Association between routine cell salvage use for lower segment caesarean section and post-operative iron infusion and anemia.

PURPOSE: Intraoperative cell salvage is central to Patient Blood Management including for lower segment caesarean section. Prior to April 2020, we initiated intraoperative cell salvage during caesarean section based on risk assessment for hemorrhage and patient factors. As the pandemic broadened, we mandated intraoperative cell salvage to prevent peri-partum anemia and potentially reduce blood product usage. We examined the association of routine intraoperative cell salvage on maternal outcomes. METHODS: We conducted a single-center non-overlapping before-after study of obstetric patients undergoing lower segment caesarean section in the 2 months prior to a change in practice ('usual care = selective intraoperative cell salvage', n = 203) and the 2 months following ('mandated intraoperative cell salvage', n = 228). Recovered blood was processed when a minimal autologous reinfusion volume of 100 ml was expected. Post-operative iron infusion and length of stay were modelled using logistic or linear regression, using inverse probability weighting to account for confounding. RESULTS: More emergency lower-segment caesarean sections occurred in the Usual Care group. Compared to the Usual Care group, post-operative hemoglobin was higher and anemia cases fewer in the Mandated intraoperative cell salvage group. Rates of post-partum iron infusion were significantly lower in the Mandated intraoperative cell salvage group (OR = 0.31, 95% CI = 0.12 to 0.80, P = 0.016). No difference was found for length of stay. CONCLUSION: Routine cell salvage provision during lower segment caesarean section was associated with a significant reduction in post-partum iron infusions, increased post-operative hemoglobin and reduced anemia prevalence.

Testing equivalence of two doses of intravenous iron to treat iron deficiency in pregnancy: A randomised controlled trial.

OBJECTIVE: To test the equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy. DESIGN: Parallel, two-arm equivalence randomised controlled trial with an equivalence margin of 5%. SETTING: Single centre in Australia. POPULATION: 278 pregnant women with iron deficiency. METHODS: Participants received either 500 mg (n = 152) or 1000 mg (n = 126) of intravenous ferric carboxymaltose in the second or third trimester. MAIN OUTCOME MEASURES: The proportion of participants requiring additional intravenous iron (500 mg) to achieve and maintain ferritin >30 microg/L (diagnostic threshold for iron deficiency) at 4 weeks post-infusion, and at 6 weeks, and 3-, 6- and 12-months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth and safety outcomes. RESULTS: The two doses were not equivalent within a 5% margin at any time point. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500-mg group compared with 5/67 (8%) in the 1000-mg group: difference in proportions, 0.283 (95% confidence interval [CI] 0.177-0.389). Overall, participants in the 500-mg arm received twice the repeat infusion rate (0.81 [SD = 0.824] versus 0.40 [SD = 0.69], rate ratio 2.05, 95% CI 1.45-2.91). CONCLUSIONS: Administration of 1000 mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500- mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained.

The contribution of red blood cell transfusion to neonatal morbidity and mortality.

Anaemia of prematurity will affect 90% of all very preterm infants, resulting in at least one red blood cell (RBC) transfusion. A significant proportion of preterm infants require multiple transfusions over the course of hospital admission. Growing evidence supports an association between transfusion exposure and adverse neonatal outcomes. In adults, transfusion-associated sepsis, transfusion-related acute lung injury and haemolytic reactions are the leading causes of transfusion-related morbidity and mortality; however, these are seldom recognised in newborns. The association between transfusion and adverse outcomes remains inconclusive. However, the evidence from preclinical studies demonstrates that RBC products can directly modulate immune cell function, a pathway termed transfusion-related immunomodulation (TRIM), which may provide a mechanism linking transfusion exposure with neonatal morbidities. Finally, we discuss the impact of TRIM on transfusion medicine, how we may address these issues and the emerging areas of research aimed at improving the safety of transfusions in this vulnerable population.

Treatment of iron deficiency and iron deficiency anemia with intravenous ferric carboxymaltose in pregnancy.

PURPOSE: To evaluate the efficacy and safety of intravenous ferric carboxymaltose administration to pregnant women with varying severities of iron deficiency anemia and iron deficiency without anemia. METHODS: In this prospective observational study of local obstetric practice, we analyzed data from 863 pregnant women with iron deficiency according to anemia status and severity. All women were treated with intravenous ferric carboxymaltose in pregnancy. Treatment efficacy was assessed by repeat hemoglobin measurements at 3 and 6 week post-infusion and ferritin levels, where available. Safety was assessed by analysis of adverse events, fetal heart rate monitoring, and newborn health outcome data. RESULTS: Ferric carboxymaltose significantly increased hemoglobin in women with mild, moderate, and severe iron deficiency anemia and women with iron deficiency alone at 3 and 6 week post-infusion (p < 0.01 for all). No hemoconcentration occurred in iron-deficient women without anemia. No serious adverse events were recorded, with minor temporary side effects (including local skin irritation, nausea, and headache) occurring in 96 (11%) women. No adverse fetal or neonatal outcomes were observed. CONCLUSIONS: Ferric carboxymaltose infusion corrects iron deficiency or various degrees of iron deficiency anemia efficaciously and safely pregnant women, and does not cause hemoconcentration.

The Important Role for Intravenous Iron in Perioperative Patient Blood Management in Major Abdominal Surgery: A Randomized Controlled Trial.

OBJECTIVE: To determine if preoperative intravenous (IV) iron improves outcomes in abdominal surgery patients. SUMMARY BACKGROUND DATA: Preoperative iron deficiency anemia (IDA) occurs frequently; however if left untreated, increases the risk of blood transfusion allogeneic blood transfusion (ABT). Limited evidence supports IDA treatment with preoperative IV iron. This randomized controlled trial aimed to determine whether perioperative IV iron reduced the need for ABT. METHODS: Between August 2011 and November 2014, 72 patients with IDA were assigned to receive either IV iron or usual care. The primary endpoint was incidence of ABT. Secondary endpoints were various hemoglobin (Hb) levels, change in Hb between time points, length of stay, iron status, morbidity, mortality, and quality of life 4 weeks postsurgery. RESULTS: A 60% reduction in ABT was observed in the IV iron group compared with the usual care group (31.25% vs 12.5%). Hb values, although similar at randomization, improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care (P = 0.01) by the day of admission. The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group (1.9 vs 0.9 g/dL, P = 0.01), and a shorter length of stay (7.0 vs 9.7 d, P = 0.026). There was no difference in discharge Hb levels, morbidity, mortality, or quality of life. CONCLUSIONS: Administration of perioperative IV iron reduces the need for blood transfusion, and is associated with a shorter hospital stay, enhanced restoration of iron stores, and a higher mean Hb concentration 4 weeks after surgery.

Novel insights, challenges and practical implications of DOHaD-omics research.

Research investigating the developmental origins of health and disease (DOHaD) has never had the technology to investigate physiology in such a data-rich capacity and at such a microlevel as it does now. A symposium at the inaugural meeting of the DOHaD Society of Australia and New Zealand outlined the advantages and challenges of using "-omics" technologies in DOHaD research. DOHaD studies with -omics approaches to generate large, rich datasets were discussed. We discuss implications for policy and practice and make recommendations to facilitate successful translation of results of future DOHaD-omics studies.

Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on cerebral oxygen kinetics.

BACKGROUND: The underlying neuro-protective mechanisms of antenatal magnesium sulfate (MgSO(4)) in infants born preterm remain poorly understood. Early neonatal brain injury may be preceded by low cerebral blood flow (CBF) and elevated cerebral fractional tissue oxygen extraction (cFTOE). This study investigated the effect of antenatal MgSO(4) on cerebral oxygen delivery, consumption, and cFTOE in preterm infants. METHODS: CBF and tissue oxygenation index were measured, and oxygen delivery, consumption, and cFTOE calculated within 24 h of birth and at 48 and 72 h of life in 36 infants ≤ 30 wk gestation exposed to MgSO(4) and 29 unexposed infants. RESULTS: Total internal carotid blood flow and cerebral oxygen delivery did not differ between the groups at the three study time-points. Cerebral oxygen consumption and cFTOE were lower in infants exposed to antenatal MgSO(4) (P = 0.012) compared to unexposed infants within 24 h of delivery. This difference was not evident by 48 h of age. Fewer infants in the MgSO(4) group developed P/IVH by 72 h of age (P = 0.03). CONCLUSION: Infants exposed to MgSO(4) had similar systemic and cerebral hemodynamics but lower cFTOE compared to nonexposed. These findings suggest reduced cerebral metabolism maybe a component of the neuro-protective actions of antenatal MgSO(4).

Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy.

Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect? Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999-2008; n=172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios. Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose-response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone. Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.

Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain.

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this, its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from five time points on four sessions across nine healthy researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days, we hypothesized that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (df: 1, 148.24; F: 10.41; p = 0.002). As the magnitude of the CAR is regulated by the "master" circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral "slave" CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity.

The impact of Aboriginal status, cigarette smoking and smoking cessation on perinatal outcomes in South Australia.

OBJECTIVE: To assess the impact of Aboriginal status, active cigarette smoking and smoking cessation during pregnancy on perinatal outcomes. DESIGN: Retrospective cohort study from 1 January 1999 to 31 December 2008. SETTING: All singleton births in South Australia. PARTICIPANTS: Population-based birth records of pregnancies to Aboriginal women (n = 4245) and non-Aboriginal women (n = 167 746). MAIN OUTCOME MEASURES: Adjusted odds ratios (aORs) and 95% CIs for adverse maternal and neonatal outcomes according to Aboriginal status and maternal smoking in pregnancy. RESULTS: Active cigarette smoking during pregnancy was associated with an increased risk of adverse perinatal outcomes, including premature labour (Aboriginal, 1-10 cigarettes per day: aOR, 1.69; 95% CI, 1.28-2.23; non-Aboriginal, 1-10 cigarettes per day: aOR, 1.46; 95% CI, 1.34-1.58), preterm birth (Aboriginal, 1-10 cigarettes per day: aOR, 1.40; 95% CI, 1.14-1.73; non-Aboriginal, 1-10 cigarettes per day: aOR, 1.48; 95% CI, 1.39-1.57), intrauterine growth restriction (Aboriginal, 1-10 cigarettes per day: aOR, 2.33; 95% CI, 1.77-3.08; non-Aboriginal, 1-10 cigarettes per day: aOR, 2.65; 95% CI, 2.48-2.83) and small for gestational age (Aboriginal, 1-10 cigarettes per day: aOR, 2.49; 95% CI, 2.06-3.00; non-Aboriginal, 1-10 cigarettes per day: aOR, 2.29; 95% CI, 2.20-2.40). For both Aboriginal and non-Aboriginal women who smoked 11 or more cigarettes per day the aOR for these outcomes increased. Smoking cessation in the first trimester reduced these risks to levels comparable with non-smokers. The risk of each adverse outcome was greater in Aboriginal than non-Aboriginal women for all smoking categories; however, interactions between Aboriginal status and smoking were not significant, indicating an equal contribution of smoking to poor outcomes in both populations. CONCLUSIONS: Smoking cessation or reduction during pregnancy would significantly improve outcomes in both Aboriginal and non-Aboriginal women. This should be made a clear priority to improve pregnancy outcomes for all women.

Interventions for managing asthma in pregnancy.

BACKGROUND: Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies. OBJECTIVES: To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion.We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy. MAIN RESULTS: We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias.Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training.The eight included trials were assessed under seven separate comparisons. Pharmacological interventionsPrimary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions. SECONDARY OUTCOMES: inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no other differences were observed, except for higher treatment adherence with theophylline. Four of the five trials did not report on adverse effects. Non-pharmacological interventionsPrimary outcomes: in one trial, the use of a FENO-based algorithm was shown to significantly reduce asthma exacerbations (RR 0.61; 95% CI 0.41 to 0.90; 220 women); and a trend towards fewer neonatal hospitalisations was observed (RR 0.46; 95% CI 0.21 to 1.02; 214 infants). No exacerbations occurred in one trial assessing pharmacist-led management; this approach did not reduce neonatal intensive care admissions (RR 1.50; 95% CI 0.27 to 8.32; 58 infants). One trial (64 women) assessing PMR did not report on exacerbations or neonatal intensive care admissions. SECONDARY OUTCOMES: the use of a FENO-based algorithm to adjust therapy led to some improvements in quality of life scores, as well as more frequent use of inhaled corticosteroids and long-acting ß-agonists, and less frequent use of short-acting ß-agonists (one trial, 220 women). The FENO-based algorithm was associated with fewer infants with recurrent episodes of bronchiolitis in their first year of life, and a trend towards fewer episodes of croup for infants. Pharmacist-led management improved asthma control scores at six months (one trial, 60 women); PMR improved lung function and quality of life measures (one trial, 64 women). No other differences between comparisons were observed. AUTHORS' CONCLUSIONS: Based on eight included trials, of moderate quality overall, no firm conclusions about optimal interventions for managing asthma in pregnancy can be made. Five trials assessing pharmacological interventions did not provide clear evidence of benefits or harms to support or refute current practice. While inhaled magnesium sulphate for acute asthma was shown to reduce exacerbations, this was in one small trial of unclear quality, and thus this finding should be interpreted with caution. Three trials assessing non-pharmacological interventions provided some support for the use of such strategies, however were not powered to detect differences in important maternal and infant outcomes. While a FENO-based algorithm reduced exacerbations, the effects on perinatal outcomes were less certain, and thus widespread implementation is not yet appropriate. Similarly, though positive effects on asthma control were shown with PMR and pharmacist-led management, the evidence to date is insufficient to draw definitive conclusions.In view of the limited evidence base, further randomised trials are required to determine the most effective and safe interventions for asthma in pregnancy. Future trials must be sufficiently powered, and well-designed, to allow differences in important outcomes for mothers and babies to be detected. The impact on health services requires evaluation. Any further trials assessing pharmacological interventions should assess novel agents or those used in current practice. Encouragingly, at least five trials have been identified as planned or underway.

Intravenous ferric carboxymaltose for anaemia in pregnancy.

BACKGROUND: Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with significant maternal, fetal and infant morbidity. Current options for treatment are limited: these include oral iron supplementation, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a new treatment option that may be better tolerated.The study was designed to assess the safety and efficacy of iron deficiency anaemia (IDA) correction with intravenous ferric carboxymaltose in pregnant women with mild, moderate and severe anaemia in the second and third trimester. METHODS: Prospective observational study; 65 anaemic pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40 weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient report of well-being in the postpartum period. Safety was assessed by analysis of adverse drug reactions and fetal heart rate monitoring during the infusion. RESULTS: Intravenous ferric carboxymaltose infusion significantly increased Hb values (p < 0.01) above baseline levels in all women. Increased Hb values were observed at 3 and 6 weeks post infusion and up to 8 weeks post-infusion. Ferritin values increased significantly after the infusion. Only 4 women had repeat ferritin values post-partum which remained above baseline levels. Fetal heart rate monitoring did not indicate a drug related negative impact on the fetus. Of the 29 (44.6%) women interviewed, 19 (65.5%) women reported an improvement in their well-being and 9 (31%) felt no different after the infusion. None of the women felt worse. No serious adverse effects were found and minor side effects occurred in 13 (20%) patients. CONCLUSIONS: Our prospective data is consistent with existing observational reports of the safe and effective use of ferric carboxymaltose in the treatment of iron deficiency anaemia in pregnancy.

Differential effects of docosahexaenoic acid on preterm and term placental pro-oxidant/antioxidant balance.

Docosahexaenoic acid (DHA) supplementation in pregnancy may confer some clinical benefits; however, this compound can exert pro-oxidant effects. In this study, we investigated the effects of DHA on pro-oxidant/antioxidant balance in term and preterm placental explants, assessing oxidative stress marker concentrations, antioxidant capacity and pro-inflammatory cytokine production. Term (n=8) and preterm (n=9) placental explants were exposed to lipopolysaccharide (LPS, 1 ng/ml), DHA (1, 10 and 100 µM), and DHA and LPS simultaneously or pre-treated with DHA for 24  h prior to LPS treatment. The production of malondialdehyde (MDA, lipid peroxidation), 8-hydroxy-2-deoxy guanosine (8-OHdG, oxidative DNA damage) and pro-inflammatory cytokines (tumour necrosis factor α (TNFα), interleukin 6 and interferon-γ) and total antioxidant capacity were measured. DHA at a concentration of 100 µM induced oxidative stress in term placentas, while at all the three concentrations, it induced oxidative stress in preterm placentas. DHA and LPS resulted in reduced MDA levels in term (P<0.005) and preterm (P=0.004) placentas and reduced 8-OHdG levels in preterm placentas (P=0.035). DHA pre-treatment, but not co-treatment with LPS, reduced 8-OHdG levels (P<0.001) in term placentas. DHA increased antioxidant capacity only in term placentas (P<0.001), with lower antioxidant capacity being observed overall in preterm placentas compared with term placentas (P≤0.001). In term placentas, but not in preterm ones, DHA co-treatment and pre-treatment reduced LPS-induced TNFα levels. The ability of DHA to alter placental pro-oxidant/antioxidant balance is dependent on the DHA concentration used and the gestational age of the placental tissue. DHA has a greater capacity to increase oxidative stress in preterm placentas, but it offers greater protection against inflammation-induced oxidative stress in term placentas. This appears to be a result of DHA altering placental antioxidant capacity. These data have implications for the timing and concentration of DHA supplementation in pregnancy.

The impact of iodine supplementation and bread fortification on urinary iodine concentrations in a mildly iodine deficient population of pregnant women in South Australia.

Mild iodine deficiency during pregnancy can have significant effects on fetal development and future cognitive function. The purpose of this study was to characterise the iodine status of South Australian women during pregnancy and relate it to the use of iodine-containing multivitamins. The impact of fortification of bread with iodized salt was also assessed. Women (n = 196) were recruited prospectively at the beginning of pregnancy and urine collected at 12, 18, 30, 36 weeks gestation and 6 months postpartum. The use of a multivitamin supplement was recorded at each visit. Spot urinary iodine concentrations (UIC) were assessed. Median UICs were within the mildly deficient range in women not taking supplements (<90 µg/L). Among the women taking iodine-containing multivitamins UICs were within WHO recommendations (150-249 µg/L) for sufficiency and showed an increasing trend through gestation. The fortification of bread with iodized salt increased the median UIC from 68 µg/L to 84 µg/L (p = .011) which was still in the deficient range. Pregnant women in this region of Australia were unlikely to reach recommended iodine levels without an iodine supplement, even after the mandatory iodine supplementation of bread was instituted in October 2009.

Fetal glucocorticoid-regulated pathways are not affected by inhaled corticosteroid use for asthma during pregnancy.

RATIONALE: Inhaled corticosteroids (ICS) are currently advised for the control of asthma during pregnancy, despite the lack of evidence regarding potential systemic effects on maternal, placental, and fetal systems. OBJECTIVES: To determine maternal plasma concentrations of cortisol, estriol, osteocalcin, and corticotropin-releasing hormone in pregnant women with asthma (n = 156) and without asthma (n = 51). METHODS: During each trimester of pregnancy, the use and dose of ICS was recorded and blood samples were collected. Ultrasound was performed at 18 and 30 weeks' gestation, and birth weight and fetal sex were recorded at delivery. MEASUREMENTS AND MAIN RESULTS: Maternal hormone concentrations were not affected by the presence of asthma; however, they were inhibited by ICS use in a dose-dependent manner. This was dependent on fetal sex: in pregnancies with a female, ICS was inversely associated with maternal cortisol in first trimester and inversely associated with maternal osteocalcin in second and third trimester. When pregnant with a male, no effect of ICS dose was observed on maternal cortisol, estriol, or osteocalcin levels, whereas corticotropin-releasing hormone levels were increased with ICS use only in the first trimester. CONCLUSIONS: Maternal glucocorticoid-regulated systems appeared susceptible to ICS only when pregnant with a female. Fetal adrenal function appeared unaffected by ICS in pregnancies of both males and females. This provides clinically important information suggesting that ICS do not exert effects on glucocorticoid-regulated pathways in the fetus, and therefore are unlikely to contribute to adverse effects on fetal growth and development.

Effect of washed versus unwashed red blood cells on transfusion-related immune responses in preterm newborns.

Objectives: Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion-related pro-inflammatory cytokine production. This may be because of alterations in recipient immune responses. Methods: This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro-inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks' gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. Results: By the third transfusion, infants receiving unwashed blood had an increase in IL-17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL-17A (P = 0.013), TNF (P = 0.048), IL-6 (P = 0.001), IL-8 (P = 0.037), IL-12 (P = 0.001) and IFN-γ (P = 0.001). The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12 (P = 0.001), IL-17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine). Conclusion: The pro-inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.

Placental cytokine expression covaries with maternal asthma severity and fetal sex.

In the presence of maternal asthma, we have previously reported reduced placental blood flow, decreased cortisol metabolism, and reductions in fetal growth in response to maternal asthma and asthma exacerbations. We have proposed that these changes in placental function and fetal development may be related to activation of proinflammatory pathways in the placenta in response to maternal asthma. In the present study, we examined the influence of maternal asthma severity, inhaled glucocorticoid treatment, maternal cigarette use, placental macrophage numbers, and fetal sex on placental cytokine mRNA expression from a prospective cohort study of pregnant women with and without asthma. Placental expression of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-5 mRNA were all increased significantly in placentae of female fetuses whose mothers had mild asthma, but no changes were observed in placentae of male fetuses. The proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were negatively correlated with female cord blood cortisol, but there were no such correlations in placentae from males. Multivariate analysis indicated the strongest predictor of both cytokine mRNA expression in the placenta and birth weight was fetal cortisol but only in females. Placental cytokine mRNA levels were not significantly altered by inhaled glucocorticoid use, placental macrophage numbers, cigarette use, moderate-severe asthma, or male sex. These data suggest that placental basal cytokine mRNA expression is sex specifically regulated in pregnancies complicated by asthma, and interestingly these changes are more prevalent in mild rather than severe asthma.