Biologics in pregnancy – for the obstetrician

Abstract

Key content The authors discuss commencing biologics in pregnancy and the potential side effects. Infection is a particular risk, which may be atypical or present atypically. While there is no evidence of teratogenicity, these drugs cross the placenta and neonatal cord drug levels may exceed those of maternal drug levels. If possible, anti‐tumour necrosis factor (TNF) agents should be discontinued midtrimester but the gestation to which each drug can be used is slightly different. Neonates exposed in utero to anti‐TNF agents beyond the recommended gestation should not be given live attenuated vaccines for the first 6 months of life and any infections promptly treated. Data are lacking on the long‐term effects of biologics on children exposed in utero. However, the benefits of controlling active autoimmune disease in the mother often outweigh the small risk to the exposed infants. Learning objectives To know the biologics most commonly used in pregnancy. To understand the literature regarding safety of the common biologics in pregnancy. To be able to counsel a woman taking a biologic about the potential benefits and risks of taking it at different gestations. To be able to counsel a woman receiving biologics in pregnancy about vaccinations for her baby after birth. Ethical issues Biologic agents are relatively new drugs that are being increasingly used in young women because of their perceived ‘fertility sparing’ benefits despite a lack of high quality evidence. Most women who have been prescribed biologics are often refractory to other treatments, and therefore these agents are required for disease control. The decision to continue or discontinue these drugs in pregnancy, especially late pregnancy, is particularly contentious. The long‐term effect of biologics on infants exposed in utero is not known and the decision to use these drugs has to be balanced against the risk of severe maternal flares.

Prescribing for pregnancy: inflammatory bowel disease

“…Biological drugs are IgG antibodies; IgA is the predominant immunoglobulin excreted in breast milk. The very low concentrations of anti-TNF molecules that may be present in breastmilk are unlikely to be absorbed orally or to result in neonatal immunosuppression, and studies assessing the effects of anti-TNF agents on breastfed infants have provided substantial reassurance 44 45. A prospective study found that breastfed infants of mothers receiving biologics (eg, infliximab, adalimumab and ustekinumab), immunomodulators or combination therapies had similar risks of infection and rates of milestone achievement at 12 months compared with non-breastfed infants or infants unexposed to these drugs 46.…”

The use of biologics for autoimmune rheumatic diseases in fertility and pregnancy

“…This review paper will endeavour to summarise the European League Against Rheumatism (EULAR) and British Society in Rheumatology (BSR) guidelines 2016 shown in Table 3 24,25,47 and focus on developments since publication of the guidelines. Supplementary Table 1.…”

“…However, basic physiology indicates that breastmilk is predominantly IgA (not IgG1); the large structure of most biologic molecules means that they are less likely to be excreted in breastmilk. Additionally, such large proteinaceous molecules are denatured and digested by passage through the infant's gastrointestinal tract and therefore do not attain significant levels in breastfed infants, 47 and hence why parenteral administration is necessary to achieve a therapeutic response. All breastmilk studies completed to date have borne this out by consistently showing a steady decline in breastfed infant drug levels despite ongoing maternal dosing.…”

The Contribution of Community Pharmacists to the Rational Management of Drug Use in Pregnancy: Practical Recommendations

“…Enfeksiyona meyil yaptığı da bilinen bu ilaçların kullanılması gereken durumlarda eczacının daha dikkatli olması gerekmektedir. 22 Gebelikte ilacın embriyo ve fetüs üzerine etkisi, maruz kalınan madde kadar gestasyon yaşı ile de ilişkilidir. 19 Örneğin; blastogenezis döneminde (fertilizasyondan yaklaşık 15-21 gün sonrası) ilacın etkisi "hep ya da hiç prensibi"ne göre gerçekleşmekte; bir başka deyişle embriyo ölmekte ya da etkilenmeden yaşamaya devam etmektedir.…”