1 Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Greece.
2 Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
3 University of Massachusetts Cancer Center, Worcester, MA, USA.
4 Department of Epidemiology, School of Public Health, Shanghai Medical University, Shanghai, China.
5 Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
Correspondence: Dimitrios Trichopoulos, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. E-mail: dtrichop{at}hsph.harvard.edu
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Abstract |
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Methods In the context of a cohort study, 296 Caucasian pregnant women in Boston, USA and 329 Chinese pregnant women in Shanghai, China were followed to term. Birth size characteristics of the baby and maternal anthropometry were measured using standardized protocols. Analyses were conducted through multiple regression procedures.
Results No significant difference was found between US and Chinese newborns with respect to gestational age. Among US women, pregravid oral contraceptive use was strongly associated with higher birthweight. In both US and Chinese women, birthweight was positively associated with height, pre-pregnancy body mass index, and weight gain during pregnancy. More importantly, the difference in these three maternal variables between the two samples fully explains the birthweight difference between the two populations.
Conclusions We postulate that babies in China may have lower birthweight because their mothers anthropometry imposes constraints on the growth of the fetus. When Chinese women migrate to the US, they tend to grow taller and heavier so that their babies can reach, on the average, a higher birthweight. The recurrence of this process in successive generations could explain why eventually Chinese Americans tend to have comparable birth and adult anthropometric characteristics, as well as comparable breast cancer rates, to those of Caucasian Americans.
Accepted 13 June 2002
There is a vast literature concerning determinants of gestational duration and intrauterine growth.15 Most of the literature focuses on determinants and means of prevention of preterm birth and/or intrauterine growth retardation, which can affect survival as well as development in childhood.6 During the last 20 years, however, there has also been interest in the possibility that perinatal events and conditions, intimately linked to birth size parameters, may have long-term consequences on the occurrence of common diseases in adulthood, including cardiovascular diseases and some forms of cancer, particularly breast cancer.79
We have compared determinants of birthweight using an identical protocol in two populations, one Caucasian in Boston, USA and the other Chinese in Shanghai, China. Our objective was to gain insight into the causes of birthweight difference between these populations and the way this difference may be related to the contrasting incidence of breast cancer in the two populations.
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Materials and Methods |
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Baseline demographic information was abstracted from the medical records of consenting participants at the 16th week visit. In both Boston and Shanghai gestational age was defined as the time since the first day of the last menstrual period. At the 27th week visit, an authorized health professional conducted a confidential interview with the study participant and abstracted relevant routine data from her records. Maternal characteristics included the womans age (years), weight before pregnancy (kg), height (cm), body mass index (BMI) (kg/m2), education (up to high school or more than high school), and previous live birth (yes, no). Characteristics related to the pregnancy were also recorded. These included the weight gained by the time of the two visits (kg), history of smoking, coffee, tea and alcohol consumption, and administration of antibiotics during pregnancy. At delivery, the placenta was weighed (g) before discarding; additional information concerning the delivery and the newborn was ascertained from medical records and paediatric charts. This included total gestation duration (weeks), birthweight (g), birth length (cm), head circumference (cm), and gender. Information concerning questionnaire administration and medical record reviewing has also been given in an earlier publication.10 Smoking during pregnancy was coded as current smoker during pregnancy versus not current smoker during pregnancy. Caffeine intake was computed summing caffeine contents from daily intake of cups of coffee and tea together. Pre-eclampsia was based on physicians diagnosis of this condition during pregnancy and urogenital infection was determined from the existence of a cervical or bladder infection.
The statistical analysis initially relied on simple cross-tabulations. Subsequently, birthweight was evaluated as a continuous variable through multiple linear regression. Analyses were undertaken first within study centre, that is, separately for Caucasian and Asian women. Direct comparison between the two study sites was performed with adjustment for different covariates. The analyses were conducted using SAS Software version 8.0.
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Results |
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Discussion |
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The present study is of moderate size, but the statistical power was sufficient to allow documentation of the important findings concerning maternal anthropometry in relation to birthweight. The data were collected in a standardized way and with an identical protocol in the two settings. There is also no evidence for the operation of important biases, since the findings were generally compatible with those reported by other investigators and those expected from the socio-cultural environment in the two populations.15
The results of our study complement those of an earlier paper by Wen and colleagues.11 These authors have compared birthweight distributions between Chinese and Caucasian infants and found that the lower mean birthweight in Chinese infants is due to slower fetal growth towards the end of the third trimester. We postulate that Chinese babies in China have lower birthweight because the lower height and pre-pregnancy BMI of their mothers imposes constraints on the growth of the fetus towards the end of the pregnancy. The literature concerning changes in somatometry and particularly birthweight among Chinese and Chinese migrating to the US is limited.1214 The existing evidence, however, suggests that when Chinese women migrate to the US, they tend to grow taller and heavier and their babies tend to have higher birthweight.1114 This is likely to recur in successive generations, so that eventually Chinese Americans have comparable anthropometric characteristics to Caucasian Americans and, indeed, comparable breast cancer rates.1517
Established adult life risk factors for breast cancer explain little of the more than fourfold difference in the incidence of this disease between the US and China.18 This has led to the hypothesis that early life events and conditions may influence subsequent risk for breast cancer.19,20 Birthweight has been associated with breast cancer risk in a number of studies,2123 but the breast cancer risk gradient in relation to birthweight is again too limited to explain the difference in breast cancer incidence between the US and China or Japan. It has been hypothesized, however, that a critical determinant of breast cancer risk may be mammary gland mass, which is indeed considerably larger among Caucasians than among Chinese.20,24 Indeed, mammary gland mass is likely to be a predictor of the number of immature mammary cells that are susceptible to carcinogenic initiation.24 In ethnic contrasts, but not necessarily in individual intra-ethnic comparisons, birthweight may be related to mammary gland mass in a non-linear way, so that small differences in birthweight (and pre-adolescence growth patterns) generate large differences in mammary gland mass in adult life. In this context and in an admittedly speculative way, our study provides support to the ideas that perinatal influences and mammary gland mass are important determinants of adult life breast cancer risk. Indeed, our findings could allow an explanation of the pattern of increase of breast cancer incidence among the Asian Americans over successive generations.16,17 The cycle whereby bigger women give birth to bigger babies who, in turn, may have a larger pool of stem cells for mammary gland development in adolescence is compatible with the increasing trends in breast cancer incidence that have been noted in most populations during periods of economic growth and prosperity.25
KEY MESSAGES
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Acknowledgments |
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References |
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2 Kramer MS, Olivier M, McLean F, Dougherty GE, Willis DM, Usher RH. Determinants of fetal growth and body proportionality. Pediatrics 1990;86:1826.[Abstract]
3 Shiono PH, Behrman RE. Low birth weight: analysis and recommendations. The Future of Children 1995;5:418.[Medline]
4 Paneth NS. The problem of low birthweight. The Future of Children 1995;5:1934.[Medline]
5 Rall Chomitz V, Cheung LWY, Lieberman E. The role of lifestyle in preventing low birth weight. The Future of Children 1995;5:12138.[Medline]
6 Hack M, Klein NK, Gerry Taylor H. Long-term developmental outcomes of low birth weight infants. The Future of Children 1995;5: 17696.[Medline]
7 Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet 1989;2:57780.[ISI][Medline]
8 Signorello LB, Trichopoulos D. Perinatal determinants of adult cardiovascular disease and cancer. Scand J Soc Med 1998;26:16165.[ISI][Medline]
9 Potischman N, Troisi R. In-utero and early life exposures in relation to risk of breast cancer. Cancer Causes Control 1999;10:56173.[CrossRef][ISI][Medline]
10 Lipworth L, Hsieh CC, Wide L et al. Maternal pregnancy hormone levels in an area with a high incidence (Boston, USA) and in an area with a low incidence (Shanghai, China) of breast cancer. Br J Cancer 1999;79:712.[CrossRef][ISI][Medline]
11 Wen SW, Kramer MS, Usher RH. Comparison of birth weight distributions between Chinese and Caucasian infants. Am J Epidemiol 1995; 141:117787.[Abstract]
12 Wang X, Guyer B, Paige DM. Differences in gestational age-specific birthweight among Chinese, Japanese and white Americans. Int J Epidemiol 1994;23:11928.[Abstract]
13 Singh GK, Yu SM. Birthweight differentials among Asian Americans. Am J Public Health 1994;84:144449.[Abstract]
14 Zhang B, Yip R, Wen F, Wang B. Comparison of birth weight by gestational age between China and the United States. Chin Med J (Engl) 1997;110:14851.[ISI][Medline]
15 Trichopoulos D, Yen S, Brown J, Cole P, MacMahon B. The effect of westernization on urine estrogens, frequency of ovulation, and breast-cancer riska study of ethnic Chinese-women in the orient and the USA. Cancer 1984;53:187192.[ISI][Medline]
16 Ziegler RG, Hoover RN, Pike MC et al. Migration patterns and breast-cancer risk in Asian-American women. J Natl Cancer Inst 1993;85: 181927.[Abstract]
17 Ziegler RG, Hoover RN, Nomura AMY et al. Relative weight, weight change, height, and breast cancer risk in Asian-American women. J Natl Cancer Inst 1996;88:65060.
18 Hsieh C-C, Trichopoulos D, Katsouyanni K, Yuasa S. Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study. Int J Cancer 1990;46:796800.[ISI][Medline]
19 Trichopoulos D. Hypothesis: Does breast cancer originate in utero? Lancet 1990;335:93940.[ISI][Medline]
20 Adami H-O, Signorello LB, Trichopoulos D. Towards an understanding of breast cancer etiology. In: Adami H-O, Trichopoulos D (eds). Progress and enigmas in cancer epidemiology. Seminars in Cancer Biology 1998;8:25562.[CrossRef][ISI][Medline]
21 Ekbom A, Trichopoulos D, Adami HO, Hsieh CC, Lan SJ. Evidence of prenatal influences on breast cancer risk. Lancet 1992;340:101518.[ISI][Medline]
22 Michels KB, Trichopoulos D, Robins JM et al. Birthweight as a risk factor for breast cancer. Lancet 1996;348:154246.[CrossRef][ISI][Medline]
23 Vatten LJ, Maehle BO, Lund Nilsen TI et al. Birth weight as a predictor of breast cancer: a case-control study in Norway. Brit J Cancer 2002; 86:8991.[CrossRef][ISI][Medline]
24 Trichopoulos D, Lipman R. Mammary gland mass and breast cancer risk. Epidemiology 1992;3:52326.[ISI][Medline]
25 World Health Organization, Regional Office for Europe. Health for All Database. WHO, Copenhagen, 1999.