Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

A pilot randomised controlled trial investigating a Mediterranean diet intervention in pregnant women for the primary prevention of allergic diseases in infants.

BACKGROUND: Observational studies suggest a potentially protective role of the Mediterranean diet (MD) in allergic diseases, including asthma. Large scale randomised controlled trials (RCTs) are needed to test the hypothesised allergy-prevention benefits of a MD during pregnancy. The present two-arm pilot RCT in pregnant women at high-risk of having a child who would develop allergic disease investigated maternal recruitment, retention and acceptability of an MD dietary intervention in the UK. The trial also assessed the effect of the intervention on MD adherence scores at 12 and at 24 weeks post-randomisation. METHODS: Thirty women were recruited at around 12 weeks of gestation. Retention was high (28 out of 30; 93%). The intervention was acceptable to participants. Mean (SD) adherence to the MD at baseline was 12.4 (2.9) in the intervention arm (n = 14) and 13.0 (1.9) in the control arm (n = 16), where 24 represents maximal adherence. There was a favourable short-term change in MD score: the adjusted mean difference (intervention - control) in the change in MD score from baseline to 12 weeks post-randomisation was 2.4 (95% confidence interval = 0.6-4.2, P = 0.012). CONCLUSIONS: The trial provides important insights into recruitment, retention and sustaining the dietary intervention, which will be used in the design of a large RCT.

Maternal vitamin D and E intakes during early pregnancy are associated with airway epithelial cell responses in neonates.

BACKGROUND: Antenatal factors including maternal diet may predispose to airway disease, possibly by impacting on fetal airway development. OBJECTIVE: This cohort study tested the hypothesis that maternal vitamin D and E status in early pregnancy is associated with airway epithelial cell (AEC) responses in new born infants and examined constitutive and TNFα/IL-1ß, house dust mite (HDM) extract or lipopolysaccharide (LPS)-stimulated neonatal AEC responses in vitro. METHODS: Maternal dietary vitamin D and E intakes (plasma 25[OH]D3 or α-tocopherol) were characterized at 10-12 weeks gestation. Neonatal nasal AECs were collected soon after birth and cultured to tertiary passage. Constitutive and stimulated - TNFα/IL-1ß, HDM extract or LPS - secretory responses (VEGF, RANTES, MCP-1, IL-17A, IFN-γ, GM-CSF, eotaxin, MIP1-α, MIP1-ß, ICAM, IL-6, IL-8, IL-10, TNF) in 139 AEC cultures were quantified. RESULTS: AEC mediator release was greater following TNF-α/IL-1ß, HDM or LPS stimulation compared to constitutive release. Increased maternal dietary vitamin D was associated with significant increases in IL-10 release by AEC after stimulation with TNF-α/IL-1ß (P = 0.024) or HDM (P = 0.049). Maternal plasma α-tocopherol at 10-12 weeks gestation was positively associated with MIP1α (Spearman's rho 0.242, P = 0.009) and IL-3 (ρ 0.189, P = 0.043) responses after TNF-α/IL-1ß stimulation and negatively associated with TNF (ρ -0.404, P = 0.011) and MIP1ß (ρ -0.322, P = 0.046) responses after LPS stimulation. DISCUSSION: Neonatal AECs respond to pro-inflammatory and allergenic stimuli in vitro demonstrating their potential to function as components of the innate immune response. Our findings suggest that associations exist between maternal micronutrient intake during early pregnancy and aspects of stimulated neonatal airway epithelial cell secretory function that may in turn impact on the development of asthma and/or allergic rhinitis in later life.

Employment in adults with cystic fibrosis.

BACKGROUND: Chronic ill-health may significantly impact on an individual's ability to work. This not only relates to disease severity but also to psychosocial factors such as illness perception and coping strategies. AIMS: To explore the factors associated with employment status in adults with cystic fibrosis (CF). METHODS: Subjects recruited from adult CF clinics in Aberdeen, Birmingham and Newcastle completed questionnaires assessing health-related quality of life (HRQoL), workplace productivity (presenteeism) and employment. Clinical data indicative of disease severity were also recorded. RESULTS: A total of 254 subjects were recruited, 41 from Aberdeen, 63 from Birmingham and 150 from Newcastle. Sixty-five per cent of subjects were in employment or education. If employed/self-employed, median hours worked was 37.3h/week. Forty per cent reported stopping a job due to CF; 47% felt CF had affected career choice and 24% changed duties because of CF. Ten per cent had taken a pay cut and 23% reported workplace discrimination due to CF. Multivariate modelling demonstrated that employment status was independently associated with educational attainment, centre and the HRQoL domains of role and health perception and is independent of clinical parameters of disease severity. CONCLUSIONS: Adults with CF reported that CF impacted on their ability to work. Employment appeared to be most strongly associated with educational attainment, locality and HRQoL domains and not clinical parameters of severity. Specific guidance is needed for both adults with CF and potential employers, with appropriate targeted interventions aimed at improving health perceptions and coping strategies.

Household carbon monoxide (CO) concentrations in a large African city: An unquantified public health burden?

Carbon monoxide (CO) is a poisonous gas produced by incomplete combustion of carbon-based fuels that is linked to mortality and morbidity. Household air pollution from burning fuels on poorly ventilated stoves can lead to high concentrations of CO in homes. There are few datasets available on household concentrations of CO in urban areas of sub-Saharan African countries. CO was measured every minute over 24 h in a sample of homes in Nairobi, Kenya. Data on household characteristics were gathered by questionnaire. Metrics of exposure were summarised and analysis of temporal changes in concentration was performed. Continuous 24-h data were available from 138 homes. The mean (SD), median (IQR) and maximum 24-h CO concentration was 4.9 (6.4), 2.8 (1.0-6.3) and 44 ppm, respectively. 50% of homes had detectable CO concentrations for 847 min (14h07m) or longer during the 24-h period, and 9% of homes would have activated a CO-alarm operating to European specifications. An association between a metric of total CO exposure and self-reported exposure to vapours >15 h per week was identified, however this were not statistically significant after adjustment for the multiple comparisons performed. Mean concentrations were broadly similar in homes from a more affluent area and an informal settlement. A model of typical exposure suggests that cooking is likely to be responsible for approximately 60% of the CO exposure of Nairobi schoolchildren. Household CO concentrations are substantial in Nairobi, Kenya, despite most homes using gas or liquid fuels. Concentrations tend to be highest during the evening, probably associated with periods of cooking. Household air pollution from cooking is the main source of CO exposure of Nairobi schoolchildren. The public health impacts of long-term CO exposure in cities in sub-Saharan Africa may be considerable and should be studied further.

Breastfeeding and introduction of complementary foods during infancy in relation to the risk of asthma and atopic diseases up to 10 years.

BACKGROUND: It has been hypothesized that changes in diet during early life may have contributed to the increase in childhood asthma and atopy. The long-term effect of the timing and content of infant feeding on the incidence of asthma and atopic diseases in children is unclear. OBJECTIVE: To investigate the associations between duration of breastfeeding and the timing of introduction of complementary foods during the first 6 months and parental-reported asthma, wheeze and atopic eczema up to 10 years of age. METHODS: Infant feeding practices (breastfeeding and introduction of complementary foods) of 1924 singleton children participating in the Study of Eczema and Asthma To Observe the influence of Nutrition (SEATON) birth cohort were prospectively collected up to 6 months with outcomes (wheeze, atopic eczema and asthma) being assessed at 1, 2, 5 and 10 years. Data were analysed using generalized estimating equations and discrete hazards models with adjustment for confounders. RESULTS: By 6 months, 59% and 35% of mothers had stopped exclusive and total breastfeeding, respectively. Although formula feeding was adversely associated with wheeze in the past 12 months (adjusted OR for no formula feeding: 070, 95% CI 0.50-0.97), and the introduction of biscuits/bread after 5 months of age adversely associated with atopic eczema (adjusted OR 1.34, 95% CI 1.06-1.69), these results lost their statistical significance after adjustment for multiple testing. Stratification of the results by the presence of eczema by 6 months of age and family atopic history did not substantially differ from the results of the whole study population. CONCLUSION AND CLINICAL RELEVANCE: Our results suggest that the nature of infant feeding during the first 6 months seems not to substantially influence the long-term risk of asthma and atopic diseases in children, nor in children at high risk of atopic disease because of a family history of atopic disease.

Confounding and effect modification in studies of diet and childhood asthma and allergies.

OBJECTIVE: To propose a comprehensive set of confounders and effect modifiers that should be considered in epidemiologic investigations. METHODS: Two reviewers independently critiqued studies included in a recent systematic review and extracted data on the confounders and effect modifiers that were considered and the approaches used to justify inclusion. RESULTS: Of the 62 studies reviewed, 20 were cohort, 16 case-control, 25 cross-sectional studies, and one ecologic study. All cohort, cross-sectional, and ecologic studies had some adjustment for confounding or consideration of effect modification, but this was only the case for 7/16 (44%) case-control studies. Of the 53 studies that considered confounding or effect modification, 39/53 (74%) gave no justification for the inclusion of the variables considered. Studies that justified the inclusion of the variables did so based on empirical evidence (n = 10), conceptual justification (n = 7), or a combination of the two (n = 3). Confounding was handled mainly by using regression modeling, but some case-control studies utilized matching and anova. Ten studies handled effect modification by stratification, eight tested for interaction, and five used both strategies. CONCLUSIONS: We have found substantial shortcomings in the handling of confounding and effect modification in studies of diet and development of childhood asthma/allergies. Selection of variables should be based on conceptual considerations and empirical evidence. Using this approach, we have proposed a comprehensive set of confounders and effect modifiers that need to be considered in future studies.

Chronic respiratory disease in adult outpatients in three African countries: a cross-sectional study.

BACKGROUND: The greatest burden of chronic respiratory disease is in low- and middle-income countries, with recent population-based studies reporting substantial levels of obstructive and restrictive lung function.OBJECTIVE: To characterise the common chronic respiratory diseases encountered in hospital outpatient clinics in three African countries.METHODS This was a cross-sectional study of consecutive adult patients with chronic respiratory symptoms (>8 weeks) attending hospital outpatient departments in Ethiopia, Kenya and Sudan. Patients were assessed using a respiratory questionnaire, spirometry and chest radiography. The diagnoses of the reviewing clinicians were ascertained.RESULT: A total of 519 patients (209 Kenya, 170 Ethiopia, 140 Sudan) participated; the mean age was 45.2 years (SD 16.2); 53% were women, 83% had never smoked. Reviewing clinicians considered that 36% (95% CI 32-40) of patients had asthma, 25% (95% CI 21-29) had chronic bronchitis, 8% (95% CI 6-11) chronic obstructive pulmonary disease (COPD), 5% (95% CI 4-8) bronchiectasis and 4% (95% CI 3-6) post-TB lung disease. Spirometry consistent with COPD was present in 35% (95% CI 30-39). Restriction was evident in 38% (95% CI 33-43). There was evidence of sub-optimal diagnosis of asthma and COPD.CONCLUSION: In Ethiopia, Kenya and Sudan, asthma, COPD and chronic bronchitis account for the majority of diagnoses in non-TB patients with chronic respiratory symptoms. The suboptimal diagnosis of these conditions will require the widespread use of spirometry.

Improving access to affordable quality-assured inhaled medicines in low- and middle-income countries.

BACKGROUND: Access to affordable inhaled medicines for chronic respiratory diseases (CRDs) is severely limited in low- and middle-income countries (LMICs), causing avoidable morbidity and mortality. The International Union Against Tuberculosis and Lung Disease convened a stakeholder meeting on this topic in February 2022.METHODS: Focused group discussions were informed by literature and presentations summarising experiences of obtaining inhaled medicines in LMICs. The virtual meeting was moderated using a topic guide around barriers and solutions to improve access. The thematic framework approach was used for analysis.RESULTS: A total of 58 key stakeholders, including patients, healthcare practitioners, members of national and international organisations, industry and WHO representatives attended the meeting. There were 20 pre-meeting material submissions. The main barriers identified were 1) low awareness of CRDs; 2) limited data on CRD burden and treatments in LMICs; 3) ineffective procurement and distribution networks; and 4) poor communication of the needs of people with CRDs. Solutions discussed were 1) generation of data to inform policy and practice; 2) capacity building; 3) improved procurement mechanisms; 4) strengthened advocacy practices; and 5) a World Health Assembly Resolution.CONCLUSION: There are opportunities to achieve improved access to affordable, quality-assured inhaled medicines in LMICs through coordinated, multi-stakeholder, collaborative efforts.

Parental occupation is a risk factor for childhood wheeze and asthma.

The present birth cohort study investigated whether or not childhood wheeze and asthma are associated with parental exposure to occupational sensitisers that cause asthma. Parental occupation, from the Avon Longitudinal Study of Parents and Children (ALSPAC), was related to wheeze, asthma, ventilatory function, airway responsiveness and atopic sensitisation in children aged 0-102 months. Occupation was recorded for 11,193 mothers and 9,473 fathers antenatally, and for 4,631 mothers and 5,315 fathers post-natally. Childhood respiratory outcomes were not associated with parental occupational exposure to diisocyanates, glues/resins, dyes, animal dust, solder, enzymes and wood dust. Maternal post-natal occupational exposure to latex and/or biocides/fungicides increased the likelihood of childhood wheeze and asthma. High levels of latex or biocide/fungicide exposure were associated with an OR (95% CI) of 1.26 (1.07-1.50) and 1.22 (1.02-2.05), respectively, for wheezing up to 81 months. Combined maternal latex and biocide/fungicide exposure increased the likelihood of childhood wheeze (1.22 (1.03-1.43)) and asthma. High paternal occupational flour dust exposure was associated with an increased likelihood of wheeze after 30 months (2.31 (1.05-5.10)) and asthma by 91 months (3.23 (1.34-7.79)). Maternal occupational exposure to latex and/or biocides and paternal exposure to flour dust increases the risk of childhood asthma. Further studies in this area are justified.

Antioxidants and allergic disease: a case of too little or too much?

Speculation persists as to the possible role, if any, of dietary antioxidants in allergic disease. While it has been hypothesized that the recent increase in allergic disease is a consequence of declining dietary antioxidant intake, an alternative hypothesis proposes that the increase in allergic disease is due to increasing antioxidant intake. Dietary trends are conflicting; the intake of some antioxidants has declined, for others intakes are likely to have increased. Animal model studies demonstrate that antioxidant supplementation at the time of primary and subsequent allergen exposure attenuates allergic inflammatory responses. The data from human studies are less clear. Observational epidemiological studies of humans are beset by several methodological limitations associated with the assessment of diet and predominantly focus on asthma. Most observational studies report potentially beneficial associations between dietary antioxidants and allergic outcomes, but a small minority report potentially adverse associations. Human intervention studies suggest that single antioxidant supplements confer minimal, if any clinical benefit in adults with asthma, however, there is still scope for studies in children, atopic dermatitis, allergic rhinitis (AR) and of antioxidant combinations. More recently, it has been suggested that dietary antioxidants in the developmental context of fetal and infant development influence the development childhood asthma and atopic sensitization possibly by affecting the first interactions between the neonatal immune system and allergens. While a small number of birth cohort studies have reported potentially beneficial associations between maternal intake of some antioxidants during pregnancy and childhood asthma, there is very limited data suggesting associations between maternal antioxidant intake and childhood atopic dermatitis and AR. The available epidemiological, animal, molecular and immunological data suggest that there are associations between antioxidants and asthma and to a much lesser extent, atopic dermatitis and AR. However, the exact nature of the relationships and the potential for therapeutic intervention remain unclear.

An application of the United Kingdom Working Party diagnostic criteria for atopic dermatitis in Scottish infants.

The United Kingdom Working Party diagnostic criteria for atopic dermatitis have been characterized in infants and children; however, the need for visual confirmation of flexural dermatitis by a trained investigator limits their use in large epidemiologic studies. We have administered the complete United Kingdom Working Party criteria in a postal questionnaire format to the mothers of year old infants and determined the concordance between mothers' and trained investigator's reports of visual flexural dermatitis. Based on mothers' responses to the questionnaire, 59 infants with atopic dermatitis and 59 controls were identified. In subsequent home interviews conducted by a trained investigator, the United Kingdom criteria questions were repeated and sites of current visible dermatitis were identified by mothers and the investigator as per United Kingdom Working Party protocol. Agreement between the mothers' postal and home interview responses was high: kappa= 0.75-0.94 for individual criteria; kappa= 0.93 for diagnosed atopic dermatitis. Agreement between the mothers' and investigator's observations of visible flexural dermatitis was high for all sites: kappa= 0.88-1.0. The results demonstrate that mothers are able to apply the United Kingdom criteria and accurately report visible flexural dermatitis in their year old infants. The postal application of the United Kingdom Working Party's diagnostic criteria for atopic dermatitis in year old infants appears to be a practical, reliable, epidemiologic tool in the investigation of atopic dermatitis with results comparable with formal application of the criteria by a trained investigator.

Measurement of T-helper cytokines secreted by cord blood mononuclear cells in response to allergens.

It has been proposed that in utero factors may predispose towards the development of childhood atopy. To test this hypothesis, it will be necessary to measure T-helper cell (Th) cytokines secreted by human cord blood mononuclear cells (CBMC) stimulated by allergens. However, to date, it has proven impossible to measure allergen-specific CBMC secretion of the key Th cytokine interleukin-4 (IL-4) using conventional sandwich ELISA techniques. We report for the first time the successful measurement of IL-4 secreted by CBMC stimulated by the allergens timothy grass pollen and house dust mite extract. The method is an adaptation of a novel cell-based ELISA (celELISA), which demonstrated an increased (up to 20-fold) sensitivity to detect IL-4. The method is simple, precise, is no more costly than a conventional ELISA, and can identify individuals in a general population whose CBMC exhibit different cytokine biases in response to allergens. The frequency distribution of IL-4 and interferon-gamma (IFN-gamma) CBMC responses to allergens in the general population approximates to a log-normal distribution, which will permit the application of linear regression techniques in the identification of in utero factors which influence Th bias.

Abnormal fucosylation of ileal mucus in cystic fibrosis: I. A histochemical study using peroxidase labelled lectins.

Peroxidase conjugated lectins were used to analyse the glycoproteins of small intestinal mucins in normal infants and those with cystic fibrosis to ascertain whether there are any detectable histochemical differences in saccharide composition. A significant decrease in Lotus tetragonolobus (LTG) binding fucose was shown in normal small intestinal mucin starting around 36 weeks' gestation with total absence of staining at term and beyond. In contrast, the age matched patients with cystic fibrosis showed persistent and intense LTG binding of fucose. These results provide the first clear histochemical evidence that cystic fibrosis mucin is abnormal and confirm the findings of previous biochemical studies.

Inhibitory effects of Montelukast on mediator release by nasal epithelial cells from asthmatic subjects with or without allergic rhinitis.

AIMS: This study tested inhibitory effects of in vitro Montelukast treatment on nasal airway epithelial cells (AEC) cultured from asthmatic patients treated with Montelukast with and without concomitant allergic rhinitis. We further examined the effect of Montelukast withdrawal in these patients on cytokine release from cultured nasal AEC. METHODS: Nasal AEC were collected by brushings from subjects with a history of stable (no exacerbations or change in medication for ≥ 1 month) physician confirmed mild/moderate asthma whose asthma symptoms were documented to benefit from Montelukast treatment (NCT01230437). Release of the following mediators by nasal AEC were measured: IL-8, IL-6, IL-10, GM-CSF, RANTES, eotaxin and IFN-γ. Nasal AEC were cultured before and one week after withdrawal of their Montelukast treatment. RESULTS: Forty two asthmatics were recruited. Nasal AEC were successfully cultured in 17 at the first assessment, 14 at the second assessment and in 10 individuals at both assessments. Nasal AEC release was no different between asthmatics with or without allergic rhinitis. Montelukast significantly suppressed the release of IL-8 (p = 0.016), IL-6 (p = 0.006), RANTES (p = 0.002) and IFN-γ (p = 0.046), in a dose dependent manner in unstimulated cultures but not in those stimulated with IL-1/TNF. Withdrawal of Montelukast treatment, was associated with increased IL-8 and RANTES secretion in unstimulated nasal AEC cultured from subjects with asthma and allergic rhinitis but not with asthma alone. CONCLUSIONS: Montelukast treatment for asthma symptoms reversibly suppresses nasal AEC release of pro-inflammatory mediators (i.e. IL-8 and RANTES) but only in those cells cultured from subjects with concomitant allergic rhinitis.