Purpose Pregnancies ending before gestational week 12 are common but not notified to the Medical Birth Registry of Norway. Our goal was to develop an algorithm that more completely detects and dates pregnancy outcomes by using diagnostic codes from primary and secondary care registries to complement information from the birth registry. Methods We used nationwide linked registry data between 2008 and 2018 in a hierarchical manner: We developed an algorithm to arrive at unique pregnancy outcomes, considering codes within 56 days as the same event. To infer gestational age of pregnancy outcomes before gestational week 12, we used the median gestational week of pregnancy markers (45 ICD-10 codes and 9 ICPC-2 codes). When no pregnancy markers were available, we assigned outcome-specific gestational age estimates. The performance of the algorithm was assessed by blinded clinicians. Results Using only the medical birth registry, we identified 649,703 pregnancies, including 1,369 (0.2%) miscarriages and 3,058 (0.5%) elective terminations. With the new algorithm, we detected 859,449 pregnancies, including 642,712 live-births (74.8%), 112,257 miscarriages (13.1%), 94,664 elective terminations (11.0%), 6,429 ectopic pregnancies (0.7%), 2,564 stillbirths (0.3%), and 823 molar pregnancies (0.1%). The median gestational age was 10 +0 weeks (IQR 10 +0-11 +3) for miscarriages and 8 +0 weeks (IQR 8 +0-9 +6) for elective terminations. Gestational age could be inferred using pregnancy markers for 66.3% of miscarriages and 47.2% of elective terminations. Conclusion The pregnancy algorithm improved the detection and dating of early non-live pregnancy outcomes that would have gone unnoticed if relying solely on the medical birth registry information.

Aim: Pregnant women are hypothesized to have low adherence to prescribed medication, because of concerns about toxicity and harmful effects on the unborn child. However, very little is known about the actual adherence to prescribed medication during pregnancy. We determined to what extent women follow treatment recommendations regarding prescribed medication use in mid-pregnancy. Methods: Dutch women participating in the PRIDE Study completed a six-week diary on medication use. Additionally, pharmacy records were obtained. For each medication dispensed, we determined three measures of adherence: 1) whether use was reported in the diary (actual use), 2) difference between dispensing date and date of first reported use (initiation time), and 3) proportion of days with at least the correct number of doses taken (implementation adherence). Results: During the six-weeks study period, 235 of 816 women (29%) were prescribed medication. Actual use was highest for medications used for chronic conditions (88%; 95% confidence interval [95% CI] 81-93), followed by medication for pregnancy-related conditions (79%; 95% CI 71-86) and medication for occasional and short-time use (69%; 95% CI 60-77). We observed a ≥1 day delay in treatment initiation for 42% of medications dispensed for the first time in the study period. For medications that were actually used, mean implementation adherence was 74.2% (95% CI 69.3-79.2). Conclusion: Although actual use of medications dispensed was high, many pregnant women did not adhere to treatment recommendations. This non-adherence may impact maternal and child health and lead to exposure misclassification in studies in perinatal pharmacoepidemiology relying on administrative databases.

Objective: To determine associations of calcium-based antacid and PPI use during pregnancy with late-onset preeclampsia (≥34 weeks of gestation), taking into account dosage and timing of use. Design: Prospective cohort study. Setting: This study used data from the PRIDE Study (2012-2019) and Dutch Pregnancy Drug Register (2014-2019). Sample: A total of 9,058 pregnant Dutch women aged ≥18 years. Methods: Data were collected through web-based questionnaires and obstetric records. We estimated risk ratios (RRs) for late-onset preeclampsia for any use and trajectories of calcium-based antacid and PPI use before gestational day 238, and hazard ratios for time-varying exposures after gestational day 237. Main outcome measure: Late-onset preeclampsia. Results: Late-onset preeclampsia was diagnosed in 2.6% of pregnancies. Any use of calcium-based antacids (RR 1.2 [95% CI 0.9-1.6]) or PPIs (RR 1.4 [95% CI 0.8-2.4]) before gestational day 238 was not associated with late-onset preeclampsia. Use of low-dose calcium-based antacids in gestational weeks 0-16 (<1g/day; RR 1.8 [95% CI 1.1-2.9]) and any use of PPIs in gestational weeks 17-33 (RR 1.6 [95% CI 1.0-2.8]) seemed to increase risks of late-onset preeclampsia. We did not observe associations between late-onset preeclampsia and use of calcium-based antacids and PPIs after gestational day 237. Conclusions: In this prospective cohort study, use of calcium-based antacids and PPIs during pregnancy was not found to reduce the risk of late-onset preeclampsia. Funding: Netherlands Organisation for Health Research and Development [ZonMw; grant number 848018010].

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The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. 1154 COVID-19 patients admitted to 6 hospitals in the Netherlands between March and May 2020 were included. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (RR 1.02 (95% CI; 0.80-1.30) or length of hospital stay (7.0 [4-12] vs 7.0 {4-12] days, p=0.69), although we observed a lower risk of pulmonary embolism (RR 0.19 (95% CI; 0.05-0.80). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID-19 patients.