Exposure to Smoking in Early Life Associated with Thinner RNFL in Young Adults

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An analysis of optic nerve status in young adults suggests the largest RNFL deficits were found in those exposed to tobacco smoke during both fetal life and childhood.

Exposure to maternal smoking during pregnancy was associated with a thinner peripapillary retinal nerve fiber layer (RNFL) and macula in young adults, with the largest deficits observed in those exposed to tobacco smoke during both fetal life and childhood, according to a new analysis.1

The investigator team, led by Linna Zhu, University of Copenhagen, indicated a dose–response relationship between the number of cigarettes smoked during pregnancy and RNFL deficit. But, a lack of association between RNFL thickness and active smoking at 18 years suggests the optic nerve may be most vulnerable during prenatal life and early childhood.

“These distinct and high-reproducible stages of damage to the central nervous system in relation to early-life exposure to tobacco smoke underline the relevance of a continued effort to control and limit the spread of this toxic agent,” investigators wrote.

Prior research has linked maternal smoking during pregnancy with a thinner peripapillary RNFL in childhood, making the optic nerve more vulnerable to glaucoma. As data from Europe report an 8.1% prevalence of maternal smoking during pregnancy, investigators cited the considerable scope of the issue.

In the current study, they aimed to analyze the effect of multiple pre- and postnatal exposures, including smoking and air pollution, on optic nerve status in young adults due to the critical nature of this period for development. Adults aged 18 years who participated in the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) cohort were included in the study population.

The study registered maternal smoking 2 weeks after birth and categorized it into smoking or not smoking during pregnancy. If mothers had smoked during pregnancy, they were questioned on how many cigarettes they had smoked per week and in which trimesters they smoked. Passive smoking during childhood was categorized as exposure or non-exposure during the first 7 years of life, while smoking at 18 years of age was categorized as smoking or not smoking within the last 4 weeks.

Other measures including exposure to air pollution, diagnosis of atopic diseases, and corticosteroid treatment were assessed by investigators. RNFL thickness was measured using optical coherence tomography (OCT). Macular thickness was measured as the average distance between the internal limiting membrane and the retinal pigment epithelium within the cube.

The final analysis consisted of 269 of 350 participants with eye examination data in COPSAC2000. Of these 269 participants, 124 (46%) were male and the mean age was 17.6 years. Data showed the mean peripapillary RNFL thickness was 94.6 μm and the mean overall macular thickness was 284.3 μm.

In multivariate analysis, maternal smoking during pregnancy, lower birth weight, and longer ocular axial length were significantly associated with RNFL deficits. Data showed the 60 (22.3%) participants whose mothers had smoked during pregnancy had a thinner peripapillary RNFL (adjusted mean difference, −4.6 μm; 95% confidence interval [CI], −7.7 to −1.5 μm, P = .004).

Then, in subgroup analysis, investigators found those with exposure to smoking during pregnancy combined with passive smoking during childhood had the thinnest mean peripapillary RNFL thickness. These results remained significant after adjusting for age, sex, birth weight, axial length, alcohol use, and corticosteroid use (adjusted mean difference, –9.6 μm; 95% CI, –13.4 to –5.8 μm; P <.0001).

An increasing number of cigarettes smoked during pregnancy was linked to thinner peripapillary RNFL (mean difference, − 0.002 μm/cigarette; 95% CI, −0.003 to −0.001μm/cigarette; P = .009). Smoking during pregnancy was additionally associated with a macular thickness deficit (–4.7 μm; 95% CI, –9.0 to –0.4 μm; P = .03).

On the other hand, adjusted analyses revealed a lack of association between higher indoor concentrations of particulate matter 2.5 with thinner RNFL or a macular deficit. There were no differences observed among participants who smoked at 18 years compared with non-smokers on RNFL or macular thickness.

Although the main limitation of the study is the population size, investigators noted that the study was able to reproduce earlier findings of RNFL deficits related to maternal smoking.

“The principal new observation is that maternal smoking during pregnancy and passive smoking during childhood work in conjunction to produce additive, statistically independent detrimental effects on the inner retina and, by anatomical extension, on the optic nerve,” they wrote.


  1. Zhu L, Munch IC, Pedersen C, et al. Associations of pre- and postnatal exposures with optic nerve status in young adults [published online ahead of print, 2023 Mar 10]. Acta Ophthalmol. 2023;10.1111/aos.15657. doi:10.1111/aos.15657