Developmental Origins Of Health And Disease Research Articles

Developmental Programming in Animal Models: Critical Evidence of Current Environmental Negative Changes.

The Developmental Origins of Health and Disease (DOHaD) approach answers questions surrounding the early events suffered by the mother during reproductive stages that can either partially or permanently influence the developmental programming of children, predisposing them to be either healthy or exhibit negative health outcomes in adulthood. Globally, vulnerable populations tend to present high obesity rates, including among school-age children and women of reproductive age. In addition, adults suffer from high rates of diabetes, hypertension, cardiovascular, and other metabolic diseases. The increase in metabolic outcomes has been associated with the combination of maternal womb conditions and adult lifestyle–related factors such as malnutrition and obesity, smoking habits, and alcoholism. However, to date, “new environmental changes” have recently been considered negative factors of development, such as maternal sedentary lifestyle, lack of maternal attachment during lactation, overcrowding, smog, overurbanization, industrialization, noise pollution, and psychosocial stress experienced during the current SARS-CoV-2 pandemic. Therefore, it is important to recognize how all these factors impact offspring development during pregnancy and lactation, a period in which the subject cannot protect itself from these mechanisms. This review aims to introduce the importance of studying DOHaD, discuss classical programming studies, and address the importance of studying new emerging programming mechanisms, known as actual lifestyle factors, during pregnancy and lactation.

Development and the art of nutritional maintenance.

Development from early conceptus to a complex, multi-cellular organism is a highly ordered process that is dependent on an adequate supply of nutrients. During this process, the pattern of organ growth is robust, driven by a genetic blueprint and matched to anticipated body mass with high precision and with built-in physiological reserve capacity. This apparent canalisation of the developmental process is particularly sensitive to variation in environmental stimuli, such as inappropriate drug or hormone exposure, or pattern of nutrient delivery. Significant variation in any of these factors can profoundly affect fetal and neonatal growth patterns, with later detriment for physiological function and/or reserve capacity of the resultant adult, with potential health impact. This paradigm shift in science has become known as the Developmental Origins of Health and Disease (DOHaD). Over the last 30 years, many animal and clinical studies have vastly expanded our fundamental knowledge of developmental biology, particularly in the context of later effects on health. In this horizons article, we discuss DOHaD through the lens of nutritional quality (e.g. micronutrient, amino acid, NSP intake). The concept of ‘Quality’ was considered undefinable by Robert Persig in his book, ‘Zen and the Art of Motorcycle Maintenance’. Here, development and the art of nutritional maintenance will define quality in terms of the pattern of nutrient intake, the quality of development and how each interact to influence later health outcomes.

The Developmental Origins of Health and Disease: Adolescence as a Critical Lifecourse Period to Break the Transgenerational Cycle of NCDs-A Narrative Review.

Noncommunicable diseases (NCDs), including type 2 diabetes and cardiovascular disease, represent a significant and growing global health burden. To date, a primary focus has been on treatment approaches to NCDs once manifested rather than strategies aimed at prevention. In this context, there is clear evidence that a range of adverse early life exposures can predispose individuals towards a greater risk of developing NCDs across the lifecourse. These risk factors can be passed to future generations, thus perpetuating a cycle of disease. This concept, preferentially termed “developmental programming”, forms the basis of the Developmental Origins of Health and Disease (DOHaD) framework. To date, DOHaD has focused on preconception, pregnancy, lactation and, more recently, paternal health at the time of conception. However, it is becoming increasingly clear that investment in the window of adolescence is perhaps the most critical developmental window. Adolescence is a period where lifestyle behaviours become entrained. Therefore, a focus on adolescent behaviours, health literacy and emotional development may afford the best opportunity to break the cycle of NCDs. As the next generation of parents, adolescents should therefore be considered a priority group in advancing appropriate and informed actions aimed at reducing NCD risk factors across the lifecourse. This advancement requires a more comprehensive community understanding and uptake of DOHaD knowledge and concepts. NCD prevention strategies have typically entailed siloed (and often disease-specific) approaches with limited efficacy in curbing NCD prevalence and breaking the transgenerational transmission of disease traits. Recent findings across various disciplines have highlighted that a lifecourse systems approach is required to establish a comprehensive and sustainable framework for NCD intervention. A whole community approach with a particular focus on adolescents as potential agents of change is necessary to break the disease cycle.

Utility of preclinical models of altered maternal nutrition to support the developmental origins of health and disease hypothesis.

A clear link has been established between alterations in the early life environment and the risk for developing a range of cardiometabolic diseases in later life, a process preferentially termed developmental programming. In particular, alterations in the maternal nutritional environment have been associated with a range of adverse health outcomes in offspring across the lifecourse; effects that can be passed on to future generations. Following from the early epidemiological observations that provided the basis for the developmental origins of health and disease (DOHaD) hypothesis, a range of animal models were developed to examine the impact of early life programming and provide empirical data to support the emerging framework. These models became key tools to aid in our understanding of developmental programming as allowed investigation of potential mechanisms, strategies for intervention and transgenerational effects. The study published by Langley and Evans (Clin. Sci. 1994;86(2):217–222; DOI:10.1042/CS0860217), using a rat model of maternal low protein exposure, was one of the first to highlight the impact of an altered maternal nutritional environment on programming of elevated blood pressure in offspring. This work became a hallmark study in the DOHaD field by demonstrating key proof of principle to support the early epidemiological associations and characterizing a key preclinical model that has contributed greatly to our understanding of mechanisms underpinning developmental programming—particularly in the area of cardiovascular and renal function.

Litter Size Reduction as a Model of Overfeeding during Lactation and Its Consequences for the Development of Metabolic Diseases in the Offspring.

Overfeeding during lactation has a deleterious impact on the baby’s health throughout life. In humans, early overnutrition has been associated with higher susceptibility to obesity and metabolic disorders in childhood and adulthood. In rodents, using a rodent litter size reduction model (small litter) to mimic early overfeeding, the same metabolic profile has been described. Therefore, the rodent small litter model is an efficient tool to investigate the adaptive mechanisms involved in obesogenesis. Besides central and metabolic dysfunctions, studies have pointed to the contribution of the endocrine system to the small litter phenotype. Hormones, especially leptin, insulin, and adrenal hormones, have been associated with satiety, glucose homeostasis, and adipogenesis, while hypothyroidism impairs energy metabolism, favoring obesity. Behavioral modifications, hepatic metabolism changes, and reproductive dysfunctions have also been reported. In this review, we update these findings, highlighting the interaction of early nutrition and the adaptive features of the endocrine system. We also report the sex-related differences and epigenetic mechanisms. This model highlights the intense plasticity during lactation triggering many adaptive responses, which are the basis of the developmental origins of health and disease (DOHaD) concept. Our review demonstrates the complexity of the adaptive mechanisms involved in the obesity phenotype promoted by early overnutrition, reinforcing the necessity of adequate nutritional habits during lactation.

Methylation pattern of polymorphically imprinted nc886 is not conserved across mammalia.

BackgroundIn humans, the nc886 locus is a polymorphically imprinted metastable epiallele. Periconceptional conditions have an effect on the methylation status of nc886, and further, this methylation status is associated with health outcomes in later life, in line with the Developmental Origins of Health and Disease (DOHaD) hypothesis. Animal models would offer opportunities to study the associations between periconceptional conditions, nc886 methylation status and metabolic phenotypes further. Thus, we set out to investigate the methylation pattern of the nc886 locus in non-human mammals.DataWe obtained DNA methylation data from the data repository GEO for mammals, whose nc886 gene included all three major parts of nc886 and had sequency similarity of over 80% with the human nc886. Our final sample set consisted of DNA methylation data from humans, chimpanzees, bonobos, gorillas, orangutangs, baboons, macaques, vervets, marmosets and guinea pigs.ResultsIn human data sets the methylation pattern of nc886 locus followed the expected bimodal distribution, indicative of polymorphic imprinting. In great apes, we identified a unimodal DNA methylation pattern with 50% methylation level in all individuals and in all subspecies. In Old World monkeys, the between individual variation was greater and methylation on average was close to 60%. In guinea pigs the region around the nc886 homologue was non-methylated. Results obtained from the sequence comparison of the CTCF binding sites flanking the nc886 gene support the results on the DNA methylation data.ConclusionsOur results indicate that unlike in humans, nc886 is not a polymorphically imprinted metastable epiallele in non-human primates or in guinea pigs, thus implying that animal models are not applicable for nc886 research. The obtained data suggests that the nc886 region may be classically imprinted in great apes, and potentially also in Old World monkeys, but not in guinea pigs.

Prenatal Environment and Neurodevelopmental Disorders.

The internal and external environment of the mother during the developmental stages of the fetus affects the offspring’s health. According to the developmental origins of health and disease (DOHaD) theory, environmental factors influence the offspring and also affect health in adulthood. Recently, studies based on this theory have gained attracted attention because of their clinical utility in identifying the risk groups for various diseases. Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) can be caused by exposure to certain prenatal environments during pregnancy. This review describes the latest findings on the effect of prenatal environment on the onset mechanism of NDDs based on the DOHaD theory. Unravelling the molecular mechanisms underlying the pathogenesis of NDDs is important, because there are no therapeutic drugs for these disorders. Furthermore, elucidating the relationship between the DOHaD theory and NDDs will contribute to the popularization of preventive medicine.

A biosocial return to race? A cautionary view for the postgenomic era.

Recent studies demonstrating epigenetic and developmental sensitivity to early environments, as exemplified by fields like the Developmental Origins of Health and Disease (DOHaD) and environmental epigenetics, are bringing new data and models to bear on debates about race, genetics, and society. Here, we first survey the historical prominence of models of environmental determinism in early formulations of racial thinking to illustrate how notions of direct environmental effects on bodies have been used to naturalize racial hierarchy and inequalities in the past. Next, we conduct a scoping review of postgenomic work in environmental epigenetics and DOHaD that looks at the role of race/ethnicity in human health (2000–2021). Although there is substantial heterogeneity in how race is conceptualized and interpreted across studies, we observe practices that may unwittingly encourage typological thinking, including: using DNA methylation as a novel marker of racial classification; neglect of variation and reversibility within supposedly homogenous racial groups; and a tendency to label and reify whole groups as pathologized or impaired. Even in the very different politico‐economic and epistemic context of contemporary postgenomic science, these trends echo deeply held beliefs in Western thinking which claimed that different environments shape different bodies and then used this logic to argue for essential differences between Europeans and non‐Europeans. We conclude with a series of suggestions on interpreting and reporting findings in these fields that we feel will help researchers harness this work to benefit disadvantaged groups while avoiding the inadvertent dissemination of new and old forms of stigma or prejudice.

Taurine: A Maternally Derived Nutrient Linking Mother and Offspring.

Mammals can obtain taurine from food and synthesize it from sulfur-containing amino acids. Mammalian fetuses and infants have little ability to synthesize taurine. Therefore, they are dependent on taurine given from mothers either via the placenta or via breast milk. Many lines of evidence demonstrate that maternally derived taurine is essential for offspring development, shaping various traits in adults. Various environmental factors, including maternal obesity, preeclampsia, and undernutrition, can affect the efficacy of taurine transfer via either the placenta or breast milk. Thus, maternally derived taurine during the perinatal period can influence the offspring’s development and even determine health and disease later in life. In this review, I will discuss the biological function of taurine during development and the regulatory mechanisms of taurine transport from mother to offspring. I also refer to the possible environmental factors affecting taurine functions in mother-offspring bonding during perinatal periods. The possible functions of taurine as a determinant of gut microbiota and in the context of the Developmental Origins of Health and Disease (DOHaD) hypothesis will also be discussed.

Impact of COVID-19 pandemic on research and careers of early career researchers: a DOHaD perspective.

The COVID-19 pandemic has exposed several inequalities worldwide, including the populations' access to healthcare systems and economic differences that impact the access to vaccination, medical resources, and health care services. Scientific research activities were not an exception, such that scientific research was profoundly impacted globally. Research trainees and early career researchers (ECRs) are the life force of scientific discovery around the world, and their work and progress in research was dramatically affected by the COVID-19 pandemic. ECRs are a particularly vulnerable group as they are in a formative stage of their scientific careers, any disruptions during which is going to likely impact their lifelong career trajectory. To understand how COVID-19 impacted lives, career development plans, and research of Developmental Origins of Health and Disease (DOHaD) ECRs, the International DOHaD ECR committee formed a special interest group comprising of ECR representatives of International DOHaD affiliated Societies/Chapters from around the world (Australia and New Zealand, Canada, French Speaking DOHaD, Japan, Latin America, Pakistan and USA). The anecdotal evidence summarized in this brief report, provide an overview of the findings of this special interest group, specifically on the impact of the evolving COVID-19 pandemic on daily research activities and its effects on career development plans of ECRs. We also discuss how our learnings from these shared experiences can strengthen collaborative work for the current and future generation of scientists.

Caring for biosocial complexity. Articulations of the environment in research on the Developmental Origins of Health and Disease

The research field of Developmental Origins of Health and Disease (DOHaD) provides a framework for understanding how a wide range of environmental factors, such as deprivation, nutrition and stress, shape individual and population health over the course of a lifetime. DOHaD researchers face the challenge of how to conceptualize and measure ontologically diverse environments and their interactions with the developing organism over extended periods of time. Based on ethnographic research, I show how DOHaD researchers are often eager to capture what they regard as more ‘complex’ understandings of the environment in their work. At the same time, they are confronted with established methodological tools, disciplinary infrastructures and institutional contexts that favor simplistic articulations of the environment as distinct and mainly individual-level variables. I show how researchers struggle with these simplistic articulations of nutrition, maternal bodies and social determinants as relevant environments, which are sometimes at odds with the researchers’ own normative commitments and aspirations.

Circuits of Time: Enacting Postgenomics in Indigenous Australia

Some Indigenous Australians have embraced developmental origins of health and disease (DOHaD) and epigenetic discourses to highlight the legacies of slow violence in a settler colonial context. Despite important differences between Indigenous and scientific knowledges, some Indigenous scholars are positioning DOHaD and epigenetics as a resource to benefit their communities. This article argues that time plays a crucial role of brokering disparate knowledge spaces in Indigenous discourses of postgenomics, with both Indigenous cosmological frames and DOHaD/epigenetics centring a circular temporal model. Drawing on interview data with scientists who work in Indigenous health, and broader ethnographic work in Indigenous Australian contexts where epigenetics is deployed, this article explores how different circularities of space and time become entangled to co-produce narratives of historical trauma. We use the concept of biocircularity to understand the complex ways that Indigenous and postgenomic temporalities are separated and connected, circling each other to produce a postcolonial articulation of postgenomics as a model of collective embodiment and distributed responsibility.

Bovine Animal Model for Studying the Maternal Microbiome, in utero Microbial Colonization and Their Role in Offspring Development and Fetal Programming.

Recent developments call for further research on the timing and mechanisms involved in the initial colonization of the fetal/infant gut by the maternal microbiome and its role in Developmental Origins of Health and Disease (DOHaD). Although progress has been made using primarily preterm infants, ethical and legal constraints hinder research progress in embryo/fetal-related research and understanding the developmental and mechanistic roles of the maternal microbiome in fetal microbial imprinting and its long-term role in early-life microbiome development. Rodent models have proven very good for studying the role of the maternal microbiome in fetal programming. However, some inherent limitations in these animal models make it challenging to study perinatal microbial colonization from a biomedical standpoint. In this review, we discuss the potential use of bovine animals as a biomedical model to study the maternal microbiome, in utero microbial colonization of the fetal gut, and their impact on offspring development and DOHaD.

Early programming of reproductive health and fertility: novel neuroendocrine mechanisms and implications in reproductive medicine.

BACKGROUNDAccording to the Developmental Origins of Health and Disease (DOHaD) hypothesis, environmental changes taking place during early maturational periods may alter normal development and predispose to the occurrence of diverse pathologies later in life. Indeed, adverse conditions during these critical developmental windows of high plasticity have been reported to alter the offspring developmental trajectory, causing permanent functional and structural perturbations that in the long term may enhance disease susceptibility. However, while solid evidence has documented that fluctuations in environmental factors, ranging from nutrient availability to chemicals, in early developmental stages (including the peri-conceptional period) have discernible programming effects that increase vulnerability to develop metabolic perturbations, the impact and eventual mechanisms involved, of such developmental alterations on the reproductive phenotype of offspring have received less attention.OBJECTIVE AND RATIONALEThis review will summarize recent advances in basic and clinical research that support the concept of DOHaD in the context of the impact of nutritional and hormonal perturbations, occurring during the periconceptional, fetal and early postnatal stages, on different aspects of reproductive function in both sexes. Special emphasis will be given to the effects of early nutritional stress on the timing of puberty and adult gonadotropic function, and to address the underlying neuroendocrine pathways, with particular attention to involvement of the Kiss1 system in these reproductive perturbations. The implications of such phenomena in terms of reproductive medicine will also be considered.SEARCH METHODSA comprehensive MEDLINE search, using PubMed as main interface, of research articles and reviews, published mainly between 2006 and 2021, has been carried out. Search was implemented using multiple terms, focusing on clinical and preclinical data from DOHaD studies, addressing periconceptional, gestational and perinatal programming of reproduction. Selected studies addressing early programming of metabolic function have also been considered, when relevant.OUTCOMESA solid body of evidence, from clinical and preclinical studies, has documented the impact of nutritional and hormonal fluctuations during the periconceptional, prenatal and early postnatal periods on pubertal maturation, as well as adult gonadotropic function and fertility. Furthermore, exposure to environmental chemicals, such as bisphenol A, and maternal stress has been shown to negatively influence pubertal development and gonadotropic function in adulthood. The underlying neuroendocrine pathways and mechanisms involved have been also addressed, mainly by preclinical studies, which have identified an, as yet incomplete, array of molecular and neurohormonal effectors. These include, prominently, epigenetic regulatory mechanisms and the hypothalamic Kiss1 system, which likely contribute to the generation of reproductive alterations in conditions of early nutritional and/or metabolic stress. In addition to the Kiss1 system, other major hypothalamic regulators of GnRH neurosecretion, such as γ-aminobutyric acid and glutamate, may be targets of developmental programming.WIDER IMPLICATIONSThis review addresses an underdeveloped area of reproductive biology and medicine that may help to improve our understanding of human reproductive disorders and stresses the importance, and eventual pathogenic impact, of early determinants of puberty, adult reproductive function and fertility.

Birthweight moderates the association between chronological age and infants' abilities to respond to cues for joint attention.

Infants born preterm are more likely than ever to survive, but relatively little is known about the factors that influence their subsequent sociocognitive development. Responding to joint attention (RJA) is a pivotal skill that is likely supported by biological preparedness at birth and ex-utero social experience. The goals of this study are to evaluate the relative roles of chronological age, gestation duration, and birthweight for early RJA and examine birthweight as a potential moderator of the associations between chronological age and RJA. This study leveraged a mixed longitudinal design of infants (N=256, obs=421) from 8 to 16 months of chronological age. Results show that chronological age and gestation duration both explain unique variation in RJA. Further, birthweight exhibits quadratic relations with RJA. Birthweight moderates the association between chronological age and RJA; infants born heavier demonstrate faster RJA growth compared to those born smaller. Findings suggest that birth weight, an index of nutrient sufficiency in utero and biological preparedness, may constrain or afford early RJA development, consistent with the Developmental Origins of Health and Disease (DoHAD) hypothesis. Findings inform our understanding of the roles of biological preparedness and experience in shaping RJA and help disaggregate potential mechanisms of prematurity-related challenges to social cognitive development.

Placental genomics mediates genetic associations with complex health traits and disease

As the master regulator in utero, the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we perform distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 traits, integrating placental multi-omics from the Extremely Low Gestational Age Newborn Study. At P ; < ; 2.5times {10}^{-6}, we detect 248 GTAs, mostly for neonatal and metabolic traits, across 176 genes, enriched for cell growth and immunological pathways. In aggregate, genetic effects mediated by placental expression significantly explain 4 early-life traits but no later-in-life traits. 89 GTAs show significant mediation through distal genetic variants, identifying hypotheses for distal regulation of GTAs. Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A, both associated with waist-hip ratio in TWAS, and multiple genes involved in metabolic pathways. These results suggest profound health impacts of placental genomic regulation in developmental programming across the life course.

Understanding the Links among Maternal Diet, Myelination, and Depression: Preclinical and Clinical Overview.

Depression is one of the most common mental disorders in the general population, and multiple mechanisms are involved in the etiology of this disease, including myelination. According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, maternal diet affects the lifetime of the individual during adulthood and may contribute to the development of neuropsychiatric disorders. Additionally, the intensive processes of myelination contribute to the development of the central nervous system in the perinatal period, while any alterations during this crucial process providing the physiological functioning of neurons may lead to neuropsychiatric disorders in the next generation. The present review summarizes the current knowledge on the role of the myelin-related changes in depression, as well as the crosstalk among maternal malnutrition, myelination, and depression in preclinical and clinical settings.

Developmental Origins of Metaflammation; A Bridge to the Future Between the DOHaD Theory and Evolutionary Biology.

Metabolic syndrome refers to obesity-associated metabolic disorders that increase the risk of type 2 diabetes, coronary diseases, stroke, and other disabilities. Environmental imbalance during the early developmental period affects health and increases susceptibility to non-communicable diseases, including metabolic syndrome, in later life; therefore, the Developmental Origins of Health and Disease (DOHaD) theory was established. According to the DOHaD theory, the hypothesis of the energy-saving ‘Thrifty Phenotype’ in undernourished fetuses is one of the well-accepted schemes as a risk of developing metabolic syndrome. This phenotype is evolutionarily advantageous for survival of the fittest in a hangry environment after birth, a strong selection pressure, but increases the risk of developing metabolic syndrome under an obesogenic diet according to the ‘Mismatch’ hypothesis. Increasing evidences support that chronic inflammation pathophysiologically connects obesity to metabolic disorders in metabolic syndrome, leading to the concept of ‘Metaflammation’. ‘Metaflammation’ in humans is proposed to originate from the evolutionary conservation of crosstalk between immune and metabolic pathways; however, few studies have investigated the contribution of evolutionary maladaptation to the pathophysiology of ‘Metaflammation’. Therefore, it is promising to investigate ‘Metaflammation’ from the viewpoint of selective advantages and its ‘Mismatch’ to an unexpected environment in contemporary lifestyles, in consideration of the principal concept of evolutionarily conserved nutrient sensing and immune signaling systems.

Early programming of hypertension.

Hypertension (HTN) is a modifiable risk factor for cardiovascular disease (CVD) and should be included in the study of developmental origins of health and disease (DOHaD). during gestation and perinatal life may affect developmental plasticity, during which the fetus adapts to environmental conditions that pose During intrauterine and perinatal development, different environmental factors have an impact on the early programming of noncommunicable diseases (NCDs). This review provides a summary of the evidence that connects the fetus' plasticity and adaptive changes to unfavorable environmental factors that alter the adult phenotype in the development of HTN. Such adaptive changes result from epigenetic changes that favor the development of HTN and CVD in adulthood with intergenerational implications. Lastly, we mention preventive strategies to limit or reverse any variable that may alter developmental programming leading to HTN later in life.

Effect of maternal smoking during pregnancy on gestational weight gain and birthweight: A stratified analysis by pregestational weight status.

INTRODUCTIONIn Japan, low birthweight (LBW) of infants is a major public health concern. Gestational weight gain (GWG) may be associated with LBW of infants. On the other hand, maternal smoking during pregnancy is a well-known factor associated with infant birthweight. Thus, this study aimed to examine the effect of maternal smoking during pregnancy on GWG and birthweight stratified by pregestational weight status.METHODSA retrospective cohort study was designed, which included three hospitals of Yamanashi Prefecture, Japan. The study included babies born between 2013 and 2014 from mothers having singleton pregnancies. The outcomes analyzed were GWG (difference between maternal weight measured at prenatal check-up just before delivery and pregestational weight based on information from clinical records) and birthweight of infants stratified by pregestational maternal body mass index (BMI).RESULTSThis study included 1150 singleton babies and their mothers. After excluding individuals with incomplete data, the final number of analyzed participants was 1078. The mean maternal age at delivery was 31.3 ± 5.1 years. The mean pregestational BMI was 21.3 ± 3.4 kg/m2. The mean GWG was 10.0 ± 4.1 kg. After adjusting for confounding factors, maternal smoking during pregnancy was positively associated with GWG in all categories (underweight: p<0.0001; normal weight: p<0.0001; overweight: p=0.01). Maternal smoking during pregnancy was also significantly associated with lower birthweight in underweight and normal-weight mothers (underweight: p=0.04, normal-weight: p=0.03).CONCLUSIONSMaternal smoking status is significantly associated with higher GWG and lower birthweight. Based on the Developmental Origins of Health and Disease (DOHaD) hypothesis, the growth of infants born from smoking mothers needs close observation.