Postnatal Environment Research Articles

Longitudinal Associations Between Physical Health Conditions in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms at Age 17 Years

Although evidence suggests significant cross-sectional relationships between attention-deficit/hyperactivity disorder (ADHD) and several physical health conditions, less is known about their longitudinal associations. We investigated the cumulative effect of childhood physical health conditions on ADHD symptoms at age 17 years, controlling for environmental factors, ADHD medication status, and ADHD symptoms at age 3 years. Using Millennium Cohort Study data (weighted n= 8,059), we assessed whether 4 physical health clusters (sensory, neurological, atopic, and cardio-metabolic) were associated with scores on the ADHD subscale from the Strengths and Difficulties Questionnaire at age 17 years. Environmental factors were grouped into 5 cumulative risk indices: prenatal, perinatal, postnatal environment, postnatal maternal well-being, and sociodemographic factors. Regression analyses determined whether each physical health cluster was associated with ADHD score while controlling for environmental factors, ADHD medication, and earlier symptoms. Sensory, neurological, and cardio-metabolic clusters were all significantly associated with ADHD symptoms (β range= 0.04-0.09, p< .001). The overall model explained 2% of the variance. This rose to 21% (ΔR2= 0.06) after adjusting for confounders. The sensory (β= 0.06) and neurological (β= 0.06) clusters remained significant (R2= 0.21, ΔR2= 0.06), but the cardio-metabolic cluster was no longer a significant predictor. Sensory or neurological conditions in childhood were associated with higher ADHD symptoms aged 17 after adjustment of confounders. This was not the case for atopic or cardio-metabolic conditions. These findings have implications for the care of children with sensory/neurological conditions and future research examining ADHD etiopathophysiology.

The Uterine Environment and Childhood Obesity Risk: Mechanisms and Predictions.

Childhood obesity is a growing health problem in many populations, hence the urgent need to unravel the underlying mechanisms. Some evidence suggests that exposure to suboptimal intrauterine environments can program foetal metabolic health, with adverse consequences in later life, including susceptibility to childhood obesity. Factors such as high and low foetal birth weight, excessive gestational-weight-gain, maternal stress and smoking are all associated with increased risk of childhood obesity in observational studies. Animal models, where both genetic background and the postnatal environment can be carefully controlled, suggest that several different mechanisms, including epigenetic changes, dysregulation of adipose tissue development and programming of appetite, may be key drivers of developmental programming of childhood obesity. However, the influence of genetics and the post-natal environment are much more difficult to disentangle as independent effects in human studies, which are also complicated by low follow-up rates. Suboptimal intrauterine environments interact with maternal and foetal genetics and with the postnatal environment to contribute to the risk of childhood obesity. Maternal metabolic challenges, for example obesity and insulin resistance, contribute to the risk of foetal overgrowth and subsequent adiposity in childhood. To protect the long-term health of populations, research focusing on effective means of identifying and intervening in the transgenerational cycle of childhood obesity is required.

Hand-Rearing Method for Infant Marmosets.

The common marmoset (Callithrix jacchus) is a small and highly social New World monkey with high reproduction rates, which has been proven to be a compelling non-human primate model for biomedical and neuroscience research. Some females give birth to triplets; however, the parents cannot raise all of them. To save these infants, we have developed a hand-rearing method for raising newborn marmosets. In this protocol, we describe the formula of the food, the time for feeding, the configuration of the temperature and humidity, as well as the adaptation of the hand-reared infants to the colony environment. This hand-rearing method significantly increases the survival rate of marmoset infants (without hand-rearing: 45%; with hand-rearing: 86%) and provides the opportunity to study the development of marmoset infants with similar genetic backgrounds raised in different postnatal environments. As the method is practical and easy to use, we anticipate that it could also be applied to other labs working with common marmosets.

Position in the laying order has sex-specific consequences for reproductive success in adult black-headed gulls.

Mothers who produce multiple offspring within one reproductive attempt often allocate resources differentially; some maternally derived substances are preferentially allocated to last-produced offspring and others to first-produced offspring. The combined effect of these different allocation regimes on the overall fitness of offspring produced early or late in the sequence is not well understood, partly because production order is often coupled with birth order, making it difficult-to-separate effects of pre-natal maternal allocation from those of post-natal social environments. In addition, very little is known about the influence of laying order on fitness in later life. In this study, we used a semi-natural captive colony of black-headed gulls to test whether an offspring's position in the laying order affected its early-life survival and later-life reproductive success, independent of its hatching order. Later-laid eggs were less likely to hatch, but among those that did, survival to adulthood was greater than that of first-laid eggs. In adulthood, the laying order of females did not affect their likelihood of breeding in the colony, but male offspring hatched from last-laid eggs were significantly less likely to gain a breeding position than earlier-laid males. In contrast, later-laid female parents hatched lower proportions of their clutches than first-laid females, but hatching success was unrelated to the laying order of male parents. Our results indicate that gull mothers induce complex and sex-specific effects on both the early survival of their offspring and on long-term reproductive success through laying order effects among eggs of the same breeding attempt.

Maternal stress during the third trimester of pregnancy and the neonatal microbiome

Objectives Preliminary research suggests that maternal prenatal stress may alter the development of the fetal microbiome and resulting microbial composition after birth. However, the findings of existing studies are mixed and inconclusive. The purpose of this exploratory study was to assess whether maternal stress during pregnancy is associated with the overall number and diversity of various microbial species in the infant gut microbiome or the abundance of specific bacterial taxa. Methods Fifty-one women were recruited during their third trimester of pregnancy. The women completed a demographic questionnaire and Cohen’s Perceived Stress Scale at recruitment. A stool sample was collected from their neonate at one month of age. Data on potential confounders, such as gestational age and mode of delivery, were extracted from medical records to control for their effects. 16s rRNA gene sequencing was used to identify the diversity and abundance of microbial species, along with multiple linear regression models to examine the effects of prenatal stress on microbial diversity. We employed negative binomial generalized linear models to test for differential expression of various microbial taxa among infants exposed to prenatal stress and those not exposed to prenatal stress. Results More severe symptoms of prenatal stress were associated with a greater diversity of microbial species in the gut microbiome of neonates (β = .30, p = .025). Certain microbial taxa, such as Lactobacillus and Bifidobacterium, were enriched among infants exposed to greater maternal stress in utero, while others, such as Bacteroides and Enterobacteriaceae, were depleted in contrast to infants exposed to less stress. Conclusions Findings suggest that mild to moderate stress exposure in utero could be associated with a microbial environment in early life that is more optimally prepared to thrive in a stressful postnatal environment. Adaptation of gut microbiota under conditions of stress may involve upregulation of bacterial species, including certain protective microorganisms (e.g. Bifidobacterium), as well as downregulation of potential pathogens (e.g. Bacteroides) via epigenetic or other processes within the fetal/neonatal gut-brain axis. However, further research is needed to understand the trajectory of microbial diversity and composition as infant development proceeds and the ways in which both the structure and function of the neonatal microbiome may mediate the relationship between prenatal stress and health outcomes over time. These studies may eventually yield microbial markers and gene pathways that are biosignatures of risk or resilience and inform targets for probiotics or other therapies in utero or during the postnatal period.

Development of cortical folds in the human brain: An attempt to review biological hypotheses, early neuroimaging investigations and functional correlates

The folding of the human brain mostly takes place in utero, making it challenging to study. After a few pioneer studies looking into it in post-mortem foetal specimen, modern approaches based on neuroimaging have allowed the community to investigate the folding process in vivo, its normal progression, its early disturbances, and its relationship to later functional outcomes. In this review article, we aimed to first give an overview of the current hypotheses on the mechanisms governing cortical folding. After describing the methodological difficulties raised by its study in fetuses, neonates and infants with magnetic resonance imaging (MRI), we reported our current understanding of sulcal pattern emergence in the developing brain. We then highlighted the functional relevance of early sulcal development, through recent insights about hemispheric asymmetries and early factors influencing this dynamic such as prematurity. Finally, we outlined how longitudinal studies have started to relate early folding markers and the child’s sensorimotor and cognitive outcome. Through this review, we hope to raise awareness on the potential of studying early sulcal patterns both from a fundamental and clinical perspective, as a window into early neurodevelopment and plasticity in relation to growth in utero and postnatal environment of the child.

Plasticity in parental behavior and vasopressin: responses to co-parenting, pup age, and an acute stressor are experience-dependent.

The impact of variation in parental caregiving has lasting implications for the development of offspring. However, the ways in which parents impact each other in the context of caregiving is comparatively less understood, but can account for much of the variation observed in the postnatal environment. Prairie voles (Microtus ochrogaster) demonstrate a range of postnatal social groups, including pups raised by biparental pairs and by their mothers alone. In addition to the challenges of providing parental care, prairie vole parents often experience acute natural stressors (e.g., predation, foraging demands, and thermoregulation) that could alter the way co-parents interact. We investigated how variation in the experience of raising offspring impacts parental behavior and neurobiology by administering an acute handling stressor on prairie vole families of single mothers and biparental parents over the course of offspring postnatal development. Mothers and fathers exhibited robust behavioral plasticity in response to the age of their pups, but in sex-dependent ways. Pup-directed care from mothers did not vary as a function of their partner's presence, but did covary with the number of hypothalamic vasopressin neurons in experience-dependent ways. The relationship between vasopressin neuron numbers and fathers' behaviors was also contingent upon the stress handling manipulation, suggesting that brain-behavior associations exhibit stress-induced plasticity. These results demonstrate that the behavioral and neuroendocrine profiles of adults are sensitive to distinct and interacting experiences as a parent, and extend our knowledge of the neural mechanisms that may facilitate parental behavioral plasticity.

Postnatal nutrition environment reprograms renal DNA methylation patterns in offspring of maternal protein-restricted stroke-prone spontaneously hypertensive rats.

Maternal malnutrition hampers the offspring health by manipulating the epigenome. Recent studies indicate that the changes in DNA methylation could be reversed by afterbirth nutrition supplementation. In this study, we used DNA methylation arrays to comprehensively investigate the DNA methylation status of the renal promoter regions and the effects of postnatal protein intake on DNA methylation. We fed stroke-prone spontaneously hypertensive (SHRSP) rat dams a normal diet or a low-protein diet during pregnancy, and their 4-week-old male offspring were fed a normal diet or a high-/low-protein diet for 2 weeks. We found that the methylation status of 2,395 differentially methylated DNA regions was reprogrammed, and 34 genes were reset by different levels of postnatal protein intake in the offspring. Among these genes, Adora2b, Trpc5, Ar, Xrcc2, and Atp1b1 are involved in renal disease and blood pressure regulation. Our findings indicate that postnatal nutritional interventions can potentially reprogram epigenetic changes, providing novel therapeutic and preventive epigenetic targets for salt-sensitive hypertension.

Developmental changes in electrophysiological properties of auditory cortical neurons in the Cntnap2 knockout rat.

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole-cell patch-clamp recordings were conducted in wildtype and Cntnap2-/- littermates at 3 postnatal age ranges (P8-12, P18-21, and P70-90). Consistent changes across age were seen in all measures of intrinsic membrane properties and spontaneous synaptic input. Intrinsic cell properties such as action potential half widths, rheobase, and action-potential firing frequencies were different between wildtype and Cntnap2-/- rats predominantly during the juvenile stage (P18-21), whereas adult Cntnap2-/- rats showed higher frequencies of spontaneous and mini excitatory post-synaptic currents (sEPSC; mEPSC), with lower sEPSC amplitudes. These results indicate that intrinsic cell properties are altered in Cntnap2-/- during the juvenile age, leading to a hyperexcitable phenotype during this stage of synaptic remodeling and refinement. While intrinsic properties eventually normalize by reaching adulthood, changes in synaptic input, potentially caused by the differences in intrinsic membrane properties, seem to manifest in the adult age and are presumably responsible for the hyperreactive behavioral phenotype. In conjunction with a previous study, the present results also indicate a large influence of breeding scheme, i.e., pre- or postnatal environment, on the impact of Cntnap2 on cellular physiology.

Effects of cross-fostering experience on emotion in adolescent Kunming mice

Abstract Parent–infant bonds are critical early postnatal environment in mammals. Unstable parent–infant bonds, such as maternal separation, paternal deprivation, and neonatal social isolation have negative effects on emotion, cognition, addiction, and social behaviours in the animal’s whole lifespan. Another unstable parent–infant bond, cross-fostering, in which pups were randomly exchanged to other parents has mostly focused on kin recognition and anxiety-like behavioural changes in adult. But its effects on adolescence, particularly on autism spectrum disorder, are poorly understood. Whole cross-fostering model was used in the present study. The results showed that with cross-fostering, adolescent Kunming mice buried more marbles, expressed higher levels of anxiety and depression. Cross-fostering attenuated prosocial behaviours and reduced the activity of adolescence when encountering another individual in social interaction test. Taken together, our results demonstrate that experiencing whole cross-fostering in early life is more likely to induce autism-, anxiety-, and depression- like behaviours in adolescence.

Examining litter specific variability in mice and its impact on neurodevelopmental studies

Our current understanding of litter variability in neurodevelopmental studies using mice may limit translation of neuroscientific findings. Higher variance of measures across litters than within, often termed intra-litter likeness, may be attributable to both pre- and postnatal environment. This study aimed to assess the litter-effect within behavioral assessments (2 timepoints) and anatomy using T1-weighted magnetic resonance images across 72 brain region volumes (4 timepoints) (36 C57bl/6J inbred mice; 7 litters: 19F/17M). Between-litter comparisons of brain and behavioral measures and their associations were evaluated using univariate and multivariate techniques. A power analysis using simulation methods was then performed on modeled neurodevelopment and to evaluate trade-offs between number-of-litters, number-of-mice-per-litter, and sample size. Our results show litter-specific developmental effects, from the adolescent period to adulthood for brain structure volumes and behaviors, and for their associations in adulthood. Our power simulation analysis suggests increasing the number-of-litters in experimental designs to achieve the smallest total sample size necessary for detecting different rates of change in specific brain regions. Our results demonstrate how litter-specific effects may influence development and that increasing the litters to the total sample size ratio should be strongly considered when designing neurodevelopmental studies.

High-fat diet consumption by male rat offspring of obese mothers exacerbates adipose tissue hypertrophy and metabolic alterations in adult life.

Obese mothers' offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers' offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.

The reduced number of nephrons with shortening renal tubules in mouse postnatal adverse environment.

The intrauterine adverse environment during nephrogenesis reduces the nephron number, probably associates with impaired ureteric bud (UB) branching. The kidneys in C57/BL6 mice were irradiated with a single dose of 10 gray (10 Gy) as adverse environment on postnatal day 3 (irradiated PND3 kidneys) after UB branching ceased. The renal functions and pathological findings of irradiated PND3 kidneys were compared with those of non-irradiated control and 10 Gy irradiation on PND14 (irradiated PND14 kidney) from 1 to 18 months. The number and density of glomeruli in irradiated PND3 kidneys were reduced by 1 month with renal dysfunction at 6 months. The morphologically incomplete glomeruli with insufficient capillaries were involuted by 1 month in the superficial cortex. Reduced tubular numbers and developmental disability with shortening renal tubules occurred in irradiated PND3 kidneys with impaired urine concentration at 6 months. Hypertrophy of glomeruli developed, and occasional sclerotic glomeruli appeared in the juxtamedullary cortex with hypertension and albuminuria at 12 to 18 months. The reduced number of nephrons with shortening renal tubules occurred with impaired renal functions in a postnatal adverse environment after cessation of UB branching, and glomerular hypertrophy with occasional glomerulosclerosis developed accompanied with hypertension and albuminuria in the adulthood. The reduced number of nephrons with shortening renal tubules occurred with impaired renal functions in a postnatal adverse environment after cessation of ureteric bud branching. The reduced number of glomeruli were associated with not only the impaired formation of glomeruli but also involution of morphologically small incomplete glomeruli after an adverse environment. The insufficiently developed nephrons were characterized by the shortening renal tubules with impaired urine concentration. In addition, glomerular hypertrophy and occasional glomerulosclerosis developed with hypertension and albuminuria in adulthood. The present study can help to understand the risk of alternations of premature nephrons in preterm neonates.

The metabolic conditioning of obesity: A review of the pathogenesis of obesity and the epigenetic pathways that "program" obesity from conception.

Understanding the developmental origins of health and disease is integral to overcome the global tide of obesity and its metabolic consequences, including atherosclerotic cardiovascular disease, type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease. The rising prevalence of obesity has been attributed, in part, to environmental factors including the globalization of the western diet and unhealthy lifestyle choices. In this review we argue that how and when such exposures come into play from conception significantly impact overall risk of obesity and later health outcomes. While the laws of thermodynamics dictate that obesity is caused by an imbalance between caloric intake and energy expenditure, the drivers of each of these may be laid down before the manifestation of the phenotype. We present evidence over the last half-century that suggests that the temporospatial evolution of obesity from intrauterine life and beyond is, in part, due to the conditioning of physiological processes at critical developmental periods that results in maladaptive responses to obesogenic exposures later in life. We begin the review by introducing studies that describe an association between perinatal factors and later risk of obesity. After a brief discussion of the pathogenesis of obesity, including the systemic regulation of appetite, adiposity, and basal metabolic rate, we delve into the mechanics of how intrauterine, postnatal and early childhood metabolic environments may contribute to adult obesity risk through the process of metabolic conditioning. Finally, we detail the specific epigenetic pathways identified both in preclinical and clinical studies that synergistically "program" obesity.

Protective role of endorepellin in renal developmental programming.

Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway.

The presence of a mother counteracts prenatal stress in a precocial bird

In many species, prenatal maternal stress leads to long-lasting changes in physiological and behavioural individual characteristics. However, these prenatal effects can be modulated by the postnatal environment and especially by maternal care. The impact of maternal care on the modulation of prenatal maternal stress effects has been investigated mainly in mammalian models but, surprisingly, remains little explored in avian species. In this study, we determined the extent to which the subsequent effects of prenatal maternal stress on offspring growth and emotional responses are modulated by the presence of an adoptive mother during postnatal development using a precocial bird, the Japanese quail, Coturnix coturnix japonica , as our study species. All experimental quail chicks were the offspring of females that experienced an environmental stressor induced by a socially unstable environment during laying and egg production. Previous reports showed that social instability of laying quail increased their offspring's emotional reactivity and that this was related to an increase in yolk testosterone levels in their eggs. In this study, offspring hatched from socially unstable females were raised either with or without adoptive mothers. We found that mothered chicks were lighter during their first 3 weeks of age and that their emotional reactivity was lower (i.e. as shown by increased exploratory behaviours in a novel environment, decreased neophobic responses in the home cage and decreased responses to social separation) relative to nonmothered chicks. Thus, our results highlight that maternal care could counteract the phenotypic consequences of prenatally stress-exposed birds. Our results clearly highlight that even in precocial species the presence of the mother has a fundamental importance in modulating the effects of prenatal conditions on the ontogeny of offspring behaviour and that this might be a key mechanism driving phenotypic plasticity in wild populations. • Maternal care in Japanese quail counteracts prenatal stress effects. • Mothered chicks have a lower level of emotional reactivity than nonmothered ones. • Maternal care's influences are similar in mammals and birds.

Growing up in a crowd: social environment shapes the offspring's early exploratory phenotype in a colonial breeding species.

In colonial breeding species, the number of adverse social interactions during early life typically varies with breeding density. Phenotypic plasticity can help deal with this social context, by allowing offspring to adjust their behaviour. Furthermore, offspring may not be unprepared since mothers can allocate resources to their embryos that may pre-adjust them to the post-hatching conditions. Thus, we hypothesize that lesser black-backed gull chicks raised in dense breeding areas, with greater exposure to intra-specific aggression, show higher levels of anxiety and lower levels of exploration compared to chicks in low-density areas, and that this is facilitated by prenatal effects. To test this, we cross-fostered clutches within and across pre-defined high- and low-breeding density areas. We measured chicks' anxiety and exploration activity in an open-field test that included a novel and a familiar object. We found that both pre- and post-natal social environment contributed nearly equally and shaped the offspring's exploratory behaviour, but not its anxiety, in an additive way. Post-natal effects could reflect a learned avoidance of intra-specific aggression, yet identifying the pathways of the prenatal effects will require further study.

Prenatal programming of developmental trajectories for obesity risk and early pubertal timing.

The thrifty phenotype and fetal overnutrition hypotheses are two developmental hypotheses that originated from the developmental origins of health and disease (DOHaD) perspective. The DOHaD posits that exposures experienced prenatally and early in life may influence health outcomes through altering form and function of internal organs related to metabolic processes. Obesity risk and early pubertal timing might be influenced by similar mechanisms. The thrifty phenotype hypothesis is primarily characterized by experiencing a deprivation of nutrients during gestation paired with an energy rich postnatal environment. The fetal overnutrition hypothesis says that obesity experienced prenatally will be associated with increased lifetime risk of obesity in the offspring. Both hypotheses were tested by examining developmental pathways from genetic and prenatal risk through early growth trajectories (birth to 7 years) to pubertal timing at age 11 years. Participants included 361 children adopted at birth (57% male; 57% non-Hispanic White, 11% Black, 9% Hispanic; adoptive family income Mdn = $70,000-$100,000, birth family income Mdn = < $15,000). Associations between boys' childhood body mass index (BMI) and pubertal timing were confounded by genetics, prenatal risk, and early growth. The thrifty phenotype hypothesis was partially supported for boys' childhood BMI (at ages 4 to 7 years). Both hypotheses were partially supported for girls' childhood BMI but not pubertal timing. A novel Gene × Prenatal Risk interaction showed that genetic risk predicted girls' childhood BMI most strongly at adequate compared with at excessive levels of gestational weight gain. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Resource scarcity but not maternal separation provokes unpredictable maternal care sequences in mice and both upregulate Crh-associated gene expression in the amygdala

Early life adversity (ELA) is a major risk factor for the development of pathology, including anxiety disorders. Neurodevelopmental and behavioral outcomes following ELA are multifaceted and are influenced heavily by the type of adversity experienced and sex of the individual experiencing ELA. It remains unclear what properties of ELA portend differential neurobiological risk and the basis of sex-differences for negative outcomes. Predictability of the postnatal environment has emerged as being a core feature supporting development, with the most salient signals deriving from parental care. Predictability of parental care may be a distinguishing feature of different forms of ELA, and the degree of predictability afforded by these manipulations may contribute to the diversity of outcomes observed across models. Further, questions remain as to whether differing levels of predictability may contribute to differential effects on neurodevelopment and expression of genes associated with risk for pathology. Here, we tested the hypothesis that changes in maternal behavior in mice would be contingent on the type of ELA experienced, directly comparing predictability of care in the limited bedding and nesting (LBN) and maternal separation (MS) paradigms. We then tested whether the predictability of the ELA environment altered the expression of corticotropin-releasing hormone (Crh), a sexually-dimorphic neuropeptide that regulates threat-related learning, in the amygdala of male and female mice. The LBN manipulation reliably increased the entropy of maternal care, a measure that indicates lower predictability between sequences of dam behavior. LBN and MS rearing similarly increased the frequency of nest sorties and licking of pups but had mixed effects on other aspects of dam-, pup-, and nest-related behaviors. Increased expression of Crh-related genes was observed in pups that experienced ELA, with gene expression measures showing a significant interaction with sex and type of ELA manipulation. Specifically, MS was associated with increased expression of Crh-related genes in males, but not females, and LBN primarily increased expression of these genes in females, but not males. The present study provides evidence for predictability as a distinguishing feature of models of ELA and demonstrates robust consequences of these differing experience on sex-differences in gene expression critically associated with stress responding and sex differences in risk for pathology.

Neonatal reticulocytes among preterm infants of small for gestational age.

We previously reported that higher reticulocyte counts were observed in earlier preterm infants. Here we present an additional study that focused on reticulocyte counts among preterm infants of small for gestational age (SGA). To assess the relationship between SGA and perinatal variables during the early postnatal period. A single-center study was undertaken at Ohta Nishinouchi Hospital between April 1, 2016 and June 30, 2021, using blood samples prospectively collected from infants admitted to the neonatal intensive care unit. These were assessed by univariate analysis and multivariate logistic regression analysis. A total of 467 preterm infants were analyzed, 367 (78.6%) non-SGA and 100 (21.4%) SGA. The median [interquartile range (IQR)] GA (weeks) for the two groups was 33 (31-35) and 34 (31-36), respectively (p=0.058). The median (IQR) BW (g) for the two groups was 1888 (1480 to 2195) and 1381 (1019 to 1782), respectively (p<0.001). There were significant relationships between SGA and BW (p<0.001, OR, 0.997; 95% CI, 0.996 to 0.998), umbilical artery pH (p=0.038, OR, 0.031; 95% CI, 0.010 to 0.827), Apgar at 5min (p<0.001, OR, 1.816; 95% CI, 1.301 to 2.536), nucleated erythrocyte count (p=0.027, OR, 1.013; 95% CI, 1.001 to 1.024), reticulocyte count (p<0.001, OR, 0.992; 95% CI, 0.988 to 0.995) and chorioamnionitis (p=0.019, OR, 0.427; 95% CI, 0.210 to 0.868). These results suggest that preterm infants with SGA adapted more rapidly to the postnatal environment than did non-SGA preterm infants. Moreover, a lower reticulocyte count among preterm infants born SGA may be an indicator of good adaptation to the extra-uterine environment during the early postnatal period.