Maternal Response Research Articles

Supplemental Material for Maternal Contingent Responsiveness Moderates Temperamental Risk to Support Adaptive Infant Brain and Socioemotional Development Across the First Year of Life

Supplemental Material for Maternal Contingent Responsiveness Moderates Temperamental Risk to Support Adaptive Infant Brain and Socioemotional Development Across the First Year of Life

Diet-Induced Obesity in Mice Affects the Maternal Gut Microbiota and Immune Response in Mid-Pregnancy.

Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)). C57BL/6 mice were fed a high-fat diet or low-fat diet from 8 weeks before mating and during pregnancy. At GD12, we analyzed the gut microbiota composition in the feces and immune responses in the intestine (Peyer's patches, mesenteric lymph nodes) and the peripheral circulation (spleen and peripheral blood). Maternal obesity reduced beneficial bacteria (e.g., Bifidobacterium and Akkermansia) and changed intestinal and peripheral immune responses (e.g., dendritic cells, Th1/Th2/Th17/Treg axis, monocytes). Numerous correlations were found between obesity-associated bacterial genera and intestinal/peripheral immune anomalies. This study shows that maternal obesity impacts the abundance of specific bacterial gut genera as compared to lean mice and deranges maternal intestinal immune responses that subsequently change peripheral maternal immune responses in mid-pregnancy. Our findings underscore the opportunities for early intervention strategies targeting maternal obesity, ideally starting in the periconceptional period, to mitigate these obesity-related pregnancy effects.

Pregnancy Establishment and Diagnosis in Livestock.

This comprehensive review explores the complex processes of reproduction, pregnancy establishment, and pregnancy diagnostic methods in cattle, sheep, goats, swine, horses, and camelids. It provides an overview of the history of pregnancy detection and an in-depth exploration of the physiology of pregnancy in livestock. The detection of conceptus tissue and fluids, conceptus-produced hormones, and maternal responses to conceptus signals, crucial for pregnancy diagnosis, are also discussed in detail, as are emerging methods for pregnancy diagnosis in livestock species. Overall, this review emphasizes the direct impact of pregnancy diagnosis and efficient pregnancy management for profitability of livestock enterprises.

Terapi Kneading Massage dan Teknik Breathing Exercise Diapragmatic (BED) dalam Mengurangi Intensitas Nyeri dan Kecemasan Persalinan

Childbirth is a physiological event experienced by some women. The birth process has uncomfortable effects including pain and anxiety. The aim of this research is Kneading Massage Therapy and Diaphragmatic Breathing Exercise (BED) Techniques to Reduce the Intensity of Labor Pain and Anxiety. The method used is a case study with pre-test post-test treatment. The population, namely all mothers giving birth at the Mandiraja 2 Community Health Center in December 2023, was 25 respondents. The sample used was 5 maternal respondents who experienced pain and anxiety using the Accidental Sampling technique. The results obtained after administering Kneading Massage Therapy and Diaphragmatic Breathing Exercise Technique (BED) showed a decrease in the pain scale from before therapy of 5.6 (moderate pain) to around 2.6 (mild pain) after therapy and a decrease in anxiety scale from 40 .4 (moderate anxiety) before therapy to 29.9 (low anxiety) after therapy. So it can be concluded that Kneading Massage Therapy and the Diaphragmatic Breathing Exercise (BED) technique can reduce the intensity of pain and anxiety childbirth.

3DMOUSEneST: a volumetric label-free imaging method evaluating embryo-uterine interaction and decidualization efficacy.

Effective interplay between the uterus and the embryo is essential for pregnancy establishment; however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here, we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extra-embryonic tissues) growth. We demonstrate that decidual nest volume is a measurable indicator of decidualization efficacy and correlates with the probability of early pregnancy progression based on a logistic regression analysis using Smad1/5 and Smad2/3 conditional knockout mice with known implantation defects. 3DMOUSEneST has great potential to become a principal method for studying decidual fibrillar collagen and characterizing mouse models associated with early embryonic lethality and fertility issues.

High fat diet consumption and social instability stress impair stress adaptation and maternal care in C57Bl/6 dams

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal and offspring health and behaviour, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas use of psychosocial stress interventions in female mice are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and intermittent social stress on maternal health and behaviour, we developed a novel maternal stress model using adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing output revealed anxiety-like behaviours remained similar across all groups prior to pregnancy. However, integrated anxiety z-scores revealed a mixed anxious profile amongst HF+/SIS+ females prior to pregnancy. HF+/SIS+ females also did not show reduced plasma ACTH and corticosterone levels that were observed in our other HF+ and HF- stress groups after SIS exposure. Further, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with previous exposure to SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.

Diagnostic tests for the prediction of histological chorioamnionitis and funisitis in pregnant women with preterm premature rupture of membranes: A systematic review.

Infection of the amniotic cavity is an important driver and/or consequence of preterm prelabour rupture of membranes (PPROM). Prediction of infection is challenging, limiting guidance for interventions during the antenatal period. Infection typically triggers a host inflammatory response, and non-invasive indirect markers of the maternal or fetal inflammatory response have been reported in the context of PPROM and intra-amniotic infection. Some of these markers have also been tested in amniotic fluid (AF) samples. This study compared markers of the inflammatory response in women with PPROM against the outcome standard of histological chorioamnionitis (HCA) or funisitis (FUS). Searches were conducted for studies reporting diagnostic test sensitivity and specificity for proven HCA or FUS in pregnant women with PPROM after 20 weeks' gestation. Weighted mean pooled sensitivity (Se), specificity (Sp), positive predictive value, negative predictive value, diagnostic odds ratio and 95% confidence intervals were calculated for each of the selected diagnostic tests. Except ultrasonographic detection of fetal thymic involution, almost all index tests analysed showed relatively low sensitivity. Maternal white cell count, interleukin-6 (IL-6) and AF IL-6 had credible specificity. Testing of AF markers, while more consistent than serum markers, showed no clear diagnostic accuracy improvement. There is a clear lack of evidence for the reliability of any individual diagnostic test to assist in the detection of HCA or FUS in women with PPROM. Combining several markers into a predictive model for improved diagnosis may be worth investigating.

Omega-3 reverses the metabolic and epigenetically regulated placental phenotype acquired from preconceptional and peri-conceptional exposure to air pollutants

Air pollution is detrimental to pregnancy adversely affecting maternal and child health. Our objective was to unravel epigenetic mechanisms mediating the effect of preconception, periconception, and gestational exposure to inhaled air pollutants (AP) upon the maternal and placental-fetal phenotype and explore the benefit of an omega-3 rich dietary intervention. To this end, we investigated intranasal instilled AP during 8 weeks of preconception, periconception, and gestation (G; D0 to 18) upon GD16-19 maternal mouse metabolic status, placental nutrient transporters, placental-fetal size, and placental morphology. Prepregnant mice were glucose intolerant and insulin resistant, while pregnant mice were glucose intolerant but displayed no major placental macro-nutrient transporter changes, except for an increase in CD36. Placentas revealed inflammatory cellular infiltration with cellular edema, necrosis, hemorrhage, and an increase in fetal body weight. Upon examination of placental genome-wide epigenetic processes of DNA sequence specific 5′-hydroxymethylation (5′-hmC) and 5′-methylation (5′-mC) upon RNA sequenced gene expression profiles, revealed changes in key metabolic, inflammatory, transcriptional, and cellular processing genes and pathways. An omega-3 rich anti-inflammatory diet from preconception (8 weeks) through periconception and gestation (GD0-18), ameliorated all these maternal and placental-fetal adverse effects. We conclude that preconceptional, periconceptional and gestational exposures to AP incite a maternal inflammatory response resulting in features of pre-existing maternal diabetes mellitus with injury to the placental-fetal unit. DNA 5′-mC more than 5′-hmC mediated AP induced maternal inflammatory and metabolic dysregulation which together alter placental gene expression and phenotype. A dietary intervention partially reversing these adversities provides possibilities for a novel nutrigenomic therapeutic strategy.

Maternal prenatal systemic inflammation indexes predicts premature neonatal respiratory distress syndrome

Neonatal respiratory distress syndrome (NRDS) is one of the leading causes of neonatal mortality in low-income countries. It is caused by a lack of surface-active substances in the lungs, and the maternal inflammatory response plays an important role in the formation of surface-active substances in the fetal lungs. We aimed to investigate the correlation between maternal prenatal systemic inflammatory indices and respiratory distress syndrome in preterm neonates. This is a retrospective case–control study that collected data from all patients who delivered between 28 and 36 weeks of gestation at Longhua District People's Hospital in Shenzhen City and whose infants were admitted to the neonatal unit, newborns with respiratory distress syndrome were in the experimental group (NRDS group), and newborns without NRDS were in the control group (non-NRDS group). To minimize the effect of confounders on the results, propensity score matching was performed on baseline characteristics. Totally, 524 patients were included (93 in the NRDS group and 431 in the non-NRDS group), and 71 matched pairs (142 patients). The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI) and neutrophil lymphocyte to platelet ratio (NLPR) were higher in the NRDS group than in the non-NRDS group (p < 0.05). The ROC curves of NLR, dNLR, SII, SIRI, AISI and NLPR for the diagnosis of NRDS were plotted, and it was found that the combined diagnostic efficacy of these six systemic inflammatory markers was better (AUC: 0.643, P = 0.003). Patients were divided into two groups based on the cut-off values determined from the ROC curves, and analysis using binary regression models revealed that SII ≥ 1199.94 (OR, 2.554; 95% CI 1.245–5.239, P = 0.011) and NLPR ≥ 0.0239 (OR, 2.175; 95% CI 1.061–4.459, P = 0.034) were independent risk factors predicting NRDS. Maternal prenatal SII ≥ 1199.94 and NLPR ≥ 0.0239 are independent risk factors for NRDS, and clinicians may be used to prevent neonatal respiratory distress in advance to reduce the incidence of NRDS.

Maternal choline supplementation modulates cognition and induces anti-inflammatory signaling in the prefrontal cortices of adolescent rats exposed to maternal immune activation

Maternal infection has long been described as a risk factor for neurodevelopmental disorders, especially autism spectrum disorders (ASD) and schizophrenia. Although many pathogens do not cross the placenta and infect the developing fetus directly, the maternal immune response to them is sufficient to alter fetal neurodevelopment, a phenomenon termed maternal immune activation (MIA). Low maternal choline is also a risk factor for neurodevelopmental disorders, and most pregnant people do not receive enough of it. In addition to its role in neurodevelopment, choline is capable of inducing anti-inflammatory signaling through a nicotinic pathway. Therefore, it was hypothesized that maternal choline supplementation would blunt the neurodevelopmental impact of MIA in offspring through long-term instigation of cholinergic anti-inflammatory signaling.To model MIA in rats, the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) was used to elicit a maternal antiviral innate immune response in dams both with and without choline supplementation. Offspring were reared to both early and late adolescent stages (postnatal days 28 and 50, respectively), where anxiety-related behaviors and cognition were examined. After behavioral testing, animals were euthanized, and their prefrontal cortices (PFCs) were collected for analysis. MIA offspring demonstrated sex-specific patterns of altered cognition and repetitive behaviors, which were modulated by maternal choline supplementation. Choline supplementation also bolstered anti-inflammatory signaling in the PFCs of MIA animals at both early and late adolescent stages. These findings suggest that maternal choline supplementation may be sufficient to blunt some of the behavioral and neurobiological impacts of inflammatory exposures in utero, indicating that it may be a cheap, safe, and effective intervention for neurodevelopmental disorders.

Maternal immune response during pregnancy and neurodevelopmental outcomes: A longitudinal approach

Background and objectivesThe neurodevelopment of the offspring is suggested to be influenced by the maternal immune system's responses throughout pregnancy, which in turn is also vulnerable to maternal psychosocial stress conditions. Therefore, our main goal was to investigate whether maternal peripheral immunological biomarkers (IB) during two stages of gestation are associated with distinct neurodevelopmental trajectories in the first two years of life. As a second goal, we also explored the association between maternal distal (childhood) and proximal (gestation) stressful experiences and the immunological markers assessed during pregnancy. MethodsMaternal childhood trauma, depressive and anxiety symptoms, and peripheral IB (IFNγ, IL-10, IL1β, IL6, IL8, TNFα, EGF, IL13, IL17, IL1Ra and IL4) were measured at baseline (8–16 weeks of pregnancy) and at 30 weeks of pregnancy in 160 women. The participants had the blood samples collected from two randomized clinical trials conducted by the same team and methods in the same community. A Principal Component Analysis (PCA) was implemented to create meaningful composite variables that describe the cytokines joint variation. Finally, linear mixed-effects modeling was used to investigate the influence of inflammatory biomarkers, maternal childhood trauma, anxiety, and depressive symptoms on Bayley's III scores trajectories. ResultsThe IB profile during the 3rd trimester of pregnancy predicted the offspring's neurodevelopmental trajectories in the first two years of life. The components derived from PCA were important predictors and captured different immune responses, reflecting both pro- and anti-inflammatory states. Maternal stressful experiences did not correlate with the immunological markers. Although not a reliable predictor alone, maternal psychosocial stress at the 1st trimester of pregnancy interacted with the mother's immune response while predicting the neurodevelopmental scores during the first two years of life. ConclusionsOur results underscore the importance of the maternal immune response during pregnancy in shaping the neurodevelopmental trajectory of the offspring. Additionally, we observed that the maternal distress at the early stages of pregnancy has an incremental effect on the neurodevelopmental outcome but depends upon the immune response.

Legal issues in the implementation of Maternal Death Surveillance and Response: a scoping review.

The Maternal Death Surveillance and Response (MDSR) system is designed to continuously identify and review all maternal deaths. It aims to help countries understand the scale and distribution of maternal deaths, identify their causes, and inform corrective measures to address the challenge. Despite the growing adoption of the MDSR by numerous low- or middle-income countries, its implementation faces various challenges, including legal ones. This scoping review was conducted to map legal issues and challenges that arise during the implementation of the MDSR. It adapted the Bain and Kongnyuy framework, categorizing legal issues into data, people, use of findings, and legal regulation. Literature was retrieved from seven databases, complemented by additional online searches. We included studies published in English between 2010 and November 2022 that report on legal issues arising during the implementation of MDSR. Out of 1174 studies screened, 31 were selected for review. The review highlighted the limited attention given to the legal dimension of the MDSR by the research community. It also documented the lack of adequate legal framework essential for the system's effective implementation. Inadequate safeguards for informational privacy and the lack of confidentiality reinforce a prevalent sense of being blamed, mainly among health workers. Consequently, widespread under-reporting and intentional misattribution of causes of maternal death, defensive referrals, and disengagement from the MDSR process were reported. We recommend that implementing countries regulate the gathering and use of MDSR data through appropriate laws and legally ensure that the MDSR data are only used for the intended purpose. Appropriate complaint-handling mechanisms are needed in health systems to prevent the misuse of the MDSR. Future studies on MDSR implementation would benefit from involving legal experts, considering the multifaceted legal dimensions of the MDSR.

Effects of a Prenatal Anxiety Randomized Controlled Trial Intervention on Infant Development in Pakistan

ObjectiveGiven that infant development is influenced by caregiver mental health, we tested whether an intervention to reduce antenatal anxiety could affect infant development. A secondary aim was to test depressive symptoms, maternal responsiveness, and maternal infant bonding as mediators of this relationship. MethodsBetween 2020 and 2022, pregnant women participated in a randomized controlled trial of the Happy Mother-Healthy Baby (HMHB) program based on cognitive behavioral therapy. We collected data on child development from 202 intervention and 198 control participants in a public hospital in Pakistan. Child development was measured using the Ages and Stages Questionnaires-Version 3 at six weeks postpartum. Using intent-to-treat analyses, we examined whether the intervention was associated with performance on the five ASQ-3 domains. Causal mediation analysis was used to assess depressive symptoms, bonding, and maternal-infant responsiveness as mediators. ResultsSocio-demographic characteristics were evenly distributed between study arms. Intervention arm infants showed a 2.1-point increase (95% CI: 0.12, 4.17) in communication scores compared to controls. Though not achieving statistical significance, intervention infants also showed a 2.0-point increase (95% CI: −0.06, 4.09) in gross motor development performance. Bonding, depression, and responsiveness were mediators between the intervention and infant communication (Bindirect=1.94 (95% CI: 0.86, 3.25) depression; Bindirect= 0.57 (95% CI: 0.09, 1.16) bonding; Bindirect= 0.53 (95% CI: 0.01, 1.21) responsiveness; and Bindirect= 1.94 (95% CI: 0.86, 3.25)). Bonding, responsiveness, and depression mediated 25%, 23%, and 87% of the total association, respectively. ConclusionsHMHB positively affected infant communication at six-week follow-up. Larger studies with longer follow-up are needed to confirm and extend these findings. Trial registrationClinicalTrials.gov NCT03880032; https://clinicaltrials.gov/ct2/show/NCT03880032

Relationship Between Level of Maternal Knowledge about Nutrition of Pregnant Women with the Incidence of Stunting in Children Under Five

ABSTRACT Stunting can be caused by several factors, including poor nutritional intake during pregnancy in toddlers. Some of them are readiness to become mothers where this is motivated by a very high rate of early marriage. Unpreparedness in facing motherhood can affect perceptions in parenting. This study aims to determine the relationship between the level of maternal knowledge about nutrition of pregnant women with the incidence of stunting in children under five in Sisir Village, Batu City with a cross-sectional analytical descriptive design involving 56 respondents consisting of maternal respondents and toddlers aged 1-5 years with purposive sampling techniques. Data were collected with maternal knowledge level questionnaires during pregnancy and z score graphs. Results: Data analysis using Spearman Rank test with α = 0.05. The results showed that the significance value (sig) or p value was 0.009. Because the value of sig (0.009) &gt; (0.05) with a correlation value of 0.347, the results of the data obtained from respondents mean h0 rejected h1 accepted. There is a relationship between the level of knowledge of parents and the incidence of stunting in toddlers. The results of the study concluded that there is a significant relationship between the level of knowledge of parents and the incidence of stunting in toddlers. Discussion: In Batu city comb sub-district. It is hoped that mothers can try to find knowledge and information related to nutrition and other factors that can cause stunting, and mothers can start paying attention to nutrition during pregnancy for preventive measures against the impact of stunting on the development of the next child at birth. Keywords: Maternal Knowledge, Gestation Period, Incidence Of Stunting

Trends and causes of maternal mortality in Indonesia: a systematic review

BackgroundThe maternal mortality ratio (MMR) in Indonesia is among the highest in Southeast Asia. We aim to describe trends in the MMR and causes of maternal deaths in Indonesia over the past decades, regionally and nationally.MethodsWe performed a systematic review and conducted a search using PubMed, Embase, Global Health, CINAHL, Cochrane, Portal Garuda, and Google Scholar from the inception of the database to April 2023. We included all studies on the incidence and/or the causes of maternal deaths in Indonesia. The MMR was defined as the number of maternal deaths per 100,000 live births. Maternal death causes were assessed and reclassified according to the WHO International Classification of Disease Maternal Mortality (ICD-MM).ResultsWe included 63 studies that reported the MMR (54 studies) and/or the causes of maternal deaths (44 studies) in Indonesia from 1970 to 2022, with a total of 254,796 maternal deaths. The national MMR declined from 450 to 249 (45%) between 1990 and 2020. Great differences in MMR exist across the country, with the lowest in Java-Bali and the highest (more than twice the national MMR) in Sulawesi and Eastern Indonesia. Between 1990 and 2022, the proportion of deaths due to hemorrhage and sepsis decreased, respectively from 48 to 18% and 15–5%, while the share of deaths due to hypertensive disorders and non-obstetric causes increased, respectively from 8 to 19% and 10–49%.ConclusionDespite the steady decline of maternal deaths in Indonesia, it remains one of the highest in Southeast Asia, with enormous disparities within the country. Hypertensive disorders and non-communicable diseases make up a growing share of maternal deaths, making maternal death reduction strategies increasingly challenging. National Maternal Death Surveillance and Response needs to be prioritized to eliminate preventable maternal deaths in Indonesia.Registration of systematic reviewsPROSPERO, CRD42022320213.

Mid-pregnancy circulating cytokine levels, placental efficiency and their relationship with preterm birth.

To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD). Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20+0 to 25+6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve. Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1β, TNFβ, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%. IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response.

"My baby is ready to learn"-The role of infant pointing in redirecting maternal responses to be more informative.

Caregivers may perceive pointing as an indication of infants' readiness to learn, thereby increasing their tendency to label objects regardless of the infant's gesture type and context. This was investigated in this study by tracking 35 infants at home at the ages of 11 and 13months and observing their interactions with their mothers during object manipulation. We focused on four types of communicative gestures: typical giving gestures, gestures contingent on exploration, gestures contingent on play, and pointing. We analyzed maternal response tendencies, including affirmation, naming, discourse, and pretense. The results revealed that when infants reached the age of 13months, they tripled their pointing production; in turn, the maternal response changed entirely, with naming becoming the preferred response to all types of gestures. Furthermore, when infants were 13months old and offered an object contingent on play acts, mothers increased their pretense acts sevenfold. Based on the most informative responses to infants among those examined, we argue that an increase in the number of pointing gestures may gradually be associated with the establishment of the maternal perception that an infant is ready to learn and a subsequent increase in naming and pretense production by the mother.

Differential effects of purified low molecular weight Poly(I:C) in the maternal immune activation model depend on the laboratory environment

The Poly (I:C) (polyriboinosinic-polyribocytidilic acid) paradigm of maternal immune activation (MIA) is most widely used as experimental model for the evaluation of the effects of gestational infection on the brain and behavior of the progeny. We have previously reported significant batch-to-batch variability in the effects of Poly (I:C), purchased from the same supplier (Sigma–Aldrich), on maternal and fetal immune responses and found these differences to be dependent on the relative amount of synthetic double-stranded RNA fragments in the high versus low molecular weight (LMW) range contained in the compound. We here resorted to Poly (I:C) purified for LMW dsRNA fragments to establish a MIA paradigm with increased reproducibility and enhanced standardization in an effort to refine the MIA paradigm and characterize its effect on offspring behavior. We found that the parallel application of LMW Poly (I:C) in two different MIA-experienced laboratories (Vienna and Zurich) yielded differential outcomes in terms of maternal immune responses and behavioral phenotypes in the offspring generation. In both experimental sites, administration of LMW Poly (I:C) induced a significant sickness response and cytokine induction in the pregnant dam and fetal brains, while the expected deficit in sociability as one main behavioral outcome parameter in the MIA progeny, was only present in the Zurich, but not the Vienna cohort. We conclude that although using Poly (I:C) purified for a defined molecular weight range reduces batch-to-batch variability, it does not make the MIA model more reliable and robust. The differential response in behavioral phenotypes of the MIA offspring between the two laboratories illustrates the highly complex interaction between prenatal and postnatal milieus - including the laboratory environment - that determine offspring phenotypic outcomes after MIA. Consequently, establishing a new MIA protocol or implementing the MIA model firstly under new or changed environmental conditions must include the assessment of offspring behavior to ensure solid and reproducible experimental outcomes.

Co-regulation, relationship quality, and infant distress vocalizations observed during mother-infant interactions: Influences of maternal depression and different contexts.

Mother-infant interactions are co-regulated and provide the foundation for mother-infant relationship quality. The implications of maternal depression and contextual demands (i.e., reinstating the interaction following maternal unavailability and vocalized infant distress) on observationally coded co-regulation in mother-infant dyads (n=40) at 4-months was investigated. Associations among co-regulation patterns and mother-infant relationship quality was also examined. Dyads participated in Still-Face (SF) and Separation (SP) procedures, with periods of maternal emotional and physical unavailability. Co-regulation was captured using the Revised Relational Coding System. Relationship quality was examined using the Emotional Availability Scales. Dyads in the depressed group had significantly more unilateral exchanges than the non-depressed group following the SF and SP perturbations. The depressed group also had significantly more distress vocalizations during the SP perturbation than the non-depressed group. Co-regulation in the depressed group was less disrupted by the SF perturbation. Positive relationship quality dimensions (maternal sensitivity, structuring, and infant responsiveness) were associated with more symmetrical and less unilateral co-regulation regardless of the interaction period. There were also context-specific results pertaining to patterns of co-regulation and associated maternal hostility and infant responsiveness. Results highlight co-regulatory differences in depressed mothers and their infants and how these differences are exacerbated by contextual demands.

Norepinephrine versus phenylephrine affects prethrombotic response in patients undergoing cesarean section under spinal anesthesia: a randomized, double-blind, controlled study.

Venous thromboembolism (VTE) is one of the most common and serious complications of cesarean section in parturients. Norepinephrine (NE) has been shown to activate coagulation. The aim of this study was to compare the effect of a fixed-rate prophylactic norepinephrine infusion and a fixed-rate prophylactic phenylephrine（PHE） infusion under spinal anesthesia for caesarean section on the prethrombotic response. Sixty-six women undergoing cesarean section under spinal anesthesia were randomly assigned to the NE group or PHE group, starting simultaneously with the administration of the subarachnoid solution, a "study drug" solution containing either NE or PHE was pumped intravenously at a constant rate of 15 ml/h until the end of the operation. Plasma coagulation factor VIII activity (FVIII: C), Fibrinogen, and D-dimer levels were measured in blood samples obtained on admission to the operating theatre and at the end of the procedure. Compared with preoperative levels, there were no significant differences in postoperative fibrinogen and D-dimer levels in the NE group, except for a decrease in FVIII: C levels (P = 0.003). However, postoperative levels of FVIII: C (P = 0.009), fibrinogen (P = 0.035) and D-dimer (P = 0.025) were increased in the NE group compared with postoperative levels in the PHE group. NE does not affect the maternal prethrombotic response and can be safely used in cesarean sections. Compared with PHE infusion, NE infusion increased the level of coagulation molecules, suggesting that NE maybe more beneficial for women with high intraoperative bleeding requiring hemostasis.