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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 all possible pregnancy outcomes (i.e., miscarriages, elective terminations, ectopic pregnancies, molar pregnancies, stillbirths, and live births) 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 the UiO pregnancy algorithm to arrive at unique pregnancy outcomes, considering codes within 56 days as the same event. To estimate the gestational age of pregnancy outcomes identified in the primary and secondary care registries, we inferred the median gestational age of pregnancy markers (45 ICD‐10 codes and 9 ICPC‐2 codes) from pregnancies registered in the medical birth registry. 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 1369 (0.2%) miscarriages and 3058 (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%), 6429 ectopic pregnancies (0.7%), 2564 stillbirths (0.3%), and 823 molar pregnancies (0.1%). The median gestational age was 10+1 weeks (IQR 10+0–12+2) 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 UiO 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. [ABSTRACT FROM AUTHOR]

Mycotoxins are toxic secondary metabolites produced by various fungi that can contaminate food crops, which, in turn, may lead to human exposure. Chronic exposure to mycotoxins can cause adverse health effects including reproductive and developmental toxicity. Pregnant women and their foetuses present a vulnerable group for exposure to mycotoxins that can cross the placenta. Human biomonitoring of mycotoxins provides a real-life approach to estimate internal exposure. In this pilot study, 24-h urine samples from 36 pregnant Dutch women were analysed for aflatoxin M1 (AFM1), total deoxynivalenol (DON), de-epoxy-deoxynivalenol (DOM-1), total zearalenone (ZEN), total α-zearalenol (α-ZEL), total β-zearalenol (β-ZEL) and total zearalanone (ZAN), where 'total' refers to mycotoxins and their conjugated forms. Serum samples from these women were analysed for fumonisin B1 (FB1) and ochratoxin A (OTA). All samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The most prevalent mycotoxins were total DON, total ZEN and OTA, with a detection frequency of 100%. DOM-1, total α-ZEL and total β-ZEL were detected but to a lesser extent, while AFM1, total ZAN and FB1 were undetected. Median concentrations were 4.75 μg total DON/L, 0.0350 μg DOM-1/L, 0.0413 μg total ZEN/L, 0.0379 μg total α-ZEL/L, 0.0189 μg total β-ZEL/L, and 0.121 μg OTA/L. The calculated median concentration for total ZEN and its metabolites was 0.105 μg/L. Based on two separate risk assessment approaches, total DON exposure in this group was considered to be of low concern. Similarly, exposure to total ZEN and its metabolites in this group was of low concern. For OTA, the risk of non-neoplastic effects was of low concern based on exposure in this group, and the risk of neoplastic effects was of low concern in the majority of participants in this group. The findings of this pilot study confirm the presence of mycotoxins in the urine and serum of pregnant Dutch women, with total DON, total ZEN, and OTA most frequently detected. Exposure to all measured mycotoxins was considered to be of low concern in this group, except for exposure to OTA, which was of low concern for the majority of participants. The study's findings offer valuable insights but should be confirmed using a larger and more diverse sample of the Dutch general population. [ABSTRACT FROM AUTHOR]

Objectives Several types of epidemiologic studies suffer from decreasing participation rates, resulting in potential selection bias and delay or termination of studies. We aimed to determine the feasibility of online methods for recruitment of pregnant women into a prospective cohort study. Methods In addition to traditional recruitment through prenatal care providers, we advertized participation in the PRegnancy and Infant DEvelopment (PRIDE) Study, an ongoing prospective cohort study with long-term follow-up in The Netherlands enrolling women in early pregnancy, through Google AdWords (30 days) and Facebook Ads (31 and 27 days) campaigns between September 2016 and January 2017. We calculated costs per eligible participant and compared demographics, health-related characteristics, and follow-up rates between participants recruited through online methods and prenatal care providers. Results During the study period, we recruited six women through AdWords ([euro]54.28 per participant), 59 through Facebook ([euro]10.17 per participant), and 327 through prenatal care providers (no valid cost estimate available). Facebook participants seemed to be younger (29.0 vs. 30.7 years), to have a higher body mass-index and/or low/intermediate education (27.0 vs. 24.0 kg/m.sup.2 and 41 vs. 25%, respectively), and to start prenatal care in secondary care more often (12 vs. 5%) than participants recruited through prenatal care providers. Item non-response and loss to follow-up rates were higher among women recruited online than among those recruited through prenatal care providers. Conclusion Google AdWords did not contribute substantially, but Facebook Ads may complement traditional recruitment methods of pregnant women into prospective cohort studies, despite challenges that may threaten internal validity., Author(s): Marleen M. H. J. van Gelder [sup.1] [sup.2] , Tom H. van de Belt [sup.2] , Lucien J. L. P. G. Engelen [sup.2] , Robin Hooijer [sup.2] , Sebastian [...]

Purpose: Pregnant women are at higher risk of severe illness and adverse pregnancy outcomes due to a SARS‐CoV‐2 infection, which can be prevented by vaccination. Observational studies are needed to ascertain the safety of COVID‐19 vaccination during pregnancy. We aimed to determine whether COVID‐19 vaccination before and during pregnancy is associated with the risk of miscarriage. Methods: In this cohort study, we included 4640 pregnant women (mean age: 32.8 ± 3.7 years) from the Dutch Pregnancy Drug Register between February 2021 and August 2022. Information on COVID‐19 vaccinations, miscarriage, and confounders was self‐reported, using web‐based questionnaires. The hazard ratio (HR) of miscarriage (in gestational weeks 6–20) after a COVID‐19 vaccination, was estimated using the survival analyses. A COVID‐19 vaccination during pregnancy (≥1 COVID‐19 vaccination between week 2 and 20 of pregnancy) was included as a time‐dependent exposure and vaccination prior to pregnancy was included as a binary exposure. Results: A total of 3202 pregnant women (69%) received ≥1 COVID‐19 vaccine in gestational week 2–20. We observed no association of vaccination during pregnancy with the risk of miscarriage (adjusted HR = 1.29, 95% CI = 0.93–1.74). Vaccination prior to pregnancy, however, was associated with a decreased risk of miscarriage (adjusted HR = 0.69, 95% CI = 0.48–0.99). Conclusions: We demonstrated that COVID‐19 vaccination during pregnancy is not associated with an increased risk of miscarriage in gestational weeks 6–20. This study adds to the growing body of evidence demonstrating the safety of COVID‐19 vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

Aims: Pregnant women are hypothesized to have low adherence to prescribed medication, because of concerns about 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 6‐week diary on medication use. Additionally, pharmacy records were obtained. For each medication dispensed, we determined 3 measures of adherence: (i) whether use was reported in the diary (actual use); (ii) difference between dispensing date and date of first reported use (initiation time); and (iii) proportion of days with at least the correct number of doses taken (implementation adherence). Results: During the 6‐week study period, 235 of 816 women (29%) were dispensed 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. Mean implementation adherence was 74.2% (95% CI 69.3–79.2) for medications that were actually used. Conclusion: Although actual use of medications dispensed was high, many pregnant women did not adhere to treatment recommendations. This nonadherence may impact maternal and child health and lead to overestimation of medication use in studies in perinatal pharmacoepidemiology relying on administrative databases. [ABSTRACT FROM AUTHOR]

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. This study included 1154 COVID‐19 patients admitted to 6 hospitals in the Netherlands between March and May 2020. 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. In total, 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 (risk ratio 1.02 [95% confidence interval; 0.80–1.30]) or length of hospital stay (7.0 [4–12] vs. 7.0 [4–12] days, P =.69), although we observed a lower risk of pulmonary embolism (0.19 [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. [ABSTRACT FROM AUTHOR]

Background: Large birth cohort studies are extremely valuable in assessing associations between early life exposures and long-term outcomes. Establishing new birth cohorts is challenging due to declining participation rates. Online methods of data collection may increase feasibility, but have not been evaluated thoroughly.Objective: The primary objective of the ongoing PRegnancy and Infant DEvelopment (PRIDE) Study is to identify exposures during pregnancy and in early life that may affect short-term or long-term health of mother and/or child. In this manuscript, we aimed to evaluate methods of recruitment and online data collection applied.Population: Dutch women aged ≥18 years in early pregnancy.Design: Prospective cohort study.Methods: Initially, only prenatal care providers recruited participants, but alternative recruitment methods were added as a result of disappointing participation rates, including collaboration with "Moeders voor Moeders" (organisation that visits women in early pregnancy) and Facebook advertisements. Data on demographic characteristics, obstetric history, maternal health, life style factors, occupational exposures, nutrition, pregnancy complications, and infant outcomes are primarily collected through Web-based questionnaires at multiple time points during and after pregnancy. Additional data collection components include paternal questionnaires, blood and saliva sampling, and linkage to medical records.Preliminary Results: By September 2019, 9573 women were included in the PRIDE Study, of which 1.3% completed paper-based questionnaires. Mean age of the women analysed was 30.6 years, 71.1% had a high level of education, 57.2% were primiparae, and mean gestational age at enrolment was 9.9 (range 3, 37) weeks, with slight differences between recruitment methods. Pregnancy outcome was known for 89.8%. Retention rate at 6 months after the estimated date of delivery was estimated at 70%. Multiple validation studies conducted within the PRIDE Study indicated high data quality.Conclusion(s): Although challenging and time-consuming, online methods for recruitment and data collection may enable the establishment of new birth cohort studies. [ABSTRACT FROM AUTHOR]

Introduction: We performed an independent validation study of all published first trimester prediction models, containing non-invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated.Material and Methods: Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies.Results: The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models.Conclusions: The best performing prediction models showed acceptable performance measures and may enable more personalized medicine-based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the safety of medication use during pregnancy relies on observational studies: However, confounding in observational studies poses a threat to the validity of estimates obtained from observational data. Newer methods, such as marginal structural models and propensity calibration, have emerged to deal with complex confounding problems, but these methods have seen limited uptake in the pregnancy medication literature. In this article, we provide an overview of newer advanced methods for confounding control and show how these methods are relevant for pregnancy medication safety studies. [ABSTRACT FROM AUTHOR]