25.10.2014

Hypospadias difficulty getting pregnant

Even though hypospadias is something that some men are born with, it is treatable bay a surgery that is conducted during the first year of life. Also men who are born with hypospadias are also more likely to be born with what is called an undescended testicle as well. Hypospadias is a birth defect in boys in which the opening of the urethra (the tube that carries urine from the bladder to the outside of the body) is not located at the tip of the penis.
Women can take steps before and during pregnancy to reduce the risk of having a baby born with birth defects.
An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors.
We conducted a case–control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls.
A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring.
Hypospadias is a male birth defect in which the urethral orifice is abnormally located on the ventral side of the penis.
Reported associations between hypospadias and low birth weight, preterm birth, and signs of preeclampsia (Akre et al.
The data for this study were collected as part of a joint Danish–Swedish case–control study of both hypospadias and cryptorchidism. Each Swedish administrative region has a single pediatric surgery clinic to which all hypospadias cases are referred upon discovery.
For each hypospadias case, we randomly selected one or two control boys without known malformations or chromosomal abnormalities from the Swedish Medical Birth Register (one control per case during the first half of the study, and two controls per case during the second half), born within 6 months of and in the same county as the case. In our questionnaire, we asked mothers of boys recruited from the DNBC to confirm that their sons had (cases) or did not have (controls) hypospadias. When we restricted our analysis by excluding cases with cleaved prepuce or glandular or coronary hypospadias from the Stockholm clinic and their matched controls, we obtained results similar to those presented in Table 2, albeit with wider CIs (data not shown). Our maternal diet finding complements a previously reported strong positive association between maternal vegetarian diet and hypospadias risk (North and Golding 2000).
Several authors have suggested that hypospadias may be caused by abnormal levels of pregnancy hormones resulting from impaired placental function or exposure to disruptive exogenous hormones (Akre et al. Nausea in early pregnancy is believed to be caused by the early surge of pregnancy hormones, particularly hCG; the onset and peak of nausea and vomiting in early pregnancy parallel the hCG curve (Furneaux et al. Several previous studies have found associations between hypospadias risk and preterm birth and low birth weight (Akre et al. Case ascertainment in Sweden involved examination by a pediatric urologist, thus ensuring the specificity of the hypospadias diagnosis among the Swedish cases.
In conclusion, consistent with a previous hypothesis-generating study (North and Golding 2000), we found a strongly increased risk of hypospadias associated with a maternal diet lacking in fish and meat. Such steps include taking a daily multivitamin with folic acid (400 micrograms), not smoking, and not drinking alcohol during pregnancy.
If you are pregnant or thinking about becoming pregnant, talk with your doctor about ways to increase your chance of having a healthy baby.
Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.
In Western countries, the prevalence of hypospadias varies from 2 to 8 cases per 1,000 live births, with increases in prevalence reported over time in several populations (Czeizel et al.
We recruited hypospadias cases without concomitant malformations or chromosomal abnormalities from the clinics at Karolinska University Hospital (Stockholm) and Uppsala Academic Hospital, which together serve a population with almost 50,000 live births per year.


To investigate the effects of our exposure variables in the most severely affected group of hypospadias cases possible, we repeated the analyses restricted to more severe cases from this clinic (n = 77) and their matched controls. In the univariate analyses, we found the following variables to be positively associated with risk of hypospadias: low maternal age, high maternal body mass index (BMI), low maternal education, pregnancy hypertension, proteinuria during pregnancy, lack of nausea during pregnancy, no meat consumption during pregnancy, no or low intake of fish during pregnancy, maternal passive smoking during pregnancy, low birth weight, low gestational age at birth, and neonatal jaundice (Table 1).
Likewise, maternal age, maternal education, and proteinuria were not significantly associated with hypospadias risk in the final model.
Compared with maternal nausea in the first trimester, the absence of maternal nausea during pregnancy almost doubled the risk of hypospadias, whereas boys whose mothers experienced nausea only in the third trimester had a significant 7-fold increased risk (Table 2).
Being born preterm (? 36 gestational weeks) was associated with a 9-fold increased risk of hypospadias, compared with being born in gestational week 40 or 41 (Table 2). A pregnancy diet lacking in meat and fish, a high maternal prepregnancy BMI, and absence of nausea during early pregnancy all independently increased hypospadias risk. Those using non-hormonal contraceptive methods such as condoms and “natural” methods had a significantly decreased OR for the risk hypospadias in the crude analysis, but not in the multivariable analysis. Two-thirds of the cases in Denmark we identified through nationwide registers, using ICD codes for hypospadias. Furthermore, we found positive associations between the absence of nausea during pregnancy, maternal hypertension, high BMI, and risk of hypospadias.
We invited mothers of boys with a hypospadias diagnosis, confirmed by a pediatric urologist in the periods March 2000 through September 2001 and September 2003 through March 2005, to participate in our case–control study; 204 (95%) of 214 women accepted the invitation. More than 101,000 pregnant women recruited during 1996–2002 gave birth to nearly 94,000 children between 1997 and 2003. Apart from a few extra questions in the Danish questionnaire regarding the ascertainment of hypospadias, the questionnaires used in Sweden and Denmark were identical. We defined “severe” hypospadias in this case as having the urethral orifice proximal to the glandular corona. Use of nonhormonal forms of contraception at the time of conception was negatively associated with hypospadias risk (Table 1).
Passive maternal exposure to tobacco smoke during pregnancy increased the risk of hypospadias by 88%. Nonhormonal contraceptive methods per se are unlikely to be protective against hypospadias, but women employing them should have less exposure to exogenous hormones in the period just before conception than those who become pregnant immediately after stopping oral contraceptive use or while still using oral contraceptives. However, because there are no well-established etiologies for hypospadias, for most exposures mothers of cases would have been unlikely to systematically over- or underreport their exposure status compared with control mothers.
Most of these findings are compatible with a role for placental insufficiency in the etiology of hypospadias.
Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at three months of age.
Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.
Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data.
If hypospadias is not treated it can lead to problems later in life, such as difficulty performing sexual intercourse or difficulty urinating while standing. Because the doctor might need to use the foreskin to make some of the repairs, a baby boy with hypospadias should not be circumcised. We excluded controls if a) information on hypospadias (n = 4) or cryptorchidism (n = 5) was missing, b) their mothers claimed they had hypospadias (n = 1), or c) they were reported to have cryptorchidism (n = 4). The association between low consumption of meat and risk of hypospadias was also stronger after adjustment.


In contrast, active maternal smoking in the first trimester was not significantly associated with hypospadias risk. First-trimester nausea is considered to be a sign of a healthy pregnancy, because it is associated with lower risks of miscarriage and premature birth (Cnattingius et al. Although the sensitivity of the registers for the milder forms of hypospadias may be low, registration of the more severe hypospadias is probably fairly complete.
However, when we restricted the analysis to Swedish cases of known severity and focused on more severe forms of hypospadias, we found no indication of different etiologic patterns for the severe cases that could indicate that our results are not generalizable to less severe cases, nor did we see any clear sign of a dose–response relation between any exposure and degree of hypospadias. Although the estimated prevalence at birth of hypospadias in Sweden is 0.0033, our case detection rate seems reasonable, because we restricted the study to isolated malformations that were discovered at an early age. For boys, the first postpartum interview, which occurred when the infant was approximately 6 months of age, included questions about hypospadias as well as other birth defects and chromosomal abnormalities.
In particular, reduced levels of human chorionic gonadotropin (hCG) have been suggested as a candidate in the etiology of hypospadias (Czeizel et al.
Furthermore, it is unlikely that boys are falsely registered with the condition (high specificity of the registers for hypospadias). For example, it is unlikely that lack of nausea is perceived by laymen to be a problem, making it improbable that our finding of an increased risk of hypospadias associated with lack of nausea could be explained by differential recall.
We found an association between hypospadias risk and exposure to passive smoking, but no association with active maternal smoking. Although we know that urethral development, occurring during gestational weeks 7–16, is regulated by androgens, the causes of most hypospadias cases are unknown (Baskin and Ebbers 2006). In the question regarding nausea during pregnancy, we asked those who stated that they had been nauseous to specify the trimester of nausea, and permitted them to specify more than one trimester.
In contrast, the absence of nausea may reflect potential problems with the pregnancy and is associated with low hCG levels (Cnattingius et al. In our data, we found an increased risk of hypospadias among the offspring of overweight and obese women, with a dose–response relationship between BMI and hypospadias risk.
Several gene defects, including defects in genes coding for the androgen receptor, are associated with hypospadias but account for only a small proportion of cases (Nelson et al. As discussed in more detail below, our findings of associations between an increased risk of hypospadias and no maternal nausea during early pregnancy, low weight for gestational age, preterm birth, gestational hypertension, and maternal overweight may all potentially be explained by impaired placental hormone production. Our finding that the absence of nausea during early pregnancy was associated with increased hypospadias risk therefore lends support to the hypothesis that abnormally low hCG levels resulting from placental insufficiency in early pregnancy may be involved in the etiology of hypospadias. It seems plausible that our findings of increased risks of hypospadias associated with both gestational hypertension and obesity, despite their statistical independence, share pathogenetic mechanisms, possibly through their link to impairment of placental function and growth during early pregnancy. To date, only a few studies have reported positive associations between hypospadias and environmental exposures, but reports of links with prenatal exposure to diethylstilbestrol (Brouwers et al. Our additional finding that hypospadias risk is associated with gestational hypertension, which in turn is associated with preeclampsia and placental dysfunction (Ros et al. Our observation that nausea only during late pregnancy (“abnormal” nausea) was associated with an increased risk of hypospadias is more difficult to explain, because the closing of the urethral orifice occurs early in pregnancy.
2005) and provides further support for the notion that placental dysfunction is involved in the etiology of hypospadias. With the results of these previous studies in mind, in the present case–control study we investigated the relationships between hypospadias risk and maternal diet, exposure to exogenous hormones, and exposures thought to reflect placental function. On the other hand, little is known about the mechanisms underlying nausea in late pregnancy, but its etiology is likely to differ from that of nausea in early pregnancy, and it may reflect some process initiated at the beginning of pregnancy that has some bearing on the development of hypospadias.



Dreampt about being pregnant with a baby girl
Unable to get pregnant a second time


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