The father’s gestational age at birth was linearly related to that of his offspring (Fig. 1A). Compared with fathers born at 37 weeks, fathers born at 42 weeks had offspring born, on average, 2 days later (283.2 days vs 281.3 days, P < .001). A mother’s gestational age at birth was even more strongly related to that of her offspring (Figure 1B). Children whose mother’s gestational age was 42 weeks were delivered, on average, 4 days later than children whose mother’s gestational age was 37 weeks (284.7 days vs 280.0 days, P < .001).
We hypothesized that a rapidly growing fetus might trigger delivery earlier. We first examined the parent’s birth weight as a predictor of the growth of the child (Fig. 2). Offspring birth weight increases by 145 g for every kilogram increase in father’s birth weight (95% confidence interval [CI] 140–150). As with gestational age, the effect was even stronger between mother and child, with the child’s birth weight increasing by 251 g per kilogram of the mother’s birth weight (95% CI 246–256).
Using the parent’s birth weight as a predictor of the fetal growth of the child, we explored the independent role of fetal growth on time of delivery. Since the parent’s gestational age could confound this association, we restricted this analysis to parents born at 40 or 41 completed weeks of gestation. The children of fathers with higher birth weights were born earlier than children of fathers with lower birth weights (Fig. 3A), and the association appears to be linear. The child’s gestational age was reduced by 0.79 days per kilogram increase in father’s birth weight (95% CI 0.45–1.12, P < .001). An opposite effect was found with mother and child (Fig. 3B). The child’s gestational age increased by 0.86 days per kilogram increase in mother’s birth weight (95% CI 0.51–1.21, P < .001).
We also used multiple linear regression analysis to adjust for the simultaneous effects of parents’ birth weight and gestational age on the gestational age of their child. After adjustment, a 1-kg increase in father’s birth weight was associated with a 0.65-day earlier delivery of his child (95% CI 0.40–0.90) (Table 3). Independently, the father’s gestational age was still positively associated with the gestational age of his child (0.58 days per each week of the father’s gestational age, 95% CI 0.48–0.67). The effect of mother’s birth weight on gestational age of her child was unchanged after adjustment (0.44 day increase per kilogram birth weight of the mother, 95% CI 0.18–0.69), with the effect of the mother’s gestational age on the child’s gestational age (1.22 days per week, 95% CI 1.12–1.32) twice the father’s. These estimates were also adjusted for the mother’s and father’s age and year of birth of the child. Further adjustment for the couple’s marital status and the mother’s education had virtually no effect on the estimates. When analyses were performed separately for boy and girl offspring, we found no indication of difference in estimated effects.
There are few studies of determinants of gestational age across generations. This study confirms previously reported effects of the mother’s gestational age7,8 and her birth weight9 on the offspring’s gestational age. However, those earlier studies did not provide particular insights on the biological mechanisms involved. Our additional data on fathers provide useful contrasts with the mothers’ effects on gestational age at birth and suggest possible mechanisms for the triggering of delivery in humans.
An association of the father’s own gestational age with the gestational age of his offspring has also been seen in retrospective data from England.8 The association presumably reflects alleles passed from the father to fetus and involved in onset of delivery. This supports other evidence showing that the fetus can help initiate the onset of labor and delivery. Although the triggering mechanisms themselves are unknown, a cascade of physiological changes takes place in the fetus and the mother before the delivery.1–5,10,11 There is experimental evidence from both sheep and horses that endocrine changes in the fetus (especially cortisol) may play a key role in triggering delivery. Evidence of a similar fetal regulation of cortisol before delivery has been described in humans.1,4 A recent study in mice has suggested that surfactant protein-A secreted in fetal lungs initiates delivery.12 Genetic regulation of similar mechanisms in humans may contribute to the heritable component of length of pregnancy between father and offspring in our data.
However, the association in gestational age between mother and child is much stronger than the association between father and child. This suggests that the mother contributes in additional ways to her offspring’s gestational age. One added component could be alleles passed from the grandmother to the mother that affects the maternal phenotype. A woman’s capacity to carry a baby for longer may itself be heritable and perhaps related to her body size or structure. Genetic variation in the length of the follicular phase could also contribute (given that gestational age in these data are defined from the onset of the last menstrual period). If so, a woman’s gestational age at birth would, to some degree, be a product of her own mother’s reproductive capacity, which the woman in turn may inherit.
The association of gestational age between mother and child is a result of maternal, as well as fetal, contributions, whereas the association between father and child should result only from a contribution through the fetus. Because the observed association between mother and child was almost exactly twice that of father and child, we might infer that the contribution of the mother’s heritable phenotype is similar in magnitude to the contribution of the fetus’ heritable phenotype.
In contrast, there is a striking difference between parents in the association of their own birth weight (adjusted for their gestational age) with the gestational age of their offspring. Mothers with higher birth weights have children with longer gestational age. Fathers with higher birth weights have children with shorter gestational age. How can this be explained? The fathers provide the simpler case, because their contribution is solely through the genotype of the fetus. We know that fathers with higher birth weights tend to have larger offspring (Fig. 2) and thus offspring who grow faster in utero. The fact that these fathers also tend to have offspring with shorter gestational age suggests that faster fetal growth triggers delivery sooner. Indirect evidence from studies of twins is consistent with this conclusion.13 More directly, a study of half siblings in dairy cattle showed that bulls producing larger fetuses also produced calves that delivered earlier.6
If faster-growing fetuses trigger delivery earlier, why do we not see the same association between the mother’s birth weight and her offspring’s gestational age? This may be because the mother’s birth weight is also associated with maternal factors that improve her capacity to carry a pregnancy. A mother’s weight at birth may be associated with such adult characteristics as pelvic size or uterine size. If so, these aspects of maternal capacity apparently counterbalance the expected negative correlation between the mother’s size at birth and the length of her pregnancies. The opposing effects of the mother’s birth weight make the net effect of her birth weight the weakest association in our analysis (Table 2). However, this relationship emerges clearly in the simpler setting of father and offspring.
Obstetric management may also contribute to shorter gestation of larger babies. However, it is not clear how this could explain the opposing effects of the father’s and mother’s birth weights. The possibility that more rapid fetal growth contributes to shorter gestational age deserves further consideration.
Our study was restricted to parents born at term from normal, spontaneous deliveries. Pathologic mechanisms such as preeclampsia14 (which have both a maternal and a fetal component) are more likely to be involved in preterm or postterm deliveries. Such pathologies may have their own patterns of familial recurrence.15–17 By restricting parents to those delivered vaginally at term (and their offspring who were delivered vaginally), our analysis focuses on natural regulation processes. Our results were not altered when we removed all families having a preeclamptic pregnancy.
Environmental and social conditions that persist across generations may, in principle, contribute to the associations we observe, although there are, in fact, few environmental factors known to affect gestational age. Even cigarette smoking, which can increase the risk of preterm delivery, has only a weak effect on mean gestational age.18 Such environmental factors are therefore not likely to represent major confounding in our analysis.
Registration of Norwegian mothers and children in our sample should be close to 100%. Information on fathers is missing for 8% of births in the Registry,14 and paternity may be incorrect for a small percent of others. Such errors would tend to obscure the associations between father and offspring. Similarly, errors in gestational age estimated from last menstrual period or birth weight would tend to reduce the estimated effects. It is therefore unlikely that the effects we see could result from systematic bias. Improvements and changes in obstetric care may also have affected the associations we see between parents’ and offspring length of pregnancy. This should, however, also have the effect of weakening the observed associations.
In conclusion, our data suggest that both the fetal and the maternal system influence the length of pregnancy through mechanisms that are subject to genetic influence. An association between the father’s and child’s gestational age supports a role of the fetus and placenta in triggering delivery. Furthermore, the link between a higher weight at birth for the father and a shorter gestation for his offspring suggests an effect of fetal growth on the duration of pregnancy.
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© 2006 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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