While pregnancy does not occur commonly while patients are in a pediatric gastroenterology practice, the possibility of becoming pregnant certainly influences our choice of medications. With inflammatory bowel disease (IBD), I rarely recommend methotrexate in young women due to its teratogenicity. With regard to the anti-TNF agents, there is less data available. Two recent studies add some insight into this issue.
The first study ((Clin Gastroenterol Hepatol 2013; 11: 318-21) followed 31 pregnancies in 28 women with IBD (2006-2011). 18 patients received infliximab (IFX) and 13 adalimumab (ADA). Most were receiving lower doses; only one IFX patient was receiving 10 mg/kg/dose and only two ADA patients were receiving weekly dosing. Levels of anti-TNF agents were measured from cord blood from 18 newborns (12 IFX, 6 ADA).
- 28 live births. 3 miscarriages (1 IFX, 2 ADA). No congenital malformations were noted.
- Mean cord IFX level was 6.4 mcg/mL. A level of 2.8 mcg/mL was noted in the early discontinuation group –stopping 10 weeks prior to delivery .
- Mean ADA level was 1.7 mcg/mL in five infants. One infant had an undetectable level. All mothers had stopped ADA at gestational week 22.
In the second study (Clin Gastroenterol Hepat 2013; 11: 286-92) there were 31 pregnant patients. Anti-TNF treatment: Certolizumab (CZP) (n=10), IFX (n=11), ADA (n=10). Serum levels were measured at birth in the mother, infant, and in cord blood. Then, levels were followed monthly until undetectable. Among women receiving IFX, two were receiving 10 mg/kg/dose. Women were identified through the Crohn’s Colitis Foundation of America Pregnancy IBD and Neonatal Outcomes (PIANO) Registry.
- IFX was detectable for 2-7 months postpartum (median interval prior to delivery and last dose was 35 days). Median IFX level in the cord was 160% that of the mother.
- ADA was detectable for at least 11 weeks in infant’s circulation (median interval prior to delivery and last dose was 5.5 weeks). Median ADA in the cord was 153% of the mother.
- Median CZP in the cord was 3.9% that of the mother.
- No congenital anomalies or complications were reported in any of the infants.
Bottomline from these studies:
Stopping these drugs after the second trimester lowers the level of these medications in the infant. This likely results in a lower likelihood of the infant developing an opportunistic infection but also results in a low risk for the mother of an IBD flareup. Certolizumab pegol has very low levels of placenta transfer.
- -J Am Acad Dermatol 2011; 65: 870. Death noted in infant whose mother took IFX after BCG vaccination.
- -J Crohns Colitis 2011; 5: 555-8. Low levels of IFX detected in infants from nursing mothers with IBD (1/200th of the maternal level in serum 2 to 3 days after infusion).
- -Clin Gastroenterol & Hep 2010; 8: 509. n=2377. Crohn dz assoc w prematurity but not birth defects.
- -Gastroenterol 2003;124: 9-17. Safety of 6-MP in pregnancy. n=155, at least 1 pregnancy. No adverse effect noted.
- -Clin Gastroenterol & Hepatology; 2006: 4: 1255. Infliximab crosses placenta but was not detected breastmilk.
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