Acute otitis media (AOM) and respiratory tract infections are common in early childhood and are major contributors to antibiotic use. The oral probiotic Streptococcus salivarius K12 has demonstrated antimicrobial and immunomodulatory activity in vitro, and preventive effects in children with recurrent AOM. We aim to determine the efficacy of S. salivarius K12 in preventing AOM in the general infant population. We conducted a multicentre, double-blind, randomised, placebo-controlled trial in Wellington and Christchurch, New Zealand. Children were enrolled at 3–6 months of age, their households were randomised 1:1, and daily study product was given from age 6 to 24 months. The primary outcome was the rate of doctor-recorded AOM. Secondary outcomes included time to first AOM episode, respiratory infections, antibiotic prescribing and healthcare utilisation. Analyses were by intention to treat using mixed-effects negative binomial regression adjusted for region and, for the primary outcome, prior AOM, with random effects for general practice and family. A total of 428 children were randomised by household and 368 (86

BACKGROUND:In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results. METHODS:Women 18-49 years old were randomized 2:1 to receive 1 dose of RSVPreF3-Mat (n = 3557) or placebo (n = 1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months postbirth and safety until 12 months postbirth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months postpartum/birth) and safety in mothers and infants. RESULTS:Efficacy (with 95% credible interval) in infants until 6 months postbirth was 65.5% (37.5%-82.0%) against any MA-RSV-LRTD, 69.0% (33.0%-87.6%) against severe MA-RSV-LRTD, and 50.1% (-3.6% to 75.8%) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8% to 77.3%) in low- and middle-income and 75.9% (46.1%-91.5%) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months postbirth. CONCLUSIONS:Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months postbirth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk. Clinical Trials Registration. NCT04605159.

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b).

Lay Summary What Is the Context? Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. What is New? In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11-15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. What Is the Impact? RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers. Background In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. Methods In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 mu g), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. Results RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 mu g RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. Conclusions RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. In this phase 2 observer-blind, placebo-controlled, randomized clinical trial, RSVPreF3 maternal vaccination during late second or third trimester had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns.

Objective An imbalance in autonomic nervous system (ANS) activity may play a role in asthma, but it is unclear whether this is associated with specific pathophysiology. This study assessed ANS activity by measuring heart rate variability (HRV) in eosinophilic (EA) and non-eosinophilic asthma (NEA) and people without asthma. Methods HRV, combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), skin prick tests to measure atopy, and spirometry tests were conducted in teenagers and young adults (14-21 years) with (n = 96) and without (n = 72) generally well-controlled asthma. HRV parameters associated with sympathetic and parasympathetic ANS branches were analyzed. EA and NEA were defined using a 2.5% sputum eosinophil cut-point. Airway hyperreactivity (AHR) was defined as >= 15% reduction in FEV1 following saline challenge. Results HRV parameters did not differ between asthmatics and non-asthmatics or EA and NEA. They were also not associated with markers of inflammation, lung function or atopy. However, increased absolute low frequency (LF mu s(2); representing increased sympathetic nervous system (SNS) activity) was found in asthmatics who used beta-agonist medication compared to those who did not (median: 1611, IQR 892-3036 vs 754, 565-1592; p < 0.05) and increased normalized low frequency (LF nu) was found in those with AHR compared to without AHR (64, 48-71 vs 53, 43-66; p < 0.05). Conclusion ANS activity (as measured using HRV analysis) is not associated with pathophysiology or inflammatory phenotype in young asthmatics with generally well-controlled asthma. However, enhanced SNS activity can be detected in asthmatics with AHR or who use beta-agonist medication.

Aims: To assess the role of neural and remodelling pathways, alongside inflammatory mechanisms, in eosinophilic (EA) and non-eosinophilic asthma (NEA). Methods: 111 asthmatics and 62 non-asthmatics (14-21 years) underwent sputum induction testing. Twenty-four mediators were measured in supernatant. EA (n=52) and NEA (n=59) were defined using a sputum eosinophil cut-point of 2.5%. Results: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, p=0.03), periostin (33.8 vs 9.4 pg/mL, p=0.01), and eosinophil cationic protein (ECP; 220.1 vs 83.7 ng/mL, p=0.03) were found in asthmatics compared to non-asthmatics. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, p=0.02) but not NEA (27.8 vs 22.4 ng/mL, p=0.22). EA had higher levels of inflammatory (ECP: 496 vs 100.3 ng/mL, p=<0.01; interleukin-1β: 286 vs 209.3 pg/mL, p=0.03; histamine: 5805 vs 3173 pg/mL, p=<0.01) and remodelling (vascular endothelial growth factor: VEGF; 3.3 vs 2.5 ng/mL, p=0.03; periostin: 47.7 vs 22.1 pg/mL, p=0.04) mediators compared to NEA. Whilst macrophage counts were correlated with neural mediators such as neurokinin A (r=0.27, p=0.01), nociceptin (r=0.30, p=0.02), and nerve growth factor-β: NGF-β; r=0.19, p=0.04), granulocytes correlated with inflammatory and remodelling mediators; e.g., ECP and VEGF correlated with neutrophils (r=0.53 & r=0.33 respectively, p≤0.01) and eosinophils (r=0.53& r=0.29 respectively, p≤0.01). Conclusions: Inflammatory cells/mediators were often associated with neural and remodelling mediators, suggesting that these mechanisms coexist with inflammation. Neural and remodelling pathways may not play a role in NEA, but nociceptin may be important in EA.

Background: Neural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA).Objective: To assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma.Methods: A total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%. Results: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P & LE; .01; interleukin-1b: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P & LE; .01).Conclusion: Elevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.& COPY; 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

ABSTRACT Background: Neural mechanisms may play an important role in non-eosinophilic asthma. This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic and non-eosinophilic asthma and non-asthmatics. Methods: Thirty-eight asthmatics and nineteen non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), atopy, and spirometry tests, followed by capsaicin challenge. Eosinophilic (EA) and non-eosinophilic asthma (NEA) were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity (AHR) was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. Results: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared to non-asthmatics (n=19) (geometric mean C5: 58.3μM, 95% confidence interval 24.1-141.5 vs 193.6μM, 82.2-456.0; p<0.05). There was a similar (but non-significant) difference in capsaicin sensitivity in NEA compared with EA (n=18), (58.3μM, 24.1-141.5 vs 191.0μM, 70.9-514.0; p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control, or treatment were observed. Conclusion: Non-eosinophilic asthma, but not eosinophilic asthma, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of non-eosinophilic asthma.

We have previously shown that probiotic supplementation with Lactobacillus rhamnosus HN001 (HN001) led to a reduced incidence of gestational diabetes mellitus (GDM). Here we investigate whether HN001 supplementation resulted in alterations in fasting lipids, insulin resistance, or bile acids (BAs) during pregnancy. Fasting plasma samples collected at 24–30 weeks’ gestation, from 348 women randomised at 14–16 weeks’ gestation to consume daily probiotic HN001 (n = 172) or a placebo (n = 176) were analysed for lipids, insulin, glucose and BAs. Women supplemented with HN001 had lower fasting glucose compared with placebo (p = 0.040), and lower GDM. Significant differences were found in fasting insulin, HOMA-IR, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein (HDL)-c, triglycerides, total cholesterol, and BAs by GDM status. Lower fasting conjugated BAs were seen in women receiving HN001. A significant decrease of glycocholic acid (GCA) was found in older (age ≥ 35) women who received HN001 (p = 0.005), while GDM women showed significant reduced taurodeoxycholic acid (TDCA) (p = 0.018). Fasting conjugated BA was positively correlated with fasting glucose (r = 0.136, p = 0.020) and fasting insulin (r = 0.113, p = 0.036). Probiotic HN001 supplementation decreases conjugated BAs and might play a role in the improvement of glucose metabolism in women with pregnancy.

OBJECTIVE:To describe the phenotypic spectrum in patients with MBD5-associated neurodevelopmental disorder (MAND) and seizures; features of MAND include intellectual disability, epilepsy, psychiatric features of aggression and hyperactivity, and dysmorphic features including short stature and microcephaly, sleep disturbance, and ataxia. METHODS:We performed phenotyping on patients with MBD5 deletions, duplications, or point mutations and a history of seizures. RESULTS:Twenty-three patients with MAND and seizures were included. Median seizure onset age was 2.9 years (range 3 days-13 years). The most common seizure type was generalized tonic-clonic; focal, atypical absence, tonic, drop attacks, and myoclonic seizures occurred frequently. Seven children had convulsive status epilepticus and 3 nonconvulsive status epilepticus. Fever, viral illnesses, and hot weather provoked seizures. EEG studies in 17/21 patients were abnormal, typically showing slow generalized spike-wave and background slowing. Nine had drug-resistant epilepsy, although 3 eventually became seizure-free. All but one had moderate-to-severe developmental impairment. Epilepsy syndromes included Lennox-Gastaut syndrome, myoclonic-atonic epilepsy, and infantile spasms syndrome. Behavioral problems in 20/23 included aggression, self-injurious behavior, and sleep disturbance. CONCLUSIONS:MBD5 disruption may be associated with severe early childhood-onset developmental and epileptic encephalopathy. Because neuropsychiatric dysfunction is common and severe, it should be an important focus of clinical management.

Background: Neural pathways may play a role in non-eosinophilic asthma, but this has rarely been studied. Aims: To assess whether non-eosinophilic asthma is characterised by increased sensory nerve sensitivity compared to eosinophilic asthmatics and controls. Methods: We recruited 38 asthmatics (18 eosinophilic and 20 non-eosinophilic) and 19 non-asthmatics (14-21 years) who underwent a capsaicin challenge, combined sputum induction and airway hyperreactivity (AHR), exhaled nitric oxide (FENO), atopy and spirometry tests. Sensory nerve sensitivity was defined as the lowest capsaicin concentration that evoked 2 (C2) or 5 (C5) coughs. Results: Non-eosinophilic asthmatics (NEA; eosinophil cut-point <2.5%) had a significantly lower C5 (heightened sensitivity) compared to controls (C5: Geometric Mean (GM) 58.3, 95% CL 24.1-141.5 vs 193.6, 82.2-456.0; p<0.05). C5 was also lower in NEA when compared to eosinophilic asthmatics (EA), but this did not reach statistical significance (58.3, 24.1-141.5 vs 191.0, 70.9-514.0; p=0.07). C5 was associated with ethnicity and sensitivity analyses excluding non-Europeans (n=8) (thus reducing confounding) resulted in a more pronounced difference between EA and NEA (p<0.05). No differences in C2 were found (control, 28.0, 12.3-63.6; EA, 41.5, 13.6-126.6; NEA, 17.9, 9.0-37.1). FEV1 was significantly reduced from baseline after capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found across the groups. No other associations with demographic characteristics or other clinical outcomes were observed. Conclusion: Heightened airway sensory sensitivity may play a role in non-eosinophilic asthma.

Pathogenic variants in GNB5 cause an autosomal recessive neurodevelopmental disorder with neonatal sinus bradycardia. Seizures or epilepsy occurred in 10 of 22 previously reported cases, including 6 children from one family. We delineate the epileptology of GNB5 encephalopathy. Our nine patients, including five new patients, were from seven families. Epileptic spasms were the most frequent seizure type, occurring in eight of nine patients, and began at a median age of 3 months (2 months to 3 years). Focal seizures preceded spasms in three children, with onset at 7 days, 11 days, and 4 months. One child presented with convulsive status epilepticus at 6 months. Three children had burst suppression on electroencephalography (EEG), three had hypsarrhythmia, and one evolved from burst suppression to hypsarrhythmia. Background slowing was present in all after age 3 years. Magnetic resonance imaging (MRI) showed cerebral atrophy in one child and cerebellar atrophy in another. All nine had abnormal development prior to seizure onset and ultimately had profound impairment without regression. Hypotonia was present in all, with contractures developing in two older patients. All individuals had biallelic pathogenic variants in GNB5, predicted by in silico tools to result in protein truncation and loss‐of‐function. GNB5 developmental and epileptic encephalopathy is characterized by epileptic spasms, focal seizures, and profound impairment.

IntroductionA gap exists in the literature regarding dose–response associations of objectively assessed housing quality measures, particularly dampness and mould, with hospitalisation for acute respiratory infection (ARI) among children.MethodsA prospective, unmatched case–control study was conducted in two paediatric wards and five general practice clinics in Wellington, New Zealand, over winter/spring 2011–2013. Children aged <2 years who were hospitalised for ARI (cases), and either seen in general practice with ARI not requiring admission or for routine immunisation (controls) were included in the study. Objective housing quality was assessed by independent building assessors, with the assessors blinded to outcome status, using the Respiratory Hazard Index (RHI), a 13-item scale of household quality factors, including an 8-item damp–mould subscale. The main outcome was case–control status. Adjusted ORs (aORs) of the association of housing quality measures with case–control status were estimated, along with the population attributable risk of eliminating dampness–mould on hospitalisation for ARI among New Zealand children.Results188 cases and 454 controls were studied. Higher levels of RHI were associated with elevated odds of hospitalisation (OR 1.11/unit increase (95% CI 1.01 to 1.21)), which weakened after adjustment for season, housing tenure, socioeconomic status and crowding (aOR 1.04/unit increase (95% CI 0.94 to 1.15)). The damp–mould index had a significant, adjusted dose–response relationship with ARI admission (aOR 1.15/unit increase (95% CI 1.02 to 1.30)). By addressing these harmful housing exposures, the rate of admission for ARI would be reduced by 19% or 1700 fewer admissions annually.ConclusionsA dose–response relationship exists between housing quality measures, particularly dampness–mould, and young children’s ARI hospitalisation rates. Initiatives to improve housing quality and to reduce dampness–mould would have a large impact on ARI hospitalisation.

Antibiotics are commonly prescribed for infants. In addition to increasing concern about antibiotic resistance, there is a concern about the potential negative impact of antibiotics on the gut microbiota and health and development outcomes. The aim of this study was to investigate the association between early life antibiotic exposure and later neurocognitive outcomes. Participants were infants born to mothers enrolled in the probiotics study. The initial study was designed to evaluate the effect of two different probiotics on allergy outcomes in childhood. Antibiotic exposure was based on parent report and categorised according to the following timing of the first exposure: 0–6 months, 6–12 months, 12–24 months or not at all. At 11 years of age, children’s neurocognitive outcomes were assessed using psychologist-administered, parent-report and self-report measures. The relationship between the timing of antibiotic exposure and neurocognitive outcomes was examined using regression models. Of the 474 participants initially enrolled, 342 (72%) children had a neurocognitive assessment at 11 years of age. After adjustment for mode of delivery, probiotic treatment group assignment, income and breastfeeding, children who had received antibiotics in the first 6 months of life had significantly lower overall cognitive and verbal comprehension abilities, increased risk of problems with metacognition, executive function, impulsivity, hyperactivity, attention-deficit hyperactivity disorder, anxiety and emotional problems. These results provide further evidence that early exposure to antibiotics may be associated with detrimental neurodevelopmental outcomes.

Probiotics for preventing illness or improving health have become increasingly popular with consumers, researchers, and producers, both dairy companies and alternative medicine providers. They are widely available in foods such as yoghurt and as freeze dried capsules. They are used both for their general health effects on the gut including reducing travellers and antibiotic related diarrhoea. Their most important and best researched use is in the treatment of necrotising enterocolitis in premature babies where they reduce incidence, severity and mortality. The ultimate 'probiotic' mixture might be healthy human faeces which have been used for transplantation in patients with antibiotic resistant Clostridioides difficile infections with some success. Studies of allergy prevention using probiotics have shown mixed results. In New Zealand however, a specific strain of Lactobacillus rhamnosus (HN001) given from birth for two years has been shown to reduce the prevalence of allergic disease in infants throughout childhood. Further studies have shown a reduction in gestational diabetes amongst mothers who consume the probiotic during pregnancy. An important feature of the clinical use of probiotics is that different strains within the same species may have very different effects.

Aim To determine whether probiotic supplementation in early life improves neurocognitive outcomes assessed at 11 years of age. Methods Results A total of 474 children who were born March 2004-Aug 2005 participated in a two-centre randomised placebo-controlled trial of infants at risk of developing allergic disease. Pregnant women were randomised to take Lactobacillus rhamnosus strain HN001, Bifidobacterium animalis subsp. lactis strain HN019 or placebo daily from 35 weeks gestation until six months if breastfeeding, and their infants the same treatment from birth to two years. Intelligence, executive function, attention, depression and anxiety were assessed when the children were 11 years of age. A total of 342 (72.2%) children were assessed (HN001 n = 109, HN019 n = 118 and placebo n = 115). Overall, there were no significant differences in the neurocognitive outcomes between the treatment groups. Conclusion HN001 and HN019 given in early life were not associated with neurocognitive outcomes at 11 years of age in this study. However, we cannot exclude that other probiotics may have a beneficial effect. Further clinical trials are indicated.

BackgroundIn a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35weeks of gestation until 6months post-partum if breastfeeding and their child from birth to age 2years halved the risk of eczema during the first 2years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented. MethodsIn this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6x10(9) colony-forming units) was taken daily by mothers from 14-16weeks of gestation till 6months post-partum if breastfeeding, but was not given directly to the child. Women were recruited from the same study population as the first study, where they or their partner had a history of treated asthma, eczema or hay fever. ResultsWomen were randomized to HN001 (N=212) or placebo (N=211). Maternal-only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD10, wheeze or atopic sensitization in the infant by 12months. This contrasts with the mother and child intervention study, where HN001 was associated with reductions in eczema (hazard ratio (HR): 0.39, 95% CI 0.19-0.79, P=.009) and SCORAD (HR=0.61, 95% 0.37-1.02). However, differences in the HN001 effect between studies were not significant. HN001 could not be detected in breastmilk from supplemented mothers, and breastmilk TGF-/IgA profiles were unchanged. ConclusionMaternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

Clinical & Experimental AllergyVolume 48, Issue 5 p. 604-606 RESEARCH LETTER Is yoghurt an acceptable alternative to raw milk for reducing eczema and allergy in infancy? J. Crane, Corresponding Author J. Crane julian.crane@otago.ac.nz University of Otago, Wellington, New Zealand Correspondence Julian Crane, Wellington School of Medicine and Health Sciences, University of Otago, Wellington South, New Zealand. Email: julian.crane@otago.ac.nzSearch for more papers by this authorC. Barthow, C. Barthow University of Otago, Wellington, New ZealandSearch for more papers by this authorE. A. Mitchell, E. A. Mitchell University of Auckland, Auckland, New ZealandSearch for more papers by this authorT. V. Stanley, T. V. Stanley University of Otago, Wellington, New ZealandSearch for more papers by this authorG. Purdie, G. Purdie University of Otago, Wellington, New ZealandSearch for more papers by this authorJ. Rowden, J. Rowden University of Auckland, Auckland, New ZealandSearch for more papers by this authorJ. Kang, J. Kang University of Otago, Wellington, New ZealandSearch for more papers by this authorF. Hood, F. Hood University of Otago, Wellington, New ZealandSearch for more papers by this authorP. Barnes, P. Barnes University of Otago, Wellington, New ZealandSearch for more papers by this authorP. Fitzharris, P. Fitzharris Auckland Hospital, Auckland, New ZealandSearch for more papers by this authorR. Maude, R. Maude Victoria University, Wellington, New ZealandSearch for more papers by this authorP. Stone, P. Stone University of Auckland, Auckland, New ZealandSearch for more papers by this authorR. Murphy, R. Murphy University of Auckland, Auckland, New ZealandSearch for more papers by this authorK. Wickens, K. Wickens University of Otago, Wellington, New ZealandSearch for more papers by this author J. Crane, Corresponding Author J. Crane julian.crane@otago.ac.nz University of Otago, Wellington, New Zealand Correspondence Julian Crane, Wellington School of Medicine and Health Sciences, University of Otago, Wellington South, New Zealand. Email: julian.crane@otago.ac.nzSearch for more papers by this authorC. Barthow, C. Barthow University of Otago, Wellington, New ZealandSearch for more papers by this authorE. A. Mitchell, E. A. Mitchell University of Auckland, Auckland, New ZealandSearch for more papers by this authorT. V. Stanley, T. V. Stanley University of Otago, Wellington, New ZealandSearch for more papers by this authorG. Purdie, G. Purdie University of Otago, Wellington, New ZealandSearch for more papers by this authorJ. Rowden, J. Rowden University of Auckland, Auckland, New ZealandSearch for more papers by this authorJ. Kang, J. Kang University of Otago, Wellington, New ZealandSearch for more papers by this authorF. Hood, F. Hood University of Otago, Wellington, New ZealandSearch for more papers by this authorP. Barnes, P. Barnes University of Otago, Wellington, New ZealandSearch for more papers by this authorP. Fitzharris, P. Fitzharris Auckland Hospital, Auckland, New ZealandSearch for more papers by this authorR. Maude, R. Maude Victoria University, Wellington, New ZealandSearch for more papers by this authorP. Stone, P. Stone University of Auckland, Auckland, New ZealandSearch for more papers by this authorR. Murphy, R. Murphy University of Auckland, Auckland, New ZealandSearch for more papers by this authorK. Wickens, K. Wickens University of Otago, Wellington, New ZealandSearch for more papers by this author First published: 14 February 2018 https://doi.org/10.1111/cea.13121Citations: 5 Funding information This study was funded by grants and support from the Health Research Council of NZ (HRC 11/318) and Fonterra Co-operative Group Ltd, NZ (Fonterra). Fonterra contributed funds, provided and maintained quality control of the study capsules and performed the participant randomization for the study. Fonterra had no role in the design, analysis or writing of this article. E Mitchell is supported by Cure Kids. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume48, Issue5May 2018Pages 604-606 RelatedInformation

Background In a two-centre randomized placebo-controlled trial of Lactobacillus rhamnosus HN001 (HN001) (6 x 10(9) colony-forming units [cfu]) or Bifidobacterium lactis HN019 (HN019) (9 x 10(9) cfu) taken daily from 35-week gestation to 6 months' post-partum in mothers while breastfeeding and from birth to age 2 years in infants, we showed that HN001 significantly protected against eczema development at 2, 4 and 6 years and atopic sensitization at 6 years. There was no effect of HN019. We report here the findings for 11 year outcomes. Methods At age 11 years, eczema was defined as previously using the UK Working Party's Diagnostic Criteria. Asthma, wheeze, hay fever and rhinitis were defined based on the International Study of Asthma and Allergies in Childhood (ISAAC) questions. Atopic sensitization was defined as one or more positive responses (mean wheal diameter >= 3 mm) to a panel of food and aeroallergens. Analysis was intention-to-treat using hazard ratios to assess probiotic effects on the 11-year lifetime prevalence and relative risks for point or 12-month prevalence at 11 years. Results Early childhood HN001 supplementation was associated with significant reductions in the 12-month prevalence of eczema at age 11 years (relative risk [RR] = 0.46, 95% CI 0.25-0.86, P = 0.015) and hay fever (RR = 0.73, 95% CI 0.53-1.00, P = 0.047). For the lifetime prevalence, HN001 was associated with a significant reduction in atopic sensitization (hazard ratio [HR] = 0.71, 95% CI 0.51-1.00, P = 0.048), eczema (HR = 0.58, 95% CI 0.41-0.82, P = 0.002) and wheeze (HR = 0.76, 95% CI 0.57-0.99, P = 0.046). HN019 had no significant effect on these outcomes. Conclusion This is the first early probiotic intervention to show positive outcomes for at least the first decade of life across the spectrum of allergic disease.