Chromosomal radiosensitivity of Down syndrome lymphocytes at different stages of the cell cycle

Summary Data on 151 non-mosaic 47,XXY males from Sardinia, previously reported by Filippi (1986), were analysed for associations with parental ages at birth, sib order and sex ratio among siblings. The results confirm those of earlier Scottishbased studies in that: (1) there was a significant increase in risk of 47,XXY livebirths at advanced parental ages; (2) maternal age, and maternal age alone, was sufficient to explain the effect; (3) there were no independent effects of paternal age or sib order once maternal age had been taken into account; (4) there was no evidence of any distortion of the sex ratio among siblings. Estimates of relative risk at different maternal ages were compatible with those from the Scottish studies, and pooled estimates are therefore derived. They suggest, for example, that the risk at maternal age 40 years is 2–3 times that at age 30 years. In 33 cases, the parental origin of the supernumerary X chromosome was determined by analysing the segregation of genetic markers. The mean parental ages of 19 maternal cases were significantly raised above those of controls, whereas those of 14 paternal cases were slightly, and marginally significantly, reduced. The conclusions were essentially unaffected by whether the Sardinian population, the siblings of cases or a group of 94 unrelated Sardinian males were used as controls.     

Rates of trisomies 21, 18, 13 and other chromosome abnormalities in about 20 000 prenatal studies compared with estimated rates in live births

Summary Data were analyzed on the results of 19675 prenatal cytogenetic diagnoses reported to two chromosome registries on women aged 35 or over for whom there was no known cytogenetic risk for a chromosome abnormality except parental age. The expected rates at amniocentesis of 47,+21; 47,+18; 47,+13; XXX; XXY; XYY; and other clinically significant cytogenetic defects by maternal age were obtained from a regression analysis on the observed rates, using a first degree exponential model. After an adjustment for maternal age, these rates were compared with previously estimated rates by maternal age in live births. The rates of 47,+21 at amniocentesis and live birth are approximately parallel, with the latter about 80% of the amniocentesis rates. The rates of 47,+18 at amniocentesis and live birth are approximately parallel, with the live birth rates about 30% of the amniocentesis rates, consistent with high fetal mortality of 47,+18 after amniocentesis. The rates of 47,+13 at amniocentesis indicate an increase in maternal age that is not as marked as thar previously estimated in live births. The rates at amniocentesis for XXX and XXY increase with maternal age, with the rates of XXY almost identical to those estimated previously in live births, suggesting no late fetal mortality of XXY. The rates of XYY show a slight decrease with maternal age also consistent with little late fetal mortality of XYY. No consistent trend with age is seen for the pooled group of other clinically significant defects.     

Paternal-age and birth-order effect on the human secondary sex ratio.

Because of conflicting results in previous analyses of possible maternal and paternal effects on the variation in sex ratio at birth, records of United States live births in 1975 were sorted by offspring sex, live birth order (based on maternal parity), parental races, and, unlike prior studies, ungrouped parental ages. Linear regression and logistic analysis showed significant effects of birth order and paternal age on sex ratio in the white race data (1.67 million births; 10,219 different combinations of independent variables). Contrary to previous reported results, the paternal-age effect cannot be ascribed wholly to the high correlation between paternal age and birth order as maternal age, even more highly correlated with birth order, does not account for a significant additional reduction in sex-ratio variation over that accounted for by birth order alone.     

Determinants of the sex ratio at birth: review of recent literature

The fact that more boys are born than girls (104-107 boys for every 100 girls) has been known since 1662. Factors determining the sex ratio at birth rate are of 2 kinds: factors determining the primary sex ratio, i.e., sex ratio at conception, and factors determining the survival of the embryo in utero. Y-bearing and X-bearing sperm may have different motility or different survival time. The age of the ovum at fertilization and the chemical balance of the female genital tract have an effect on sex ratio at conception. High levels of circulating gonadotropins may imply a lower sex ratio at birth as well as a higher rate of dizygotic twinning. Male conception also appears to be higher early and late in the menstrual cycle. The fact that women exposed to higher coital rates conceive earlier in the menstrual cycle may account for the greater number of boys born during wars. Prenatal male mortality is reportedly highest between gestational months 3-5, lower between months 6-8, and higher again st term. Also, immunological interaction between mother and embryo may account for some sex selective spontaneous abortions. 3 sociodemographic determinants of sex ratio at birth are thought to be maternal age, paternal age, and birth order. Higher prenatal male mortality may be correlated with socioeconomic conditions, since higher socioeconomic status lowers prenatal mortality in general. The effects of parental age, birth order, and parity are less clear. Race is also a factor, since the sex ratio at birth for blacks is lower (102-104) than for whites (106). 14 univariate and 19 multivariate studies of effects of maternal age, paternal age, parity, birth order, race, and socioeconomic status on sex ratio at birth, with sample sizes in the millions from various countries have been analyzed. More boys are born to younger parents, and lower order births have a higher proportion of males than do higher order births. In the multivariate analyses, when the effects of paternal and and birth order are controlled for, the effect of maternal age weakens, and the effect of paternal age appears to be stronger. The effect of birth order remains but is very small, and the effect of race persists independent of any effect of other variables. Maternal age, parity, and birth order are positively correlated with proportion of male stillbirths. The results of the multivariate analyses show all of the effects to be very small, but that maternal age has no effect on sex ratio at birth; paternal age and birth order have a negative effect, and the racial effect persists independent of any other effect. The racial effect is clearly biologically determined at conception because blacks have higher levels of circulating gonadotropin and therefore a higher probability of conceiving girls. Parents in higher socioeconomic classes are more likely to have sons, but the effect is largely due to the excess male mortality during most of the gestational period.     

Sex ratio in the offspring of parents with chronic radiation exposure from nuclear testing in Kazakhstan

The former Soviet Union conducted a nuclear test program in the Semipalatinsk region of northeastern Kazakhstan in 1949-1989. The population in the vicinity of the test site was chronically exposed to radiation fallout, especially from above-ground tests during 1949-1956. Male:female sex ratio has been proposed as a measure of reproductive health, with some reports suggesting an alteration in the sex ratio of offspring of parents exposed to radiation. We investigated the impact of radiation exposure and other factors on the sex ratio in the population inhabiting the exposed region. A total of 11,464 singleton births of 3,992 mothers exposed to radiation during 1949-1956 were analyzed. The overall sex ratio was 1.07, similar to the current sex ratio in Kazakhstan (1.06). The sex ratio increased from 1.04 where mothers received <20.0 cSv to 1.12 where mothers received > or =60.0 cSv. However, the linear trend across exposures was not significant (P = 0.42). No consistent association was found between the sex ratio and the time since parental radiation exposure, parental age at exposure, or year of birth. Sex ratio was significantly associated with maternal age, birth order and possibly ethnicity but not with paternal age, parental educational level or season. In conclusion, no significant association was found between radiation exposure level and sex ratio, but some previously suggested demographic factors were positively associated with sex ratio.     

A genetic study of Hirschsprung disease

Hirschsprung disease, or congenital aganglionic megacolon, is commonly assumed to be a sex-modified multifactorial trait. To test this hypothesis, complex segregation analysis was performed on data on 487 probands and their families. Demographic information on probands and the recurrence risk to relatives of probands are presented. An increased sex ratio (3.9 male:female) and an elevated risk to sibs (4%), as compared with the population incidence (0.02%), are observed, with the sex ratio decreasing and the recurrence risk to sibs increasing as the aganglionosis becomes more extensive. Down syndrome was found at an increased frequency among affected individuals but not among their unaffected sibs, and the increase was not associated with maternal age. Complex segregation analysis was performed on these family data. The families were classified into separate categories by extent of aganglionosis. For cases with aganglionosis beyond the sigmoid colon, the mode of inheritance is compatible with a dominant gene with incomplete penetrance, while for cases with aganglionosis extending no farther than the sigmoid colon, the inheritance pattern is equally likely to be either multifactorial or due to a recessive gene with very low penetrance. A model of gene action with random effects during morphogenesis is compatible with our observations.     

Reexamination of paternal age effect in Down's syndrome

Summary The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47,+21 cases was studied. The mean paternal age was 0.16 year greater than in the entire population of live births after controlling for maternal age. There was no evidence for a significant paternal age effect at the 0.05 level. For 242 of these Down's syndrome cases, control subjects were selected by rigidly matching in a systematic manner. Paternal age was the variable studied, with maternal age and time and place of birth controlled. There was no statistically significant association between paternal age and Down's syndrome. After adjustment for maternal age, these two studies were not consistent with an increase of paternal age in Down's syndrome.     

Estimates of sperm sex chromosome disomy and diploidy rates in a 47,XXY/46,XY mosaic Klinefelter patient

A 47,XXY/46,XY male was investigated for the incidence of aneuploidy in sperm sex chromosomes using a three-colour X/Y/18 fluorescence in situ hybridisation (FISH) protocol. A total of 1701 sperm nuclei were analysed. The ratio of X-bearing to Y-bearing sperm did not differ from the expected 1 : 1 ratio although there were more 23,Y sperm than 23,X sperm (844 vs 795). There was a significantly increased proportion of disomy XY and XX sperm compared with normal controls (0.41% vs 0.10%, P < 0.001 and 0.29% vs 0.04%, P < 0.01). However, the incidence of YY sperm was similar to the controls (0.06% vs 0.02%). The diploidy rate was also significantly increased (1.7% vs 0.13%, P < 0.0001), as was disomy 18 (0.71% vs 0.01%) and 25,XXY (0.47% vs 0%). The results support the hypothesis that some 47,XXY cells are able to undergo meiosis and produce mature spermatozoa. Patients with mosaic Klinefelter syndrome with severe oligozoospermia have significantly elevated incidences of disomy XY and XX sperm and may be at a slightly increased risk of producing 47,XXX and 47,XXY offspring. Additionally, they may be at risk of producing offspring with autosomal trisomies. Hence, patients with Klinefelter mosaicism scheduled for intracytoplasmic sperm injection intervention should first undergo FISH analysis of their sperm to determine their risk. Received: 16 November 1998 / Accepted: 16 February 1999     

Stillbirth pattern in an isolated mediterranean population: La Alpujarra, Spain

This study attempted to analyze the effect of several factors on the stillbirth pattern in a relatively isolated rural population, La Alpujarra (Spain), during the first half of the 20th century. The study was a retrospective analysis from a total sample of 2199 births to 525 mothers, allowing for birth year of mother, maternal age, parental inbreeding, family size, birth order, sex, single/twin delivery, and birth interval. Binomial probability distribution of stillbirths provided no evidence for any significantly increased risk in relation to family size. Analysis of covariance (ANCOVA) of stillbirth risk in affected families indicated a significant effect for sex of the child, parental consanguinity, and birth year of mother. Logistic regression showed increased risk in twin delivery and pregnancy order one, but not for birth order other than one. Multivariate analysis of variance (MANOVA) testing for differences between affected and unaffected families supported a temporal decrease of stillbirths during the period studied. Although the birth interval average was significantly shorter in affected families (p < 0.0001), this association did not hold, in a more detailed analysis, for individual intervals in these families (p = 0.20). There was no significant effect of maternal age on stillbirths in the whole sample or limited to first pregnancies. These results suggest that birth order one and twin delivery were the main determinants of the stillbirth pattern in La Alpujarra. Furthermore, our data indicate that the decline in stillbirth rate began before medical facilities for perinatal care became available, which was not until after 1950. The temporal decrease in stillbirth rates may therefore be related to an increasing social attention to deliveries rather than to prenatal care medical facilities.     

Factors influencing prereproductive mortality in the isolated and preindustrial western Mediterranean population of La Alpujarra, 1900-1950

We study the effects of several variables on the prereproductive mortality pattern in the isolated and rural population of La Alpujarra, located on the western Mediterranean coast (southeast Spain), in the first half of the 20th century. The study is a retrospective analysis from a total sample of 2,200 deliveries, 2,085 of which were born alive and 171 of which did not survive to the 20th birthday. The potential influences of birthdate of children, twinning, firstborn, parental inbreeding, and sex on Alpujarran mortality were analyzed through logistic regression. Parity, family size, and birth interval effects were estimated through the difference between observed and expected mortality rates. In every case four age groups of mortality were considered because of the large influence of child growth: neonatal (less than 1 month of life), postneonatal infant (between 1 month and 1 year old), childhood (1-5 years old), and youth (5-20 years old). The Alpujarran prereproductive mortality pattern can be summarized as the result of three main risk factors: biodemographic, biomechanical, and social and health determinants. In general, every factor showed a decreased effect as children grew. The most significant determinants were birthdate of children, which is more related to increased mother's awareness of child care than to health improvement, and family size associated with decreasing alimentary resources as the sibling number increased. Male mortality was higher than female mortality in children older than 1 year but not for infant mortality, possibly as a result of a reproductive behavior favorable to males. Although firstborn status and twinning appeared associated with high mortality, maternal age and birth interval were related to low risk, but these influences always ceased after the first month of life. Parental inbreeding did not show any effect on infant, childhood, or youth mortality.     

Reduced recombination and paternal age effect in Klinefelter syndrome

Summary The parental origin of the additional sex chromosome was studied in 47 cases with an XXY sex chromosome consitution. In 23 cases (49%), the error occurred during the first paternal meiotic division. Maternal origin of the additional chromosome was found in the remaining 24 cases (51%). Centromeric homo- versus heterozygosity could be determined in 18 out of the 24 maternally derived cases. According to the centromeric status and recombination rate, the nondisjunction was attributable in 9 cases (50%) to an error at the first maternal meiotic division, in 7 cases (39%) to an error at the second maternal meiotic division and in 2 cases (11%) to a nullo-chiasmata nondisjunction at meiosis II or to postzygotic mitotic error. No recombination, and in particular none in the pericentromeric region, was found in any of the 9 cases due to nondisjunction at the first maternal meiotic division. Significantly increased paternal age was found in the paternally derived cases. Maternal age was significantly higher in the maternally derived cases due to a meiotic I error compared with those due to a meiotic II error. There were no significant clinical differences between patients with respect to the origin of the additional X chromosome.     

Maternal expenditure in the polygynous and monomorphic guanaco: suckling behavior, reproductive effort, yearly variation, and influence on juvenile survival

We investigated patterns of maternal expenditure and its influenceon juvenile survival in the polygynous monomorphic guanaco (Lama guanicoe)in southern Chile from 1990 to 1994. Birth weight and growth rate(until age 1) of males and females were similar. Suckling ratesof males and females were not significantly different, althoughmothers of males rejected suckling attempts more often thanmothers of females during fall and winter. Mothers with sonsterminated suckling bouts in equal proportion as did motherswith daughters. Our estimated level of reproductive effort for guanacosfalls within the range of species exhibiting no sex-biased maternal expenditureon offspring. Mean yearly birth weight was negatively correlated withpopulation density. Mean suckling time throughout the year differedamong cohorts, as did the mean number of suckling attempts andrejected suckling attempts per hour throughout the year. Juvenilesurvival was estimated until age 1. Of the model with five covariatesincluding juvenile sex, birth weight, adult female aggressiontoward taggers, mean suckling time, and population density,only mean suckling time and population density were significantly relatedto survival. The risk ratio for mean suckling time indicatesthat the risk of mortality increases as suckling time increases,whereas the risk ratio for population density indicates thatthe risk of mortality decreases as population density increases.Under some conditions increasing population density may be correlatedwith lower offspring birth weight, yet enhanced juvenile survival.This effect on survival was possibly associated with the numberof predators on the study area from year to year.     

Parental age and the risk of childhood acute myeloid leukemia: results from the Childhood Leukemia International Consortium

BackgroundParental age has been associated with several childhood cancers, albeit the evidence is still inconsistent.AimTo examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0–14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies.Material/methodsWe analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants <1 year-old vs. children 1–14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1–14 years), and recruitment time period.ResultsAdjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers ≥40-year-old (OR = 6.87; 95% CI: 2.12–22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year.ConclusionsAn increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.     

The association between maternal nutrient intake during pregnancy and the risk of sporadic unilateral retinoblastoma among offspring

Previous studies have associated maternal diet during pregnancy with the development of sporadic unilateral retinoblastoma (RB), but few studies have focused on the role of individual nutrients. The aim of this study is to investigate the association between maternal nutrient intake during pregnancy and the development of sporadic unilateral RB in the offspring.A modified food frequency questionnaire, with additional questions on supplement use, was completed via a phone interview. Cases were recruited from hospitals and controls were comprised of friends and relatives of the patient without a history of cancer. Overall, 168 sporadic unilateral RB cases and 145 controls were included in case-control study. We performed logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI), adjusting for child’s age, child’s sex, parental race/ethnicity, maternal education, total calorie intake during pregnancy, maternal age at birth, maternal smoking during pregnancy, pre-pregnancy body mass index, maternal weight gain during pregnancy, paternal age at birth, and maternal multivitamin use in the year before pregnancy.In the adjusted model, the interquartile (IQR) increase in vitamin A intake, which was measured in retinol activity equivalent (RAE; OR: 0.64, 95 % CI: 0.46–0.90), and vitamin D intake (OR: 0.62, 95 % CI: 0.42–0.91) significantly reduced the risk of sporadic unilateral RB.These findings suggest that a higher intake of vitamins A and D can be a protective factor for sporadic unilateral RB. Further analyses in consideration of multi-exposures such as parental occupational exposures are warranted to discover the complex etiology of sporadic unilateral RB. In addition, the role of nutritional epigenetics for how maternal nutrient intake influences the risk of sporadic unilateral RB in the offspring still needs to be explored.     

Cardiac functioning and blood pressure of 47,XYY and 47,XXY men in a double-blind, double-matched population survey.

This paper reports the electrocardiogram measures and blood pressure of 12 men with 47,XYY, 14 men with 47,XXY, and 52 matched controls with 46,XY. The abnormal karyotypes were identified in a systematic population search for XYY and XXY men. The subjects and their matched controls were examined in a double-blind fashion. Electrocardiogram measures of 47,XYY and 47,XXY men were found to differ from those of 46,XY controls. The XYYs had longer P-R intervals, shorter QRS complexes, and nonsignificantly longer R-R intervals than their matched controls. The XXYs showed longer R-R intervals and trends for for prolonged P-R intervals and shorter QRS complexes when compared with their controls. Trends toward increased within-group variability in the XYY and XXY groups were observed in five of six variance tests, suggesting that the sex chromosome aneuploids have a cardiac condition anomaly. Blood pressure measures of 47,XYY and 47,XXY men were found not to differ from those of 46,XY men. None of the measures revealed a significant difference between the XYYs and the XXYs.     

High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862–1994

We wished to determine the influence of parental age at the birth of a retinoblastoma patient on the risk of sporadic hereditary retinoblastoma. The parental age at birth of 941 patients of the Dutch retinoblastoma register (1862–1994) was identified and compared between sporadic hereditary and nonhereditary patients. In a subcohort (1936–1994), a comparison was made with parental age at birth in the general population, as obtained from the Central Bureau of Statistics. Missing birth dates of the parents of retinoblastoma patients were traced with the help of the municipal registries and the Central Bureau of Genealogy. The mean paternal age was 10.7 months higher and the mean maternal age was 11.0 months higher in the sporadic hereditary retinoblastoma patients than in parents of nonhereditary patients. In the subcohort, the mean paternal and maternal ages of sporadic hereditary patients were also higher (12.4 and 11.5 months, respectively) than those of the general population. All differences were statistically significant. This study shows that a high parental age is associated with an enhanced risk of sporadic hereditary retinoblastoma. Received: 10 November 1995 / Revised: 11 January 1996     

Infant male sex as a risk factor for shoulder dystocia but not for cephalopelvic disproportion: An independent or confounded effect?

Background: Shoulder dystocia (ShD) and cephalopelvic disproportion (CPD) share some common risk factors. Whether infant male sex is an independent risk factor for ShD, or if the risk is confounded by other known factors, is uncertain.Objective: The aim of this study was to explore the unconfounded effect of infant male sex on the risk for ShD and its interaction with other risk factors compared with CPD.Methods: A retrospective data analysis was conducted of deliveries in Lamphun Hospital, Lamphun, Thailand. All vaginal deliveries complicated by ShD were collected as ShD cases. All labors terminated by cesarean delivery (CD) due to CPD were collected as CD/CPD cases. Vaginal deliveries that took place immediately before or after the index ShD cases were collected as controls. Multivariable adjusted odds ratios (AORs) for infant male sex and its 95% CI in cases of ShD and CD/CPD were computed by multichotomous logistic regression controlling for other obstetric risks. The effects of maternal height, gestational age, and birth weight on the risk for ShD or CD/CPD among male or female infants was also explored. Stability of the effect of the risk between male and female infants was tested with Chow tests.Results: Thirty-five ShD cases and 199 CD/CPD cases were collected, as were 586 controls. Infant male sex was a significant independent risk factor for ShD (AOR = 5.00; 95% CI, 1.83-13.61; P = 0.002), but not for CD/CPD (AOR = 1.09; 95% CI, 0.75-1.59; P = NS). For CD/CPD, the effects of maternal height, gestational age, and birth weight were similar for male and female infants, but the corresponding effect on ShD was more pronounced in male than in female infants (P < 0.001 for all comparisons).Conclusions: Infant male sex is a risk factor for ShD independent of other known risks. Male sex also amplified the existing effects of short maternal height, extended gestational age, and greater birth weight. If infant sex is known to be male before delivery, the obstetrician may consider avoiding vaginal delivery in mothers who have other strong risks for ShD.     

Perinatal risk factors for hay fever--a study among 2550 Finnish twin families.

Previous studies have suggested that perinatal factors influence the risk for asthma but population studies on perinatal factors and risk for hay fever are few. We studied the effect of perinatal factors on the risk for hay fever among adolescent twins by a questionnaire study involving five consecutive nation-wide birth cohorts of 16-year-old twins and their parents. The risk for parent-reported, doctor-diagnosed hay fever in the adolescents associated with several perinatal characteristics was assessed with logistic regression analysis among individuals and by a discordant pair analysis. In the univariate analysis of the birth factors, the risk for hay fever increased with increasing birth weight (p for trend = 0.048, OR for those > or = 3000 g 1.35, 95% CI 0.91-2.02 compared to those < 2000 g) and gestational age (p for trend = 0.04, OR for those born after 40 weeks of gestation 2.24, 95% CI 1.03-4.86, compared to those born before 33 weeks of gestation) and was lower in those subjects hospitalised in the neonatal period (OR 0.74, 95% CI 0.58-0.93). Because of significant interactions between parental hay fever status and birth factors (ponderal index, p = 0.03 and maternal age p = 0.04), stratified analysis were performed. The positive association between birth weight and hay fever was most obvious among adolescents with no parental history of hay fever (p for trend = 0.03). Similar, though not significant, trends were found with other birth factors among these families, whereas no such trend was found among adolescents with parental hay fever, suggesting that gestational maturity increases the risk for hay fever in the absence of genetic predisposition. However, of the perinatal factors only neonatal hospitalisation (OR 0.75, 95% CI 0.59-0.96) remained a significant risk factor for the development of hay fever, when adjusted for non-perinatal factors.     

Effect of paternal age on the birth sex ratio in captive populations of aye‐aye (Daubentonia madagascariensis (Gmelin))

For the management of captive populations of zoo animals, it is important to elucidate factors that affect the offspring birth sex ratio. On the basis of the sex allocation theory, the Trivers–Willard and mate attractive/quality hypotheses predict that maternal and paternal conditions affect offspring birth sex ratios. We examined these predictions for the birth sex ratio of aye‐aye Daubentonia madagascariensis (Gmelin) by analyzing the pedigree information in the International Studbook. We found that the birth sex ratio of the aye‐aye was affected by the paternal age, but not maternal age and other environmental factors (birth year, season, and institution). The younger the sire, the more the offspring sex ratio was biased toward males. These results are useful for the effective population management of captive aye‐aye and illustrated the usefulness of the sex allocation theory in the sex ratio management of zoo animals.