Pregnancy in Rheumatology Patients Exposed to Anti-tumour Necrosis Factor (TNF)-α Therapy

C. H. Roux; O. Brocq; V. Breuil; C. Albert; L. Euller-Ziegler


Rheumatology. 2007;46(4):695-698. 

In This Article

Abstract and Introduction

Objectives: Anti-tumour necrosis factor (TNF)-α therapies are considered category B drugs for pregnancy. Although sometimes prescribed to women of reproductive age, data in humans are limited with regard to safety for a developing fetus. The objectives of the present article are to report experience of anti-TNF-α use in pregnancy, and review the international literature.
Methods: Since 1999 the present authors have used anti-TNF-α (infliximab, etanercept, adalimumab) to treat patients with various chronic rheumatic conditions. All patients were prospectively followed during their treatment time and data were systematically collected.
Results: In a group of 442 patients treated with anti-TNF, three women with RA unexpectedly became pregnant One treated with etanercept chose a therapeutic termination at two and a half months, despite of any ultrasound anomaly, and satisfactory fetal growth. The other two patients (one with adalimumab exposure and one with etanercept exposure) delivered healthy infants. The following perinatal complications were observed: prematurity, neonatal jaundice, neonatal urinary Escherichia coli infection and adrenal congenital hyperplasia of probable hereditary origin.
Conclusions: To date, there is no evidence that TNF-α antagonists are associated with embryo toxicity, teratogenicity or increased pregnancy loss. However, caution should be taken when anti-TNF agents are used during pregnancy, as human experience is still extremely limited, particularly in patients with rheumatic diseases among whom there are several alarming reports. The potential risk should be balanced against the known risks associated with DMARDs and steroid therapy. Large registries will be necessary before firm conclusions can be drawn.

Tumour necrosis factor (TNF)-α has an important role in pregnancy. Mouse models have shown it to be one of several cytokines with a potent modulatory effect on early development.[1] By inducing cyclo-oxygenase 2 gene expression in early pregnancy,[2] TNF-α controls cyclo-oxygenases, thereby affecting blastocyst implantation, endometrial vascular permeability and uterine deciduation. It plays a role in the induction of labour, in synergy with other inflammatory cytokines to induce uterine contractions.[3] Levels in amniotic fluid and serum are high at the onset of labour and in pathological conditions such as infection and fetal growth retardation. TNF-α production is low in the first gestational trimester, but increases thereafter, reaching a peak at the onset of labour.[3] It may mediate recurrent spontaneous abortion, and higher concentrations of serum TNF-α and of serum soluble TNF receptor 1 have been observed in women with unexplained early spontaneous abortion.[4] Anti-TNF-α is often prescribed to women of reproductive age who have rheumatological disorders, raising questions about its effect on pregnancy.


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