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Although the etiology of handedness is unclear,1–4 brain lateralization is probably determined during embryogenesis,4 and more than 80% of fetuses show more right-arm than left-arm movements as early as at 10 gestational weeks.5,6 Nonright-handedness is considered by some to be a marker of neurotoxic exposures during fetal life7,8 and has been associated with schizophrenia,9,10 autism,11 homosexuality,12 and asthma.13 Exposure to abnormal steroid levels during fetal life is a possible cause.12,14,15 In this study, we examined the association between handedness and fecundity measured by time to pregnancy.16–19
We used data from 2 regional population-based birth cohorts in Denmark: the Aalborg-Odense Birth Cohort (1984–1987)20,21 and the Aarhus Birth Cohort (1990–1992).22,23 Both studies collected data through questionnaires on sociodemographic, environmental, and lifestyle factors during pregnancy, and the children were followed up since birth. Detailed information on the study populations is available in the online version of this article.
In the follow-up questionnaires, we collected information on parents’ handedness by asking the parent the following questions: “Which hand does your child’s biologic mother use the most?” and “Which hand does your child’s biologic father use the most?” The response categories were (1) exclusively the right hand, (2) mostly the right hand, (3) both hands equally, (4) mostly the left hand, or (5) exclusively the left hand. We defined parents as strong dextral, dextral, mixed-handed, sinistral, and strong sinistral, respectively.
Time to Pregnancy
In the pregnancy questionnaires, women were asked if their pregnancy was planned (yes, no, don’t know), if they had ever been examined or treated for infertility (yes, no), and for how long they had tried to become pregnant before succeeding (3 categories for the Aalborg-Odense Birth Cohort: 0–6, 7–12, and >12 months; and exact number of months for the Aarhus Birth Cohort). We restricted all analyses to planned pregnancies.
We calculated fecundity ratios (FRs) by using discrete-time survival analysis with complementary log-log link, which has an interpretation in terms of hazard ratio (HR) and is more appropriate and robust to the choice of time-to-pregnancy categories than logit link,24–27 in STATA 9.1 (StataCorp, College Station, TX, USA). Strong dextrals were used as the reference category. We defined fecundity as the probability of conception in a given time-to-pregnancy category, conditionally on not having conceived in the previous interval. The discrete-time survival analysis with complementary log-log link expresses the hazard as a ratio of the incidence (conception) density to the survival function. In the Aarhus Birth Cohort, we additionally performed Cox regression by treating time to pregnancy (in months) as a continuous variable. Data were analyzed separately for mothers and fathers, as well as for each birth cohort.
Reported handedness may correlate with age, especially in older parents, if they had been “corrected” as children. Different lateralization, perception of being different, or living in a world designed for right-handed people may result in different lifestyles, which could, in turn, affect fecundity. We thus examined whether including parents’ age at the time of birth of the child (<25, 25–29, 30–34, 35+ years) and mother’s smoking before pregnancy (yes, no) in the models for each cohort changed the estimates. We also examined our results in the Aalborg-Odense Birth cohort by further adjusting for alcohol intake, coffee consumption, and body mass index before pregnancy in women, and for smoking and alcohol intake in men.
In the Aalborg-Odense Birth Cohort we had 5808 couples for analysis, with 10.0% left- or mixed-handed women and 12.5% left- or mixed-handed men. In the Aarhus Birth Cohort we had 3426 couples, with 9.2% left- or mixed-handed women and 12.4% left- or mixed-handed men (eTable1).
Mixed-handed individuals had a lower fecundity in the Aalborg-Odense Birth Cohort, regardless of adjustment. We saw similar estimates in the Aarhus Birth Cohort (Table 1). Estimates in the Aarhus Birth Cohort were unchanged when treating time to pregnancy as a continuous variable in Cox regression models (adjusted HR 0.94 [95% confidence interval = 0.74–1.19] for mixed-handed women and 0.87 [0.72–1.04] for mixed-handed men; eTable 2). Further adjustment for alcohol intake, coffee consumption, and body mass index before pregnancy in women, and for smoking and alcohol intake in men in the Aalborg-Odense Birth Cohort did not change the results (data not shown).
Some types of handedness run in families,28 and familial handedness may represent a distinct phenotype. Excluding mixed-handed women or men whose children were mixed-handed or left-handed had no effect on the estimates in either cohort (Aalborg-Odense Birth Cohort: adjusted HR 0.85 [0.68–1.07] and 0.81 [0.69–0.96] for mixed-handed women and men, respectively; Aarhus Birth Cohort: adjusted HR 0.96 [0.64–1.43] and 0.87 [0.70–1.08] for mixed-handed women and men, respectively).
We found a modest association between mixed-handedness and a longer time to pregnancy in 2 Danish birth cohorts. Our findings suggest that handedness and fecundity may share a common genetic background or common causes, perhaps operating during fetal life.
Our study populations arose from parents enrolled in 2 birth cohorts (the Aalborg-Odense and the Aarhus birth cohorts). Participation at enrollment was high (87% and 95%, respectively), but moderate for the follow-up questionnaires (74% and 72%, respectively). However, it is unlikely that participation depended on both time to pregnancy and handedness. It is also highly unlikely that respondents reported handedness differentially depending on their time to pregnancy, because the information on time to pregnancy was provided at least a decade earlier. Information on time to pregnancy was obtained in the pregnancy questionnaires, and the recall period was less than 1 year in both cohorts. The distribution of handedness as well as that of time to pregnancy were comparable with results from other studies.22,29
In most cases the mother reported handedness for herself and the child’s father by answering 1 question for each, and the resulting distribution of handedness was close to the expected.29 We do not know whether those reporting equal use of both hands referred to the ability to perform the same task or different tasks. As expected, there were more nonright-handed or mixed-handed men than women, and the frequency of mixed-handedness was lower than what has been reported in more detailed assessments.30,31 We cannot rule out that using a different set of questions would have yielded different results.32
In addition to psychopathologic disorders,9 weak lateralization has been associated with a wide range of conditions including impaired spatial performance, dyslexia, and asthma.13 Prenatal stress has been studied as a potential cause of mixed-handedness.30,33,34 In line with these reports, we found an association of lower fecundity with mixed-handedness but not left-handedness. This may suggest that abnormal levels of steroids in fetal life lead to incomplete lateralization, manifested as mixed-handedness. However, our and others’ findings do not necessarily imply that mixed-handedness is pathologic. Some “corrected” left-handers could be among the right- and, more likely, mixed-handed individuals, and the stress of having to operate with the nonprimary hand may have resulted in compromised fertility or other adverse health conditions. It is thus expected that mixed-handed individuals would appear to deviate from the statistical norm, whereas the influx of “corrected” left-handers into the group of right-handers would not be noticeable.35
Our results suggest that mixed-handedness is associated with lower fecundity, perhaps because these 2 traits share a common etiology, but other explanations are also possible. Future studies should examine direct associations between hormonal levels during fetal life and subsequent handedness, as well as fecundity later in life.
We thank Clarice R. Weinberg and Freya Kamel for helpful comments on an earlier version of this manuscript.
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