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.

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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.

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
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Published: Report no: ut202105 Registration no: SBU 2020/898
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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
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