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Evidence has emerged that childhood leukemia is initiated in utero. High birth weight is one of the few birth-related factors that has been associated with childhood leukemia, albeit not consistently. The authors conducted a meta-analysis of studies of the association between birth weight and childhood leukemia risk. Study-specific odds ratios for leukemia were calculated, using a cutoff at 4,000 g of birth weight. The authors also evaluated whether the association between birth weight and leukemia followed a log-linear dose-response-like pattern. They calculated summary estimates using weighted averages of study-specific odds ratios from dichotomous and trend analyses. Eighteen studies (published between 1962 and 2002) were included, encompassing 10,282 children with leukemia. Children weighing 4,000 g or more at birth were at higher risk of acute lymphoblastic leukemia than children weighing less (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.17, 1.37). Furthermore, data were consistent with a dose-response-like effect (OR = 1.14/1,000-g birth weight increase, 95% CI: 1.08, 1.20). Studies of acute myeloid leukemia indicated a similar increase in risk for children weighing 4,000 g or more at birth (OR = 1.27, 95% CI: 0.73, 2.20) and a dose-response-like effect (OR = 1.29/1,000 g, 95% CI: 0.80, 2.06), but results varied across studies. Our findings support a relation between birth weight and childhood acute lymphoblastic leukemia risk and emphasize the need for additional studies of the biologic mechanisms underlying this association. [ABSTRACT FROM AUTHOR]

Although cryptorchidism is the most common birth defect in boys affecting 4–9 percent of newborns and 1–2 percent of boys 1 year of age, the etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of cryptorchidism. Using Danish health registers, they identified 25,395 boys diagnosed with cryptorchidism in a cohort of 1,022,713 boys born in 1977–2005. Using binomial log-linear regression, they estimated recurrence risk ratios (RRRs) of cryptorchidism for male twin pairs and first-, second-, and third-degree relatives of a cryptorchidism case. The RRR in same-sex twins was 10.1 (95% confidence interval (CI): 7.78, 13.1). The RRR among first-degree relatives was significantly higher among brothers (RRR = 3.52, 95% CI: 3.26, 3.79) than for offspring of a cryptorchidism case (RRR = 2.31, 95% CI: 2.09, 2.54). The RRR was also found to be significantly higher in maternal (RRR = 2.12, 95% CI: 1.74, 2.60) than paternal (RRR = 1.28, 95% CI: 1.01, 1.61) half brothers. In conclusion, inherited factors were found to have a moderate influence on the risk of cryptorchidism. The data are compatible with the hypothesis that maternal factors operating in utero are important for the risk of cryptorchidism. [ABSTRACT FROM AUTHOR]

Although cryptorchidism is the most common birth defect in boys affecting 4–9 percent of newborns and 1–2 percent of boys 1 year of age, the etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of cryptorchidism. Using Danish health registers, they identified 25,395 boys diagnosed with cryptorchidism in a cohort of 1,022,713 boys born in 1977–2005. Using binomial log-linear regression, they estimated recurrence risk ratios (RRRs) of cryptorchidism for male twin pairs and first-, second-, and third-degree relatives of a cryptorchidism case. The RRR in same-sex twins was 10.1 (95% confidence interval (CI): 7.78, 13.1). The RRR among first-degree relatives was significantly higher among brothers (RRR = 3.52, 95% CI: 3.26, 3.79) than for offspring of a cryptorchidism case (RRR = 2.31, 95% CI: 2.09, 2.54). The RRR was also found to be significantly higher in maternal (RRR = 2.12, 95% CI: 1.74, 2.60) than paternal (RRR = 1.28, 95% CI: 1.01, 1.61) half brothers. In conclusion, inherited factors were found to have a moderate influence on the risk of cryptorchidism. The data are compatible with the hypothesis that maternal factors operating in utero are important for the risk of cryptorchidism. [ABSTRACT FROM AUTHOR]

Hypospadias is one of the most common birth defects. However, its etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of hypospadias. Using Danish health registers, they identified 5,380 boys diagnosed with hypospadias in a cohort of 1,201,790 boys born in 1973–2005. Using binomial log-linear regression, they estimated recurrence risk ratios of hypospadias for male twin pairs and first-, second-, and third-degree relatives of a hypospadias case, which were 50.8 (95% confidence interval [CI]: 34.2, 75.5), 11.6 (95% CI: 9.75, 13.7), 3.27 (95% CI: 2.47, 4.34), and 1.33 (95% CI: 0.94, 1.88), respectively. Recurrence risk ratios did not differ for family members of a hypospadias case related to the same degree. In addition, the authors found no difference in the recurrence risk ratio for maternal compared with paternal second- and third-degree relatives of a hypospadias case. In conclusion, hypospadias was found to have a strong familial component and also to aggregate within more-distant relatives. Importantly, hypospadias was equally transmitted through the paternal and maternal sides of a family, and recurrence risk ratios for brothers and sons of a hypospadias case were similar. These findings indicate that genetic rather than intrauterine environmental factors have a principal role in causing familial hypospadias. [ABSTRACT FROM AUTHOR]