Sex differences in birth defects: a study of opposite-sex twins

BACKGROUND: Sex differences in structural birth defects are often confounded by environmental risk factors. Opposite-sex twins provide a unique model for detecting sex differences in birth defects while maximally controlling environmental risk factors in a natural setting. METHODS: Population data from the Florida Birth Defects Registry were analyzed. A total of 4,768 pairs of twins who were discordant for sex and born between 1996 and 2001 were analyzed. The McNemar test was used to compare the differences between a male twin and his twin sister for the risk of developing specific defects and organ-system defects. RESULTS: Of 4,768 twin pairs, 225 males (4.72%) and 175 females (3.67%) had birth defects. Among opposite-sex twin pairs, males had a 29% higher risk for birth defects than their twin sisters. Compared to their twin sisters, males had a 5.4 times higher risk for pyloric stenosis and a 2.4 times higher risk for obstructive genitourinary defect, but only one-tenth the risk for congenital hip dislocation. CONCLUSIONS: Sex differences in birth defects exist between opposite-sex twins.     

The risk of birth defects in dichorionic twins conceived by assisted reproductive technology.

The purpose of this study was to examine whether dichorionic twins conceived by assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI], in vitro fertilization [IVF], gamete-intrafallopian tube transfer [GIFT]) have a higher risk of birth defects compared to dichorionic twins conceived naturally. We reviewed the medical records of 406 mothers with dichorionic twin pregnancies, who received continuous antenatal care from < or = 20 weeks of gestation and gave birth to infants after > or = 24 weeks of gestation in our institute. Birth defects were diagnosed at the time of hospital discharge according to the International Classification of Diseases, 10th Revision. Occurrence of birth defects was compared between twins conceived by ART and those conceived naturally using logistic regression analysis. Overall, 51 of 812 infants (51/812 = 6.2%) had birth defects. The incidence of birth defects in ART-conceived twins was significantly higher than that of naturally conceived twins with an odds ratio of 6.9 (95% confidence interval [CI] 2.1, 22.5), 3.7 (95% CI 1.2, 12.0), and 4.3 (95% CI 1.4, 14.3) for ICSI, IVF, and GIFT, respectively. The higher frequency of birth defects in ART-conceived twins was still significant after adjusting for higher maternal age in the ART group, with an adjusted odds ratio of 6.7 (95% CI 2.1, 21.9), 3.6 (95% CI 1.1, 11.5), and 3.7 (95% CI 1.2-11.8) for ICSI, IVF, and GIFT, respectively. Dichorionic twins conceived by ART, compared to dichorionic twins conceived naturally, had a much higher risk for birth defects diagnosed at hospital discharge.     

Maternal intake of vitamin E and birth defects,national birth defects prevention study, 1997 to 2005

BACKGROUND In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy‐adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy‐adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35) and all CHDs combined. Among CHD sub‐types, we observed associations with left ventricular outflow tract obstruction defects, and its sub‐type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01–2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09–1.87). CONCLUSION: Selected quartiles of energy‐adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure‐response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings. Birth Defects Research (Part A), 100:647–657, 2014. © 2014 Wiley Periodicals, Inc.     

Familial resemblance for anthropometric traits in dizygotic twins and siblings

Familial resemblance for fifty anthropometric traits was studied on a sample of 45 MZ, 101 DZ twin pairs and their 125 singleton siblings. Intraclass correlation coefficients were significant for all the traits. However, resemblance within DZ twin pairs was significantly greater than within sibs for 22 variables, showing that the former had a more correlated environment than the latter. The study also showed that head and facial traits were relatively more stable to the environmental factors than the body traits and hence more suitable for cross-cultural comparisons. The study listed measures of girth and skinfold, thickness as the most labile traits.     

Association between reported venlafaxine use in early pregnancy and birth defects,national birth defects prevention study, 1997–2007

BACKGROUND

Few epidemiologic studies have investigated the use of venlafaxine (Effexor XR capsules, Product Monograph, Wyeth, Montreal, Canada), an antidepressant used to treat major depression and anxiety disorders in adults, during pregnancy. Our objective was to determine whether use of venlafaxine during pregnancy is associated with specific birth defects.

METHODS

We used data from the National Birth Defects Prevention Study (NBDPS), a population‐based, case‐control study in the United States. Our analysis included mothers with pregnancies affected by one of 30 selected birth defects (cases) and babies without birth defects (controls) with estimated dates of delivery between 1997 and 2007. Exposure was any reported use of venlafaxine from 1 month preconception through the third month of pregnancy. We calculated adjusted odds ratios (aORs) and 95% Fisher Exact confidence intervals (CIs) for 24 birth defect groups for which at least 400 case mothers were interviewed. Our adjusted analyses controlled for maternal age and race/ethnicity.

RESULTS

Among the 27,045 NBDPS participants who met inclusion criteria, 0.17% (14/8002) of control mothers and 0.40% (77/19,043) of case mothers reported any use of venlafaxine from 1 month preconception through the third month of pregnancy. Statistically significant associations were found for anencephaly, atrial septal defect (ASD) secundum, or ASD not otherwise specified, coarctation of the aorta, cleft palate, and gastroschisis.

CONCLUSIONS

Our data suggest associations between periconceptional use of venlafaxine and some birth defects. However, sample sizes were small, CIs were wide, and additional studies are needed to confirm these results. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Behavioral inhibition as a function of relationship in preschool twins and siblings.

Monozygotic (MZ) twins spend more time with each other and are more genetically alike than are dizygotic (DZ) twins or nontwin siblings and therefore probably experience less diversity in their playmates than DZ twins, who in turn may experience less diversity than other-age siblings. Thus MZ twins may be more inhibited than DZ twins, who may in turn be more inhibited than nontwin siblings. To test this, 205 children (42 MZ twins, 94 DZ twins, and 69 nontwin siblings) were assessed in a playroom laboratory during free play with an unfamiliar peer. Children's inhibition was rated based on latency to touch a toy for the first time and amount of time spent interacting with the other child. Additionally, the Child Behavior Checklist (CBCL) withdrawn scale was used to assess inhibition according to parent report. Behavioral ratings showed that MZ and DZ twins did not significantly differ on the inhibition or withdrawn ratings. DZ twins were significantly more inhibited than were nontwin siblings, according to laboratory ratings. Greater inhibition of twins during the free peer play situation can be explained by their relative lack of experience in playing with children who are less genetically and phenotypically like themselves. Parental ratings showed exactly the opposite pattern, suggesting a rater bias effect.     

Paternal age and the occurrence of birth defects

The association between paternal age and the occurrence of birth defects was studied using data collected in Metropolitan Atlanta. Paternal-age information for babies born with defects was obtained from birth certificates, hospital records, and interviews with mothers; for babies born without defects, the information was obtained from birth certificates. Several statistical techniques were used to evaluate the paternal-age-birth-defects associations for 86 groups of defects. Logistic regression analysis that controlled for maternal age and race indicated that older fathers had a somewhat higher risk for having babies with defects, when all types of defects were combined; an equivalent association for older mothers was not found. Logistic regression analyses also indicated modestly higher risks for older fathers for having babies with ventricular septal defects and atrial septal defects and substantially higher risks for having babies with defects classified in the category chondrodystrophy (largely sporadic achondroplasia) and babies with situs inversus. An association between elevated paternal age and situs inversus has not been reported before; the magnitude of the estimated increased risk for situs inversus was about the same as that found in this study for chondrodystrophy.     

The genetic liability to disability retirement: a 30-year follow-up study of 24,000 Finnish twins

Background

No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders.

Methods

The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement.

Results

The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71).

Conclusions

A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation.     

Sex differences in the prevalence of human birth defects: a population-based study.

BACKGROUND: Sex differences in the prevalence of several human birth defects have often been reported in the literature, but the extent of sex differences for most birth defects is unknown. To determine the full extent of sex differences in birth defects in a population, we examined population-based data from the Metropolitan Atlanta Congenital Defects Program (MACDP). METHODS: MACDP records were analyzed for 1968 through 1995. We determined the sex-specific prevalence of all major birth defects, using the total number of live births by sex during these years as the denominator. For each specific defect, we calculated a relative risk with regard to sex on the basis of the ratio of prevalence among males to prevalence among females. Male-female relative risks were also determined for total major birth defects and for several broad categories of defects. RESULTS: The overall prevalence of major defects at birth was 3.9% among males and 2.8% among females. All but two of the major categories of birth defects (nervous system defects and endocrine system defects) had a higher prevalence among males. Defects of the sex organs were eight and one-half times more prevalent among males and accounted for about half of the increased risk of birth defects among males relative to females. Urinary tract defects were 62% more prevalent among males, and gastrointestinal tract defects were 55% more prevalent among males. Among specific defect types, twofold or greater differences in prevalence by sex were common. CONCLUSIONS: Our data indicate that sex differences in the prevalence of specific human birth defects are common, and male infants are at greater risk for birth defects than female infants. Several mechanisms have been proposed to account for these differences.