Extrapyramidal syndrome in a breastfed child, relevance of toxicological analysis

Abstract

The passage of drugs in breast milk may be responsible for toxicity in breastfed children. We report here a case of passage of metoclopramide, an antiemetic neuroleptic, in breast milk, causing an extrapyramidal syndrome in the child, revealed in blood and hair. Case: a 21-week-old child was brought by his parents to the pediatric neurology department for consultation following two episodes of unexplained extrapyramidal syndrome. The little G., fed by mixed breastfeeding, presented a first episode of unexplained acute dystonia (generalized hypertonia with legs in extension and arms flexed against the chest, ceiling gaze, opisthonos) and two weeks later, a new episode of acute extrapyramidal syndrome, which resolved in a few hours. Both events required emergency hospitalization. During the second episode, diazepam 0.5 mg/kg IV was initiated, unsuccessfully. The anamnesis revealed that the mother had taken a rectal suppository of metoclopramide (10 mg) 48 hours before the first episode. An MRI was performed on arrival at the emergency room. Blood toxicology analysis was performed two days after the first episode. A 3-cm strand of brown hair was collected one month after the second episode. The entire sample (13 mg) was analyzed without segmentation. It should also be noted that the father had retractile capsulitis, treated with codeine paracetamol, and that the child had received paracetamol for teething. The child had no further episodes of dystonia since the second event. The MRI was normal. The child's blood toxicology analysis revealed the presence of metoclopramide at a concentration of 8 ng/mL. Hair analysis revealed metoclopramide at a relatively high concentration (1058 pg/mg), as well as paracetamol (31 ng/mg), lidocaine (34 pg/mg), diazepam (3 pg/mg) and its metabolite nordazepam (5 pg/mg), and codeine (16 pg/mg) in the analyzed hair of child G. The presence of diazepam and its metabolite can be explained by medical care. The low concentration of codeine without its metabolite morphine, may suggest an external contamination by the environment, contact with people who had consumed this molecule (bedding, caressing, etc.), especially the child's father. The presence of metoclopramide in the blood and hair is compatible with a passage of breast milk to the child. According to the literature, less than 5% of the maternal dose is found in the child. Adverse effects such as intestinal disorders, drowsiness, agitation, hypertonia have already been described in breastfed children (EMA. Metoclopramide Assessment report, 2013). This case illustrates the passage into breast milk of rectally administered metoclopramide in the mother and the toxic effects of this molecule in the child. The interpretation of hair analysis in infants remains nevertheless delicate to discriminate consumption from environmental contamination.