Innate and adaptive immune interactions at the fetal-maternal interface in healthy human pregnancy and preeclampsia

Maternal immune tolerance of the fetus is indispensible for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface – the decidua, the site of implantation and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, preeclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages) make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3+ regulatory T (Treg) cells are crucial for ensuring immune tolerance towards the semi-allogeneic fetus. Additionally, another population of CD4+HLA-G+ suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy

Review of simulation in paediatrics: The evolution of a revolution

Recent changes in medical education have highlighted the importance of experiential learning. Simulation is one model that has gained significant attention in the last decade and has been widely adopted as a training and assessment tool in medical education. Paediatric simulation has been utilized to teach various skills including resuscitation and trauma management, procedural skills and team training. It is also a valuable tool for health care educators, as it allows learners to achieve competence without putting patients at risk. Recent literature demonstrates increased retention of knowledge and skills after simulation based training. Further research is required to improve current simulation curriculums, develop validated assessment tools and to demonstrate improved clinical outcomes after simulation based training. We conducted an online search of original and review articles related to simulation and paediatric medical education and provide an overview of the role and utility of simulation in paediatrics

Feeding Modalities and the Onset of the Neonatal Abstinence Syndrome

AbstractBreast milk has been reported to ameliorate the severity and outcome of neonatal abstinence syndrome (NAS). The mechanism of this beneficial effect of breast milk on NAS remains unclear, as the negligible amount of methadone transmitted via breast milk is unlikely to have an impact on NAS. The aim of this study was to compare the impact of different feeding modalities on the onset of NAS.A retrospective medical record review was conducted on one hundred and ninety-four methadone maintained mother/infant dyads. Infants were categorized on the first 2 days of life as predominantly breastfed, fed expressed human breast milk or formula fed. The feeding categories were then analyzed using the onset of NAS as the outcome measure. After adjusting for confounders, there was no significant effect of the modality of feeding on the rates of NAS requiring treatment (p=0.11). Breastfeeding significantly delayed the onset of NAS (p=0.04)The act of breastfeeding in the first two days of life had no effect on whether an infant required treatment for NAS when compared to those fed EBM or formula. This only suggests that the advantages of breastfeeding on NAS cannot be substantiated in a small cohort and should not discourage breastfeeding

Spaced scenario demonstrations improve knowledge and confidence in pediatric acute illness management

Objectives: Nationally accredited simulation courses such as advance pediatric life support and pediatric advance life support are recommended for health care professionals (HCPs) at two yearly intervals as a minimum requirement, despite literature evidence suggesting rapid decline in knowledge shortly after course completion. The objective of this study was to evaluate an observation-based, educational intervention program aimed at improving previously acquired knowledge and confidence in managing critical illnesses. Methods: A prospective cohort longitudinal study was conducted over a 6-month period. Participants were assessed with a knowledge based questionnaire immediately prior to and after observing 12 fortnightly critical illness scenario demonstrations (CISDs). The outcome measure was performance on questionnaires. Regression analysis was used to adjust for potential confounders. Questionnaire practice effect was evaluated on 30 independent HCPs not exposed to the CISDs. Results: Fifty-four HCPs (40 doctors and 14 nurses) participated in the study. All participants had previously attended nationally accredited simulation courses with a mean time since last attendance of 1.8 ± 0.4 years. The median number of attendances at CISD was 6 (2–12). The mean questionnaire scores at baseline (17.2/25) were significantly lower than the mean post intervention questionnaire scores (20.3/25), p = 0.003. The HCPs self-rated confidence in managing CISD was 6.5 times higher at the end of the program in the intervention group (p = 0.002) than at baseline. There was no practice effect for questionnaires demonstrated in the independent sample. Conclusion: The educational intervention program significantly improved the knowledge and confidence of the participants in managing pediatric critical illnesses. The CISD program provides an inexpensive, practical, and time effective method of facilitating knowledge acquisition and retention. Despite the distinctively different approach, this study has shown the effectiveness of the participant being an observer to enhance pediatric resuscitation skills.6 page(s

Gestational diabetes independently increases birth length and augments the effects of maternal BMI on birth weight: a retrospective cohort study.

Objective To investigate the effect of the interaction between gestational diabetes (GDM) and maternal body mass index (BMI) on the individual neonatal growth parameters.Design Retrospective cohort studySetting A tertiary maternity service in Sydney, Australia, between 2005 and 2009.Population A cohort of 8859 women.Methods Generalized linear models.Main Outcome MeasuresNeonatal growth parameters, represented by z-scores for infant birth weight, birth length and head circumference in GDM and non-GDM groups. Results Only GDM alone had an independent and positive effect on birth length (p=0.02) but not on birth weight or head circumference. In addition, in pregnancies complicated with GDM, the association between maternal weight and birth weight was significantly stronger (p<0.001). In combination, GDM and maternal BMI significantly affected z-score differences between birth weight and birth length (p<0.001), in that underweight mothers had babies which were lighter relative to their length and inversely obese mothers had babies which were heavier relative to their length. Conclusions GDM independently influences birth length and increases the association between maternal BMI and birth weight. In accordance with the hypothesis of the fetal origins of health and disease, the pronounced effects of GDM on fetal growth patterns demonstrated in this study are likely to influence long-term health outcomes in children

Altered Fetal Head Growth in Preeclampsia: a Retrospective Cohort Proof of Concept Study

BackgroundPreeclampsia is associated with fetal growth restriction and low birth weights. Neurotrophins, which mediate neuronal growth and development, are also increased in the placenta and cord blood in preeclampsia. Hence, the aim of this study was to determine whether fetal head growth is altered in preeclampsia, adjusting for growth restriction and other confounding variables.MethodsThis research included a retrospective cohort study, looking at fetal head circumference at birth, plus a case control study examining fetal head circumference at mid-gestation.The head circumference at birth analysis consisted of 14,607 pregnancies (preeclampsia=382, control=14,225), delivered between 7/2006-6/2012 at Nepean Hospital, Australia. Head circumference at birth, in addition to other maternal and fetal variables, was sourced from the Nepean Obstetric Database.The head circumference at mid-gestation study consisted of 756 pregnancies (preeclampsia=248, control=508), delivered within the same data collection period at Nepean Hospital. Head circumference at mid-gestation was retrieved from an earlier ultrasound scan.Exclusion criteria included >1 fetus, illegal drug use, alcohol consumption, chronic or gestational hypertension.Generalised linear models (GLM) were used to analyse fetal head circumference in preeclampsia versus controls, adjusting for confounding variables.ResultsHead circumference increased at a greater rate in preeclampsia versus controls, adjusted for gestation, fetal gender, birth weight and length, smoking, maternal BMI and growth restriction. At mid-gestation, there was no difference in head circumference between preeclampsia and controls.ConclusionsFor the first time, this research has suggested increased fetal head growth in preeclampsia, adjusted for confounders. This finding may be explained by altered fetal exposure to neurotrophins in preeclampsia. The long term neurodevelopmental consequences of preeclampsia remains unclear

The Effect of Cigarette Smoking during Pregnancy on Endocrine Pancreatic Function and Fetal Growth: A Pilot Study

IntroductionCigarette smoking in pregnancy is a common cause of fetal growth restriction. We aimed to investigate endocrine pancreatic function of mother–infant dyads in relation to cigarette smoking, as a possible mechanism for the poor fetal growth.MethodsProspective study of smoking mothers (10 cigarettes or more per day, self-reported to the midwife) and non-smoker control mothers during their first pregnancy. Insulin, glucose, C-peptide, HbA1C, fructosamine, prolactin, serotonin, and cortisol were measured in maternal blood at 24–26 weeks and in umbilical cord blood at birth. Cotinine was also measured in cord blood.ResultsOf 37 smokers and 36 non-smokers recruited, cord blood was obtainable from 38 babies (19 in each group). In utero cigarette exposure was associated with lower birthweight (3,035 ± 490 versus 3,405 ± 598 g, p = 0.005), with linear modeling of the smoking cohort showing a 41 g reduction for every increase of one cigarette smoked per day (95% CI −71 to −11 g, p = 0.010). There were no differences between groups in indices of maternal or perinatal endocrine pancreatic dysfunction. Heavier smoking independently correlated with higher maternal fasting levels of glucose (p = 0.044) and C-peptide (p = 0.011). We did not observe any significant associations between the daily number of cigarettes and any of the cord blood parameters. We also looked for differences between cohorts based on infant gender. Serotonin levels were higher in smoking mothers with male fetuses (p = 0.01 to p = 0.004).ConclusionEndocrine pancreatic dysfunction does not appear to be a major contributing factor to nicotine-associated fetal growth restriction. The higher serotonin levels in smoking mothers carrying male infants is of uncertain significance but could be a manifestation of gender differences in susceptibility to the long-term effects of cigarette smoking

Gestational diabetes independently increases birth length and augments the effects of maternal BMI on birth weight : a retrospective cohort study

Objective: To investigate the effect of the interaction between gestational diabetes mellitus (GDM) and maternal body mass index (BMI) on the individual neonatal growth parameters. Design: Retrospective cohort study. Setting: A tertiary maternity service in Sydney, Australia, between 2005 and 2009. Population: A cohort of 8859 women. Methods: Generalized linear models. Main outcome measures: Neonatal growth parameters, represented by z-scores for infant birth weight (BW), birth length (BL), and head circumference (HC) in GDM and non-GDM groups. Results: Only GDM alone had an independent and positive effect on BL (p = 0.02) but not on BW or HC. In addition, in pregnancies complicated with GDM, the association between maternal weight and BW was significantly stronger (p < 0.001). In combination, GDM and maternal BMI significantly affected z-score differences between BW and BL (p < 0.001), in that underweight mothers had babies that were lighter relative to their length and inversely obese mothers had babies that were heavier relative to their length. Conclusion: GDM independently influences BL and increases the association between maternal BMI and BW. In accordance with the hypothesis of the fetal origins of health and disease, the pronounced effects of GDM on fetal growth patterns demonstrated in this study are likely to influence long-term health outcomes in children.6 page(s