Influenza vaccination during pregnancy and risk of selected major structural congenital heart defects, National Birth Defects Prevention Study 2006-2011.

BACKGROUND: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. METHODS: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. RESULTS: Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. CONCLUSIONS: Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

Prepregnancy exposure to dietary arsenic and congenital heart defects.

INTRODUCTION: Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects. METHODS: We used maternal self-reported dietary assessments and arsenic concentration estimates in food items to estimate average daily exposure to dietary arsenic during the year before pregnancy for mothers of 10,446 unaffected control children and 6,483 case children diagnosed with CHDs. Using tertiles of dietary exposure to total arsenic (all species) and inorganic arsenic, we applied logistic regression analysis to estimate associations for middle and high tertiles, compared with the low tertile. RESULTS: Positive associations (odds ratio [OR] ≥ 1.2) for total arsenic were observed in both tertiles for perimembranous ventricular septal defect (VSD) and high tertile only for double outlet right ventricle-transposition of the great arteries (DORV-TGA), partial anomalous pulmonary venous return (PAPVR), and tricuspid atresia. Positive associations were also observed in both tertiles (tricuspid atresia) and high tertile only (DORV-TGA, conoventricular VSD, PAPVR, and pulmonary atresia) for inorganic arsenic. Most remaining associations were near or below unity. DISCUSSION: Exploration of maternal dietary exposure to total and inorganic arsenic and CHDs produced few positive associations but was limited by available food item concentrations. Future research requires expanded collection of dietary data, improved estimates of concentrations, and consideration of nondietary sources of arsenic exposure.

Increased interstage morbidity and mortality following stage 1 palliation in patients with genetic abnormalities.

BACKGROUND: Hypoplastic left heart syndrome and single ventricle variants with aortic hypoplasia are commonly classified as severe forms of CHD. We hypothesised patients with these severe defects and reported genetic abnormalities have increased morbidity and mortality during the interstage period. METHODS AND RESULTS: This was a retrospective review of the National Pediatric Cardiology Quality Improvement Collaborative Phase I registry. Three patient groups were identified: major syndromes, other genetic abnormalities, and no reported genetic abnormality. Tukey post hoc test was applied for pairwise group comparisons of length of stay, death, and combined outcome of death, not a candidate for stage 2 palliation, and heart transplant. Participating centres received a survey to establish genetic testing and reporting practices. Of the 2182 patients, 110 (5%) had major genetic syndromes, 126 (6%) had other genetic abnormalities, and 1946 (89%) had no genetic abnormality. Those with major genetic syndromes weighed less at birth and stage 1 palliation. Patients with no reported genetic abnormalities reached full oral feeds sooner and discharged earlier. The combined outcome of death, not a candidate for stage 2 palliation, and heart transplant was more common in those with major syndromes. Survey response was low (n = 23, 38%) with only 14 (61%) routinely performing and reporting genetic testing. CONCLUSIONS: Patients with genetic abnormalities experienced greater morbidity and mortality during the interstage period than those with no reported genetic abnormalities. Genetic testing and reporting practices vary significantly between participating centres.

An interlaboratory study evaluating the interpretation of forensic glass evidence using refractive index measurements and elemental composition.

Seventeen laboratories participated in three interlaboratory exercises to assess the performance of refractive index, micro X-ray Fluorescence Spectroscopy (µXRF), and Laser Induced Breakdown Spectroscopy (LIBS) data for the forensic comparison of glass samples. Glass fragments from automotive windshields were distributed to the participating labs as blind samples and participants were asked to compare the glass samples (known vs. questioned) and report their findings as they would in casework. For samples that originated from the same source, the overall correct association rate was greater than 92% for each of the three techniques (refractive index, µXRF, and LIBS). For samples that originated from different vehicles, an overall correct exclusion rate of 82%, 96%, and 87% was observed for refractive index, µXRF, and LIBS, respectively. Special attention was given to the reporting language used by practitioners as well as the use of verbal scales and/or databases to assign a significance to the evidence. Wide variations in the reported conclusions exist between different laboratories, demonstrating a need for the standardization of the reporting language used by practitioners. Moreover, few labs used a verbal scale and/or a database to provide a weight to the evidence. It is recommended that forensic practitioners strive to incorporate the use of a verbal scale and/or a background database, if available, to provide a measure of significance to glass forensic evidence (i.e., the strength of an association or exclusion).

Impact of Shared Plans of Care on Healthcare Utilization by Children with Special Healthcare Needs and Mental Health Diagnoses.

OBJECTIVES: We assessed how shared plans of care (SPoC), a care coordination tool, impact healthcare utilization of a cohort of children with special healthcare needs (CSHCN) and mental health conditions. METHODS: Data, including emergency department (ED) visits, hospitalizations, and primary care visits, were collected through chart review of CSHCN. A Poisson generalized linear mixed model was used to analyze healthcare utilization data for CSHCN. RESULTS: Our results showed a decrease in primary care visits, hospitalizations, and ED visits for CSHCN after SPoC implementation, though only primary care visits reached significance. Mental health care visits were specifically found to decrease by 39% following employment of SPoC. CONCLUSIONS FOR PRACTICE: The use of SPoCs in CSHCN had a positive impact on healthcare utilization suggesting widespread use of this tool improved care coordination in this population.

A realistic phantom of the human head for PET-MRI.

BACKGROUND: The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) (PET-MRI) is a unique hybrid imaging modality mainly used in oncology and neurology. The MRI-based attenuation correction (MRAC) is crucial for correct quantification of PET data. A suitable phantom to validate quantitative results in PET-MRI is currently missing. In particular, the correction of attenuation due to bone is usually not verified by commonly available phantoms. The aim of this work was, thus, the development of such a phantom and to explore whether such a phantom might be used to validate MRACs. METHOD: Various materials were investigated for their attenuation and MR properties. For the substitution of bone, water-saturated gypsum plaster was used. The attenuation of 511 keV annihilation photons was regulated by addition of iodine. Adipose tissue was imitated by silicone and brain tissue by agarose gel, respectively. The practicability with respect to the comparison of MRACs was checked as follows: A small flask inserted into the phantom and a large spherical phantom (serving as a reference with negligible error in MRAC) were filled with the very same activity concentration. The activity concentration was measured and compared using clinical protocols on PET-MRI and different built-in and offline MRACs. The same measurements were carried out using PET-CT for comparison. RESULTS: The phantom imitates the human head in sufficient detail. All tissue types including bone were detected as such so that the phantom-based comparison of the quantification accuracy of PET-MRI was possible. Quantitatively, the activity concentration in the brain, which was determined using different MRACs, showed a deviation of about 5% on average and a maximum deviation of 11% compared to the spherical phantom. For PET-CT, the deviation was 5%. CONCLUSIONS: The comparatively small error in quantification indicates that it is possible to construct a brain PET-MRI phantom that leads to MR-based attenuation-corrected images with reasonable accuracy.

Conduction of a round-robin test on a real sample for the identification of gunshot residues by SEM/EDX.

A round-robin test on the identification of GSR particles by SEM/EDX and involving eleven Institutes was conducted on a real sample, in order to evaluate the possibilities/limitations of using such sample to get additional information (compared to the analysis of the usual synthetic sample used within the framework of the ENFSI proficiency test) about the performances of the SEM/EDX systems. Each Institute was asked to analyse this sample following its own standard operating procedure, and by using all the systems in house, whenever available. Between each Institute, a check of the sample was performed by the organizing Institute (NICC), in order inter alia to monitor any degradation and/or contamination of the sample. A total of about 30 analyses were performed on the sample. For each particle of interest identified on the real sample, the detection effectiveness was monitored, as well as the classification allotted by each Institute. The Institutes were also asked to report some of their measurement parameters, and to send the results as they would have been communicated in their own case report. A quite good agreement was observed with regard to the classification of the particles of interest, since a broad consensus was reached for approximately 75% of these particles. A different classification risk exists for some classes, the barium/antimony classes being probably the most critical, as traces of lead may cause the particles to shift (or not) from the consistent with GSR upper-class to the characteristic of GSR upper-class; in the end, the decision to shift from one class to another strongly depends on local rules. At the end of the campaign, a survey sent to collect experience and lessons learned from this exercise showed that analysing a real sample definitively offers an added value, especially in terms of classification process (during the automatic run and when performing the manual review) of particles.

Outpatient Surgery.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Determine those patients appropriate for outpatient surgery. 2. Choose appropriate anesthetics. 3. Manage patients with cardiac disease. 4. Limit complications occurring intraoperatively. SUMMARY: This article provides continuing medical education information regarding the current state of practice concerning outpatient surgery. A thorough preoperative evaluation is necessary to identify comorbid conditions and patients at risk for pulmonary compromise. Guidelines are provided on the use of sedatives, analgesics, and reversal agents. The management of patients with coronary artery stents and/or cardiac rhythm management devices is discussed. Effective surgical team communication is crucial to ensure that everyone is aware of conditions that may require adjustments from the usual healthy patients. Lastly, suggestions are provided to avoid intraoperative problems such as drug reactions and pressure ulcers. As our aging population presents for an increasing number of procedures, plastic surgeons must ensure that patient safety is a priority.

Capsular Contracture in Implant-Based Breast Reconstruction: Examining the Role of Acellular Dermal Matrix Fenestrations.

BACKGROUND: Acellular dermal matrices have been proposed to decrease the incidence of capsular contracture in implant-based breast reconstructions. The authors have modified acellular dermal matrices with fenestrations to facilitate greater lower pole expansion and improve contour. The effect of fenestrations on the ability of matrices to suppress capsule formation, however, has not been examined. METHODS: A retrospective review of all fenestrated acellular dermal matrix-assisted, implant-based breast reconstructions performed by the two senior authors, with a minimum of 1-year follow-up after permanent implant placement, was completed. Patient demographics, details of extirpative and reconstructive procedures, and complications were examined. Capsular contractures were scored according to the Baker grading scale and compared to those reported in the literature. RESULTS: Thirty patients (50 breasts) underwent fenestrated acellular dermal matrix-assisted reconstruction, with mean follow-up times of 3.3 and 2.6 years after expander placement and implant exchange, respectively. Seven patients (23 percent) had a body mass index greater than 30 kg/m, three (10 percent) were active smokers, and six breasts (12 percent) were irradiated. Complications included one infection (2 percent), six cases (12 percent) of incisional superficial skin necrosis, and one (2 percent) tissue expander extrusion. Zero breasts had clinically significant Baker grade III/IV capsular contracture. The average Baker grade was 1.1. CONCLUSIONS: Fenestrated acellular dermal matrices decrease capsular contracture to rates similar to what is seen with nonfenestrated matrices. Further research is necessary to determine whether this observation is a result of decreased need for inferolateral acellular dermal matrix coverage to achieve these effects or modified physical interaction of acellular dermal matrices with surrounding soft tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Evaluating visual perception for assessing reconstructed flap health.

BACKGROUND: Detecting failing tissue flaps before they are clinically apparent has the potential to improve postoperative flap management and salvage rates. This study demonstrates a model to quantitatively compare clinical appearance, as recorded via digital camera, with spatial frequency domain imaging (SFDI), a noninvasive imaging technique using patterned illumination to generate images of total hemoglobin and tissue oxygen saturation (stO2). METHODS: Using a swine pedicle model in which blood flow was carefully controlled with occlusion cuffs and monitored with ultrasound probes, throughput was reduced by 25%, 50%, 75%, and 100% of baseline values in either the artery or the vein of each of the flaps. The color changes recorded by a digital camera were quantified to predict which occlusion levels were visible to the human eye. SFDI was also used to quantify the changes in physiological parameters including total hemoglobin and oxygen saturation associated with each occlusion. RESULTS: There were no statistically significant changes in color above the noticeable perception levels associated with human vision during any of the occlusion levels. However, there were statistically significant changes in total hemoglobin and stO2 levels detected at the 50%, 75%, and 100% occlusion levels for arterial and venous occlusions. CONCLUSIONS: As demonstrated by the color imaging data, visual flap changes are difficult to detect until significant occlusion has occurred. SFDI is capable of detecting changes in total hemoglobin and stO2 as a result of partial occlusions before they are perceivable, thereby potentially improving response times and salvage rates.

ANG II modulation of cardiac growth and remodeling in immature fetal sheep.

ANG II increases fetal blood pressure and stimulates fetal heart growth; however, little is known regarding its direct effects on cardiomyocytes in vivo. We sought to determine whether ANG II stimulates heart growth and cardiomyocyte hypertrophy and/or hyperplasia in utero in the immature fetal heart independent of the effects on cardiac afterload. In twin gestation, fetal sheep at ∼100 days gestation (term 145 days), one fetus received a chronic (6 days) infusion of ANG II alone (50 µg·kg(-1)·min(-1)) or ANG II plus nitroprusside (NTP) to attenuate the increase in blood pressure; noninstrumented twins served as controls. ANG II alone, but not ANG II + NTP resulted in a significant increase in heart mass (left and right ventricle + septum, corrected for body weight) compared with controls. ANG II, but not ANG II+NTP, also significantly increased cardiomyocyte area compared with control and increased the percentage of binucleated myocytes. ANG II with or without concomitant infusion of NTP increased cardiac PCNA expression, a marker of proliferation. Steady-state protein expression of terminal mitogen-activated protein kinases, cyclin B1, cyclin E1, and p21 were similar among groups. We conclude that in vivo, ANG II increases fetal cardiac mass via cardiomyocyte hypertrophy, differentiation, and to a lesser extent hyperplasia. The effects of ANG II on hypertrophy appear dependent upon the increase in blood pressure (mechanical load), whereas effects on proliferation are load-independent.

Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep.

BACKGROUND: Angiotensin II (ANG II) stimulates fetal heart growth, although little is known regarding changes in cardiomyocyte endowment or the molecular pathways mediating the response. We measured cardiomyocyte proliferation and morphology in ANG II-treated fetal sheep and assessed transcriptional pathway responses in ANG II and losartan (an ANG II type 1 receptor antagonist) treated fetuses. METHODS: In twin-gestation pregnant sheep, one fetus received ANG II (50 µg/kg/min i.v.) or losartan (20 mg/kg/d i.v.) for 7 d; noninstrumented twins served as controls. RESULTS: ANG II produced increases in heart mass, cardiomyocyte area (left ventricle (LV) and right ventricle mononucleated and LV binucleated cells), and the percentage of Ki-67-positive mononucleated cells in the LV (all P < 0.05). ANG II and losartan produced generally opposing changes in gene expression, affecting an estimated 55% of the represented transcriptome. The most prominent significantly affected biological pathways included those involved in cytoskeletal remodeling and cell cycle activity. CONCLUSION: ANG II produces an increase in fetal cardiac mass via cardiomyocyte hypertrophy and likely hyperplasia, involving transcriptional responses in cytoskeletal remodeling and cell cycle pathways.

Enhanced cryoprecipitate for skin graft and donor site wound healing in pigs.

Due to similarities in skin characteristics, the authors hypothesise that a pig model would most accurately show the ability of autologous, enhanced cryoprecipitate (eCryo) to improve the wound healing of split-thickness skin grafts (STSGs) and corresponding donor sites. Fifty-two STSGs (5 × 5 cm) were fashioned and treated according to a randomised protocol with an autologous eCryo-treated and a control group. Macroscopic assessment, histological evaluation and cellular composition were completed at days 7, 14, 21 and 28. Thirty-two donor sites were also created and assessed in a similar manner. Histologic analysis showed enhancement of healing over all time points for eCryo-treated donor sites. All other results showed no statistically significant improvement with the use of eCryo. Autologous cryoprecipitate appears to be a safe, inexpensive and easy-to-use alternative to fibrin glue, which carries risks and is, in many cases, prohibitively expensive. Further studies are necessary to evaluate the full potential of eCryo. Interestingly, eCryo application may improve donor site aesthetic appearance. We believe that a pig model most reliably simulates eCryo's behaviour in humans to accurately reflect its future clinical applicability.

Evidence-based value of subcutaneous surgical wound drainage: the largest systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to determine the evidenced-based value of prophylactic drainage of subcutaneous wounds in surgery. METHODS: An electronic search was performed. Articles comparing subcutaneous prophylactic drainage with no drainage were identified and classified by level of evidence. If sufficient randomized controlled trials were included, a meta-analysis was performed using the random-effects model. Fifty-two randomized controlled trials were included in the meta-analysis, and subgroups were determined by specific surgical procedures or characteristics (cesarean delivery, abdominal wound, breast reduction, breast biopsy, femoral wound, axillary lymph node dissection, hip and knee arthroplasty, obesity, and clean-contaminated wound). Studies were compared for the following endpoints: hematoma, wound healing issues, seroma, abscess, and infection. RESULTS: Fifty-two studies with a total of 6930 operations were identified as suitable for this analysis. There were 3495 operations in the drain group and 3435 in the no-drain group. Prophylactic subcutaneous drainage offered a statistically significant advantage only for (1) prevention of hematomas in breast biopsy procedures and (2) prevention of seromas in axillary node dissections. In all other procedures studied, drainage did not offer an advantage. CONCLUSIONS: Many surgical operations can be performed safely without prophylactic drainage. Surgeons can consider omitting drains after cesarean section, breast reduction, abdominal wounds, femoral wounds, and hip and knee joint replacement. Furthermore, surgeons should consider not placing drains prophylactically in obese patients. However, drain placement following a surgical procedure is the surgeon's choice and can be based on multiple factors beyond the type of procedure being performed or the patient's body habitus. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Quantitative assessment of partial vascular occlusions in a swine pedicle flap model using spatial frequency domain imaging.

The use of tissue transfer flaps has become a common and effective technique for reconstructing or replacing damaged tissue. While the overall failure rate associated with these procedures is relatively low (5-10%), the failure rate of tissue flaps that require additional surgery is significantly higher (40-60%). The reason for this is largely due to the absence of a technique for objectively assessing tissue health after surgery. Here we have investigated spatial frequency domain imaging (SFDI) as a potential tool to do this. By projecting wide-field patterned illumination at multiple wavelengths onto a tissue surface, SFDI is able to quantify absolute concentrations of oxygenated and deoxygenated hemoglobin over a large field of view. We have assessed the sensitivity of SFDI in a swine pedicle flap model by using a controlled vascular occlusion system that reduced blood flow by 25%, 50%, 75%, or 100% of the baseline values in either the vein or artery. SFDI was able to detect significant changes for oxygenated hemoglobin, deoxygenated hemoglobin, or tissue oxygen saturation in partial arterial occlusions of at least 50% and partial venous occlusions of at least 25%. This shows SFDI is sensitive enough to quantify changes in the tissue hemoglobin state during partial occlusions and thus has the potential to be a powerful tool for the early prediction of tissue flap failure.

Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in response to pressure overload.

Novel percutaneous transcatheter intervention for refractory active endocarditis as a bridge to surgery-angiovac aspiration system.

Guidelines for the treatment of active right-sided endocarditis are not well defined. We report the first novel use of an aspiration catheter system for transcatheter therapy of refractory active right sided endocarditis on a bioprosthetic valve in a high-risk surgical patient as a bridge to surgical intervention.

CaMKII determines mitochondrial stress responses in heart.

Myocardial cell death is initiated by excessive mitochondrial Ca(2+) entry causing Ca(2+) overload, mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner membrane potential (ΔΨm). However, the signalling pathways that control mitochondrial Ca(2+) entry through the inner membrane mitochondrial Ca(2+) uniporter (MCU) are not known. The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated in ischaemia reperfusion, myocardial infarction and neurohumoral injury, common causes of myocardial death and heart failure; these findings suggest that CaMKII could couple disease stress to mitochondrial injury. Here we show that CaMKII promotes mPTP opening and myocardial death by increasing MCU current (I(MCU)). Mitochondrial-targeted CaMKII inhibitory protein or cyclosporin A, an mPTP antagonist with clinical efficacy in ischaemia reperfusion injury, equivalently prevent mPTP opening, ΔΨm deterioration and diminish mitochondrial disruption and programmed cell death in response to ischaemia reperfusion injury. Mice with myocardial and mitochondrial-targeted CaMKII inhibition have reduced I(MCU) and are resistant to ischaemia reperfusion injury, myocardial infarction and neurohumoral injury, suggesting that pathological actions of CaMKII are substantially mediated by increasing I(MCU). Our findings identify CaMKII activity as a central mechanism for mitochondrial Ca(2+) entry in myocardial cell death, and indicate that mitochondrial-targeted CaMKII inhibition could prevent or reduce myocardial death and heart failure in response to common experimental forms of pathophysiological stress.

Sex-specific programming of hypertension in offspring of late-gestation diabetic rats.

BACKGROUND: The intrauterine environment strongly influences adult disease susceptibility. We used a rat model of third-trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness. METHODS: Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 d) and partially controlled with insulin injections. Hemodynamic function was evaluated in 6-12-mo-old offspring. RESULTS: Male but not female offspring of diabetic mothers (ODM) had significantly increased blood pressure as compared with controls; heart rate (HR) was similar. For both sexes, HR baroreflex responses were similar as were in vivo hemodynamic responses to angiotensin II, nitric oxide synthase inhibition, and ganglionic blockade. Aortic contractility to angiotensin II was similar in the two groups. Nitric oxide synthase inhibition and the Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate, but not the superoxide dismutase-mimetic Tempol, significantly increased contractile responses to angiotensin II in controls but not ODM. Reduced nicotinamide adenine dinucleotide phosphate-stimulated superoxide production was greater in male ODM than in controls (P < 0.05). CONCLUSION: Exposure to hyperglycemia in utero results in sex-specific cardiovascular changes in adult offspring. Impaired nitric oxide-reactive oxygen species signaling may play a significant role in the hemodynamic phenotype of ODM.