Oxidative stress along the gut-kidney axis is a risk factor for developing arterial hypertension in offspring from dams fed a high-fat diet. Considering the antioxidant capacity of probiotic strains, this study evaluated the effects of a daily multistrain formulation with Limosilactobacillus fermentum 139, 263, and 296 on blood pressure (BP), renal function, and oxidative stress and along the gut-kidney axis in male offspring from dams fed a high-fat high-cholesterol (HFHC) diet during pregnancy and lactation. Dams were fed a diet control or HFHC diet during pregnancy and lactation. At 100 days of age, part of the male offspring from dams fed a HFHC diet received Limosilactobacillus fermentum formulation for 4 weeks (HFHC + Lf) daily. After the 4-week intervention, BP (tail-cuff plethysmography) and urinary and biochemical variables were measured. In addition, malondialdehyde levels, enzymatic activities of superoxide dismutase, catalase, glutathione-S-transferase, and nonenzymatic antioxidant defense (thiols content) were measured in the colon and renal cortex. Male offspring from dams fed a HFHC had increased blood pressure, impaired renal function, and oxidative stress along the gut-kidney axis. Administration of Limosilactobacillus fermentum reduced systolic, diastolic, and mean blood pressure levels and alleviated renal function impairment and oxidative stress along the gut-kidney axis in male offspring from dams fed a HFHC diet. Administration of Limosilactobacillus fermentum formulation attenuated programmed hypertension in the HFHC group through oxidative stress modulation along the gut-kidney axis.

While metabolic disorders such as obesity and diabetes are costly and deadly to the current population, they are also extremely detrimental to the next generation. Much of the current literature focuses on the negative impact of poor maternal choices on offspring disease, while there is little work examining maternal behaviors that may improve offspring health. Research has shown that voluntary maternal exercise in mouse models improves metabolic function in offspring. In this study, we hypothesized that controlled maternal exercise in a mouse model will effect positive change on offspring obesity and glucose homeostasis. Female mice were separated into three groups: home cage, sedentary, and exercise. The sedentary home cage group was not removed from the home cage, while the sedentary wheel group was removed from the cage and placed in an immobile wheel apparatus. The exercise group was removed from the home cage and run on the same wheel apparatus but with the motor activated at 5–10 m/min for 1 h/d prior to and during pregnancy. Offspring were subjected to oral glucose tolerance testing and body composition analysis. There was no significant difference in offspring glucose tolerance or body composition as a consequence of the maternal exercise intervention compared to the sedentary wheel group. There were no marked negative consequences of the maternal controlled exercise intervention. Further research should clarify the potential advantages of the controlled exercise model and improve experimental techniques to facilitate translation of this research to human applications.

Studies on childhood feeding and current food consumption, according to the NOVA classification, in adults are scarce. The objective of this study was to evaluate the relationship between childhood dietary practices and the current consumption of different categories of processed foods in young adults using data from the Nutritionists’ Health Study (NutriHS) cohort. A cross-sectional analysis was performed using data of 392 on nutrition undergraduate students or nutritionists aged ≥18 years. Current food consumption was assessed using a food frequency questionnaire and the NOVA classification. The investigated childhood eating practices included fruit and vegetable intake, exclusive breastfeeding, and other breastfeeding practices. Participants breastfed with introduction of solid, semi-solid or soft foods before 6 months had higher current consumption of processed foods than those who were not breastfed (β = 4.30; 95% confidence interval [CI] = 0.56–8.04) and those who did not have the habits of eating fruits and vegetables during childhood consumed less unprocessed and minimally processed foods in adulthood than those who ate fruits and vegetables during infancy (β = −3.76; 95% CI = −0.82 to −6.70). Further, later introduction of infant formula or other types of milk between 3 and 5 months of age had a lower current consumption of ultra-processed foods than those fed infant formula or other types of milk before 1 month age of life (β = −3.09; 95% CI = −6.12 to −0.06). In conclusion, childhood feeding practices were linked to food consumption in adult life in NutriHS cohort, highlighting that the first 1000 days of life seems to impact on food choices during adulthood, with potential to protect against nutrition-related diseases later in life.

Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6–10 gestation week human embryos and on IA septal regions. To investigate the topology of embryonic intestine development, we conducted 3D reconstruction. We showed that a 6–7th gestation week embryonic gut has no lumen, but filled with mesenchyme cells and vacuoles of a monolayer of epithelial cells. A narrow gut lumen was formed by gestation week-9, the gut was filled with numerous vacuoles of different sizes, some vacuoles were merging with the developing embryonic gut wall. At gestation week-10, a prominent lumen was developed, only few vacuoles were present and were merging with the intestine wall. At IA septal regions, vacuoles were located in the submucous layer, covered by a single layer of epithelium without glandular structure, and surrounded with fibrous tissue. The mucosal epithelium was developed with lamina propria and basement membrane, but the submucosa and the longitudinal smooth muscle layers were not properly developed. Hence, the vacuoles in IA septum could represent a remnant of vacuoles of embryonic gut. In conclusion, the fusion of vacuoles with the developing intestine wall associates with the disappearance of vacuoles and gut lumen formation in human embryos, and perturbation of these developmental events could lead to IA.

The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women’s Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6–7 lbs. 15 oz, 8–9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn’s disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6–7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing <6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions.

Maternal obesity programs the offspring to metabolic diseases later in life; however, the mechanisms of programming are yet unclear, and no strategies exist for addressing its detrimental transgenerational effects. Obesity has been linked to dipeptidyl peptidase IV (DPPIV), an adipokine, and treatment of obese individuals with DPPIV inhibitors has been reported to prevent weight gain and improve metabolism. We hypothesized that DPPIV plays a role in maternal obesity-mediated programming. We measured plasma DPPIV activity in human maternal and cord blood samples from normal-weight and obese mothers at term. We found that maternal obesity increases maternal and cord blood plasma DPPIV activity but only in male offspring. Using two non-human primate models of maternal obesity, we confirmed the activation of DPPIV in the offspring of obese mothers. We then created a mouse model of maternal high-fat diet (HFD)-induced obesity, and found an early-life increase in plasma DPPIV activity in male offspring. Activation of DPPIV preceded the progression of obesity, glucose intolerance and insulin resistance in male offspring of HFD-fed mothers. We then administered sitagliptin, DPPIV inhibitor, to regular diet (RD)- and HFD-fed mothers, starting a week prior to breeding and continuing throughout pregnancy and lactation. We found that sitagliptin treatment of HFD-fed mothers delayed the progression of obesity and metabolic diseases in male offspring and had no effects on females. Our findings reveal that maternal obesity dysregulates plasma DPPIV activity in males and provide evidence that maternal inhibition of DPPIV has potential for addressing the transgenerational effects of maternal obesity.

Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4–6 months, 7–12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.

Nutrition and the incidence of diseases during early life are considered environmental factors that determine people’s height when they become adults. While there is extensive literature focusing on the relationship between physical growth, general mortality and infant mortality rates, few studies analyse the impact of certain disease groups on the final height of historical populations. Using regional mortality rates by causes of death, the main objective of this study is to determine the onset of the disease environment during early life for populations born in Spain between 1916 and 1930, and its relationship with the stature reached at 21 years of age. A population-averaged model is performed on epidemic-infectious, gastrointestinal, and congenital diseases during the gestation period and first year of life. The disease burden in early life had a statistically significant negative effect on adult stature. These results support the premise that an improvement in the disease environment could lead to a greater number of short children surviving and therefore a decrease in the average height.

Numerous studies have shown associations between maternal stress and poor birth outcomes, but evidence is unclear for causal inference. Natural disasters provide an opportunity to study effects of quasi-randomized hardship with an accurate measure of onset and duration. In a population-based quasi-experimental study, we examined the effect of maternal exposure to the January 1998 Québec ice storm on birth outcomes by comparing pregnant mothers who lived in an area hard hit by the ice storm with those in two unaffected regions. In a total of 147,349 singleton births between 1995 and 2001, we used a difference-in-differences method to estimate the effects of the ice storm on gestational age at delivery (GA), preterm birth (PTB), weight-for-gestational-age z-scores (BWZ), large for gestational age (LGA), and small for gestational age (SGA). After adjusting for maternal and sociodemographic characteristics, there were no differences between the exposed and the unexposed mothers for birth outcomes. The estimated differences (exposed vs. unexposed) were 0.01 SDs (95% CI: −0.02, 0.05) for BWZ; 0.10% point (95% CI: −0.95%, 1.16%) for SGA; 0.25% point (95% CI: −0.78%, 1.28%) for LGA; −0.01 week (95% CI: −0.07, 0.05) for GA; and 0.16% point (95% CI: −0.66%, 0.97%) for PTB. Neither trimester-specific nor dose–response associations were observed. Overall, exposure to the 1998 Québec ice storm as a proxy for acute maternal stress in pregnancy was not associated with poor birth outcomes. Our results suggest that acute maternal hardship may not have a substantial effect on adverse birth outcomes.

Maternal overnutrition-induced fetal programming predisposes offspring to cardiovascular health issues throughout life. Understanding how these adverse cardiovascular effects are regulated at the maternal–fetal crosstalk will provide insight into the mechanisms of these cardiovascular diseases, which will help in further identifying potential targets for intervention. Here, we uncover a role of oxidative stress caused by prenatal overnutrition in governing cardiac damage. Mice exposed to maternal obesity showed remarkable pathological cardiomyocyte hypertrophy (p male < 0.001, Cohen’s d male = 1.77; p female < 0.001, Cohen’s d female = 1.94), increased collagen content (p male < 0.001, Cohen’s d male = 2.13; p female < 0.001, Cohen’s d female = 2.71), and increased levels of transforming growth factor β (TGF-β) (p male < 0.001, Cohen’s d male = 3.02; p female < 0.001, Cohen’s d female = 4.52), as well as left ventricular dysfunction in adulthood. To cope with increased oxidative stress in the myocardial tissue of offspring from obese mothers, we sought to decrease the effect of oxidative stress and prevent the development of these cardiovascular conditions with use of the antioxidant N-acetylcysteine during pregnancy. As predicted, after treatment with the antioxidant, there was greatly mitigated cardiomyocyte hypertrophy (p male < 0.001, Cohen’s d male = 1.31; p female < 0.001, Cohen’s d female = 0.82) and cardiac fibrosis, including decreased composition of collagen fibers (p male < 0.01, Cohen’s d male = 1.45; p female < 0.05, Cohen’s d female = 1.23) and reduced levels of TGF-β (p male < 0.05, Cohen’s d male = 1.83; p female < 0.01, Cohen’s d female = 3.81). We also observed improved left ventricle contractile function together with the alleviation of enhanced oxidative stress in the myocardial tissue of offspring. Collectively, these results established a crucial role of oxidative stress in prenatal overnutrition-associated ventricular remodeling and cardiac dysfunction. Our findings provided an important target for intervention of cardiovascular disease in overnutrition-related fetal programming.

Infant neurodevelopment is a complex process which may be affected by different events during pregnancy, such as hypertensive disorders of pregnancy (HDP). We conducted a prospective cohort study to compare the prevalence of neurodevelopmental disorders in infants born to mothers with and without HDP at six months of age. Participants attended the Health Observatory of Instituto de Desarrollo e Investigaciones Pediátricas “Prof. Dr. Fernando E. Viteri” during 2018 and 2019. Infant neurodevelopment was assessed with the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III). Data were analyzed using Chi-square, Student’s t-test and Mann–Whitney test. Of the 132 participating infants, 68 and 64 were born to mothers with and without HDP, respectively. At six months, the prevalence of risk of neurodevelopmental delay was significantly higher in infants born to mothers with than without HDP (27.9% vs. 9.4%; p = 0.008) (odds ratio, 3.71; 95% confidence interval, 1.30; 12.28). In conclusion, infants born to mothers with HDP had three times increased risk of neurodevelopmental delay at six months of age.

The addition of reproductive fluids (RF) to the culture media has shown benefits in different embryonic traits but its long-term effects on the offspring phenotype are still unknown. We aimed to describe such effects in pigs. Blood samples and growth parameters were collected from piglets derived from in vitro-produced embryos (IVP) with or without RF added in the culture media versus those artificially inseminated (AI), from day 0 to month 6 of life. An oral glucose tolerance test was performed on day 45 of life. We show here the first comparative data of the growth of animals produced through different assisted reproductive techniques, demonstrating differences between groups. Overall, there was a tendency to have a larger size at birth and faster growth in animals derived from in vitro fertilization and embryo culture versus AI, although this trend was diminished by the addition of RFs to the culture media. Similarly, small differences in hematological indices and glucose tolerance between animals derived from AI and those derived from IVP, with a sex-dependent effect, tended to fade in the presence of RF. The addition of RF to the culture media could contribute to minimizing the phenotypical differences between the in vitro-derived and AI offspring, particularly in males.

Health in pregnancy and infancy can affect the risk of chronic non-communicable diseases. We aimed to describe leptin and adiponectin concentrations in low birth weight (LBW) infants and identify possible associations with maternal nutritional status, adequacy for gestational age, nutritional recovery, and current dietary intake. A cross-sectional study with LBW infants (9–12 months) including maternal background and pre-pregnancy nutritional condition was performed. From the Infants: anthropometry at birth and current was expressed as z-score (weight: WAZ, length, head circumference), nutritional recovery, dietary intake, leptin, and adiponectin blood concentrations. The mean age of the 54 infants was 10.0 ± 1.5 months, 32 (59.3%) were female, 36 (66.7%) preterm, 23 (42.6%) small for gestational age (SGA), and 25 pregnancies (46.3%) were twin. Almost all (98%) of the infants intake energy and protein above the recommendation, and 47 (87.6%) consumed ultra-processed foods. At the time of the assessment, 8 (14.8%) were overweight and 4 (7.4%) had short stature. SGA infants showed faster weight recovery (WAZ 1.54; 95% CI 1.17, 1.91; p = 0.001), higher leptin’s concentration (3.0 ng/ml (1.7, 3.0) versus 1.6 ng/ml (0.9, 2.6); p = 0.032)), and leptin/adiponectin ratio (0.13 ± 0.08 versus 0.07 ± 0.07; p = 0.018). The pre-gestational BMI was a modifier of the effect of WAZ on leptin levels (p = 0.027) in LBW infants. Higher pre-gestational BMI increased the effect of WAZ variation (birth and current) on leptin levels. Concluding, LBW infants showed early changes in leptin and adiponectin concentrations, influenced by maternal (pre-gestational BMI), intrauterine (gestational age adequacy – SGA), and postnatal weight gain. This combination of factors may increase the risk of NCD for this group of children.

Cardiovascular diseases are the main cause of mortality worldwide, and childhood excess weight/obesity are strong correlators of accumulated risk in later life. A relationship between maternal preeclampsia and offspring’s childhood obesity is recognized, but most studies fail to control for strong confounders. Our goal is to analyze the association between preeclampsia and childhood excess weight/obesity, after accounting for important confounders. We recruited 5133 women with singleton pregnancies during admission for delivery. Sixty-seven pregnancies were complicated by preeclampsia. Maternal and children outcomes were assessed at 10 years of age. We analyzed the association between preeclampsia and childhood excess weight/obesity by fitting a linear regression model (using offspring body mass index (BMI) z-score at 10 years of age) and a logistic regression model (using excess weight/obesity status). We then controlled both models for known confounders, namely maternal prepregnancy BMI, parity, and smoking during pregnancy. At 10 years of age, offspring of preeclamptic mothers had a higher BMI z-score and were more likely classified as overweight/obese, but these differences were not statistically significant. After controlling for maternal prepregnancy BMI, parity, and smoking during pregnancy, there was a high magnitude change in the beta coefficient of preeclampsia in the linear (0.175; −0.014) and the logistic regression models (1.48; 1.23) suggesting that the association between preeclampsia and childhood excess weigh/obesity is significantly confounded by these variables. These confounders also showed a significant association with childhood obesity. This finding suggests that in utero exposure to preeclampsia seems to have less impact in childhood obesity than the previously described confounders.

Maternal adversity and prenatal stress confer risk for child behavioral health problems. Few studies have examined this intergenerational process across multiple dimensions of stress; fewer have explored potential protective factors. Using a large, diverse sample of mother–child dyads, we examined associations between maternal childhood trauma, prenatal stressors, and offspring socioemotional-behavioral development, while also examining potential resilience-promoting factors. The Conditions Affecting Neurocognitive Development and Learning and Early Childhood (CANDLE) study prospectively followed 1503 mother–child dyads (65% Black, 32% White) from pregnancy. Exposures included maternal childhood trauma, socioeconomic risk, intimate partner violence, and geocode-linked neighborhood violent crime during pregnancy. Child socioemotional-behavioral functioning was measured via the Brief Infant Toddler Social Emotional Assessment (mean age = 1.1 years). Maternal social support and parenting knowledge during pregnancy were tested as potential moderators. Multiple linear regressions (N = 1127) revealed that maternal childhood trauma, socioeconomic risk, and intimate partner violence were independently, positively associated with child socioemotional-behavioral problems at age one in fully adjusted models. Maternal parenting knowledge moderated associations between both maternal childhood trauma and prenatal socioeconomic risk on child problems: greater knowledge was protective against the effects of socioeconomic risk and was promotive in the context of low maternal history of childhood trauma. Findings indicate that multiple dimensions of maternal stress and adversity are independently associated with child socioemotional-behavioral problems. Further, modifiable environmental factors, including knowledge regarding child development, can mitigate these risks. Both findings support the importance of parental screening and early intervention to promote child socioemotional-behavioral health.

There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

Maternal exercise has shown beneficial effects on mother and child. Literature confirm progeny’s cognition improvement, and upregulation in neurotrophins, antioxidant network, and DNA repair system. Considering that there is a lack of information demonstrating the impact of maternal exercise on offspring’s skeletal muscle, we aimed to investigate the mitochondrial and redox effects elicited by maternal swimming. Adult female Wistar rats were divided into three groups: control sedentary, free swimming, and swimming with overload (2% of the body weight). Exercised groups were submitted weekly to five swimming sessions (30 min/day), starting 1 week prior to the mating and lasting to the delivery. Gastrocnemius and soleus muscle from 60-day-old offspring were analyzed. Our results clearly showed a sex-dependent effect. Male soleus showed increased mitochondrial functionality in the overload group. Female muscle from the overload group adapted deeply. Considering the redox status, the female offspring delivered to overload exercised dams presented reduced oxidants levels and protein damage, allied to downregulated antioxidant defenses. We also observed an increase in the mitochondrial function in the gastrocnemius muscle of the female offspring born from overload exercised dams. Soleus from female delivered to the overload exercise group presented reduced mitochondrial activity, as well as reduced reactive species, protein carbonyls, and antioxidant network, when compared to the male. In conclusion, maternal exercise altered the redox status and mitochondrial function in the offspring’s skeletal muscle in a sex-dependent way. The clinical implication was not investigated; however, the sexual dimorphism in response to maternal exercise might impact exercise resilience in adulthood.

Increased population longevity could be influenced by early life factors. Some areas have long-lived populations, also in a historical perspective. We aimed to study these factors in Halland, an area with the highest life expectancy in Sweden. We collected archival data on gestational age and birth characteristics from 995 live singleton full-term births at the Halmstad Hospital, Halland, from the period 1936 to 1938 and compared these to 3364 births from three hospitals in nearby Scania for the period 1935–1945. In addition, data were obtained on maternal and offspring characteristics from the national Swedish Medical Birth Register during 1973–2013. The results show that when controlling for background maternal and offspring characteristics, mean birth weight (BW) and mean birth length were higher in Halland than in Scania, but the proportion of low birth weight (LBW) and small for gestational age (SGA) was lower. However, mean BW for Halland did not differ from the rest of Sweden in recent years 2004–2013. We also conducted a mortality follow-up for children born in Scania, which showed that LBW, being born SGA, or short birth length reduced survival. In conclusion, the high mean life expectancy in Halland compared to the rest of Sweden could have been associated with beneficial early life factors influencing birth size in the past. In more recent decades the mean BW of Halland is not different from the national mean. Thus, longevity could be expected to become more equal to the national mean in the future.

Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.

We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.

Children with marasmus had lower weight-for-height z-scores (WHZ) (−3.8 ± 0.9 vs. −2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (−4.6 ± 1.1 vs. −3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg−1.min−1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.

Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.

Consistent with cumulative risk hypotheses of psychopathology, studies examining prenatal adversity and later mental health largely suggest that pre and postnatal stress exposures have summative effects. Fewer data support that a mismatch in stress levels between pre- and postnatal life increases risk (the mismatch hypothesis). In this retrospective cohort study using data from the 1983 Ontario Child Health Study (OCHS), we examined interactions between birth weight status and childhood/adolescent stress to predict major depression in adulthood. Ninety-five participants born at low birth weight (LBW; <2500 g) and 972 normal birth weight (NBW) control participants completed the Composite International Diagnostic Interview Short-Form Major Depression module at 21–34 years of age. A youth risk scale consisting of five stressful exposures (family dysfunction, socioeconomic disadvantage, parental criminality, maternal mental illness, exposure to other life stresses) indexed child/adolescent adversity. Birth weight groups did not differ by childhood risk score nor depression levels. A significant interaction was observed between birth weight and the youth risk scale whereby exposure to increasing levels of exposure to childhood/adolescent adversity predicted increased levels of depression in the NBW group, but lower rates in those born at LBW. Consistent with the mismatch hypothesis, data from a large, longitudinally followed cohort suggest that the mental health of adults born LBW may be more resilient to the adverse effects of childhood/adolescent stress. Taken in the context of previous studies of low birth weight infants, these findings suggest that the nature of associations between gestational stress and later mental health may depend on the magnitude of prenatal stress exposure, as well as the degree of resilience and/or plasticity conferred by their early-life environment.