Covid-19 and pregnancy

This is an answer from SBU's enquiry service that provides quick answers to narrow questions. The answer compiles scientific studies that examined the risk of serious illness or death from covid-19 during a pregnancy.

Reading time approx. 13 minutes Published: February 4, 2021 Publication type:

SBU Enquiry Service

Consists of structured literature searches to highlight studies that can address questions received by the SBU Enquiry Service from Swedish healthcare or social service providers. We assess the risk of bias in systematic reviews and when needed also quality and transferability of results in health economic studies. Relevant references are compiled by an SBU staff member, in consultation with an external expert when needed.

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Published: February 4, 2021 Report no: ut202105 Registration no: SBU 2020/898

Question

What scientific studies are there on covid-19 effects on pregnant women when it comes to the risk for serious disease, mortality and admission to the ICU?

Identified literature

Table 1. Systematic reviews with low/medium risk of bias.

Included studies	Population/Intervention	Outcome
Allotey et al., 2020 (1)
77 cohort studies (55 comparative, 22 non-comparative) 45 of 77 studies included covid-19 related outcomes Quality Assessment: Newcastle-Ottawa Scale All studies scored high to moderate quality assessment scores (low to moderate risk of bias) Setting: 26 studies US (34%) 24 China (31%) 7 Italy 6 Spain 14 Other countries	Population: Pregnant or recently pregnant (post-partum or post-abortion) women. Exposure: Confirmed or suspected covid-19 infection. Confirmed covid-19: Laboratory confirmation, irrespective of symptoms. All included studies used RT-PCR. Suspected covid-19: Covid-19 diagnosis based on clinical or radiological findings. 13 118 pregnant or recently pregnant women with confirmed or suspected covid-19 included in review	Outcomes related to covid-19 (percent, 95% CI) All cause mortality (26 studies/ n=11 580): 0.1% (0.0%–0.7%) Severe covid (21 studies/n=2 271) 13% (6%–21%) Admission to ICU (17 studies/n=10 901) 4% (2%–7%) Invasive ventilation (13 studies/n=10 713): 3% (1%–5%) ECMO (9 studies/n=1 935): 0.4% (0.1%–0.9%) Comparative outcomes (OR, 95% CI): Pregnant women with covid-19 vs. non-pregnant women of reproductive age with covid-19 All-cause mortality (4 studies/n=91 609): 0.81 (0.49–1.33) Admission to ICU (4 studies/n=91 606): 1.62 (1.33–1.96) Invasive ventilation: (4 studies/n=91 606): 1.88 (1.36 – 2.60) Pregnant women with covid-19 vs. pregnant women without covid-19 All-cause mortality (1 study/n = 1 121) 18.08 (1.00-327.83) Admission to ICU (1 study/n=1 121): 71.63 (9.81 - 523-06)
Risk factors
52 of 77 studies included risk factors for covid-19 and complications	Pre-existing risk factors Age (≥35 years) Obesity (body mass index ≥30) Non-white Any comorbidity Chronic hypertension Pre-existing diabetes Comparison: Pregnant women with covid-19 without pre-existing risk factors.	Odds Ratio, 95% CI Obesity Severe disease (3 studies/n=877) 2.38 (1.67–3.39) Maternal death (2 studies/n=596) 2.57 (0.97–6.82) Chronic hypertension Severe disease (2 studies/n=858) 2.0 (1.14–3.48) Maternal death (2 studies/n=596) 3.38 (1.17 – 9.75) Pre-existing diabetes Severe disease (2 studies/n=858) 2.51 (1.31–4.80) ICU admission (2 studies/n=181) 2.88 (0.44–18.96) Maternal death (2 studies/n=596) 6.63 (0.27–161.45)
Authors' conclusion: “Emerging comparative data indicate the potential for an increase in the rates of admission to intensive care units and invasive ventilation in pregnant women compared with non-pregnant women. Mothers with pre-existing comorbidities will need to be considered as a high risk group for covid-19, along with those who are obese and of greater maternal age.”

Table 2. Primary studies with low or moderate risk for bias.

Article	Study design	Population	Outcomes	Overall risk of bias
Badr DA, Mattern J, Carlin A, Cordier AG, Maillart E, El Hachem L, El Kenz H, Andronikof M, De Bels D, Damoisel C, Preseau T. Are clinical outcomes worse for pregnant women at≥ 20 weeks’ gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching. American Journal of Obstetrics & Gynecology. 2020 Nov 1;223(5):764-8. (2)	Retrospective case-control Multicentre study: 4 university hospitals Setting: France and Belgium	N=190 Women of reproductive age with confirmed Sars-Cov-2 infection. Case: Pregnant ≥20 weeks gestation (n=83) Control: Non pregnant (n=107) Covid-19 diagnosis confirmed by RT-PCR of nasopharyngeal swab samples Propensity score matching on variables: age; ethnicity; weight; height; BMI; preexisting medical conditions (diabetes I and II; hypertension; asthma), symptoms, physical examination, pregnancy status, gestational age at initial presentation	(After propensity score matching) ICU admission: Case: 11.08% Control: 2.38% Endotracheal intubation: Case: 10.16% Control: 1.67%	Moderate
DeBolt CA, Bianco A, Limaye MA, Silverstein J, Penfield CA, Roman AS, Rosenberg HM, Ferrara L, Lambert C, Khoury R, Bernstein PS. Pregnant women with severe or critical COVID-19 have increased composite morbidity compared to non-pregnant matched controls. American Journal of Obstetrics and Gynecology. 2020 Nov 20. (3)	Retrospective case-control Multicentre study: 4 academic medical centres Setting: USA	N = 132 Women of reproductive age with confirmed Sars-Cov-2 infection hospitalized with severe or critical disease Case: Pregnant (n=38) Control: Non pregnant (n=94) Covid-19 diagnosis confirmed by RT-PCR	ICU admission: OR: 4.9 (95% CI: 1.2–19.5) Case: n=15 (39.5%) Control: n=16 (17%) Intubation or Mechanical ventilation: Case: n=2 (6.9%) Control: n=1 (1.3%) ECMO: Case: n=0 Control:n= 0 Death: Case: n=0 Control: n=0	Moderate
Menezes, M. O., Takemoto, M. L. S., Nakamura‐Pereira, M., Katz, L., Amorim, M. M. R., … Salgado, H. O. (2020). Risk factors for adverse outcomes among pregnant and postpartum women with acute respiratory distress syndrome due to COVID‐19 in Brazil. International Journal of Gynecology & Obstetrics. (4)	Retrospective case-control Register study: Data from the national surveillance system in Brazil. Setting: Brazil	N= 2475 Pregnant women with acute respiratory disease (any flu-like symptom in association with either dyspnea or respiratory distress, or oxygen saturation over 95%.) Case: Adverse event (n = 590) Control: No adverse event (n = 1885)	Composite outcome (death, ICU-admission or invasive ventilation). Obesity: OR: 2.12 (95% CI: 1.38 to 3.27) Diabetes: 1.66 (95% CI: 1.18 to 2.35) ICU-Admission Obesity: OR: 1.91 (95% CI: 1.23 to 2.97) Diabetes: OR: 1.63 (95% CI: 1.07 to 2.19)	Moderate
Takemoto, M. L. S., Menezes, M. O., Andreucci, C. B., Knobel, R., Sousa, L. A. R., Katz, L., … Menezes, M. O. (2020). Clinical characteristics and risk factors for mortality in obstetric patients with severe COVID‐19 in Brazil: a surveillance database analysis. BJOG: An International Journal of Obstetrics & Gynaecology. (5)	Retrospective case-control Register study: Data from the national surveillance system in Brazil. Setting: Brazil	N= 978 Pregnant women with acute respiratory disease (any flu-like symptom in association with either dyspnea or respiratory distress, or oxygen saturation over 95%.) Case: Death (n = 124) Control: Cure (n = 854)	Death Obesity: OR: 2.48 (95% CI: 1.65 to 3.72) Diabetes: OR: 1.82 (95% CI: 1.01 to 3.28)	Moderate
Prabhu M, Cagino K, Matthews KC, Friedlander RL, Glynn SM, Kubiak JM, Yang YJ, Zhao Z, Baergen RN, DiPace JI, Razavi AS. Pregnancy and postpartum outcomes in a universally tested population for SARS‐CoV‐2 in New York City: a prospective cohort study. BJOG: An International Journal of Obstetrics & Gynaecology. 2020 Nov;127(12):1548-56. (6)	Prospective cohort Multicentre study: 3 hospitals Setting: USA	N=675 Pregnant women ≥20 weeks gestation admitted to labour and delivery units All women tested for Sars-Cov-2 infection on day of admission Case: Sars-Cov-2 positive (1) Symptomatic (n=15) (2) Asymptomatic (n=55) Control: Sars-Cov-2 negative (n=605) Covid-19 diagnosis confirmed RT-PCR	ICU admission: Symptomatic: n=1 (6.7%) Asymptomatic: n=0 Control: n=0 Need for respiratory support: Symptomatic: n=2 (13.3%) Asymptomatic: n=1 (1.8%) Control: n=0 Death: Case: n=0 Control: n=0	Moderate
Ríos-Silva M, Murillo-Zamora E, Mendoza-Cano O, Trujillo X, Huerta M. COVID-19 mortality among pregnant women in Mexico: A retrospective cohort study. Journal of global health. 2020 Dec;10(2). (7)	Retrospective cohort National Surveillance Database of Covid-19 Setting: Mexico	N=19 606 All pregnant and/or Sars-Cov-2 infected women of reproductive age registered in national Covid-19 database Case: Pregnant women with confirmed Sars-Cov-2 infection (n=448) Control 1: Non pregnant with confirmed Sars-Cov-2 infection (n=17 942) Control 2: Pregnant without Sars-Cov-2 infection (n=1 216) Covid-19 diagnosis confirmed by RT-PCR	Admission to ICU: Case: n=14 (10.2%) Control 1: n=227 (7.4%), p = 0,2 Control 2: n=20 (6%) Mechanical ventilation: Case: n=7 (5.1%) Control 1: n=174 (5.7%) Control 2: n=06 (1.8%) Death: Case: n=10 (2.2%) Control 1: n=484 (2.7%) Control 2: n=7 (0.6%)	Moderate
Zambrano LD, Ellington S, Strid P, Galang RR, Oduyebo T, Tong VT, Woodworth KR, Nahabedian III JF, Azziz-Baumgartner E, Gilboa SM, Meaney-Delman D. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–October 3, 2020. Morbidity and Mortality Weekly Report. 2020 Nov 6;69(44):1641. (8)	Retrospective cohort National Surveillance database of Covid-19 cases Setting: USA	N=409 462 Women of reproductive age with confirmed Sars-Cov-2 infection Case: Pregnant (n=23 434) Control: Non pregnant (n=386 028) Covid-19 diagnosis confirmed by RT-PCR	ICU admission: Case = 245 (10.5%) Control = 1492 (3.9%) OR: 3.0 (95% CI: 2.6–3.4) Invasive ventilation: Case = 67 (2.9%) Control = 412 (1.1%) OR: 2.9 (95% CI: 2.2–3.8) Death: Case = 34 (1.5%) Control = 447 (1.2%) OR: 1.7 (95% CI: 1.2–2.4)	Moderate

References

Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ (Clinical research ed). 2020;370:m3320.
Badr DA, Mattern J, Carlin A, Cordier A-G, Maillart E, El Hachem L, et al. Are clinical outcomes worse for pregnant women at ≥20 weeks' gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching. Am J Obstet Gynecol. 2020;223(5):764-8.
DeBolt CA, Bianco A, Limaye MA, Silverstein J, Penfield CA, Roman AS, et al. Pregnant women with severe or critical COVID-19 have increased composite morbidity compared to non-pregnant matched controls. Am J Obstet Gynecol. 2020.
Menezes MO, Takemoto MLS, Nakamura-Pereira M, Katz L, Amorim MMR, Salgado HO, et al. Risk factors for adverse outcomes among pregnant and postpartum women with acute respiratory distress syndrome due to COVID-19 in Brazil. International Journal of Gynecology and Obstetrics. 2020;151(3):415-23.
Takemoto M, Menezes MO, Andreucci CB, Knobel R, Sousa L, Katz L, et al. Clinical characteristics and risk factors for mortality in obstetric patients with severe COVID-19 in Brazil: a surveillance database analysis. BJOG : an international journal of obstetrics and gynaecology. 2020;127(13):1618-26.
Prabhu M, Cagino K, Matthews KC, Friedl, er RL, Glynn SM, et al. Pregnancy and postpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: a prospective cohort study. BJOG: An International Journal of Obstetrics and Gynaecology. 2020;127(12):1548-56.
Ríos-Silva M, Murillo-Zamora E, Mendoza-Cano O, Trujillo X, Huerta M. COVID-19 mortality among pregnant women in Mexico: A retrospective cohort study. Journal of global health. 2020;10(2):020512.
Zambrano LD, Ellington S, Strid P, Galang RR, Oduyebo T, Tong VT, et al. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status - United States, January 22-October 3, 2020. MMWR Morbidity and mortality weekly report. 2020;69(44):1641-7.

Literature search

Medline via OvidSP 11 dec 2020

Risk of severe Covid-19 in pregnant women

/ = Term from the MeSH controlled vocabulary; .sh = Term from the MeSH controlled vocabulary; exp = Term from MeSH including terms found below this term in the MeSH hierarchy; .ab,ti = Abstract or title; .tw = Abstract or title; .kf = Keywords; .kw = Keywords, exact; .af = All fields; AdjX = Proximity operator with a specified number, adj3 retrieves records with search terms within two terms from each other; * = Truncation; “ “ = Citation Marks; searches for an exact phrase
Search terms		Items found
Population:
1.	Prenatal Care/
2.	Exp Pregnancy/
3.	Pregnant Women/
4.	(prenatal or antenatal or prepartum or pregnancy or pregnant).ab,kf,ti.
5.	1 or 2 or 3 or 4	1 047 068
Intervention:
6.	Exp Coronavirus/
7.	Exp Coronavirus Infections/
8.	(covid* or sars cov* or sarscov* or corona virus or coronavirus or ncov).ab,kf,ti
9.	6 or 7 or 8	102 360
Outcome:
10.	Critical Care/
11.	Critical Illness/
12.	Mortality/
13.	Intensive Care Units/ or Coronary Care Units/ or Respiratory Care Units/
14.	(intensive or icu or critical* or ventilat* or mortality).ab,kf,ti
15.	((severe or acut) adj2 (disease or covid or symptom* or case* or infection or ill*)).ab.kf.ti.
16.	(respiratory adj2 (distress or failure)).ab,kf,ti
17.	or/10-15	2 150 580
Limits:
18.	Years: 2019-2021
Final	5 AND 9 AND 17 AND 18	608

Embase via embase.com 12 dec 2020

Risk of severe Covid-19 in pregnant women

/de = Term from the EMTREE controlled vocabulary; /exp = Term from EMTREE including terms found below this term in the EMTREE hierarchy; /mj = Major Topic; :ti,ab,kw = Title, abstract or author keywords; NEAR/x = Proximity operator with a specified number, NEAR/3 retrieves records with search terms within two terms from each other; * = Truncation; ’ ’ = Citation Marks; searches for an exact phrase
Search terms		Items found
Population:
1.	‘pregnancy’/exp
2.	‘pregnant woman’/de
3.	‘prenatal care’/exp
4.	(pregnant OR pregnancy OR prepartum OR prenatal OR antenatal):ti,ab,kw
5.	1 OR 2 OR 3 OR 4	1 121 142
Intervention:
6.	‘coronavirus disease 2019’/de
7.	(covid* or sars cov* or sarscov* or corona virus or coronavirus or ncov):ti,ab,kw
8.	6 OR 7	96 801
Outcome:
9.	‘intensive care’/exp
10.	‘intensive care unit’/de
11.	‘critical illness’/exp
12.	‘mortality’/de
13.	(intensive OR icu OR critical OR ventilat* OR mortality OR death):ti,ab,kw
14.	((severe OR acut) NEAR/2 (disease OR covid OR symptom* OR case OR infection OR ill*)):ti,ab,kw
15.	(respiratory NEAR/2 (distress OR failure):ti,ab,kw
16.	9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15	4 239 902
Limits:
17.	Year 2019-2121
Final	5 AND 8 AND 16 AND 17	859

Epistemonikos, Covid-19 Evidence section 12 dec 2020

Risk of severe Covid-19 in pregnant women

Search terms		Items found
Population:
1.	Covid-19 section total	71 518
2.	Pregnancy subset	1 357
Outcome:
3.	(“critical care” OR “intensive care” OR “critical illness” OR ventilat* OR “severe covid” OR “severe symptoms” OR “severe infection” OR mortality OR “respiratory distress” OR “respiratory failure”)
Final	2 AND 3	339

Page published February 4, 2021

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