General Obstetrics and Gynecology: Obstetrics
Familial aggregation of small-for-gestational-age births: The importance of fetal genetic effects

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Objective

This study was undertaken to disentangle the maternal genetic, fetal genetic, and environmental effects for the risk of having small-for-gestational-age (SGA) offspring.

Study design

By cross-linking the population-based Swedish Multi-Generation and Medical Birth Registers, we extracted 2,193,142 births between 1973 and 2001 with both parents identified. Odds ratios (OR) were calculated to estimate the relative risks, and generalized linear mixed models were used to estimate the contribution of genetic and environmental effects.

Results

Women whose full sisters had an offspring born SGA had a significantly increased risk of having a SGA offspring themselves (OR = 1.8, 95% CI 1.7-1.9), whereas the corresponding risk for brothers was lower (OR = 1.3, 95% CI 1.2-1.4). Thirty-seven percent of the liability was explained by fetal (including both maternal and paternal) genetic effects and 9% by maternal genetic effects.

Conclusion

Genetic factors account for almost half of the liability to have SGA births. These effects are primarily caused by fetal genes.

Section snippets

Data sources

The Swedish Multi-Generation Register includes 8.5 million children born since 1932, who are linked with their biological parents, resulting in a total of 11 million unique individuals.7 Since 1973, data on all births in Sweden (including information on demographics, reproductive history, and complications during pregnancy, delivery, and the neonatal period) are collected prospectively and recorded in the Medical Birth Register. By the end of 2001, there were 2.9 million births recorded,

Results

Among the 2,193,142 singleton births, the incidence of SGA births was 4.2% in the first pregnancy and 2.3% in the following pregnancies.

Table II presents the distribution of SGA births and the corresponding ORs in the different sibships. For example, in the 227,905 families joined by full sisters, there were 200,893 families in which none of the sisters had a SGA birth; 25,255 families in which 1 sister had a SGA birth; 1,690 families in which 2 sisters had SGA births; and 67 families in which

Comment

Our results corroborate previous findings that familial factors influence risk of SGA.5, 6, 16 Further, we could show that approximately 46% of the variation in liability to giving birth to a SGA offspring can be explained by genetic factors, of which fetal genes constitute 37% and maternal genes 9%. There is variability among individuals in their susceptibility to SGA births; about 46% of this variability is due to genes and 54% is due to environmental factors.

To our knowledge, this is the

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    Funded by the Swedish Council for Working Life and Social Research (project 2003-0274).

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