Risk factors for severe disease and impact of severity on pregnant women with COVID-19: a case–control study based on data from a nationwide survey of maternity services in Japan

Objective To identify independent risk factors for severe COVID-19 in pregnant women and to evaluate the impact of disease severity on preterm birth. Design A case–control study based on data from a nationwide questionnaire-based survey of maternity services in Japan. Setting A questionnaire was mailed to all 2135 delivery institutions in Japan between July and August 2021. A total of 1288 institutions responded (60% of all delivery institutions in Japan). 566 facilities reported having cared for pregnant women with COVID-19, and 722 facilities reported having had no such patients. Participants One thousand and forty-three hospitalised and non-hospitalised pregnant women diagnosed with COVID-19 between July 2020 and 30 June 2021. Primary and secondary outcome measures The primary outcome was progression to severe COVID-19. The secondary outcome was preterm birth due to COVID-19 infection. Results 56 cases (5.4%) were severe, and 987 (94.6%) were non-severe. Multivariable logistic regression analysis showed that gestational age≥24 weeks (adjusted OR (aOR) 6.68, 95% CI 2.8 to 16.0) and maternal age≥32 years (aOR 2.40, 95% CI 1.3 to 4.3) were independently associated with severe cases. Using the Kaplan-Meier method, the probability of continued pregnancy at 14 days after diagnosis for severe cases was 0.57 between 24 and 31 weeks’ gestation and 0.27 between 32 and 36 weeks’ gestation. The probability for non-severe cases was 1.0 between 24 and 31 weeks’ gestation and 0.8 between 32 and 36 weeks’ gestation. Among the patients with COVID-19 in the preterm period, preterm birth due to infection was significantly more common in severe than non-severe cases (48% vs 6%, p< 0.0001). Conclusions Severe COVID-19 in pregnant women was associated with gestational age≥24 weeks and maternal age≥32. The rate of preterm delivery due to the infection was significantly higher in severe COVID-19 cases.