Prenatal Events Research Articles

Changes in cytokine and cytokine receptor levels during postnatal development of the human dorsolateral prefrontal cortex

In addition to their traditional roles in immune cell communication, cytokines regulate brain development. Cytokines are known to influence neural cell generation, differentiation, maturation, and survival. However, most work on the role of cytokines in brain development investigates rodents or focuses on prenatal events. Here, we investigate how mRNA and protein levels of key cytokines and cytokine receptors change during postnatal development of the human prefrontal cortex. We find that most cytokine transcripts investigated (IL1B, IL18, IL6, TNF, IL13) are lowest at birth and increase between 1.5 and 5 years old. After 5 years old, transcriptional patterns proceeded in one of two directions: decreased expression in teens and young adults (IL1B, p = 0.002; and IL18, p = 0.004) or increased mean expression with maturation, particularly in teenagers (IL6, p = 0.004; TNF, p = 0.002; IL13, p < 0.001). In contrast, cytokine proteins tended to remain elevated after peaking significantly around 3 years of age (IL1B, p = 0.012; IL18, p = 0.026; IL6, p = 0.039; TNF, p < 0.001), with TNF protein being highest in teenagers. An mRNA-only analysis of cytokine receptor transcripts found that early developmental increases in cytokines were paralleled by increases in their ligand-binding receptor subunits, such as IL1R1 (p = 0.033) and IL6R (p < 0.001) transcripts. In contrast, cytokine receptor-associated signaling subunits, IL1RAP and IL6ST, did not change significantly between age groups. Of the two TNF receptors, the ‘pro-death’ TNFRSF1A and ‘pro-survival’ TNFRSF1B, only TNFRSF1B was significantly changed (p = 0.028), increasing first in toddlers and again in young adults. Finally, the cytokine inhibitor, IL13, was elevated first in toddlers (p = 0.006) and again in young adults (p = 0.053). While the mean expression of interleukin-1 receptor antagonist (IL1RN) was highest in toddlers, this increase was not statistically significant. The fluctuations in cytokine expression reported here support a role for increases in specific cytokines at two different stages of human cortical development. The first is during the toddler/preschool period (IL1B, IL18, and IL13), and the other occurs at adolescence/young adult maturation (IL6, TNF and IL13).

Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation.

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.

Abstract 56: DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressures in Response to Weight-Loss Diets

Introduction: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life. Hypothesis: DNAm levels of genes related to both birthweight and blood pressure were associated with changes in blood pressures in response to dietary weight-loss interventions. Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm levels as the average methylation level within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793). Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes. Results: We found that the regional DNAm at LINC00319, but not the other genes, showed different associations with 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among participants assigned low- or high-fat diets (P for interaction &lt; 0.05 for all, Figure ). In response to low-fat diet, per standard deviation higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in SBP (β: -1.481; standard error [SE]: 0.632; P = 0.020) and DBP (β: -1.096; SE: 0.413; P = 0.009). Three trajectories of changes in SBP and DBP were identified, and participants with higher baseline regional DNAm at LINC00319 were less likely to have stable or increased blood pressure levels. Conclusions: Our findings indicate that higher regional DNAm level at LINC00319 was significantly associated with greater long-term reduction in blood pressure in response to a low-fat diet, suggesting people with higher regional DNAm levels benefited more from eating a low-fat weight-loss diet.

Prenatal maternal stress and the severity of autism spectrum disorder: A cross-sectional study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to several genetic and environmental factors including antenatal stress. Hence, we aimed to examine whether a mother's stress during pregnancy is associated with the severity of autism spectrum disorder in children. The study was conducted with 459 mothers of children with autism (aged 2-14 years) who were attending rehabilitation and educational centers in the two major cities of Makkah and Jeddah in Saudi Arabia. Environmental factors, consanguinity, and ASD family history were assessed using a validated questionnaire. The Prenatal Life Events Scale questionnaire was used to assess whether the mothers were exposed to stress during pregnancy. Two models of ordinal regression analysis were conducted including gender, child age maternal age, parental age, maternal education, parental education, income nicotine exposure, mother taking medication during pregnancy, family history of ASD, gestation, consanguinity, exposure of prenatal life events (in model 1), and severity of prenatal life events (in model 2). Family history of ASD showed a statistically significant association with the severity of ASD in both regression models (p = .015, odds ratio [OR]: 4.261 in Model 1, and p = .014, OR: 4.901 in model 2). In model 2, the moderate severity prenatal life events showed higher statistically significant adjusted odds ratio for ASD severity compared to no stress (p = .031; OR: 3.82). Within the limitations of this study, prenatal stressors showed some potential contribution to ASD severity. Family history of ASD was the only factor that showed a persistent association with ASD severity. A study that assesses the effect of COVID-19 stress on ASD prevalence and severity is recommended.

Early systemic inflammation induces neurodevelopmental disorders: results from ARTEMIS, a French multicenter study of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders and meta-analysis.

Prenatal immune-mediated events are known risk factors for neurodevelopmental disorders in the offspring (NDD). Although the brain continues to develop for years after birth and many postnatal factors alter the regular trajectory of neurodevelopment, little is known about the impact of postnatal immune factors. To fill this gap we set up ARTEMIS, a cohort of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders (jRSAID), and assessed their neurodevelopment. We then complemented our results with a systematic review and meta-analysis. In ARTEMIS, we used unsupervised and supervised analysis to determine the influence of jRSAID age at onset (AO) and delay in introduction of disease-modifying therapy (DMT) on NDD (NCT04814862). For the meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane, and Web of Science up to April 2022 without any restrictions on language, or article type for studies investigating the co-occurence of jRSAID and NDD (PROSPERO- CRD42020150346). 195 patients were included in ARTEMIS. Classification tree isolated 3 groups of patients (i) A low-risk group (AO > 130 months (m)) with 5% of NDD (ii) A medium-risk group (AO < 130 m and DMT < 2 m) with 20% of NDD (iii) and a high-risk-group (AO < 130 m and DMT > 2 m) with almost half of NDD. For the meta-analysis, 18 studies encompassing a total of (i) 46,267 children with jRSAID; 213,930 children with NDD, and 6,213,778 children as controls were included. We found a positive association between jRSAID and NDD with an OR = 1.44 [95% CI 1.31; 1.57] p < 0.0001, [I2 = 66%, Tau2 = 0.0067, p < 0.01]. Several sensitivity analyses were performed without changing the results. Metaregression confirmed the importance of AO (p = 0.005). Our study supports the association between jRSAID and NDD. AO and DMT have pivotal roles in the risk of developing NDD. We plead for systematic screening of NDD in jRSAID to prevent the functional impact of NDD.

Pregnancy-Specific Stress and Racial Discrimination Among U.S. Women.

Adverse birth outcomes among children born to women of color (WOC) have been associated with discrimination during pregnancy; however, little research has explored stressed caused by discrimination as well as pregnancy-specific stress. The purpose of this study was to examine differences in stress and racial discrimination (lifetime and during pregnancy) between U.S. women of different racial/ethnic groups. Women between 18 and 45 years (n = 198; 101 non-Hispanic White, 58 Black, and 39 other WOC [i.e., Hispanic, Asian/Pacific Islander, American Indian, Mixed Race]) completed an online, cross-sectional survey between December 2019 and March 2020. Participants reported pregnancy-specific stress using the pregnancy distress questionnaire (PDQ) and pregnancy life events scale (PLE) and discrimination via the general ethnic discrimination scale (GED). ANOVAs explored differences between racial/ethnic groups' stress and discrimination. We found non-Hispanic White (p < 0.05) and other WOC (p < 0.01) reported higher distress during pregnancy than Black women, and other WOC (p < 0.05) reported more stressful prenatal life events (p < 0.05) than non-Hispanic Whites. However, Black (p < 0.001) and other WOC (p < 0.001) both experienced more ethnic discrimination throughout their lifetime and during their pregnancy than non-Hispanic Whites. Also, Black women experienced five times the stress from these encounters than White women (p < 0.001). Previously developed pregnancy distress questionnaires may be better suited for non-Hispanic White populations and may miss important experiences unique to marginalized populations such as racial/ethnic discrimination. Adaptations to pregnancy-related stress scales are warranted given the toxicity of discrimination during pregnancy.

GENE POLYMORPHISM AS A PREDICTOR DEVELOPMENT OF THE CHILDREN DISEASE

Neonates suffering from severe birth asphyxia may develop hypoxic ischemic encephalopathy and in some cases to permanent neurological damage. Around 20 – 50% of neonates with birth asphyxia who have hypoxic ischemic encephalopathy symptoms die in the neonatal period. Our study aims to clarify the role and impact of gene polymorphisms on the occurrence of hypoxic-ischemic encephalopathy. Hypoxic-ischaemic encephalopathy is a common cause of death and disability in newborns. It causes long-term or permanent damage, such as cerebral palsy, epilepsy, and certain forms of mental retardation. Autoregulation may be impaired during various neonatal disease and states including prematurity, hypoxic-ischemic encephalopathy, intraventricular haemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation. As infants are especially sensitive to changes in cerebral blood flow, both hypoperfusion and hyperperfusion can cause significant neurologic injury. All of these conditions impair cerebral blood flow, leading to ischemia and hypoxia and trigger a cascade of deleterious biochemical events that seriously and permanently injure the brain. The nitric oxide produced by NOS3 plays a critical role in maintaining cerebral blood circulation and preventing neuronal injury. Mild exposure to ischemia activates enzyme NOS3 and produces small amounts of nitric oxide with subsequent relaxation of blood vessels and vasodilatation. Genetic factors could also affect the processes of autoregulation and destruction following hypoxic-ischemic injury. An underlying genetic predisposition that increases or decreases the degree of injury after a prenatal hypoxic ischemic event may affect the clinical course and prognosis. Except of therapeutic hypothermia, which currently is the only treatment available, a considerable number of newborns still have adverse outcomes. Therefore, there is a pressing need for novel better prognostic and diagnostic tools to improve outcome.

Beyond Medically Complex Pregnancy: A Scoping Review to Understand How Complexity in Pregnancy is Conceptualized.

The goal of this scoping review was to better understand how complexity in pregnancy is conceptualized. Specific objectives were to (1) identify factors that are conceptualized in the literature as complicating or impacting pregnancy; and (2) summarize tools and programs that have been implemented to support pregnant people with complex care needs. Electronic databases were searched from January 2000 to July 2020 and supplemented by bibliographic searches and citation chaining, to identify articles that described at least one nonmedical and one medical risk factor during pregnancy. We focused on complexity prior to the onset of labor and only included primary studies conducted in middle- or high-income countries. More than 6000 records were screened independently by 3 reviewers at the abstract and title level. Fourteen articles met inclusion criteria. Eight studies described antenatal risk scoring systems, including the Florida Healthy Start Prenatal Risk Screen, the Kindex risk screening tool, the prenatal event history calendar, and the Rotterdam Reproductive Risk Reduction score card. We abstracted 85 medical factors and 25 nonmedical factors from the literature. Nonmedical factors that were conceptualized as complicating pregnancy or birth could be grouped into 4 domains: characteristics of the childbearing person (7 factors), socioeconomic conditions (7 factors), family and social life (5 factors), and psychoemotional health (6 factors). We found limited scholarly research and few assessment tools that broaden the discussion of complexity in pregnancy beyond medical multimorbidity. Multiple dimensions of health should be integrated into a complexity framework for pregnancy that account for the diverse contexts and needs of pregnant people. An important part of this process is the development of a shared language to describe complexity that is strength based and acknowledges how environments, health care encounters, and the larger sociocultural context can affect pregnant people's medical status in pregnancy.

A predictive ensemble classifier for the gene expression diagnosis of ASD at ages 1 to 4 years

Autism Spectrum Disorder (ASD) diagnosis remains behavior-based and the median age of diagnosis is ~52 months, nearly 5 years after its first-trimester origin. Accurate and clinically-translatable early-age diagnostics do not exist due to ASD genetic and clinical heterogeneity. Here we collected clinical, diagnostic, and leukocyte RNA data from 240 ASD and typically developing (TD) toddlers (175 toddlers for training and 65 for test). To identify gene expression ASD diagnostic classifiers, we developed 42,840 models composed of 3570 gene expression feature selection sets and 12 classification methods. We found that 742 models had AUC-ROC ≥ 0.8 on both Training and Test sets. Weighted Bayesian model averaging of these 742 models yielded an ensemble classifier model with accurate performance in Training and Test gene expression datasets with ASD diagnostic classification AUC-ROC scores of 85–89% and AUC-PR scores of 84–92%. ASD toddlers with ensemble scores above and below the overall ASD ensemble mean of 0.723 (on a scale of 0 to 1) had similar diagnostic and psychometric scores, but those below this ASD ensemble mean had more prenatal risk events than TD toddlers. Ensemble model feature genes were involved in cell cycle, inflammation/immune response, transcriptional gene regulation, cytokine response, and PI3K-AKT, RAS and Wnt signaling pathways. We additionally collected targeted DNA sequencing smMIPs data on a subset of ASD risk genes from 217 of the 240 ASD and TD toddlers. This DNA sequencing found about the same percentage of SFARI Level 1 and 2 ASD risk gene mutations in TD (12 of 105) as in ASD (13 of 112) toddlers, and classification based only on the presence of mutation in these risk genes performed at a chance level of 49%. By contrast, the leukocyte ensemble gene expression classifier correctly diagnostically classified 88% of TD and ASD toddlers with ASD risk gene mutations. Our ensemble ASD gene expression classifier is diagnostically predictive and replicable across different toddler ages, races, and ethnicities; out-performs a risk gene mutation classifier; and has potential for clinical translation.

The epidemiology and disease burden of congenital TORCH infections among hospitalized children in China: A national cross-sectional study.

Congenital TORCH (Toxoplasma gondii (T. gondii), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV)) infections are associated with a variety of adverse prenatal and neonatal events, including miscarriage, malformations and developmental abnormalities, and they remain an issue that cannot be neglected in China. However, the current research focuses more on the general screening of TORCH in women of childbearing age, and the medical information of children hospitalized due to congenital and perinatal TORCH infections has not been described in detail. This study summarized and analyzed the epidemiological characteristics, clinical manifestations, length of stay (LOS), and the disease burden of hospitalized children diagnosed with congenital TORCH infections in 27 children's hospitals in China. Based on the face sheet of discharge medical records (FSMRs) of hospitalized children in 27 tertiary children's hospitals collected in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE), we summarized and analyzed the epidemiological characteristics, clinical manifestations, LOS, the disease burden (in US dollars, USD) and potential risk factors for hospitalized children diagnosed with congenital toxoplasmosis, congenital rubella syndrome, congenital cytomegalovirus infection, and congenital HSV in 27 children's hospitals in China from 2015 to 2020. One hundred seventy-three patients aged 0-<1 year were hospitalized for congenital TORCH infections. Among infections with TORCH, hospitalization with congenital toxoplasmosis was the least common, with only five cases were reported (2.89%), while the LOS was the highest. The proportion of patients with congenital rubella syndrome (CRS) was 15.61%, and 86% of children hospitalized with CRS had cardiovascular malformations, and the economic burden was the highest. Congenital CMV infection cases accounted for the largest proportion (76.30%). Overall, 5.20% of patients were infected with HSV, and the expense of hospitalization for congenital HSV infection was relatively low. In the present study, the hospitalization proportion due to congenital TORCH infection was extremely low (17.56 per 100,000 neonates), indicating that China's congenital TORCH infection prevention and control policies remain effective. The lowest proportion of patients was hospitalized with congenital toxoplasmosis, while the LOS was the longest. The economic burden of CRS was heavy, and infants are recommended be vaccinated against RV in a timely manner. Congenital CMV infections accounted for the largest proportion of patients, suggesting that the disease burden of congenital CMV infection cannot be ignored, and the prevention of congenital CMV infection during pregnancy is still an important issue that needs to pay attention. The expense of hospitalization for congenital HSV infection was relatively low, while the disease burden increases significantly when patients develop complications. These data illustrate the importance of improving screening for congenital TORCH infections in the early diagnosis and treatment of neonatal patients.

Alternative technique of intrauterine myelomeningocele repair to decrease the incidence of unfavorable maternal and fetal outcomes.

The aim of the study was to determine the effectiveness of an alternative method of open fetal surgery to prevent severe unfavorable prenatal events, both for the mother and the fetus. In this study, the previously published results for a cohort of 46 patients, who had undergone intrauterine myelomeningocele repair (IUMR) at our Center by 2014, constituted the retrospective control group (CG). The MOMS protocol had been applied for hysterotomy, with an automatic uterine stapling device. The study group (SG) n = 57 was assembled during a prospective observation. IUMR was performed using an alternative method of hysterotomy, with the typical opening and closure of the uterus, without automatic stapling device, as described by Moron et al. Additionally, our single-center results were compared with the post-MOMS findings of other centers: CHOP (Children' S HOSPITAL OF PHILADELPHIA: ) and VUMC (Vanderbilt University Medical CENTER: ). No cases of delivery before 30 weeks of gestation (0%, 0/55) were observed in the study group, which is a statistically significant difference (p < 0.05) as compared to controls (15/44). Statistically significantly lower incidence of chorioamniotic separation (5.4% (3/55) vs CHOP 22.9% (22/96), p < 0.001) and contractile activity resulting in preterm labor (16.3% (9/55) vs CHOP 37.5% (36/96), p < 0.05) was found in the study group. Premature rupture of the membranes was statistically significantly less common in the study group as compared to controls, CHOP and VUMC (SG 12.7% (7/55) vs CG 52.2% (24/46), p < 0.001; vs CHOP 32.3% (31/96), p < 0.001; vs VUMC 22% (9/43), p < 0.01, respectively). The presented IUMR method is associated with improved perinatal outcomes, i.e., lower rates of preterm delivery at < 30 weeks of gestation, preterm premature rupture of membranes, and uterine contractility resulting in preterm delivery. That, in turn, results in lower prematurity rates and, consequently, more favorable neonatal outcomes.

Anencephaly and Its Associated Congenital Anomalies: A Case Report of a Delivery in a Rural Hospital, in Eastern Uganda

Introduction: Anencephaly also called cranioschisis is part of neural tube defects spectrum which occur when the neural tube fails to close normally during the 3rd and 4th weeks of development leading to fetal loss, still birth or neonatal death. Literature show that causation of anencephaly is multifactorial involving interaction of genetics and the environment though not well characterized. In this case report, we present the features of anencephaly and its different clinical associated malformations.&#x0D; Methods: A case report study design was employed to explore the prenatal and antenatal events that resulted into an anencephaly delivery. The intra-natal and immediate postnatal fetal observations and outcome were documented. We also documented the care given to the mother throughout ANC, time of delivery and postnatally until discharge.&#x0D; Results: 29-year G2P1+0 at 29W2D, presented with 2 days’ sudden progressive per vaginal bleeding and clear non-foul discharge on 2nd day of admission with no history of abdominal pain, fever or trauma. Two days later she was delivered by Caesarean section to a grossly neural malformed preterm baby boy with APGAR score 6 at 1 minute and 4 at 5 minutes. Birth weight and length were 1.5 kg and 48.6cm respectively. The baby life indicators deteriorated progressively and finally died at 36 minutes after time of delivery.&#x0D; Conclusion: Although interaction between genomic and environmental factors that play a key role in the causation of anencephaly can not clearly be evaluated, there is an understanding of pre-natal and antenatal factors that predispose to this case such as lack of Folate and or interference with its bioavailability, use of teratogenic drugs taken during pregnancy and antenatal maternal conditions. We therefore recommend routine supply of folate to girls and women intending or risk to conceive 3 months before pregnancy through first trimester and health education about use of native drugs and any other conventional medicines during pregnancy.

Can helminth and malaria infections affect sex ratio at birth in sub-Saharan Africa? Ideas and hypothesis.

The sex ratio (ratio of boys to girls) at birth (SRB) is about 1.05 (about 105 males to 100 females) under normal conditions and could be an indicator for monitoring demographic changes. Generally, in comparison with female fetuses, the male fetus is biologically weaker and more vulnerable to prenatal events. SRB is influenced by various factors, such as maternal malnourishment. Remarkably, maternal malnourishment and less energy intake are pivotal factors for declining SRB in humans. As estimates, the SRB is below the normal range in sub-Saharan Africa (1.03) than the normal range (1.05). On the other hand, both malaria and helminth infections are hyperendemic in sub-Saharan Africa and both diseases are associated with maternal malnourishment. Hence, an important question arises, could declining SRB in sub-Saharan Africa be influenced by malaria and helminth infections? Cumulative evidence suggests that malaria and helminth infections could influence SRB by induction of maternal malnourishment. This hypothesis provides new ideas about the variation of SRB in some regions of the world where helminths and malaria are endemic.

Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity.

Preterm birth before the gestational age of 32 weeks is associated with the occurrence of specific white matter damage (WMD) that can compromise the neurological outcome. These white matter abnormalities are embedded in more global brain damage defining the encephalopathy of prematurity (EoP). A global reduction in white matter volume that corresponds to chronic diffuse WMD is the most frequent form in contemporary cohorts of very preterm infants. This WMD partly results from alterations of the oligodendrocyte (OL) lineage during the vulnerability window preceding the beginning of brain myelination. The occurrence of prenatal, perinatal and postnatal events in addition to preterm birth is related to the intensity of WMD. Systemic inflammation is widely recognised as a risk factor of WMD in humans and in animal models. This review reports the OL lineage alterations associated with the WMD observed in infants suffering from EoP and emphasizes the role of systemic inflammation in inducing these alterations. This issue is addressed through data on human tissue and imaging, and through neonatal animal models that use systemic inflammation to induce WMD. Interestingly, the OL lineage damage varies according to the inflammatory stimulus, i.e., the liposaccharide portion of the E.Coli membrane (LPS) or the proinflammatory cytokine Interleukin-1β (IL-1β). This discrepancy reveals multiple cellular pathways inducible by inflammation that result in EoP. Variable long-term consequences on the white matter morphology and functioning may be speculated upon according to the intensity of the inflammatory challenge. This hypothesis emerges from this review and requires further exploration.

Stressful life events in pregnancy: A risk factor for exclusive breastfeeding among high-income mothers

ObjectiveThe aim of this study was to examine the association between prenatal stressful life events in pregnancy and breastfeeding initiation, exclusivity, and duration, defined according to the WHO. Study designFeeding practices were prospectively collected from 425 puerperae living in an industrialized area of Northeast Italy starting on the second day post-partum, when they filled out the Life Experience Survey (LES, 1978). ResultsIn this sample, analysis revealed that at discharge 65/358 (18.16 %) puerperae presented with a negative LES score and 293/358 (81.84 %) with a positive LES score. Puerperae with negative LES scores were more likely to adopt formula at discharge, either to complement breast milk or to substitute breast milk altogether (16/65; 24.62 % vs 43/293; 14.68 %; RR = 1.64 and 95 % CI: 1.01–2.70), and they were also more likely to adopt exclusive formula feeding at the 3rd month of life (8/48; 16.66 % versus 18/242; 7.44 %; RR = 2.03 and 95%CI: 1.06–3.86). At the 6th month of life, there were significantly less puerperae with a negative LES score who were breastfeeding exclusively (1/48; 2.08 vs 44/249; 17.67 %; RR = 0.11 and 95 % CI: 0.01–0.84) and correspondingly there were significantly more puerperae with a negative LES score who were using formula feeding with weaning practices (20/48; 41.67 % vs 35/249; 14.06 %; RR =3.14 and 95 % CI: 1.82–5.04). ConclusionsIdentification of specific barriers to breastfeeding related to negative life events in pregnancy may help direct providers' anticipatory guidance to improve breastfeeding rates in high-risk populations.

Prenatal Negative Life Events and Childhood Allergies: The Japan Environment and Children’s Study (JECS)

Background: It is inconclusive whether prenatal negative life events are a risk for the development of allergic diseases in children or whether social capital modifies the association. The objective of this study was to examine whether women’s experiences of such events during pregnancy were associated with the development of allergic diseases in their offspring at 3 years old and whether social capital moderated this association. Methods: We used data from 81,337 mother-child pairs who participated in the Japan Environment and Children’s Study. This is a prospective birth cohort recruited between January 2011 and March 2014. We examined the associations between prenatal maternal negative life events (e.g., bereavement, financial, and marital problems) during pregnancy and allergic diseases (asthma, eczema, and food allergies) in children after adjustment for covariates using multivariate logistic regression. We also examined interactions between these life events and social capital, measured as two items, social cohesion and social support. Results: Prenatal negative life events were significantly associated with doctor-diagnosed asthma at 3 years old with a dose-response relationship (one life event vs. none: adjusted odds ratio 1.13, 95% confidence interval [CI]: 1.07–1.20; two life events vs. none: adjusted odds ratio 1.24, 95% CI: 1.13–1.36; three or more life events vs. none: adjusted odds ratio 1.26, 95% CI: 1.10–1.46; p for trend <0.01). Similar results were observed for eczema and food allergies. There were no interactions between life events and social capital. Conclusion: Prenatal negative life events may be a risk factor for allergies in children. There was no modification of the effect of these events by social capital.

Is the Unequal Treatment of Maternal and Paternal Liability Under the Congenital Disabilities (Civil Liability) Act 1976 Justified?

Under the Congenital Disabilities (Civil Liability) Act 1976 (CDCLA) a child born disabled as a result of an occurrence prior to its birth can bring a claim against the individual responsible for that occurrence. Significantly, mothers are exempt from liability (except in relation to negligent driving) but fathers are not. Since the CDCLA came into force in 1976, there have been significant shifts in the landscape in which it operates: a more gender-neutral model of parenting; transmission of an infection to a sexual partner can be a criminal offence; and growing evidence regarding the impact of prenatal events. In addition, there is a trend for presenting prenatal harm as a problem of individual behaviour. This article presents a timely consideration of the potential for parental liability under the CDCLA and asks whether restricting the exemption of parental liability to mothers but not fathers can be justified. It is argued that the reasons for unequal parental liability in relation to gestational harm are not sufficient to justify restricting the broad exemption to mothers but not fathers and a change in the law is required to bring the CDCLA up to date with advances in the criminal law, society, and medical science.

Relationship Between Placental Weight and Placental Pathology With MRI Findings in Mild to Moderate Hypoxic Ischemic Encephalopathy.

IntroductionThe placenta plays a critical role in fetal growth and development. Examination of the placenta may provide information on the timing and extent of adverse prenatal and perinatal events. Multiple studies demonstrate an association between placental changes and hypoxic-ischemic encephalopathy (HIE), but there are limited data on the association between placental pathology and MRI changes in HIE. This study assesses the relationship between placental pathology and MRI abnormalities in infants with HIE after receiving therapeutic hypothermia.MethodsA retrospective study of 138 full-term infants who underwent therapeutic hypothermia for HIE at a single delivery center. Using logistic regression models, placental pathology and MRI results were analyzed to determine if placental abnormalities are associated with more significant MRI abnormalities. Placentas matched by gestational age and birthweight from a sample of convenience were included for comparison.ResultsOf the 138 infants who underwent therapeutic hypothermia for HIE, 84 had placental pathology and MRIs available. Of these, 30 had normal, and 54 had abnormal MRIs. Placental changes are not observed more frequently in the HIE cohort with abnormal MRI. Increased placenta weight: birthweight ratio is independently associated with increased odds of moderate-severe HIE compared to a convenient sample.ConclusionIn a study sample of babies with HIE, placental pathology was not associated with subsequent abnormal MRI findings. Compared to matched controls, babies with HIE had an elevation in placental weight/birthweight.

Concentration-dependent change in hypothalamic neuronal transcriptome by the dietary fatty acids: oleic and palmitic acids

Prenatal high-fat diet exposure increases hypothalamic neurogenesis events in embryos and programs offspring to be obesity-prone. The molecular mechanism involved in these dietary effects of neurogenesis is unknown. This study investigated the effects of oleic and palmitic acids, which are abundant in a high-fat diet, on the hypothalamic neuronal transcriptome and how these changes impact neurogenesis events. The results show the differential effects of low and high concentrations of oleic or palmitic acid treatment on differential gene transcription. Gene ontology analysis uncovered significant gene enrichment in several cellular pathways involved in gene regulation and protein production, particularly with proliferation, migration, and cell survival. The enriched signaling pathways include Wnt, integrin, PDGF, and apoptosis, in addition to endocrine function signaling pathways CCKR and GnRH. Further examination of proliferation and migration shows low concentrations of oleic acid to stimulate proliferation and high concentrations of both oleic and palmitic acid to stimulate apoptosis. Oleic acid also reduces hypothalamic neuronal migration, with little effect from palmitic acid. The results show the two most abundant fatty acids in a high-fat diet impact hypothalamic neuronal proliferation and migration. The results also uncovered potential signaling pathways affected by oleic and palmitic acid and suggest one mechanism of prenatal high-fat diet-induced neurogenesis events may be through these two abundant fatty acids.

Behavioural Disorders in Dogs and Cats: A Review

Psychiatry is a specialized branch of medicine that studies behavioural disorders in humans and animals. In dogs and cats, behavioural problems are analogous to human psychiatric diseases, with the most common psychopathologies addressed being generalized anxiety disorder, obsessive compulsive disorder, separation anxiety and post-traumatic stress disorder. The level of bizarre behaviours displayed by the pets varies due to a variety of factors such as hereditary, prenatal dam modification and events during their neonatal and socializing phase. The behavioural changes recorded in dogs and cats include trembling, vocalizing, urinating, soiling, defecating, salivating, hiding, destructiveness, aggression, fear and obsessive behaviours. It is critical to remember that other medical complications, that can produce similar behavioural changes, must be addressed for the animal’s specific therapy. For the treatment of behavioural disorders in pets, different therapeutic agents (like Tricyclic antidepressants, selective serotonin reuptake inhibitors, benzodiazepines and a typical antidepressants) are used together with the behavioural modification strategies.