Julia F Simard1,2,3, Marios Rossides3, Anna-Karin Wikström3,4, Titilola Falasinnu1, Kristin Palmsten5, Elizabeth V Arkema3. 1. Department of Epidemiology and Population Health, Stanford Medicine, Stanford, CA, USA. 2. Division of Immunology and Rheumatology, Department of Medicine, Stanford Medicine, Stanford, CA, USA. 3. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 4. Department of Women's and Children's Health, Uppsala University, Stockholm, Sweden. 5. HealthPartners Institute, Minneapolis, MN, USA.
Abstract
BACKGROUND: Early-onset preeclampsia, traditionally defined as presenting before 34 gestational weeks, is associated with even higher risks of perinatal death, placental abruption, and stroke, than late-onset preeclampsia. OBJECTIVE: We estimated the degree of misclassification in a high-risk population of lupus pregnancies and a general population comparator when gestational age at delivery defined preeclampsia phenotype compared to first preeclampsia diagnosis. METHODS: Patients with lupus and general population comparators from Sweden with ≥1 singleton pregnancy in the Medical Birth Register with a documented ICD code for preeclampsia were included (2002-2016). We used gestational age at delivery (<34 versus ≥34 weeks) to phenotype preeclampsia early- versus late-onset and then reclassified based on first preeclampsia diagnosis date in the Patient Register. We cross-tabulated the two definitions and calculated sensitivity using the visit-based definition as the reference standard for general population and lupus pregnancies, overall and among nulliparous women. RESULTS: 331 pregnancies were diagnosed with preeclampsia, of which 322 were in both registers. Of those, 58 were early-onset based on gestational age at delivery (n = 29 in lupus pregnancies). Overall, 9% of early-onset preeclampsia in lupus (sensitivity 91%, 95% confidence interval [CI] 75, 98) was misclassified as late-onset compared to 19% in the general population (sensitivity 81%, 95% CI 64, 92). We noted similar misclassification (4% vs 22%) among nulliparous women. CONCLUSIONS: In the general population, early-onset preeclampsia was more likely misclassified as late-onset than in the high-risk lupus population. Relying on gestational age at delivery to phenotype preeclampsia, this way underestimates the occurrence of early-onset preeclampsia. This also suggests that the burden of early-onset preeclampsia as a public health concern may be under-reported, although this may be more applicable to milder preeclampsia where expectant management is employed. Research of biological and maternal predictors of early-onset preeclampsia may be dealing with differentially misclassified outcomes or samples.
BACKGROUND: Early-onset preeclampsia, traditionally defined as presenting before 34 gestational weeks, is associated with even higher risks of perinatal death, placental abruption, and stroke, than late-onset preeclampsia. OBJECTIVE: We estimated the degree of misclassification in a high-risk population of lupus pregnancies and a general population comparator when gestational age at delivery defined preeclampsia phenotype compared to first preeclampsia diagnosis. METHODS: Patients with lupus and general population comparators from Sweden with ≥1 singleton pregnancy in the Medical Birth Register with a documented ICD code for preeclampsia were included (2002-2016). We used gestational age at delivery (<34 versus ≥34 weeks) to phenotype preeclampsia early- versus late-onset and then reclassified based on first preeclampsia diagnosis date in the Patient Register. We cross-tabulated the two definitions and calculated sensitivity using the visit-based definition as the reference standard for general population and lupus pregnancies, overall and among nulliparous women. RESULTS: 331 pregnancies were diagnosed with preeclampsia, of which 322 were in both registers. Of those, 58 were early-onset based on gestational age at delivery (n = 29 in lupus pregnancies). Overall, 9% of early-onset preeclampsia in lupus (sensitivity 91%, 95% confidence interval [CI] 75, 98) was misclassified as late-onset compared to 19% in the general population (sensitivity 81%, 95% CI 64, 92). We noted similar misclassification (4% vs 22%) among nulliparous women. CONCLUSIONS: In the general population, early-onset preeclampsia was more likely misclassified as late-onset than in the high-risk lupus population. Relying on gestational age at delivery to phenotype preeclampsia, this way underestimates the occurrence of early-onset preeclampsia. This also suggests that the burden of early-onset preeclampsia as a public health concern may be under-reported, although this may be more applicable to milder preeclampsia where expectant management is employed. Research of biological and maternal predictors of early-onset preeclampsia may be dealing with differentially misclassified outcomes or samples.
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