No Long-Term Safety Issues Associated with Exposure to Anti-TNF-alpha Agents in utero

A small Italian study found no evidence that use of anti-TNF-alpha agents during pregnancy affects the health or development of children in their first 2 years of life.

Researchers followed 24 children whose mothers had used such medications to treat chronic arthritides during pregnancy and 24 children whose comparably ill mothers had avoided the drugs. They compared the children at birth and then compared their growth, health, response to vaccinations and achievement of developmental milestones.

“No differences in birth parameters, congenital malformations, and developmental steps in the first 24 months of life were found between cases and controls. Growth parameters were within the curves of the general population,” the researchers wrote in a study abstract presented at the 2015 Congress of the European League Against Rheumatism.

“No relevant infectious diseases nor post-vaccine complications were noted in the 6 children exposed to anti-TNF-alfa during the 2nd-3rd trimester of gestation. Neurodevelopmental problems were recorded in 2 children: an autism spectrum disorder in one male exposed to etanercept in the 2nd-3rd trimester and a language delay in a male control. Globally, the long-term follow-up of children supports the safety of use of anti-TNF-alfa agents, either preconceptionally or during the 2nd-3rd trimester of pregnancy.”

Children from the study and control groups were comparable in gestation (mean, 38 weeks; interquartile range [IQR] 37-39 weeks vs. mean, 39 weeks; IQR 38-40 weeks), birth weight (mean, 3,118 g; IQR, 2,745-3,471 g vs. mean, 3,260 g; IQR 3,080-3,735), birth length (mean, 49 cm; IQR 48-51 cm vs. mean, 50 cm; IQR, 49-52 cm) and head circumference at birth (mean, 35 cm; IQR, 33-36 cm vs. mean, 34 cm; IQR 34-36 cm).

Children from both groups grew at the same rate. Mean weight at 24 months was 12,750 grams in the study group (IQR, 10,500-13,603 g) and 12,000 grams in the control group (IQR, 11,313-13,150 g). They were also, on average, about the same age when they learned to sit up (6 months, IQR, 6-7 months for both groups), learned to walk (12 months, IQR, 11-13 months vs. 13 months; IQR 12-14 months) and learned to speak simple sentences (16 months; IQR, 13-18 months vs. 18 months; IQR, 12-20 months).

Pathological conditions were comparable at birth and during the first year of life.

There was some concern that exposure in uteroto drugs that suppress the immune system might alter responses to vaccinations, but children in the study group underwent vaccination without any severe reactions. The vaccinations, moreover were effective. Only 1 child developed chicken pox after being vaccinated against it, a child who was exposed to etanercept in the first trimester of pregnancy.

The researchers did note that their study group was not only small but also heterogeneous. Only 1 study group child was exposed to certolizumab and only 3 were exposed to adalimumab. The other 20 were exposed to etanercept. Exposure timing varied as well. Only 6 of the study group children were exposed during the second or third trimester of pregnancy. The other 18 were exposed early in the first trimester, before their mothers realized they were pregnant.