Hearing loss is a substantial public health problem with profound social and economic consequences in
the developing world. The World Health Organization (WHO) estimates that there are 360 million people
living with disabling hearing loss globally, and 80% of these individuals are from low- and middle-income
countries. The epidemiology of hearing impairment remains poorly defined in most impoverished
societies. Middle ear infections in childhood are a key determinant; however, congenital anomalies
may also comprise an important etiology and may arise from gestational malnutrition.
While evidence exists that preventable vitamin A deficiency exacerbates the severity of ear infections
and, consequently, hearing loss, antenatal vitamin A deficiency during sensitive periods of fetal development
may represent an etiologically distinct and virtually unexplored causal pathway. Evidence from
multiple animal systems clearly shows that fetal inner ear development requires adequate vitamin A
nutriture to proceed normally. Inner ear malformations occur in experimentally imposed maternal
vitamin A deficiency in multiple species in a dose–response manner. These anomalies are likely due to
the loss of retinoic acid-dependent regulation of both hindbrain development and otic morphogenic
processes.
Based on in vivo evidence in experimental animals, we hypothesize that preventable gestational
vitamin A deficiency, especially during early stages of fetal development, may predispose offspring to
inner ear malformations and sensorineural hearing loss. As vitamin A deficiency affects an estimated
20 million pregnant women globally, we hypothesize that, in undernourished settings, routine provision
of supplemental vitamin A at the recommended allowance throughout pregnancy may promote normal
inner ear development and reduce risk of an as yet unknown fraction of sensorineural hearing loss. If our
hypothesis proves correct, gestational vitamin A deficiency would represent a potentially preventable
etiology of sensorineural hearing loss of substantial public health significance.