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).

Results:

• 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.

Results:

• 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.

Related references:

• -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.