Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

Optimal placental function is critical for fetal development, and therefore a crucial consideration for understanding the developmental origins of health and disease (DOHaD). The structure of the fetal side of the placental vasculature is an important determinant of fetal growth and cardiovascular development. There are several imaging modalities for assessing feto-placental structure including stereology, electron microscopy, confocal microscopy, micro-computed tomography, light-sheet microscopy, ultrasonography and magnetic resonance imaging. In this review, we present current methodologies for imaging feto-placental vasculature morphology ex vivo and in vivo in human and experimental models, their advantages and limitations and how these provide insight into placental function and fetal outcomes. These imaging approaches add important perspective to our understanding of placental biology and have potential to be new tools to elucidate a deeper understanding of DOHaD.

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.

Chronic kidney disease continues to be under recognised and is associated with a significant global health burden and costs. An adverse intrauterine environment may result in a depleted nephron number and an increased risk of chronic kidney disease. Antenatal ultrasound was used to measure the foetal renal parenchymal thickness (RPT), as a novel method to estimate nephron number. Foetal renal artery blood flow was also assessed. This prospective, longitudinal study evaluated the foetal kidneys of 102 appropriately grown and 30 foetal growth-restricted foetuses between 20 and 37 weeks gestational age (GA) to provide vital knowledge on the influences foetal growth restriction has on the developing kidneys. The foetal RPT and renal artery blood flow were measured at least every 4 weeks using ultrasound. The RPT was found to be significantly thinner in growth-restricted foetuses compared to appropriately grown foetuses [likelihood ratio (LR) = 21.06, P ≤ 0.0001] and the difference increases with GA. In foetuses with the same head circumference, a growth-restricted foetus was more likely to have a thinner parenchyma than an appropriately grown foetus (LR = 8.9, P = 0.0028), supporting the principle that growth-restricted foetuses preferentially shunt blood towards the brain. No significant difference was seen in the renal arteries between appropriately grown and growth-restricted foetuses. Measurement of the RPT appears to be a more sensitive measure than current methods. It has the potential to identify infants with a possible reduced nephron endowment allowing for monitoring and interventions to be focused on individuals at a higher risk of developing future hypertension and chronic kidney disease.

Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta’s transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.

Cardiovascular diseases (CVD) are important consequences of adverse perinatal conditions such as fetal hypoxia and maternal malnutrition. Cardiac magnetic resonance imaging (CMR) can produce a wealth of physiological information related to the development of the heart. This review outlines the current state of CMR technologies and describes the physiological biomarkers that can be measured. These phenotypes include impaired ventricular and atrial function, maladaptive ventricular remodeling, and the proliferation of myocardial steatosis and fibrosis. The discussion outlines the applications of CMR to understanding the developmental pathways leading to impaired cardiac function. The use of CMR, both in animal models of developmental programming and in human studies, is described. Specific examples are given in a baboon model of intrauterine growth restriction (IUGR). CMR offers great potential as a tool for understanding the sequence of dysfunctional adaptations of developmental origin that can affect the human cardiovascular system.

Maternal nutrition is an environmental determinant for offspring growth and development, especially in critical periods. Nutritional imbalances during these phases can promote dysregulations in food intake and feeding preference in offspring, affecting body composition. The aim of this review is to summarize and discuss the effects of maternal high-fat diet (HFD) on offspring feeding behavior and body composition. A search was performed in the PUBMED, SCOPUS, Web of Science, and LILACS databases. Inclusion criteria were studies in rodents whose mothers were submitted to HFD that assessed outcomes of food or caloric intake on offspring and food preference associated or not with body weight or body composition analysis. At the end of the search, 17 articles with the proposed characteristics were included. In these studies, 15 articles manipulated diet during pregnancy and lactation, 1 during pregnancy only, and 1 during lactation only. Maternal exposure to a HFD leads to increased food intake, increased preference for HFDs, and earlier food independence in offspring. The offspring from HFD mothers present low birthweight but become heavier into adulthood. In addition, these animals also exhibited greater fat deposition on white adipose tissue pads. In conclusion, maternal exposure to HFD may compromise parameters in feeding behavior and body composition of offspring, impairing the health from conception until adulthood.

The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the literature was conducted using PubMed, Embase, and CINAHL (01/2000–09/2019). Data from rodent (9 studies) and human models (48 studies, 5 meta-analyses) were included and reviewed using PRISMA guidelines. Evidence from rodent models suggests that intermittent maternal hypoxia results in mixed changes in birth weight (BW) followed by accelerated postnatal growth, while maternal sleep fragmentation results in normal BW followed by later metabolic derangement. Human studies support that maternal SDB is associated with both SGA and LGA, both of which may predispose offspring to later obesity. Evidence also suggests a link between SDB, inflammation, and oxidative stress that may impact maternal metabolism and/or placental function. SDB is common in pregnancy and affects fetal growth and development. Given that SDB has significant potential to adversely influence the intrauterine metabolic environment, larger, prospective studies in humans are urgently needed to fully elucidate the effects of this exposure on offspring metabolic risk.

Early growth pattern is increasingly recognized as a determinant of later obesity. This study aimed to identify the association between weight gain in early life and anthropometry, adiposity, leptin, and fasting insulin levels in adolescence. A cross-sectional study was conducted in 366 school children aged 11–13 years. Weight, height, and waist circumference (WC) were measured. Fat mass (FM) was assessed using bioelectrical impedance analysis. Blood was drawn after a 12-h fast for insulin and leptin assay. Birth weight and weight at 6 months and at 18 months were extracted from Child Health Development Records. An increase in weight SD score (SDS) by ≥0.67 was defined as accelerated weight gain. Linear mixed-effects modeling was used to predict anthropometry, adiposity, and metabolic outcomes using sex, pubertal status, accelerated weight gain as fixed factors; age, birth weight, and family income as fixed covariates, and school as a random factor. Children with accelerated weight gain between birth and 18 months had significantly higher body mass index (BMI) SDS, WC SDS, height SDS, %FM, fat mass index (FMI), fat free mass index (FFMI), and serum leptin levels in adolescence. Accelerated weight gain between 6 and 18 months was associated with higher BMI SDS, WC SDS, %FM, and FMI, but not with height SDS or FFMI. Accelerated weight gain at 0–6 months, in children with low birth weight, was associated with higher height SDS, BMI SDS, WC SDS, %FM, and FMI; in children with normal birth weight, it was associated with BMI SDS, WC SDS, height SDS, and FFMI, but not with %FM or FMI. Effects of accelerated weight gain in early life on anthropometry and adiposity in adolescence varied in different growth windows. Accelerated weight gain during 6–18 months was associated with higher FM rather than linear growth. Effects of accelerated weight gain between 0 and 6 months varied with birth weight.

Infant colic is a condition of unknown cause which can result in carer distress and attachment difficulties. Recent studies have implicated the gut microbiota in infant colic, and certain probiotics have demonstrated possible efficacy. We aim to investigate whether the intestinal microbiota composition in infants with colic is associated with cry/fuss time at baseline, persistence of cry/fuss at 4-week follow-up, or child behavior at 2 years of age. Fecal samples from infants with colic (n = 118, 53% male) were analyzed using 16S rRNA sequencing. After examining the alpha and beta diversity of the clinical samples, we performed a differential abundance analysis of the 16S data to look for taxa that associate with baseline and future behavior, while adjusting for potential confounding variables. In addition, we used random forest classifiers to evaluate how well baseline gut microbiota can predict future crying time. Alpha diversity of the fecal microbiota was strongly influenced by birth mode, feed type, and child gender, but did not significantly associate with crying or behavioral outcomes. Several taxa within the microbiota (including Bifidobacterium, Clostridium, Lactobacillus, and Klebsiella) associate with colic severity, and the baseline microbiota composition can predict further crying at 4 weeks with up to 65% accuracy. The combination of machine learning findings with associative relationships demonstrates the potential prognostic utility of the infant fecal microbiota in predicting subsequent infant crying problems.

Stressful events during the prenatal period have been related to hyperactive hypothalamic–pituitary–adrenal (HPA) axis responses as well as metabolic changes in adult life. Moreover, regular exercise may contribute to the improvement of the symptoms associated with stress and stress-related chronic diseases. Therefore, this study aims to investigate the effects of exercise, before the gestation period, on the metabolic changes induced by prenatal stress in adult mice. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS) and exercise before the gestational period plus PNS (EX + PNS). When adults, the plasmatic biochemical analysis, oxidative stress, gene expression of metabolic-related receptors and sex differences were assessed in the offspring. Prenatal stress decreased neonatal and adult body weight when compared to the pregestational exercise group. Moreover, prenatal stress was associated with reduced body weight in adult males. PNS and EX + PNS females showed decreased hepatic catalase. Pregestational exercise prevented the stress-induced cholesterol increase in females but did not prevent the liver mRNA expression reduction on the peroxisome proliferator-activated receptors (PPARs) α and γ in PNS females. Conversely, PNS and EX + PNS males showed an increased PPARα mRNA expression. In conclusion, pregestational exercise prevented some effects of prenatal stress on metabolic markers in a sex-specific manner.

Low gestational weight gain (GWG) is a known risk factor of low birthweight. Although studies have previously examined the associations between GWG and birthweight, the period-specific effects of low GWG in each trimester remain unclear. This study aimed to quantify the trimester-specific direct effects of low GWG in Japanese women on birthweight. Using perinatal data from a cohort study, we analyzed pregnant women delivered at an obstetrics/gynecology hospital between October 2006 and May 2010. We focused on women with a pre-pregnancy body mass index (BMI) below 25 kg/m2. The exposure was low GWG. The gestation period was subdivided into trimesters, and the direct effects of low trimester-specific GWG on birthweight were estimated using marginal structural models. These models were guided by a direct acyclic graph that incorporated potential confounders, including pre-pregnancy BMI, age, smoking during pregnancy, height, and parity. We analyzed 563 women and their families. The mean cumulative GWG by the end of the first, second, and third trimesters was 0.9, 6.2, and 10.7 kg, respectively. Approximately 14.0% of the women gained total weight below the range recommended by Japanese Ministry of Health, Labour and Welfare. The direct effects of low GWG on birthweight were 65.9 g (95% confidence interval: 11.4, 120.5), −195.4 g (−263.4, −127.4), and −188.8 g (−292.0, −85.5) for the first, second, and third trimesters, respectively. Insufficient weight gain in the second and third trimesters had a negative impact on birthweight after adjusting for pre-pregnancy BMI and other covariates.

Alterations in the maternal environment may impact on the fetal development. The objective of this study was to investigate the gastrointestinal consequences of maternal hypothyroidism for the male offspring from Wistar rats. The pregnant rats were divided into three groups: control (C – received water), experimental 1 [E1 – received methimazole (MMI) solution] during gestation and lactation, and experimental 2 (E2 – received MMI solution) during gestation. Maternal parameters evaluated: free T3 and T4, bodyweight variation, and water/food intake. Offspring parameters evaluated: litter size, number of male/female, free T3 and T4, stomach area, gastric ulcer susceptibility, small intestine length and weight, small intestine and distal colon motility, the stomach and intestinal weight–body weight ratio (SW/BW–IW/BW), and the accumulation of intestinal fluid. Maternal T3 and T4 from E1 were decreased when compared to the other groups. There were no differences for maternal water/food intake and weight gain, litter size, and number of males and females. Regarding to offspring, free T3, SW/BW, IW/BW, and intestinal fluid accumulation were not different between the groups, but T4 was decreased in E1. However, 30-day-old pups from E1 and E2 were smaller with lower stomach and small intestine. Even more, E1 presented a lower ulcer index when compared to the C, while E2 had a higher distal colon transit. It can be concluded that maternal hypothyroidism impaired the total body development, as well as gastric and intestinal development, besides interfering with the susceptibility to the ulcer and intestinal transit of male offspring from Wistar rats.

Clinical and experimental studies show an association between maternal periodontitis and adverse outcomes during gestation. On the other hand, there were no studies evaluating the impact of maternal periodontitis on the offspring. Thus, our objective was to investigate the repercussion of maternal periodontitis on the development of asthma in the offspring. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after birth, the puppies were sensitized and challenged with ovalbumin (OVA) in order to induce asthmatic response. Our results showed that maternal periodontitis reduced cellular infiltrate in the parenchyma of offspring, tracheal responsiveness, lung edema, and anti-OVA antibodies, without alter mucus as well as cytokines production. We concluded that periodontitis has relevant impact on the offspring’s immune system, blunting the response to allergic and inflammatory stimulus. This study shows the important role of oral health during pregnancy and opens possibilities for future studies in order to explain the effects of periodontitis during pregnancy in the offspring.

A preconception Virtual Patient Advocate (VPA) called “Gabby” supported African-American women to decrease their preconception health risks and may be a scalable resource to increase women’s access to preconception care. Aims were to assess the acceptability of a preconception VPA in women living in Australia and document the changes required to adapt Gabby to suit an Australian context. Taking a descriptive qualitative approach, nonpregnant female participants (n = 31), aged 18–45 years, living in metropolitan and regional Victoria, Australia interacted with Gabby. Focus groups (n = 7) that gathered participants’ perspectives of their experience with Gabby ran in July–August 2019 before being transcribed verbatim and thematically analyzed. Six interrelated themes and 12 subthemes were identified. Participants found VPAs to be an acceptable provider of health information with potential to increase women’s access preconception health advice. Gabby was considered to be trustworthy and was able to develop rapport with participants in a relatively short time. Context-specific, relevant, tailored and trustworthy information and advice were considered more important that Gabby’s physical appearance. Participants had strong opinions about potential technological advancements (e.g., reminders and rewards) and addressing navigation issues to increase Gabby’s acceptability. Participants envisaged that they would use Gabby for readily available and evidence-based information before seeking advice from a health professional if required. Overall, the concept VPAs to provide preconception advice and Gabby were acceptable to participants. Future development of VPAs, Gabby, and other online technology-based resources should consider women’s high expectations of the online health information they choose to interact with.

Prenatal glucocorticoid overexposure has been shown to programme adult cardiovascular function in a range of species, but much less is known about the long-term effects of neonatal glucocorticoid overexposure. In horses, prenatal maturation of the hypothalamus–pituitary–adrenal axis and the normal prepartum surge in fetal cortisol occur late in gestation compared to other precocious species. Cortisol levels continue to rise in the hours after birth of full-term foals and increase further in the subsequent days in premature, dysmature and maladapted foals. Thus, this study examined the adult cardiovascular consequences of neonatal cortisol overexposure induced by adrenocorticotropic hormone administration to full-term male and female pony foals. After catheterisation at 2–3 years of age, basal arterial blood pressures (BP) and heart rate were measured together with the responses to phenylephrine (PE) and sodium nitroprusside (SNP). These data were used to assess cardiac baroreflex sensitivity. Neonatal cortisol overexposure reduced both the pressor and bradycardic responses to PE in the young adult males, but not females. It also enhanced the initial hypotensive response to SNP, slowed recovery of BP after infusion and reduced the gain of the cardiac baroreflex in the females, but not males. Basal diastolic pressure and cardiac baroreflex sensitivity also differed with sex, irrespective of neonatal treatment. The results show that there is a window of susceptibility for glucocorticoid programming during the immediate neonatal period that alters cardiovascular function in young adult horses in a sex-linked manner.

Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7–17) months were used to estimate Horvath’s DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: −0.79 to 2.34 for low/medium education; 0.96, 95% CI: −1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath’s method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.