Children of mothers treated with adalimumab or infliximab for inflammatory bowel disease should have any live vaccines delayed until they are at least 12 months old, Australasian research concludes.
Among 80 mothers and their children, cord blood levels of adalimumab at birth were 21% higher than the mothers’ blood levels, and levels of infliximab were 97% higher.
It took an average of four months for the infants to clear adalimumab and 7.3 months for infliximab, with no drug detected in any child after 12 months.
“Live vaccines should therefore be avoided for up to 1 year, unless drug clearance is documented, and pregnant women should be educated on risks of anti-TNF use,” the research team wrote in Gastroenterology.
Current international guidelines recommend that live vaccines, including MMR, rotavirus, oral polio and varicella, be avoided only for the first six months.
The recommendation came under scrutiny when a 4 month-old child whose mother was treated with infliximab died after a BCG vaccination.
The study was conducted at tertiary centres in Denmark, Christchurch, Brisbane, Sydney, Melbourne, Adelaide and Perth between March 2012 and November 2014.
Adalimumab and infliximab levels were measured in the mother and cord blood at birth, then every three months in the infants until they were no longer detectable.
“Because IBD incidence peaks in the second and third decades, anti-TNF exposure is common during the reproductive years,” the team said.
“IBD has no particular gender predilection, and women with IBD commonly wish to bear children, regardless of anti-TNF treatment. Knowledge of its safety therefore remains a key issue.”
Maternal clinical remission in IBD is highly desirable, as active IBD increases the risk of prematurity, low birth weight, small for gestational age, and low APGAR scores.
Studies of antenatal exposure to TNF inhibitors had generally been reassuring, showing no increase in adverse neonatal outcomes including congenital malformations, but much less was known about rates of drug clearance and its implications.
Elevated levels of the drugs in the babies at birth reflected fetal accumulation as pregnancy progressed, and levels at birth reflected the time since the last treatment.
However, it was not possible to reliably predict when treatment should be stopped during pregnancy to predict undetectable levels at birth. In fact, most women continued treatment into their third trimester, reflecting the severity of their disease.
“Breastfeeding did not affect anti-TNF clearance, adding evidence to the lack of any significant transfer of drug to the breast milk,” they said.
“These results underpin the advice to women to continue breastfeeding on anti-TNF treatment.”