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Objectives To monitor for a signal of major teratogenicity by determining the risk of all birth major defects following in utero exposure to sumatriptan, naratriptan, and the sumatriptan/naproxen sodium combination product (tablets marketed in the United States as Treximet [GlaxoSmithKline, Research Triangle Park, NC, USA]), and to monitor for unusual patterns of defects that might suggest teratogenicity. Background The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to anti-migraine drugs in pregnancy is likely. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry captured data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. Methods In this primarily prospective, observational study, health care professionals from anywhere in the world enrolled, on a voluntary basis, women exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen sodium combination product during their pregnancies. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The proportion of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. Results The registry enrolled 680 evaluable exposed pregnant women, which resulted in 689 infants and fetuses (outcomes). Of these outcomes, 626 were exposed to sumatriptan, 57 were exposed to naratriptan (seven were exposed to both sumatriptan and naratriptan), and six were exposed to the sumatriptan/naproxen sodium combination product. Twenty outcomes with major birth defects were reported among 528 outcomes exposed in the first trimester to sumatriptan. The estimated risk of major birth defects following first-trimester sumatriptan exposure is 4.2% (20/478 [95% confidence interval [CI] 2.6%–6.5%]). Among 52 first-trimester exposures to naratriptan, major birth defects were reported in one outcome, an infant with exposure to both sumatriptan and naratriptan [birth defect risk of 2.2% (1/46 [95% CI 0.1%–13.0%]). No major defects were reported among the five outcomes with first-trimester exposure to the sumatriptan/naproxen sodium combination products. Conclusions The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry detected no signal of teratogenicity associated with major birth defects for sumatriptan. This finding is consistent with results from other observational studies using a variety of control groups. Enrollment in the registry was insufficient to permit definitive conclusions of the risks associated with naratriptan or sumatriptan/naproxen sodium tablets, or to assess the risk of individual birth defects in any of the products studied. Low enrollment and high rates of loss to follow up within the registry over an extended period of time led the registry's scientific advisory committee to conclude that continuation of the registry beyond its 16 years would offer little additional power to rule out more moderate increases in the risk of birth defects. Data from the other ongoing surveillance sources constitute an important element of post-marketing surveillance of these medications. The lack of a signal of major teratogenicity with sumatriptan across these several sources of data is encouraging.

Purpose To refine a preliminary analysis identifying a possibly increased prevalence of malformations among infants born to women exposed to paroxetine in the first trimester. Methods This study used data from UnitedHealthcare, a large U.S. insurer, using datasets originally for a study of bupropion in pregnancy. We identified women with a live-born delivery between January 1995 and September 2004. We classified women according to their first trimester mono- or mono/polytherapy exposure to paroxetine and other antidepressants. We confirmed malformation cases by medical record abstraction. We calculated the adjusted odds ratios (AORs) through logistic regression. Results For paroxetine, there were 815 infants among 791 women exposed as monotherapy, and 1020 infants among 989 women exposed as mono- or polytherapy. For other antidepressants, there were 4198 infants among 4072 women exposed as monotherapy, and 4936 infants among 4767 women exposed as mono- or polytherapy. AORs for all congenital malformations associated with paroxetine were 1.89 (95%CI 1.20–2.98) for monotherapy, and 1.76 (95%CI 1.18–2.64) for mono- or polytherapy. AORs for cardiovascular malformations associated with paroxetine were 1.46 (95%CI 0.74–2.88) for monotherapy, and 1.68 (95%CI 0.95–2.97) for mono- or polytherapy. Conclusions These more detailed paroxetine findings confirm previous findings of analyses of these data among women exposed to all types of antidepressants. The present findings are consistent with other recent results suggesting the possibility of a modestly increased occurrence of congenital malformations following first trimester exposure to paroxetine compared to other antidepressants. Copyright © 2007 John Wiley & Sons, Ltd.

BACKGROUND: As part of an effort to validate the General Practice Research Database (GPRD) for future studies of medication use in pregnancy, this study examined whether the rates of all, and specific types of, congenital heart defects obtained from the GPRD are similar to those obtained from UK national systems. METHODS: The prevalence rates of heart defects for 2001–2003 were determined from the GPRD and compared with both the National Congenital Anomaly System (NCAS) and the European Concerted Action of Congenital Anomalies and Twins (EUROCAT). Rate ratios (RRs) and 95% CIs were calculated comparing the prevalence of all congenital heart defects as well as specific types of heart defects in the three data sources. In addition, the effect of the child's age on the frequency of heart defects in the GPRD was determined. RESULTS: The prevalence of heart defects in the GPRD was more than twice as high as in the NCAS and slightly higher than in the EUROCAT. All differences were statistically significant. The prevalence of specific heart defects varied across the GPRD, NCAS, and EUROCAT. The measured prevalence of congenital heart defects in the GPRD was higher if calculated including children up to age 6. CONCLUSIONS: The comparisons of the GPRD prevalence rates to national prevalence estimates demonstrate that the GPRD can serve as a more complete source of background prevalence for the most commonly occurring congenital heart defects, which is essential to properly assess possible associations between maternal exposures and congenital heart defects. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc.

Objective The purpose of this research was (1) to validate that ventricular septal defect (VSD), tetralogy of Fallot (TOF), and coarctation of the aorta (COA) can be studied in the UK General practice research database (GPRD) and (2) to understand which of the available GPRD components (computerized medical records, questionnaires, and maternal/infant free text) provide maximal information about these heart defects. Methods Using a practitioner questionnaire, the positive predictive value (PPV) of the computerized medical record for VSD, TOF, and COA were determined. Both infant and maternal free text was examined. Concordance between the infant free text information and questionnaires was calculated. The proportion of infant information captured in the maternal free text was determined. Results A 93% response rate was achieved. Based on questionnaire responses, an overall PPV of 93.5% was achieved (VSD = 95%, TOF = 90%, COA = 100%). Approximately half of the records contained infant free text information including information on the type and size of VSD, echocardiogram findings, and surgery. Concordance between the infant's free text and questionnaire information occurred in most of the cases (92–100%). The proportion of infant information in the maternal free text was low (4–19%). Conclusion The GPRD computerized medical records are sufficient to assess VSD, TOF, and COA. This study confirms that maternal free text provides a low yield of limited information pertaining to the infants' defect, while the infant free text may provide an additional information usually obtainable from practitioner questionnaires. The information provided by an infant free text may limit the need for practitioner questionnaire validation. Copyright © 2007 John Wiley & Sons, Ltd.

Objective: To evaluate the occurrence of stroke/TIA symptoms and ischemic stroke events among those with a lifetime history of migraine or other headaches with some migraine features in a biracial cohort of older adults. Methods: Participants were 12,750 African-American and white men and women from the Atherosclerosis Risk in Communities Study (1993 to 1995). The participants were queried about their lifetime headache history and characterized using modified International Headache Society diagnostic criteria. Stroke/TIA symptoms were classified using a computerized diagnostic algorithm, and ischemic stroke events were identified and validated using medical records. Multivariate logistic regression was used to assess the relationship between headache types and stroke/TIA symptoms and ischemic stroke events. Results: Migraine with aura was strongly associated with stroke symptoms (odds ratio [OR] 5.46, 95% CI: 3.64 to 8.18), TIA symptoms (OR 4.28, 95% CI: 3.02 to 6.08), and verified ischemic stroke events (OR 2.81, 95% CI: 1.60 to 4.92). Similarly, other headaches with aura were significantly associated with stroke symptoms (OR 3.68, 95% CI: 2.26 to 5.99) and TIA symptoms (OR 4.53, 95% CI: 3.08 to 6.67). In contrast, the associations for migraine without aura and other headaches without aura were not as consistent or robust. Conclusions: Migraines and other headaches, particularly those accompanied by aura, were associated with an increased occurrence of stroke/TIA symptoms and ischemic stroke events.

OBJECTIVE—The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up. RESEARCH DESIGN AND METHODS—We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development. RESULTS—Patients with diabetes were much more likely to develop CHF than patients without diabetes (incidence rate 30.9 vs. 12.4 cases per 1,000 person-years, rate ratio 2.5, 95% CI 2.3–2.7). The difference in CHF development rates between persons with and without diabetes was much greater in younger age-groups. In addition to age and ischemic heart disease, poorer glycemic control (hazard ratio 1.32 per percentage point of HbA1c) and greater BMI (1.12 per 2.5 units of BMI) were important predictors of CHF development. CONCLUSIONS—The CHF incidence rate in type 2 diabetes may be much greater than previously believed. Our multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity. Younger patients may benefit most from risk factor modification.

We examined the association between menstrual patterns and risk of developing adult-onset diabetes in a prospective study of 668 white, college-educated women who completed menstrual diaries throughout their reproductive years. We calculated summary measures of cycle length and variability and bleeding duration for agesor = 22, 23-27, 28-32, and 33-37 years. The analysis included 35,418 person-years of follow-up and 49 self-reported cases of diabetes (median age at diagnosis, 63 years). There was no association between diabetes risk and age at menarche, mean cycle length, cycle variability, or frequency of long cycles (42 days). Longer bleeding periods in the mid- and late reproductive years were somewhat associated with an increased risk of diabetes (adjusted rate ratio 1.4, 95% confidence interval 1.0-1.8 per day increase in bleeding duration for menses during ages 28-32). These results do not support the association of long or irregular menstrual cycles with post-menopausal diabetes incidence, but do suggest a possible association of longer bleeding duration with subsequent onset of diabetes.

Objective: Glaxo Wellcome becomes aware of prenatal exposures to its medications as early as the clinical trial phase of development. An international process for monitoring prenatal exposure to all Glaxo Wellcome medicines has been developed. For specific products there are prospective pregnancy registries. Study Design: The registries are observational, case-registration, and follow-up studies designed to detect evidence of teratogenicity associated with specific medications. After prenatal exposure to the registry medication, pregnancies are registered prospectively, through voluntary reports by health care providers. An advisory committee of independent scientists for each registry reviews data and advises in dissemination of information. Risk of birth defects, as defined by the Centers for Disease Control and Prevention, is compared with published risks both in women in the general population and in women with the underlying condition being treated, if available. Results: The following data show results from the prospective first-trimester exposures registered since establishment of each registry. The published risk of birth defects in the general population range is 3% to 5%, and the risk in women with epilepsy is 6% to 9%. The proportions of outcomes with birth defects are as follows: in the Acyclovir (antiviral medication) Pregnancy Registry (1984-1998) (19/581), 3.3% (95% confidence interval, 2.0%-5.2%); in the Lamotrigine (monotherapy and polytherapy antiepileptic medication) Pregnancy Registry (1992–September 1998) (8/123), 6.5% (95% confidence interval, 3.1%-12.8%); in the Sumatriptan (migraine medication) Pregnancy Registry (1996–October 1998) (7/183), 3.8% (95% confidence interval, 1.7%-8.0%). The Valacyclovir, Bupropion, and Naratriptan registries have insufficient data for analysis. Conclusion: None of the registries has provided a risk estimate exceeding that expected in the disorder treated, and no pattern of defects has been observed. Whereas information from the larger registries is reassuring regarding risk, these studies cannot rule out possible small excess risks from use of these drugs in pregnancy. Data obtained through these registries are shared with the medical community as a supplement to animal toxicology studies to assist in weighing potential risks and benefits of treatment for individual patients. The success of the registries depends on the continued willingness of the obstetrics and gynecology community to notify the registries of prenatal exposures. (Am J Obstet Gynecol 2000;182:159-63.)

Objective Blood pressure changes during menopausal transition have not been studied previously using a biracial sample. We investigated whether menopausal transition was associated with change in blood pressure in African-American or white women. Design, setting and participants The prospective multicenter study, the Atherosclerosis Risk In Communities (ARIC) Study (1987-95) was utilized. Included were never-users of hormone replacement therapy (3,800 women, 44% of the original sample). Main outcome measure Changes in blood pressure were adjusted for baseline age and body mass index, baseline blood pressure, antihypertensive use, ARIC field center and weight change. The menopausal transition group was compared to the non-transition group, separately, by ethnicity. Results Women undergoing the menopausal transition did not differ significantly in regard to systolic blood pressure change [5.2, 95% confidence interval (CI) 4.0-6.4] from non-transitional women (4.6, 95% CI 4.0-5.2); adjustment for age, baseline systolic blood pressure and other factors did not alter this finding. Transitional women had significantly less diastolic blood pressure change (-0.5, 95% CI -1.1 to 0.2) than non-transitional women (-2.0, 95% CI -2.4 to -1.7, P= 0.000) but, after adjustment for other covariates, the result was not significant African-American women had significantly (P= 0.003) higher systolic blood pressure change compared to white women, but this difference became non-significant (P= 0.21) after restricting the sample to women younger than 55 years of age. Interactions between menopausal transition and ethnicity were not significant, either in systolic blood pressure or diastolic blood pressure change. Conclusion Menopausal transition is not associated with significant blood pressure change in African-American or white women.

Objectives.— To monitor for a signal of major teratogenicity by determining the risk of all major defects following in utero exposure to sumatriptan and naratriptan. To monitor for unusual patterns of birth defects that might suggest teratogenicity. Background.— The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to these drugs in pregnancy is likely. The Sumatriptan and Naratriptan Pregnancy Registry captures data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. Methods.— Healthcare professionals from anywhere in the world can enroll, on a voluntary basis, women exposed to sumatriptan or naratriptan during their pregnancies in this primarily prospective, observational study. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The percentage of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. Results.— Data are available on pregnancy outcomes from 599 exposed women. Among 479 first-trimester exposures to sumatriptan, 20 outcomes with major birth defects were reported (4.6%, 95% confidence interval [CI] 2.9-7.2%). The risk of major birth defects following exposure to sumatriptan during any trimester was 4.7% (95% CI 3.1-7.0%). No distinctive pattern of major birth defects among exposed infants was noted. There were 50 first-trimester exposures to naratriptan with 1 reported birth defect in a fetus with exposure to both sumatriptan and naratriptan. Conclusions.— The risk of all major birth defects following first-trimester exposure to sumatriptan was 4.6% (95% CI 2.9-7.2%). This coupled with a consistent failure of additional epidemiological studies to observe a signal for major teratogenicity gives a level of reassurance concerning the safety of sumatriptan in pregnancy. There are too few data on naratriptan to draw definitive conclusions, and the sample size for sumatriptan remains too small to detect any but very large increases in specific birth defects.

BACKGROUND: Several studies have evaluated maternal first trimester paroxetine use and the prevalence of congenital defects, particularly cardiac defects. To synthesize current epidemiologic information, a meta-analysis was conducted. METHODS: A systematic literature search was conducted for original research published from January 1, 1992, through September 30, 2008. Results were extracted using predefined criteria, and authors were contacted for additional information when necessary. Compiled results were evaluated for funnel plot asymmetry, heterogeneity, and study characteristic associations. Where appropriate, fixed-effect summary estimates were calculated and sensitivity analyses performed. RESULTS: Twenty reports (11 including results for aggregated congenital and combined cardiac defects, six for aggregated congenital defects only, and three for combined cardiac defects only) met prespecified inclusion criteria. There was little evidence of funnel plot asymmetry or overall heterogeneity. Summary estimates were produced for combined cardiac defects (prevalence odds ratio [POR], 1.46; 95% confidence interval [CI], 1.17–1.82) and aggregated congenital defects (POR, 1.24; 95% CI, 1.08–1.43) and first trimester paroxetine use. Some study characteristics may be associated with differential POR estimates for paroxetine and either combined cardiac or aggregated congenital defects. CONCLUSIONS: This meta-analysis found little evidence of publication bias or overall statistical heterogeneity and only weak evidence of associations with some study characteristics. Although subject to limitations, the summary estimate indicates an increased prevalence of combined cardiac defects with first trimester paroxetine use. The summary estimate also indicates an increased prevalence of aggregated congenital defects with paroxetine; however, this association may be explained, in part, by the increased prevalence of combined cardiac defects. Birth Defects Research (Part A), 2010. © 2009 Wiley-Liss, Inc.

Background Increased risk for CHF in persons with type 2 diabetes is well established. Our objectives were to estimate the CHF risk associated with specific therapies for diabetes and to determine the differences in incidence rates of CHF associated with adding various antidiabetic agents. Methods Subjects were members of the Kaiser Permanente Northwest (KPNW) diabetes registry as of 1 January 1998, with no prior history of CHF (n = 8063). We identified their therapy as of that date and then defined the start of the subject study period as the date when their drug regimen changed, either by switching to or by adding another antidiabetic drug. We defined the new therapy as the index therapy and the date of initiating the new therapy as the index date. Follow-up on the patients was done until the index therapy was discontinued or changed, or until 31 December 2002, whichever came earlier. We calculated the incidence rate of CHF in patients on various therapeutic regimens adjusting for age, gender, diabetes duration, existing ischemic heart disease, hypertension, renal insufficiency and glycemic control (HbA1c). Results CHF incidence rates were highest in index therapy categories that included insulin and lowest in regimens that included metformin. When insulin was added to an initial therapy, CHF incidence was increased 2.33 times (p < 0.0001) and 2.66 times (p < 0.0001) compared to the addition of sulphonylurea or metformin respectively. Conclusions Our findings support the theory that elevated serum insulin levels promote the development of cardiac disease. Consistent with the UKPDS, metformin may offer some protection from incident CHF relative to sulphonylurea or insulin. Copyright © 2004 John Wiley & Sons, Ltd.

The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up.We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development.Patients with diabetes were much more likely to develop CHF than patients without diabetes (incidence rate 30.9 vs. 12.4 cases per 1,000 person-years, rate ratio 2.5, 95% CI 2.3-2.7). The difference in CHF development rates between persons with and without diabetes was much greater in younger age-groups. In addition to age and ischemic heart disease, poorer glycemic control (hazard ratio 1.32 per percentage point of HbA(1c)) and greater BMI (1.12 per 2.5 units of BMI) were important predictors of CHF development.The CHF incidence rate in type 2 diabetes may be much greater than previously believed. Our multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity. Younger patients may benefit most from risk factor modification.

Objective.—To evaluate the lifetime prevalence of migraine and other headaches lasting 4 or more hours in a population-based study of older adults. Background.—Migraine and other headaches not fulfilling migraine criteria are common afflictions. Yet the health and social effects of these conditions have not been fully appreciated, particularly among older adults. Methods.—The study included 12 750 participants in the Atherosclerosis Risk in Communities (ARIC) Study from 4 US communities. Prevalence estimates of a lifetime history of migraine and other headaches lasting 4 or more hours were obtained for race and gender groups. A cross-sectional analysis was done to assess the relationship between headache type, by aura status, and various sociodemographic and health-related indices. Results.—Compared to education beyond high school, having completed less than 12 years of education was significantly associated with an increased occurrence of migraine with aura (prevalence odds ratio [POR], 1.47; 95% confidence interval [CI], 1.08 to 2.01). Family income less than $16 000, compared to family income of $75 000 or greater, was significantly associated with migraine with aura (POR, 1.68; 95% CI, 1.07 to 2.64), migraine without aura (POR, 1.56; 95% CI, 1.14 to 2.14), and other headaches with aura (POR, 1.89; 95% CI, 1.14 to 3.13). The prevalence odds ratio was higher in each headache category, particularly for those with an aura, for those with hypertension versus normotension and for those who perceived their general health as poor compared to those whose perception was excellent. Conclusions.—A lifetime history of migraine with aura and other headaches with aura was more common among whites, women, and younger participants. Further investigation of headaches lasting 4 or more hours, particularly by aura status, is warranted.

Objectives: Glaxo Wellcome (G.W.) becomes aware of prenatal exposures to its medications from as early as the clinical trial phase of development. An international process for monitoring prenatal exposure to all G.W. medicines has been developed utilizing a passive surveillance system and, for specific products, pregnancy registries. Additionally, G.W. jointly sponsors the multi-company Antiretroviral and North American Antiepileptic Drug (AED) Pregnancy Registries. Study Design: The registries are observational, case-registration and follow-up studies designed to detect evidence of teratogenicity associated with specific medications. Pregnancies are registered prospectively following prenatal exposure to the registry medication. An advisory committee for each registry reviews data and assists in dissemination of information. Committee members include independent scientists with expertise in fields such as obstetrics, teratology, epidemiology, pediatrics, and the relevant therapeutic areas. Results: The following data are from the prospective first-trimester exposures in each registry. Through December 1996, the proportion of outcomes in the Acyclovir Pregnancy Registry with birth defects (n = 17/505) is 3.4% (95% CI 2.0%, 5.4%). Through March 1997, the proportion of outcomes in the Lamotrigine Pregnancy Registry with birth defects (n = 4/76) is 5.3% (95% CI 1.7%, 13.6%). Through April 1997, the proportion of outcomes in the Sumatriptan Pregnancy Registry with birth defects (n = 5/148) is 3.4% (95% CI 1.3%, 8.1%). The newer Valacyclovir and Bupropion Pregnancy Registries have insufficient data for analysis. None of the registries have provided a risk estimate exceeding that expected in the general population, and no pattern of defects has been observed. Conclusions: The outcomes accumulated to date represent a sample of insufficient size for reaching conclusions regarding the possible teratogenic risk of using these drugs in pregnancy. Data obtained through these registries are shared with the medical community as a supplement to animal toxicology studies and to assist in weighing potential risks and benefits of treatment for individual patients. The success of the registries depends on the continued willingness of the OB/GYN community to notify the registries of prenatal exposures.

Background: Health professionals often need to make medical management decisions by weighing potential risk versus benefit. Because 50% of pregnancies in the United States are unplanned, the likelihood for unintentional first-trimester exposure to medications is high and increases when women of childbearing potential (ages 15–44) are taking medications used to treat chronic or recurrent conditions, such as migraine. Prospective collection of pregnancy exposure and outcome data is one method for providing data to the medical community as a tool for making risk assessments. Methods: The Sumatriptan Pregnancy Registry is an international, exposure-registration and follow-up study to prospectively collect prenatal sumatriptan exposure and outcome data. An advisory committee reviews data and assists in disseminating information. Committee members include independent scientists with expertise in obstetrics, pediatrics, neurology, internal medicine, epidemiology, clinical genetics, and teratology. Results: As of April 30, 1997, 181 outcomes were prospectively reported from pregnancies involving use of sumatriptan. Of the 171 outcomes where earliest exposure was in the first trimester there were 143 infants without birth defects, 4 live infants with birth defects, 1 stillbirth with birth defects [12 spontaneous pregnancy losses, 2 stillbirths, and 9 induced abortions without birth defects]. The proportion of outcomes involving birth defects, 5/148, 3.4% (95% CI 1.3%, 8.1%), does not differ from the expected proportion in the general population. Conclusions: To date, no pattern has emerged in either the prospectively or retrospectively reported defects. Registry data are disseminated to interested health care providers who are then in a more informed position when making medical management decisions. However, more data are needed before definitive conclusions can be drawn about the safety of sumatriptan use in pregnancy.

Several studies have reported increased mortality risk with early natural menopause. More recently, mortality risk was reported to be reduced among women who gave birth at ageor =40 years. The association between reproductive history and mortality was explored among 826 women in a prospective study involving 18,959 person-years of follow-up (from age 50 to 1990-1991) and 108 deaths. After adjustment for age and other covariates, the risk ratio among parous women was 1.53 (95% confidence interval: 0.58, 4.07) for natural menopause at ageor =45 years compared withor =51 years. In contrast to a previous report, however, the highest estimated mortality risk was seen among women who gave birth in their forties (adjusted risk ratio = 2.14, 95% confidence interval: 1.05, 4.38) compared with having a last birth at ages 30-34 years.This paper studied the association between menopausal and reproductive history and mortality risk in a cohort of 826 women in a prospective study involving 18,959 person-years of follow-up (from age 50 to 1990-91) and 108 deaths. According to studies, the risk of mortality was reduced among women who gave birth at age 40 or older. After an adjustment for age and other covariates, the risk ratio among parous women was 1.53 (95% confidence interval: 0.58, 4.07) for natural menopause at age 45 or younger compared with age 51 or older. Contrary to a previous report, the highest estimated mortality risk was seen among women who gave birth in their 40s (adjusted risk ratio = 2.14; 95% confidence interval: 1.05, 4.38) compared with having a last birth at ages 30-34.

Background: Sumatriptan is an acute treatment for migraine which is often used by women in their child-bearing years, and who become unexpectedly pregnant. Within the context of the post-marketing use of sumatriptan injection for the acute treatment of migraine, and in compliance with approved labeling, we wished to compare perinatal pregnancy outcomes in women who did and did not use the drug after conception. Methods: Open-label, prospective study conducted in 12,339 migraineurs (including 9,861 women) whose demography and consumption pattern of sumatriptan injections were typical, and were predicted to include 150 pregnancies. Outcome of pregnancy was the end-point. Results: There were 168 of 173 pregnancies that were well-documented. Sumatriptan was only used prior to conception in 92 cases. There were 76 first trimester exposures to sumatriptan. There were no differences in pregnancy outcome between the two groups. Conclusions: Perinatal and pregnancy outcome did not differ between patients who had and had not used sumatriptan after conception, at the resolution of these sample sizes. This study design complements the ongoing pregnancy registry, which is now widened to patients exposed to all formulations of sumatriptan.

The data on the menstrual cycle as a health endpoint and as a risk factor for chronic disease are inadequate. Specifically, the data on menstrual cycle length and blood loss do not have the detail on within-woman variability needed to allow women and clinicians to anticipate certain bleeding changes that tend to develop at different life stages, to distinguish between potentially pathologic alterations from short-term aberrations, and to recognize bleeding patterns that may be risk factors for the development of chronic disease. Lack of data on bleeding changes in premenopausal and menopausal women concerns many health professionals considering the many physician visits for abnormal bleeding and the prevalence of hysterectomy among women aged more than 35. Thus, development of objective criteria on how much bleeding is too much is needed so women can determine whether their daily blood loss is or is not a concern. Women also need more information on what constitutes menstrual dysfunction. Some basic research needs include definition of population patterns of gynecologic disease, identification of potentially modifiable risk factors, the influence of recreational activity in gynecologically mature women, influence of hard physical activity in the context of women's daily work life, interaction of low weight and physical activity in developing countries, effects of work stress, effects of family interactions, effects of violence, environmental risk factors (e.g., pesticides), and physiologic variation across the menstrual cycle. Research on menstrual cycle-related risk factors for chronic disease could explain women's long term health status and identify preventive strategies for premenopausal women. Current women's health research tends to ignore hormonal influences. The limited available research on immune parameters suggests that follicular/luteal classification may not be able to detect meaningful variation. In conclusion, a comprehensive research program would fill the many gaps in scientific knowledge about the menstrual cycle.