Maternal Serum Alpha-Fetoprotein Level during Pregnancy and Isolated Cryptorchidism in Male Offspring

Abstract

Cryptorchidism is thought to result from a disruption of the androgen-estrogen balance in utero. Alpha-fetoprotein (AFP) interacts with and may modulate fetal responses to estrogens. Using a cohort of boys born to women participating in a Danish maternal serum AFP screening program between 1980 and 1994, the authors explored whether AFP levels (as reflected by maternal serum AFP levels in gestational weeks 14-22) were associated with the risk of isolated cryptorchidism in male offspring. Cryptorchidism diagnoses and covariate information were obtained from Denmark's national health registries. Risk ratios for cryptorchidism by maternal serum AFP multiples of the median were estimated by use of log-linear binomial regression. Of 25,418 boys, 663 (2.6%) were diagnosed with cryptorchidism. After adjustment for confounders, boys with maternal serum AFP levels greater than or equal to 2.5 times the median had a 63% (95% confidence interval: -2, 172) greater risk of cryptorchidism than did boys with maternal serum AFP levels within 25% of the median. High fetal AFP levels may contribute directly to events producing cryptorchidism; alternatively, elevated maternal serum AFP levels may reflect placental dysfunction, some aspect of which contributes to cryptorchidism.

Undescended testis: current theories of etiology

“…Not all studies, however, suggest that the risk of cryptorchidism is increasing in defined populations [6][7][8]. Sijstermans et al…”

“…While the ratio of nonsyndromic to syndromic cryptorchidism was greater than 6 : 1 in a large cohort [8] this anomaly remains a feature of at least 393 syndromes (Winter-Baraitser dysmorphology database, http:// www.lmdatabases. com).…”

“…Other diseases associated with intrauterine growth restriction [41], including trisomy 21 [42], genetic imprinting disorders (Prader-Willi [43] and Silver-Russell syndromes [44]) and abdominal wall defects [45] are known to be associated with cryptorchidism. Recently, Boyd and colleagues [8] observed a direct correlation between elevated maternal a-fetoprotein (AFP) levels in mid-gestation and nonsyndromic cryptorchidism; elevated AFP is also correlated with fetal growth restriction [41]. While this finding has yet to be explained or corroborated, Boyd et al suggest that high AFP may reflect abnormal regulation of fetal production or increased passage into the maternal circulation in the presence of an abnormal placenta [8].…”

Accuracy of Cryptorchidism Diagnoses and Corrective Surgical Treatment Registration in the Danish National Patient Registry

“…14 Several prenatal exposures have been evaluated by aggregating data from these cohorts with cryptorchidism end points from the DNPR, including maternal alcohol consumption, tobacco smoking, use of weak analgesics, pregnancy levels of alphafetoprotein and parental occupational exposures to potentially endocrine disrupting chemicals. [15][16][17][18][19][20][21][22] Despite these research efforts, less attention has been given to the validity of the registry data on cryptorchidism. 23 Validity reflects the probability of being registered given that one has cryptorchidism, and the probability of having cryptorchidism given that one is registered.…”

Autism Spectrum Disorders and Maternal Serum alpha-Fetoprotein Levels during Pregnancy

“…25 Besides the well documented classical role of MS-AFP in screening for NTDs, 26 there is growing evidence suggesting a potential beneficial role of MS-AFP in the prediction of other disorders, such as preterm birth 27 and adverse maternal or fetal outcomes in general. 28 Previous population-based studies have also documented the association between MS-AFP and cryptorchidism 29 and maternal breast cancer during pregnancy, 30 yet the literature is limited about the role of AFP in ASD.…”