Nongenetic risk factors for infantile cataracts: Systematic review of observational studies

Methodological quality of the review: Medium confidence

Author: Nalbandyan M, Papadopoulos EA, Leckman-Westin E, Browne ML.

Region: United States of America (USA), Canada and Hungary

Sector: Biomedical

Subsector: Risk

Equity focus: Infants (aged up to 12 months of age)

Review type: Other review

Quantitative synthesis method: Narrative synthesis

Qualitative synthesis method: Not applicable

Background:
Cataracts are a major cause of childhood blindness, with approximately 200,000 children worldwide being blind due to bilateral cataracts. Blindness has a negative impact on the quality of a child’s life and is associated with increased health care costs, thus reduction of childhood blindness is a priority issue in public health.

Objectives:
Identify and evaluate observational studies on infantile cataracts, summarise known nongenetic risk factors, identify gaps in the literature and provide directions for future research.

Main findings:
Authors included 110 articles in the review, where 77 were cross-sectional, case reports, or case series. The remaining 33 cohort and case-control studies were evaluated for methodological quality, relevant data was extracted, and statistically significant associations were described.

Out of the 77 cross-sectional studies, case report or case series, a number of cross-sectional studies, case report and case series linked infantile cataract to maternal rubella, toxoplasmosis, herpes simplex, varicella, and cytomegalovirus virus infections during pregnancy. Also, cases of infantile cataracts were described among mothers who had vitamin D deficiency or were on total parenteral nutrition during pregnancy. Maternal use of some medications, anticoagulants, antibiotic linezolid, mycophenolate mofetil, illicit drugs and maternal exposure to mercury during pregnancy were also reported among cases with infantile cataract. Also, cataracts were detected among infants with hypoglycaemia, generalised infection and spiroplasma, infants that were on total parental nutrition, and infants born after in vitro fertilisation. Finally, cataract formation was frequently observed among infants undergoing laser treatment for retinopathy of prematurity.

The 33 cohort and case-control studies had either excellent (n=31) or good (n=2) methodological quality and 32 of the studies used population-based data. 31 articles were published in the USA, one article in Canada, and one article in Hungary. Nine studies reported statistically significant associations with infant characteristics (preterm birth, low birth weight), maternal occupations and diseases during pregnancy (untreated hypertension, infections), and paternal sociodemographics (younger age, employment in sawmill industry during pregnancy).

Methodology:
Authors searched the following databases PubMed, Ovid MEDLINE, Web of Science, and Scopus, from inception through March 2018, for studies on infantile cataracts. In addition, authors screened the bibliographies of eligible articles and consulted with experts in the field. Searches were limited to studies written in English only.

Cohort, case-control, cross-sectional studies, case reports, and case series, investigating nongenetic risk factors for infantile cataracts, published in peer-reviewed journals, were eligible for the review. The review excluded ecological studies, animal studies, review articles, letters to editors and meeting abstracts. Screening of studies, data extraction and quality assessment of included studies was conducted by two reviewers independently. Quality assessment tool and data extraction tool were piloted on a random selection of studies.

Authors narratively synthesised the evidence and mentioned it was not possible to conduct a meta-analysis due to the heterogeneity of included studies.

Applicability/external validity:
Authors did not discuss the generalisability of the results, but highlighted some limitations which need to be considered when interpreting the results: only English publications were included, and the conclusion of this review is focused mainly on a single data source.

Geographic focus:
Authors included studies conducted in the USA, Canada and Hungary. Findings are associated with the socio-economic demographics of these regions, so their findings may not be applicable to other settings.

Summary of quality assessment:
Although authors used rigorous methods to analyse findings of included studies, this review may be prone to publication bias which may impact on the reliability of study findings.