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The use of anti-VEGF agents in pregnancy

Eye (2024)Cite this article

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The use of anti-vascular endothelial growth factor (VEGF) agents in pregnancy is a concern. VEGF plays an important role in embryogenesis [1,2,3], has an essential role in normal pregnancy (e.g. implantation/placentation) and has been implicated in several obstetric complications (pre-eclampsia, miscarriage, intrauterine growth restriction, preterm delivery) [4, 5]. Drug manufacturer and regulator advice is to avoid anti-VEGF use in pregnancy unless the benefits outweigh the risks of treatment. This risk-benefit analysis is complex and emotionally fraught, compounded by the lack of adequate human studies.

Ong et al. recently reviewed the available clinical literature on the experience of using intravitreal anti-VEGF agents in pregnancy [6]. The available evidence comprises case reports and case series. The total number of patients was low (42 pregnancies in 41 women). Their comprehensive review is reassuring in that most pregnancies were uncomplicated and adverse pregnancy outcomes only occurred in patients with pre-existing risk factors for obstetric complications. An important point to highlight is that there have been no reported cases of foetal malformations where the mother received intravitreal anti-VEGF injections during pregnancy.

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References

  1. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435–9.

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380:439–42.

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Haigh JJ. Role of VEGF in organogenesis. Organogenesis. 2008;4:247–56.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Andraweera PH, Dekker GA, Roberts CT. The vascular endothelial growth factor family in adverse pregnancy outcomes. Hum Reprod Update. 2012;18:436–57.

    Article  CAS  PubMed  Google Scholar 

  5. Andraweera PH, Dekker GA, Laurence JA, Roberts CT. Placental expression of VEGF family mRNA in adverse pregnancy outcomes. Placenta. 2012;33:467–72.

    Article  CAS  PubMed  Google Scholar 

  6. Ong AY, Kiire CA, Frise C, Bakr Y, de Silva SR. Intravitreal anti-vascular endothelial growth factor injections in pregnancy and breastfeeding: a case series and systematic review of the literature. Eye. 2023:1–3. https://doi.org/10.1038/s41433-023-02811-6.

  7. Pentšuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res Part B Dev Reprod Toxicol. 2009;86:328–44.

    Article  Google Scholar 

  8. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007;7:715–25.

    Article  CAS  PubMed  Google Scholar 

  9. Brambell FW, Hemmings WA, Oakley CL. The relative transmission of natural and pepsin-refined homologous antitoxin from the uterine cavity to the foetal circulation in the rabbit. Proc R Soc Lond Ser B Biol Sci. 1959;150:312–7.

    ADS  CAS  Google Scholar 

  10. Miller RK, Mace K, Polliotti B, DeRita R, Hall W, Treacy G. Marginal transfer of ReoPro™(Abciximab) compared with immunoglobulin G (F105), inulin and water in the perfused human placenta in vitro. Placenta. 2003;24:727–38.

    Article  CAS  PubMed  Google Scholar 

  11. Mariette X, Förger F, Abraham B, Flynn AD, Moltó A, Flipo RM, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77:228–33.

    Article  CAS  PubMed  Google Scholar 

  12. FDA – USA. Faricimab prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf.

  13. Firan M, Bawdon R, Radu C, Ober RJ, Eaken D, Antohe F, et al. The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of γ-globulin in humans. Int Immunol. 2001;13:993–1002.

    Article  CAS  PubMed  Google Scholar 

  14. Avery RL, Castellarin AA, Steinle NC, Dhoot DS, Pieramici DJ, See R, et al. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina. 2017;37:1847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Krohne TU, Liu Z, Holz FG, Meyer CH. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. Am J Ophthalmol. 2012;154:682–6.

    Article  CAS  PubMed  Google Scholar 

  16. Carneiro ÂM, Costa R, Falcão MS, Barthelmes D, Mendonça LS, Fonseca SL, et al. Vascular endothelial growth factor plasma levels before and after treatment of neovascular age‐related macular degeneration with bevacizumab or ranibizumab. Acta Ophthalmol. 2012;90:e25–30.

    Article  CAS  PubMed  Google Scholar 

  17. Zehetner C, Kirchmair R, Huber S, Kralinger MT, Kieselbach GF. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol. 2013;97:454–9.

    Article  PubMed  Google Scholar 

  18. European Medicines Agency – European Public Assessment Report. Vabysmo. 2022; 101. https://www.ema.europa.eu/en/documents/assessment-report/vabysmo-epar-public-assessment-report_en.pdf.

  19. FDA – USA. Bevacizumab toxicology data. 2004. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/STN-125085_Avastin_Toxr.pdf.

  20. FDA – USA. Aflibercept review. 2019 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/125387Orig1s061.pdf.

  21. European Medicines Agency – European Public Assessment Report Variation. Lucentis. 2011 https://www.ema.europa.eu/en/documents/variation-report/lucentis-h-c-715-ii-0020-epar-assessment-report-variation_en.pdf.

  22. FDA – USA. Faricimab pharmacology/toxicology review. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/761235Orig1s000PharmR.pdf.

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Authors and Affiliations

  1. Cwm Taf Morgannwg University Health Board, Ysbyty Cwm Rhondda, Llwynypia, CF40 2LX, UK

    Kevin Gallagher & Ahmed Bilal

  2. Aneurin Bevan University Health Board, Newport, UK

    Ffion Brown

  3. Betsi Cadwaladr University Health Board, Bangor, UK

    Ahmed Al-Janabi

  4. St Thomas’ Hospital London, London, UK

    Nigel Davies

Authors
  1. Kevin Gallagher
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  2. Ffion Brown
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  3. Ahmed Bilal
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  4. Ahmed Al-Janabi
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  5. Nigel Davies
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Contributions

KG conceived the work, KG/FB/AB/AJ acquired data, all authors reviewed/interpreted data, KG/FB/AB/AJ contributed to drafting the manuscript. KG/ND revised the manuscript. All authors approved the final version and agree to be accountable for all aspects of the work.

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Correspondence to Kevin Gallagher.

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Gallagher, K., Brown, F., Bilal, A. et al. The use of anti-VEGF agents in pregnancy. Eye (2024). https://doi.org/10.1038/s41433-024-02992-8

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