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To the Editor: Rates of twinning declined from the 1950s through the 1970s in many countries^1-2 even after controlling for age and parity² but began to increase again in the 1980s.¹ Monozygotic twinning is considered an essentially random event with constant rates around the world, although recent evidence suggests that it may be more likely among women undergoing infertility treatment.¹ Changes in twinning rates are thus largely attributable to dizygotic twinning, which is influenced by maternal age, race, family history,^{1, 3} and, possibly, height and weight.^3-4 Widespread use of infertility drugs is presumably the main cause of the recent increase in dizygotic twinning in most industrialized countries.¹ We examined the relationship between twinning and maternal height and body mass index (BMI) in a large national cohort.

Methods
We used the Danish National Birth Registry to identify 62 073 singleton and twin births from the 24th gestational week occurring between 1998 and 2001 to women participating in the Danish National Birth Cohort,⁵ a nationwide study that enrolled women early in pregnancy and that was approved by the National Scientific Ethics Committee. About 60% of all eligible women were informed about the study, depending on the cooperation of general practitioners, and about 60% agreed to participate. The overall rate of twinning in the cohort was 2.2%, close to the national rate of 2.0% for the same period.⁶

Information on maternal height and prepregnancy weight was reported in an interview during the second trimester of pregnancy and was missing for 989 births (1.6%), which we excluded. We excluded all but the most recent pregnancy for the 1798 women who had more than 1 birth during the study period (n = 1801 pregnancies). Among women who reported taking longer than 6 months to conceive, we exluded 3816 who also reported having received infertility treatment. We thus analyzed 55 467 births.

We used multivariable logistic regressions to analyze the relationships between BMI and height among all twins, as well as just among opposite-sex twins. The latter subset would include only dizygotic twins. Each model included BMI, height, mother's age, and parity, all treated as categorical variables. Information on sex was missing for 9 twin pairs and 160 singletons (due to stillbirth). Information on parity was missing for 32 cases, which were thus excluded in the multivariable analyses. We divided height into quartiles and for BMI we chose 20 instead of 18.5 as the cut point for lean women in order to include in this category a sufficient number of twins to produce reliable estimates.

Results
The twinning rate was 1.3% among women who did not report infertility treatment and 15.5% among women who did. Treated women had a higher BMI than those not reporting treatment. However, among women taking longer than 1 year to conceive there was no significant difference in the distribution of BMI between treated (n = 3264) and untreated (n = 4535) individuals (²₃ = 1.56, P = .67).

Increasing BMI and height correlated with twinning among untreated women (Table 1), even after multivariable adjustment (Table 2). The association with BMI was slightly stronger when examining only opposite-sex twins.

View this table: [in this window] [in a new window] Table 1. Frequency of Twins (per 1000 Births) as a Function of Height (Quartiles) and Body Mass Index Among Women Not Reporting Infertility Treatment

View this table: [in this window] [in a new window] Table 2. Adjusted Odds of Twinning as a Function of BMI and Height (Quartiles) Among Women Not Reporting Infertility Treatment

Because cycle abnormalities may reflect hormonal disturbances, we repeated the analysis among the 40 389 women (with 557 twin deliveries) who reported regular menstrual cycles (26-30 days). Compared with a BMI of 20 to 24.9, the odds ratio associated with a BMI below 20 was 0.71 (95% confidence interval [CI], 0.54-0.92) and that associated with a BMI of 30 or more was 1.39 (95% CI, 1.05-1.84).

In Denmark, stillbirths are registered after 28 completed gestational weeks. Earlier deliveries in which 1 twin is stillborn thus may be wrongly registered as singleton. When we included only live births (55298 deliveries with 708 twin pairs), the odds ratios were 0.72 (95% CI, 0.57-0.91) and 1.44 (95% CI, 1.13-1.83) for women with a BMI below 20 and those with a BMI of 30 or more, respectively, compared with women with a normal BMI.

Comment
We found that a BMI of less than 20 was associated with a lower risk of twinning, and that a BMI of 30 or more was associated with a higher risk. The association was slightly stronger for opposite-sex twins. We found a similar trend for height.

Given the widespread increase in obesity, especially in developed countries,^7-8 this association may explain part of the observed increase in twinning. In the early 1960s, 9.3% of US women aged 20 to 39 years had a BMI of 30 or more, but this proportion increased to 28.4% in 1999-2000.⁸ In Denmark, the proportion of women with a BMI of 30 or more in the general population increased from 5.5% in 1987 to 9.5% in 2000.⁹

Treatment of some obese women who might have conceived naturally could alter the magnitude of the association, but probably not to any large degree. Furthermore, the BMI-twinning association had been reported when use of infertility drugs was not as widespread.^3-4

Funding/Support: Dr Basso is supported by a grant from the Danish Medical Research Council (No. 22-00-0008). The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, and the Augustinus Foundation.

Role of the Sponsors: The Danish Medical Research Council, the Danish National Research Foundation, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, and the Augustinus Foundation played no role in the study design; in the collection, analysis, or interpretation of data; or in the writing and the decision to submit the manuscript for publication.

Olga Basso, MD, PhD
ob{at}soci.au.dk

Ellen Aagaard Nohr, MHS
Danish Epidemiology Science Centre
University of Århus
Århus, Denmark

Kaare Christensen, MD, PhD
Epidemiology, Institute of Public Health, and the Danish Twin Registry
University of Southern Denmark
Odense

Jørn Olsen, MD, PhD
Danish Epidemiology Science Centre
University of Århus

1. Tong S, Short RV. Dizygotic twinning as a measure of human fertility. Hum Reprod. 1998;13:95-98. FREE FULL TEXT 2. Rachootin P, Olsen J. Secular changes in the twinning rate in Denmark 1931 to 1977. Scand J Soc Med. 1980;8:89-94. WEB OF SCIENCE | PUBMED 3. MacGillivray I, ed, Campbell DM, ed, Thompson B, ed. Twinning and Twins. London, England: John Wiley & Sons; 1988. 4. Hemon D, Berger C, Lazar P. The etiology of human dizygotic twinning with special reference to spontaneous abortions. Acta Genet Med Gemellol (Roma). 1979;28:253-258. PUBMED 5. Olsen J, Melbye M, Olsen SF, et al. The Danish National Birth Cohort—its background, structure and aim. Scand J Public Health. 2001;29:300-307. FULL TEXT | WEB OF SCIENCE | PUBMED 6. Dansk Selskab for Obstetrik og Gynekologi (Danish Society of Obstetrics and Gynecology) Web site. Available at: http://www.dsog.dk/. Accessed February 25, 2004. 7. Seidell JC, Flegal KM. Assessing obesity: classification and epidemiology. Br Med Bull. 1997;53:238-252. FREE FULL TEXT 8. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002;288:1723-1727. FREE FULL TEXT 9. Danish Institute of Public Health. The Danish Health and Morbidity Survey 2000: summary. Available at: http://susy.si-folkesundhed.dk/menu.asp. Accessed February 18, 2004.

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2004;291:1564-1566.

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