Delivery as a traumatic event: prevalence, risk factors, screening & treatment

This review looks at the evidence for postnatal posttraumatic stress disorder (PTSD). Postnatal traumatic stress responses are divided into: appraisal of birth as traumatic, traumatic stress responses (severe symptoms of intrusions and avoidance that do not fulfil criteria for PTSD), and PTSD. Evidence is examined for the prevalence of these types of responses after birth, and for prenatal, perinatal, and postnatal vulnerability and risk factors. Screening tools that could be used are outlined and possible intervention and treatment approaches considered. Various conceptual and methodological issues are also raised. It is concluded that up to 10% of women have severe traumatic stress responses to birth although only 1-2% of women actually develop chronic postnatal PTSD. The limited research available suggests that a history of psychiatric problems, mode of delivery, and low support during labour put women at increased risk of postnatal PTSD, although there is unlikely to be a simple relationship between mode of delivery and traumatic stress responses. A model of the possible pathways between vulnerability/risk factors and postnatal PTSD is proposed. Current evidence suggests that brief cognitive-behavioural therapy (CBT) interventions should be used with women who have a severe traumatic stress response, and longer CBT interventions with women with postnatal PTSD. More research is needed to further explore and confirm prenatal, birth, and postnatal risk factors

Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype

Susceptibility loci CNVs with incomplete penetrance accurate diagnosis with uncertain prognosis

Chromosomal microarray analysis (CMA) is the first-tier test for developmental delay, autism spectrum disorders, and congenital abnormalities in postnatal diagnosis and for ultrasound abnormalities in prenatal diagnosis. The detection of variants with clinical significance by CMA, when compared to karyotype, can increase up to 10-20% in postnatal diagnosis and up to 5-18% in prenatal diagnosis. Nevertheless CMA also detects incomplete penetrance neuro-Susceptibility Loci Copy Number Variants (SL-CNV), which although having clinical significance have an uncertain prognosis. The aim of this study is to identify from the literature a set of SLCNV, and the corresponding penetrance for each variant, determining their occurrence in our cohort of postnatal samples ran between January 2012 and August 2018 and prenatal samples ran between January 2015 and August 2018. We have established a 21 SL-CNV set, and from a total of 835 postnatal samples and 317 prenatal samples we have identified 36 and 11 cases, respectively, with a variant in one of the 21 established SLCNV. The percentage of cases with a SL-CNV is relatively similar between postnatal samples (4.5%) and prenatal samples (3.5%), although the reason of referral for the two groups is not completely overlapping and also the total number of prenatal samples represents about half of the time span of the postnatal samples, which might have underestimated their occurrence. The estimated penetrance for each of the established SL-CNV present some inter-publication variability, especially concerning samples with different phenotypes. Nevertheless some variants show concordance. Estimating the penetrance for SL-CNV, and their clinical impact for the patient or carriers in the family, is a complex task. Only time, analysis of larger cohorts, and future knowledge of genotype-environment-phenotype interactions will overcome this difficulty, decreasing uncertainty for the around 4% of patients diagnosed by CMA.info:eu-repo/semantics/publishedVersio

Increase in neuroexcitability of unmyelinated C-type vagal ganglion neurons during initial postnatal development of visceral afferent reflex functions

BACKGROUND: Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs). METHODS: To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A- and C-type VGNs at different developmental stages using whole-cell patch clamping. RESULTS: C-type VGNs underwent significant age-dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX-S and TTX-R Na(+) currents were also confirmed and well simulated by computer modeling. Although 4-AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4-AP- and iberiotoxin-sensitive K(+) current activity, whereas less developmental changes were verified in A-types. CONCLUSION: These data demonstrate for the first time that the neuroexcitability of C-type VGNs increases significantly compared with A-types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function

Integrating Statistical Evidence and Legal Theory to Challenge the Selection of Grand and Petit Jurors

The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid (LCPUFA) ratio, resulting in an abnormal postnatal immune maturation. The timing of allergy-preventive probiotic and ω-3 LCPUFA interventions is critical, as early-life events occurring during critical windows of immune vulnerability can have long-term impact on immune development. The maternal dietary and microbial environment during pregnancy may programme the immune development of the child. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment, but potentially also increasing disease susceptibility in the offspring if exposures are mismatched. Although the importance of fetal programming mostly has been studied in cardiovascular and metabolic disease, this hypothesis is also very attractive in the context of environmentally influenced immune-mediated diseases. This review focuses on how prenatal, perinatal or postnatal ω-3 LCPUFA interventions regulate childhood immune and allergy development, and if synergistic effects may be obtained by simultaneous probiotic supplementation. We propose that combined pre- and postnatal preventive measures may be most efficacious. Increasing knowledge on the immunomodulatory effects of prenatal, perinatal and postnatal interventions will help to direct future strategies to combat the allergy epidemic.Funding Agencies|Swedish Research Council||Ekhaga Foundation||Research Council for the South-East Sweden||Swedish Asthma and Allergy Association||Olle Engkvist Foundation||Vardal Foundation - for Health Care Sciences and Allergy Research||</p

Effect of androgen treatment during foetal and/or neonatal life on ovarian function in prepubertal and adult rats

We investigated the effects of different windows of testosterone propionate (TP) treatment during foetal and neonatal life in female rats to determine whether and when excess androgen exposure would cause disruption of adult reproductive function. Animals were killed prepubertally at d25 and as adults at d90. Plasma samples were taken for hormone analysis and ovaries serial sectioned for morphometric analyses. In prepubertal animals, only foetal+postnatal and late postnatal TP resulted in increased body weights, and an increase in transitory, but reduced antral follicle numbers without affecting total follicle populations. Treatment with TP during both foetal+postnatal life resulted in the development of streak ovaries with activated follicles containing oocytes that only progressed to a small antral (smA) stage and inactive uteri. TP exposure during foetal or late postnatal life had no effect upon adult reproductive function or the total follicle population, although there was a reduction in the primordial follicle pool. In contrast, TP treatment during full postnatal life (d1-25) resulted in anovulation in adults (d90). These animals were heavier, had a greater ovarian stromal compartment, no differences in follicle thecal cell area, but reduced numbers of anti-Mullerian hormone-positive smA follicles when compared with controls. Significantly reduced uterine weights lead reduced follicle oestradiol production. These results support the concept that androgen programming of adult female reproductive function occurs only during specific time windows in foetal and neonatal life with implications for the development of polycystic ovary syndrome in women

Postnatal origins of undernutrition.

Obesity and nutrition-related chronic disorders are fast rising in developing countries. But undernutrition--stunting, underweight, wasting and micronutrient deficiencies--still affect millions of preschool children in both rural and urban settings increasing the risks of morbidity and mortality, impairing cognitive development, reducing productivity and increasing the risk of chronic diseases in later life. In addition undernutrition has a transgenerational effect. Here I review the evidence for a synergistic effect of inadequate nutrition (breastfeeding, complementary feeding), infection, and inappropriate mother-child interactions on growth and nutritional deficiencies. Underlying socioeconomic, environmental and genetic factors are also explored. Finally some perspectives on how urbanization and globalization may affect the prevalence and distribution of undernutrition are discussed. Fighting child under-nutrition is still an urgent necessity and a moral imperative

Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF- II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A- immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs