Thirty studies were included in the review. There were 13 small cohorts (between 4 and 515 (exposed) women in each cohort), 13 case reports (ranging between 1 and 14 cases), one randomised controlled trial (RCT; n=20), one large cohort study (n=19,429) and 2 large case-control studies.
Hydroxychloroquine and chloroquine (8 studies).
One RCT (n=20) comparing hydroxychloroquine with placebo, 2 controlled cohorts (165 exposed and 114 control) exposed to hydroxychloroquine, 3 cohorts (52 pregnancies in total) exposed to hydroxychloroquine, and 2 cohorts (48 pregnancies) exposed to hydroxychloroquine or chloroquine, failed to find an increased risk of congenital malformations.
Methotrexate (13 studies).
Two cohorts (n=38) and 24 case reports of pregnancies exposed to methotrexate reported 12 incidences of minor and major abnormalities. In total, there were 10 terminated pregnancies (of which three had abnormalities) and 12 spontaneous abortions.
Sulfasalazine (3 studies).
One case-control study (22,865 malformations and 38,151 health controls) and a birth registry (n=576,873) reported no significant association between sulfasalazine and malformations. One case report of a neonate with holoprosencephaly born to a woman undergoing continuous treatment with sulfasalazine before and during pregnancy was also identified.
Azathioprine and mercaptopurine (6 studies).
cohort (n=19,429) of which 13 pregnancies were exposed to azathioprine or mercaptopurine, one cohort (n=39) exposed to mercaptopurine, and one case report of azathioprine reported 8 minor or major malformations including 1 death. There were 4 terminations, 9 miscarriages, 1 neonatal death and 2 foetal deaths/losses reported amongst women exposed to azathioprine or mercaptopurine.
There were no significant data on the use of other DMARDs for antirheumatic treatment in pregnancy.