29 research outputs found
Ethnic differences in kidney function in childhood: the Born in Bradford Cohort Renal Study [version 1; peer review: awaiting peer review]
No full textBackground: Endstage kidney failure rates are higher in South Asians
than in White Europeans. Low birth weight is associated with adult
chronic kidney disease and is more common in South Asians. Foetal
kidney size was smaller in South Asians in the Born in Bradford (BiB)
birth cohort. As part of BiB follow up, we aimed to investigate if there
were ethnic differences in kidney function and blood pressure in early
childhood and whether this was mediated by foetal kidney size.
Methods: Serum creatinine, cystatin C, urea, and urinary albumin to
creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol
binding protein (RBP) were analysed in blood and urine samples from
those who participated in the BiB follow-up at 7-11 years. Ethnicity
was categorised by parental self-report as White European and South
Asian. Estimated glomerular filtration rate (eGFR) was calculated using
Schwartz, and cystatin C Zappitelli and Filler equations. Linear
regression was used to examine the association between ethnicity
and eGFR, PCR and blood pressure.
Results: 1591 children provided blood (n=1403) or urine (n=625)
samples. Mean eGFR was 92 ml/min/1.73m2 (standard deviation (SD)
9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257).
CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m2, 14 (2.4%)
had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic
blood pressure was higher in South Asian children (difference 2.04
mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models
between ethnicity and any eGFR or urinary measure at this age.
Conclusions: There was no evidence of significant ethnic differences
in kidney function at pre-pubertal age despite differences in kidney
volume at birth. Longitudinal follow-up is required to track ethnic
patterns in kidney function and blood pressure as children develop
through puberty
Role of foetal kidney size on kidney function in childhood: the born in bradford cohort renal study
No full textBackground: Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7–11 years. Methods: Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm 3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7–11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. Results: Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. Conclusion: Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required. </p
Cytomegalovirus, Epstein-Barr virus and varicella zoster virus infection in the first two years of life: a cohort study in Bradford, UK.
No full textBACKGROUND: Cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella-zoster virus (VZV) are common herpesviruses frequently acquired in childhood, which establish persistent, latent infection and are likely to impact the developing immune system. Little is known about the epidemiology of CMV and EBV infections in contemporary UK paediatric populations, particularly whether age at infection differs by ethnic group. METHODS: Children enrolled in the Born in Bradford Allergy and Infection Study had a blood sample taken and a questionnaire completed at 12 and 24 months of age. Ordered logistic regression quantified associations between ethnicity and other risk factors and age at CMV/EBV/VZV infection (<12 months, 12-24 months, uninfected at 24 months). RESULTS: Pakistani children (n = 472) were more likely to be infected with CMV and EBV at a younger age than White British children (n = 391) (CMV: adjusted odds ratio (OR) 2.53, 95% confidence interval (CI) 1.47-4.33; EBV: adjusted OR 2.16, 95% CI 1.43-3.26). Conversely, Pakistani children had lower odds of being VZV infected in the second year than White British children (adjusted OR 0.57, 95% CI 0.33-0.97). There was a strong association between increasing birth order and later CMV infection in Pakistani children. CONCLUSIONS: We report large differences in CMV and EBV incidence in the first 2 years between Pakistani and White British children born in Bradford, which cannot be explained by differences in risk factors for infection. Our data will inform the optimum schedule for future CMV and EBV vaccination programmes
Maternal iodine status in a multi-ethnic UK birth cohort: associations with autism spectrum disorder
No full textBackground: maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring.Methods: urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26–28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child’s primary care records through a series of logistic regression models with restricted cubic splines.Results: median (inter-quartile range) UIC was 76 μg/L (46, 120) and I:Cr was 83 μg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8–12 years (p = 0·3).Conclusions: there was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight
Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort
No full textBackgroundSevere iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes.MethodsMaternal iodine status was estimated from spot urine samples collected at 26–28 weeks’ gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score.ResultsThere was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies.ConclusionLower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered
Prenatal and Postpartum Maternal Iodide Intake from Diet and Supplements, Urinary Iodine and Thyroid Hormone Concentrations in a Region of the United Kingdom with Mild-to-Moderate Iodine Deficiency
No full textIodine is essential for normal thyroid function, supporting healthy fetal and child development. Io-dine requirements increase in pregnancy, but many women in regions without salt iodisation have insufficient intakes. We explored associations between iodide intake and urinary iodine concentra-tion (UIC), urinary iodine:creatinine ratio (I:Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. 246 pregnant women aged 18-40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter, at around 12, 26 and 36 weeks gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24-hour re-calls. During pregnancy, median (IQR) dietary iodide intake was 101µg/day (54, 142), with 42% from dairy and 9% white fish. Including supplements, intake was 143µg/day (94, 196), with 49% < UK reference nutrient intake (140µg/day). Women with Pakistani heritage had 129µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) high-er UIC, 5% (3%, 7%) higher I:Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I:Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency
Maternal iodine status in a multi-ethnic UK birth cohort: associations with child cognitive and educational development
No full textBackground: Maternal iodine requirements increase during pregnancy to supply thyroid hormones critical for fetal neurodevelopment. Iodine insufficiency may result in poorer cognitive or child educational outcomes but current evidence is sparse and inconsistent. Objectives: To quantify the association between maternal iodine status and child educational outcomes. Methods: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6971 mothers at 26-28 weeks' gestation participating in the Born in Bradford cohort. Maternal iodine status was examined in relation to child school achievement (early years foundation stage (EYFS), phonics, and Key Stage 1 (KS1)), other learning outcomes, social and behavioural difficulties, and sensorimotor control in 5745 children aged 4-7 years. Results: Median (interquartile range) UIC was 76 µg/L (46, 120), and I:Cr was 83 µg/g (59, 121). Overall, there was no strong or consistent evidence to support associations between UIC or I:Cr and neurodevelopmental outcomes. For instance, predicted EYFS and phonics scores (primary outcomes) at the 25th vs 75th I:Cr percentiles (99% confidence intervals) were similar, with no evidence of associations: EYFS scores were 32 (99% CI 31, 33) and 33 (99% CI 32, 34), and phonics scores were 34 (99% CI 33, 35) and 35 (99% CI 34, 36), respectively. Conclusions: In the largest single study of its kind, there was little evidence of detrimental neurodevelopmental outcomes in children born to pregnant women with iodine insufficiency as defined by World Health Organization–outlined thresholds. Alternative functional biomarkers for iodine status in pregnancy and focused assessment of other health outcomes may provide additional insight.</p
Metabolomics datasets in the Born in Bradford cohort [version 1; peer review: awaiting peer review]
No full textMetabolomics is the quantification of small molecules, commonly known as metabolites. Collectively, these metabolites and their interactions within a biological system are known as the metabolome. The metabolome is a unique area of study, capturing influences from both genotype and environment. The availability of high-throughput technologies for quantifying large numbers of metabolites, as well as lipids and lipoprotein particles, has enabled detailed investigation of human metabolism in large-scale epidemiological studies. The Born in Bradford (BiB) cohort includes 12,453 women who experienced 13,776 pregnancies recruited between 2007-2011, their partners and their offspring. In this data note, we describe the metabolomic data available in BiB, profiled during pregnancy, in cord blood and during early life in the offspring. These include two platforms of metabolomic profiling: nuclear magnetic resonance and mass spectrometry. The maternal measures, taken at 26-28 weeks' gestation, can provide insight into the metabolome during pregnancy and how it relates to maternal and offspring health. The offspring cord blood measurements provide information on the fetal metabolome. These measures, alongside maternal pregnancy measures, can be used to explore how they may influence outcomes. The infant measures (taken around ages 12 and 24 months) provide a snapshot of the early life metabolome during a key phase of nutrition, environmental exposures, growth, and development. These metabolomic data can be examined alongside the BiB cohorts' extensive phenotype data from questionnaires, medical, educational and social record linkage, and other 'omics data
Ethnic differences in kidney function in childhood: the Born in Bradford Cohort Renal Study
No full textBackground: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was different by foetal kidney size. Methods: Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. Results: 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m 2 (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m 2, 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. Conclusions: There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty
The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.
No full textBackground: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD
