Grandmother Age Research Articles

Predictors and moderators of treatment efficacy in reducing custodial grandmothers’ psychological distress

It is increasingly recommended that hypothesis-generating studies be conducted after initial RCTs in order to identify moderators of differential treatment efficacy on individual outcomes. Such analyses are important because they help clarify the best inclusion and exclusion criteria or choice of stratification for maximizing power in subsequent RCTs, reduce the chances of discarding interventions that may appear to lack efficacy when only average treatment effects are taken into consideration, and facilitate the matching of individual clients to treatment alternatives. We identified predictors and moderators of treatment-related change in psychological distress among custodial grandmothers (n = 343) assigned within a prior RCT to behavior parent training (BPT), cognitive behavior therapy (CBT), or information only control (IOC) conditions. Latent change scores in psychological distress were estimated for each grandmother across pre-test to post-test and pre-test to six months, as indicated by self-reported and clinical ratings of depression and anxiety symptoms. These estimates served as outcomes in classification and regression tree analyses conducted separately within the CBT and BPT conditions to identify predictors of treatment efficacy. Matched groups based upon identified predictors were then formed across all RCT conditions, and Predictor × RCT Condition interactions were computed to test for moderation of differential treatment efficacy. Grandmother age was the only predictor and moderator of BPT efficacy at both measurement points, whereas multifaceted predictors and moderators emerged for CBT which varied by time since treatment.

Paternal Grandmother Age Affects the Strength of Wolbachia-Induced Cytoplasmic Incompatibility in Drosophila melanogaster.

Wolbachia are obligate intracellular bacteria that are globally distributed in half of all arthropod species. As the most abundant maternally inherited microbe in animals, Wolbachia manipulate host reproduction via reproductive parasitism strategies, including cytoplasmic incompatibility (CI). CI manifests as embryonic death when Wolbachia-modified sperm fertilize uninfected eggs but not maternally infected eggs. Thus, CI can provide a relative fitness advantage to Wolbachia-infected females and drive the infection through a population. In the genetic model Drosophila melanogaster, the Wolbachia strain wMel induces variable CI, making mechanistic studies in D. melanogaster cumbersome. Here, we demonstrate that sons of older paternal D. melanogaster grandmothers induce stronger CI than sons of younger paternal grandmothers, and we term this relationship the "paternal grandmother age effect" (PGAE). Moreover, the embryos and adult sons of older D. melanogaster grandmothers have higher Wolbachia densities, correlating with their ability to induce stronger CI. In addition, we report that Wolbachia density positively correlates with female age and decreases after mating, suggesting that females transmit Wolbachia loads that are proportional to their own titers. These findings reveal a transgenerational impact of age on wMel-induced CI, elucidate Wolbachia density dynamics in D. melanogaster, and provide a methodological advance to studies aimed at understanding wMel-induced CI in the D. melanogaster model.IMPORTANCE Unidirectional cytoplasmic incompatibility (CI) results in a postfertilization incompatibility between Wolbachia-infected males and uninfected females. CI contributes to reproductive isolation between closely related species and is used in worldwide vector control programs to drastically lower arboviral vector population sizes or to replace populations that transmit arboviruses with those resistant to transmission. Despite decades of research on the factors that influence CI, penetrance is often variable under controlled laboratory conditions in various arthropods, suggesting that additional variables influence CI strength. Here, we demonstrate that paternal D. melanogaster grandmother age influences the strength of CI induced by their sons. Older D. melanogaster females have higher Wolbachia densities and produce offspring with higher Wolbachia densities that associate with stronger CI. This work reveals a multigenerational impact of age on CI and expands our understanding of host-Wolbachia interactions and the biology of CI induced by the Wolbachia strain infecting the most widely used arthropod model, D. melanogaster.

Limits to Fitness Benefits of Prolonged Post-reproductive Lifespan in Women

Recent advances in medicine and life-expectancy gains have fueled multidisciplinary research into the limits of human lifespan [1-3]. Ultimately, how long humans can live for may depend on selection favoring extended longevity in our evolutionary past [4]. Human females have an unusually extended post-reproductive lifespan, which has been explained by the fitness benefits provided from helping to raise grandchildren following menopause [5, 6]. However, formal tests of whether such grandmothering benefits wane with grandmother age and explain the observed length of post-reproductive lifespan are missing. This is critical for understanding prevailing selection pressures on longevity but to date has been overlooked as a possible mechanism driving the evolution of lifespan. Here, we use extensive data from pre-industrial humans to show that fitness gains from grandmothering are dependent on grandmother age, affecting selection on the length of post-reproductive lifespan. We find both opportunities and ability to help grandchildren declined with age, while the hazard of death of women increased greatly in their late 60s and 70s compared to menopausal ages, together implying waning selection on subsequent longevity. The presence of maternal grandmothers aged 50-75 increased grandchild survival after weaning, confirming the fitness advantage of post-reproductive lifespan. However, co-residence with paternal grandmothers aged 75+ was detrimental to grandchild survival, with those grandmothers close to death and presumably in poorer health particularly associated with lower grandchild survival. The age limitations of gaining inclusive fitness from grandmothering suggests that grandmothering can select for post-reproductive longevity only up to a certain point.

Correlation between Heredity Factor and Menarcheal Age among Adolescent Aged 9–15 Years Old

Background: Menarche is a sign of maturity of the female reproductive function. It is influenced by many factors, such as heredity, general health status, nutrition, and socioeconomic status. The purpose of this study is to determine the correlation of heredity and menarcheal age. Methods: This study was a cross-sectional analytic study conducted from September–October 2014 in Bandung using a multi-stage sampling technique and it was conducted in twelve elementary schools and junior high schools. A total of 123 subjects were included in this study. The instrument of this study was questionnaire containing menarcheal age of subject, older sister, biological mother, and maternal grandmother. The data were analyzed using Spearman correlation and linear regression test with the level of significance was determined at p<0.05. Results: Among 123 data, the majority of subjects had experienced menarche at the age of 11 (39%) and 12 years (36.6%) with an average of 11.46 years old. Based on the Spearman correlation and multiple linear regression tests, there was a correlation between heredity and menarcheal age. (P=0.00). Conclusions: There is a correlation between heredity and menarcheal age, with the highest correlation is between subject’s and older sister’s menarcheal age. DOI: 10.15850/amj.v4n2.1081

The Utility of the Family Empowerment Scale With Custodial Grandmothers.

The Family Empowerment Scale (FES) was developed specifically to assess empowerment in families with emotional disorders. Its relevance to custodial grandfamilies is reflected in the difficulties in grandchildren's social, emotional, and behavioral functioning, wherein such difficulties may be explained via either reactions to changes in their family structure or in their responses to the newly formed family unit. Utilizing 27 items derived from the 34-item version of the FES, which had represented differential levels of empowerment (family, service system, community) as indexed by one's attitudes, knowledge, and behavior, we explored the factor structure, internal consistency, construct, and convergent validity of the FES with grandparent caregivers. Three-hundred forty-three ( M age = 58.45, SD = 8.22, n Caucasian = 152, n African American = 149, n Hispanic = 38) custodial grandmothers caring for grandchildren between ages 4 and 12 years completed the 27 FES items and various measures of their psychological well-being, grandchild psychological difficulties, emotional support, and parenting practices. Factor analysis revealed three factors that differed slightly from the originally proposed FES subscales: Parental Self-Efficacy/Self-Confidence, Service Activism, and Service Knowledge. Each of the factors was internally consistent, and derived factor scores were moderately interrelated, speaking to the question of convergent validity. The construct validity of these three factors was evidenced by meaningful patterns of statistically significant correlations with grandmothers' psychological well-being, grandchild psychological difficulties, emotional support, and parenting practices. These factor scores were independent of grandmother age, health, and education. These findings suggest the newly identified FES factors to be valuable in understanding empowerment among grandmother caregivers.

ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis.

We were intrigued by the pedigrees in the paper by Ceroni et al1 in the October 2014 issue that explored the association between ZNF277 microdeletions and specific language disorder (SLI). The authors make the case for ZNF277 microdeletions contributing to the risk of SLI while acknowledging that there was little evidence of co-segregation of these microdeletions with SLI in their discovery pedigree plus eight other families. The authors only discuss this discrepancy in terms of reduced penetrance, that is, unaffected siblings that carry the microdeletion, but say little about the reverse discordance in two of their three multiplex families, that is, where one of the two affected siblings has inherited the maternal microdeletion and the other has not. This reverse discordance has been reported in multiplex families with autistic spectrum disorder (ASD) in which a putative risk copy number variation (CNV) is segregating.2 This paper on ASD, and our finding of a maternal grandmother age effect in ASD prompted us to propose the meiosis mismatch methylation (3M) hypothesis.3 This states that, in female early meiosis I, the pairing of a chromosome carrying a microdeletion with a wild-type homologue increases the chance of abnormal methylation due to chromosome looping through misaligned pairing, such as would occur with silencing of a transposon.4 This in turn results in the functional silencing of the wild-type gene when transmitted to offspring. 3 M predicts that all offspring of a woman carrying a risk CNV are at risk of the condition even though only half inherit the CNV. Independently, around the time of formulating the 3 M hypothesis, an ASD family was reported in which one affected sibling had inherited a maternal deletion containing the oxytocin receptor gene (OXTR) and the other affected sibling had no deletion, but had epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation.5 We suggest that it would be useful to examine at least the DNA methylation status of the maternally inherited ZNF277 allele in the siblings that have SLI but not the microdeletion.

Psychological distress in African American grandmothers raising grandchildren: The contribution of child behavior problems, physical health, and family resources

Diminished psychological health has been identified among caregiving grandmothers. The intent of this investigation was to examine psychological distress levels, as well as their predictors, in a sample of 480 caregiving African American grandmothers, mean age 56 years. Almost 40% (39.8%) of participants had clinically elevated psychological distress scores. Results of hierarchical multiple regression indicated that internalizing and externalizing child behavior problems, poor grandmother physical health, younger age of grandmother, and lack of family resources predicted 31% of the variance in psychological distress. Results provide direction for nursing interventions aimed at enhancing the psychological well-being of caregiving grandmothers.

Abstract A15: The role of family communication in cancer screening practices.

Abstract Black and Latina women experience the highest disparities in incidence and mortality of cervical cancer and breast cancer mortality in spite of lower incidence than non-Hispanic white women. Among diverse and low literacy populations, family centered networks represent an important mechanism for communication about health concerns, including preventive screening practices. The purpose of the study is to examine the associations between family communication, demographic factors, and breast and cervical cancer health literacy. Black (n=216), Latina (n=65), and Arab (n=233) women enrolled in a randomized trial of Kin KeeperSM, a cancer prevention intervention delivered by community health workers. Self-reported family communication scores (FACES) were cross-tabulated with age, education, literacy scores and presence of grandmother. Analyses were replicated by race and ethnicity. Black and Arab women are the most likely to have a college degree or more and also the most likely to rate their health as excellent compared to Latina respondents. Blacks had the lowest family communication scores while Arabs had the highest family communication scores. Among Blacks, lower FACES score associated with lower cervical cancer literacy and with presence of a grandmother. FACES scores were higher among those who had lower educational attainment(less than a high school degree) and lower among all race/ethnic groups who rated their health status as poor. The unique contribution of this study is the inclusion of Arab women and its focus on family communication scores. The implications of these data are that for low-income diverse groups there are disparities in family communication, and that family network is an important and viable resource for the transmission of health cancer literacy information. Note: This abstract was withdrawn after the Program and Proceedings were printed and was not presented at the conference. Citation Format: Adnan Hammad, Karen Patricia Williams, Ruth E. Zambrana, Cristian Meghea. The role of family communication in cancer screening practices. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A15.

Needs for Information About Supportive Resources: A Predictor of Needs for Service and Service Use in African American Grandmother Caregivers

This study's purpose was to explore relationships among perceived needs for information about resources, service needs, and service use. Ninety-three African-American grandmothers aged 36 to 78 who were primary caregivers for their biological grandchildren participated. Relationships among variables were analyzed using hierarchical multiple regression, controlling for grandmothers' demographic characteristics. While grandmother age and number of grandchildren predicted needs for information about resources, such needs predicted both perceived service need and service use. Findings not only underscore the importance of sensitivity to variation across persons in needs for information about services among African American grandmother caregivers but also emphasize the key roles that such needs play in predicting both needs for services and the use of a variety of social, medical, and legal services.

Maternal grandmothers with advanced age reproduction are more likely to have Down syndrome grandchildren

Down syndrome (DS), trisomy 21, is the most common chromosomal syndrome that affects one in 600800 live births. The advanced maternal age is the only well known risk factor to cause DS. Our study revealed that many young mothers produced DS children than advanced age mothers in India. A total of 150 suspected DS cases were investigated cytogenetically. Randomly selected 200 healthy families in South India were used as controls. Logistic regression was performed on case-control dataset which was generated by randomly selecting the child from each of the control families. Pedigree analyses indicated that the maternal grandmothers had advanced age during conception of their daughters who gave birth to DS child. Case-control status was used as dependent variable, whereas parental and grandparental age was used as covariates. Logistic regression was reported as odds ratios, univariate and multivariate. The age of maternal grandmother showed highly significant difference in odds ratio, indicating that the advanced age of maternal grandmother was the possible risk factor. Therefore, it is important to sort-out the effect of advanced age mothers vs grandmothers on increased frequency of DS reported in different populations.

Young Mothers Produce More Chromosomal Syndrome Babies in Mysore, South India

Chromosomal syndromes contribute significantly to reproductive failure, birth defects, mental retardation, delayed puberty, and hermaphrodites in humans. It has been estimated that at least 5% of all human conceptions are aneuploids, most of them resulting in pregnancy loss. The well-established factor to produce babies with chromosomal syndromes is advanced age of mothers. However, in India, more of young mothers give birth to babies with chromosomal syndromes. The present study has been attempted to investigate the possible causes. A total of 175 children with chromosomal aneuploidy and 300 controls were screened for cytogenetic investigation from major hospitals of Mysore city. Genetic register was established, pedigree was constructed and degree of consanguinity was studied for the cases where parental consanguinity was evident. Cytogenetic and statistical analysis were carried out using logistic regression. Logistic regression of case-control study of babies with chromosomal aneuploidy revealed that the odds ratio was significant for advanced father and maternal grandmother's age when all the variables were used together. The effect of age of father and age of maternal grandmother were increased in odds by 16% and 46% per extra year respectively. Along with the established risk factors like advanced age of parents, maternal grandmother's age is also the potential possible risk factor for the manifestation of babies with chromosomal aneuploidy in young mothers.

Older mothers are not at risk of having grandchildren with sporadic mtDNA deletions

PurposeSingle large-scale mitochondrial DNA deletions account for a quarter of mitochondrial disease cases and occur sporadically with unknown risk factors. Mitochondrial DNA deletions accumulate with age in many tissues. Primordial germ cells, the precursors of oocytes are made by our grandmothers, therefore we wanted to determine whether age of maternal grandmother is a risk factor for sporadic mitochondrial DNA deletions. MethodsTwenty-nine patients with sporadic single mitochondrial DNA deletions from the Newcastle UK cohort provided dates of birth for mothers and maternal grandmothers plus father and paternal grandmother (healthy controls). ResultsMean age for grandmothers at birth of a mother of an affected patient was 28.5 years (SD ± 6.9) for single mitochondrial DNA deletions maternal grandmothers and 28.2 years (SD ± 6.1) for healthy control paternal grandmothers. ConclusionMaternal grandmother age is not a risk factor for sporadic mitochondrial DNA deletions, an important observation in a population where many women are delaying reproduction.

Parental and grandparental ages in the autistic spectrum disorders: a birth cohort study.

BackgroundA number of studies have assessed ages of parents of children with autistic spectrum disorders (ASD), and reported both maternal and paternal age effects. Here we assess relationships with grandparental ages.Methods and FindingsWe compared the parental and grandparental ages of children in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC), according to their scores in regard to 4 autistic trait measures and whether they had been given a diagnosis of ASD. Mean maternal and paternal ages of ASD cases were raised, but this appears to be secondary to a maternal grandmother age effect (P = 0.006): OR = 1.66[95%CI 1.16, 2.37] for each 10-year increase in the grandmother's age at the birth of the mother. Trait measures also revealed an association between the maternal grandmother's age and the major autistic trait–the Coherence Scale (regression coefficient b = 0.142, [95%CI = 0.057, 0.228]P = 0.001). After allowing for confounders the effect size increased to b = 0.217[95%CI 0.125, 0.308](P<0.001) for each 10 year increase in age.ConclusionsAlthough the relationship between maternal grandmother's age and ASD and a major autistic trait was unexpected, there is some biological plausibility, for the maternal side at least, given that the timing of female meiosis I permits direct effects on the grandchild's genome during the grandmother's pregnancy. An alternative explanation is the meiotic mismatch methylation (3 M) hypothesis, presented here for the first time. Nevertheless the findings should be treated as hypothesis generating pending corroborative results from other studies.

Age of mother and grandmother in relation to a subject's breast cancer risk

Background:On theoretical grounds, the age of the grandmother and the age of the mother at delivery of her daughter may affect the breast cancer risk of the granddaughter.Methods:We used the data relating to the Diagnostic Research Mamma-carcinoma cohort (DOM (Diagnostisch Onderzoek Mammacarcinoom) 3), which comprises a population-based sample of 12 178 women aged 41–63 years at enrolment in 1982–85 and followed up until 2000. During follow-up 340 postmenopausal breast cancer cases were identified. To these we applied a case–cohort design together with a random sample from the baseline cohort (n=1826). Of these study participants, we were able to retrieve the birth dates of 998 mothers (309 cases, 689 controls), and for 547 of these we also retrieved the birth dates of the grandmothers (197 cases, 350 controls). A weighted Cox proportional hazards model was used to estimate the hazard ratios (HRs) for the effect of the age of the grandmother and the age of the mother on the breast cancer risk of the index women, while adjusting for potential confounders.Results:Compared with the reference group aged 25–29.9 years, the group with the lowest maternal age (<25 years) had an age-adjusted HR of 0.77 (95% CI 0.19–3.12) and the group with the highest maternal age (⩾40 years) had an age-adjusted HR of 1.58 (95% CI 0.01–267.81), P-value for trend=0.62. Compared with the same reference group, the group with the lowest grandmaternal age (<25 years) had an age-adjusted HR of 0.53 (95% CI 0.24–1.17) and the group with the highest grandmaternal age (⩾40 years) had an age-adjusted HR of 7.29 (95% CI 1.20–44.46), P for trend=0.04. The associations did not change significantly after additional adjustment for various risk factors for breast cancer, neither for maternal age nor for grandmaternal age.Conclusion:This study does not suggest a major role of maternal age at delivery or grandmaternal age at delivery of the mother for the (grand)daughters' breast cancer risk.

Chronic inflammation, C-reactive protein, and breast health: future directions to predict, prevent, personalize and inspire consumerism in the mitigation of breast cancer

Breast cancer incidence has dropped dramatically with further reductions predictably linked to lifestyle/behavioral and environmental changes. About 98% of malignant breast conditions emanate within the epithelial cell compartment in the breast ductal system. Premalignant cell damage in this lining signals a biochemical cascade that deliver inflammatory proteins to the site. One protein, CRP, is associated with carcinogenic risk. An inflammation cell milieu amendable to efficient, low cost, preventive interventions that impede biochemical/molecular conversion to cancer would offer a 'disruptive innovation' with public health implications. Nipple aspirate (NAF), a non-invasively obtained tissue sample, is a rich source of protein markers manufactured by the ductal system. First, Lithgow's dissertation determined if CRP relates to reproductive, nutrition, and body composition and activity factors. Results were that age at first pregnancy, gravidity, wean time from breast-feeding last baby, %fat, and BMI, with p < .05, and serum triglycerides (p = .01), were related significantly to CRP levels in NAF. A model derived from selective factors significantly (p = .05) accounted for the variance in CRP in NAF. Second, Lithgow evaluated if risk factors, as identified by the Gail model, were associated with NAF CRP levels. CRP in NAF significantly (p = .04) and positively related to breast cancer risk as predicted by the Gail model. A third bio-cultural study offers a perspective breast microenvironment that challenges western views of the female breast. Proteins prevalent in grandmother age (35 – 70 years of age)breast fluids collected in an investigation of the use of re-lactation in response to a goal to reduce infant exposure to HIV transferred in mother's breast milk found that these grandmothers could re-establish a nutritious/adequate milk supply equivalent with the cell and protein components of human milk. The inflammatory hypothesis, as a potential preventive base to support breast-feeding support for maternal health, systematic testing of NAF, serial expression of NAF, dietary supplements and other innovations taken together promise further reductions of breast cancer incidence. The western view of female breast pathophysiology may benefit from a 'disruptive innovation' philosophy applied to the translational model of knowledge development that is predictive, preventive, personalized, and participatory in the mitigation of breast cancer.

Advanced Maternal Grandmother Age is a Risk Factor in Causing Sex Chromosomal Aneuploidy

KEYWORDS Turner syndrome; Klinefelter syndrome; young mother; nondisjunction; maternal grandmother age ABSTRACT Majority of the chromosomal abnormalities are incompatible with embryonic or fetal survival but trisomy 21 and sex chromosomal trisomies have a much higher viability surviving to term. In India, increased numbers of children with sex chromosomal aneuploidy are born to young mothers. Therefore, detailed analysis of the families with sex chromosomal aneuploidy is needed to find out the possible causative factors for nondisjunction. Twenty five families of suspected sex chromosomal aneuploidy children were investigated for cytogenetic analysis and pedigrees were constructed for these families. As controls 100 randomly selected families belonging to different religions were used. Of the 25 sex chromosomal aneuploidy cases studied, 16 were Turners with 45, XO chromosomes and 9 were Klinefelters with 47, XXY chromosomes. The number of sex chromosomal aneuploidy births was greater for the young mothers than the advanced age mothers. The logistic regression of case-control study of sex chromosomal aneuploidy children revealed that the odds ratio for the age of maternal grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. For every year of advancement of age of the maternal grandmother, the risk (odds) of births of sex chromosomal aneuploidy children increases by 36%. Therefore, the age of the maternal grandmother at the time of birth of mother is a risk factor for the occurrence of sex chromosomal aneuploidy.

Advanced Maternal Grandmother Age is a Risk Factor in Causing Sex Chromosomal Aneuploidy

Advanced Maternal Grandmother Age is a Risk Factor in Causing Sex Chromosomal Aneuploidy

Grandmothers, Caregiving, and Family Functioning

We used McCubbin's Resiliency Model of Family Stress, Adjustment and Adaptation ( McCubbin, Thompson, & McCubbin, 2001) to examine how demographic factors, family stress, grandmother resourcefulness, support, and role reward affect perceptions of family functioning for grandmothers raising grandchildren, grandmothers living in multigenerational households, and grandmothers not caregiving for grandchildren. A sample of 486 grandmothers completed a mailed questionnaire. We used structural equation modeling to (a) test the effects of demographic factors (i.e., grandmother's age, race, marital status, and employment), family stressful life events and strain, grandmother's resourcefulness, subjective and instrumental support, and role reward on perceptions of family functioning for each grandmother group; (b) evaluate differences in the measurement and structural models between the grandmother groups using multisample analysis; and (c) test the model on the full sample, coding for caregiver status. The models did not differ significantly by grandmother group; therefore we assessed the composite model using a multisample analysis. We found general support for the resiliency model and equivalence of the models across grandmother groups. Less support, resourcefulness, and reward, and more intrafamily strain and stressful family life events contributed to perceptions of worse family functioning. Findings demonstrate the importance of the quality of family functioning for grandmothers in all types of families.

Grandparents’ age and the risk of Down's syndrome in Norway

High maternal age is a well-recognized risk factor for Down's syndrome. There are also several studies of a possible effect of paternal age, but no consistent evidence of an association is found. Less is known about any effects of the age of grandparents. Objective. To assess whether maternal or paternal grandparents' age is associated with the risk of Down's syndrome. We used logistic regression analyses with data from the Medical Birth Registry of Norway, adjusting for possible confounding factors. We found no evidence of an association with the risk of Down's syndrome either for a maternal grandmother's age (odds ratio 0.9, 95% confidence interval 0.6-1.5 per 10-year increase in grandmother's age) or for any of the other grandparents' age. High maternal age remains the only well-established age-related risk factor for Down's syndrome. There is little evidence that the increased risk represented by older mothers is passed on to offspring of her non-affected daughters.

Influence of advanced age of maternal grandmothers on Down syndrome.

BackgroundDown syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%), mosaic trisomy 21 (2–4%) and translocation (3–4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction.MethodsWe investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression.ResultsOut of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%.ConclusionBesides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.