February 15, 2012

Gout is characterized by recurrent attacks of acute inflammatory arthritis caused by crystals of uric acid deposited in joints, tendons, and surrounding tissues. About half of cases involve the big toe, but it can present as gouty tophi (a deposit of monosodium urate crystals in the joints, cartilage, bone, and throughout the body that may break out through the skin), kidney stones, or urate nephropathy.

Acute gouty arthritis is an uncommon condition in women of reproductive potential, as only about 10%-15% of cases involve women and it typically occurs after menopause (J. Rheumatol. 1994;21:1365-6). *A 2006 study from Britain described 158 subjects with a dominantly inherited disorder known as familial juvenile hyperuricemic nephropathy (Nucleosides Nucleotides Nucleic Acids 2006;25:1071-5). The disorder – characterized by hyperuricemia, gout, and potentially fatal renal disease – affects children, young women (some pregnant) and men equally. The gout drug allopurinol is the treatment of choice for this genetic metabolic disease.

By  Gerald G. Briggs, B.PHARM., FCCP

The incidence of gout during women’s childbearing years is 1.5 cases per 10,000 patient-years. Maternal gout may be associated with an increased risk of pregnancy complications and adverse outcomes. In a study of 473,529 women in Taiwan with singleton live births in 2001-2003, 4,361 (0.9%) had been diagnosed with gout in the 2 years before giving birth. In a subgroup of 3,261 subjects with a reliable diagnosis, gout significantly increased the risk of preeclampsia, preterm birth, cesarean delivery, low birth weight, and small-for-gestational age infants. However, the authors acknowledged that because of the large sample size and the small magnitude of the outcomes, the clinical relevance of their findings may be questionable. (Int. J. Gynaecol. Obstet. 2010;109:157-8). No mention was made of the agents used for gout treatment in their population.

There are currently five drugs that can be used to treat gout: allopurinol (Zyloprim), colchicine (Colcrys), febuxostat (Uloric), pegloticase (Krystexxa), and probenecid. All have a Food and Drug Administration pregnancy risk category C. A sixth agent, sulfinpyrazone (Anturane), a uricosuric agent, has been withdrawn from the market, but there are no reports describing its use to treat gout in pregnant women.

Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid. The human pregnancy data are limited but have not shown an association with developmental toxicity. In contrast, a 2011 case report described multiple structural defects in a newborn whose mother had taken allopurinol throughout pregnancy to prevent kidney stones. The defects were diaphragmatic hernia; unilateral microtia and absence of external auditory canal; micrognathia; microphthalmia; optic nerve hypoplasia; hypoplasia of the corpus callosum; unilateral renal agenesis; pulmonary agenesis; and cleft lip and palate. The authors suggested that the drug caused the defects, but a chromosome microdeletion/duplication syndrome could not be ruled out (Am. J. Med. Genet. Part A 2011;155:2247-52).

The occurrence of primary gout with gouty nephropathy is a rare complication. In one case, a woman with gout and a markedly decreased creatinine clearance (30-35 mL/min), was treated with allopurinol (300 mg/day) throughout gestation, and gave birth at 35 weeks to a healthy female infant. Although there is a high rate of recurrence immediately post partum, the woman had no recurrence of gout during or after pregnancy. This is consistent with the increased incidence of gout flares in postmenopausal woman and during menses (Am. J. Obstet. Gynecol. 1979;133:107-8).

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