Type 2 diabetes mellitus increases the risk of circumcision among men aged between 30 and 69 years using a nationwide population-based dataset in Taiwan: a five-year follow-up study.

BACKGROUND: Diabetes is an important factor in the development of penile inflammation. We studied whether type 2 diabetes (DM), with/without hypertension and hyperlipidemia increased the risk of circumcision among men aged between 30 and 69 using a population-based dataset in Taiwan during a 5-year follow-up period. METHODS: The research data in this study were obtained from Taiwan's National Health Insurance Research Database between 1997 and 2010. We identified 23,197 patients who had a new diagnosis of DM and randomly matched 115,985 subjects as controls. We observed whether circumcision was the treatment after a new DM diagnosis. The initial step involved analyzing the data using Poisson regression analysis. To address potential confounding factors, this study employed propensity score matching based on three variables. Additionally, a Cox regression with a Gamma frailty was utilized to compare outcomes between different groups. RESULTS: Poisson regression analysis showed that DM (RR = 1.75, 95CI = 0.10 ~ 1.22), but not hypertension (RR = 1.14, 95CI=-0.44 ~ 0.70), hyperlipidemia (RR = 0.94, 95CI=-0.66 ~ 0.53), or age (RR = 0.83, 95CI=-0.43 ~ 0.62), had an impact on circumcision treatment. Cox regression with a frailty model found that DM was a risk factor associated with circumcision (HR = 2.31, 95% CI = 1.74 ~ 3.06, p-value < 0.01), whereas no significant difference was noted between circumcision and hypertension (HR = 1.10, 95% CI = 0.80 ~ 1.51), hyperlipidemia (HR = 1.05, 95% CI = 0.79 ~ 1.40), or age (HR = 1.00, 95% CI = 0.99 ~ 1.02). CONCLUSIONS: Type 2 diabetes mellitus, but not hypertension, hyperlipidemia or age increases the risk of circumcision in men aged between 30 and 69 years.

Conservative Bladder Management and Medical Treatment in Chronic Spinal Cord Injury Patients.

To review the available data on non-surgical management for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI) and provide the most updated knowledge for readers. We categorized the bladder management approaches into storage and voiding dysfunction separately; both are minimally invasive, safe, and efficacious procedures. The main goals for NLUTD management are to achieve urinary continence; improve quality of life; prevent urinary tract infections and, last but not least, preserve upper urinary tract function. Annual renal sonography workups and regular video urodynamics examinations are crucial for early detection and further urological management. Despite the extensive data on NLUTD, there are still relatively few novel publications and there is a lack of high-quality evidence. There is a paucity of new minimally invasive and prolonged efficacy treatments for NLUTD, and a partnership between urologists, nephrologists and physiatrists is required to promote and ensure the health of SCI patients in the future.

Current Surgical Treatment for Neurogenic Lower Urinary Tract Dysfunction in Patients with Chronic Spinal Cord Injury.

This study aimed to present a comprehensive literature review of the efforts of a spinal cord injury workgroup in Taiwan regarding urologic surgery for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI). Surgical procedures should be viewed as a final option for managing patients with SCI who have persistent symptoms and complications that cannot be resolved by other means. Surgeries can be grouped according to their purpose: reducing bladder pressures, reducing urethra resistance, increasing urethra resistance, and urinary diversion. The choice of surgery depends on the type of LUTD based on urodynamic tests. Additionally, cognitive function, hand motility, comorbidities, efficacy of surgery, and related complications should be considered.

Safety and antibody response of recipients who unexpectedly received undiluted prime dose of BNT162b2 COVID-19 vaccine in Taiwan.

We reported 25 recipients (14 females and 11 males) aged from 18 to 65 years who unexpectedly received a primary dose of undiluted BNT162b2 vaccine (180 µg). The most common adverse reactions included injection site pain (n = 22), followed by fever (9), fatigue (8), chest tightness (6), and dizziness (6). The most common laboratory abnormalities were anemia (n = 4) and elevated liver transaminase level (4), followed by abnormal leukocyte counts (3) and elevated D-dimer level (3). The adverse reactions and laboratory abnormalities of these recipients were mild and spontaneously recovered within a few weeks. Significant elevations of anti-SARS-CoV-2 spike IgG titers after a booster dose of the BNT162b2 were found. Similar to reports of BNT162b2 clinical trials, the adverse reactions and laboratory abnormalities of these recipients were mild, and they spontaneously recovered within a few weeks. These results provide clinical and immunological effects of undiluted BNT162b2 vaccine inoculation.

Therapeutic efficacy and cognitive adverse events of overactive bladder medication in patients with central nervous system Disorders-A cohort study.

PURPOSE: This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders. METHODS: Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE). RESULTS: 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment. CONCLUSION: OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.

Effectiveness and Safety of Intradetrusor OnabotulinumtoxinA Injection for Neurogenic Detrusor Overactivity and Overactive Bladder Patients in Taiwan-A Phase IV Prospective, Interventional, Multiple-Center Study (Restore Study).

We conducted a phase IV, pre/post multi-center study to evaluate the efficacy and safety of intradetrusor onabotulinumtoxinA injection in patients with neurogenic detrusor overactivity (NDO, n = 119) or overactive bladder (OAB, n = 215). Patients received either 200U (i.e., NDO) and 100U (i.e., OAB) of onabotulinumtoxinA injection into the bladder, respectively. The primary endpoint for all patients was the change in the PPBC questionnaire score at week 4 and week 12 post-treatment compared with baseline. The secondary endpoints were the changes in subjective measures (i.e., questionnaires: NBSS for patients with NDO and OABSS for those with OAB) at week 4 and week 12 post-treatment compared with baseline. Adverse events included symptomatic UTI, de novo AUR, gross hematuria and PVR > 350mL were recorded. The results showed that compared with baseline, PPBC (3.4 versus 2.4 and 2.1, p < 0.001) and NBSS (35.4 versus 20.4 and 18.1, p < 0.001) were significantly improved at 4 weeks and 12 weeks in NDO patients. In addition, compared with baseline, PPBC (3.5 versus 2.3 and 2.0, p < 0.001) and OABSS (9.1 versus 6.2 and 5.7, p < 0.001) were significantly improved at 4 weeks and 12 weeks in OAB patients. Eight (6.7%) had symptomatic UTI and 5 (4.2%) had de novo AUR in NDO patients. Twenty (9.3%) had symptomatic UTI but no de novo AUR in OAB patients. In conclusion, we found that intradetrusor onabotulinumtoxinA injections were safe and improved subjective measures related to NDO or OAB in our cohort.

Adding mirabegron after intravesical onabotulinumtoxinA injection improves therapeutic effects in patients with refractory overactive bladder.

OBJECTIVES: To investigate whether adding an anticholinergic or beta-3 agonist can improve the therapeutic effect of intravesical onabotuliumtoxinA injection in patients with refractory overactive bladder (OAB). METHODS: Ninety OAB patients who received an intravesical 100-U onabotulinumtoxinA injection 1 month previously were consecutively invited into a prospective, randomized, open-label study. They were randomly adding on solifenacin 5 mg daily (QD) (30 patients), mirabegron 50 mg QD (31 patients), or no medication (29 patients, control). All enrolled patients completed a 3-day voiding diary, Overactive Bladder Symptom Score (OABSS) and Urgency Severity Scale (USS) questionnaires, Global Response Assessment (GRA) scale, and uroflowmetry at baseline (1 month after intravesical onabotulinumtoxinA injection) and 3-, 6-, 9-, and 12-month follow-up. The primary end point was the effective therapeutic outcome defined as no OAB wet during the 12-month period. The secondary end point included changes of GRA, OABSS, and the parameters of the voiding diary at 3 months. RESULTS: The baseline data were comparable among the three groups. The percentage of OAB wet in the mirabegron-added-on group was significantly less than that in the solifenacin-added-on and onabotulinumtoxinA-only groups at four different time points (P = .02). At 3 months, the changes of GRA, OABSS, USS, urge urinary incontinence, frequency, nocturia episodes, and functional bladder capacity in the mirabegron-added-on group were significantly greater than those in the other groups. No serious adverse events were reported. CONCLUSIONS: Adding mirabegron could increase the therapeutic effects, mainly on OAB symptoms and GRA scale, after intravesical onabotulinumtoxinA injection in refractory OAB patients.

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A.

Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely "botulinum toxin A" (BoNT-A) and "overactive bladder", with or without the additional keywords "detrusor overactivity", "diabetes mellitus", "inflammation", and "urodynamic study". We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.

Factors associated with antimuscarinic drug persistence and increasing drug persistence after switching to mirabegron for overactive bladder patients.

PURPOSE: To evaluate long-term antimuscarinic drug persistence and its associated characteristics in patients with overactive bladder (OAB) treated with antimuscarinic agents. We also assessed the efficacy and safety of switching from solifenacin to mirabegron in patients refractory to antimuscarinic therapy. METHODS: In this prospective, open-label, 48-month study, 416 patients (mean age, 70.6 ± 12.4 years) were enrolled. All patients completed the overactive bladder symptom score and urgency severity score questionnaires, along with initial and follow-up uroflowmetry. All patients received antimuscarinic solifenacin 5 mg daily. Mirabegron (25 mg daily) was suggested in patients that were refractory to antimuscarinic therapy or had intolerable side effects. RESULTS: The mean solifenacin persistence was 6.6 ± 8.1 months (range, 0.5-48 months). Only 81 (19.5%) patients had drug persistence of ≥12 months. Male sex, age, cerebral vascular accident, maximum flow rate, and post-void residual were associated with solifenacin persistence in the univariate analysis. Age (odds ratio [OR], 0.14; 95% CI, 0.08-0.21) was the only independent predictor in the multivariate logistic regression. Of the 416 patients, 171 (60.8%) changed from solifenacin to mirabegron for due to the persistence of OAB symptoms. The switch resulted in a significantly longer period of actual OAB pharmacotherapy (9.3 ± 9.2 vs 13.3 ± 9.3 months, p < 0.001). CONCLUSION: Long-term drug persistence of solifenacin was low during the 2-year follow-up. Age was an independent factor associated with longer drug persistence. Switching from solifenacin to mirabegron was an effective and safe alternative for OAB patients that were refractory to solifenacin treatment.

Higher urge severity score predicts resumption of overactive bladder (OAB) medication following discontinuation of mirabegron treatment in patients with OAB.

OBJECTIVES: This study investigated factors predicting the resumption of mirabegron following its discontinuation with successful treatment of overactive bladder (OAB). METHODS: In all, 374 OAB patients reporting an improvement in subjective symptoms after a minimum of 3 months treatment with mirabegron 25 mg, q.d., were screened. Those wanting to continue with the medication (n = 109) were excluded from the study. The remaining 265 patients discontinued mirabegron and their outcomes were evaluated at baseline (discontinuation) and 1, 3, 6, 9, and 12 months using the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Urgency Severity Scale (USS), Patient's Perception of Bladder Condition (PPBC), and Global Response Assessment (GRA), as well as uroflowmetry and post-void residual (PVR). RESULTS: After mirabegron discontinuation, 203 patients completed follow-up. The mean (±SD) duration from discontinuing medication to resumption of mirabegron was 2.25 ± 1.17 months (range 1-12 months). Compared with the 111 (54.7%) patients who did not resume mirabegron, the 92 (45.3%) patients who resumed mirabegron had a higher USS at time of discontinuation (1.18 ± 1.76 vs. 0.65 ± 1.33; P = 0.017). The USS was a strong predictor of mirabegron resumption (P = 0.02; odds ratio 1.315; 95% confidence interval 1.051-1.646). CONCLUSIONS: Among OAB patients who were successfully treated with mirabegron for ≥3 months, nearly half requested resumption of mirabegron after discontinuation. A higher USS was found to predict retreatment after discontinuation of mirabegron in OAB patients.

Videourodynamic findings of lower urinary tract dysfunctions in men with persistent storage lower urinary tract symptoms after medical treatment.

OBJECTIVE: To analyze the underlying lower urinary tract dysfunctions by video-urodynamic studies in men who have persistent storage symptoms after initial drug therapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). METHODS: The medical records of 614 men ≥40 years of age with LUTS and an International Prostate Symptom Score of ≥8 were retrospectively analyzed. All patients had persistent storage symptoms after medical treatment for at least 6 months. A video-urodynamic study was done to investigate the underlying bladder or bladder outlet dysfunction. Predictors of bladder outlet obstruction (BOO) by baseline urine flow metrics and prostate parameters were investigated. RESULTS: The final results revealed bladder neck dysfunction (BND) in 137/614 (22.3%), benign prostatic obstruction (BPO) in 246/614 (40.1%), detrusor overactivity (DO) in 193/614 (31.4%), and DO with detrusor underactivity (DO+DU) in 38/614 (6.2%) patients. Among the patients, 221/281 (78.6%) with a total prostatic volume (TPV) ≥40 ml had BOO, including 43/281 (15.3%) with BND and 178/281 (63.3%) with BPO. If we combined TPV ≥40 ml and Qmax <12 ml/s as predictors of BOO, BOO was found in 176/215 (81.8%) patients including 34/215 (15.8%) with BND and 142/215 (66.0%) with BPO. BOO was also found in 48.8% of men with a TPV <40ml, and in 36.3% of men with TPV< 40 ml and Qmax ≥ 12 ml/s. In 102 men with TPV <40 ml and Qmax ≥12 ml/s, 64 (62.7%) had DO. CONCLUSION: BOO, including BND and BPO, comprise 62.4% (383/614) of men with persistent storage symptoms after initial medical treatment for LUTS/BPH. In men who have persistent storage symptoms after medical treatment for LUTS/BPH, BOO should be carefully investigated and appropriate management being given to improve LUTS.

The effects of maternal smoking exposure during pregnancy on postnatal outcomes: A cross sectional study.

BACKGROUND: The purpose of this article was to evaluate the effect of maternal smoking exposure during pregnancy on postnatal outcomes. METHODS: This prospective study enrolled 278 pregnant women in the third trimester, who were asked to complete a questionnaire which included inquires about the nature and extent of smoking exposure during their pregnancy. In addition to the questionnaire, each study subject provided urine sample for the measurement of cotinine. Using data generated from this inquiry, we analyzed the association between maternal smoking exposure and birth outcomes. RESULTS: From the 278 enrollees in this study, a minority of subjects (7.2%) smoked, while 40.6% of the study subjects were exposed to environmental tobacco smoke during pregnancy. There was significantly higher birth weight (3205.2 ± 373.1 vs 3089.7 ± 363.0 vs 2959.0 ± 403.7 g, p = 0.004), larger chest size (33.1 ± 1.7 cm vs 32.7 ± 1.5 cm vs 32.0 ± 1.7 cm, p = 0.009), higher bilirubin on postnatal day 3 (8.9 ± 1.6 vs 8.6 ± 1.5 vs 7.8 ± 1.4 mg/dL, p = 0.015), but lower maternal urinary cotinine level (83.7 ± 132.4 vs 153.2 ± 96.0 vs 800.5 ± 1027.8 µg/g creatinine, p < 0.001) in smoking-free status than in passive or active smoking status. Significant risks of birth weight < 2500 g (AOR 3.93 (95% CI 1.61-9.59), p = 0.003) and maternal urinary cotinine ≥ 143 µg/g creatinine (AOR 3.38 (95% CI 2.02-5.66), p < 0.001) were observed as smoking exposure increased. There was significantly higher birth weight (p = 0.048), larger chest size (p = 0.045), and higher bilirubin level on postnatal day 3 (p < 0.001) in the group with cotinine <143 µg/g creatinine than in the group with cotinine ≥ 143 µg/g creatinine. CONCLUSION: Our results demonstrated that maternal smoking exposure during pregnancy is associated with low birth weight and small chest circumference. Although the incidence of active smoking in Taiwanese pregnant women is low, most of them are exposed to passive smoking environment. Further studies are required to evaluate useful interventions to enhance a smoking-free environment during pregnancy.

Influence of seafood and vitamin supplementation on maternal and umbilical cord blood mercury concentration.

BACKGROUND: The purpose of this study was to examine the influence of maternal seafood consumption and vitamin supplementation during pregnancy on maternal and umbilical cord blood mercury (Hg) concentration. METHODS: In this study of 145 healthy pregnant women (mean age 28.1±5.2 years), we administered questionnaires, collected paired maternal/umbilical cord blood samples, and measured the anthropometrics of newborns. Blood Hg concentration was assayed by inductively coupled plasma-mass spectrometry. RESULTS: Sixty-one of these women (42.1%) used vitamins >3 times/wk prenatally. Seventy-eight of our study participants (61.9%) reported eating higher amounts of seafood during pregnancy. We found a strong correlation (r=0.76, p<0.001) between Hg levels in the paired maternal/umbilical cord blood samples. Mothers with high seafood consumption had a 2.91-fold greater risk (adjusted odds ratio 2.91, 95% confidence interval: 1.04-8.15, p=0.042) of high Hg levels (>5.8 µg/L). However, mothers whose prenatal vitamin intake was >3 times/wk were found to have low Hg levels (≤5.8 µg/L) (adjusted odds ratio 0.06, 95% confidence interval: 0.01-049, p=0.008). CONCLUSION: High seafood consumption was an independent risk factor for high maternal Hg level, while vitamin supplementation was a protective factor. Further study is needed to investigate the specific effect of vitamins on Hg level.

Efficacy and Adherence of Flexibly Adding on a Second Antimuscarinic Agent for Patients with Refractory Overactive Bladder.

OBJECTIVES: To evaluate the efficacy and adverse events (AE) of flexibly adding on oxybutynin ER in patients with overactive bladder (OAB) refractory to monotherapy with the first muscarinic antagonist. METHODS: A total of 129 patients with refractory OAB were enrolled in a prospective, open-label protocol. Inclusion criteria were persistent symptoms or partial response to 3-month behavioral therapy and an optimized dose of one antimuscarinic agent. At baseline, weeks 4, and 12 after the oxybutynin ER (5-15 mg once a day) was flexibly added, we assessed the OAB symptom indexes and Patient Perception of Bladder Condition, uroflowmetry, and post-void residual, along with the therapeutic effect, AE, and tolerability. Patients continuing combined antimuscarinic therapy were followed up to 12 months. RESULTS: Compared with baseline, all OAB symptom indexes significantly decreased at all visits. A total of 32 (24.8%) and 25 (19.4%) patients reported successful therapeutic effect at weeks 4 and 12, respectively. Twenty-four (18.6%) and 44 (34.1%) patients discontinued therapy at weeks 4 and 12, respectively. Only 31 (24.0%) patients continued the combined medication for up to 12 months. Discontinuation of the combined medication was noted in 28 (21.7%) patients due to AE and in 70 (54.3%) due to lack of efficacy. CONCLUSIONS: Flexibly adding on a second antimuscarinic agent is effective and safe for only some OAB patients dissatisfied with the first antimuscarinic treatment in the short-term period. The patients' dropout rate is high and the long-term efficacy of the combination of two antimuscarinic agents is limited.

Urothelial Dysfunction and Chronic Inflammation in Diabetic Patients with Overactive Bladder.

OBJECTIVES: To investigate urothelial dysfunction, suburothelial inflammation, and muscarinic receptor expression in diabetic patients with overactive bladder (OAB). METHODS: A total 19 patients with OAB and diabetes mellitus (DM), 14 OAB patients without DM, and 10 healthy control subjects were enrolled in the study. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and apoptosis tests on the bladder urothelium and suburothelium were performed. Tissue muscarinic receptor M2, M3, and purinergic receptor P2X3 levels were measured by Western blotting. Video urodynamic studies were analyzed in relation to immunofluorescence and western blotting results. RESULTS: The mean age of the controls, OAB patients without and with DM were comparable (62.9 ± 6.9, 58.4 ± 21.3, and 68.9 ± 11.3 years, respectively, P = 0.25). E-cadherin and mast cell expression in the bladder urothelium samples of the DM-OAB group and the OAB group without DM differed significantly from those of the control group (all P < 0.05). However, immunofluorescence analyses including E-cadherin, mast cells, apoptotic cell counts, and ZO-1 were comparable between OAB patients with and without DM. In addition, M3 muscarinic protein expression in the bladders of OAB patients with and without DM was significantly higher than that in the control subjects. The video urodynamic parameters did not correlate with the immunofluorescence data, M2 and M3 muscarinic receptor data, or P2X3 protein expression. CONCLUSION: Urothelial dysfunction and chronic suburothelial inflammation may contribute to the pathogeneses of OAB. However, DM does not aggravate the severity of urothelial inflammation in OAB patients.

Maternal and umbilical cord blood levels of mercury, manganese, iron, and copper in southern Taiwan: A cross-sectional study.

BACKGROUND: The effect of maternal exposure to essential minerals and heavy metals on fetus is an important issue, which affects women around the world. Few data are available on the concentration of both essential minerals and heavy metals in maternal/fetal medicine. The aims of this study were to (1) assess the correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired maternal/fetal blood samples, and (2) study potential confounding factors during pregnancy. METHODS: Our study recruited 145 healthy pregnant women with a mean age of 28.06 years, gathering information by collecting interviewer-administered questionnaires. Paired maternal/fetal blood samples were collected by delivery. RESULTS: There was a positive correlation of Hg (r = 0.78, p<0.001), Mn (r = 0.31, p<0.001), Fe (r = 0.17, p = 0.038), and Cu (r = 0.21, p = 0.010) in paired maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly associated with lower maternal Hg (adjusted odds ratio 0.272, p = 0.005) and lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg, Mn, and Fe levels were higher than corresponding maternal levels, while median fetal Cu level was lower than maternal Cu level. CONCLUSION: There was a positive correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this series. Our findings have raised the possibility of reducing maternal Hg and Cu by way of prenatal vitamin supplementation.