Three years after her diagnosis with CD, the patient was discovered to be pregnant with her second child. The patient was successfully treated with mesalamine and infliximab when she was discovered to be 12 wk pregnant. The patient was informed that her disease could potentially worsen, nutritional deficiencies could develop, and that her medications could be potentially harmful to the fetus. The patient understood the risks and decided to proceed with the pregnancy after multiple discussions regarding the side effects and potential teratogencity of her medications. She continued to take daily mesalamine and received a total of six doses of infliximab during her pregnancy with the last infusion occurring approximately 2 wk before delivery.

A healthy male infant weighing 7 pounds 6 ounces was born at thirty-nine weeks’ gestation by an uncomplicated caesarian birth. The patient desired to breastfeed the infant while continuing to receive her mesalamine and infliximab. Again, the potential dangers of her medications were discussed with particular emphasis on their impact on breastfeeding. After taking the discussion under advisement, the patient decided to attempt to begin breastfeeding and to continue treatment with infliximab.

Infliximab (Remicade; Centocor Inc, Malvern, PA) is a chimeric monoclonal antibody to tumor necrosis factor-alpha (TNF-α)[⁴]. It is indicated for inducing and maintaining clinical remission in moderately to severely active CD and UC patients that have had an inadequate response to conventional therapy and maintenance of remission[⁵]. Infliximab is increasingly used to treat pregnant women and data on its safety during pregnancy are scarce. Infliximab is listed as a pregnancy category B medication and the product label states that “It is not known whether infliximab can cause fetal harm when administered to a pregnant woman[⁴]”. Most clinicians believe that the chimeric structure of the infliximab molecule containing a human IgG1 constant region, limits placental transfer during the first trimester[⁶]. However, the safety of infliximab beyond the first trimester is unknown because IgG subclasses are readily passed into the fetus during the second and third trimesters[⁷]. Until recently, the medical literature contained no evidence that engineered therapeutic antibodies could cross the placenta when administered to expectant mothers. A recent case report documents clinically significant fetal exposure to infliximab via placental transfer and a prolonged half-life of the medication in newborns[²]. The presumed mechanism of fetal exposure to infliximab is transplacental maternal IgG antibody transfer beginning in the second trimester and peaking at term. No fetal abnormalities were apparent in this case, but the long-term implications of infliximab exposure during early childhood development are unknown. These findings suggest that pregnant patients should avoid therapeutic antibody treatments after thirty weeks’ gestation and if necessary, the expectant mother can be bridged with steroids to control the disease activity until delivery[^2,8].

Limited clinical data are available on the safety of infliximab in pregnancy, because no controlled study is available in pregnant women. The manufacturer’s safety database contains information on the outcomes of 131 pregnant women who received infliximab for rheumatoid arthritis or IBD[⁹]. An analysis performed on this safety database suggests no significant difference in pregnancy outcomes in women with infliximab exposure[⁷]. A published retrospective review of 10 pregnancies in CD patients in which infliximab was continued throughout the course of the pregnancy reported favorable fetal and maternal outcomes[⁷]. The limited clinical results available suggest that the benefits of infliximab in attaining response and maintaining remission in pregnant IBD patients might outweigh the risks of drug exposure to the fetus[¹⁰].

The primary concern of the case we report is the safety of infliximab while breastfeeding, because many drugs and immunoglobulins are excreted in human milk. The infliximab product label states that “It is not known whether infliximab is excreted in human milk or absorbed systemically after ingestion[⁴]”. A commercially available infliximab assay was used to measure drug levels in breast milk taken daily from our patient over a 30 d time period. No infliximab was detected in our patient’s breast milk. Other published reports only tested breast-feeding mothers for one or two days but the results were consistent with our data[²]. We believe the daily testing performed on our patient’s breast milk before and immediately after receiving an infliximab infusion clearly demonstrates that infliximab is not excreted in breast milk in any clinically significant amount.

Several case reports have recently emerged describing the off-label usage of other biologics during pregnancy. A pregnant woman with treatment-refractory CD who failed treatment with infliximab was successfully treated with adalimumab (Humira; Abbott Laboratories, Chicago, IL), a recombinant human IgG1 monoclonal anti-TNF antibody[^11,12]. The pregnancy was uncomplicated and at 6 mo, the infant showed normal growth and develo-pment[¹³]. Another case reported the use of etanercept (Enbrel; Amgen, Thousand Oaks, CA), a soluble TNF receptor fusion protein that binds to and inactivates TNF, in an uneventful pregnancy of a patient with refractory rheumatoid arthritis[¹⁴]. Etanercept has been shown to be excreted in breast milk, but it is not known whether the drug can be absorbed orally because it is such a large protein[¹⁵].