Hypospadias Is Related to Birth Weight in Discordant Monozygotic Twins

Fredell, Louise; Lichtenstein, Paul; Pedersen, Nancy L.; Svensson, Jan‐Olof; Nordenskjöld, Agneta

doi:10.1097/00005392-199812010-00084

Cited by 53 publications

(39 citation statements)

References 9 publications

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“…The results of this study, showing both low weight and length at birth in children with MPH of undefined aetiology, confirm the data of previous studies [4,5,6,12,14] demonstrating an association between intrauterine growth retardation and genital ambiguity in male patients. Our results also show that birth length was more severely decreased than birth weight, indicating that early intrauterine growth retardation may be associated with abnormal testicular differentiation.…”

Section: Discussionsupporting

confidence: 91%

“…Recently, several articles have been published indicating a possible relationship between idiopathic MPH or isolated hypospadias and prenatal growth retardation. In 1998, Fredell et al [6], studying 18 pairs of monozygotic twins, reported a significant increase in the frequency of hypospadias in the twin with a lower birth weight. In 1999, Francois et al [5], studying 29 children with MPH, observed a higher frequency of low birth weight and complications in early pregnancy among cases of idiopathic MPH.…”

Section: Introductionmentioning

confidence: 99%

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Idiopathic male pseudohermaphroditism is associated with prenatal growth retardation

et al. 2005

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Idiopathic male pseudohermaphroditism is associated with prenatal growth retardation

et al. 2005

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“…A study of 18 twin pairs in which one twin had hypospadias and one did not, found that in 16 pairs, the healthy twin brother weighed on average 500 g more at birth than the twin with hypospadias [28]. As monozygotic twins share the same intrauterine environment and genotype, this study supports the hypothesis that fetal growth and the risk of hypospadias are strongly associated.…”

Section: Hypospadiassupporting

confidence: 77%

“…The strongest indication of an association between intrauterine growth and hypospadias comes from monozygotic twins [28, 29]. A study of 18 twin pairs in which one twin had hypospadias and one did not, found that in 16 pairs, the healthy twin brother weighed on average 500 g more at birth than the twin with hypospadias [28].…”

Section: Hypospadiasmentioning

confidence: 99%

Low Birth Weight and Male Reproductive Function

et al. 2006

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Scientific interest in morbidity in children born small for gestational age (SGA) has increased considerably over the last few decades. The elevated risk of cardiovascular and metabolic diseases in adulthood in individuals born SGA has been well documented, whereas data on gonadal development are limited. Prospective studies, case-control investigations and registry surveys show that impaired intrauterine growth increases the risks of congenital hypospadias, cryptorchidism and testicular cancer approximately two- to threefold. Although few studies focus on the effect of intrauterine growth on male pubertal development, testicular hormone production or sperm quality, available evidence points towards a subtle impairment of both Sertoli cell and Leydig cell function. Animal studies support the hypothesis that impaired perinatal growth restriction, depending on the timing, can affect postnatal testis size and function into adulthood. Current human data, however, are often based on highly selected hospital populations and lack precise distinctions between low birth weight, SGA, timing of growth restriction and a differentiation of catch-up growth patterns. Despite the methodological inadequacies of individual study results, the combined evidence from all data leaves little doubt that fetal growth restriction is associated with increased risk of male reproductive health problems, including hypospadias, cryptorchidism and testicular cancer.

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“…One possible explanation is that placental insufficiency in providing the fetus with nutrients and gonadotropins may lead to both growth retardation and hypospadias [13,14,17,34]. Placental insufficiency may also explain the increased occurrence of hypospadias in twins [13,14,34]. However, familial clustering suggests a genetic component in the etiology of hypospadias [12].…”

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confidence: 99%

Risk factors for hypospadias

et al. 2006

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Despite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this case-referent study, we evaluated a wide spectrum of potential risk factors for hypospadias. Cases were identified from the hospital information system, and referents were recruited through the parents of the cases. Both parents of cases and referents completed written questionnaires that they received through the mail. Logistic regression analyses were used to assess the independent contribution of different factors to the risk of hypospadias. The final database included 583 cases and 251 referents. Hypospadias more often occurred in children whose father had hypospadias (OR=9.7; 95%CI: 1.3-74.0) and in children with a low birth weight (OR=2.3; 95%CI: 1.2-4.2). Indications for elevated risks were found when mothers were DES-daughters (OR=3.5; 95%CI: 0.8-15.6), fathers were subfertile (OR=1.8; 95%CI: 0.7-4.5), the parents had undergone fertility treatment (OR=2.3; 95%CI: 0.9-5.8), and in twin or triplet pregnancies (OR=2.0; 95%CI: 0.8-5.1). Maternal use of iron supplements (OR=2.2; 95%CI: 0.8-6.0), maternal smoking (OR=1.5; 95%CI: 1.0-2.4), paternal prescriptive drug use (OR=2.6; 95%CI: 1.1-6.6), and paternal exposure to pesticides (OR=2.1; 95%CI: 0.6-7.1) during the 3 months immediately prior to conception or in the first trimester of pregnancy also appeared to increase the risk of hypospadias. The associations found in this study support the hypothesis that genetic predisposition, placental insufficiency, and substances that interfere with natural hormones play a role in the etiology of hypospadias.

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Hypospadias Is Related to Birth Weight in Discordant Monozygotic Twins

Abstract: Environmental factors associated with low birth weight are involved in the etiology of hypospadias.

Cited by 53 publications

References 9 publications

Idiopathic male pseudohermaphroditism is associated with prenatal growth retardation

Idiopathic male pseudohermaphroditism is associated with prenatal growth retardation

Low Birth Weight and Male Reproductive Function

Risk factors for hypospadias

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