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Meta-Analysis
. 2022 Jul;129(8):1236-1246.
doi: 10.1111/1471-0528.17093. Epub 2022 Feb 16.

Fetal and maternal outcomes after maternal biologic use during conception and pregnancy: A systematic review and meta-analysis

Laura J O'Byrne  1   2 , Safi G Alqatari  3 , Gillian M Maher  1   4 , Aoife M O'Sullivan  3 , Ali S Khashan  1   4 , Grainne P Murphy  3 , Fergus P McCarthy  1   2
Affiliations
Meta-Analysis

Fetal and maternal outcomes after maternal biologic use during conception and pregnancy: A systematic review and meta-analysis

Laura J O'Byrne et al. BJOG. 2022 Jul.

Abstract

Background: Biologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy.

Objective: To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy.

Search strategy: PubMed and EMBASE databases were searched through January 1998-July 2021.

Selection criteria: Peer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data.

Data collection and analysis: Two authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence.

Main results: Thirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; I2 = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I2 = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I2 = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I2 = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I2 = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I2 = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I2 = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I2 = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I2 = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I2 = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I2 = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I2 = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low.

Conclusion: We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.

Keywords: medical disorders in pregnancy; systematic reviews.

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Conflict of interest statement

None declared. Completed disclosure of interests form available to view online as supporting information.

Figures

FIGURE 1
FIGURE 1
Metaprop proportions for congenital malformations
FIGURE 2
FIGURE 2
Metaprop proportions of preterm delivery with anti‐tumour necrosis factor‐α (TNF‐α) use only
See this image and copyright information in PMC

Comment in

References

    1. Maniadakis N, Toth E, Schiff M, Wang X, Nassim M, Szegvari B, et al. A targeted literature review examining biologic therapy compliance and persistence in chronic inflammatory diseases to identify the associated unmet needs, driving factors, and consequences. Adv Ther. 2018;35(9):1333–55. 10.1007/s12325-018-0759-0. - DOI - PMC - PubMed
    1. Jacobs P, Bissonnette R, Guenther LC. Socioeconomic burden of immune‐mediated inflammatory diseases – focusing on work productivity and disability. J Rheumatol. 2011;38(Suppl 88):55–61. 10.3899/jrheum.110901. - DOI - PubMed
    1. Tsao NW, Lynd LD, Sayre EC, Sadatsafavi M, Hanley G, De Vera MA. Use of biologics during pregnancy and risk of serious infections in the mother and baby: a Canadian population‐based cohort study. BMJ Open. 2020;29(3):316–27. 10.1136/bmjopen-2018-023714. - DOI - PMC - PubMed
    1. Bröms G, Kieler H, Ekbom A, Gissler M, Hellgren K, Lahesmaa‐Korpinen A‐M, et al. Anti‐TNF treatment during pregnancy and birth outcomes: a population‐based study from Denmark, Finland, and Sweden. Pharmacoepidemiol Drug Saf. 2020;29(3):316–27. 10.1002/pds.4930. - DOI - PubMed
    1. Kvien TK, Uhlig T, Ødegård S, Heiberg MS. Epidemiological aspects of rheumatoid arthritis: the sex ratio. Ann N Y Acad Sci. 2006;1069(1):212–22. 10.1196/annals.1351.019 - DOI - PubMed

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