Hypertension (HTN) remains a common complication after kidney transplantation among paediatric patients. Although low birth weight (LBW) has been implicated as an important risk factor for cardiovascular diseases, its effect on transplantation patients has not yet been addressed. It is essential to determine whether children with LBW who undergo transplantation are more likely to develop post-transplantation HTN. For this study, the medical records of 96 kidney recipients were retrospectively examined. A total of 83 patients fulfilled the inclusion criteria. Overall, post-transplantation HTN was observed in 54% of the recipients. Multivariate logistic regression revealed that time from transplantation >14 months (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.31–10.06; P = 0.013), current CKD (OR 2.6; 95% CI 1.01–7.20; P = 0.045), presence of LBW (OR 3.6; 95% CI 1.04–12.32; P = 0.044) and current overweight/obesity (OR 3.7; 95% CI 1.02–13.91; P = 0.047) were associated with post-transplantation HTN. In conclusion, our data provide evidence for the first time that LBW is a significant predictive factor in the development of post-transplantation HTN. This finding has important clinical implications as it serves to alert clinicians about this additional risk factor in paediatric patients undergoing kidney transplant.

The ability of “comfort-food” (CF) diet to revert long-term effects of early-life stress (ELS) is less well known. The objective of this study was to verify if the chronic exposure to CF diet in animals submitted to ELS could relief the stress response at behavioral, neuroendocrine, and neurobiochemical levels, via differences in glucocorticoid receptors expression in brain areas involved in the stress response. From the second day of life, litters of Wistar rats and their mothers were submitted to the reduced nesting material protocol (ELS). In adult life, ELS and a control group were exposed chronically to two diet schemes: standard rat chow only or both “CF” diet, containing fat (34%) and sugar (20%) and a diet similar to the standard diet. Anxiety-like behavior, neuroendocrine response stress, leptin, GR, SOCS-3, pSTAT3, and the abdominal fat were evaluated. The anxiety-like behavior results showed that ELS group when exposed to comfort food were not different from the others groups. Chronic exposure to CF diet induced an anxiety-like behavior in the control group. Groups chronically exposed to CF diet had lower levels of corticosterone over time independent of the neonatal group. The ELS group exposed to the “CF” diet had higher levels of hippocampal GR, lower levels of hypothalamic SOCS-3 and greater accumulation of abdominal fat. Chronic CF diet consumption is able to reduce corticosterone levels independent of the neonatal history, but is associated with anxiety-like behavior in animals without previous history of trauma. Metabolic disturbances like increased adiposity and altered SOCS-3 seem to be a result of multiple insults (neonatal trauma followed by chronic CF diet). We highlight that the Control-chow and ELS-chow data were previously published, and are included in this study for comparative analysis.

A large body of evidence has shown that stress throughout life is associated with health trajectories, but the combination of adverse experiences at different stages of the life course is not yet well understood. This study examines the interactions between childhood adversity, adulthood adversity, and adult physical and mental health. Using data from The Childhood Retrospective Circumstances Study (CRCS) supplement to the Panel Study of Income Dynamics (PSID), we created indices of early life adversity (EAI) and adult adversity (AAI). We used logistic regression to examine the effects of EAI and AAI, adjusting for age, sex, race/ethnicity, health behaviors, and childhood health as covariates in all models. We repeated this analysis for the outcomes of fair/poor health, two or more chronic conditions, and psychological distress in adulthood. For all the three outcomes, our findings suggest increasing salience of adult adversity among those who experienced higher levels of early adversity. Individuals with high EAI and high AAI exhibited the highest odds of fair/poor health (OR = 5.71), chronic conditions (OR = 3.06), and psychological distress (OR = 13.08) compared to those with low EAI and low AAI. These findings are consistent with the accumulation of risk or dual risk model of stress and health. Adversity in childhood amplifies the health risks associated with stress in adulthood for multiple health outcomes.

Whether maternal obesity and gestational weight gain (GWG) are associated with early-childhood development in low-income, urban, minority populations, and whether effects differ by child sex remain unknown. This study examined the impact of prepregnancy BMI and GWG on early childhood neurodevelopment in the Columbia Center for Children’s Environmental Health Mothers and Newborns study. Maternal prepregnancy weight was obtained by self-report, and GWG was assessed from participant medical charts. At child age 3 years, the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Intelligence were completed. Sex-stratified linear regression models assessed associations between prepregnancy BMI and pregnancy weight gain z-scores with child PDI and MDI scores, adjusting for covariates. Of 382 women, 48.2% were normal weight before pregnancy, 24.1% overweight, 23.0% obese, and 4.7% underweight. At 3 years, mean scores on the PDI and MDI were higher among girls compared to boys (PDI: 102.3 vs. 97.2, P = 0.0002; MDI: 92.8 vs. 88.3, P = 0.0001). In covariate-adjusted models, maternal obesity was markedly associated with lower PDI scores in boys [b = −7.81, 95% CI: (−13.08, −2.55), P = 0.004], but not girls. Maternal BMI was not associated with MDI in girls or boys, and GWG was not associated with PDI or MDI among either sex (all-P > 0.05). We found that prepregnancy obesity was associated with lower PDI scores at 3 years in boys, but not girls. The mechanisms underlying this sex-specific association remain unclear, but due to elevated obesity exposure in urban populations, further investigation is warranted.

Although bariatric surgery is approved for a woman of child-bearing age with an interest in subsequent pregnancy, reports of in utero growth issues during pregnancy have garnered a closer look at the impact of maternal surgical weight loss on the pre- and postpartum periods. Offspring of dams having received vertical sleeve gastrectomy (VSG) are born small-for-gestational age and have increased risk for metabolic syndrome later in life. Here, we aimed to determine whether the postnatal catch-up growth trajectory of bariatric offspring may be affected by milk composition. Milk samples were collected at postnatal day 15/16 from dams having received VSG surgery and fed a high-fat diet (HFD) (H-VSG), Sham surgery and fed chow (C-Sham), or Sham surgery and fed HFD (H-Sham). Milk obtained from H-VSG dams had elevated glucose (P < 0.05) and significantly reduced triglyceride content (P < 0.01). Milk from H-Sham dams had the lowest amount of milk protein (P < 0.05). Fatty acid composition measured by fractionation was largely not affected by surgery but rather maternal diet. No difference was observed in milk leptin levels; however, insulin, adiponectin, and growth hormone levels were significantly increased in milk from H-VSG animals. H-Sham had the lowest level of immunoglobulin (Ig)A, whereas IgG was significantly reduced in H-VSG. Taken together, the quality of milk from H-VSG dams suggests that milk composition could be a factor in reducing the rate of growth during the lactation period.

Several life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.

The reported associations between birth weight and childhood cardiovascular disease (CVD) risk factors have been inconsistent. In this study, we investigated the relationship between birth weight and CVD risk factors at 11 years of age. This study used longitudinally linked data from three cross-sectional datasets (N = 22,136) in West Virginia; analysis was restricted to children born full-term (N = 19,583). The outcome variables included resting blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and lipid profile [total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL, and triglycerides (TG)]. Multiple regression analyses were performed, adjusting for child’s body mass index (BMI), sociodemographics, and lifestyle characteristics. Unadjusted analyses showed a statistically significant association between birth weight and SBP, DBP, HDL, and TG. When adjusted for the child’s BMI, the association between birth weight and HDL [b = 0.14 (95% CI: 0.11, 0.18) mg/dl per 1000 g increase] and between birth weight and TG [b = –0.007 (–0.008, –0.005) mg/dl per 1000 g increase] remained statistically significant. In the fully adjusted model, low birth weight was associated with higher LDL, non-HDL, and TGs, and lower HDL levels. The child’s current BMI at 11 years of age partially (for HDL, non-HDL, and TG) and fully mediated (for SBP and DBP) the relationship between birth weight and select CVD risk factors. While effects were modest, these risk factors may persist and amplify with age, leading to potentially unfavorable consequences in later adulthood.