Risk of adverse pregnancy outcomes prior to the onset of an autoimmune rheumatic disease: a systematic review

OBJECTIVES: An increased risk of adverse maternal and fetal pregnancy complications including pre-eclampsia, intrauterine growth restriction and small for gestational age, is well-described in women with autoimmune rheumatic disease (ARD) compared with the general population (GP). It is less clear however, whether this risk of adverse pregnancy outcome (APO) also exists in women with "preclinical ARD" (preARD) before they are diagnosed with an ARD many years post-partum. Therefore, we have undertaken a systematic review of available evidence on APO in patients who subsequently were diagnosed with a rheumatic disease to identify whether there is an increased risk in preARD. METHODS: The present study was reported in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using the online PubMed database. PreSLE and preRA patients were defined as those who, over the subsequent years, developed Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA) according to international classification criteria. RESULTS: A total of 176 articles were screened and 27 original articles selected for final analysis. PreRA was the most studied group with 15 studies of > 1600 pregnancies and preSLE was the second most studied preARD in pregnancy with 14 studies of > 1000 pregnancies. We found that patients who subsequently develop SLE have an increased burden of poor pregnancy outcomes compared with pregnant women from the GP but less APO compared with SLE pregnancies. In contrast, a similar rate of APO was found when preRA were compared with GP pregnancies. CONCLUSION: Our findings of an increased risk of APO in certain preARD highlights the relevance of an obstetric history during the first rheumatology appointment and the need for novel screening strategies to predict APO. Further research is required to elucidate the immune basis of adverse pregnancy outcomes in preclinical and clinical ARD

A systematic review of live vaccine outcomes in infants exposed to biologic disease modifying anti-rheumatic drugs in utero

OBJECTIVES: Transplacental passage of certain biologic- and targeted synthetic DMARDs leads to detectable levels in the neonate, which may impact on the safety of live vaccines. Guidelines advise delaying live vaccine administration in biologic exposed infants until they are 7 months old. METHODS: A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in infants exposed to biologic or targeted synthetic DMARDs in-utero. RESULTS: Studies included 276 in-utero exposures to adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and ustekinumab. Live vaccine exposures <12 months of age included BCG (n = 215), rotavirus (n = 46) and MMR (n = 12). We identified no reactions following MMR, 7 mild reactions to rotavirus vaccination, and 8 reactions to BCG including one death. All infants with an adverse reaction to BCG had been exposed to infliximab in-utero, and 6 had received BCG in the first month of life. A freedom of information request to the Medicines and Healthcare products Regulatory Agency revealed 4 fatal disseminated BCG infections in infants exposed to TNF inhibitors in-utero, including infliximab, adalimumab and one unspecified TNF inhibitor. CONCLUSION: Most evidence for clinically harmful effect was for early administration of the BCG vaccine to infants exposed in-utero to TNF inhibitors with high transplacental transfer rates