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ORIGINAL RESEARCH |
From the *Pregnancy and Perinatology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland; Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Bethesda, Maryland; and Infant, Child and Women's Health Statistics Branch, National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Georgia.
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ABSTRACT |
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METHODS: We analyzed 51,783 pregnancies (561 twin) in the Collaborative Perinatal Project, which took place at 12 hospitals in the United States from 1959 to 1966. The occurrence of twinning was compared according to maternal self-reported prepregnant body mass index (BMI) of less than 20, 20–24.99, 25–29.99, and 30 kg/m2 or greater, before and after adjustment for confounding factors.
RESULTS: There was a statistically significant trend for increased risk of total twinning with increasing BMI (P < .001). The odds of monozygous twinning were not significantly related to BMI, but the odds of dizygous twinning were significantly related to increased BMI. After adjusting for maternal race, age, parity, and height, the odds of dizygous twinning were still significantly elevated among women with a BMI of 30 or more, and the trend for increasing risk of dizygous twinning with increasing BMI was significant (P = .001). The trend for increased twinning with increasing height was also significant. Women in the tallest quartile of height had a significantly increased odds ratio for dizygous twin pregnancies, although not of the same magnitude as women with BMI over 30.
CONCLUSION: We confirmed the association of maternal weight and height with dizygotic twinning in a U.S. population among which fertility drugs were not a factor.
LEVEL OF EVIDENCE: II-2
Increasing use of fertility drugs is considered the primary cause of the recent increase in dizygotic twinning in most developed countries. However, a recent report from a Danish population indicates that twinning is more common among obese than nonobese women. Basso et al,16 in analyzing the Danish National Birth Registry, had to make assumptions regarding fertility treatments and the zygosity of like-sex twins. Because obesity has become more prevalent among reproductive-aged women over the past several decades,17,18 this association is of considerable public health importance. Therefore, we sought to confirm this relationship in a U.S. cohort of pregnancies that occurred before the widespread use of fertility drugs and in which zygosity was determined for the vast majority of twins.
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MATERIALS AND METHODS |
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Demographic, socioeconomic, medical, genetic/familial, and behavioral information on the women, including self-reported height and prepregnant weight (in inches and pounds, respectively) were collected at entry into the study. They were then converted to metric units and used to calculate BMI as weight in kilograms divided by the square of height in meters. Maternal BMI was divided into the same 4 categories used by Basso et al:16 less than 20, 20–24.99, 25–29.99, and 30 or greater. Women with a BMI less than 20 served as the reference group. To examine the effect of height independently of BMI, the same analysis was performed with quartiles of height in centimeters as the independent variable.
We used multiple logistic regression to analyze the relationship between several maternal characteristics as independent variables and the plurality of the pregnancy (twin or singleton) as the dependent variable, controlling for confounders. In addition, information on zygosity, determined by a combination of gender, placental pathology, and analysis of nine blood groups20 was available for 81% of twin records. Therefore, the outcome of twinning, was further classified as monozygous or dizygous twin pregnancy. Chi-squared test for trend21 was used to examine distributions of maternal characteristics across BMI categories. These characteristics included maternal race (black, other), maternal age (continuous in years), parity (nulliparous, multiparous), and height (in quartiles). Women could have had more than one pregnancy represented in the database. To adjust for the nonindependence of repeated pregnancies to the same woman in the Collaborative Perinatal Project, generalized estimating equations22 were used to obtain odds ratios and 95% confidence intervals through use of PROC GENMOD in SAS 8.1 (SAS Institute, Cary, NC).
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RESULTS |
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The effect of maternal height on twinning was not as strong as that of BMI (Table 3). There was no linear trend in odds ratios with increasing maternal height for monozygous twin pregnancies (P = .25). However, women in the tallest quartile of height had a significantly increased odds ratio for dizygous twin pregnancies, although not of the same magnitude as women with BMI over 30. The trend for increased twinning with increasing height was also significant (P = .01). Adjustment for maternal age, race, parity, and BMI had little effect on the odds ratios for maternal height.
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DISCUSSION |
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Between 1980 and 2002, the twin birth rate increased by 65% (from 18.9 to 31.1 per 1,000 live births or from 1.9% to 3.1% of all births) in the United States.24 An estimated one third of the increase in multiple births since the late 1970s and early 1980s has been attributed to the shift in maternal age distribution; the remainder is assumed to be the result of increased use of ovulation-inducing drugs and assisted reproductive technologies.25 Unlike triplets and other higher order multiples, where 70% are attributable to the use of ovulation-inducing drugs and assisted reproduction, only 18–34% of twin births can be attributed to these factors.26
The biologic association of maternal weight with dizygotic twinning may be mediated through elevated follicle-stimulating hormone (FSH) levels. Increased FSH concentrations have been demonstrated in women with an increased rate of dizygotic twinning.27,28 This rise in FSH is consistent with the increased occurrence of dizygotic twinning with the use of fertility drugs, which mimic naturally occurring elevated gonadotropins. Spontaneous dizygotic twinning is increased in certain families and is associated with raised concentrations of FSH.29 The mean FSH levels are highest in women who have had 2 sets of twins previously, intermediate in women who have had only 1 set of twins, and lowest in non–twin-prone women who have had singletons only.6 Spontaneous dizygotic twinning has been noted to decrease with both urbanization and starvation. FSH levels also increase with age and account for part of the maternal age effect.30 However, we are unaware of any direct relationship between obesity and elevated FSH.
Twins are at increased risk for a variety of adverse pregnancy outcomes and have significantly increased perinatal morbidity and mortality compared with singletons9,31 This report confirms the association of maternal weight and dizygotic twinning in the U.S. population, in the absence of fertility drugs. The influence of maternal weight as a factor for twinning will continue to grow in importance as the percentage of obese women in the United States continues to rise.
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Footnotes |
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Address reprint requests to: Uma M. Reddy, MD, MPH, 6100 Executive Boulevard, Room 4B03F, Bethesda, MD 20892–7510; e-mail: reddyu{at}mail.nih.gov.
Received August 13, 2004. Received in revised form October 27, 2004. Accepted December 2, 2004.
doi:10.1097/01.AOG.0000153491.09525.dd
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REFERENCES |
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