Age, Sex, and Racial Differences in Neuroimaging Use in Acute Stroke: A Population-Based Study.

BACKGROUND AND PURPOSE: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. MATERIALS AND METHODS: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. RESULTS: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12-1.61; P < .01), and in the younger group, the association between race and advanced imaging was not statistically significant. Age by race interaction persisted in the academic center subgroup (P < .01), but not in the nonacademic center subgroup (P = .58). No significant association was found between sex and advanced imaging. CONCLUSIONS: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type.

Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy Outcomes.

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI (20 to < 25 kg/m2), and high BMI (≥ 25 kg/m2). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).

Health Status and Lifestyle Habits of US Medical Students: A Longitudinal Study.

BACKGROUND: Evidence shows that physicians and medical students who engage in healthy lifestyle habits are more likely to counsel patients about such behaviors. Yet medical school is a challenging time that may bring about undesired changes to health and lifestyle habits. AIMS: This study assessed changes in students' health and lifestyle behaviors during medical school. SUBJECTS AND METHODS: In a longitudinal study, students were assessed at both the beginning and end of medical school. Anthropometric, metabolic, and lifestyle variables were measured at a clinical research center. Data were collected from 2006 to 2011, and analyzed in 2013-2014 with SAS version 9.3. Pearson's correlations were used to assess associations between variables and a generalized linear model was used to measure change over time. RESULTS: Seventy-eight percent (97/125) of participants completed both visits. At baseline, mean anthropometric and clinical measures were at or near healthy values and did not change over time, with the exception of increased diastolic blood pressure (P = 0.01), high-density lipoprotein-cholesterol (P < 0.001), and insulin (P < 0.001). Self-reported diet and physical activity habits were congruent with national goals, except for Vitamin D and sodium. Dietary intake did not change over time, with the exceptions of decreased carbohydrate (percent of total energy) (P < 0.001) and sodium (P = 0.04) and increased fat (percent of total energy) and Vitamin D (both P < 0.01). Cardiovascular fitness showed a trend toward declining, while self-reported physical activity increased (P < 0.001). CONCLUSIONS: Students' clinical measures and lifestyle behaviors remain generally healthy throughout medical school; yet some students exhibit cardiometabolic risk and diet and activity habits not aligned with national recommendations. Curricula that include personal health and lifestyle assessment may motivate students to adopt healthier practices and serve as role models for patients.

Population-based study of wake-up strokes.

OBJECTIVE: Previous studies have estimated that wake-up strokes comprise 8%to 28% of all ischemic strokes, but these studies were either small or not population-based. We sought to establish the proportion and event rate of wake-up strokes in a large population-based study and to compare patients who awoke with stroke symptoms with those who were awake at time of onset. METHODS: First-time and recurrent ischemic strokes among residents of the Greater Cincinnati/Northern Kentucky region (population 1.3 million) in 2005 were identified using International Classification of Diseases-9 codes 430-436 and verified via study physician review. Ischemic strokes in patients aged 18 years and older presenting to an emergency department were included. Baseline characteristics were ascertained, along with discharge modified Rankin Scale scores and 90-day mortality. RESULTS: We identified 1,854 ischemic strokes presenting to an emergency department, of which 273 (14.3%) were wake-up strokes. There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score. The adjusted wake-up stroke event rate was 26.0/100,000. Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor. CONCLUSIONS: Within our population, approximately 14% of ischemic strokes presenting to an emergency department were wake-up strokes. Wake-up strokes cannot be distinguished from other strokes by clinical features or outcome. We estimate that approximately 58,000 patients with wake-up strokes presented to an emergency department in the United States in 2005.

Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT.

Patients undergoing auto-SCT for neuroblastoma present a unique population to study transplant-associated thrombotic microangiopathy (TA-TMA), due to standardized chemotherapy and later exposure to radiation and cis-retinoic acid (cis-RA). We retrospectively analyzed 20 patients after auto-SCT to evaluate early clinical indicators of TA-TMA. A total of 6 patients developing TA-TMA (30% prevalence) were compared with 14 controls. Four of six patients were diagnosed with TA-TMA by 25 days after auto-SCT. Compared with controls, TA-TMA patients had higher average systolic and diastolic blood pressure levels during high-dose chemotherapy and developed hypertension by day 13 after auto-SCT. Proteinuria was a significant marker for TA-TMA, whereas blood and platelet transfusion requirements were not. Serum creatinine did not differ between groups post transplant. However, patients with TA-TMA had a 60% decrease in renal function from baseline by nuclear glomerular filtration rate, compared with a 25% decrease in those without TA-TMA (P=0.001). There was no TA-TMA-related mortality. Significant complications included end-stage renal disease (n=1) and polyserositis (n=3). Patients with TA-TMA were unable to complete cis-RA therapy after auto-SCT. We suggest that careful attention to blood pressure and urinalysis will assist in the early diagnosis of TA-TMA, whereas serum creatinine seems to be an insensitive marker for this condition.

How important is surrogate consent for stroke research?

BACKGROUND: Patients with stroke may have cognitive deficits that impact their capacity to provide informed consent for research. Some institutional review boards restrict surrogate consent to persons who have specific legal authority to provide it. We examined the importance of surrogate consent in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial, the study that led to the only US Food and Drug Administration-approved treatment for acute ischemic stroke. METHODS: The NINDS rt-PA Stroke Trial randomized subjects with ischemic stroke to treatment with recombinant tissue plasminogen activator (rt-PA) or placebo. We compared the baseline characteristics and clinical outcomes of subjects enrolled by self-consent with those of subjects enrolled by surrogate consent. RESULTS: Surrogate consent was used to enroll 439 of 624 (70%) subjects. Subjects enrolled by surrogate consent were older (68.5 vs 63.4 years, p < 0.001), had more severe strokes (median NIH Stroke Scale score 17 vs 9, p < 0.001), and were less likely to make a good recovery (p < 0.001 for all measures) than patients who provided their own consent. There was no interaction between method of consent and response to rt-PA. If the trial had used the same sample size and recruited at the same rate but excluded patients who could not provide their own consent, it would have taken 12.5 years to complete. CONCLUSIONS: The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial would not have been completed in a timely fashion without subjects enrolled by surrogate consent. Furthermore, exclusion of subjects who could not provide their own consent would have severely limited the generalizability and value of trial results.

Microscopic computed tomography imaging of the cerebral circulation in mice: feasibility and pitfalls.

This study evaluates the utility and practical limitations of microcomputerized X-ray tomography (CT) as a research tool for examination of the cerebral circulation in mice. Six micro CT angiograms of the circle of Willis (COW) from six mice were obtained by scanning whole head and brain specimen perfused with a radio-opaque silicone contrast agent. Two-dimensional volume rendered images were postprocessed from three-dimensional image datasets using a partially automated high-throughput model that generated 10 surface projections for each specimen. The image processing model employed a straightforward global thresholding and computerized component labeling software algorithm. Postprocessed images were analyzed and results correlated with microdissection. Micro CT demonstration of COW vessels and their branch anatomy was assessed. 71% of COW vessels were completely demonstrated, 26% were partially demonstrated, and 3% were not demonstrated. All cases of nondemonstration and most cases of partial demonstration resulted from scan coverage or postprocessing clip error. Thresholding effect caused pseudostenosis of 8% of COW vessels and accounted for a minority of partial demonstration cases. No imaging artifacts were caused by contrast extravasation or ineffective contrast perfusion. Volume averaging caused minor angioarchitectural distortion of 58% of COW vessels. Ninety-five percent of COW > or =50 microm and 52% of COW vessels <50 microm were correctly identified by micro CT. Micro CT of the murine COW using a high-throughput image processing model is feasible. Angioarchitectural distortion due to volume averaging and thresholding effect can occur and pathological findings should be confirmed.

Consequences of smoking and caffeine consumption during pregnancy in women with type 1 diabetes.

OBJECTIVE: To test the hypothesis that, in women with type 1 diabetes, prenatal smoking and caffeine consumption during pregnancy are associated with an increased risk of adverse maternal and perinatal outcomes. METHODS: A secondary analysis of data on pregnant women with type 1 diabetes from an interdisciplinary program of Diabetes in Pregnancy. Women were interviewed monthly, by a trained non-medical member of the research team, using a standardized questionnaire, to ascertain daily smoking habits and caffeine consumption. RESULTS: Smoking and caffeine information were available on 191 pregnancies, 168 progressing beyond 20 weeks of gestation. Early pregnancy smoking (OR 3.3, 95% CI 1.2, 8.7) and caffeine consumption (OR 4.5, 95% CI 1.2, 16.8) were associated with increased risk of spontaneous abortion when controlling for age, years since diagnosis of diabetes, previous spontaneous abortion, nephropathy and retinopathy. Smoking throughout pregnancy was significantly associated with decreased birth weight and prolonged neonatal hospital stay. Smoking throughout pregnancy (OR 0.2, 95% 0.1, 1.0) and caffeine consumption after 20 weeks (OR 0.3, 95% CI 0.1, 1.0) were associated with reduced risk of pre-eclampsia. CONCLUSIONS: Caffeine consumption during early pregnancy, regardless of glycemic control, increases the risk of spontaneous abortion. Smoking throughout pregnancy and caffeine consumption are associated with reduced risk of pre-eclampsia.

Pregnancy outcome and progression of diabetic nephropathy. What's next?

OBJECTIVES: The first objective was to assess the association of renal function with maternal and fetal pregnancy outcome in women with diabetic nephropathy. The second objective was to examine the feasibility of a multicenter surveillance program to determine the rates of maternal and fetal pregnancy complications in women with diabetic nephropathy, and to study the effect of pregnancy on the natural history of diabetic renal disease. METHODS: In order to address the first objective, we analyzed data from women with type 1 diabetes and nephropathy enrolled in the Diabetes in Pregnancy Program at our institution. Women were assigned to one of three groups according to enrolment serum creatinine concentration: < or = 1.0 mg/dl, > 1.0 to 1.5 mg/dl and > 1.5 mg/dl. A pilot surveillance program at six centers included women experiencing pregnancy complicated by diabetic nephropathy. In both studies, medical and obstetric history, and maternal and neonatal outcomes, were recorded. Statistical analysis included chi2, logistic regression and analysis of variance. RESULTS: There were 72 pregnancies in 58 women with diabetic nephropathy who enrolled in the pregnancy program. High serum creatinine concentration at enrolment was associated with delivery before 32 weeks' gestation, very low birth weight and increased incidence of neonatal hypoglycemia, independent of quantity of total urinary protein excretion and glycemic control in any trimester. To date, pilot surveillance data have been obtained from six centers on 16 women. Serum creatinine concentrations ranged from 0.4 to 1.1 mg/dl and creatinine clearance from 32 to 317 m/min. Gestational age at delivery ranged from 22 to 39 weeks. CONCLUSIONS: High serum creatinine concentration at enrolment is a risk factor for adverse maternal and neonatal outcome, independent of quantity of total urinary protein excretion and glycemic control during any trimester. A multicenter surveillance program is needed, in order to study less frequent maternal and neonatal outcomes as well as the long-term effects of pregnancy on the natural course of diabetic renal disease.

Does the combined antenatal use of corticosteroids and antibiotics increase late-onset neonatal sepsis in the very low birth weight infant?

OBJECTIVE: The purpose of this study was to determine whether the combined use of maternal antenatal corticosteroids and antibiotic therapy is associated with an increased risk of late-onset neonatal sepsis among very low birth weight infants. STUDY DESIGN: The outcomes of infants admitted to the 3 Cincinnati neonatal intensive care units between May 1991 and May 2000 were retrospectively evaluated. Late-onset neonatal sepsis was defined either as the occurrence of a positive blood culture obtained after 72 hours of life with clinical signs of sepsis or as the need for >5 consecutive days of antibiotic therapy for presumed sepsis that initiated after 72 hours of life. Wilcoxon rank sum, chi-square test, and multiple logistic regression were used for analysis. RESULTS: Among the parturients delivering the study infants, 434 women (24%) received corticosteroids only, 175 women (9%) received antibiotics only, 819 women (46%) received both corticosteroids and antibiotics, and 370 women (20%) received neither corticosteroids nor antibiotics. Among 1978 study infants, there were 732 infants (41%) with late-onset neonatal sepsis. By univariate analysis, the odds ratio for late-onset neonatal sepsis caused by combined corticosteroid and antibiotic use was 0.96 (95% CI, 0.89%, 1.04%). Multiple logistic regression analysis was used to evaluate the risk of combined corticosteroids and antibiotic use after controlling for potential covariates and confounders. After controlling for outborn birth (odds ratio, 1.3; 95% CI, 1.0%-1.8%), increasing gestational age at delivery (odds ratio, 0.63; 95% CI, 0.60%-0.66%), interaction between white race and male gender (P =.01) and interaction between antibiotics and prolonged rupture of membranes (P =.02), the use of corticosteroids and antibiotics was not associated with an increased risk of late-onset neonatal sepsis (P =.9). CONCLUSION: The combined use of maternal corticosteroids and antibiotic therapy is not associated with an increased risk for late-onset neonatal sepsis.

Leptin in the ovine fetus correlates with fetal and placental size.

OBJECTIVE: The purpose of this study was to detect the presence of leptin and its receptor in ovine fetal tissues and to examine the relationship between circulating leptin concentrations and fetal and placental weights on gestational day 138 (GD138) of ovine pregnancy (term, 145 days). STUDY DESIGN: Pregnant sheep (n = 18) were instrumented on GD 110 to facilitate measurement and chronic reduction of uterine blood flow and produce intrauterine growth restriction. Four animals that served as controls were euthanized on GD 138 to obtain fetal tissues to determine the presence of ovine leptin and its receptor by reverse transcriptase-polymerase chain reaction. Seven instrumented animals were randomized into the control group, and 7 instrumented animals were randomized into the uterine blood flow restricted group (reduction equaled approximately 50% on GD 138). Maternal and fetal blood samples were obtained on day 138 to measure plasma leptin concentrations, and animals were euthanized for the determination of fetal morphometrics and placental weight. RESULTS: Expression of RNA for ovine leptin and its receptor were observed in fetal liver, skeletal muscle, kidney, heart, and placenta. Fetal body weight, ponderal index, and placental weight were significantly decreased by approximately 40% in the blood flow restricted group as compared with controls. Fetal leptin concentrations were increased by 45% in the uteroplacental blood flow restricted group (P =.01). Maternal leptin concentrations were not significantly different between the 2 groups and did not correlate with fetal concentrations. Fetal leptin concentrations had an inverse relationship with uterine blood flow (r = -0.73; P =.004), fetal body weight (r = -0.78; P =.002), and placental weight (r = -0.68; P =.01). CONCLUSION: Ovine fetal tissues express RNA for leptin and its receptor. Circulating leptin concentrations in the ovine intrauterine growth restriction fetus were significantly elevated on gestational day 138 compared with controls. Fetal leptin concentrations were inversely related to uterine blood flow and fetal and placental weight. These findings suggest that fetal leptin may be involved in an adaptive response to intrauterine growth restriction.

A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor.

OBJECTIVE: The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor. STUDY DESIGN: Three hundred thirty women at > or = 32 weeks gestation with a Bishop score < or = 6 and an indication for induction were randomized to 1 of 3 double-blinded groups: (1) 25 microg orally administered misoprostol plus 25 microg vaginally administered misoprostol, (2) orally administered placebo plus 25 microg vaginally administered misoprostol, or (3) 25 microg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis. RESULTS: There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P < .05) and 36% in the oral group (P < .05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P < .05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P < .05). Uterine tachysystole occurred least frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus-vaginal group; P < .05). Uterine hyperstimulation also occurred least frequently in the oral misopro-stol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P < .05). CONCLUSION: At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.

Fetal weight and progression of diabetic retinopathy.

OBJECTIVE: To test the hypothesis that progression of diabetic retinopathy in pregnancy is associated with reduced fetal growth and related neonatal morbidity. METHODS: Women with type 1 diabetes (n = 205) were enrolled before 14 weeks' gestation in a prospective study of diabetes in pregnancy and treated with intensive insulin therapy. They had serial ophthalmologic evaluations before 20 weeks' gestation and in late gestation or postpartum. Subjects were divided into two groups based on whether retinopathy progressed (progression group) or remained unchanged (no progression group). RESULTS: Retinopathy progressed in 59 of 205 women (29%) and was associated with advanced White classification (P =.001): three (5%) were class B, 14 (23%) class C, 24 (41%) class D, and 18 (30%) class F-RF. Reduced fetal growth was associated with progression of retinopathy. Mean birth weight was lower (P =.02), and more infants were small for gestational age (P =.02) and had low birth weights (P =.02) in the progression group. More large-for-gestational-age infants were noted in the no-progression group (P =.04). Birth weight percentile distributions showed a shift of the curve to the left in the progression group (P =.03). There were no differences in gestational age at delivery, macrosomia, preterm delivery, respiratory distress syndrome, neonatal hypoglycemia, or neonatal death. Small for gestational age was associated with chronic hypertension (odds ratio [OR] 6.4; 95% confidence interval [CI] 1.5, 27.9) and retinopathy progression (OR 4.7; 95% CI 1.2, 23.8). CONCLUSION: Development and progression of diabetic retinopathy during pregnancy were associated with reduced fetal growth manifested as increased rate of small-for-gestational-age and low-birth-weight infants.

Dietary fiber intakes and insulin requirements in pregnant women with type 1 diabetes.

OBJECTIVE: To determine whether higher dietary fiber intake (water soluble and insoluble) is associated with lower insulin requirements and better glycemic control in pregnant women with type 1 diabetes consuming a self-selected diet. DESIGN: A longitudinal, observational study. SUBJECTS: Pregnant women (n=141) with type 1 diabetes participating in an interdisciplinary program examining the effects of glycemic control on pregnancy outcome (Diabetes and Pregnancy Program, University of Cincinnati Medical Center). MEASUREMENTS: We determined total, water soluble and insoluble fiber intakes from 3-day food records kept each trimester during pregnancy. Outcome measures were insulin dose, pre-meal blood glucose, and glycated hemoglobin concentrations. STATISTICAL ANALYSES: Correlation coefficients, multiple regression, mixed-model analysis of variance. RESULTS: Mean intakes (g/day) of total, water soluble fiber, and insoluble fiber were 14.0 (range, 1.8-33.1), 4.8 (range, 0.6-10.5) and 9.0 (range, 1.1-24.0), respectively. In the second and third trimesters of pregnancy, insulin requirements were inversely associated with total, water soluble, and insoluble fiber intakes; the correlation coefficients ranged from -0.22 to -0.17 (P=.02 to .08). Insulin requirements associated with a higher fiber intake (20.5 g/day) were 16% to 18% lower than for a lower fiber intake (8.1 g/day). These relations remained after adjustment for body weight, disease severity and duration, insulin type, and study year in the second (P=.03 to .10) but not in the third trimester. Pre-meal blood glucose and glycated hemoglobin concentrations were not associated with fiber intake. CONCLUSIONS: Among pregnant women with type 1 diabetes, higher fiber intake is associated with lower daily insulin requirements. Dietary fiber intake should be considered when counseling patients about the management of blood glucose concentrations.

Temporal changes in brain volume and cognition in a randomized treatment trial of vascular dementia.

OBJECTIVE: To measure changes in brain and ischemic volume over time by magnetic resonance imaging (MRI) as part of a randomized treatment trial of vascular dementia. METHODS: Participants who met criteria for vascular dementia underwent comprehensive neurological and neuropsychological testing on entrance, during, and at completion of the 1-year study. For those centers who had easily available MRI, MRI of the brain was to be performed on entry and completion of the study. Image analysis was performed on all balanced and T2-weighted MR films to determine ventricular, sulcal, ischemic, and hemispheric brain volumes. RESULTS: Of the 105 patients who met the criteria for vascular dementia, 40 had a baseline MRI study that met protocol requirements and was of excellent image quality. The baseline ventricular volume in these 40 patients with high-quality MR correlated with most measures of cognitive and behavioral function, including the total Alzheimer's Disease Assessment Score (ADAS) (r = 0.51, P = .0024), as well as activities of daily living (r = 0.61, P = .0002). The baseline ischemic brain volume correlated well only with the gait and postural stability scale (r = 0.74, P = .009). Of the 40 participants, 25 had MRI studies at baseline and at completion of the study that were comparable and of excellent image quality. For these 25 patients, the mean ventricular volumes increased by 9% over the study year (P = .001) and the mean ischemic brain volume increased by 18% (P = .01). Temporal changes in the sulcal and nonischemic brain volume did not reach significance. None of the 14 clinical score measures changed significantly between baseline and completion of the study in these 25 patients. CONCLUSION: In summary, ventricular volume correlated well with cognitive measures in patients with vascular dementia and was a more sensitive marker for change during the study year than the clinical scales used in this study. This study also points out the practical limitations of brain imaging as a surrogate measure of clinical outcome in multicenter randomized treatment trials of brain disease.

A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels.

OBJECTIVE: To evaluate the impact of a focused preconceptional and early pregnancy program specializing in the care of women with Type 1 diabetes on perinatal mortality and congenital malformations. METHODS: This clinical study included women with Type 1 diabetes in an interdisciplinary Diabetes in Pregnancy Program Project Grant (PPG) funded by the NIH (1978-1993); these women were enrolled preconceptionally or during the first trimester (up to 14 weeks) and had pregnancies continuing beyond 20 weeks gestation. Strict glucose control was implemented and adherence assessed. Antepartum fetal surveillance was started at 32 weeks gestation. All live-born infants and stillbirths were examined. A retrospective comparison analysis of the period before PPG I (1973-1978) and after cessation of funding (1993-1999) was performed, specifically evaluating perinatal mortality and congenital malformation rates. Data were analyzed using analysis of variance, chi2, and Fisher's exact test. RESULTS: Three hundred and six women were enrolled in three 5-year periods: PPG I (1978-1983) n = 111, PPG II (1983-1988) n = 103, and PPG III (1988-1993) n = 92. Entry and interval glycohemoglobin A1 concentrations obtained decreased with each consecutive PPG. An emphasis on preconception care began in 1984, with preconception enrollment reaching 23% for PPG II and increasing in PPG III to 37%. As preconception enrollment increased, perinatal mortality rate decreased from 3% for PPG I and 2% for PPG II, to 0% in PPG III, and the congenital malformation rate decreased to a low 2.2% by PPG III. Comparison data collected for the period before PPG 1 (1973-1978) n = 79 revealed a perinatal mortality rate of 7% and a congenital malformation rate of 14%. Also, a postprogram retrospective analysis of the period 1993-1999 (n = 82) revealed an increase in perinatal mortality, with one death compared to none in PPG III, and a congenital malformation rate of 3.65% compared to 2.2% during PPG III. The preconception enrollment for this period decreased (19.5%). CONCLUSIONS: A program emphasizing preconceptional care, strict glycemic control preconceptionally and throughout gestation, and the use of antepartum fetal surveillance was associated with a significant decrease in the rate of perinatal mortality and congenital malformations in infants of women with Type 1 diabetes. However, ongoing improved outcome appears to depend on the availability of funding for a specialized preconception program.

The effect of early discharge after vaginal delivery on neonatal readmission rates.

OBJECTIVE: To determine the effect of a structured program for early neonatal discharge from a tertiary medical center on the risk of neonatal readmission. METHODS: An early-discharge program was instituted at our tertiary medical center in July 1993, with the objective of discharging mothers and infants within 24 hours after vaginal birth. The readmission rate of vaginally delivered infants during the early-discharge period (July 1, 1993, through March 31, 1995) was compared with the rate during a conventional-discharge period (January 1, 1992, through June 30, 1993). Analyses were performed to examine two groups within the early-discharge group: those discharged within 24 hours of vaginal delivery; and those discharged within 1 hospital day of vaginal delivery. RESULTS: During the early-discharge period, 1.24% of neonates were readmitted within 10 days of birth, compared with 1.35% during the conventional-discharge period. In the early-discharge period group, infants born vaginally and discharged within 24 hours of birth had a readmission rate of 1.46% compared with 1.14% for those who stayed longer than 24 hours after delivery. Similarly, the readmission rate was no different for infants who were discharged within 1 hospital day. The primary indications for readmission in both periods were infections and jaundice. CONCLUSION: Implementation of a structured program for early neonatal discharge does not have an association with increased risk of neonatal readmission to the hospital.

Deficient counterregulation: a possible risk factor for excessive fetal growth in IDDM pregnancies.

OBJECTIVE: The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS: Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24-28 and at 32-34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS: All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244-764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05). CONCLUSIONS: Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.

Does pregnancy increase the risk for development and progression of diabetic nephropathy?

OBJECTIVE: This study was designed to determine whether pregnancy and increasing parity in women with insulin-dependent diabetes mellitus (1) increases the risk for diabetic nephropathy and (2) accelerates the progression of diabetic nephropathy. STUDY DESIGN: The study included women with insulin-dependent diabetes mellitus who enrolled in our diabetes-in-pregnancy trial with a pregnancy that continued beyond 20 weeks' gestation and who were delivered between 1978 and December 31, 1991, to allow for a minimum of 3 years' follow-up. Pregnancy and follow-up information was obtained from the medical records and from our computerized database. For patients followed up elsewhere, information was obtained from their current physicians. Life-table analysis was used to determine (1) the risk for nephropathy developing de novo as a function of duration of disease and the association of this risk with parity and (2) the risk of renal failure developing in women with preexisting nephropathy and its association with parity. RESULTS: The study population included 182 pregnant women with insulin-dependent diabetes mellitus: 46 with overt nephropathy (group F) and 136 without nephropathy (group NF). Pregnancy and increasing parity did not increase the overall risk for nephropathy (44% after 27 years of diabetes). In group NF 10% had nephropathy within 10.1 +/- 4.2 years of the pregnancy. Proteinuria appearing during pregnancy and glycemic control during pregnancy were significantly associated with the subsequent development of nephropathy. In group F 26% had end-stage renal disease after a median period of 6 years from the pregnancy. Pregnancy or increasing parity did not increase the risk for renal failure in women with nephropathy. CONCLUSIONS: Our data support the premise that pregnancy in women with insulin-dependent diabetes mellitus does not increase the risk of subsequent nephropathy and does not accelerate progression of renal disease in women with preexisting nephropathy.

Counterregulatory hormonal responses to hypoglycemia during pregnancy.

OBJECTIVE: To evaluate the counterregulatory responses to insulin-induced hypoglycemia in healthy women and in women with insulin-dependent diabetes during pregnancy and in the nonpregnant state. METHODS: Hypoglycemia was induced using the hypoglycemic clamp technique in 17 women with insulin-dependent diabetes and in ten healthy controls, both in the nonpregnant state (study 1), at 24-28 weeks' gestation (study 2), and at 32-34 weeks' gestation (study 3). Plasma glucose concentrations were decreased to 60 mg/dL and maintained at this level for 1 hour. Blood samples were drawn every 15 minutes to measure epinephrine, glucagon, growth hormone, and cortisol concentrations. Statistical analyses compared counterregulatory responses between women with and without diabetes, and between the pregnant and nonpregnant state. RESULTS: Women with diabetes had significantly diminished peak epinephrine responses to hypoglycemia compared with controls (mean +/- standard error of the mean [SEM]): 52 +/- 11 versus 191 +/- 42 pg/mL in study 1, 30 +/- 9 versus 102 +/- 47 pg/mL in study 2, and 38 +/- 10 versus 148 +/- 38 pg/mL in study 3 (P < .05). Their responses during pregnancy were also diminished compared with their own nonpregnant epinephrine responses. Women with diabetes also had no recognizable cortisol or glucagon responses to hypoglycemia, and in healthy controls the glucagon responses were significantly diminished during pregnancy compared with their own nonpregnant responses. In both groups, growth hormone responses (mean +/- SEM) diminished progressively during pregnancy from study 1 (14.6 +/- 2.5 and 12.5 +/- 5.2 ng/mL) to study 2 (4.4 +/- 1.1 and 7.3 +/- 2.7 ng/mL) to study 3 (2.5 +/- 0.9 and 4.4 +/- 2.3 ng/mL) in women with diabetes and in controls, respectively. CONCLUSION: Counterregulatory epinephrine and growth hormone responses to hypoglycemia are diminished in women with insulin-dependent diabetes during pregnancy. This may be due, in part, to an independent effect of pregnancy, contributing to the increased incidence of hypoglycemia in these patients during pregnancy.