Micronuclei, reproduction and child health.

The current review looks for relationships between results from biomarker studies with micronucleus and health effects related to reproduction and children. In adults, an age related increase in MN is well known as well as associations with environmental exposures especially air pollution from traffic and smoking. Literature searches in PubMED and SCOPUS were performed with the following keywords reproduction, children, micronuclei, health effects. In total 162 studies were identified with the keyword children. Concerning children and health and children and environmental exposures, the titles and abstracts of a total of 162 publications were screened for language, inclusion of data from children and selected according to a study selection chart. 9 studies were included for children and health, and 21 studies for children and environmental exposures, with 12 in buccal cells and 9 in lymphocytes. The publications were read and included in tables if data on controls was available. MN frequencies were collected for peripheral blood lymphocytes (PBLs), reticulocytes or buccal cells (BC) and reported as Mean ± SD or Median (IQR). The Mean frequency Ratio, MRi, corresponding to the MN mean for study persons divided by MN mean for control persons was stated as reported in the publication or calculated by us from the data in the publication, where possible. Our systematic analysis revealed a number of positive associations of MN frequencies as a marker of increased health risk in relation to reproduction as well as child health. The majority of studies reported with children concerns exposures of children as well as maternal exposures and newborn health with MN as a biomarker of exposure. Exposure monitoring by MN as biomarker is also reported in studies of school children however most often not related to health effects. The MRis are found in ranges from 1 to 5.5 most studies around 2. As far as MN frequencies in children and exposure are concerned, the MRis range from 0.9 to 5.5, with a range from 1.3-4.9 for lymphocytes and from 1.5 to 2.5 in buccal cells, except for two studies with no differences found between cases and controls. Only one study is available for MRi calculation in reticulocytes with the value of 2.3. These data are supporting MN as a relevant biomarker for children health. However, the data is mostly from small studies with different protocol leaving out the possibility of metanalyses and even statistical comparisons among studies. The actual risk from elevated MNs in children waits large cohort studies with pooled datasets as performed with MN measured in adults. Introduction of buccal cells as non invasive alternative to lymphocytes is increasing and as with the lymphocytes standardised protocols are recommended to enable comparative studies and metaanalyses.

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Declaration of Competing Interest We declare no conflicts of interest and no financial support for this work