Optimizing an algorithm for the identification and classification of pregnancy outcomes in German claims data.

For studying drug utilization and safety in pregnancy based on administrative health care data, the reliable identification and classification of pregnancy outcomes in the data is essential. We aimed to optimize an existing algorithm for the identification and classification of pregnancy outcomes in the German Pharmacoepidemiological Research Database (GePaRD) with a particular focus on births. We reconsidered all codes used by the original algorithm and applied it to data of GePaRD from 2006 to 2014. Longitudinal records of pregnancies were used to identify targets for enhancing the algorithm's specificity. We checked the plausibility of the results, eg, regarding the age distribution of persons with pregnancy outcomes. Based on 20 longitudinal records of pregnancies, we compared the outcome classification by clinical experts with the results of the modified algorithm. Our algorithm identified 1 235 261 pregnancy outcomes in the database, with the majority (94%) being live births, classified as preterm (10%), term (78%), and (12%) births after the expected delivery date. The median age of pregnant women was 32 years (Q1 28; Q3 35). Implausible sequence of outcomes (for example, an induced abortion within a pregnancy categorized as ending in a live birth) were rare (0.03%). The case profile review by clinical experts resulted in the same outcome type and date as the algorithm in 95%. Our algorithm led to plausible results regarding the identification and classification of pregnancy outcomes. It will be an important foundation for studies on drug utilization and drug safety during pregnancy based on GePaRD.

Wentzell N ，Schink T ，Haug U ，Ulrich S ，Niemeyer M ，Mikolajczyk R ... -  《-》

Evaluation of pregnancy outcome records in the German Pharmacoepidemiological Research Database (GePaRD).

Routine health care data are a valuable source for the assessment of risks of drugs during pregnancy. Therefore, the aim of the current analysis was the evaluation of pregnancy outcome records in German health insurance data. We used the German Pharmacoepidemiologic Research Database including data of more than 15 million insurants (about 18% of the German population). Among 10-49 year-old women, we identified six categories of pregnancy outcomes: term births, preterm births, stillbirths, induced abortions, spontaneous abortions and ectopic pregnancies. In order to assess the validity of these records, we have set our results in relation to representative data for the corresponding outcomes in Germany. We also investigated whether pregnancy markers (diagnoses, procedures or medical services which indicate an existing pregnancy) can be used to identify pregnancies. In total, we identified 94 261 pregnancy outcomes in 2005. The percentage of births outside hospital (1.2%) and of preterm births (11.6%), the rate of stillbirths (3 per 1000 live births) and the rate of ectopic pregnancies (20 per 1000 live births) agreed well with representative data for Germany. Compared to epidemiological data, the occurrence of spontaneous abortions was underestimated (5.4% of all pregnancies). There were 4.1 induced abortions per 100 live births, compared to 18.1 in national data. Positive predictive values and sensitivities of markers varied across marker categories and for different pregnancy outcomes. Completeness of pregnancy outcomes recorded in the database varied by pregnancy outcome. This should be taken into account in studies of drug safety in pregnancy.

Mikolajczyk RT ，Kraut AA ，Garbe E 《-》

Estimating the Beginning of Pregnancy in German Claims Data: Development of an Algorithm With a Focus on the Expected Delivery Date.

Background: Estimating the beginning of pregnancy is crucial when studying drug safety in pregnancy, but important information in this regard, such as the last menstrual period (LMP), is generally not recorded in claims databases. The beginning of pregnancy is therefore usually estimated by subtracting a median length of pregnancy from the date of birth. Due to the variability in pregnancy lengths, this might result in non-negligible errors. German claims data may offer the possibility to estimate the beginning of pregnancy more precisely based on the expected delivery date (EDD) which can be coded once or more often during a pregnancy. Purpose: To estimate the beginning of pregnancy in German claims data focusing on the potential of the expected delivery date (EDD). Methods: We included data of all pregnancies in women aged 12-50 years ending in a live birth between 2006 and 2015 identified in the German Pharmacoepidemiological Research Database (GePaRD). We assessed the number of coded EDDs per pregnancy and the concordance if ≥ 2 EDDs were coded. We estimated the beginning of pregnancy by subtracting 280 days from the EDD or the most frequent EDD (in case of discordant EDDs). To examine plausibility, we determined the distribution of pregnancy lengths and assessed whether the gestational age at which prenatal examinations were coded was plausible. For pregnancies without EDD, the beginning was estimated by subtracting the respective observed median lengths of pregnancy for preterm births, term births, and births after due date from the actual dates of birth. Results: In 82.4% of pregnancies, at least one EDD was available (thereof 6.1% with only one EDD and 80.9% with ≥ 2 EDDs that were all concordant). The maximal difference between discordant EDDs was in median 5 days (interquartile range: 3-7 days). Based on the EDD, the median length of pregnancy was 276 days for term births and in 84.7% of pregnancies the second antibody screening test was performed in the recommended interval ± 2 weeks. In pregnancies without EDD the respective proportion was 84.9%. Conclusions: By using the EDD, the beginning of pregnancy can plausibly be estimated in German claims data.

Schink T ，Wentzell N ，Dathe K ，Onken M ，Haug U ... -  《Frontiers in Public Health》

Detecting and Dating Early Non-live Pregnancy Outcomes: Generation of a Novel Pregnancy Algorithm From Norwegian Linked Health Registries.

Nordeng H ，Lupattelli A ，Engjom HM ，van Gelder MMHJ ... -  《-》

Investigating drug safety in pregnancy based on the German Pharmacoepidemiological Research Database (GePaRD): A proof-of-concept analysis on the association between valproate and spina bifida.

Large health-care databases are increasingly used for research on drug utilization and safety in pregnancy. For the German Pharmacoepidemiological Research Database (GePaRD), covering ~20% of the German population, algorithms have been developed to identify pregnancies, to estimate their date of onset and to link mothers to their babies. Using this methodology, we aimed to conduct a proof-of-concept analysis on the known association between valproate (VPA) exposure in early pregnancy and spina bifida in the exposed child. We identified all pregnancies in GePaRD between 2006 and 2016 in women aged 12 to 50 years. To each VPA dispensation of these women, an exposure period was assigned, based on the dispensation date and the number of defined daily doses in the dispensed package. A pregnancy was classified as exposed to VPA in the critical time window if this exposure period overlapped with the first 55 days of pregnancy. Risk ratios were calculated for spina bifida in live births and induced abortions comparing VPA-exposed ones to all pregnancies. Overall, we identified 1 271 384 pregnancies fulfilling the inclusion criteria. Of these, 668 pregnancies (0.053%) were classified as exposed to VPA in the critical time window regarding spina bifida. An induced abortion accompanied by a diagnosis of spina bifida was observed in one of the VPA-exposed pregnancies (0.15%) and in 154 of all pregnancies (0.012%), yielding a risk ratio of 12.4 (95% confidence interval [CI]: 1.7-88.2). Out of 775 875 pregnancies ending in a live birth, 366 (0.047%) were classified as VPA exposed. A diagnosis of spina bifida was coded in 3 of 366 VPA-exposed live births (0.82%) and in 260 of all live births (0.03%), yielding a relative risk of 24.5 (95% CI: 7.9-76.0). Our proof-of-concept analysis based on GePaRD showed a strong association between intrauterine exposure to VPA and occurrence of spina bifida. The results are plausible and consistent with the literature, supporting the suitability of GePaRD and the developed algorithms to conduct studies on drug safety in pregnancy.

Haug U ，Kollhorst B ，Schink T ，Thöne K ，Dathe K ，Schaefer C ，Onken M ... -  《-》