Table 1.

Illustrative compound- or formulation-specific serious adverse drug reactions in neonates as reported in the literature (illustrations are provided chronologically to illustrate that this remains an ongoing issue 10–17)

Compound/formulation	Clinical syndrome	Developmental pharmacology/toxicology
Oxygen, preterm (1951) [10]	‘Retinopathy of prematurity’	Early neonatal overexposure to oxygen results in microvascular retinal overgrowth
Sulfonamides (1956) [11]	‘Kernicterus’	Highly albumin-bound antibiotics, competitive with endogenous compounds, including bilirubin. This results in higher free bilirubin concentrations and subsequent kernicterus
Chloramphenicol (1959) [12]	‘Grey baby syndrome’	Impaired glucuronidation capacity, which results in accumulation of chloramphenicol and subsequent mitochrondial dysfunction, circulatory collapse and death
Benzyl alcohol (1982) [13]	‘Gasping syndrome’	Benzyl alcohol, coadministered as a preservative in parenteral formulations, results in accumulation in preterm neonates because of their limited metabolic (alcohol dehydrogenase) clearance capacity. Accumulation results in metabolic acidosis, followed by seizures, bradycardia, gasping respiration and hypotension preceding cardiovascular collapse and, ultimately, death
Dexamethasone (2000) [14]	‘Cerebral palsy’	High-dose dexamethasone exposure in neonatal life results in an increased risk of subsequently displaying cerebral palsy during infancy, probably due to increased neuronal apoptosis
Oxygen, preterm (2000) [15]	‘Bronchopulmonary dysplasia’	Early neonatal overexposure to oxygen results in an increased incidence of bronchopulmonary dysplasia (chronic lung disease of prematurity)
Lopinavir/ritonavir syrup (2005) [16]	‘Alcohol accumulation’	Kaletra® syrup contains both ethanol and propylene glycol. Impaired metabolic clearance results in accumulation and subsequent hyperosmolality, lactic acidosis, renal toxicity, central nervous system impairment, cardiac arrhythmia, haemolysis and collapse
Ceftriaxone + calcium (2009) [17]	‘Cardiovascular collapse’	Simultaneous administration of calcium-containing infusions and ceftriaxone results in intravascular precipitate, as observed during autopsy