Absolute and relative risk of adverse health outcomes comparing pregnant women with and without SARS-CoV-2 infection
| Outcomes | Studies (n) | Included studies*† | Confirmed COVID-19 case | COVID-19-negative comparison | Relative risk (95% CI)¶ | I2% (P value) | ||
| Events/total | Pooled risk (95% CI)§ | Events/total | Pooled risk (95% CI)§ | |||||
| Critical care indicators | ||||||||
| ICU admission | 8 | c d e1* e2 f h j k | 78/1299 | 0.03 (0.00 to 0.09) | 17/5361 | 0.00 (0.00 to 0.01) | 3.81 (2.03 to 7.17) | 0 (0.67) |
| Ventilation | 7 | c d e1* e2 f h j | 21/796 | 0.02 (0.01 to 0.04) | 0/4091 | 0.00 (0.00 to 0.00) | 15.23 (4.32 to 53.71) | 0 (0.81) |
| Any critical care | 7 | c d e1* e2 f h j* | 73/771 | 0.04 (0.00 to 0.13) | 10/3964 | 0.00 (0.00 to 0.01) | 5.48 (2.57 to 11.72) | 0 (0.73) |
| Pneumonia | 6 | c e1* e2 f h j* | 124/711 | 0.18 (0.05 to 0.37) | 13/3862 | 0.01 (0.00 to 0.02) | 23.46 (3.03 to 181.39) | 91 (0) |
| Maternal mortality and morbidity | ||||||||
| Maternal death | 10 | a* c* d* e1* e2* f* g h i j* | 38/368 | 0.07 (0.00 to 0.22) | 3/1122 | 0.00 (0.00 to 0.02) | 7.68 (1.70 to 34.61) | 30.49 (0.24) |
| Haemorrhage | 6 | a c g h i k | 109/1136 | 0.08 (0.04 to 0.14) | 795/7273 | 0.07 (0.03 to 0.13) | 1.22 (0.76 to 1.98) | 68.35 (0.01) |
| Placental abruption | 5 | a f h j k | 15/928 | 0.01 (0.00 to 0.03) | 56/4258 | 0.01 (0.00 to 0.02) | 1.55 (0.75 to 3.21) | 0 (0.55) |
| Hypertensive disorders of pregnancy (diagnosed at or after COVID-19) | 3 | a b j | 24/255 | 0.08 (0.01 to 0.20) | 254/3396 | 0.06 (0.01 to 0.14) | 1.33 (0.89 to 1.98) | 0 (0.8) |
| Hypertensive disorders of pregnancy (diagnosed at any time) | 10 | a b c e1 e2 g h i j k | 178/1570 | 0.09 (0.05 to 0.14) | 497/9902 | 0.06 (0.04 to 0.09) | 1.25 (1.04 to 1.50) | 0 (0.87) |
| Pre-eclampsia | 9 | a b d e1 e2 f i j k | 100/1360 | 0.06 (0.04 to 0.08) | 324/7417 | 0.04 (0.02 to 0.06) | 1.42 (1.13 to 1.78) | 0 (0.62) |
| Eclampsia | 7 | a* b* e1* e2* i j* k* | 0/133 | – | 2/613 | 0.00 (0.00 to 0.01) | 0.92 (0.04 to 19.04) | 0 (0) |
| Pre-eclampsia or eclampsia | 10 | a b c e1 e2 g h i j k | 138/1570 | 0.07 (0.04 to 0.11) | 399/9902 | 0.04 (0.02 to 0.05) | 1.46 (1.17 to 1.81) | 0 (0.57) |
| Thromboembolic disease | 8 | a c d* e1* e2* g* i* j* | 2/265 | 0.01 (0.00 to 0.02) | 7/4881 | 0.00 (0.00 to 0.00) | 5.50 (1.12 to 27.12) | 0 (0.46) |
| Preterm labour | 6 | c e1* e2 g i j | 33/508 | 0.06 (0.03 to 0.10) | 190/4674 | 0.04 (0.02 to 0.05) | 1.59 (0.87 to 2.89) | 43.18 (0.13) |
| Preterm labour—COVID onset <37 weeks | 4 | c g i j | 17/223 | 0.07 (0.03 to 0.12) | 114/3546 | 0.03 (0.02 to 0.04) | 2.47 (1.28 to 4.79) | 17.31 (0.3) |
| C-section | 10 | a c d e1 e2 g h i j k | 499/1505 | 0.34 (0.28 to 0.40) | 2609/9066 | 0.30 (0.25 to 0.36) | 1.10 (1.01 to 1.20) | 0 (0.88) |
| Intrapartum C-section | 8 | a c e1* e2 g h i j | 166/792 | 0.22 (0.14 to 0.30) | 1053/7095 | 0.17 (0.12 to 0.23) | 1.14 (0.97 to 1.34) | 0 (0.66) |
| Fetal and neonatal mortality and morbidity | ||||||||
| Stillbirth** | 12 | a b c d* e1 e2 f g h i j* k | 14/1602 | 0.01 (0.00 to 0.02) | 64/10 060 | 0.01 (0.00 to 0.01) | 1.08 (0.53 to 2.16) | 0 (0.97) |
| Perinatal death†† | 9 | a c d e1 e2 f g i j* | 7/931 | 0.00 (0.00 to 0.01) | 48/8078 | 0.01 (0.00 to 0.01) | 1.23 (0.58 to 2.61) | 0 (0.93) |
| Early neonatal death†† | 9 | a c d e1 e2 f g i j* | 1/928 | 0.00 (0.00 to 0.00) | 23/8071 | 0.00 (0.00 to 0.00) | 1.37 (0.47 to 4.01) | 0 (0.85) |
| Neonatal death†† | 10 | a c d e1 e2 f g h i j* | 4/1064 | 0.00 (0.00 to 0.01) | 30/8118 | 0.00 (0.00 to 0.00) | 1.71 (0.71 to 4.12) | 0 (0.8) |
| NICU admission at birth‡‡ | 7 | a c d e2 f g j | 110/661 | 0.21 (0.06 to 0.41) | 472/6976 | 0.07 (0.05 to 0.08) | 1.86 (1.12 to 3.08) | 73.78 (0) |
| Adverse birth outcomes | ||||||||
| Very low birth weight (<1500 g) | 12 | a b c d e1 e2 f g h i j* k | 30/1646 | 0.01 (0.01 to 0.03) | 169/10 129 | 0.01 (0.01 to 0.02) | 1.12 (0.74 to 1.71) | 0 (0.99) |
| Low birth weight (<2500 g) | 12 | a b c d e1 e2 f g h i j k | 198/1670 | 0.12 (0.08 to 0.16) | 926/10 260 | 0.09 (0.07 to 0.11) | 1.19 (1.02 to 1.40) | 0 (0.6) |
| Small for gestational age (3rd centile) | 12 | a b c d e1 e2 f g h i j k | 48/1670 | 0.03 (0.01 to 0.05) | 293/10 260 | 0.03 (0.02 to 0.05) | 1.05 (0.77 to 1.43) | 0 (0.67) |
| Small for gestational age (10th centile) | 12 | a b c d e1 e2 f g h i j k | 136/1670 | 0.08 (0.05 to 0.12) | 885/10 260 | 0.09 (0.07 to 0.12) | 0.96 (0.80 to 1.15) | 0 (0.56) |
| Moderate preterm birth (<34 weeks) | 12 | a b c d e1 e2 f g h i j k | 80/1666 | 0.05 (0.03 to 0.07) | 354/10 218 | 0.03 (0.02 to 0.04) | 1.37 (1.05 to 1.79) | 0 (0.84) |
| Moderate preterm birth (<34 weeks)—COVID onset <34 weeks‡ | 7 | b c d g i j k | 48/448 | 0.12 (0.04 to 0.23) | 241/5623 | 0.04 (0.02 to 0.06) | 2.92 (1.88 to 4.54) | 34.74 (0.16) |
| Preterm birth (<37 weeks) | 12 | a b c d e1 e2 f g h i j k | 234/1666 | 0.14 (0.10 to 0.19) | 1054/10 218 | 0.10 (0.08 to 0.14) | 1.27 (1.07 to 1.49) | 11.96 (0.33) |
| Preterm birth (<37 weeks)—COVID onset <37 weeks‡ | 7 | b c d g i j k | 129/610 | 0.24 (0.15 to 0.35) | 742/5623 | 0.12 (0.08 to 0.17) | 1.71 (1.28 to 2.29) | 50.31 (0.06) |
*Included studies for each estimate are categorised as follows: (a) Ahlberg et al, Sweden19; (b) Akelo and Tippett Barr (2021), Kenya; (c) Bevilacqua and Laurita Longo (2020), Italy; (d) Brandt (2020), New Brunswick, USA; (e1) Crovetto (2020), Spain, Cohort I; (e2) Crovetto (2020), Spain, Cohort II; (f) Kalafat et al, Turkey22; (g) Le Doare (2021), Uganda; (h) Nachega (2021), Multi-country Africa; (i) Nunes (2021), South Africa; (j) Poon (2021), China-Hong Kong; (k) Sakowicz (2021), Chicago, USA.
†Asterisks indicate there is zero total outcome event for a given study. These studies are not included in the ‘Events/Total’ and pooled risk estimates.
‡These outcomes (preterm labour, very preterm birth before 34 weeks’ gestation and preterm birth before 37 weeks’ gestation) were included in the sensitivity analyses where we restrict confirmed COVID-19 cases to those with confirmed COVID-19 onset prior to 37 weeks’ gestation (or 34 weeks for moderate preterm birth). The full comparison group is used for each of the sensitivity analyses.
§Pooled absolute risks are calculated using Freeman-Tukey transformed proportions, pooled from all participating studies with at least one adverse event for the given outcome, using a DerSimonian-Laird random-effects inverse-variance model meta-analysis.
¶Relative risks are calculated by pooling unadjusted relative risks from all participating studies with at least one adverse event for the given outcome using a DerSimonian-Laird random-effects model meta-analysis. For any study with zero event in one arm (COVID-19 cases or COVID-negative comparisons), we used a continuity correction of 0.5.
**The outcome presented here is stillbirth occurring at or after 28 weeks’ gestational age per WHO definition.
††The outcome ‘neonatal death’ is reported by nine participating studies. However, most studies were not designed to follow-up neonates until 28 days after birth. The count of neonatal deaths is likely an underestimate.
‡‡The outcome ‘NICU Admission at Birth’ is defined as admission to the neonatal intensive care unit or the equivalent for all studies except for Crovetto (2020), Spain, Cohort II, where the outcome also includes ‘admission to high-dependency care unit’.
C-section, caesarean section; ICU, intensive care unit; NICU, neonatal intensive care unit.