Effect of Lactobacillus rhamnosus Probiotic in Early Pregnancy on Plasma Conjugated Bile Acids in a Randomised Controlled Trial.

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.

Food 4 Health - He Oranga Kai: Assessing the efficacy, acceptability and economic implications of Lactobacillus rhamnosus HN001 and ß-glucan to improve glycated haemoglobin, metabolic health, and general well-being in adults with pre-diabetes: study protocol for a 2 × 2 factorial design, parallel group, placebo-controlled randomized controlled trial, with embedded qualitative study and economic analysis.

BACKGROUND: The rates of pre-diabetes and type 2 diabetes mellitus are increasing worldwide, producing significant burdens for individuals, families, and healthcare systems. In New Zealand, type 2 diabetes mellitus and pre-diabetes disproportionally affect Maori, Pacific, and South Asian peoples. This research evaluates the efficacy, acceptability, and economic impact of a probiotic capsule and a prebiotic cereal intervention in adults with pre-diabetes on metabolic and mental health and well-being outcomes. METHODS: Eligible adults (n = 152) aged 18-80 years with pre-diabetes (glycated haemoglobin 41-49 mmol/mol) will be enrolled in a 2 × 2 factorial design, randomised, parallel-group, placebo-controlled trial. Computer-generated block randomization will be performed independently. Interventions are capsulated Lactobacillus rhamnosus HN001 (6 × 109 colony-forming units/day) (A) and cereal containing 4 g ß-glucan (B), placebo capsules (O1), and calorie-matched control cereal (O2). Eligible participants will receive 6 months intervention in the following groups: AB, AO1, BO2, and O1O2. The primary outcome is glycated haemoglobin after 6 months. Follow-up at 9 months will assess the durability of response. Secondary outcomes are glycated haemoglobin after 3 and 9 months, fasting glucose, insulin resistance, blood pressure, body weight, body mass index, and blood lipid levels. General well-being and quality of life will be measured by the Short-Form Health Survey 36 and Depression Anxiety Stress Scale 21 at 6 and 9 months. Outcome assessors will be blind to capsule allocation. An accompanying qualitative study will include 24 face-to-face semistructured interviews with an ethnically balanced sample from the ß-glucan arms at 2 months, participant focus groups at 6 months, and three health professional focus groups. These will explore how interventions are adopted, their acceptability, and elicit factors that may support the uptake of interventions. A simulation model of the pre-diabetic New Zealand population will be used to estimate the likely impact in quality-adjusted life years and health system costs of the interventions if rolled out in New Zealand. DISCUSSION: This study will examine the efficacy of interventions in a population with pre-diabetes. Qualitative components provide rich description of views on the interventions. When combined with the economic analysis, the study will provide insights into how to translate the interventions into practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617000990325. Prospectively registered on 10 July 2017.

Daily decision-making about food during pregnancy: a New Zealand study.

Pregnancy has always been a life-changing event for women and their families, but societal concern about pregnancy and motherhood has become intense in the digital age. The role of health promotion agencies and others supplying health-related resources about lifestyle behaviours is both important and in need of scrutiny. Ever increasing advice for pregnant women, their families and health professionals, abounds. This study of decision making during pregnancy investigated how women made everyday decisions during pregnancy about food and drink, as well as dietary supplements and medications, alcohol and recreational drugs. This qualitative interview study was a side-arm to a double-blind randomized, placebo-controlled trial conducted with pregnant women in Wellington New Zealand, 2013-2016. Data from interviews with 20 women were analysed using inductive thematic analysis. In relation to decision-making about lifestyle behaviours, five themes emerged-Information about food; Wanted and unwanted advice; Worry, anxiety and indecision; Making daily decisions about food; Changes in decision making over time. Participating women talked more about food selection and restriction advice than any other lifestyle topic. Analysis demonstrated concern about information accuracy and overload from multiple, diverse sources. Women described learning how to assess resource credibility, how to develop decision-making skills, and who to trust. The study raises important questions about how the health information environment, despite best intentions, can be confusing or potentially harmful. The study underlines the continued importance of the role health professionals have in not only interpreting information to discuss individualized advice, but also in empowering pregnant women to develop lifestyle-related decision-making skills.

Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years.

BACKGROUND: In a two-centre randomized placebo-controlled trial of Lactobacillus rhamnosus HN001 (HN001) (6 × 109 colony-forming units [cfu]) or Bifidobacterium lactis HN019 (HN019) (9 × 109 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.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

BACKGROUND: In a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35 weeks of gestation until 6 months post-partum if breastfeeding and their child from birth to age 2 years halved the risk of eczema during the first 2 years 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. METHODS: In this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6 × 109 colony-forming units) was taken daily by mothers from 14-16 weeks of gestation till 6 months 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. RESULTS: Women were randomized to HN001 (N = 212) or placebo (N = 211). Maternal-only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD ≥ 10, wheeze or atopic sensitization in the infant by 12 months. 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-ß/IgA profiles were unchanged. CONCLUSION: Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

Indoor visible mold and mold odor are associated with new-onset childhood wheeze in a dose-dependent manner.

Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case-control study involving 150 children with new-onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new-onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new-onset wheezing in a dose-dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new-onset wheezing. The association between mold and new-onset wheeze was not modified by atopic status, suggesting a non-allergic association.

Hair nicotine at 15 months old, tobacco exposure and wheeze or asthma from 15 months to 6 years old.

OBJECTIVE: To investigate the relationship between hair nicotine levels at 15 months of age and prior parent-reported smoking exposure, and the risk of wheezing and current asthma from 15 months to 6 years of age. STUDY DESIGN: We measured hair nicotine levels at 15 months of age in 376 of 535 infants enrolled in a prospective birth cohort in Christchurch, New Zealand. We obtained detailed information from parents about smoking exposure during pregnancy and in the home at 3 and 15 months of age. Data for demographics, wheezing, and asthma were obtained from yearly questionnaires up to age 6 years. We assessed hair nicotine levels in relation to reported smoke exposure in pregnancy and up to age 15 months, and the association between high levels of hair nicotine and annual reports of current wheeze and current asthma using multiple logistic regression. RESULTS: Hair nicotine increased with numbers of smokers and daily cigarettes smoked at home, and was also strongly associated with smoking in pregnancy. High level of hair nicotine was associated with increased risk of wheeze (Odds ratio 2.30, P = 0.001) and, though not significant, of current asthma (Odds ratio 2.02, P = 0.056) at 15 months of age, after controlling for socio-economic status, ethnicity, body mass index, respiratory infections in the first 3 months of life, and duration of exclusive breastfeeding. At older ages the associations were non-significant. CONCLUSION: In children aged 15 months hair nicotine level was related to smoking exposure, and was associated with increased risk of wheeze and asthma.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

BACKGROUND: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. METHODS/DESIGN: The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. DISCUSSION: The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.

Differential effects of two probiotics on the risks of eczema and atopy associated with single nucleotide polymorphisms to Toll-like receptors.

BACKGROUND: There is strong evidence to support a genetic predisposition to eczema and more recently studies have suggested that probiotics might be used to prevent eczema by modifying the expression of putative allergy-associated genes. The aim of this present study was to investigate whether two probiotics, Lactobacillus rhamnosus HN001 (HN001) and Bifidobacterium animalis subsp. lactis HN019 (HN019), can modify the known genetic predisposition to eczema conferred by genetic variation in the Toll-like receptor (TLR) genes in a high-risk infant population. METHODS: We selected 54 SNPs in the Toll-like receptor genes. These SNPs were analysed in 331 children of sole European ancestry as part of a double-blind, randomized, placebo-controlled trial examining the effects of HN001 and HN019 supplementation on eczema development and atopic sensitization. RESULTS: The data showed that 26 TLR SNPs interacted with HN001 resulting in a significantly reduced risk of eczema, 18 for eczema severity as defined by SCORAD ≥ 10 and 20 for atopic sensitization compared to placebo. There were only two SNPs that interacted with HN019 resulting in a reduced risk of eczema, eczema severity or atopy. CONCLUSIONS: This is the first study to show that the negative impact of specific TLR genotypes may be positively affected by probiotic supplementation. HN001 exhibits a much stronger effect than HN019 in this respect.

A measure for quantifying the impact of housing quality on respiratory health: a cross-sectional study.

BACKGROUND: Damp and mould in homes have been established as risk factors for respiratory health. There is a need for a relatively straightforward assessment of the home that quantifies this risk. METHODS: Using data from 891 New Zealand houses, the utility of a Respiratory Hazard Index quantifying key attributes related to damp and mould was tested by studying its associations with self-reported respiratory symptoms. RESULTS: A dose-response relationship was found whereby each unit increase in the Respiratory Hazard Index was associated with an 11% increase in the odds of at least one episode of wheezing/whistling in the chest over the last 12 months (relative odds of 1.11 with a 95% CI 1.04%-1.20%). An 11% increase in the odds of an asthma attack over the last 12 months was estimated (relative odds of 1.11 with a 95% CI 1.01%-1.22%). These estimates were adjusted for household crowding levels, age, sex and smoking status. There was suggestive evidence of more steeply increasing odds of respiratory symptoms with increasing levels of the Respiratory Hazard Index for children aged under 7. In the worst performing houses according to the Index, a 33% reduction in the number of people experiencing respiratory symptoms (relative risk 0.67 with 95% CI 0.53 to 0.85) could be expected if people were housed in the best performing houses. CONCLUSIONS: This study showed that increased evidence of housing conditions supporting dampness and mould was associated with increased odds of respiratory symptoms. A valid housing assessment tool can provide a rational basis for investment in improved housing quality to improve respiratory health.

Breastfeeding protects against current asthma up to 6 years of age.

OBJECTIVE: To investigate the effects of breastfeeding on wheezing and current asthma in children 2 to 6 years of age. STUDY DESIGN: Infants (n=1105) were enrolled in a prospective birth cohort in New Zealand. Detailed information about infant feeding was collected using questionnaires administered at birth and at 3, 6, and 15 months. From this, durations of exclusive and any breastfeeding were calculated. Information about wheezing and current asthma was collected at 2, 3, 4, 5, and 6 years. Logistic regression was used to model associations between breastfeeding and outcomes with and without adjustment for confounders. RESULTS: After adjustment for confounders, each month of exclusive breastfeeding was associated with significant reductions in current asthma from 2 to 6 years (all, P<.03). Current asthma at 2, 3, and 4 years was also reduced by each month of any breastfeeding (all, P<.005). In atopic children, exclusive breastfeeding for ≥ 3 months reduced current asthma at ages 4, 5, and 6 by 62%, 55%, and 59%, respectively. CONCLUSION: Breastfeeding, particularly exclusive breastfeeding, protects against current asthma up to 6 years. Although exclusive breastfeeding reduced risk of current asthma in all children to age 6, the degree of protection beyond 3 years was more pronounced in atopic children.

Asthma, atopy and exhaled nitric oxide in a cohort of 6-yr-old New Zealand children.

BACKGROUND: Exhaled nitric oxide has been promoted as a non-invasive measure of airway inflammation, with clinical utility for the diagnosis and management of asthma. AIM: We studied associations between exhaled nitric oxide, asthma and atopy in a variety of clinically relevant phenotypes in a cohort of 6-yr-old children. METHOD: Asthma was defined using standard questionnaire criteria, atopy was measured using skin prick tests (SPT) and specific IgE to common allergens, and exhaled nitric oxide was measured using a chemiluminescence analyser according to American and European Thoracic Society criteria. RESULTS: Exhaled nitric oxide was strongly related to atopy and in particular to sensitization to house dust mites. Children with non-allergic asthma had no increase in exhaled nitric oxide compared with non-asthmatic children. Compared with children who never wheezed both late onset and persistent, wheezing was associated with increased FE(NO), while early transient wheezing was not. Elevated levels of exhaled nitric oxide amongst children with allergic asthma were almost entirely explained by their levels of specific IgE to aeroallergens, predominantly D pteronyssinus. CONCLUSION: Airway inflammation as measured by exhaled nitric oxide in young New Zealand children is related to their level of specific IgE to aeroallergens. This has implications for the utility of nitric oxide as a diagnostic and management tool in childhood asthma and for the importance of specific IgE as a marker of asthma severity.

Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma.

OBJECTIVE: Higher maternal intake of vitamin D during pregnancy is associated with a lower risk of wheezing in offspring. The relationship between cord-blood levels of 25-hydroxyvitamin D (25[OH]D) and childhood wheezing is unknown. We hypothesized that cord-blood levels would be inversely associated with risk of respiratory infection, wheezing, and asthma. PATIENTS AND METHODS: Cord blood from 922 newborns was tested for 25(OH)D. Parents were asked if their child had a history of respiratory infection at 3 months of age or a history of wheezing at 15 months of age and then annually thereafter. Incident asthma was defined as doctor-diagnosed asthma by the time the child was 5 years old and reported inhaler use or wheezing since the age of 4 years. RESULTS: The median cord-blood level of 25(OH)D was 44 nmol/L (interquartile range: 29-78). Follow-up was 89% at the age of 5 years. Adjusting for the season of birth, 25(OH)D had an inverse association with risk of respiratory infection by 3 months of age (odds ratio: 1.00 [reference] for ≥75 nmol/L, 1.39 for 25-74 nmol/L, and 2.16 [95% confidence interval: 1.35-3.46] for <25 nmol/L). Likewise, cord-blood 25(OH)D levels were inversely associated with risk of wheezing by 15 months, 3 years, and 5 years of age (all P < .05). Additional adjustment for more than 12 potential confounders did not materially change these results. In contrast, we found no association between 25(OH)D levels and incident asthma by the age of 5 years. CONCLUSIONS: Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma.

Vitamin D status of newborns in New Zealand.

Recognition of the important non-skeletal health effects of vitamin D has focused attention on the vitamin D status of individuals across the lifespan. To examine the vitamin D status of newborns, we measured serum levels of 25-hydroxyvitamin D (25(OH)D) in the cord blood of 929 apparently healthy newborns in a population-based study in New Zealand, a country at 41 °S latitude, with strong anti-skin cancer (sun avoidance) campaigns and without vitamin D food fortification. Randomly selected midwives in two regions recruited children. The median cord blood level of 25(OH)D was 44 nmol/l (interquartile range, 29-78 nmol/l). Overall, 19 % of newborns had 25(OH)D levels < 25 nmol/l and 57 % had levels < 50 nmol/l; only 27 % had levels of 75 nmol/l or higher, which are levels associated with optimal health in older children and adults. A multivariable ordinal logistic regression model showed that the strongest determinants of low vitamin D status were winter month of birth and non-European ethnicity. Other determinants of low cord blood 25(OH)D included longer gestational age, younger maternal age and a parental history of asthma. In summary, low levels of vitamin D are common among apparently healthy New Zealand newborns, and are independently associated with several easily identified factors. Although the optimal timing and dosage of vitamin D supplementation require further study, our findings may assist future efforts to correct low levels of 25(OH)D among New Zealand mothers and their newborn children.

Breastfeeding protects against adverse respiratory outcomes at 15 months of age.

The relationship between breastfeeding, respiratory and other allergic disorders has been controversial. Our aim was to investigate the relationships between breastfeeding, respiratory outcomes, eczema and atopy at 15 months of age in a prospective birth cohort in New Zealand. A total of 1105 children were enrolled at birth, and 1011 (91.2%) were followed up at 15 months. Logistic regression was used to model associations between breastfeeding duration and respiratory outcomes, eczema and atopy after adjusting for relevant confounding variables: ethnicity, socio-economic status, parity, body mass index, smoking in pregnancy, gender and respiratory infections in the first 3 months of life. Breastfeeding was associated with a significant reduction in the risk of adverse respiratory outcomes at 15 months. After adjustment for confounders, each month of exclusive breastfeeding reduced the risk of doctor-diagnosed asthma by 20% (odds ratio 0.80, 95% confidence interval 0.71 to 0.90), wheezing by 12% (0.88, 0.82 to 0.94) and inhaler use by 14% (0.86, 0.78 to 0.93). Associations for both exclusive and additional breastfeeding durations, and respiratory outcomes remained independently significant when modelled simultaneously. Although independently associated with all respiratory outcomes, adjusting for parental history of allergic disease or maternal history of asthma did not alter our findings. Breastfeeding was not associated with eczema or atopy at 15 months. In conclusion, there was a significant protective effect of breastfeeding on infant wheezing and other adverse respiratory outcomes that may be early indicators of asthma in New Zealand children.

A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: The role of probiotics in prevention of allergic disease is still not clearly established, although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years. OBJECTIVE: To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years. METHODS: Double-blind, randomized placebo-controlled trial of infants at risk of allergic disease. Pregnant women were randomized to take Lactobacillus rhamnosus HN001 (L rhamnosus), Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding, and their infants were randomized to receive the same treatment from birth to 2 years (n = 474). The infant's cumulative prevalence of eczema and point prevalence of atopy, using skin prick tests to common allergens, was assessed at 2 years. RESULTS: Infants receiving L rhamnosus had a significantly (P = .01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30-0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58-1.41). There was no significant effect of L rhamnosus (HR, 0.74; 95% CI, 0.46-1.18) or B animalis subsp lactis (HR, 0.82; 95% CI, 0.52-1.28) on atopy. L rhamnosus (71.5%) was more likely than B animalis subsp lactis (22.6%) to be present in the feces at 3 months, although detection rates were similar by 24 months. CONCLUSION: We found that supplementation with L rhamnosus, but not B animalis subsp lactis, substantially reduced the cumulative prevalence of eczema, but not atopy, by 2 years. Understanding how Lactobacilli act to prevent eczema requires further investigation.

Effects of improved home heating on asthma in community dwelling children: randomised controlled trial.

OBJECTIVE: To assess whether non-polluting, more effective home heating (heat pump, wood pellet burner, flued gas) has a positive effect on the health of children with asthma. DESIGN: Randomised controlled trial. SETTING: Households in five communities in New Zealand. PARTICIPANTS: 409 children aged 6-12 years with doctor diagnosed asthma. INTERVENTIONS: Installation of a non-polluting, more effective home heater before winter. The control group received a replacement heater at the end of the trial. MAIN OUTCOME MEASURES: The primary outcome was change in lung function (peak expiratory flow rate and forced expiratory volume in one second, FEV(1)). Secondary outcomes were child reported respiratory tract symptoms and daily use of preventer and reliever drugs. At the end of winter 2005 (baseline) and winter 2006 (follow-up) parents reported their child's general health, use of health services, overall respiratory health, and housing conditions. Nitrogen dioxide levels were measured monthly for four months and temperatures in the living room and child's bedroom were recorded hourly. RESULTS: Improvements in lung function were not significant (difference in mean FEV(1) 130.7 ml, 95% confidence interval -20.3 to 281.7). Compared with children in the control group, however, children in the intervention group had 1.80 fewer days off school (95% confidence interval 0.11 to 3.13), 0.40 fewer visits to a doctor for asthma (0.11 to 0.62), and 0.25 fewer visits to a pharmacist for asthma (0.09 to 0.32). Children in the intervention group also had fewer reports of poor health (adjusted odds ratio 0.48, 95% confidence interval 0.31 to 0.74), less sleep disturbed by wheezing (0.55, 0.35 to 0.85), less dry cough at night (0.52, 0.32 to 0.83), and reduced scores for lower respiratory tract symptoms (0.77, 0.73 to 0.81) than children in the control group. The intervention was associated with a mean temperature rise in the living room of 1.10 degrees C (95% confidence interval 0.54 degrees C to 1.64 degrees C) and in the child's bedroom of 0.57 degrees C (0.05 degrees C to 1.08 degrees C). Lower levels of nitrogen dioxide were measured in the living rooms of the intervention households than in those of the control households (geometric mean 8.5 microg/m(3) v 15.7 microg/m(3), P<0.001). A similar effect was found in the children's bedrooms (7.3 microg/m(3) v 10.9 microg/m(3), P<0.001). CONCLUSION: Installing non-polluting, more effective heating in the homes of children with asthma did not significantly improve lung function but did significantly reduce symptoms of asthma, days off school, healthcare utilisation, and visits to a pharmacist. TRIAL REGISTRATION: Clinical Trials NCT00489762.

Atopic sensitization and the international variation of asthma symptom prevalence in children.

RATIONALE: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. OBJECTIVES: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. METHODS: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). MEASUREMENTS AND MAIN RESULTS: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01). CONCLUSIONS: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.