Utility and safety of hyperbaric oxygen therapy as a rescue treatment in complicated cases of hypospadias: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to define the current evidence and systematically summarize the relevant data regarding the utility and safety of hyperbaric oxygen therapy (HBOT) as an adjunctive treatment in complicated re-operative cases of hypospadias. METHOD: The authors systematically searched the PubMed, EMBASE, Web of Science, and Scopus databases on August 5, 2021. Patients were divided into two groups, i.e. HBOT and non-HBOT. The main outcomes were graft failure rate and the incidence of complications following urethroplasty. The proportion of patients developing adverse events due to HBOT was the secondary outcome. The pooled risk ratio and heterogeneity were calculated using the Mantel-Haenszel method and the I2 statistics respectively. The quality assessment of the included studies was performed using the Downs and Black scale. RESULT: Four studies constituting 176 patients (101 in the HBOT group) were included (Figure). Variations were observed among these studies in terms of the age of participants, the number and types of previous operations performed, and the protocol of administration of HBOT. The graft failure rate (RR 0.19; 95% CI 0.05-0.73, p = 0.02) and the incidence of complications (RR 0.40, 95% CI 0.20-0.77, p = 0.007) were significantly low in the HBOT versus the non-HBOT group. Apart from myringotomy insertion (n = 10; 9.9%) and claustrophobia (n = 1), no other adverse events were associated with HBOT. All studies had a moderate risk of bias. An almost perfect agreement (kappa = 0.956, p < 0.0001) was observed between the two investigators assessing the risk of bias. CONCLUSION: The present systematic review and meta-analysis significantly favor the administration of HBOT versus no HBOT in terms of graft failure rate and incidence of complications following urethroplasty. The available data also highlights the safety of HBOT in complicated cases of hypospadias. However, well-designed randomized controlled trials need to be conducted for an optimal comparison between the two treatment groups.

Maternal Smoking, Alcohol, and Caffeine Exposures and Risk of Hypospadias.

BACKGROUND: We examined the association of hypospadias risk with maternal smoking and consumption of alcohol and caffeine. METHODS: We analyzed data from mothers of 2437 moderate/severe cases and 5472 nonmalformed controls born from 1997 to 2011 who participated in the National Birth Defects Prevention Study (NBDPS). Exposures were assessed by maternal telephone interviews. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for mother's age, parity, race-ethnicity, education, vitamin/mineral supplement intake, obesity, and study center. RESULTS: Active smoking during the first month of pregnancy was associated with reduced risk, with smaller ORs for increasing quantity smoked; the OR for smoking >1/2 pack/day was 0.7 (95% CI, 0.5-0.9). Among nonsmokers, the OR for any secondhand smoke exposure was 0.8 (95% CI, 0.7-0.9). ORs for alcohol and caffeine consumption were near one and CIs included 1.0. In an analysis of joint exposures to smoking and alcohol and caffeine consumption, the only OR for which the 95% CI excluded 1.0 was for women who smoked, drank, and had low caffeine consumption (OR, 0.6; 95% CI, 0.4-0.8). CONCLUSION: Maternal exposure to cigarette smoke was associated with reduced risk, and women who smoked, drank, and had low caffeine intake were at lowest risk. We do not interpret these results to suggest that these exposures have overall benefit to a pregnant woman or developing fetus. They may, however, offer clues to help us understand mechanisms that lead to hypospadias. Birth Defects Research 109:1127-1133, 2017. © 2017 Wiley Periodicals, Inc.

Hypertensive Emergencies in Pregnancy.

The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders.

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.

Relationship between maternal dietary patterns and hypospadias.

Little is known about the role of maternal nutrition in the development of hypospadias, which is the most common urogenital congenital anomaly. This study investigated the relationship between maternal nutrition and the risk of hypospadias, particularly focusing on maternal food patterns. We compared 471 hypospadias cases with 490 controls in the United Kingdom. A questionnaire including information on life style, occupation, usual maternal diet and dietary supplements was administered using telephone interviews. Cases and controls were compared for individual food item intake and food patterns derived by cluster analysis. Multivariable logistic regression analysis adjusted for income, maternal age, low birthweight, smoking and folic acid supplement use was used to assess the relationship between maternal nutrition and hypospadias. Three food patterns were created with the labels 'health conscious', 'mixed' and 'non-health conscious'. 'Non-health conscious' subjects (low frequency of consumption of yoghurt, cheese, eggs, fruit and vegetables, fish, beans and pulses, olive oil and organic food) had a higher risk of hypospadias (odds ratio 1.54; 95% confidence interval 1.06, 2.26) compared with 'health conscious' subjects (high frequency of consumption of fresh fruit and vegetables, dried fruit, fresh or frozen fish, beans, pulses, soya products, olive oil and organic food), after adjustment for potential confounders. Intakes of individual foods were not strongly associated with hypospadias. We could not exclude the possibility of residual confounding, and this needs to be further investigated. We found an association between food pattern and hypospadias, with those with less health conscious food patterns having a higher risk. Further study is needed to confirm this association.

Risk factors for hypospadias.

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.

A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

OBJECTIVE: To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. SUBJECTS AND METHODS: Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. RESULTS: Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). CONCLUSION: As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.

Environmental antiandrogens: developmental effects, molecular mechanisms, and clinical implications.

Industrial chemicals and environmental pollutants can disrupt reproductive development in wildlife and humans by mimicking or inhibiting the action of the gonadal steroid hormones, estradiol and testosterone. The toxicity of these so-called environmental endocrine disruptors is especially insidious during sex differentiation and development due to the crucial role of gonadal steroid hormones in regulating these processes. This review describes the mechanism of toxicity and clinical implications of a new class of environmental chemicals that inhibit androgen-mediated sex development. For several of these chemicals, including the agricultural fungicide vinclozolin and the ubiquitous and persistent 1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the molecular mechanism of action and the adverse developmental effects on male sex differentiation have been elucidated and are used as examples. Environmental chemicals with antiandrogenic activity offer profound implications with regard to recent clinical observations that suggest an increasing incidence of human male genital tract malformations, male infertility, and female breast cancer. Finally, in light of increasing concern over the potential endocrine disrupting effects of environmental pollutants, an in vitro/in vivo investigational strategy is presented which has proved useful in identifying chemicals with antiandrogen activity and their mechanism of action.