Anti-TNF levels in newbornsUC and CD · Pregnancy
Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection
Julsgaard M, et al.
Gastroenterology 2016 · PMID 27063728 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2016.04.002 (full paper, opens in a new tab)
| Measure | Adalimumab | Infliximab |
|---|---|---|
| Infant:mother drug ratio at birth, median (95% CI) (primary endpoint) | 1.21 (0.94–1.49) | 1.97 (1.50–2.43) |
| Time to clearance in infants, mean months (95% CI) (primary endpoint) | 4.0 (2.9–5.0) | 7.3 (6.2–8.3); P<0.0001 |
| Cord level vs time from last dose to delivery | r=−0.64; P=0.0003 | r=−0.77; P<0.0001 |
No drug was detected after 12 months of age; anti-TNF plus a thiopurine raised infant infection risk vs anti-TNF alone (RR 2.7, 95% CI 1.09–6.78).
Source: Julsgaard 2016, abstract. 80 mother–infant pairs (36 adalimumab, 44 infliximab); infants were tested every 3 months until drug was undetectable.
Structured abstract
BackgroundIgG antibodies such as infliximab and adalimumab cross the placenta, but how much reaches the newborn, how long it stays, and whether it causes infections were poorly defined.
MethodsProspective cohort study (tertiary hospitals in Denmark, Australia and New Zealand, 2012–2014); not randomised. 80 patients. Primary endpoint: Cord and infant drug concentrations, time to infant clearance, and infections in the first year of life.
ResultsPrimary result. Median infant:mother drug ratio at birth 1.21 (95% CI 0.94–1.49) for adalimumab and 1.97 (1.50–2.43) for infliximab. Mean time to clearance in infants 4.0 months (2.9–5.0) for adalimumab vs 7.3 months (6.2–8.3) for infliximab; P<0.0001. No drug detected after 12 months of age.
Take-homeAt birth, infliximab levels in the newborn are about twice the mother's and adalimumab levels are similar or slightly higher; both take months to clear (infliximab longest), which matters for live vaccines; combination with a thiopurine raised infant infection risk.
| Patients | 80 |
|---|---|
| Population | Pregnant women with IBD on adalimumab (36) or infliximab (44), 39 also on a thiopurine, and their infants. |
| Comparison | No control arm: drug levels in mothers at delivery, umbilical cord blood, and infants every 3 months until undetectable; infections compared by exposure (anti-TNF plus thiopurine vs anti-TNF alone). |
| Drugs | infliximab, adalimumab, azathioprine, mercaptopurine |
| Classes | Anti-TNF, Thiopurine |
| Published | Julsgaard M, et al. Gastroenterology 2016;151:110–9. |
Key points
- The longer the gap between the last dose in pregnancy and delivery, the lower the cord level (adalimumab r=−0.64, P=0.0003; infliximab r=−0.77, P<0.0001).
- Infections were mostly mild: bacterial in 4 infants (5%) and viral in 16 (20%), all with a benign course.
- Anti-TNF plus a thiopurine carried a higher relative risk of infant infection than anti-TNF alone: RR 2.7 (95% CI 1.09–6.78); P=0.02.
- The authors advised avoiding live vaccines for up to 1 year unless drug clearance was documented.
Limitations
- Small sample; infection outcomes were few and mostly mild.
- No unexposed comparison group.
- Only infliximab and adalimumab were studied.
Commentary
This study explains why infants exposed to biologics in utero need a vaccine plan. Because IgG antibodies are actively transported across the placenta in the second and third trimesters, infant drug levels at birth often exceed the mother’s and can persist for months.
It does not argue for stopping therapy: larger data from PIANO found no increase in infant infections with biologic exposure once preterm birth and disease activity were accounted for, and active disease harms both mother and baby. What it changes is planning: tell the paediatric team which drug was used and when the last dose was given.
Guidance on live vaccines after in utero biologic exposure (rotavirus in infancy, and BCG where it is used) has evolved since this study; check the current Canadian Immunization Guide and current IBD pregnancy guidance.
Journal club
Design
Prospective cohort study (tertiary hospitals in Denmark, Australia and New Zealand, 2012–2014); not randomised. 80 patients.
Primary result. Median infant:mother drug ratio at birth 1.21 (95% CI 0.94–1.49) for adalimumab and 1.97 (1.50–2.43) for infliximab. Mean time to clearance in infants 4.0 months (2.9–5.0) for adalimumab vs 7.3 months (6.2–8.3) for infliximab; P<0.0001. No drug detected after 12 months of age.
Validity and applicability
- Small sample; infection outcomes were few and mostly mild.
- No unexposed comparison group.
- Only infliximab and adalimumab were studied.
Where it sits now
At birth, infliximab levels in the newborn are about twice the mother's and adalimumab levels are similar or slightly higher; both take months to clear (infliximab longest), which matters for live vaccines; combination with a thiopurine raised infant infection risk.
- PIANO (2021): Biologics and thiopurines, alone or together, did not increase pregnancy or infant harms; active disease did, so continue effective therapy through pregnancy.
- Intestinal ultrasound in pregnancy (2025): In pregnancy, inflammation seen on intestinal ultrasound was associated with preterm birth, low birth weight and pre-eclampsia independently of symptoms and calprotectin; consider ultrasound to monitor IBD antenatally.
Questions for discussion
- Infant infliximab levels at birth were about twice maternal levels. What placental mechanism explains this, and why is transfer greatest late in pregnancy?
- Would you stop an anti-TNF in the third trimester to lower infant exposure, given what PIANO later showed about maternal disease activity?
- How would you plan rotavirus vaccination for an infant exposed to infliximab in utero, and when would an infant drug level help?