American Journal of Epidemiology Advance Access originally published online on March 6, 2007
American Journal of Epidemiology 2007 165(10):1216-1218; doi:10.1093/aje/kwm024
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ORIGINAL CONTRIBUTIONS |
Human Sexual Size Dimorphism in Early Pregnancy
1 Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX
2 Department of Obstetrics and Gynecology, University of Cambridge, Cambridge, United Kingdom
3 Department of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland, Dublin, Ireland
4 Department of Obstetrics and Gynecology, University of Utah and Intermountain HealthCare, Salt Lake City, UT
5 The Fetal & Women's Center of Arizona, Scottsdale, AZ
6 Department of Fetal Imaging, William Beaumont Hospital, Royal Oak, MI
7 Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY
8 Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY
9 Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, CO
10 Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA
11 Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY
12 Department of Obstetrics and Gynecology, Brown University School of Medicine, Providence, RI
13 Department of Obstetrics and Gynecology, University of North Carolina Medical Center, Chapel Hill, NC
Correspondence to Dr. Radek Bukowski, Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555-1062 (e-mail: rkbukows{at}utmb.edu).
Received for publication August 21, 2006. Accepted for publication November 15, 2006.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Sexual size dimorphism is thought to contribute to the greater mortality and morbidity of men compared with women. However, the timing of onset of sexual size dimorphism remains uncertain. The authors determined whether human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. Using a prospective cohort study, conducted in 1999–2002 in the United States, they identified 27,655 women who conceived spontaneously and 1,008 whose conception was assisted by in vitro fertilization or intrauterine insemination and for whom a first-trimester measurement of fetal crown-rump length was available. First-trimester size was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. The authors evaluated the association between fetal sex, first-trimester size, and birth weight. Eight to 12 weeks after conception, males were larger than females (mean difference: assisted conception = 0.4 days, 95% confidence interval (CI): 0.1, 0.7, p = 0.008; spontaneous conception = 0.3 days, 95% CI: 0.2, 0.4, p < 0.00001). The size discrepancy remained significant at birth (mean birth weight difference: assisted conception = 90 g, 95% CI: 22, 159, p = 0.009; spontaneous conception = 120 g, 95% CI: 107, 132, p < 0.00001). These data demonstrate that human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy.
cohort studies; fetal development; pregnancy
Abbreviations: ASC, assisted conception (pregnancies resulting from conception assisted by in vitro fertilization or intrauterine insemination); CI, confidence interval;
GA, the difference in days of gestation; SPON, spontaneous conception |
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Sexual size dimorphism is a feature of humans and nonhuman primates and is thought to contribute to the greater mortality and morbidity of men compared with women (1, 2). Across populations and races, men are approximately 8 percent taller and their longevity 8 percent shorter than that of women (3). Across species, longevity of the larger of the sexes is shorter (4). Animal studies have also demonstrated that male bias in mortality disappears after adjustment for weight difference between sexes (5). The association between sexual size dimorphism and longevity is biologically plausible because larger body size requires more cell divisions, which results in shorter telomere length. In turn, shorter telomere length is inversely related to mortality in humans (6). Compatible with this hypothesis, men have shorter telomeres and longevity than do women (6, 7). The onset of sexual size dimorphism in the human is unknown. Previous studies have suggested that birth weight is determined, at least in part, in the first 12 weeks after conception (8). Here, we show that human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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We analyzed data for 27,655 women who conceived spontaneously (SPON) and 1,008 who conceived as a result of conception assisted by in vitro fertilization or intrauterine insemination (ASC) from a previously described, prospective cohort study conducted in 1999–2002 in the United States (9). The ASC and SPON pregnancies were assessed separately to determine the effect of uncertainty regarding menstrual dating. Women in this cohort were followed throughout pregnancy, and data on pregnancy outcome, including birth weight, were collected prospectively. All pregnancies ended in livebirth of a singleton infant without evidence of chromosomal or congenital abnormality. Other fetal or maternal complications were not excluded. We measured fetal crown-rump length 8–12 weeks after conception by using ultrasound. All measurements were performed by specially trained ultrasound technicians according to a standardized protocol (10), and gestational age estimates were centrally calculated by using Hadlock criteria (11).
The observed size of the embryo or fetus was related to the expected size on the basis of the date of conception (estimated as 14 days after the first day of the last menstrual period for SPON pregnancies and precisely known for ASC pregnancies). The difference between the actual and predicted crown-rump length was expressed as the difference in days of gestation ( GA), that is, the estimated postconception age according to crown-rump length minus the estimated number of days after conception. Positive GA values indicate a larger than expected fetus and negative values a smaller than expected fetus. We confined analysis of SPON pregnancies to those with a GA of between –7 and 7 days because differences outside this range more likely reflect error in menstrual dating. The associations between GA, fetal sex, and birth weight were modeled by using multivariable linear regression with fractional polynomials to assess linearity. The large size and composition of the study population from low-risk pregnancies enrolled in 15 centers representing all major geographic areas of the United States assure its representativeness and generalizability of the findings.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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There were 28,663 pregnancies; 3.5 percent were considered ASC, and 51.1 percent of the fetuses were male. Eight to 12 weeks after conception, male fetuses were larger than females (mean difference: ASC = 0.4 days, 95 percent confidence interval (CI): 0.1, 0.7, p = 0.008; SPON = 0.3 days, 95 percent CI: 0.2, 0.4, p < 0.0001). The size discrepancy remained significant at birth (mean birth weight difference: ASC = 90 g, 95 percent CI: 22, 159, p = 0.009; SPON = 120 g, 95 percent CI: 107, 132, p < 0.0001) (figures 1 and 2). The association between
GA and fetal sex was not materially affected by adjustment for maternal height, weight, parity, race, gestational age at delivery, and smoking status (adjusted coefficient: ASC = 0.4 days, 95 percent CI: 0.1, 0.7, p = 0.015; SPON = 0.3 days, 95 percent CI: 0.3, 0.4, p < 0.0001).
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, mean; thick T-shaped lines, standard deviation) and female (•, mean; thin T-shaped lines, standard deviation) fetuses and the fitted values from multivariable linear regression (dashed line, females; solid line, males) are plotted for each day of
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Previous studies have suggested that placental function in the first trimester of pregnancy is an important determinant of fetal growth, preterm birth, and risk of stillbirth (8, 12). Consistent with this finding, periconceptual manipulation of maternal diet alters the outcome of ovine pregnancy (13). Our data demonstrate that sexual size dimorphism is evident in the human fetus in the first trimester of pregnancy. We conclude that sex-dependent effects on size-related differences in morbidity and mortality in adult life (1, 2, 14) may be determined in the first weeks after conception.
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ACKNOWLEDGMENTS |
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The First and Second Trimester Evaluation of Risk for Fetal Aneuploidy–FASTER Research Consortium was funded by the National Institute of Child Health and Human Development, grant RO1 HD 38652.
Conflict of interest: none declared.
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References |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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- Samaras TT, Storms LH, Elrick H. Longevity, mortality and body weight. Ageing Res Rev (2002) 1:673–91.[CrossRef][ISI][Medline]
- Kajantie E, Osmond C, Barker DJ, et al. Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000 person-years. Int J Epidemiol (2005) 34:655–63.
[Abstract/Free Full Text] - Samaras TT, Elrick H, Storms LH. Is height related to longevity? Life Sci (2003) 72:1781–802.[CrossRef][ISI][Medline]
- Promislow DE. On size and survival: progress and pitfalls in the allometry of life span. J Gerontol (1993) 48:B115–23.[ISI][Medline]
- Rollo CD. Growth negatively impacts the life span of mammals. Evol Dev (2002) 4:55–61.[CrossRef][ISI][Medline]
- Cawthon RM, Smith KR, O'Brien E, et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet (2003) 361:393–5.[CrossRef][ISI][Medline]
- Benetos A, Okuda K, Lajemi M, et al. Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension (2001) 37:381–5.[ISI][Medline]
- Smith GC, Stenhouse EJ, Crossley JA, et al. Early-pregnancy origins of low birth weight. Nature (2002) 417:916.[CrossRef][Medline]
- Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med (2005) 353:2001–11.
[Abstract/Free Full Text] - Malone FD, D'Alton ME. First-trimester sonographic screening for Down syndrome. Obstet Gynecol (2003) 102:1066–79.
[Abstract/Free Full Text] - Hadlock FP, Shah YP, Kanon DJ, et al. Fetal crown-rump length: reevaluation of relation to menstrual age (5–18 weeks) with high-resolution real-time US. Radiology (1992) 182:501–5.
[Abstract/Free Full Text] - Smith GC, Stenhouse EJ, Crossley JA, et al. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab (2002) 87:1762–7.
[Abstract/Free Full Text] - Bloomfield FH, Oliver MH, Hawkins P, et al. A periconceptional nutritional origin for noninfectious preterm birth. Science (2003) 300:606.
[Free Full Text] - Barker DJ, Winter PD, Osmond C, et al. Weight in infancy and death from ischaemic heart disease. Lancet (1989) 2:577–80.[ISI][Medline]
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