scholarly journals The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

2012 ◽  
Vol 216 (2) ◽  
pp. R19-R31 ◽  
Author(s):  
Christophe Breton
Keyword(s):  
Birth Weight ◽  
Energy Balance ◽  
Maternal Obesity ◽  
Therapeutic Option ◽  
Cell Metabolism ◽  
Brain Maturation ◽  
High Birth Weight ◽  
Fat Cell ◽  
Maternal Undernutrition ◽  
Increased Risk

Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life. High birth weight due to maternal obesity or diabetes, inappropriate early post-natal nutrition and rapid catch-up growth may also sensitise to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of foetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set point. The hypothalamus–adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level. The perinatal period largely corresponds to the period of brain maturation, neuronal differentiation and active adipogenesis in rodents. Numerous dams and/or foetus/neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents. These models showed several common offspring hypothalamic consequences such as impaired neurogenesis, neuronal functionality, nuclei structural organisation and feeding circuitry hardwiring. These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways, leptin/insulin resistance and hyperphagia. Impaired hypothalamic sympathetic outflow to adipose tissue and/or reduced innervation may also account for modified fat cell metabolism. Thus, enhanced adipogenesis and/or lipogenesis capacities may predispose the offspring to fat accumulation. Abnormal hypothalamus–adipose axis circadian rhythms were also evidenced. This review mainly focuses on studies in rodents. It highlights hormonal and epigenetic mechanisms responsible for long-lasting programming of energy balance in the offspring. Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans.

Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Christophe Breton
Keyword(s):  
Adipose Tissue ◽  
Birth Weight ◽  
Energy Homeostasis ◽  
Maternal Obesity ◽  
Maternal Nutrition ◽  
The Body ◽  
High Birth Weight ◽  
Storage Unit ◽  
Maternal Undernutrition ◽  
Increased Risk

AbstractThe epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.

scholarly journals Birth weight trends in England and Wales (1986–2012): babies are getting heavier

2017 ◽  
Vol 103 (3) ◽  
pp. F264-F270 ◽  
Author(s):  
Rebecca Elisabeth Ghosh ◽  
Jacob Dag Berild ◽  
Anna Freni Sterrantino ◽  
Mireille B Toledano ◽  
Anna L Hansell
Keyword(s):  
Birth Weight ◽  
Maternal Age ◽  
Maternal Obesity ◽  
Disease Risk ◽  
Strong Predictor ◽  
Temporal Trends ◽  
High Birth Weight ◽  
Data Set ◽  
England And Wales ◽  
Increased Risk

IntroductionBirth weight is a strong predictor of infant mortality, morbidity and later disease risk. Previous work from the 1980s indicated a shift in the UK towards heavier births; this descriptive analysis looks at more recent trends.MethodsOffice for National Statistics (ONS) registration data on 17.2 million live, single births from 1986 to 2012 were investigated for temporal trends in mean birth weight, potential years of birth weight change and changes in the proportions of very low (<1500 g), low (<2500 g) and high (≥4000 g) birth weight. Analysis used multiple linear and logistic regression adjusted for maternal age, marital status, area-level deprivation and ethnicity. Additional analyses used the ONS NHS Numbers for Babies data set for 2006–2012, which has information on individual ethnicity and gestational age.ResultsOver 27 years there was an increase in birth weight of 43 g (95% CI 42 to 44) in females and 44 g (95% CI 43 to 45) in males, driven by birth weight increases between 1986–1990 and 2007–2012. There was a concurrent decreased risk of having low birth weight but an 8% increased risk in males and 10% increased risk in females of having high birth weight. For 2006–2012 the birth weight increase was greater in preterm as compared with term births.ConclusionsSince 1986 the birth weight distribution of live, single births in England and Wales has shifted towards heavier births, partly explained by increases in maternal age and non-white ethnicity, as well as changes in deprivation levels. Other potential influences include increases in maternal obesity and reductions in smoking prevalence particularly following the introduction of legislation restricting smoking in public places in 2007.

Nutritional manipulations in the perinatal period program adipose tissue in offspring

2013 ◽  
Vol 305 (10) ◽  
pp. E1195-E1207 ◽  
Author(s):  
Marie-Amélie Lukaszewski ◽  
Delphine Eberlé ◽  
Didier Vieau ◽  
Christophe Breton
Keyword(s):  
Adipose Tissue ◽  
Birth Weight ◽  
Perinatal Period ◽  
Leptin Resistance ◽  
High Birth Weight ◽  
Postnatal Life ◽  
Low Grade ◽  
Maternal Undernutrition ◽  
Obesity And Diabetes ◽  
Increased Risk

Epidemiological studies demonstrated initially that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates, and rapid catchup growth also increase the risk of adult-onset obesity. As stated by the Developmental Origin of Health and Disease concept, nutrient supply perturbations in the fetus or neonate result in long-term programming of individual body weight set point. Adipose tissue is a key fuel storage unit involved mainly in the maintenance of energy homeostasis. Studies in numerous animal models have demonstrated that the adipose tissue is the focus of developmental programming events in a sex- and depot-specific manner. In rodents, adipose tissue development is particularly active during the perinatal period, especially during the last week of gestation and during early postnatal life. In contrast to rodents, this process essentially takes place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several mechanisms of adipose tissue programming. Offspring from malnourished dams present adipose tissue with a series of alterations: impaired glucose uptake, insulin and leptin resistance, low-grade inflammation, modified sympathetic activity with reduced noradrenergic innervations, and thermogenesis. These modifications reprogram adipose tissue metabolism by changing fat distribution and composition and by enhancing adipogenesis, predisposing the offspring to fat accumulation. Subtle adipose tissue circadian rhythm changes are also observed. Inappropriate hormone levels, modified tissue sensitivity (especially glucocorticoid system), and epigenetic mechanisms are key factors for adipose tissue programming during the perinatal period.

scholarly journals Obstetric Anal Sphincter Injuries – Maternal, Foetal and Sociodemographic Risk Factors: A Retrospective Register-Based Study

2021 ◽  
Author(s):  
Kristin André ◽  
Andrea Stuart ◽  
Kärin Kallén
Keyword(s):  
Risk Factors ◽  
Birth Weight ◽  
Caesarean Section ◽  
Anal Sphincter ◽  
Maternal Education ◽  
Vacuum Extraction ◽  
High Birth Weight ◽  
Previous Caesarean Section ◽  
Obstetric Anal Sphincter Injuries ◽  
Increased Risk

Objective. To determine risk and protective factors of obstetric anal sphincter injuries (OASIS). Design. A retrospective register-based observational study. Setting. Sweden. Population. A cohort of 988, 988 singleton term deliveries 2005-2016 were included. Methods. Data from the Swedish Medical Birth Registry and Statistics Sweden were extracted to identify cases of OASIS and maternal and foetal characteristics. Modified Poisson Regression analyses were performed to assess risk factors. Main outcome measures. Risk ratios for OASIS with 95% confidence interval associated with maternal and foetal risk factors were calculated. Results. The rate of OASIS was 3.5% (n=34, 583). Primiparity (aRR 3.13 95% CI 3.05–3.21), vacuum extraction (aRR 2.79 95% CI 2.73–2.86), forceps (aRR 4.27 95% CI 3.86–4.72) and high birth weight (aRR 2.61 95% CI 2.50–2.72) were associated with a significantly increased risk of OASIS. Increasing maternal age and decreasing maternal height increased the risk of OASIS. Smoking (aRR 0.74 95% CI 0.70–0.79) and low maternal education (aRR 0.87 95% CI 0.83–0.92) were associated with a decreased frequency of reported OASIS. Obesity decreased the risk of OASIS (aRR 0.90 95% CI 0.87–0.94), but only after adjusting for foetal birth weight. Previous caesarean section increased the risk of OASIS (aRR 1.41; 95% CI 1.36–1.47). Conclusion. Primiparity, instrumental delivery and high birth weight increased the risk of OASIS. Risk factors including BMI, height, age, smoking, maternal education, ethnicity and previous caesarean section also contribute to the overall risk of OASIS. Keywords. Obstetric sphincter injuries, risk factors, pregnancy.

scholarly journals A comparative analysis of determinants of low birth weight and stunting among under five children of adolescent and non-adolescent mothers using 2015/16 Tanzania Demographic and Health Survey (TDHS)

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ramadhani H. Mtongwa ◽  
Charles Festo ◽  
Ester Elisaria
Keyword(s):  
Socioeconomic Status ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Adolescent Mothers ◽  
Maternal Age ◽  
Maternal Obesity ◽  
Maternal Body Mass Index ◽  
Child Birth ◽  
Maternal Undernutrition ◽  
Children Under 5

Abstract Background Tanzania is one of the Sub-Saharan African country with nearly 12 out of 60 million people being adolescent. The prevalence of child marriage is higher with one out of every three girls being married before reaching their 18th birthday, 5 % being married by the age of 15, and 31% by the age of 18 years. Literature shows early pregnancy is associated with Low Birth Weight (LBW) and stunting among children under 5 years. This paper explores variation and factors associated with low birth weight and stunting among children born by adolescent and non-adolescent mothers. Methods Data from 13,266 women with children under 5 years collected as part of the 2015/2016 TDHS was re-analyzed using STATA version 14 software while accounting for survey design. A total of 6385 women (of which 7.2% were adolescent) and 8852 women (of which 6.7% were adolescent) were involved in the analysis of child birth weight and stunting respectively. Descriptive statistics stratified by maternal age was conducted with LBW and stunting as outcome variables followed by logistic regressions models controlling for confounding variables. Results The proportion of obese or overweight adolescent and non-adolescent mothers was 11.8 and 36.5% respectively. Antenatal care (ANC) attendance, areas of residence and social economic status were very similar in the two maternal age groups. Non- adolescent mothers had reduced odds of giving birth to LBW babies compared to adolescent mothers (Adjusted Odds Ratio (AOR) = 0.34; 95% CI: 0.22–0.50). Maternal undernutrition (AOR = 2.29; 95% CI: 1.43–3.67), being divorced, separated or widowed (AOR = 1.76; 95% CI: 1.24–2.50) and having at least four ANC visits (AOR = 0.64; 95% CI: 0.49–0.83) were significantly associated with reduced odds of having a LBW. Child stunting was not associated with maternal age. Maternal high socioeconomic status (AOR = 0.69; 95% CI: 0.57–0.84) and maternal obesity or overweight (AOR = 0.77; 95% CI: 0.64–0.92) were negatively associated with stunting. Child birth weight, sex, and age were significantly associated with stunting. Conclusion Maternal age was a predictor of LBW but not stunting. ANC attendance and not living with a spouse increase the risk of LBW babies. Stunting was associated with low maternal body mass index (BMI), low socioeconomic status, child birth weight, gender, and age. A multi-sectoral approach is needed to address child nutrition problems with teenagers ‘specific intervention that offer emotional support, and health education during pregnancies for improving immediate and later life child birth outcomes.

scholarly journals Association of high birth weight with overweight and obesity in Chinese students aged 6–18 years: a national, cross-sectional study in China

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e024532 ◽  
Author(s):  
Zhiyong Zou ◽  
Zhongping Yang ◽  
Zhaogeng Yang ◽  
Xijie Wang ◽  
Di Gao ◽  
...  
Keyword(s):  
Birth Weight ◽  
Age Groups ◽  
Chinese Students ◽  
Cross Sectional Study ◽  
Overweight And Obesity ◽  
High Birth Weight ◽  
Cross Sectional Survey ◽  
Anthropometric Parameters ◽  
Cross Sectional ◽  
Increased Risk

BackgroundThe prevalence of childhood overweight and obesity in China has drastically increased 57 times over the past 30 years, and to control birth weight is an effective way to reduce the risk of overweight and obesity across the life course.ObjectiveThis paper aimed to evaluate the association of high birth weight (HBW) with overweight and obesity in Chinese students aged 6–18 years.MethodsAll students with HBW (n=4981) aged 6–18 years were selected from a cross-sectional survey from seven provinces of China, and 4981 other students with normal birth weight (NBW) were randomly sampled with matched gender, age and province. Anthropometric parameters were measured and characteristics were collected by questionnaires. Multiple logistic regression was used to estimate the OR of overweight and obesity with HBW, unadjusted and adjusted for confounding factors.ResultsParticipants with HBW revealed higher body mass index in childhood. The prevalence of overweight and obesity was significantly higher in the HBW group than in the NBW group (overweight 15.3% vs 13.1%, p<0.05; obesity 16.9% vs 10.6%, p<0.05), and the results were similar for overweight in all age groups except age 6–7, age 14–15 and age 16–18. Additionally, HBW was positively associated with overweight (OR=1.230; 95% CI 1.056 to 1.432) and obesity (OR=1.611; 95% CI 1.368 to 1.897) after adjustment for covariates.ConclusionsHBW leads to an increased risk of overweight and obesity in childhood; thus, measures to control birth weight, such as controlling gestational weight gain, should be taken from the earliest beginning of life.Trial registration numberNCT02343588; Post-results.

scholarly journals Association between birth weight and risk of abdominal obesity in children and adolescents: a school-based epidemiology survey in China

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhaogen Yang ◽  
Bin Dong ◽  
Yi Song ◽  
Xijie Wang ◽  
Yanhui Dong ◽  
...  
Keyword(s):  
Birth Weight ◽  
Regression Model ◽  
Children And Adolescents ◽  
Abdominal Obesity ◽  
Polynomial Regression ◽  
Age Groups ◽  
High Birth Weight ◽  
Fractional Polynomial ◽  
Increased Risk ◽  
Study Participants

Abstract Background Abdominal obesity is becoming an increasingly serious public health challenge in children and adolescents, there remains controversial opinions on birth weight and risk of childhood abdominal obesity. This study aims to assess the association between birth weight and the risk of abdominal obesity in childhood, as well as to compare the associations among different sex and age groups. Methods A total number of 30,486 (15,869 boys and 14,617 girls) participants aged 6–17 years old were included in this study. Participants were classified into five groups according to their birth weight. Waist-to-height ratio (WHtR) was used to define abdominal obesity. Fractional polynomial regression model was used to assess the association between birth weight and WHtR, and a multi-variable logistic regression model was applied to evaluate the risk of abdominal obesity in different birth weight groups. Results A J-shaped association was observed between birth weight and WHtR. Compared with birth weight of 2500–2999 g, high birth weight was associated with increased risk of abdominal obesity [OR (95% CI) for 3000–3499 g: 1.12(1.00–1.24); 3500–3999 g: 1.19(1.07–1.34); ≥4000 g: 1.42(1.24–1.62)]. No significant correlation was observed in children with birth weight ≤ 2499 g. Similar patterns were observed across different age groups. Abdominal obesity risk for high birth weight was particularly pronounced in boys compared to girls. Conclusions Birth weight ≥ 3000 g, especially for boys, was associated with an elevated risk of abdominal obesity in childhood and may benefit from intervention to mitigate this risk.

scholarly journals Metabolic programming in early life in humans

2019 ◽  
Vol 374 (1770) ◽  
pp. 20180123 ◽  
Author(s):  
Caroline H. D. Fall ◽  
Kalyanaraman Kumaran
Keyword(s):  
Metabolic Disease ◽  
Birth Weight ◽  
Early Life ◽  
Disease Risk ◽  
Evolutionary Medicine ◽  
Metabolic Effects ◽  
High Birth Weight ◽  
Preventive Strategy ◽  
Increased Risk

An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic disease. High birth weight caused by maternal gestational diabetes is also associated with later diabetes, suggesting that fetal over-nutrition also has programming effects. Post-natal factors (excess weight gain/obesity, smoking, poor diets and physical inactivity) interact with fetal exposures to increase disease risk. Animal studies have shown permanent metabolic effects in offspring after alterations to maternal or early post-natal diets but evidence in humans is largely limited to observational and quasi-experimental situations such as maternal famine exposure. Randomized trials of maternal nutritional interventions during pregnancy have so far had limited follow-up of the offspring. Moreover, interventions usually started after the first trimester and therefore missed key peri-conceptional or early pregnancy events such as epigenetic changes, placentation and fetal organogenesis. Recent and ongoing trials intervening pre-conceptionally and powered for long-term offspring follow-up will address these issues. While current preventive strategies for cardio-metabolic disease focus on high-risk individuals in mid-life, DOHaD concepts offer a ‘primordial’ preventive strategy to reduce disease in future generations by improving fetal and infant development. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

O-075 The association between high birth weight and long-term outcomes-implications for Assisted Reproductive Technologies: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Å Magnusson ◽  
H Laivouri ◽  
A Loft ◽  
N Oldereid ◽  
A Pinborg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Birth Weight ◽  
Psychiatric Disorders ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
High Birth Weight ◽  
Increased Risk ◽  
Meta Analyses

Abstract Study question Do high birth weight or large for gestational age (LGS) increase the risk of serious disease later in life? Summary answer High birth weight and/or LGA were associated with elevated risks for certain child malignancies, breast cancer, psychiatric disorders, childhood hypertension and diabetes type 1. What is known already Previous studies have shown that children born after frozen embryo transfer (FET) have an increased risk of being born LGA or having a high birth weight. In recent years the practice of FET in Assisted Reproductive Technology (ART) has increased rapidly. The perinatal risks of being born LGA or with a high birth weight are well studied, however less is known about the impact on long-term health and morbidity. Study design, size, duration Pubmed, Scopus and Web of Science were searched until December 2020. 11 748 abstracts were screened, 172 publications were selected for systematic review and 63 for meta-analyses. The methodological quality in terms of risk of bias was assessed by pairs of reviewers. Robin-I (www.methods.cochrane.org) was used for assessing risk of bias in original articles. For systematic reviews AMSTAR was used. For certainty of evidence the GRADE system was used. Participants/materials, setting, methods Exposures were LGA and high birth weight. Long-term morbidity outcomes were cancer, metabolic disease, cardiovascular disease and psychiatric disorders. Cancer was focused on breast cancer, child malignancies in the central nervous system (CNS), hematological malignancies and Wilm´s tumor. Metabolic diseases included diabetes type 1 and type 2. Cardiovascular diseases were focused on hypertension and other cardiovascular disorders and psychiatric disorders on schizophrenia/psychosis and cognitive disorders. Main results and the role of chance Pooled Adjusted Odds Ratios (AOR) for outcome variables were compared for birth weights &gt;4000 or &gt; 4500 g versus &lt; 4000 g. For cancer, meta-analyses showed AOR of 1.24 (95% 1.11-1.39) for development of breast cancer, AOR of 1.15 (95% CI 1.05-1.27) for development of CNS tumors, AOR of 1.29 (95% CI 1.20-1.39) for childhood leukemia and AOR 1.68 (95% CI 1.38-2.06 ) for Wilm´s tumor. For metabolic disease a meta-analysis showed AOR of 1.15 (95%CI 1.05-1.26) for the association between high birth weight and type 1 diabetes. For psychiatric diseases an association was found between high birth weight and/or LGA and schizophrenia and depression. For cardiovascular disease, an association was found between high birth weight and hypertension in childhood with an inverse association in adulthood. No difference in the risk of coronary heart disease in adults born with high birth weight compared to normal birth Limitations, reasons for caution The main limitation is that all data are based on observational studies with their inborn risk of selection bias. Our conclusions are however, mainly based on meta-analyses and/or studies with low risk of bias. Wider implications of the findings Even though high birth weight and LGA are associated with an increased risk of serious diseases, both in childhood and in adulthood, the size of these effects seems modest. However, the identified risk associations should be taken into account in stimulation strategies and when considering fresh or frozen embryo transfer. Trial registration number Not applicable

Very High Birth Weight of Offspring Is Associated with an Increased Risk of Leukemia in Their Mothers; Results of a Population-Based Cohort Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4677-4677
Author(s):  
Ora Paltiel ◽  
Rebecca Yanetz ◽  
Ronit Calderon ◽  
Orly Manor ◽  
Susan Harlap ◽  
...  
Keyword(s):  
Birth Weight ◽  
Maternal Age ◽  
Childhood Leukemia ◽  
Demographic Data ◽  
Population Based ◽  
Continuous Variable ◽  
High Birth Weight ◽  
Average Birth Weight ◽  
Multivariate Adjustment ◽  
Increased Risk

Abstract High birth weight (HBW) is related to maternal diabetes, height, BMI and weight gain during pregnancy. Many previous studies have shown an association between HBW and childhood leukemia. Postulated mechanisms have included exposure to growth factors involved in somatic growth and leukemogenesis (e.g. IGF-1), common genetic mechanisms or higher cell number in larger individuals providing increased opportunity for genetic errors. It is not known to what extent the association is due to heritable factors, intra-uterine factors or both. To our knowledge, the association between offspring’s birth weight and leukemia risk in the parents has not been addressed. Methods: We utilized data from the Jerusalem Perinatal Study, a population-based research cohort including all births in West Jerusalem between 1964 and 1976. The database contains information on birth characteristics of the newborns, obstetric complications and birth outcomes as well as demographic data on the parents. After excluding the parents of twins and offspring with congenital malformations, we linked 39,336 mothers and 38,031 fathers of live-born infants through their unique identification numbers to the Israel Cancer Registry. We examined the association between leukemia and the average birth weight of all offspring of the same mother or father, as a categorical and continuous variable, as well as the effect of having at least one offspring weighing ≥4500 gm. Fewer than 2% of parents had offspring weighing 4500 gm or more. Results: Leukemias developed in 57 mothers and 132 fathers. Controlling for maternal age, having at least 1 child weighing ≥4500 gm at birth was associated with a 3-fold increase in the risk of leukemia (hazard ratio -HR 3.4, 95% confidence interval (CI) 1.06–10.91, p=0.04), compared to having no children at the extremes of birth weight. This result was unchanged after multivariate adjustment. Furthermore having an average birth weight among all offspring of ≥4500 gm increased the risk of leukemia in mothers more than 8 fold (HR 8.3, 95% CI: 2.5–27.7, p=0.0006), after controlling for maternal age and diabetes, compared to an average birth weight of 2500–3999 gm. This result was strengthened after further multivariate adjustment for family size and socioeconomic status (HR 8.99, 95%CI: 2.8–29.27, p=0.001). In a subgroup for which these data were available (∼13,000 mothers), results were unchanged after adjusting for maternal height. Birth weight assessed as a continuous variable was not related to mother’s leukemia. Specific subgroups of leukemia in the mother which were associated with HBW were CLL (HR 11.04, p=0.002) and CML (7.84, p=0.05) but these analyses were severely limited by small numbers. There was no association between HBW and father’s risk of leukemia. Conclusions: HBW is associated with leukemia not only in infants and children, but appears to confer an increased risk among their mothers. Whether this is due to a common exposure (eg pelvic irradiation), shared genes, or epigenetic phenomena bears exploring, after confirmation of these results in other cohorts.

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