Background
Methods
Literature search strategy
Inclusion and exclusion criteria
Data extraction
Methodological quality appraisal
Statistical analysis
Results
Literature search and study characteristics
Author | Year | Region | Study design | Total | Women with RA | Women without RA | Maternal outcomes | Fetal outcomes | Quality assessment | ||
---|---|---|---|---|---|---|---|---|---|---|---|
N | Maternal age | N | Maternal age | ||||||||
Bowden | 2001 | UK | case-control | 236 | 133 | 32.7 ± 4.6 | 103 | 30.0 ± 4.5 | birth weight | 5 | |
Reed | 2006 | USA | cohort | 2802 | 243 | NA | 2559 | NA | cesarean delivery, preeclampsia | premature, LBW, SGA infant | 4 |
Mouridsen | 2007 | Denmark | case-control | 441 | 7 | NA | 434 | NA | infantile autism | 7 | |
de Man | 2009 | Netherlands | cohort | 3811 | 152 | 32.5 ± 3.7 | 3659 | 31.2 ± 4.5 | birth weight | 6 | |
Atladóttir | 2009 | Denmark | cohort | 689,196 children | NA | NA | NA | NA | autism spectrum disorder | 5 | |
Lin | 2010 | China | cohort | 11,472 | 1912 | NA | 9560 | NA | cesarean delivery, preeclampsia | premature, LBW, SGA infant | 8 |
Nørgaard | 2010 | Sweden, Denmark | cohort | 871,579 | 1199 | NA | 870,380 | NA | cesarean delivery, preeclampsia, gestational diabetes | premature, Apgar score at 5 min below 7, SGA infant, stillbirth, congenital abnormalities | 4 |
Barnabe | 2011 | Canada | cohort | 188 | 38 | 32 ± 5.5 | 150 | NA | cesarean delivery, preeclampsia, gestational diabetes, postpartum infection | premature, requiring intensive care, SGA infant, congenital defects | 5 |
Ma | 2014 | USA | cohort | 1304 | 202 | NA | 1102 | NA | premature, LBW, SGA infant | 7 | |
Bharti | 2015 | USA | cohort | 440 | 440 | 32.7 ± 4.6 | cesarean delivery | premature, SGA infant | 5 | ||
Pósfai | 2015 | Hungary | case-control | 38,151 | 68 | 26.9 ± 5.6 | 38,083 | 25.5 ± 5.3 | gestational diabetes, hypertension | birth weight, preterm birth, LBW, congenital abnormalities | 3 |
Wallenius | 2015 | Norway | cohort | 412,708 | 1578 | 32.1 ± 4.8 | 411,130 | 30.9 ± 5.1 | spontaneous abortion | stillbirth | 5 |
Atta | 2015 | Egypt | cohort | 69 | 47 | 31.1 ± 1.4 | 22 | 32.7 ± 0.9 | cesarean delivery | premature, SGA | 4 |
Rom-a | 2016 | Denmark | cohort | 1,917,723 | 13,556 | 28.46 ± 5.1 | 1,904,167 | 28.35 ± 4.9 | Juvenile Idiopathic Arthritis, Diabetes type 1, Asthma | 8 | |
Rom-b | 2016 | Denmark | cohort | 1,909,933 | 13,511 | 28 ± 5.1 | 1,896,422 | 28 ± 4.9 | Apgar score below 7, epilepsy | 7 | |
Tsai | 2017 | China | cohort | 1,893,244 | 673 | 31.97 ± 4.51 | 1,892,571 | 29.50 ± 4.80 | autism spectrum disorder | 6 | |
Bandoli | 2017 | USA | cohort | 2432 | 729 | 32.5 ± 4.8 | 1703 | 32.1 ± 5.1 | preeclampsia, maternal depression, gestational diabetes | premature, birth weight | 5 |
Galappatthy | 2017 | Sri Lanka | cohort | 165 | 80 | 35 ± 6.7 | 85 | NA | spontaneous abortion, hypertension, gestational diabetes | stillbirth, LBW | 5 |
Eudy | 2017 | USA | cross-sectional | 150 | 75 | 32.0 ± 5.2 | 75 | 31.9 ± 5.1 | spontaneous abortion, gestational diabetes, cesarean delivery, preeclampsia | premature, congenital abnormalities, NICU visit | 15 |
Jølving | 2018 | Denmark | cohort | 1,380,645 | 2106 | NA | 1,378,539 | NA | cesarean delivery | premature, SGA infant, rheumatoid arthritis, diabetes mellitus, epilepsy | 7 |
Rom | 2018 | Denmark | cohort | 1,917,723 | 13,556 | 28.46 ± 5.1 | 1,904,167 | 28.35 ± 4.9 | autism spectrum disorder | 8 | |
Lin | 2018 | China | cohort | 2707 | 34 | NA | 2673 | NA | postpartum depression | 5 | |
Zbinden | 2018 | Switzerland | cohort | 156 | 86 | 32 (22–44) | 70 | 32 (20–41) | cesarean delivery | premature, SGA infant | 7 |
Smith | 2018 | USA, Canada | cohort | 1221 | 657 | 33.14 ± 4.67 | 564 | 32.09 ± 4.7 | cesarean delivery, preeclampsia, gestational diabetes, hypertension | premature | 5 |
Aljary | 2018 | Canada | cohort | 847,607 | 6068 | NA | 841,539 | NA | cesarean delivery, preeclampsia, gestational diabetes, hypertension, postpartum hemorrhage | premature, SGA infant | 5 |
Croen | 2019 | USA | case-control | 1578 | 15 | NA | 1563 | NA | autism spectrum disorder | 7 | |
Strouse | 2019 | USA | cohort | 13,165 | 2921 | NA | 10,244 | NA | premature, congenital anomalies, LBW, SGA infant | 6 | |
Keeling | 2019 | Canada | cohort | 309,620 | 631 | 30.4 ± 5.6 | 308,989 | 29.3 ± 8.4 | cesarean delivery, gestational diabetes, hypertension | premature, SGA infant, birth weight, neonatal death within 30 days of birth, congenital anomaly | 5 |
Knudsen | 2019 | Denmark | cohort | 690,240 | 1026 | NA | 689,214 | NA | premature, birth weight | 6 | |
Nathan | 2019 | Denmark | cohort | 2,584,932 | 3749 | NA | 2,581,183 | NA | spontaneous abortion | 6 | |
Abdulrahman | 2020 | Egypt | cross-sectional | 300 | 200 | 37.84 ± 6.67 | 100 | NA | preeclampsia, gestational diabetes, cesarean delivery | LBW, paediatric ICU admission, congenital anomalies | 11 |
Bortoluzzi | 2020 | Italy | cohort | 6540 | 443 | 34 (31–37) | 6097 | 34 (30–37) | miscarriage and perinatal death | 5 | |
Knudsen | 2020 | Denmark | cohort | 738,862 | 934 | 30.01 ± 4.78 | 737,928 | 31.48 ± 4.67 | birth weight, LBW, premature, congenital abnormalities | 6 | |
Al Rayes | 2021 | Saudi Arabia | cohort | 327 | 77 | 32.78 ± 0.69 | 250 | 30.32 ± 0.84 | preeclampsia, spontaneous abortion, cesarean delivery | newborn weight, congenital abnormalities, stillbirth, preterm birth, NICU admission | 7 |
Yang | 2021 | China | case-control | 628,878 | 1188 | 29.1 ± 4.59 | 627,690 | 29.1 ± 4.59 | asthma | 5 | |
Park | 2022 | Korea | cohort | 27,675 | 1652 | 32.3 ± 3.8 | 26,023 | 31.8 ± 4.0 | preeclampsia, spontaneous abortion, cesarean delivery | premature, LBW | 6 |
Tarplin | 2022 | USA | cohort | 798 | 202 | 31 ± 5 | 596 | 27 ± 7 | preeclampsia, spontaneous abortion, cesarean delivery | premature, stillbirth | 5 |
Tsai | 2022 | China | cohort | 2,100,143 | 922 | 32.43 ± 4.42 | 2,099,221 | 30.18 ± 4.75 | preeclampsia, hypertension | stillbirth, LBW, premature, SGA infant, fetal abnormalities | 5 |
Singh | 2023 | USA | cohort | 13,516 | 1223 | NA | 12,293 | NA | preeclampsia, gestational diabetes, cesarean delivery | premature, LBW, SGA infant, Apgar score below 7, fetal abnormalities | 7 |
Raitio | 2023 | Finland | case-control | 1140 | 8 | NA | 1132 | NA | congenital anomalies | 6 | |
Bobircă | 2023 | Romania | case-control | 365 | 66 | 31.3 ± 4.4 | 299 | 29.2 ± 5.5 | cesarean delivery | premature, SGA, LBW | 7 |
Systematic review and meta-analysis of the association between maternal RA and adverse maternal/fetal outcomes
Outcomes | Number of studies | OR (95%CI) |
P
| I2 (%) |
---|---|---|---|---|
14 | 1.65 (1.53, 1.78) | < 0.001 | 13.4 | |
10 | 1.61 (1.25, 2.07) | < 0.001 | 72.0 | |
Study design | ||||
Cohort study | 1.43 (1.17, 1.75) | 0.001 | 63.9 | |
Case-control study | 10.52 (3.80, 29.12) | < 0.001 | NA | |
Cross-sectional study | 2.04 (0.40, 10.40) | 0.393 | 0.0 | |
Region | ||||
Europe | 5.05 (1.38, 18.54) | 0.015 | 80.5 | |
North America | 1.35 (1.14, 1.61) | 0.001 | 62.2 | |
Asia | 0.53 (0.05, 5.91) | 0.602 | NA | |
Africa | 2.02 (0.22, 18.32) | 0.532 | NA | |
6 | 0.66 (0.14, 3.14) | 0.597 | 99.2 | |
6 | 1.32 (1.21, 1.43) | < 0.001 | 25.8 | |
16 | 1.62 (1.43, 1.84) | < 0.001 | 87.9 | |
Study design | ||||
Cohort study | 1.63 (1.43, 1.86) | < 0.001 | 89.8 | |
Cross-sectional study | 1.34 (0.36, 4.93) | 0.663 | 85.2 | |
Case-control study | 1.44 (0.84, 2.46) | 0.183 | NA | |
Region | ||||
Europe | 1.97 (1.63, 2.38) | < 0.001 | 68.5 | |
North America | 1.60 (1.42, 1.80) | < 0.001 | 61.6 | |
Asia | 1.23 (1.14, 1.32) | < 0.001 | 0.0 | |
Africa | 2.51 (1.44, 4.38) | 0.001 | NA | |
2 | 1.64 (0.84, 3.20) | 0.146 | 69.6 |
Outcomes | Number of studies | OR/WMD (95%CI) |
P
| I2 (%) |
---|---|---|---|---|
22 | 1.57 (1.00, 2.48) | 0.052 | 98.8 | |
6 | 1.55 (1.17, 2.06) | 0.003 | 0.0 | |
13 | 1.48 (1.25, 1.75) | < 0.001 | 85.4 | |
Region | ||||
Europe | 1.55 (1.15, 2.09) | 0.004 | 53.9 | |
North America | 1.46 (1.12, 1.89) | 0.005 | 89.5 | |
Asia | 1.42 (1.01, 2.00) | 0.047 | 89.7 | |
7 | -135.10 (-244.27, -25.94) | 0.015 | 97.7 | |
Study design | ||||
Cohort study | -173.78 (-295.12, -52.43) | 0.005 | 98.2 | |
Case-control study | -23.25 (-330.96, 284.47) | 0.882 | 92.6 | |
Region | ||||
Europe | -71.64 (-146.99, 3.72) | 0.062 | 82.9 | |
North America | -162.00 (-235.49, -88.51) | < 0.001 | 78.6 | |
Asia | -342.59 (-362.97, -322.22) | < 0.001 | NA | |
12 | 1.73 (1.46, 2.06) | < 0.001 | 65.8 | |
Study design | ||||
Cohort study | 1.75 (1.46, 2.09) | < 0.001 | 72.2 | |
Case-control study | 1.16 (0.29, 4.57) | 0.833 | 66.4 | |
Cross-sectional study | 1.99 (0.72, 5.51) | 0.183 | NA | |
Region | ||||
Europe | 1.41 (0.87, 2.28) | 0.161 | 33.0 | |
North America | 1.80 (1.45, 2.25) | < 0.001 | 52.8 | |
Asia | 1.72 (1.19, 2.49) | 0.004 | 84.8 | |
Africa | 1.99 (0.72, 5.51) | 0.183 | NA | |
3 | 1.05 (0.71, 1.54) | 0.818 | 63.2 | |
4 | 1.93 (0.82, 4.56) | 0.133 | 56.0 | |
3 | 1.41 (0.76, 2.61) | 0.278 | 0.0 | |
12 | 1.24 (1.13, 1.37) | < 0.001 | 42.3 | |
2 | 1.70 (1.41, 2.06) | < 0.001 | 36.8 | |
2 | 1.23 (1.16, 1.30) | < 0.001 | 0.0 |
Systematic review and meta-analysis of the association between disease activity of RA and maternal/fetal outcomes
Outcomes | Number of studies | OR (95%CI) |
P
| I2 (%) |
---|---|---|---|---|
HAQ-DI (> 0.5 vs. ≤ 0.5) | ||||
2 | 1.34 (0.92, 1.96) | 0.131 | 0.0 | |
2 | 1.82 (1.12, 2.97) | 0.016 | 0.0 | |
2 | 3.06 (0.88, 10.66) | 0.078 | 55.0 | |
DAS28 (> 3.2 vs. ≤ 3.2) | ||||
2 | 2.29 (1.02, 5.15) | 0.044 | 0.0 | |
2 | 5.61 (2.20, 14.30) | < 0.001 | 17.8 | |
2 | 6.36 (0.18, 226.24) | 0.310 | 81.3 |
Sensitivity analysis and publication bias
Outcomes | Begg’s test | |
---|---|---|
Z |
P
| |
Preeclampsia | 0.66 | 0.511 |
Gestational diabetes | 0.72 | 0.474 |
Cesarean delivery | 0.05 | 0.964 |
Premature delivery | 1.64 | 0.102 |
SGA infant | 1.04 | 0.300 |
LBW | 0.89 | 0.373 |
Congenital abnormalities | 0.34 | 0.732 |