Transgenerational effect of early childhood famine exposure in the cohort of leningrad siege survivors’ offspring

Introduction Environmental exposure during early life development can affect disease risk in late-life period. There is little data on the transmission of phenotypic features from famine-exposed individuals to the next generations. Objective The purpose of our study was to investigate the association of parental starvation in the perinatal period and the period of early childhood with the phenotypic features observed in two generations of descendants of Leningrad Siege survivors (DLSS). Design and methods We examined 54 children and 30 grandchildren of 58 besieged Leningrad residents who suffered from starvation in early childhood and prenatal age during the Second World War. Controls from the population-based national epidemiological ESSE-RF study (n=175) were matched on sex, age and body mass index (BMI). Anthropometry, blood pressure (BP) measurement, and blood tests were performed for both groups. Sociodemographic and lifestyle information was collected via questionnaires. Phenotypes of controls and descendants (combined and children and grandchildren separately) were compared, taking into account multiple testing. Results Comparison of two generations descendants with corresponding control groups revealed significantly higher creatinine level and lower glomerular filtration rate (GFR), both in meta-analysis and in both generations independently. The mean values of GFR for all groups were detected within the normal range. Additionally, independent of the creatinine level, differences in the eating pattern were detected: insufficient fish consumption and excessive red meat consumption were significantly more frequent in the children of the Leningrad siege survivors compared with controls. BP and blood lipids did not differ between the groups. Conclusions Ancestral famine exposure in the prenatal period and early childhood may contribute to a decrease of in kidney filtration capacity and altered eating pattern in at least two generations of besieged Leningrad offspring. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement K.T., D.U., E.M., M.B., E.K., A.E., E. V., An.K., E.S., Al.K., O.R. were supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement #075-15-2022-301). M.A. was supported by Nationwide Foundation Pediatric Innovation Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Local Ethics Committee of the Almazov National Medical Research Centre (Protocol #2401-21 from the local ethics committee meeting #01-21 dated January 18, 2021). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Raw data produced in the present study constitutes sensitive personal information and is not permitted for sharing by patient consent terms. Summary data characterizations are contained in the manuscript. More detailed information is available upon reasonable request to the authors.