Validation of algorithms to identify adverse perinatal outcomes in the Medicaid Analytic Extract database

He, Min; Huybrechts, Krista F.; Dejene, Sara Z.; Straub, Loreen; Bartels, Devan; Burns, Stacey; Combs, David J.; Cottral, Jennifer; Gray, Kathryn J.; Manning‐Geist, Beryl; Mogun, Helen; Reimers, Rebecca; Hernández–Dı́az, Sonia; Bateman, Brian T.

doi:10.1002/pds.4967

Cited by 24 publications

(21 citation statements)

References 26 publications

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“…We retrieved 50 medical records from pregnancies defined with these codes for each outcome, and two physicians who were blinded to the drug exposure status reviewed the charts according to established clinical criteria and classified the outcome as present or absent. We used the resulting positive predictive values to inform probabilistic bias analyses that generated corrected relative risk estimates 13. As a second approach to assess the robustness of our findings to outcome misclassification, we matched exposed to non-exposed women (from the primary analysis for each outcome, using the propensity score) in a 1:1 ratio for outcomes with a prevalence of at least 3% in the unexposed cohort and in a 1:5 ratio for outcomes with a prevalence of less than 3% by using a nearest neighbor algorithm.…”

Section: Discussionmentioning

confidence: 99%

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Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

Huybrechts

Bateman

Bessette

et al. 2020

BMJ

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Objective To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. Design Cohort study nested in the Medicaid Analytic eXtract for 2004-13. Setting Publicly insured pregnancies in the United States. Participants Pregnant women 18 to 55 years of age and their liveborn infants. Interventions Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. Main outcome measures Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. Results Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. Conclusions On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. Trial registration EUPAS 15946.

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Section: Discussionmentioning

confidence: 99%

“…We defined postpartum hemorrhage by the presence of at least one of the ICD-9 diagnostic codes 666.xx in the maternal inpatient claims during the delivery hospital admission. All outcome definitions for the primary outcomes have been validated and shown to have a high positive predictive value 1113…”

Section: Methodsmentioning

confidence: 99%

Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

Huybrechts

Bateman

Bessette

et al. 2020

BMJ

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“…Third, the identification of outcomes in claims databases may be affected by outcome misclassification. To reduce this possibility, we used either validated or highly specific definitions of the outcomes [16,17]. We also redefined the malformation outcomes using infant claims only and extended follow-up to 1 year for infants continuously eligible for �1 year, which confirmed the primary results.…”

Section: Plos Medicinementioning

confidence: 87%

“…For gabapentin exposure in early, late, and both early and late pregnancy, we evaluated preeclampsia, preterm birth, SGA, and NICU admission (see S2 Table for specific definitions). For the definition of preeclampsia, preterm birth, and SGA, we used previously validated definitions [16,17].…”

Section: Discussionmentioning

confidence: 99%

Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset

et al. 2020

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Background Despite the widespread use, only sparse information is available on the safety of gabapentin during pregnancy. We sought to evaluate the association between gabapentin exposure during pregnancy and risk of adverse neonatal and maternal outcomes. Methods and findings Using the United States Medicaid Analytic eXtract (MAX) dataset, we conducted a population-based study of 1,753,865 Medicaid-eligible pregnancies between January 2000 and December 2013. We examined the risk of major congenital malformations and cardiac defects associated with gabapentin exposure during the first trimester (T1), and the risk of preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and neonatal intensive care unit admission (NICUa) associated with gabapentin exposure early, late, or both early and late in pregnancy. Gabapentin-unexposed pregnancies served as the reference. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using fine stratification on the propensity score (PS) to control for over 70 confounders (e.g., maternal age, race/ethnicity, indications for gabapentin, other pain conditions, hypertension, diabetes, use of opioids, and specific morphine equivalents). We identified 4,642 pregnancies exposed in T1 (mean age = 28 years; 69% white), 3,745 exposed in early pregnancy only (28 years; 67% white), 556 exposed in late pregnancy only (27 years; 60% white), and 1,275 exposed in both early and late pregnancy (29 years; 75% white). The reference group consisted of 1,744,447 unexposed pregnancies (24 years; 40% white). The adjusted RR for major malformations was 1.07 (95% CI 0.94-1.21, p = 0.33) and for cardiac defects 1.12 (0.89-1.40, p = 0.35). Requiring �2 gabapentin dispensings moved the RR to 1.40 (1.03-1.90, p = 0.03) for cardiac defects. There was a higher risk of preterm birth among women exposed to

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“…In contrast, defining major malformations based on either (1) more than one date with a code indicating a particular malformation, (2) at least one date plus a corrective surgery or procedure for that malformation, or (3) at least one date plus infant death within 30 days results in a prevalence of major congenital malformations that is in line with expectation (Figure ). Further, the validity of such approach has been demonstrated based on validation studies using medical charts and, indirectly, by replicating the association between a known risk factor (ie, prepregnancy diabetes) and malformations defined using this algorithm . For several outcomes, definitions with a high Positive Predictive Value (PPV) have been developed (Table ).…”

Section: Outcomementioning

confidence: 99%

Use of real‐world evidence from healthcare utilization data to evaluate drug safety during pregnancy

Huybrechts

Bateman

Hernández–Dı́az

2019

Pharmacoepidemiology and Drug

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Purpose Because preapproval clinical trials typically exclude pregnant women, the evidence on drug safety during pregnancy required to inform drug labeling must come from postapproval controlled observational studies. Common designs have included pregnancy registries and case‐control studies. Recently, pregnancy cohorts nested within healthcare utilization databases are increasingly being used. Despite clear advantages, these databases share some important limitations that may threaten the validity of studies emerging from them. Methods This paper describes the distinctive methodological aspects of conducting drug safety studies in healthcare utilization databases with special emphasis on design and analytic approaches to minimize biases. Results We describe considerations for study design, cohort definition, and follow‐up. We then address issues related to exposure ascertainment based on prescription fills, including the importance of the etiologically relevant window and of properly accounting for preterm births. This is followed by a discussion of advantages and challenges when ascertaining maternal and infant outcomes based on secondary data. We then explore useful approaches to address confounding within the context of pregnancy research and of the potential for selection bias when restricting the cohort to live births. Finally, we consider issues related to external validity and statistical significance. The examples are mainly drawn from a pregnancy cohort nested in the Medicaid Analytic Extract. Conclusions The approaches presented provide guidance regarding the important methodological considerations that need to be attended to in order to generate valid, minimally biased risk when using large healthcare utilization databases for drug safety surveillance in pregnancy.

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Validation of algorithms to identify adverse perinatal outcomes in the Medicaid Analytic Extract database

Cited by 24 publications

References 26 publications

Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset

Use of real‐world evidence from healthcare utilization data to evaluate drug safety during pregnancy

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