Risk factors for pre‐eclampsia in clinical practice guidelines: Comparison with the evidence

OBJECTIVE To compare pre-eclampsia risk factors identified by clinical practice guidelines (CPGs) with risk factors from hierarchical evidence review, to guide pre-eclampsia prevention. DESIGN Our search strategy provided hierarchical evidence of relationships between risk factors and pre-eclampsia, using Medline (Ovid), January 2010-January 2021. SETTING Published studies and CPGs. POPULATION Pregnant women. METHODS We evaluated strength of association and quality of evidence (GRADE). CPGs (N=15) were from previous systematic review. MAIN OUTCOME MEASURE Pre-eclampsia. RESULTS Of 78 pre-eclampsia risk factors, 13 (16.5%) arise only during pregnancy. Strength of association was usually 'probable' (n=40, 51.3%), and quality of evidence low (n=35, 44.9%). The 'major' and 'moderate' risk factors proposed by 8/15 CPGs were not well-aligned with evidence; of 10 'major' risk factors (alone warranting aspirin prophylaxis), associations with pre-eclampsia were definite (n=4), probable (n=5), or possible (n=1), based on moderate (n=4), low (n=5), or very-low (n=1) quality evidence. Obesity ('moderate' risk factor), was definitely associated with pre-eclampsia (high-quality evidence). The other ten 'moderate' risk factors had probable (n=8), possible (n=1), or no (n=1) association with pre-eclampsia, based on moderate (n=1), low (n=5), or very-low (n=4) quality evidence. Three risk factors not identified by CPGs had probable associations (high-quality): overweight, booking 'prehypertension', and early pregnancy BP 130-139/80-89mmHg. CONCLUSIONS Pre-eclampsia risk factors in CPGs are poorly aligned with evidence, particularly for the strongest risk factor, obesity. There is a lack of distinction between risk factors identifiable in early pregnancy and those arising later. A refresh of strategies advocated by CPGs is needed.