Unilateral Renal Agenesis and Urethral Atresia Associated with Ergotamine Intake during Pregnancy

Abstract

Ergotamine, an ergot alkaloid, used for the treatment and prevention of migraine attacks, is considered as a teratogenic drug and, therefore, should be avoided in pregnancy. Here, we report a newborn infant with unilateral renal agenesis, urethral atresia, and pulmonary hypoplasia associated with the use of ergotamine for the treatment of migraine attacks at early pregnancy. Genitourinary anomalies in association with ergotamine usage were rarely reported and this was the third case of renal agenesia in association with ergotamine usage in literature. We suggest that ergotamine teratogenicity may be dose dependent and should be avoided in pregnancy for the possibility of genitourinary anomalies.

• ergotamine
• renal agenesis
• urethral atresia

INTRODUCTION

Ergotamine is an ergot alkaloid that leads to vasoconstriction of vascular beds and mainly used for the treatment and prevention of migraine headaches and sometimes for the treatment of uterine bleeding.¹ It is considered as a teratogenic drug and therefore should be avoided in pregnancy. Reports of teratogenic effects depend on vasospasm, including cleft palate and limb, intestinal atresia, Poland sequence, neural tube defects, and preterm birth. An association between ergotamine use during the second and third gestational month and neural tube defects has been reported.^1,2 To the best of our knowledge, renal agenesis/dysgenesis due to ergotamine usage during pregnancy have been reported only in two patients in literature. Here, we report a newborn infant with unilateral renal agenesis, urethral atresia, and pulmonary hypoplasia as a result of ergotamine use for the treatment of migraine attacks at pregnancy.

CASE REPORT

A female infant was born at gestational week 32 with cesarian section as a result of fetal distress. Birth weight was 2130 g and head circumference 30 cm. Apgar scores were 7 and 9 after 1 and 5 minutes, respectively. Soon after the delivery, she had a mild respiratory distress, retractions, and grunting, and she was transported to our neonatal intensive care unit. We performed continuous nasal positive airway pressure. Physical examination of the patient was normal for any dysmorphic signs (Figure 1). As respiratory distress depressed, she was intubated and lung graphy showed pulmonary hypoplasia. Echocardiography was performed and did not show any major congenital anomaly, but only hypertrophy of left ventricle and large ductus arteriosus. History revealed that she was the third child of nonconsangious parents without family history and that anhydramnios was present in utero and fetal ultrasonography showed agenesis of right kidney and hydronephrosis of the left one. Her mother had used several doses of Avmigran® (including paracetamol 325 mg, ergotamine tartrate 0.75 mg, caffeine 80 mg, and mecloxamine citrate 20 mg) for migraine attacks at the first trimester of the pregnancy, daily, especially at the second to fourth week of gestation. The dosage of the inotropic agents was increased. Urethral catheterization was tried because of anuria but there was no urethral orifice. Renal ultrasonography showed agenesis of the right kidney and enlargement of the left renal pelvis to 10 mm. At the 13th hour of her life, cardiopulmonary arrest developed and she had no response to resuscitation. We could not perform any autopsy as her parents did not permit. The results of the chromosomal evaluations were normal.

Figure 1. Physical appearance of the patient.

DISCUSSION

Ergotamine in combination with caffeine, paracetamol, and mecloxamine is used for prevention and treatment of migraine attacks. Ergot alkaloids are contraindicated during pregnancy. A recent study by Bánhidy et al.³ reported an association between ergotamine exposure during pregnancy and low birth weight and preterm births, probably related to the ergotamine-induced vasoconstriction in the placenta. Similarly, animal studies on offspring of pregnant mice, rats, and rabbits showed a reduction in fetal weight.⁴ Hughes et al.⁵ reported a case with birth defects like arrested cerebral maturation and paraplegia, following maternal exposure to ergotamine, beta blockers, and caffeine and they hypothesized that ergotamine produced fetal vasoconstriction resulting in tissue ischemia and subsequent malformation.

The components of Avmigran® beyond ergotamine were shown to have no teratogenic effects.⁶ Acs et al.² evaluated a different preparation of ergotamine than ours, containing ergotamine 0.3 mg, caffeine, aminophenazone, and belladonna leaf (Kephalin®), and they stated that the use of this drug combination did not associate with an increased general risk of congenital abnormalities (OR with 95% CI: 1.5, 0.8–2.8). But among 20 cases with congenital abnormalities of pregnant women with this treatment, 2 had renal a/dysgenesis after the treatment with Kephalin in the second and/or third month of gestation (OR with 95% CI: 68.8, 7.8–605.8). They considered this association as a signal; however, they did not find an association of the higher dose of ergotamine (estimated daily dose of ergotamine drops was 1.5 mg) with a higher general risk of congenital abnormalities (OR with 95% CI: 0.7, 0.5–1.2). But among these 24 cases, 5 had neural tube defects (OR with 95% CI: 6.9, 2.0–24.2). Czeizel⁷ showed an association of ergotamine with higher risk of neural tube defects, thus the main message of Acs et al.’s paper was the confirmation on the association of larger doses of ergotamine with neural tube defects.

In this report, we present a newborn baby with unilateral renal agenesis, urethral atresia, and pulmonary hypoplasia whose mother used ergotamine at a higher dose (1.5 mg/d) in the first trimester of her pregnancy. Genitourinary anomalies in association with ergotamine usage were rarely reported and this was the third case of renal agenesia in association with ergotamine usage in literature. We suggest that ergotamine teratogenicity may be dose dependent and should be avoided during pregnancy for the possibility of genitourinary anomalies.

Declaration of interest:The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.