Research protocol authors and affiliations
Dr. Pedro Arroyo-Acevedo. Instituto Nacional de Geriatría
Dr. Marcelino Esparza-Aguilar. Instituto Nacional de Pediatría
LNCA. Verónica Martín-Martín. Instituto Nacional de Pediatría
Dr. Juan Carlos Gómez-Verján. Instituto Nacional de Geriatría
Dr. Luis Miguel Gutiérrez-Robledo. Instituto Nacional de Geriatría

Number of registry at Institutional Review Board/Research and Bioethics Research Committees:

Collaboration agreement
[Between the National Institute of Geriatrics (Mexico) and the National Institute of Pediatrics (Mexico) to carry out joint research projects, as well as education, training and updating of human resources.]

Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico. Grant CONACYT-FOSISS 2017 number 290287.

Introduction. The decline in functional capacity shows variations with age. A given genotype can give rise to different aging phenotypes influenced by the environment they will face. Early life influences, particularly during the intrauterine and neonatal stages, have been demonstrated on the risk of chronic pathologies in adulthood and different courses of the aging process. Information is needed regarding pre-industrial populations. Objectives. 1) To escribe the relationship and predictive potential of growth during the first two years of life that occurred in adverse socioeconomic situations with the health status and aging patterns at age 50 years. 2) Relate the regulation of genomic expression (transcriptome and epigenome) with anthropometric indicators of physical maturation reached at 50 years of age and potential trajectories of physical and functional decline during aging. Methods. Ambispective cohort study based on 336 births that occurred in a pre-industrial community in Mexico in 1966-67. Clinical and biochemical evaluation of 150-200 community-dwelling cohort members. Stages: 1) Recovery and validation of the historical information of the cohort. 2) Census of participants and acceptors. 3) Evaluation of the influence of the height of both parents on the growth velocity of the child (GVC) during the first two years. 4) Evaluation of the influence of the lactation pattern on GVC. 5) Evaluation of the clinical and biochemical health status of the adult members of the cohort. 6) Obtaining genetic material for analysis of the transcriptome and methylome in blood. 7) Construction of the trajectories between the growth of the child and the maximum height in adulthood. 8) Construction of child growth trajectories and morbidity due to chronic diseases in adulthood.

Tlaltizapán Cohort
From March 1st 1966 to February 28th 1967 Dr. Joaquin Cravioto, et al, from Hospital Infantil de México, recruited a birth cohort of all the 336 children born in that period in the semirural community of Tlaltizapán (Place over White Land), in the State of Morelos, Mexico. The aim of the study was to evaluate the effect of child undernutrition on growth and mental development.[1] Every pregnant woman in the community was identified and data on clinical and social variables, such as the parents’ height, weight, personal hygiene, formal education, income, household physical and sanitary conditions, and access to mass media were registered. At birth, the health status and anthropometric measurements of the infant were obtained. The children’s physical and mental development were followed for up to 14 years.[1-5].

In the community undernutrition, large family size, high number of offspring, short life expectancy, low educational status, limited contact with contemporary knowledge and traditions deeply rooted in lifestyle were prevalent. In the cohort, about the mothers, age ranged 13 to 43 years, height 133 to 165 cm, weight 32 to 86 kg, illiteracy 46.4%, schooling higher than primary 1.5%, access to TV as information media 9.8%, access to radio as information media 50%, and agricultural work as income source (66%). Home childbirth was 80%, stillbirths1.3%, early neonatal mortality 2.3%, late neonatal mortality 1.0%, and infant mortality 6.0%. Preterm newborns were observed in 2.7%, low birth weight in 12.3%, stunting at age 3 years in 26%, severe undernutrition at age 3 years in 6.8%, and severe undernutrition at age 4 years in 6.6%.[3,5-7]

Among the main contributions of the study it was shown that undernutrition, besides affecting growth, affected the brain development, which also depended on the available at home mental stimulation and socioeconomic status.[8] However and regrettably, at the time of the death of the principal investigator in 1998,[9] most of the research files were lost.

Fortunately, twenty years later, with a collaboration of the Instituto Nacional de Geriatría and the Instituto Nacional de Pediatría, we were able to trace the cohort members and update their status:

Four members died in utero, 22 died in the 1st year (mortality 65.5/1000 LB) and 6 died before age five years (mortality 17.8/1000 people). A 39.6% (133 subjects) was not located; from the remaining subjects, 118 (35.1%) still resided in the community, 10 (3.0%) in other Mexican States, and 43 (12.8%) in the U.S.A. Eighty-two (50 women and 32 men), aged 51-52 years, gave written informed consent to be clinically and biologically evaluated (methylome and transcriptome). Original data on the household´s sanitary level, family organization, family size, socioeconomic status, anthropometric values of both parents, and the mother´s reproductive history was recovered. Data on infant birth weight was recovered in 21% of the cases, increments of weight, height, and head circumference in the first six months were recovered in 56.1% of the cases and weaning age was recovered in 46% of the cases. After half a century since the cohort recruitment, the study of the cohort participants was an exceptional chance to study the influences of those antenatal and postnatal early conditions on the adult age health, disease, functioning and ageing patterns, which in tun could be applied to explain the health status of comparable populations exposed to restrictive environments.

  1. Cravioto J, Birch HG, De Licardie E, Rosales L, Vega L. The ecology of growth and development in a Mexican preindustrial community report 1: method and findings from birth to one month of age. Monogr Soc Res Child Dev. 1969 Aug;34(5):1-76.
  2. Cravioto J, de Licardie E. The long-term consequences of malnutrition. Nutr Rev 1971;29: 107-11.
  3. Cravioto J, De Licardie ER. The relation of size at birth and preschool clinical severe malnutrition. Acta Paediatr Scand. 1974;63(4):577-80.
  4. Condon-Paoloni D, Cravioto J, Johnston FE, et al. Morbidity and Growth of Infants and Young Children in a Rural Mexican Village. Am J Public Health 1977;67:651-56.
  5. Scholl T, Johnston FE, Cravioto J, DeLicardie ER, Lurie DS. The relationship of growth failure (chronic undernutrition) to the prevalence of clinically severe protein-energy malnutrition and to growth retardation in protein-energy malnutrition. Am J Clin Nutr. 1979;32(4):872-8.
  6. Sanjur DM, Cravioto J, Van Veen A, Rosales L. La alimentación de los lactantes y el destete de un medio rural preindustrial. Bol Oficina Sanit Panam. 1971 Oct;71(4):281-339.
  7. De Licardie ER, Cravioto J. Estimulación, desnutrición clínica grave y desarrollo del lenguaje en niños rurales. Gac Med Mex. 1973 Apr;105(4):333-55.
  8. Cravioto JJ, Vega-Franco L. Historical highlights of Mexican contributions to human nutrition. Arch Med Res. 1995;26 Spec No:S133-7.
  9. Arroyo P, Mandujano M. Joaquín Cravioto (1922–1998). J Nutr 2000;130:2867–69.

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