) and VLBW were defined as less than 2500 and 1500 g, respectively. We counted the number of pairs with VLBW neonates in three combinations: VLBW-VLBW, VLBW-LBW, and VLBW-over 2500 g. We compared the subsets of nulliparas and multiparas and the frequency of like- versus unlike-sex twins.

Results: The frequency of at least one VLBW twin was significantly higher among nulliparas than multiparas (odds ratio [OR] 2.3; 95% confidence interval [CI] 2.1, 2.6; P < .001). For pairs with VLBW-VLBW and VLBW-LBW combinations, a significantly higher frequency was found among nulliparas than multiparas (OR 2.0; 95% CI 1.7, 2.8; P < .001 and OR 2.6; 95% CI 2.2, 3.1; P < .001, respectively). The risk seemed to be accentuated in like-sex twins. Overall, the risk of having at least one VLBW infant was 1:5 among nulliparas and 1:12 among multiparas. The risk of having two VLBW twins among nulliparas (1:11) was double that of multiparas (1:22).

Conclusion: Nulliparas are at significantly increased risk of delivering one or two VLBW twins.

Twins are overrepresented among low birth weight (LBW) and very low birth weight (VLBW) infants and contribute substantially to neonatal morbidity and mortality figures. Powers and Kiely¹ performed a population-based analysis of all live births and infant deaths from 1985 to 1986 as reported in the US Linked Birth/Infant Death Data Sets. Twins of all races had a 9.97 relative risk (RR) for VLBW and an RR of 8.61 for LBW. Thus, although twins represented only 2.09% of live births, they accounted for a disproportionately large share of adverse pregnancy outcomes, as shown by the population-attributable risks of 15.8% for VLBW and 13.7% for LBW. Luke and Keith² evaluated the 1988 US population-based data to show that twins’ RRs for LBW and VLBW were 10.3 and 9.6, respectively, compared with those of singletons. In a recent United Kingdom perinatal mortality survey from 1982 to 1994, Glinianaia et al³ reported that VLBW twins accounted for 69% of all twin perinatal deaths. These figures conform with those of Alexander et al,⁴ who used the 1991–1995 US Natality Data Files to show that among 463,856 live-born twins, 10.12% and 52.24% were VLBW and LBW, respectively.

With this information, women expecting twins might wish to know the risk of having one or two VLBW twins by simple terms of parity and fetal sex, two variables that affect twin birth weight.^5,6 The purpose of this study was to calculate this risk in a large population database.

	Materials and Methods

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We collected data from the Israeli Birth Registry through the Central Bureau of Statistics, which includes all deliveries in Israel, as required by law. The database of 12,785 twin pairs delivered in 1993–1998 was used to select a cohort of 12,567 pairs with known maternal parity (98.3%), complete birth weight data, and neonatal sex. Data were analyzed using Microsoft Excel (Microsoft Corporation, Redmond, WA). We defined LBW and VLBW as less than 2500 and 1500 g, respectively. We identified pairs in three combinations: VLBW-VLBW, VLBW-LBW, and VLBW-over 2500 g. Then we compared the number of twin pairs in the subsets of nulliparas versus multiparas and by the frequency of like- versus unlike-sex twins.

We used True Epistat Software (Math Archives, Round Rock, TX) for statistical analysis. The power of all subgroup analyses was sensitive enough to detect differences of less than 0.5%. The ² test was used for comparing frequencies. P < .05 was considered statistically significant, and the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

	Results

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A total of 12,567 twin pairs (7709 like-sex and 4858 unlike-sex pairs) were born to 4805 nulliparas (38.2%) and 7762 multiparas (61.7%). Nulliparas and multiparas delivered 2819 (58.7%) and 4890 (63%) like-sex twins, respectively. Numbers and frequencies of twins in each combination are shown in Table 1.

There were 880 (65%) like-sex pairs and 474 (35%) unlike-sex pairs among twin births with at least one VLBW infant (Table 2). For the combination of VLBW-VLBW, there was no statistically significant difference between nulliparas with like-sex and with unlike-sex twins (8.5% versus 8.2%; P = .7). However, there were statistically significant differences between nulliparas with like-sex twins and both multiparas with like-sex twins (8.5% versus 5.0%; OR 1.8; 95% CI 1.5, 2.2; P < .001) and multiparas with unlike-sex twins (8.5% versus 3.2%; OR 2.9; 95% CI 2.2, 3.7; P < .001). There were also statistically significant differences between nulliparas with unlike-sex twins and both multiparas with like-sex twins (8.2% versus 5.0%; OR 1.7; 95% CI 1.4, 2.1; P < .001) and multiparas with unlike-sex twins (8.2% versus 3.2%; OR 2.7; 95% CI 2.1, 3.6; P < .001). In contrast to the lack of difference in nulliparas with two VLBW twins, there was a statistically significant difference between multiparas with like-sex and with unlike-sex twins (5.0% versus 3.2%; OR 1.6; 95% CI 1.2, 2.1; P < .001).

We did not analyze the VLBW-over 2500 g pairs because of their low incidence.

	Discussion

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Low birth weight is responsible for up to 60% of the infant mortality rate (up to 1 year postpartum) in the United States, carries a 40-fold increase in the risk of neonatal mortality (at less than 28 days postpartum), and increases the risk for long-term morbidity by two to three times.⁷ About 40% of VLBW survivors have one or more major impairments.⁷

We conducted a computerized literature search (PubMed, US National Library of Medicine, http://www.ncbi.nlm.nih.gov/PubMed/) for population-based studies on VLBW twins published since 1975. To the best of our knowledge, our study is the first population-based observation that evaluated the risk of delivering one or two VLBW infants in twin births. Because ORs related to population-based data might imply actual RRs, our data clearly show that nulliparas expecting twins are at a 2 to 3 times increased risk of having at least one VLBW infant. The risk of giving birth to at least one VLBW infant is 1:5 for nulliparas and 1:12 for multiparas. The risk of delivering two VLBW twins in nulliparas is twice as high as in multiparas (1:11 versus 1:22). Results from one population might differ from those in another; however, factors that might influence VLBW rates such as race, socioeconomic and insurance status, and substance abuse do not have a significantly different effect on the two tested variables.

The data further show that nulliparas who have like-sex twins have an increased risk of delivering two VLBW infants as compared with multiparas. The data also suggest that having like- or unlike-sex twins does not significantly change the risk of having a VLBW-LBW combination among the same parity groups, but changes the risk in favor of multiparas compared with nulliparas.

Our observation that nulliparas are at significantly higher risk of having one or two VLBW twins agrees with the higher natural twinning rates among multiparas, implying a genetically mediated growth-enhancing local (uterine) milieu or an extended maternal capacity to nurture twins in subsequent gestations. Our database could not differentiate between spontaneous and induced twins, so we were unable to determine whether women who conceived after infertility treatment and who lacked the genetic and parity-related growth-promoting effects were at increased risk of delivering VLBW infants.^8–10 Our data referred to live births and did not consider neonatal and infant mortality. Some idea about VLBW-related mortality in twins comes from Chen et al,¹¹ who found 69% survivors in a series of 44 VLBW pairs. Our data also did not specify risk for extremely LBW (less than 1000 g) neonates. With the advent of modern neonatal intensive care units, those neonates have a survival rate ranging from less than 40% for those who weigh less than 600 g to more than 90% for those who weigh more than 900 g.⁷

	Footnotes

 
PII S0029-7844(00)00942-X

Received February 8, 2000. Received in revised form April 3, 2000. Accepted April 27, 2000.

	References

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1. Powers WF, Kiely JL. The risks confronting twins: A national perspective. Am J Obstet Gynecol 1994;170:456–61.[Medline]

2. Luke B, Keith LG. The contribution of singletons, twins and triplets to low birth weight, infant mortality and handicap in the United States. J Reprod Med 1992;37:661–6.[Medline]

3. Glinianaia SV, Rankin J, Renwick M. Time trends in twin perinatal mortality in northern England, 1982–94. Northern Region Perinatal Mortality Survey Steering Group. Twin Res 1998;1:189–95.[Medline]

4. Alexander GR, Kogan M, Martin J, Papiernik E. What are the fetal growth patterns of singletons, twins, and triplets in the United States? Clin Obstet Gynecol 1998;41:115–25.

5. Blickstein I, Zalel Y, Weissman A. Pregnancy order: A factor influencing birth weight in twin gestations. J Reprod Med 1995;40: 443–6.[Medline]

6. Glinianaia SV, Mangus P, Harris JR, Tambs K. Is there a consequence for fetal growth of having an unlike-sexed cohabitant in utero? Int J Epidemiol 1998;27:657–9.[Abstract/Free Full Text]

7. Papageorgiou A, Bardin CL. The extremely low birth weight infant. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: Pathophysiology and management of the newborn. Philadelphia: Lippincott Williams & Wilkins, 1999;445–7.

8. McElrath TF, Wise PH. Fertility therapy and the risk of very low birth weight. Obstet Gynecol 1997;90:600–5.[Abstract]

9. Williams MA, Goldman MB, Mittendorf R, Monson RR. Subfertility and the risk of low birth weight. Fertil Steril 1991;56:668–71.[Medline]

10. Moise J, Laor A, Armon Y, Gur I, Gale R. The outcome of twin pregnancies after IVF. Hum Reprod 1998;13:1702–5.[Abstract/Free Full Text]

11. Chen SJ, Vohr BR, Oh W. Effects of birth order, gender, and intrauterine growth retardation on the outcome of very low birth weight in twins. J Pediatr 1993;123:132–6.[Medline]

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