What is Known About Critical Congenital Heart Disease Diagnosis and Management Experiences from the Perspectives of Family and Healthcare Providers? A Systematic Integrative Literature Review.

The experience of diagnosis, decision-making and management in critical congenital heart disease is layered with complexity for both families and clinicians. We synthesise the current evidence regarding the family and healthcare provider experience of critical congenital heart disease diagnosis and management. A systematic integrative literature review was conducted by keyword search of online databases, MEDLINE (Ovid), PsycINFO, Cochrane, cumulative index to nursing and allied health literature (CINAHL Plus) and two journals, the Journal of Indigenous Research and Midwifery Journal from 1990. Inclusion and exclusion criteria were applied to search results with citation mining of final included papers to ensure completeness. Two researchers assessed study quality combining three tools. A third researcher reviewed papers where no consensus was reached. Data was coded and analysed in four phases resulting in final refined themes to summarise the findings. Of 1817 unique papers, 22 met the inclusion criteria. The overall quality of the included studies was generally good, apart from three of fair quality. There is little information on the experience of the healthcare provider. Thematic analysis identified three themes relating to the family experience: (1) The diagnosis and treatment of a critical congenital heart disease child significantly impacts parental health and wellbeing. (2) The way that healthcare and information is provided influences parental response and adaptation, and (3) parental responses and adaptation can be influenced by how and when support occurs. The experience of diagnosis and management of a critical congenital heart disease child is stressful and life-changing for families. Further research is needed into the experience of minority and socially deprived families, and of the healthcare provider, to inform potential interventions at the healthcare provider and institutional levels to improve family experience and support.

New Zealand women's experiences of managing gestational diabetes through diet: a qualitative study.

BACKGROUND: For women with gestational diabetes mellitus (GDM) poor dietary choices can have deleterious consequences for both themselves and their baby. Diet is a well-recognised primary strategy for the management of GDM. Women who develop GDM may receive dietary recommendations from a range of sources that may be inconsistent and are often faced with needing to make several dietary adaptations in a short period of time to achieve glycaemic control. The aim of this study was to explore how women diagnosed with GDM perceive dietary recommendations and how this information influences their dietary decisions during pregnancy and beyond. METHODS: Women diagnosed with GDM before 30 weeks' gestation were purposively recruited from two GDM clinics in Auckland, New Zealand. Data were generated using semi-structured interviews and thematic analysed to identify themes describing women's perceptions and experiences of dietary recommendations for the management of GDM. RESULTS: Eighteen women from a diverse range of sociodemographic backgrounds participated in the study. Three interconnected themes described women's perceptions of dietary recommendations and experiences in managing their GDM through diet: managing GDM is a balancing act; using the numbers as evidence, and the GDM timeframe. The primary objective of dietary advice was perceived to be to control blood glucose levels and this was central to each theme. Women faced a number of challenges in adhering to dietary recommendations. Their relationships with healthcare professionals played a significant role in their perception of advice and motivation to adhere to recommendations. Many women perceived the need to follow dietary recommendations to be temporary, with few planning to continue dietary adaptations long-term. CONCLUSIONS: The value of empathetic, individually tailored advice was highlighted in this study. A greater emphasis on establishing healthy dietary habits not just during pregnancy but for the long-term health of both mother and baby is needed.

Variation in outcome reporting in randomized controlled trials of interventions for prevention and treatment of fetal growth restriction.

OBJECTIVE: Although fetal growth restriction (FGR) is well known to be associated with adverse outcomes for the mother and offspring, effective interventions for the management of FGR are yet to be established. Trials reporting interventions for the prevention and treatment of FGR may be limited by heterogeneity in the underlying pathophysiology. The aim of this study was to conduct a systematic review of outcomes reported in randomized controlled trials (RCTs) assessing interventions for the prevention or treatment of FGR, in order to identify and categorize the variation in outcome reporting. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched from inception until August 2018 for RCTs investigating therapies for the prevention and treatment of FGR. Studies were assessed systematically and data on outcomes that were reported in the included studies were extracted and categorized. The methodological quality of the included studies was assessed using the Jadad score. RESULTS: The search identified 2609 citations, of which 153 were selected for full-text review and 72 studies (68 trials) were included in the final analysis. There were 44 trials relating to the prevention of FGR and 24 trials investigating interventions for the treatment of FGR. The mean Jadad score of all studies was 3.07, and only nine of them received a score of 5. We identified 238 outcomes across the included studies. The most commonly reported were birth weight (88.2%), gestational age at birth (72.1%) and small-for-gestational age (67.6%). Few studies reported on any measure of neonatal morbidity (27.9%), while adverse effects of the interventions were reported in only 17.6% of trials. CONCLUSIONS: There is significant variation in outcome reporting across RCTs of therapies for the prevention and treatment of FGR. The clinical applicability of future research would be enhanced by the development of a core outcome set for use in future trials. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

KEY POINTS: Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. ABSTRACT: Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 µg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter at birth and demonstrated accelerated postnatal growth velocity. IGF1 treatment did not alter perinatal mortality, partially abrogated the reduction in newborn size in females, but not males, and reduced accelerated growth in both sexes. IGF1-mediated upregulation of somatotrophic genes in males during the early postnatal period could suggest that treatment effects are associated with delayed axis maturation, whilst treatment outcomes in females may rely on the reprogramming of nutrient-dependent mechanisms of growth. These data suggest that the growth-restricted fetus is responsive to intra-amniotic intervention with IGF1, and that sex-specific somatotrophic effects persist in the early postnatal period.

Intravenous iron versus blood transfusion for postpartum anemia: a systematic review and meta-analysis.

BACKGROUND: Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses. METHODS: A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115). RESULTS: Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I2 = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I2 = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I2 = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I2 = 84%). The overall quality of the evidence was low-moderate. DISCUSSION: For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.

Size at birth and adult fat mass in twin sheep are determined in early gestation.

Size at birth is related to adult health outcomes. Twins are born smaller than singletons; this has been assumed to be secondary to limited nutrient supply in late gestation.We hypothesised that growth trajectory in twins, and the adult consequences of being conceived a twin, are determined in early gestation. Twin pregnancies in sheep were randomised to reduction of one twin on day 42 of a 148 day pregnancy by intra-thoracic KCl (Reductions, n =46) or a sham procedure (Twins, n =22). Singleton-bearing ewes also underwent a sham procedure (n =27). Ewes lambed spontaneously. Linear measures of size at birth were similar in Twins and Reductions, and significantly less than in Singletons. Birthweight was lower in Twins and Reductions than in Singletons, and less in Twins than in Reductions (means (SEM): Singletons, liveborn n =23: 6.59 (0.17) kg; Twins, liveborn n =36: 5.23 (0.16) kg; Reductions, liveborn n =27: 5.76 (0.15) kg; all comparisons P <0.05). Reductions grew most rapidly between birth and weaning (Singletons, 20.0 (0.4) g kg⁻¹ day⁻¹; Twins, 20.0 (0.3) g kg⁻¹ day⁻¹; Reductions, 21.0 (0.3) g kg⁻¹ day⁻¹, P <0.05) and were of similar weight as Singletons by weaning; Twins remained smaller by weaning but grew most rapidly thereafter (Singletons, 1.6 (0.1) g kg⁻¹ day⁻¹; Twins, 2.1 (0.1) g kg⁻¹ day⁻¹; Reductions, 1.6 (0.1) g kg⁻¹ day⁻¹, P <0.01), so that all groups had similar weight at 2 years. However, Twins and Reductions had greater percentage fat mass than Singletons at 2 years (Singletons, 11.1 (1.1)%; Twins, 14.8 (1.2)%; Reductions, 15.5 (1.1)%, P <0.05). Thus, in twins, fetal growth trajectory, linear size at birth and adult fat mass are largely determined in early gestation. If this is also true in humans, there are important implications for interventions aimed at optimising fetal growth and pregnancy outcome.

Body composition of New Zealand-born term babies differs by ethnicity, gestational age and sex.

BACKGROUND: Body composition provides important information on nutrition and future metabolic risk. New Zealand has a diverse ethnic population for which there are no newborn body composition data. AIM: To determine body composition in a cohort of New Zealand-born term babies. STUDY DESIGN: Observational study. SUBJECTS: Healthy, term infants between 37+0 and 41+6 weeks' gestation in two hospitals in Auckland, New Zealand. OUTCOME MEASURES: Body composition by air displacement plethysmography and anthropometry measured within 5 days of birth. Parent-identified ethnicity was prioritised according to Ministry of Health criteria. Data were analysed using t-test, ANOVA with Tukey post-hoc tests, quantile regression and are mean(SD). RESULTS: 440 babies (54% male) were included. Pacific Island/Maori (PI/M) were heavier at birth than Asian/Middle Eastern/Latin American/African (Asian+) babies (3403(506) vs 3181(485) g, p < .05). PI/M and European (E) babies were longer with larger head and waist circumferences than Asian+ babies (all p < .05). Absolute fat mass (FM) was not different amongst ethnicities (E, 365(156), PI/M, 347(183), Asian+, 357(188) g) but PI/M babies had significantly lower FM% than Asian+ (9.8(4.3) vs 10.9(4.5) %, p < .05). Fat-free mass (FFM) was greater in PI/M (3056(400) g) than E (2952(345) g (p < .05) and both PI/M and E had greater FFM than Asian+ (2824(363) g, p < .05). Early term babies had less FFM than term and late-term babies (2732(370), 3012(352), 3173(302)g, p < .001) respectively. CONCLUSIONS: Asian+ babies were the smallest babies with the least FFM yet had similar FM and the highest FM%, indicative of a thin, fat phenotype from birth.

Effects of twin pregnancy and periconceptional undernutrition on maternal metabolism, fetal growth and glucose-insulin axis function in ovine pregnancy.

Although twins have lower birthweights than singletons, they may not experience the increased disease risk in adulthood reportedly associated with low birthweight. In contrast, another periconceptional event, maternal undernutrition, does not reduce birthweight but does affect fetal and postnatal physiology in sheep. We therefore studied maternal and fetal metabolism, growth and glucose-insulin axis function in late gestation in twin and singleton sheep pregnancies, either undernourished from 60 days before until 30 days after conception or fed ad libitum. We found that twin-bearing ewes had decreased maternal food intake in late gestation and lower maternal and fetal plasma glucose and insulin levels. Twin fetuses had fewer everted placentomes, grew slower in late gestation, and had a greater insulin response to a glucose challenge, but lesser response to arginine. In contrast, periconceptional undernutrition led to increased maternal food intake and a more rapid fall in maternal glucose levels in response to fasting. Periconceptional undernutrition increased the number of everted placentomes, and abolished the difference in insulin responses to glucose between twins and singletons. Thus, the physiology of twin pregnancy is quite different from that of singleton pregnancy, and is probably determined by a combination of factors acting in both early and late gestation. The inconsistency of the relationships between low birthweight and postnatal disease risk of twins may lie in their very different fetal development. These data suggest that twin pregnancy may be another paradigm of developmental programming, and indicate that twins and singletons must be examined separately in any study of fetal or postnatal physiology.

Effects of twinning and periconceptional undernutrition on late-gestation hypothalamic-pituitary-adrenal axis function in ovine pregnancy.

The relationships between reduced size at birth, increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, and increased risk of disease in adulthood are well described in singletons but are much less clear in twins. This may be because the physiological processes underlying reduced size at birth are different in singletons and twins. Periconceptional undernutrition can cause altered activity of the fetal and postnatal HPA axis without altering size at birth. However, the independent effects of periconceptional undernutrition and twinning on activity of the maternal and fetal HPA axes are not well described. We therefore studied maternal and fetal HPA axis function during late gestation in twin and singleton sheep pregnancies, either undernourished around conception or fed ad libitum. We found that twinning led to suppressed baseline HPA axis function and decreased adrenal sensitivity to ACTH stimulation but increased fetal pituitary ACTH response both to direct stimulation by CRH (ACTH area under the curve response: 29.7 +/- 2.2 vs. 17.1 +/- 1.6 ng/min x ml, P < 0.01) and to decreased cortisol negative feedback. In contrast, periconceptional undernutrition resulted in a decreased pituitary response (ACTH area under the curve response: 19.4 +/- 1.6 vs. 26.1 +/- 2.2 ng/min x ml, P = 0.02) but no difference in adrenal response. Thus, the HPA axis function of twin sheep fetuses in late gestation is very different from that of control and undernourished singletons. If the HPA axis is an important mediator between fetal adaptations and adult disease, these data may help explain why the relationship between fetal growth and postnatal physiology and disease risk is inconsistent in twins.

Cardiovascular adaptations to pregnancy in sheep and effects of periconceptional undernutrition.

The objective of this study was to describe the effects of pregnancy on blood volume and uterine blood flow in sheep, and to test the hypothesis that the effects of periconceptional undernutrition on the late-gestation fetus are mediated by alterations in these parameters. Singleton-bearing ewes that had been undernourished preconception, postconception, both, or neither, underwent estimation of blood volume in mid and late gestation, and measurement of uterine blood flow in late gestation. Seven non-pregnant ewes were also studied. Pregnancy resulted in a 31% greater red cell volume in mid-gestation (21.0+/-1.3 vs 16.1+/-0.8ml/kg, p<0.05), but no significant change in plasma or blood volume. However maternal blood volume was correlated with uterine blood flow (r(2)=0.22, p=0.05) and fetal size (r(2)=0.20, p=0.02). Uterine blood flow was 13% greater in the undernourished groups than controls (1847+/-100 vs 1641+/-79ml/min, p<0.01). The large increase in maternal blood volume integral to a successful human pregnancy was not present in sheep. The increased uterine blood flow after periconceptional undernutrition suggests that nutritional signals before and in early pregnancy influence fetal nutrient supply in late gestation.

A method for assessment of blood volume parameters in pregnant sheep using fluorescein-labelled dextran.

The assessment of blood volume parameters in clinical and research settings has been limited by methods that involve radioactivity, complex assays or are unreliable. We aimed to design a method for measuring blood volume parameters that was non-radioactive, simple, cheap and reliable. We have used a commercially available fluorescein-labelled 250kDa dextran, a large inert molecule, and have measured dilution of this through the intravascular space of pregnant ewes. From this estimation of plasma volume and measured hematocrit, we have calculated blood volume and red cell volume. The blood volume results are 6% lower than those obtained using radiolabelled red cells, but there is no significant difference in red cell volume between methods. The coefficient of variation for repeated measurements of plasma volume measurements is 3.8%. This is a simple, reliable, cheap and non-radioactive method for estimating blood volume parameters in pregnant sheep, and may prove useful in other settings.

Studies on derivation of transcobalamin 3 from granulocytes. Enhancement by lithium and elimination by fluoride of in vitro increments in vitamin B12-binding capacity.

Unsaturated vitamin B(12)-binding capacity (UBBC) of human serum is not reproducibly measurable because it increases variably in vitro in relation to time, temperature, and, in the case of plasma, anticoagulant present before removal of cells. This variable increase proved to be due to variable release in vitro of transcobalamin III (TC III) from granulocytes. UBBC increase was greatest (up to fourfold normal levels) in the presence of lithium, which is the heparin salt used in many laboratories doing UBBC studies. In vitro increase was least when blood was collected in EDTA at 0 degrees C and immediately centrifuges at 0 degrees C (T(0) sample); results equivalent to T(0) were obtained at room temperature even after several hours delay when 47 mM fluoride was present; either cold temperature or 47 mM fluoride appeared to prevent TC III release from granulocytes. The measured levels of the three transcobalamins with T(0) methods of collection, which presumably reflect most closely the in vivo circulating levels, suggest that TC I and TC III in normal plasms are of the same order of magnitude and together normally comprise less than 10% of the UBBC. Approximately 90% of the UBBC content of sonicates of peripheral blood granulocytes and of bone marrow aspirates of normal individuals appears to be TC III, with the rest being TC I. Thus, normal myelocytes, like normal granulocytes, appear to contain mainly TC III. No TC II was present in any of the sonicates. The general practice in most laboratories has been to determine serum UBBC. Because in vitro increments of up to 119% were found to occur in serum, this practice should be replaced by collection using methods that prevent such increments. Blood collected in EDTA-47 mM NaF had a stable, reproducible UBBC with no significant in vitro increment with time.EDTA-NaF UBBC was 640+/-168 (range 380-921 pg B(12) bound/ml plasma) for 12 normal adult men and 809+/-232 (range 505-1208) for normal adult women. It presumably approximates circulating UBBC and is substantially below the serum UBBC mean of 935+/-262 (range 611-1506 for the same 12 men) and 1273+/-355 (range 811-2306 for the same 10 women).

Probabilistic description of infant head kinematics in abusive head trauma.

Abusive head trauma (AHT) is a potentially fatal result of child abuse, but the mechanisms by which injury occur are often unclear. To investigate the contention that shaking alone can elicit the injuries observed, effective computational models are necessary. The aim of this study was to develop a probabilistic model describing infant head kinematics in AHT. A deterministic model incorporating an infant's mechanical properties, subjected to different shaking motions, was developed in OpenSim. A Monte Carlo analysis was used to simulate the range of infant kinematics produced as a result of varying both the mechanical properties and the type of shaking motions. By excluding physically unrealistic shaking motions, worst-case shaking scenarios were simulated and compared to existing injury criteria for a newborn, a 4.5 month-old, and a 12 month-old infant. In none of the three cases were head kinematics observed to exceed previously-estimated subdural haemorrhage injury thresholds. The results of this study provide no biomechanical evidence to demonstrate how shaking by a human alone can cause the injuries observed in AHT, suggesting either that additional factors, such as impact, are required, or that the current estimates of injury thresholds are incorrect.

The late effects of fetal growth patterns.

The immediate prenatal and postnatal consequences of reduced fetal growth have long been known. The longer term associations between reduced birth weight and adult disease risk are also now well established. Reduced fetal growth is usually detected late in gestation, and the assumption has been that this is the time when factors regulating fetal growth have their greatest effect. However, recent evidence suggests that both the growth trajectory of the fetus and its adaptive responses to the prenatal and postnatal environment may be determined in the period around the time of conception.

Variable interpretation of ultrasonograms may contribute to variation in the reported incidence of white matter damage between newborn intensive care units in New Zealand.

BACKGROUND: The incidence of cerebral white matter damage reported to the Australian and New Zealand Neonatal Network (ANZNN) varies between neonatal intensive care units (NICUs). HYPOTHESIS: Differences in the capture, storage, and interpretation of the cerebral ultrasound scans could account for some of this variation. METHODS: A total of 255 infants of birth weight <1500 g and gestation <32 weeks born between 1997 and 2002 and drawn equally from each of the six NICUs in New Zealand were randomly selected from the ANZNN database. Half had early cerebral ultrasound scans previously reported to ANZNN as normal, and half had scans reported as abnormal. The original scans were copied, anonymised, and independently read by a panel of three experts using a standardised method of reviewing and reporting. RESULTS: There was considerable variation between NICUs in methods of image capture, quality, and completeness of the scans. There was only moderate agreement between the reviewers' reports and the original reports to the ANZNN (kappa 0.45-0.51) and between the reviewers (kappa 0.54-0.64). The reviewers reported three to six times more white matter damage than had been reported to the ANZNN. CONCLUSION: Some of the reported variation in white matter damage between NICUs may be due to differences in capture and interpretation of cerebral ultrasound scans.

Characterization of certain inflammatory variables in the peripheral blood of clinically healthy dogs.

Many laboratory techniques have been developed to study and quantify the inflammatory response, including the release of acid hydrolase enzymes, leukotriene B(4) (LTB(4)) production, reactive oxygen species (ROS) production and complement conversion studies. Although extensively studied in human health and disease, the relevance of such tests in the dog is largely unknown. After isolation of the peripheral blood mononuclear cell (PBMC) and polymorphonuclear cell (PMN) fractions from the peripheral blood of 38 clinically healthy dogs, values for ROS production were similar for both cell fractions when measured by luminol-enhanced chemiluminescence (17,853+/-9,695 U/10(6) cells versus 19,138+/-14,569 U/10(6) cells for the PBMC (n=38) and PMN (n=18) fractions, respectively). However, the mean time taken to reach maximum chemiluminescence was noticeably shorter in the PBMC fraction (5.1+/-3.3 versus 10.7+/-2.5 min for PBMCs (n=36) and PMNs (n=18), respectively). Intracellular concentrations of beta-glucuronidase, beta-galactosidase and N-acetyl-beta-glucosaminidase were assayed by spectrofluorometry. Mean values for all three enzymes were higher in PBMCs (n=31-35) than in PMNs (n=10-14). Both cell fractions released 20% of the intracellular enzyme concentration when stimulated with opsonized zymosan. Following incubation with A23187 (1 microM), mean LTB(4) production was higher in PBMCs (4.45+/-2.92 ng/10(6) cells; n=27) than in PMNs (0.96+/-2.22 ng/10(6) cells; n=13) using a validated high performance liquid chromatography (HPLC) assay. Immunoprecipitation studies revealed that the mean percentage conversion of C3 to C3b following stimulation with opsonized zymosan was 57.3+/-13.4% (n=36). The results provide normal values for clinically healthy dogs that may subsequently be used in future studies investigating dogs with various inflammatory disorders.

Increased leukotriene B(4) production, complement C3 conversion and acid hydrolase enzyme concentrations in different leucocyte sub-populations of dogs with atopic dermatitis.

Various markers of the inflammatory response were measured in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) from 31 dogs with atopic dermatitis (AD). The variables assayed included chemiluminescence, acid hydrolase enzyme concentrations, leukotriene B(4) (LTB(4)) production and complement C3 conversion. The results were compared to those derived from a population of clinically healthy dogs. Dogs with AD exhibited a significant increase in median LTB(4) production in PMNs compared to controls (0.94 versus 0.00 ng/10(6) cells; P<0.01). Significant increases in the median concentrations of intracellular beta-galactosidase (PBMC fraction - 0.42 versus 0.25 mU/10(6) cells; P<0.05) (PMN fraction - 0.47 versus 0.12 mU/10(6) cells; P<0.01) and beta-glucuronidase (PBMC fraction - 0.52 versus 0.27 mU/10(6) cells; P<0.05) were also evident in the AD group. Although median maximum chemiluminescence values for both leucocyte sub-populations were higher in controls, the differences recorded were not significant (P>0.05). However, the median time taken to reach maximum chemiluminescence was significantly shorter in the PMN fraction of dogs with AD (7.00 versus 10.00 min; P<0.01). Atopic dogs had a significant increase in the median percentage conversion of complement C3 to C3b (66.0 versus 57.3%; P<0.01). The results of this study indicate a priming of the inflammatory response in dogs with AD. The role of LTB(4) in the pathogenesis of canine AD and the potential efficacy of leukotriene antagonists in the treatment of this disorder warrant further investigation.

Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues.

We have previously reported that chronic intra-amniotic supplementation of the late gestation growth-restricted (IUGR) ovine fetus with IGF-I (20 microg/day) increased gut growth but reduced liver weight and circulating IGF-I concentrations. Here we report mRNA and protein levels of IGF-I, the type 1 IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1, -2 and -3 in fetal gut, liver, muscle and placenta from fetuses in that earlier study in an attempt to explain these contrasting results. mRNA and protein were extracted from tissues obtained at post mortem at 131 days of gestation (term, 145 days) from three groups of fetuses (control, IUGR+saline and IUGR+IGF-I, n=9 per group). Control fetuses were unembolised and untreated. In the IUGR groups, growth restriction was induced from 113 to 120 days by placental embolisation; from 120 to 130 days fetuses were treated with daily intra-amniotic injections of either saline or 20 microg IGF-I. mRNA was measured by RT-PCR or real-time RT-PCR, and protein by Western blot. In liver, muscle and placenta, IGF-I mRNA and protein levels were reduced by between 8 and 30% in IGF-I-treated fetuses compared with saline-treated fetuses and controls with no change in IGF-1R mRNA or protein levels. In contrast, in the gut, IGF-I mRNA and protein levels were not significantly altered with IGF-I treatment, but IGF-1R levels were increased, especially in the jejunum. Immunolocalisation demonstrated that IGF-1R expression was confined to the luminal aspect of the gut. mRNA levels of all three IGFBPs were reduced in the gut of IGF-I-treated fetuses, but hepatic expression was significantly increased. These data demonstrated tissue-specific regulation of IGF-I, IGF-1R and IGFBPs-1, -2 and -3 in response to intra-amniotic IGF-I supplementation, though the underlying mechanisms remain obscure.

Does variation in interpretation of ultrasonograms account for the variation in incidence of germinal matrix/intraventricular haemorrhage between newborn intensive care units in New Zealand?

BACKGROUND: The incidence of germinal matrix/intraventricular haemorrhage (GM/IVH) reported to the Australian and New Zealand Neonatal Network (ANZNN) varies between neonatal intensive care units (NICUs). HYPOTHESIS: Differences in the capture, storage, and interpretation of the cerebral ultrasound scans may account for some of this variation. METHODS: A total of 255 infants with birth weight <1500 g and gestation <32 weeks born between 1997 and 2002 were randomly selected from the ANZNN database, 44 from each of the six NICUs in New Zealand. Twenty two infants from each NICU had cerebral ultrasound scans previously reported to ANZNN as normal; another 22 had scans reported as abnormal. The original scans were copied using digital photography and anonymised and independently read by a panel of three experts using a standardised method of reviewing and reporting. RESULTS: There was considerable variation between NICUs in methods of image capture and quality and completeness of the scans. However, there was little variation in the reporting of scans between the reviewers and the reports to ANZNN (weighted kappa 0.75-0.91). Grade 1 GM/IVH was generally over-reported and grade 4 under-reported to the ANZNN. CONCLUSION: For all NICUs, a high level of agreement was found between the reviewers' reports and the reports to the ANZNN. Thus the variation between NICUs in the incidence of GM/IVH reported to the ANZNN is unlikely to be due to differences in capture, storage, and interpretation of the cerebral ultrasound scans. Further investigation is warranted into the reasons for the variation in incidence of GM/IVH between NICUs.