Early Postnatal Environment Research Articles

Lifelong consequences of early postnatal light environment

Frontiers Events is a rapidly growing calendar management system dedicated to the scheduling of academic events. This includes announcements and invitations, participant listings and search functionality, abstract handling and publication, related events and post-event exchanges. Whether an organizer or participant, make your event a Frontiers Event!

Early environment and major depression in young adults: A longitudinal study

Post-natal incubator care represents an early specific environment that may affect the risk for major depression later in life. A subsample of 1212 young adults from the French-speaking general population of the region of Quebec were selected from an ongoing longitudinal study that started during their kindergarten years. Information on peri-natal condition, obstetrical complications and incubator care was collected by consulting hospital medical records. Participants were evaluated using DSM III-R based psychiatric assessment when they were 15 and 21 years old. Incubator care predicted an approximate two- to three-fold decreased risk for depressive disorder at age 21. Results from three different logistic models adjusting for family adversity and for maternal depression confirmed this relationship. Analyses were replicated for depression at age 15, showing the same association in female adolescents. This study suggests that post-natal incubator care may paradoxically decrease the occurrence of major depression later in life. This protective effect might be direct (through optimized biological, physiological and sensory parameters) or indirect (induction of specific parent–child interactions due to the perception of their infant's vulnerability). This study could enhance understanding of the links between early post-natal environment and affective disorders later in life.

Programming of hypertension: the nervous kidney

two decades after Barker and coworkers ([2][1]) described an inverse epidemiological relationship between birth weight and risk of adult cardiovascular morbidity, including hypertension, the pathophysiology of prenatally programmed hypertension remains incompletely understood. Experimental models

The neonatal ventromedial hypothalamus transcriptome reveals novel markers with spatially distinct patterning.

The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in feeding, fear, thermoregulation, and sexual activity. It is essentially unknown how VMH circuits underlying these innate responses develop, in part because the VMH remains poorly defined at a cellular and molecular level. Specifically, there is a paucity of cell-type-specific genetic markers with which to identify neuronal subgroups and manipulate development and signaling in vivo. Using gene profiling, we now identify approximately 200 genes highly enriched in neonatal (postnatal day 0) mouse VMH tissue. Analyses of these VMH markers by real or virtual (Allen Brain Atlas; http://www.brain-map.org) experiments revealed distinct regional patterning within the newly formed VMH. Top neonatal markers include transcriptional regulators such as Vgll2, SF-1, Sox14, Satb2, Fezf1, Dax1, Nkx2-2, and COUP-TFII, but interestingly, the highest expressed VMH transcript, the transcriptional coregulator Vgll2, is completely absent in older animals. Collective results from zebrafish knockdown experiments and from cellular studies suggest that a subset of these VMH markers will be important for hypothalamic development and will be downstream of SF-1, a critical factor for normal VMH differentiation. We show that at least one VMH marker, the AT-rich binding protein Satb2, was responsive to the loss of leptin signaling (Lep(ob/ob)) at postnatal day 0 but not in the adult, suggesting that some VMH transcriptional programs might be influenced by fetal or early postnatal environments. Our study describing this comprehensive "VMH transcriptome" provides a novel molecular toolkit to probe further the genetic basis of innate neuroendocrine behavioral responses.

Development of mucosal immune function in the intrauterine and early postnatal environment

There is recent evidence that immunological priming can start prenatally or in the very early life phase. This review summarizes recent progress in the field of early gut immunology with special attention to factors contributing to the intrauterine and early postnatal development of mucosal immune responses in the gut. Development and maturation of the fetal gut immune system occurs under close control of the maternal environment. Examples include maternal antibodies, cytokines, sCD14 molecules and bacterial antigens. Mouse experiments reveal that activated T cells can be detected already at birth in the fetal gut, which are supposed to be activated by signals from the maternal microbial gut flora. Human milk sCD14 is involved in the immunological priming of the developing gut immune system to Gram-negative bacteria and modulates the microbial recognition system of the gut. The development of food allergies is associated with consumption of food components like polyunsaturated fatty acids acting prenatally or in the early postnatal life span as immunomodulators. The new findings highlight the importance of very early life factors for the development of the mucosal immune functions of the gut. Therefore, the gut might be a new target to establish preventive strategies with regard to different immunologic disorders.

The effects of early environmental conditions on the reproductive and somatic development of juvenile guinea pigs ( Cavia aperea f. porcellus)

Little is known about the effects of the early environment on the development of non-seasonally reproducing species like the domestic guinea pig ( Cavia aperea f. porcellus). Although guinea pigs reproduce throughout the year, there is evidence for environmental sensitivity of their reproductive physiology. To investigate the sensitivity of juvenile body weight and puberty to differences in the prenatal and early postnatal environment, subjects were exposed to either of two experimental conditions mimicking seasonal variation: a long photoperiod with 25 °C ambient temperature (“LD/25 °C”), or a short photoperiod with 15 °C (“SD/15 °C”). Mean body weight of F1-males from LD/25 °C-conditions was higher than that of SD/15 °C-males during the whole pubertal period, although the difference was significant only during the early growth phase. Testosterone concentrations also differed significantly between the two treatment groups, pointing to an earlier pubertal onset in LD/25 °C- than SD/15 °C-males. In F1-females, treatment effects on body weight or age at first estrus were absent. This indicates that the somatic and reproductive development is more sensitive to early photoperiod and temperature conditions in male than female guinea pigs, and that other environmental factors may also play a crucial role for reproductive maturation in this species.

Social deficits in BTBR T + tf/J mice are unchanged by cross-fostering with C57BL/6J mothers

Inbred strains of mice are useful model systems for studying the interactions of genetic and environmental contributions during neurodevelopmental stages. We recently reported an inbred strain, BTBR T+tf/J (BTBR), which, as compared to the commonly used C57BL/6J (B6) strain, displays lower social interactions as juveniles, lower social approach in adult ages, and higher levels of repetitive self-grooming throughout developmental stages. The present study investigated whether the early postnatal maternal environment contributes substantially to the unusually low expression of social behaviors and high self-grooming in BTBR as compared to B6. Within 24h of birth, entire litters of pups were cross-fostered to either a dam of the same strain or a dam of the opposite strain. Control litters were left with their own mothers. Offspring were tested for juvenile play at postnatal day 21±1, for sociability at 8 weeks of age in an automated three-chambered social approach test, and for self-grooming at 9–11 weeks of age. Results indicate that deficits in play behaviors in juvenile BTBR pups were not rescued by a B6 maternal environment. Similarly, a BTBR maternal environment did not induce play deficits in B6 pups. Cross-fostering had no effect on sociability scores in adults. The high self-grooming in BTBR and low self-grooming in B6 were not affected by maternal environment. These findings favor a genetic interpretation of the unusual social behaviors and self-grooming traits of BTBR, and support the use of the BTBR inbred strain as a mouse model to study genetic mechanism of autism.

Maternal separation alters ICSS responding in adult male and female rats, but morphine and naltrexone have little affect on that behavior

Prior research has provided evidence that the early postnatal environment can have long lasting effects on both the physiology and behavior of offspring. This is modeled in rats by using a maternal separation paradigm in which pups are separated from their mother for a few hours daily during their first two postnatal weeks. While this model has been used extensively to study stress effects and anxiety, less research has been done to examine how these separations affect measures of reward and reinforcement in adulthood. The current study investigated the impact of maternal separation (MS) on intracranial self-stimulation (ICSS) maintained responding in male and female offspring, and the effects of morphine (0.3–3.0 mg/kg) and naltrexone (0.1–10 mg/kg) on that responding. Rearing condition (MS or non-handled, NH) significantly altered response rates during acquisition in both sexes, with NH offspring exhibiting the highest rates. Group differences in baseline responding on a progressive ratio (PR-2) schedule of reinforcement were evident only in females, with MS females having response rates 50% lower than NH females. Neither morphine nor naltrexone differentially affected either rearing group. Sex impacted NH offspring: males acquired responding more readily, but females had higher response rates and breakpoints during all other phases of the experiment. In MS offspring, no sex differences were observed during acquisition, but during all other phases males had higher response rates and breakpoints than females. These results indicate that maternal separation during the first two postnatal weeks can have long-term effects on responding for ICSS, but these effects do not appear tied to endogenous opioid systems in the lateral hypothalamus.

Developmental programming of obesity in mammals

Converging lines of evidence from epidemiological studies and animal models now indicate that the origins of obesity and related metabolic disorders lie not only in the interaction between genes and traditional adult risk factors, such as unbalanced diet and physical inactivity, but also in the interplay between genes and the embryonic, fetal and early postnatal environment. Whilst studies in man initially focused on the relationship between low birth weight and risk of adult obesity and metabolic syndrome, evidence is also growing to suggest that increased birth weight and/or adiposity at birth can also lead to increased risk for childhood and adult obesity. Hence, there appears to be increased risk of obesity at both ends of the birth weight spectrum. Animal models, including both under- and overnutrition in pregnancy and lactation lend increasing support to the developmental origins of obesity. This review focuses upon the influence of the maternal nutritional and hormonal environment in pregnancy in permanently programming appetite and energy expenditure and the hormonal, neuronal and autocrine mechanisms that contribute to the maintenance of energy balance in the offspring. We discuss the potential maternal programming 'vectors' and the molecular mechanisms that may lead to persistent pathophysiological changes resulting in subsequent disease. The perinatal environment, which appears to programme subsequent obesity, provides a potential therapeutic target, and work in this field will readily translate into improved interventional strategies to stem the growing epidemic of obesity, a disease which, once manifest, has proven particularly resistant to treatment.

Intracranial self‐stimulation is altered by early postnatal stress, but is unaffected by morphine or naltrexone administration in both male and female rats

Prior research has provided evidence that the early postnatal environment can have long lasting effects on both the physiology and behavior of offspring. This is modeled in rats by using a maternal separation paradigm in which rat pups are separated from their mother for a few hours daily during their first two postnatal weeks. While this model has been used extensively to study stress effects and anxiety, less research has been done to examine how these separations effect measures of reward and reinforcement in adulthood. The current study investigated the impact of maternal separation (MS) on intracranial self-stimulation (ICSS) maintained responding in male and female offspring and the effects of morphine (0.3 – 3.0 mg/kg) and naltrexone (0.1 – 10.0mg/kg) on such responding. Rearing condition (MS or nonhandled, NH) significantly altered responding during acquisition in both sexes, but only altered baseline responding on a progressive ratio (PR2) schedule of reinforcement in females. Neither morphine nor naltrexone differentially affected either rearing group. Sex impacted NH offspring, with males acquiring responding more readily, but females having higher response rates and breakpoints during all other phases of the experiment. In MS offspring, no sex differences were observed during acquisition, but during all other phases males exhibited higher response rates and breakpoints than females. These results indicate that maternal separation during the first two postnatal weeks can have long-term effects on responding for ICSS, and that these changes do not appear tied to endogenous opioid systems. This work was supported by NIH grant DA14122.

Neonatal stress and litter composition alter sucrose intake in both rat dam and offspring

The early postnatal environment can have long lasting effects on the physiology and behavior of both mother and offspring. A great deal of evidence indicates that stress during this time period is a risk factor for the future development of a multitude of disorders including substance abuse. The maternal separation paradigm is used to model such stress in rats. The current study evaluated the effects of maternal separation and litter composition on sucrose consumption, a non-drug measure of reward, in both male Long–Evans rat offspring and mother. On postnatal day 2, rats were cross-fostered, placed in single-sex or mixed-sex litters, and subsequently stressed by daily dam–pup separations during the first two postnatal weeks. The length of the separation (15 min, 1 h, or 3 h) was randomly assigned to each day. A two-bottle choice test was given to maternally separated and nonhandled offspring when they were adults, and to dams 2–4 weeks after weaning. Intake of a 10% sucrose solution or water was compared for 1 h daily across five consecutive days. Rearing condition had a profound effect on total fluid intake and sucrose solution intake by both offspring and dam, with the separated offspring and dams generally consuming a greater amount of total fluid and 10% sucrose solution than their nonhandled counterparts. Litter composition also affected consumption, with the offspring from maternally separated mixed-sex litters consuming more total fluid and 10% sucrose solution than offspring from maternally separated single-sex litters. These results indicate that early postnatal and postpartum stress can lead to changes in sucrose consumption, a non-drug measure of reward, indicating that such stress may alter the underlying brain reward mechanisms.

Behavioral and hypothalamic-pituitary-adrenal responses to anterodorsal thalami nuclei lesions and variable chronic stress in maternally separated rats

In maternally separated rats, variable chronic stress decreased the emotional reactivity and provoked a state of hypoactivity of the hypothalamic-pituitary-adrenal system at 3 months old but increased its activity after the open field test. The anterodorsal thalami nuclei control of the endocrine response under stress conditions was not manifested however its seems activate grooming behavior.The development of behavioral and endocrine response to stress is influenced by early postnatal environment. On the other hand, the anterodorsal thalami nuclei exert an inhibitory influence on the hypothalamic-pituitary-adrenal system under basal and stressful conditions. The aim of this work is to determine the magnitude of behavioral and hypothalamic-pituitary-adrenal responses to variable chronic stress in adult female rats with anterodorsal thalami nuclei lesions, previously isolated for 4.5h daily during the first 3 weeks of life. The groups were: non-maternally separated sham and lesioned, maternally separated sham and lesioned with variable chronic stress with and without open field test.At 3 months old, under variable chronic stress, maternal separation provoked an increase in ambulation in sham and lesioned animals (P<0.01) but this parameter was not modified by lesion in either non-maternally separated or maternally separated groups. Neither the lesion nor the maternal separation changed the defecation and rearing parameter. Grooming behavior was lower in maternally separated lesioned rats (P<0.05). Under variable chronic stress maternal separation decreased adrenocorticotrophin hormone in comparison with non-maternally separated (P<0.001) and the lesion did not alter this response. Regarding corticosterone concentrations, maternal separation did not affect this hormone under variable chronic stress conditions and after the open field test there was an increase of this in both non-maternally separated and maternally separated sham and lesioned (P<0.001).

Adult Consequences of Fetal Growth Restriction

Low birthweight in relation to the length of gestation, is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and type 2 diabetes. These associations extend across the whole range of birthweight, which implies that normal variations in nutrient delivery to the fetus have profound long-term effects. The associations are thought to reflect the body's plasticity during development, by which its structure and function can be permanently changed by the intra uterine and early post natal environment. Slow growth during infancy and rapid weight gain after the age of two years exacerbate the effect of slow fetal growth. Cardiovascular disease and type 2 diabetes arise through a series of interactions between environmental influences and the pathways of development that precede them.

INVESTIGATING THE NEURODEVELOPMENTAL HYPOTHESIS OF SCHIZOPHRENIA

1. An optimal intra-uterine environment is critical for normal development of the brain. It is now thought that abnormal development in a compromised prenatal and/or early postnatal environment may be a risk factor for several neurological disorders that manifest postnatally, such as cerebral palsy, schizophrenia and epilepsy. 2. The present review examines some of the effects of abnormal prenatal brain development and focuses on one disorder that has been hypothesized to have, at least in part, an early neurodevelopmental aetiology: schizophrenia. 3. The key neuropathological alterations and changes in some of the neurotransmitter systems observed in patients with schizophrenia are reviewed. Evidence in support of a neurodevelopmental hypothesis for schizophrenia is examined. 4. A summary of the animal models that have been used by researchers in an attempt to elucidate the origins of this disorder is presented. Although no animal model of a complex human disorder is ever likely to emulate deficits in all aspects of structure and function observed in patients with a neuropsychiatric illness, our findings and those of others give support to the early neurodevelopmental hypothesis. 5. Thus, it is possible that an adverse event in utero disrupts normal brain development and creates a vulnerability of the brain that predisposes an already at-risk individual (e.g. genetic inheritance) to develop the disorder later in life.

International Adoption: A Health and Developmental Prospective

Adoptions from international countries have become an option for many US families, with over 150,000 children adopted in the past 14 years. Typically, internationally adopted children present with a host of medical and developmental concerns. Issues such as growth stunting, abnormal behaviors, and significant delays in motor, speech, and language development are likely directly related to the prenatal and early postnatal environment experienced prior to adoption. The new family and its health-care team must quickly work to identify and address these issues to aid the child's integration into his or her new family. This article will examine potential issues seen in children who are being adopted, including the impact of early environment on subsequent development. We will summarize early and long-term medical issues and review the extent of developmental delays seen in children adopted internationally. Finally, we will discuss possible mechanisms leading to the observed delays, including the impact of stress on subsequent development. By understanding the extent of expected delays and the mechanisms likely causing the issues, the health-care team will be in a good position to quickly identify and develop intervention protocols that will foster the child's assimilation into his or her new family.

Early life influences on serum 1,25 (OH)2 vitamin D

There is increasing evidence to support the role of the intrauterine and early postnatal environment in determining adult bone mass and risk of fracture. The mechanisms by which this occurs are uncertain but include perturbations in several endocrine axes. Vitamin D is integrally involved in bone metabolism and is therefore an ideal candidate. This study assesses whether birthweight and weight at 1 year of age are associated with the calcium vitamin D axis in elderly women. Vitamin D metabolites, parathyroid hormone, bone mineral density and biochemical markers of bone turnover were measured in 129 healthy women (mean age 65.5 years) from the MRC Hertfordshire Cohort Study whose birthweight and weight at 1 year were available from records. Serum 1,25 (OH)2 vitamin D concentrations were reduced with increasing weight at 1 year (19.1% reduction between the lowest and highest tertiles, P <0.01). A similar, but weaker trend was seen for birthweight. These associations were not explained by serum levels of serum calcium, phosphate, PTH, creatinine or sex hormones. The association of serum calcium with 1,25 (OH)2 vitamin D was greatest in the lowest tertile with little association in the highest tertile suggesting an increased sensitivity of renal 1-alpha hydroxylase in the lowest tertile. Highest levels of 1,25 (OH)2 vitamin D were associated with low BMD and high levels of urinary N-telopeptide suggesting that vitamin D metabolism may mediate the intrauterine and early postnatal environmental effects on adult BMD.

The biological significance of skin‐to‐skin contact and maternal odours

Infant-mother bodily contact is believed to be the species-typical pattern of immediate postpartum child care. Mothers and newborns engage in mutually beneficial interactions. Maternal odours stimulate breastfeeding activity and are implicated in individual recognition. Skin-to-skin contact and exposure to maternal odours facilitate infants' adaptation to the early postnatal environment.

Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

Variation in childhood asthma among former preterm infants

Objectives The role of in utero and perinatal exposures in modifying asthma risk among children born prematurely was assessed. Study design Former preterm children (n = 251) were identified from a birth cohort. Examinations, including lung function testing, were performed at ages 8 to 11 years. Perinatal exposures were ascertained from neonatal medical records. Results Univariate predictors of asthma included male gender, African American ethnicity, maternal asthma, and birth weight. Asthmatics were less likely to have been small for gestational age (SGA) than nonasthmatics (12.4% vs 22.7%, P = .04) and had more neonatal pulmonary disease. After adjusting for maternal asthma and demographic factors, asthma was associated with chronic lung disease of infancy, neonatal mechanical ventilation and corticosteroid use, and a higher childhood body mass index. Children who were septic postbirth and girls who were SGA were less likely to have asthma (OR for sepsis, 0.2; 95% CI, 0.1–0.6; OR for girls who were SGA compared with girls who were not SGA, 0.05; CI, 0.01–0.34). Conclusions Among premature children, female SGA status and neonatal sepsis appear protective relative to the development of childhood asthma. Differential susceptibility to asthma among preterm children may relate to exposures that operate in the in utero and early postnatal environment to accelerate lung development, alter innate immunity, or both.

Prenatal and early postnatal environments are significant predictors of total immunoglobulin E concentration in Filipino adolescents.

Recent evidence suggests that atopic disease may in part be mediated by fetal growth, as well as exposure to infectious disease early in life. Few studies have been able to evaluate these associations simultaneously, or to investigate prospectively the long-term effects of early environments while adequately controlling for potentially confounding variables. To examine how prenatal growth and infectious disease in infancy are related to total IgE production in adolescence. Ninety-nine adolescents (aged 14-15 years) were selected from a larger cohort study according to the following criteria: full-term birth, currently healthy, and small-for-gestational age (N=53) or appropriate-for-gestational age (N=46). Plasma total IgE was measured with ELISA, and analysed in relation to anthropometric, nutritional, and environmental quality data collected prospectively beginning in the third trimester prior to birth. Each episode of infectious morbidity recorded at bimonthly intervals in the first 6 months of life was associated with a 0.12 log IU/mL reduction in total IgE in adolescence (P=0.004). Prenatal undernutrition was associated with increased adolescent IgE, but only under conditions of an unsanitary household environment (P=0.002). Each additional kilogram gained per month in the first 6 months of life was associated with an increase in adolescent IgE of 0.74 log IU/mL (P=0.03). Each quartile increase in weekly household income at the time of blood sampling was associated with a 0.10 log IU/mL reduction in total IgE (P=0.02). Infectious disease in infancy, as well as interactions between prenatal and postnatal environments, appear to have long-term effects on adolescent total IgE production. Future research should investigate the mechanisms behind these effects, and their implications for symptoms of atopic disease.