Familial Aggregation of Fetal Growth Restriction in a French Cohort of 7,822 Term Births between 1971 and 1985
Agnès La Batide-Alanore1,
David-Alexandre Trégouët1,
Delphine Jaquet2,
Jean Bouyer3 and
Laurence Tiret1
1 INSERM U525, Paris, France.
2 INSERM U457, Paris, France.
3 INSERM U292, Villejuif, France.
Received for publication November 5, 2001; accepted for publication March 14, 2002.
 |
ABSTRACT
|
---|
An association between fetal growth restriction and increased rates of metabolic and cardiovascular diseases in adulthood has been reported. This study evaluated familial aggregation of fetal growth restriction in term births. The population consisted of 3,505 sibships comprised of 7,822 full-term singleton infants born between 1971 and 1985 in Haguenau, France, and selected from a regional register of births. Sib-sib odds ratios were estimated for being born small for gestational age (SGA), defined as having a birth weight below the 10th percentile of the sex-specific curve of birth weight by week of gestation. SGA births were further stratified according to ponderal index (birth weight/length3). After adjustment for maternal factors, the sib-sib odds ratios were 4.8 (95% confidence interval (CI): 3.7, 6.3) for all SGA births, 7.7 (95% CI: 4.1, 14.7) for SGA births with a low ponderal index (<10th percentile), and 4.4 (95% CI: 2.3, 8.2) for SGA births with a normal ponderal index (25th75th percentile). None of the maternal factors investigated significantly influenced the magnitude of these odds ratios. This strong residual sib-sib aggregation suggests a role for genetic and/or shared environmental factors in the etiology of fetal growth restriction, especially when associated with a low ponderal index. Am J Epidemiol 2002;156:1807.
birth weight; family; fetal growth retardation; gestational age
Abbreviations:
Abbreviations: CI, confidence interval; EE, estimating equation; IUGR, intrauterine growth restriction; OR, odds ratio; SGA, small for gestational age.
 |
INTRODUCTION
|
---|
While considerable progress has been made during the past decades in reducing perinatal mortality and morbidity, the report about 10 years ago by Barker et al. (1) of an association between low birth weight and increased rates of cardiovascular and metabolic disorders in adulthood casts new light on the problem of consequences of intrauterine growth restriction (IUGR). Although this association has been largely confirmed since then (210), no definitive explanation has been proposed. Although Barker et al. initially interpreted this association as the consequence of intrauterine programming of the fetus in response to maternal undernutrition (3), McCance et al. (4), 1 year later, rather favored a genetic contribution. Despite a large quantity of literature during the past 10 years, the environmental versus genetic hypothesis is still a matter of debate. Several recent reports support the role of genetic factors in influencing the association between IUGR and complications in later life (1113). It was recently proposed that IUGR and metabolic complications in adult life might be due to phenotypes of the same insulin-resistant genotype (14).
The hypothesis of a genetic contribution common to fetal growth restriction and adult complications would imply familial recurrence of IUGR. In epidemiologic studies, IUGR is generally defined as low birth weight for gestational age. Several studies have shown a tendency in mothers to give birth to small-for-gestational-age (SGA) babies in successive pregnancies (1518) and a higher risk of low birth weight among infants born to mothers of low birth weight themselves (1821). While extrinsic maternal factors, such as pregnancy-associated hypertension and smoking, are now well-recognized risk factors for SGA births, the role of genetic factors in controlling in utero growth is less well established.
Knowledge of the extent of familial aggregation of IUGR is a preliminary step in trying to identify genetic factors. We evaluated familial aggregation of SGA births in a large population-based register of live infants born at term, before and after we adjusted for maternal characteristics. Since, besides birth weight, body proportions at birth have been shown to influence the risk of adult disease (3, 6, 8, 10, 22), we also took into account ponderal index to refine the familial risk.
 |
MATERIALS AND METHODS
|
---|
The study population was selected from a population-based register including more than 20,000 pregnancies recorded between 1971 and 1985 in the metropolitan area of the city of Haguenau, France (23). The ascertainment rate of the register was greater than 80 percent. For the present study, the sample was restricted to European, singleton livebirths without evidence of intrauterine infection, chromosomal abnormalities, or other major malformations. To exclude the effect of prematurity, only those infants born after 3742 weeks of gestation were selected. Since the study focused on familial aggregation of SGA births, the sample was restricted to infants belonging to sibships with at least two siblings, linked by the mothers identification number in the register. The study sample included 7,822 siblings belonging to 3,505 sibships.
Since growth standards for the population of Haguenau were different from those for France in general because of the large number of Germanic people living in the city, SGA births were defined by using local standards for birth weight derived from all livebirths over the 15-year period covered by the register. Gestational age was determined from the date of the mothers last menstrual period and by physical examination during pregnancy, and it was confirmed by ultrasound measurements when available. Being SGA was defined as having a birth weight below the 10th percentile of the sex-specific curve of birth weight by week of gestation. Ponderal index was calculated as birth weight/length3; percentiles of ponderal index by week of gestation were derived from all singleton livebirths recorded in the register. Subgroups of SGA births with a low ponderal index (<10th percentile) and a normal ponderal index (25th75th percentiles) were defined further.
Maternal characteristics were recorded by using a standardized questionnaire. Data were taken from the medical follow-up records of pregnancy, and mothers were identified by a register number linking their different pregnancies. The database did not include any personal identifier. Height and educational level (university vs. others) were recorded at the first pregnancy and were assumed to remain constant over time. Maternal age was recorded at each delivery. Prepregnancy weight, cigarette smoking (yes or no) during pregnancy, marital status (unmarried or married), primiparity (yes or no), and hypertension were defined for each pregnancy. Pregnancy-associated hypertension was defined as a systolic/diastolic blood pressure of more than 140/90 mmHg or by the use of an antihypertensive treatment during pregnancy.
Statistical analysis was performed by using SAS software (SAS Institute, Inc., Cary, North Carolina). Since persons within families are statistically not independent, conventional statistical methods could not be used; therefore, linear regression analyses were performed by using the estimating equation (EE) technique as implemented in the SAS/GENMOD procedure. Familial aggregation of SGA births was expressed in terms of odds ratios. The sib-sib odds ratio was defined as the odds of a child being born SGA given that his or her sibling was born SGA, divided by the odds of a child being born SGA given that his or her sibling was not born SGA. Sib-sib odds ratios were estimated by using the EE technique extended to estimation of correlation parameters (24), referred to as EE2. The EE2 approach estimates marginal odds ratios (eventually adjusted for relevant factors) and their standard errors, estimations robust to a misspecification of the dependency between the different pairs of relatives in the same family. As is common in EE2 analysis, the dependencies between marginal odds ratios were modeled by using a Gaussian correlation structure (25). Because the marginal probability of being born SGA was different between the firstborn child and subsequent siblings and the odds ratios assume symmetry between siblings of the pair, crude odds ratios were systematically adjusted for primiparity. Odds ratios were further adjusted for maternal covariates and were additionally adjusted for study period to control for potential secular trends. For this purpose, the 15-year study period was divided into three 5-year periods. For analyses stratified according to low/normal ponderal index, the reference group was composed of non-SGA newborns whose ponderal index was normal (25th75th percentile). All EE2 analyses were performed by using a binary version of the EE2 program developed by our group, described previously (26, 27). Tests of hypothesis were conducted by use of generalized Wald test statistics. A p value of 0.05 was considered significant.
 |
RESULTS
|
---|
According to the definition adopted, 751 siblings (9.6 percent) were born SGA, of whom 231 (30.8 percent) had a normal ponderal index (25th75th percentile of the whole population) and 299 (39.8 percent) had a low ponderal index (<10th percentile of the whole population). Sibships that included a single sibling born SGA accounted for 13.6 percent of the 3,505 sibships, and those that included at least two siblings born SGA accounted for 3.6 percent (table 1). The prevalence of SGA births decreased over time, but this decrease was observed for multiparous mothers only, whereas the prevalence remained constant over time for primiparous mothers (table 2). The proportion of SGA births in which the ponderal index was low or normal did not vary significantly across the three study periods (table 2). Almost all maternal characteristics changed over time (table 2). However, at least for some variables, this change was mainly the consequence of the selection scheme restricting the sample to sibships with several siblings. This selection implied that primiparous women who gave birth to no subsequent child during the study period were excluded from the study sample (which explained the decrease in primiparity over time) and that the same mothers could be surveyed at different time periods for consecutive pregnancies (explaining the increase in mothers age and weight). In contrast, the decreasing prevalence of pregnancy-associated hypertension and the increasing proportion of mothers who smoked reflected true secular trends.
View this table:
[in this window]
[in a new window]
|
TABLE 1. Distribution of sibships according to size and number of siblings being born small for gestational age, Haguenau, France, 19711985
|
|
View this table:
[in this window]
[in a new window]
|
TABLE 2. Prevalence of small-for-gestational-age births and maternal characteristics according to study period, Haguenau, France, 19711985
|
|
As expected, children born SGA were smaller regarding all body measures than children born non-SGA (table 3). Mothers in the SGA group weighed less and had a shorter stature than mothers in the non-SGA group and were more often unmarried, primiparous, and smokers (table 3). Educational level and hypertension were not significantly associated with SGA status. All variables associated with SGA status in univariate analyses remained significant in multivariate analysis.
View this table:
[in this window]
[in a new window]
|
TABLE 3. Comparison of maternal and childs characteristics for children born small for gestational age and not small for gestational age, Haguenau, France, 19711985
|
|
We further subdivided the SGA and non-SGA groups according to the number of other SGA siblings in the sibship that included the newborn under consideration (table 3). For almost all variables, there was a marked trend indicating that maternal risk factors and sibling characteristics became less favorable as the number of SGA siblings increased. In particular, the proportion of mothers who smoked during pregnancy reached 41 percent in the group with multiple SGA siblings compared with 14 percent in the group with no SGA sibling, reflecting the strong impact of this factor on the recurrence of IUGR. In the SGA group, the prevalence of pregnancy-associated hypertension increased when the child born SGA was the only one in the sibship. Since, in most instances, he or she was the firstborn child, this finding reflected the strong role of hypertension in the etiology of IUGR in primiparous mothers.
Compared with children who had a normal ponderal index, those born SGA and having a low ponderal index were characterized by a lower birth weight and a smaller thorax perimeter but a longer length (table 4). The maternal characteristics most strongly associated with a low ponderal index were primiparity and pregnancy-associated hypertension. On the other hand, mothers who smoked during pregnancy had small babies whose ponderal index was normal (table 4). The mean ponderal index was 23.4 (standard deviation, 2.5) kg/m3 for SGA infants whose mothers were hypertensive versus 24.7 (standard deviation, 2.3) kg/m3 for those whose mothers smoked during pregnancy (p < 0.001).
View this table:
[in this window]
[in a new window]
|
TABLE 4. Comparison of maternal and childs characteristics for children born small for gestational age and having a low or a normal ponderal index, Haguenau, France, 19711985
|
|
We found a strong familial aggregation of SGA births, as indicated by the odds ratios estimated for the 3,505 sibships (table 5). The crude odds ratio for being born SGA was 6.6 (95 percent confidence interval (CI): 5.1, 8.6) and decreased only slightly to 4.8 (95 percent CI: 3.7, 6.3) after adjustment for maternal covariates and study period. Stratification according to ponderal index appeared to only strengthen the familial resemblance. The crude odds ratio for being born SGA and having a low ponderal index was 8.0 (95 percent CI: 4.5, 14.1), while the crude odds ratio for being born SGA and having a normal ponderal index was 10.1 (95 percent CI: 4.9, 20.7). After adjustment for maternal factors and study period, the odds ratio for being born SGA and having a low ponderal index remained nearly unchanged, whereas the odds ratio for being born SGA and having a normal ponderal index decreased strongly (table 5). This result indicated that the risk of recurrence of SGA births associated with a normal ponderal index was influenced more strongly by maternal factors than that of SGA births associated with a low ponderal index. When we examined the impact of each factor separately, smoking seemed to have the strongest influence on the familial aggregation of SGA births in which ponderal index was normal.
View this table:
[in this window]
[in a new window]
|
TABLE 5. Sib-sib odds ratios for being born small for gestational age, before and after adjustment for maternal characteristics and according to ponderal index, Haguenau, France, 19711985
|
|
We further examined whether some factors might influence the degree of sib-sib aggregation (table 6). Neither the delay between two consecutive pregnancies nor maternal characteristics significantly modified the sib-sib odds ratio. The only-borderline differences suggested that there was less of a resemblance between the firstborn child and any subsequent sibling than between two subsequent siblings (odds ratio (OR) = 4.2 vs. OR = 6.0, p < 0.10) and that the clustering was stronger in pairs in which the mother smoked than in pairs in which the mother did not smoke (OR = 9.9 vs. OR = 4.0, p < 0.10).
View this table:
[in this window]
[in a new window]
|
TABLE 6. Sib-sib odds ratios* for being born small for gestational age, according to different factors, Haguenau, France, 19711985
|
|
Because smoking and hypertension are two major extrinsic risk factors for SGA births, we reestimated the odds ratios after exclusion of all pregnancies in which the mother was either a smoker or hypertensive. In the remaining 2,194 sibships, the adjusted sib-sib odds ratio for being born SGA was hardly modified compared with the initial value (OR = 4.6, 95 percent CI: 3.2, 6.6).
Finally, we estimated the sib-sib odds ratio when considering a more stringent definition of the SGA status by taking into account a birth weight below the 5th percentile instead of the 10th percentile. The crude odds ratio was 8.0 (95 percent CI: 5.4, 11.7), but, after adjustment for maternal covariates and study period, it decreased to 4.9 (95 percent CI: 3.2, 7.4), a value close to that obtained when the 10th percentile was considered.
 |
DISCUSSION
|
---|
Our study provided an estimation of the familial aggregation of SGA births, further stratified according to body proportionality, a factor shown to influence the risk of later complications (3, 6, 8, 10, 22). Restriction of the study population to term births enabled us to rule out any confounding effect of prematurity itself or prematurity-associated morbidity. Major maternal factors influencing the risk of SGA birth were height and weight, primiparity, smoking, and unmarried status, as reported previously (28). Pregnancy-associated hypertension was not associated with outcome in our population when we considered SGA births as a whole. However, it was more frequent in primiparous women, as already known (29), and it significantly distinguished the groups of proportionally (normal ponderal index) and disproportionally (low ponderal index) SGA births, being more frequent in the latter group of infants. This result is in agreement with the fact that women with pregnancy-related hypertension tend to have thinner infants (28). The lack of association between hypertension and the risk of SGA birth in the population as a whole might be explained by the broad definition of hypertension we used in this study, since fetal growth has been shown to be impaired mostly by severe and early-onset pregnancy-induced hypertension (28, 30). Another reason might be that our study, restricted to term births, did not focus on the most severe forms of fetal growth restriction. Unfortunately, we could not adjust our analyses for paternal factors because data were missing for a large fraction of fathers. However, it has been shown that, after adjustment for maternal characteristics, only paternal education and race significantly influence the risk of low birth weight (31). Since our study was restricted to a European population and we took into account maternal education, which strongly correlates to paternal education, we might expect that paternal factors would have only a slight impact on our results.
Our findings indicate a strong familial aggregation of IUGR. This aggregation was of a similar magnitude whether we used the 10th percentile of birth weight to define IUGR, therefore including a fraction of "almost normal" babies, or a more stringent criterion, that is, a birth weight below the 5th percentile. Whatever the threshold used, after adjustment for maternal factors, we found that a childs risk of being born SGA was more than fourfold higher when his or her sibling was born SGA than when his or her sibling was not born SGA. Moreover, subsequent siblings tended to have an even higher risk when the child born SGA was not the firstborn of the sibship, although the difference did not reach statistical significance because of a small number of pairs. Indeed, the relative risk (approximating the odds ratio) of being born SGA conditional on the status of that childs sibling reached 6.0 when the sibling born SGA was not the firstborn; this value compared with 4.2 when the sibling born SGA was the firstborn (table 6). This finding is important from both a clinical and public health perspective, since it implies that mothers who deliver a non-firstborn SGA baby are at particularly high risk of giving birth to another SGA child.
Our results are in accordance with previous studies reporting a tendency to repeat SGA births in successive pregnancies (1518) and more generally with studies showing a high familial correlation of birth weight (32, 33). Familial aggregation of SGA births may be attributable to genetic and/or shared environmental factors. However, although adjustment for measurable maternal risk factors cannot entirely control for a shared maternal environmental influence, in particular an in utero influence (34), the strong residual sib-sib aggregation suggests a role of genetic factors in the etiology of IUGR. A possible role of genetic factors is supported by several studies showing an association of low infant birth weight with low maternal birth weight (1821) and, most important, with low paternal birth weight (35). Unfortunately, information on paternal and maternal birth weights was not available in the present study.
Interestingly, familial aggregation appeared to strengthen when we stratified SGA births according to ponderal index, suggesting that proportional and disproportional IUGR have different etiologies. In support of this hypothesis, the sib-sib odds ratio for proportionally SGA births decreased from 10.1 to 4.4 after adjustment for maternal characteristics, indicating a strong impact of maternal factors, especially smoking, on the risk of familial recurrence of this type of fetal growth restriction. In contrast, for disproportionally SGA births (accounting for 40 percent of all SGA births), the sib-sib odds ratio was hardly modified after adjustment and remained higher than 7.0, suggesting that, unlike proportionally SGA births, extrinsic maternal factors had little influence on this type of growth restriction. Disproportional IUGR reflects a more important growth restriction in terms of weight than height and is recognized as an indicator of the severity of IUGR (36). This pattern of fetal growth restriction has been shown to predispose to insulin resistance and to metabolic and cardiovascular diseases in adulthood (3, 6, 8, 10, 22). The strong familial clustering suggests that common genetic factors might predispose to both impaired fetal growth and adult disease. As proposed in the "fetal insulin hypothesis" (14), fetal thinness and insulin resistance might be two manifestations of the same insulin-resistant genotype. This hypothesis is supported by the fact that insulin secreted by the fetal pancreas in response to maternal glucose concentrations is a key growth factor. The insulin-resistant genotype might involve genes encoding for angiogenic factors, metabolic factors, or growth factors.
One limitation of our study is that it relied on data collected between 1971 and 1985, a time when ultrasound examinations were not yet widely used; therefore, we had to use birth weight as a surrogate variable for defining IUGR. However, note that most of the epidemiologic studies showing that IUGR is associated with morbid consequences in adulthood have used birth weight to define IUGR (6, 8, 10). Another point deserving discussion is that, because of improvements in the medical supervision of pregnancy, the incidence of IUGR has decreased during the last few decades. However, while factors such as smoking and hypertension can easily be modified by prevention, it is likely that the fraction of IUGR cases due to genetic factors has changed less.
A better characterization of the genetic determinants of IUGR is of primary importance given its long-term consequences regarding metabolic and cardiovascular complications. It was recently shown that the risk of diabetes associated with low birth weight in the offspring was strongly related to the development of paternal diabetes, suggesting a genetic link between low birth weight and diabetes later in life (13). Similarly, the VNTR polymorphism of the insulin gene has been shown to be associated with both birth weight and type 2 diabetes (12, 37). In contrast, a polymorphism of the angiotensin-converting enzyme gene was reported to be associated with insulin response to a glucose load in young adults born SGA, but it was not associated with SGA status itself (11). We are currently performing a follow-up study of subjects born SGA, as noted in the Haguenau register; this prospective study should enable us to investigate the hypothesis of a common genetic basis to IUGR and its later complications.
 |
ACKNOWLEDGMENTS
|
---|
The authors thank Professors P. Lazar and E. Papiernick for initiating this study.
 |
NOTES
|
---|
Correspondence to Laurence Tiret, INSERM U525, Faculté de Médecine, 91 Bd de lHôpital, 75634 Paris Cedex 13, France (e-mail: tiret{at}idf.inserm.fr). 
 |
REFERENCES
|
---|
- Barker DJ, Osmond C, Golding J, et al. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989;298:5647.[ISI][Medline]
- Hales CN, Barker DJ, Clark PM, et al. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991;303:101922.[ISI][Medline]
- Barker DJ, Hales CN, Fall CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993;36:627.[ISI][Medline]
- McCance DR, Pettitt DJ, Hanson RL, et al. Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype? BMJ 1994;308:9425.[Abstract/Free Full Text]
- Valdez R, Athens MA, Thompson GH, et al. Birthweight and adult health outcomes in a biethnic population in the USA. Diabetologia 1994;37:62431.[ISI][Medline]
- Lithell HO, McKeigue PM, Berglund L, et al. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 5060 years. BMJ 1996;312:40610.[Abstract/Free Full Text]
- Leger J, Levy-Marchal C, Bloch J, et al. Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study. BMJ 1997;315:3417.[Abstract/Free Full Text]
- Leon DA, Lithell HO, Vagero D, et al. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 191529. BMJ 1998;317:2415.[Abstract/Free Full Text]
- Leeson CP, Kattenhorn M, Morley R, et al. Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation 2001;103:12648.[Abstract/Free Full Text]
- Eriksson JG, Forsen T, Tuomilehto J, et al. Early growth and coronary heart disease in later life: longitudinal study. BMJ 2001;322:94953.[Abstract/Free Full Text]
- Cambien F, Leger J, Mallet C, et al. Angiotensin I-converting enzyme gene polymorphism modulates the consequences of in utero growth retardation on plasma insulin in young adults. Diabetes 1998;47:4705.[Abstract]
- Ong KK, Phillips DI, Fall C, et al. The insulin gene VNTR, type 2 diabetes and birth weight. Nat Genet 1999;21:2623.[ISI][Medline]
- Lindsay RS, Dabelea D, Roumain J, et al. Type 2 diabetes and low birth weight: the role of paternal inheritance in the association of low birth weight and diabetes. Diabetes 2000;49:4459.[Abstract]
- Hattersley AT, Tooke JE. The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. Lancet 1999;353:178992.[ISI][Medline]
- Scott A, Moar V, Ounsted M. The relative contributions of different maternal factors in small-for-gestational-age pregnancies. Eur J Obstet Gynecol Reprod Biol 1981;12:15765.[ISI][Medline]
- Bakketeig LS, Hoffman HJ. The tendency to repeat gestational age and birth weight in successive births, related to perinatal survival. Acta Obstet Gynecol Scand 1983;62:38592.[ISI][Medline]
- Wolfe HM, Gross TL, Sokol RJ. Recurrent small for gestational age birth: perinatal risks and outcomes. Am J Obstet Gynecol 1987;157:28893.[ISI][Medline]
- Wang X, Zuckerman B, Coffman GA, et al. Familial aggregation of low birth weight among whites and blacks in the United States. N Engl J Med 1995;333:17449.[Abstract/Free Full Text]
- Hackman E, Emanuel I, van Belle G, et al. Maternal birth weight and subsequent pregnancy outcome. JAMA 1983;250: 201619.[Abstract]
- Klebanoff MA, Graubard BI, Kessel SS, et al. Low birth weight across generations. JAMA 1984;252:24237.[Abstract]
- Klebanoff MA, Yip R. Influence of maternal birth weight on rate of fetal growth and duration of gestation. J Pediatr 1987;111:28792.[ISI][Medline]
- Barker DJ, Osmond C, Simmonds SJ, et al. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 1993;306:4226.[ISI][Medline]
- Papiernik E, Bouyer J, Dreyfus J, et al. Prevention of preterm births: a perinatal study in Haguenau, France. Pediatrics 1985; 76:1548.[Abstract]
- Liang KY, Beaty TH. Measuring familial aggregation by using odds-ratio regression models. Genet Epidemiol 1991;8:36170.[ISI][Medline]
- Trégouët D, Tiret L. Applications of the estimating equations theory to genetic epidemiology: a review. Ann Hum Genet 2000;64:114.[ISI][Medline]
- Trégouët DA, Herbeth B, Juhan-Vague I, et al. Bivariate familial correlation analysis of quantitative traits by use of estimating equations: application to a familial analysis of the insulin resistance syndrome. Genet Epidemiol 1999;16:6983.[ISI][Medline]
- Plancoulaine S, Abel L, van Beveren M, et al. Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population. Lancet 2000;356:10625.[ISI][Medline]
- Kramer MS, Olivier M, McLean FH, et al. Determinants of fetal growth and body proportionality. Pediatrics 1990;86:1826.[Abstract]
- Eskenazi B, Fenster L, Sidney S. A multivariate analysis of risk factors for preeclampsia. JAMA 1991;266:23741.[Abstract]
- Odegard RA, Vatten LJ, Nilsen ST, et al. Preeclampsia and fetal growth. Obstet Gynecol 2000;96:9505.[Abstract/Free Full Text]
- Parker JD, Schoendorf KC. Influence of paternal characteristics on the risk of low birth weight. Am J Epidemiol 1992;136:399407.[Abstract]
- Beaty TH, Yang P, Munoz A, et al. Effect of maternal and infant covariates on sibship correlation in birth weight. Genet Epidemiol 1988;5:24153.[ISI][Medline]
- Beaty TH, Skjaerven R, Breazeale DR, et al. Analyzing sibship correlations in birth weight using large sibships from Norway. Genet Epidemiol 1997;14:42333.[ISI][Medline]
- Ounsted M, Scott A, Ounsted C. Transmission through the female line of a mechanism constraining human fetal growth. Ann Hum Biol 1986;13:14351.[ISI][Medline]
- Magnus P, Bakketeig LS, Hoffman H. Birth weight of relatives by maternal tendency to repeat small-for-gestational-age (SGA) births in successive pregnancies. Acta Obstet Gynecol Scand Suppl 1997;165:358.[Medline]
- Kramer M, McLean F, Olivier M, et al. Body proportionality and head and length sparing in growth-retarded neonates: a critical reappraisal. Pediatrics 1989;84:71723.[Abstract]
- Dunger DB, Ong KK, Huxtable SJ, et al. Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Nat Genet 1998; 19:98100.[ISI][Medline]