Validation of an ICD-10 case-finding algorithm for endometrial cancer in US insurance claims.

PURPOSE: To evaluate the positive predictive value (PPV) of an endometrial cancer case finding algorithm using International Classification of Disease 10th revision Clinical Modification (ICD-10-CM) diagnosis codes from US insurance claims for implementation in a planned post-marketing safety study. Two algorithm variants were evaluated. METHODS: Provisional incident endometrial cancer cases were identified from 2016 through 2020 among women aged ≥50 years. One algorithm variant used diagnosis codes for malignant neoplasms of uterine sites (C54.x), excluding C54.2 (malignant neoplasm of myometrium); the other used only C54.1 (malignant neoplasm of endometrium). A random sample of medical records of recent incident provisional cases (2018-2020) was requested for adjudication. Confirmed cases showed biopsy evidence of endometrial cancer, documentation of cancer staging, or hysterectomy following diagnosis. We estimated the PPV of the variants with 95% confidence intervals (CI) excluding cases that had insufficient information. RESULTS: Of 294 provisional cases adjudicated, 85% were from outpatient settings (n = 249). Mean age at diagnosis was 69.3 years. Among the 294 adjudicated cases (identified with the broader algorithm variant), the same 223 were confirmed endometrial cancer cases by both algorithm variants. The PPV (95% CI) for the broader algorithm variant was 84.2% (79.2% and 88.3%), and for the variant using only C54.1 was 85.8% (80.9% and 89.8%). CONCLUSION: We developed and validated an algorithm using ICD-10-CM diagnosis codes to identify endometrial cancer cases in health insurance claims with a sufficiently high PPV to use in a planned post-marketing safety study.

Lessons learned from a multi-data source research collaboration: The mirabegron post-authorization safety study program.

BACKGROUND: Many factors contribute to developing and conducting a successful multi-data source, non-interventional, post-authorization safety study (NI-PASS) for submission to multiple health authorities. Such studies are often large undertakings; evaluating and sharing lessons learned can provide useful insights to others considering similar studies. OBJECTIVES: We discuss challenges and key methodological and organizational factors that led to the delivery of a successful post-marketing requirement (PMR)/PASS program investigating the risk of cardiovascular and cancer events among users of mirabegron, an oral medication for the treatment of overactive bladder. RESULTS: We provide context and share learnings, including sections on research program collaboration, scientific transparency, organizational approach, mitigation of uncertainty around potential delays, validity of study outcomes, selection of data sources and optimizing patient numbers, choice of comparator groups and enhancing precision of estimates of associations, potential confounding and generalizability of study findings, and interpretation of results. CONCLUSIONS: This large PMR/PASS program was a long-term commitment from all parties and benefited from an effective coordinating center and extensive scientific interactions across research partners, scientific advisory board, study sponsor, and health authorities, and delivered useful learnings related to the design and organization of multi-data source NI-PASS.

Distribution of gestational age at birth by maternal and infant characteristics in U.S. birth certificate data: Informing gestational age assumptions when clinical estimates are not available.

PURPOSE: We aimed to describe the distribution of gestational age at birth (GAB) to inform the estimation of GAB when clinical or obstetric estimates are not available for perinatal pharmacoepidemiology studies. METHODS: We estimated GAB (median, mode, mean, and standard deviation) and percentage born at each gestational week in groups based on plurality and other variables for live births in CDC's U.S. birth data. RESULTS: In 2020, 3 617 213 newborns had birth certificates with nonmissing GAB. Among singletons (3 501 693), median and mode GAB were both 39 weeks. Births with lower median GAB were from women with eclampsia (37 weeks) or receiving intensive care (37 weeks); newborns receiving intensive care (37 weeks); newborns with birth weight <2500 g (35 weeks), <1500 g (28 weeks), or <1000 g (25 weeks); and newborns not discharged alive (23 weeks). Among twins (112 633), median GAB was 36 weeks (mode, 37 weeks). Additional noteworthy groups were women with 0-6 prenatal visits (median, 34 weeks) or 7-8 prenatal visits (median, 35 weeks) or aged 15-19 years (median, 35 weeks). CONCLUSIONS: Some maternal and infant groups had distinct GAB distributions in the United States. This information can be useful in estimating GAB when individual-level clinical estimates are not available, such as in database studies of medication use during pregnancy.

Perinatal pharmacoepidemiology: How often are key methodological elements reported in publications?

PURPOSE: Publications provide important information for clinicians, researchers, and patients. Key methodological elements must be reported for maximum transparency. We identified key methodological elements necessary for fully understanding perinatal pharmacoepidemiology research and quantified the proportion of studies that reported these elements in a sample of publications. METHODS: Key methodological elements were identified from guidelines from regulatory agencies, literature, and subject-matter knowledge: source of information to determine pregnancy start; mother- or father-infant linkages (process, success rate); unit of analysis; and whether non-live births and fetuses with various anomalies were included in the study population. We conducted a literature review for recent observational studies on medical product utilization or safety during pregnancy and estimated the prevalence of reporting these elements. RESULTS: Data were extracted from a random sample of 100 publications; 8% were published in epidemiology/pharmacoepidemiology journals; 85% were medical product-safety studies. Of publications for which each element was applicable, 43% reported the source for determining pregnancy start; 57%, whether the study population included multifetal pregnancies; 39%, whether it included more than one pregnancy per woman; 27%, whether it included fetuses with chromosomal abnormalities; 60%, fetuses with major congenital malformations; and 93%, non-live births. Of the 20 studies with mother-infant linkage, 35% described the process; 21% reported the linkage success rate. Among studies with more than one pregnancy/offspring per woman, 22% reported methods addressing sibling correlation. CONCLUSIONS: In this sample of pregnancy-related pharmacoepidemiology publications, completeness of reporting could have been improved. A pregnancy-specific checklist would increase transparency in the dissemination of study results.

Validation of cardiovascular outcomes and risk factors in the Clinical Practice Research Datalink in the United Kingdom.

PURPOSE: Strategies to identify and validate acute myocardial infarction (AMI) and stroke in primary-care electronic records may impact effect measures, but to an unknown extent. Additionally, the validity of cardiovascular risk factors that could act as confounders in studies on those endpoints has not been thoroughly assessed in the United Kingdom Clinical Practice Research Datalink's (CPRD's) GOLD database. We explored the validity of algorithms to identify cardiovascular outcomes and risk factors and evaluated different outcome-identification strategies using these algorithms for estimation of adjusted incidence rate ratios (IRRs). METHODS: First, we identified AMI, stroke, smoking, obesity, and menopausal status in a cohort treated for overactive bladder by applying computerized algorithms to primary care medical records (2004-2012). We validated these cardiovascular outcomes and risk factors with physician questionnaires (gold standard for this analysis). Second, we estimated IRRs for AMI and stroke using algorithm-identified and questionnaire-confirmed cases, comparing these with IRRs from cases identified through linkage with hospitalization/mortality data (best estimate). RESULTS: For AMI, the algorithm's positive predictive value (PPV) was >90%. Initial algorithms for stroke performed less well because of inclusion of codes for prevalent stroke; algorithm refinement increased PPV to 80% but decreased sensitivity by 20%. Algorithms for smoking and obesity were considered valid. IRRs based on questionnaire-confirmed cases only were closer to IRRs estimated from hospitalization/mortality data than IRRs from algorithm-identified cases. CONCLUSIONS: AMI, stroke, smoking, obesity, and postmenopausal status can be accurately identified in CPRD. Physician questionnaire-validated AMI and stroke cases yield IRRs closest to the best estimate.

Validation of Cancer Cases Using Primary Care, Cancer Registry, and Hospitalization Data in the United Kingdom.

BACKGROUND: In the United Kingdom, hospital or cancer registry data can be linked to electronic medical records for a subset of general practices and years. METHODS: We used Clinical Practice Research Datalink data (2004-2012) from patients treated for overactive bladder. We electronically identified provisional cases of 10 common cancers in General Practitioner Online Database data and validated them by medical profile review. In practices with linkage to Hospital Episodes Statistics and National Cancer Data Repository (2004-2010), we validated provisional cancer cases against these data sources. This linkage also let us identify additional cancer diagnoses in individuals without cancer diagnosis records in the General Practitioner Online Database. RESULTS: Among 50,840 patients, 1,486 provisional cancer cases were identified in the General Practitioner Online Database for 2004-2012. Medical profile review confirmed 93% of 661 cases in nonlinked practices (range, 100% of non-Hodgkin lymphomas and uterine cancer to 77% of skin melanomas) and 96% of 825 cases in linked practices (100% of kidney and uterine cancers to 92% of melanomas). In the subset of linked practices, for 2004-2010, 720 cases were confirmed, of which 68% were identifiable in the General Practitioner Online Database (range, 90% of breast to 36% of kidney cancers). CONCLUSIONS: Most cases of cancer identified electronically in the General Practitioner Online Database were confirmed. A substantial proportion of cases, especially of cancer types not typically managed by general practitioners, would be missed without Hospital Episodes Statistics and National Cancer Data Repository data (and are likely missed in nonlinked practices). See video abstract at, http://links.lww.com/EDE/B315. REGISTRATION (BEFORE STUDY CONDUCT): European Union electronic Register of Post-Authorisation Studies (EU PAS Registry) number EUPAS5529, http://www.encepp.eu/encepp/viewResource.htm?id=11107.

Comparison of cardiovascular events among treatments for overactive bladder: a Danish nationwide cohort study.

PURPOSE: The purpose of this study is to explore the cardiovascular safety of antimuscarinic drugs to treat overactive bladder (OAB) in Denmark. METHODS: This was a cohort study using data recorded in Danish registries from patients newly exposed to darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium in 2004-2012. We estimated crude and standardized incidence rates (IRs) for acute myocardial infarction (AMI); stroke; cardiovascular mortality; major adverse cardiac events (MACE, a combined endpoint of the previous three outcomes); and all-cause death for the individual and combined drugs. We also estimated crude, standardized, and propensity score-stratified incidence rate ratios (IRRs) comparing individual antimuscarinic drugs to tolterodine as the reference. RESULTS: Among 72,917 new users of OAB drugs (mean age, 66 years; 60% women), the standardized IR (95% confidence interval) per 1000 person-years for current use of any OAB drug was 2.7 (2.5-2.9) for AMI, 1.3 (1.2-1.5) for stroke, 7.8 (7.5-8.1) for MACE, 4.8 (4.5-5.0) for cardiovascular mortality, and 15.2 (14.8-15.6) for all-cause mortality. Propensity score-stratified IRRs for current use (reference, tolterodine) were close to the null for all drugs and endpoints. CONCLUSIONS: We did not identify differences in the risk of cardiovascular events or mortality among users of individual antimuscarinic OAB drugs.

Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies.

BACKGROUND: The results of observational studies evaluating and comparing the cardiovascular safety of glitazones, metformin and sufonylureas are inconsistent.To conduct and evaluate heterogeneity in a meta-analysis of observational studies on the risk of acute myocardial infarction (AMI) or stroke in patients with type 2 diabetes using non-insulin blood glucose-lowering drugs (NIBGLD). METHODS: We systematically identified and reviewed studies evaluating NIBGLD in patients with type 2 diabetes indexed in Medline, Embase, or the Cochrane Library that met prespecified criteria. The quality of included studies was assessed with the RTI item bank. Results were combined using fixed- and random-effects models, and the Higgins I(2) statistic was used to evaluate heterogeneity. Sensitivity analyses by study quality were conducted. RESULTS: The summary relative risk (sRR) (95% CI) of AMI for rosiglitazone versus pioglitazone was 1.13 (1.04-1.24) [I(2) = 55%]. In the sensitivity analysis, heterogeneity was reduced [I(2) = 16%]. The sRR (95% CI) of stroke for rosiglitazone versus pioglitazone was 1.18 (1.02-1.36) [I(2) = 42%]. There was strong evidence of heterogeneity related to study quality in the comparisons of rosiglitazone versus metformin and rosiglitazone versus sulfonylureas (I (2) ≥ 70%). The sRR (95% CI) of AMI for sulfonylurea versus metformin was 1.24 (1.14-1.34) [I(2) = 41%] and for pioglitazone versus metformin was 1.02 (0.75-1.38) [I(2) = 17%]. Sensitivity analyses decreased heterogeneity in most comparisons. CONCLUSION/INTERPRETATION: Sulfonylureas increased the risk of AMI by 24% compared with metformin; an imprecise point estimate indicated no difference in risk of AMI when comparing pioglitazone with metformin. The presence of heterogeneity precluded any conclusions on the other comparisons. The quality assessment was valuable in identifying methodological problems in the individual studies and for analysing potential sources of heterogeneity.

Effects of gestational age at enrollment in pregnancy exposure registries.

PURPOSE: This study aims to explore the influence of gestational age at enrollment, and enrollment before or after prenatal screening, on the estimation of drug effects in pregnancy exposure registries. METHODS: We assessed the associations between first trimester antiepileptic drug (AED) exposure and risk of spontaneous abortion and major congenital malformations in the North American AED Registry (1996-2013). We performed logistic regression analyses, conditional or unconditional on gestational age at enrollment, to estimate relative risk (RR) for first trimester AED users compared with non-users. We also compared first trimester users of valproic acid and lamotrigine. Analyses were repeated in women who enrolled before prenatal screening. RESULTS: Enrollment occurred earlier among 7029 AED users than among 581 non-users; it was similar among AEDs. Comparing AED users with non-users, RR (95% confidence interval) of spontaneous abortion (n = 359) decreased from 5.1 (2.3-14.1) to 2.0 (0.9-5.6) after conditioning on gestational week at enrollment and to 1.9 (0.8-5.4) upon further restriction to before-screening enrollees. RR of congenital malformations (n = 216) changed from 3.1 (1.4-8.5) to 3.2 (1.4-9.0) after conditioning on gestational week at enrollment and to 2.0 (0.7-10.1) upon further restriction to before-screening enrollees. When comparing valproic acid users and lamotrigine users, the RR of congenital malformations was not substantially changed by conditioning or restricting. CONCLUSIONS: Spontaneous abortion rates were sensitive to gestational age at enrollment. Estimates of congenital malformation risks for AED users relative to non-users were sensitive to before/after-screening enrollment. This difference was not apparent between active drugs, likely due to similar gestational age at enrollment.

Beginning and duration of pregnancy in automated health care databases: review of estimation methods and validation results.

PURPOSE: To describe methods reported in the literature to estimate the beginning or duration of pregnancy in automated health care data, and to present results of validation exercises where available. METHODS: Papers reporting methods for determining the beginning or duration of pregnancy were identified based on Pubmed searches, by consulting investigators with expertise in the field and by reviewing conference abstracts and reference lists of relevant papers. From each paper or abstract, we extracted information to characterize the study population, data sources, and estimation algorithm. We then grouped these studies into categories reflecting their general methodological approach. RESULTS: Methods were classified into 5 categories: (i) methods that assign a uniform duration for all pregnancies, (ii) methods that assign pregnancy duration based on preterm-delivery or health care related codes, or codes for other pregnancy outcomes, (iii) methods based on the timing of prenatal care, (iv) methods based on birth weight, and (v) methods that combine elements from 2 and 3. Validation studies evaluating these methods used varied approaches, with results generally reporting on the mistiming of the start of pregnancy, incorrect estimation of the duration of pregnancy, or misclassification of drug exposure during pregnancy or early pregnancy. CONCLUSIONS: In the absence of accurate information on the beginning or duration of pregnancy, several methods of varying complexity are available to estimate them. Validation studies have been performed for many of them and can serve as a guide for method selection for a particular study.

Triggers of spontaneous preterm delivery--why today?

BACKGROUND: Our goal is to study the triggers of spontaneous preterm delivery using a case-crossover design. METHODS: In a pilot study, we enrolled 50 women with spontaneous preterm labour (PTL) and 50 with preterm premature rupture of membranes (PPROM) between 2011 and 2012. To assess non-transient risk factors, we also enrolled a control group of 158 pregnant women at their regular prenatal care visits matched to cases by gestational age and calendar time. The index time was defined as the onset of PTL/PPROM (for cases) or interview (for controls). Detailed data were collected through structured interviews regarding factors of interest during the 72 h that preceded the index time. Within case subjects, we compared the frequency of transient factors from 0 to 24 h before index time with that from 48 to 72 h before index time, and estimated matched odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Previously hypothesised chronic risk factors for spontaneous preterm delivery, including mood disorders and stressful events, were more common among cases than among controls. Within cases, skipped meals [OR 4.3, 95% CI 1.2, 15.2], disturbed sleep [OR 4.5, 95% CI 1.5, 13.3], sexual activity [OR 6.0, 95% CI 0.7, 69.8], and intake of spicy foods [OR 7.0, 95% CI 1.6, 30.8] were associated with an increased risk for PTL/PPROM within the subsequent 24 h. For physical exertion and other potential risk factors evaluated, the OR was close to the null. CONCLUSION: Skipping meals and disturbed sleep may be associated with imminent PTL/PPROM; sexual activity and spicy food may trigger PTL/PPROM in susceptible women. Larger case-crossover studies will be able to evaluate the impact of modifiable risk factors and acute predictors of PTL/PPROM, and might help guide obstetrical management.

The risk of heart failure associated with the use of noninsulin blood glucose-lowering drugs: systematic review and meta-analysis of published observational studies.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at high risk of heart failure. A summary of the effects of blood glucose-lowering drugs other than glitazones on the risk of heart failure in routine clinical practice is lacking. The objective of this study was to conduct a systematic review and meta-analysis of observational studies on the risk of heart failure when using blood glucose-lowering drugs. METHODS: We systematically identified and reviewed cohort and case-control studies in which the main exposure of interest was noninsulin blood glucose-lowering medications in patients with T2DM. We searched Medline, Embase, and the Cochrane Library to identify publications meeting prespecified eligibility criteria. The quality of included studies was assessed with the Newcastle-Ottawa Scale and the RTI item bank. Results were combined using fixed and random-effects models when at least 3 independent data points were available for a drug-drug comparison. RESULTS: The summary relative risk of heart failure in rosiglitazone users versus pioglitazone users (95% CI) was 1.16 (1.05-1.28) (5 cohort studies). Heterogeneity was present (I2 = 66%). For new users (n = 4) the summary relative risk was 1.21 (1.14-1.30) and the heterogeneity was reduced (I2 = 31%);. The summary relative risk for rosiglitazone versus metformin was 1.36 (95% CI, 1.17-1.59) (n = 3). The summary relative risk (95% CI) of heart failure in sulfonylureas users versus metformin users was 1.17 (95% CI, 1.06-1.29) (5 cohort studies; I2 = 24%) and 1.22 (1.02-1.46) when restricted to new users (2 studies).Information on other comparisons was very scarce. Information on dose and duration of treatment effects was lacking for most comparisons. Few studies accounted for disease severity; therefore, confounding by indication might be present in the majority of the within-study comparisons of this meta-analysis. CONCLUSIONS: Use of glitazones and sulfonylureas was associated with an increased risk of heart failure compared with metformin use. However, indication bias cannot be ruled out. Ongoing large multidatabase studies will help to evaluate the risk of heart failure in treated patients with diabetes, including those using newer blood glucose-lowering therapies.

Patterns of prescription of antidepressants and antipsychotics across and within pregnancies in a population-based UK cohort.

Although antidepressant and antipsychotic utilization by gestational trimester has been described, longitudinal prescription patterns within pregnancies have received less attention. All mothers in the Clinical Practice Research Datalink's Mother Baby Link enrolled from 6 months before pregnancy to 3 months after delivery, with delivery date between 01/1989 and 12/2010 were included (n = 421,645). Drug use prevalence was calculated as the number of women with prescriptions for antidepressants or antipsychotics in capsules/tablets in the 3 months before pregnancy (T0), the first (T1), second (T2), or third (T3) pregnancy trimesters, or the 3 months after delivery (T4). In each pregnancy, prescriptions in T0 and T3 were compared to identify treatment discontinuation, simplification (some drugs discontinued or dose lowered), no treatment change, intensification (drugs added to prior treatment or dose increased), and start. Antidepressant use in T0 through T4 was 4.69, 2.81, 1.31, 1.34, and 5.46 %, respectively. Of 19,774 T0 antidepressant users, 79.57 % discontinued, 5.13 % simplified, 9.06 % did not change, and 2.19 % intensified treatment. 0.40 % of non-users in T0 started antidepressants by T3. Antipsychotic use in T0 through T4 was 0.57, 1.34, 0.54, 0.28 and 0.38 %. Excluding prochlorperazine, it was 0.15, 0.13, 0.08, 0.07 and 0.15 %, respectively; of 639 T0 users, 72.30 % discontinued, 7.51 % simplified, 11.11 % did not change, and 4.07 % intensified treatment. 0.03 % of non-users in T0 started antipsychotics by T3. Cross-sectional and longitudinal analyses identified a post-conception decrease in antidepressant and antipsychotic prescribing. Longitudinal treatment assessment additionally captured several treatment patterns among those who do not discontinue treatment that usually stay unrecognized.

Determining the predictive value of Read codes to identify congenital cardiac malformations in the UK Clinical Practice Research Datalink.

PURPOSES: The purposes of this study were to determine (i) the positive predictive value (PPV) of multiple Read codes used to identify congenital cardiac malformation (CCM) cases in the UK Clinical Practice Research Datalink (CPRD); (ii) the accuracy of the diagnosis date; and (iii) the source of information that the general practitioners (GPs) use for validating the diagnosis suggested by the code. METHODS: Eight hundred eighty-eight records with Read diagnostic and procedures codes for CCM, between January 1996 and November 2010, were identified from CPRD. Questionnaires were sent to GPs to verify the diagnoses and date of the code-identified events. RESULTS: A total of 719 questionnaires were returned (81% response rate). The PPV of the CCM codes was 93% (670/719). Thirty-one percent of cases had a different event date than the one recorded in the electronic medical record (EMR); 10% of these differing dates were within 30 days of the code-identified CCM date. GPs used a variety of data sources to confirm CCM diagnoses. Although the EMR was the most frequently used data source (70%), 66% reported using consultation letters, 9% reported using clinical notes or paper charts, and 35% of GPs reported using the hospital record to confirm the CCM diagnosis. CONCLUSIONS: Clinical Practice Research Datalink Read codes for CCMs have 93% PPV and most likely point to true cases. However, the accuracy of diagnosis dates and the age at diagnosis may not be as reliable. The findings of this study indicate that GPs use information beyond what is available for researchers in the EMR to confirm clinical diagnoses when responding to validation questionnaires. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Algorithms to estimate the beginning of pregnancy in administrative databases.

PURPOSE: The role of administrative databases for research on drug safety during pregnancy can be limited by their inaccurate assessment of the timing of exposure, as the gestational age at birth is typically unavailable. Therefore, we sought to develop and validate algorithms to estimate the gestational age at birth using information available in these databases. METHODS: Using a population-based cohort of 286,432 mother-child pairs in British Columbia (1998-2007), we validated an ICD-9/10-based preterm-status indicator and developed algorithms to estimate the gestational age at birth on the basis of this indicator, maternal age, singleton/multiple status, and claims for routine prenatal care tests. We assessed the accuracy of the algorithm-based estimates relative to the gold standard of the clinical gestational age at birth recorded in the delivery discharge record. RESULTS: The preterm-status indicator had specificity and sensitivity of 98% and 91%, respectively. Estimates from an algorithm that assigned 35 weeks of gestational age at birth to deliveries with the preterm-status indicator and 39 weeks to those without them were within 2 weeks of the clinical gestational age at birth in 75% of preterm and 99% of term deliveries. CONCLUSIONS: Subtracting 35 weeks (245 days) from the date of birth in deliveries with codes for preterm birth and 39 weeks (273 days) in those without them provided the optimal estimate of the beginning of pregnancy among the algorithms studied.

Use of selective serotonin reuptake inhibitors in pregnancy and cardiac malformations: a propensity-score matched cohort in CPRD.

PURPOSE: Research on the association of maternal selective serotonin reuptake inhibitor (SSRI) use and cardiac malformations in the offspring has yielded conflicting findings. We therefore sought to further investigate the association using data from a large population-based cohort in the UK. METHODS: The study population consisted of 149 464 pregnancies ending in a live birth between January/1996 and November/2010 from the Clinical Practice Research Datalink's Mother Baby Link. We created propensity-score matched cohorts of first-trimester SSRI users who did not use other antidepressants in the same gestational period ('SSRI users', n=3046) and non-antidepressant users (no use from the 3 months before pregnancy through the second trimester of pregnancy, 'non-users'; n=8991). Weighted logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of cardiac malformations overall and septal defects diagnosed in the first year of life, or in the first 6 years of life. RESULTS: Sixteen infants with cardiac malformations were identified among SSRI users; 10 of them were septal defects. Among non-users, there were 48 infants with cardiac malformations, 26 of whom had septal defects. The OR (95% CI) for cardiac malformations was 1.00 (0.50; 2.00), and for septal defects was 1.15 (0.46; 2.87). Results were similar for cardiac malformations diagnosed in the first 6 years of life, and in several sensitivity analyses that were also implemented. CONCLUSIONS: The results of this study are most compatible with no association between maternal use of SSRIs in early pregnancy and cardiac malformations or septal defects in the offspring. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.