Prenatal determinants of optic nerve hypoplasia: review of suggested correlates and future focus

Surv Ophthalmol. Nov-Dec 2013;58(6):610-9. doi: 10.1016/j.survophthal.2013.02.004.


Optic nerve hypoplasia (ONH), a congenital malformation characterized by an underdeveloped optic nerve, is a seemingly epidemic cause of childhood blindness and visual impairment with associated lifelong morbidity. Although the prenatal determinants of ONH are unknown, early case reports have led to a longstanding speculation that risky health behaviors (e.g., prenatal use of recreational drugs, alcohol) are a likely culprit. There has yet to be a systematic review of the epidemiology of ONH to assess the common prenatal features that may help focus research efforts in the identification of likely prenatal correlates. A review of the past 50 years of epidemiologic research was conducted to examine the prenatal features linked with ONH and provide direction for future research. There are select prominent prenatal features associated with ONH: young maternal age and primiparity. Commonly implicated prenatal exposures (recreational or pharmaceutical drugs, viral infection, etc.) were rare or uncommon in large cohort studies of ONH and therefore unlikely to be major contributors to ONH. Familial cases and gene mutations are rare. The preponderance of young mothers and primiparity among cases of ONH is striking, although the significance is unclear. Recent research suggests a potential role for prenatal nutrition, weight gain, and factors of deprivation. With the rapidly increasing prevalence of ONH, future research should focus on investigating the relevance of young maternal age and primiparity and exploring the recently suggested etiologic correlates in epidemic clusters of ONH.

Keywords: birth defect; epidemiology; hypopituitarism; maternal age; optic nerve hypoplasia; prenatal risk factors; septo-optic dysplasia.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Eye Abnormalities / diagnosis*
  • Eye Abnormalities / etiology
  • Eye Abnormalities / genetics
  • Female
  • Humans
  • Optic Nerve / abnormalities*
  • Pregnancy
  • Prenatal Diagnosis*
  • Prenatal Exposure Delayed Effects* / diagnosis
  • Risk Factors