Introduction

Galactorrhea in the newborn (sometimes referred to as ‘witch's milk’) was first described in the medical literature in the seventeenth century.1 It is a common condition and is seen in ∼5 to 6% of term infants with no gender preponderance.2 This condition is considered physiologic, secondary to withdrawal from maternal hormones after birth. Most of these infants present during the first week of life (between the fifth and seventh days of life) followed by a spontaneous resolution in a few weeks.3 Galactorrhea is uncommon in infants beyond 3 months of age. We describe a 3½-month-old infant who developed galactorrhea in the neonatal intensive care unit (NICU) after metoclopramide therapy.

Case

A term male neonate, with trisomy 21, with patent ductus arteriosus, stridor, and feeding intolerance was evaluated by a pediatric otorhinolaryngologist at 40 days of age. Laryngomalacia, glottic edema, and erythema were observed on flexible laryngoscopy. He was suspected to have gastroesophageal reflux-induced irritation of the airway, and was treated with metoclopramide at 0.15 mg kg−1 per dose every 8 h for 45 days. He underwent surgical closure of a patent ductus arteriosus at 1 month of life. His stay in the NICU was prolonged because of his poor ability to tolerate oral feeds and stridor. Owing to persistent stridor and respiratory distress, he was started on lansoprazole at 1.5 mg kg−1 per dose every 24 h and his metoclopramide dose was increased to 0.2 mg kg−1 per dose every 6 h (maximum dose in the standard pediatric reference handbook4). There was no improvement in the symptoms despite the escalation of metoclopramide dosage. He underwent an emergent tracheostomy at 3 months of age due to his deteriorating respiratory status because of subglottic narrowing. He was continued on metoclopramide to enhance gastric emptying. Two weeks after treatment with metoclopramide at 0.8 mg kg−1 per day, he was noted to have prominent breasts (asymmetric gynecomastia, right greater than left) with milk discharge. Endocrine work-up showed a normal thyroid profile (T4 1.67 ng per 100 ml, TSH 5.24 IU ml−1). Serum HCG (negative), estradiol (<20 pg ml−1), FSH (4.6 mIU ml−1), and LH (7 mIU ml−1) were within normal limits. Scrotal ultrasound was normal with both testes present. Serum prolactin level was elevated at 56.8 ng ml−1 (normal range—0.5 to 30 ng ml−1). When this report was received, a repeat prolactin level was checked immediately and was again high at 64.4 ng ml−1. Metoclopramide was discontinued. Gynecomastia and galactorrhea resolved within 1 week. Repeat prolactin level was within normal limits (20.6 ng ml−1) 2 weeks after discontinuing metoclopramide.

Discussion

Lactation, as opposed to breast gland proliferation, is inhibited during pregnancy by high levels of the circulating progesterone. Progesterone withdrawal occurs around the time of delivery in association with a continuing increase in prolactin levels, which initiates milk secretion in the mother.5 These changes in maternal hormones may result in bilateral breast hypertrophy and galactorrhea in infants. Prolactin levels are elevated markedly in cord blood at 170 ng ml−1 compared with adults (<20 ng ml−1) and are declined by >60% in the first week after birth.6, 7

The regulation of prolactin is unique because it is secreted consistently unless it is inhibited actively by dopamine (also called the prolactin inhibitory factor), which is produced by neurons in the hypothalamus.8 Dopamine antagonists may result in increased serum levels of prolactin. Metoclopramide is a dopamine antagonist and is used commonly as a prokinetic drug to treat gastroesophageal reflux disease in infants.9, 10, 11 Its gastrointestinal smooth muscle stimulatory effects are related to its ability to antagonize the inhibitory neurotransmitter dopamine and to augment acetylcholine release. In adults, metoclopramide has been reported to cause gynecomastia and galactorrhea from hyperprolactinemia.12 In fact, it is prescribed to improve faltering milk production in mothers of premature infants.13

The efficacy of metoclopramide with a dose range of 0.1–0.3 mg kg−1 per dose in gastroesophageal reflux has been studied in infants.14, 15 Two recent reviews have concluded that evidence for the safety and the efficacy of metoclopramide in infants for gastroesophageal reflux is inconclusive.9, 16 The only other case report of metoclopramide-induced galactorrhea in infants involved an infant with chondrodysplasia punctata.17 Similar to our patient, this infant was on a dose of 0.2 mg kg−1 four times a day and had a high prolactin level (37 ng ml−1). This dose is higher than that recommended (0.033 to 0.1 mg kg−1 per dose every 8 h) in a standard neonatal reference.18 It is interesting that the daily dose in the earlier case report and our patient (0.8 mg kg−1 per day) exceeded the dose recommended in this reference, suggesting a dose-related effect without any evidence of added benefit. Similar reports of galactorrhea in infants after the use of domperidone (a prokinetic agent not available in the United States) are present in the literature.19

We conclude that careful physical examination of breast tissue must be performed in infants on prolonged or high-dose therapy with metoclopramide. If evidence of gynecomastia or galactorrhea is found, prolactin levels should be obtained. If these levels are high, attempts to discontinue or reduce the dose of metoclopramide should be considered. An awareness of this reversible side effect of metoclopramide will result in prompt diagnosis preventing an extensive endocrine work-up and reducing parental anxiety.