Tom Norris

Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study

Although many studies have investigated the overlap between pain phenotypes and chronic fatigue syndrome (CFS) in adults, little is known about the relationship between these conditions in adolescents. The studys aim was therefore to identify whether a relationship exists between chronic widespread pain (CWP) and CFS in adolescents and investigate whether the two share common associations with a set of covariates. A questionnaire was administered to offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 17, asking about site, duration, and pain intensity, from which participants with CWP were identified. At the same research clinic, a computer-based Revised Clinical Interview Schedule was filled out, from which a classification of CFS was obtained. The relationship between selected covariates and CFS and CWP was investigated using a variety of logistic, ordinal logistic, and multinomial regressions. We identified 3,214 adolescents with complete data for all outcomes and covariates. There were 82 (2.6%) individuals classified as CFS and 145 (4.5%) as CWP. A classification of CFS resulted in an increased likelihood of having CWP (odds ratio = 3.87; 95% confidence interval, 2.05–7.31). Female adolescents were approximately twice as likely to have CFS or CWP, with multinomial regression revealing a greater sex effect for CWP compared with CFS. Those with exclusive CFS were more likely to report higher levels of pain and greater effect of pain compared with those without CFS, although associations attenuated to the null after adjustment for covariates, which did not occur in those with exclusive CWP. Multinomial regression revealed that relative to having neither CFS nor CWP, a 1-unit increase in the depression and anxiety scales increased the risk of having exclusive CFS and, to a greater extent, the risk of having comorbid CFS and CWP, but not exclusive CWP, which was only related to anxiety. Perspective In this cohort, 14.6% of adolescents with CFS have comorbid CWP. The likely greater proportion of more mild cases observed in this epidemiological study means that prevalence of overlap may be underestimated compared with those attending specialist services. Clinicians should be aware of the overlap between the 2 conditions and carefully consider treatment options offered.

Causes and temporal changes in nationally collected stillbirth audit data in high-resource settings.

Few high-income countries have an active national programme of stillbirth audit. From the three national programmes identified (UK, New Zealand, and the Netherlands) steady declines in annual stillbirth rates have been observed over the audit period between 1993 and 2014. Unexplained stillbirth remains the largest group in the classification of stillbirths, with a decline in intrapartum-related stillbirths, which could represent improvements in intrapartum care. All three national audits of stillbirths suggest that up to half of all reviewed stillbirths have elements of care that failed to follow standards and guidance. Variation in the classification of stillbirth, cause of death and frequency of risk factor groups limit our ability to draw meaningful conclusions as to the true scale of the burden and the changing epidemiology of stillbirths in high-income countries. International standardization of these would facilitate direct comparisons between countries. The observed declines in stillbirth rates over the period of perinatal audit, a possible consequence of recommendations for improved antenatal care, should serve to incentivise other countries to implement similar audit programmes.

Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study

ObjectiveTo describe 20-year risk factor trajectories according to initial weight/health status and investigate the extent to which baseline differences explain greater mortality among metabolically healthy obese (MHO) individuals than healthy non-obese individuals.MethodsThe sample comprised 6529 participants in the Whitehall II study who were measured serially between 1991–1994 and 2012–2013. Baseline weight (non-obese or obese; body mass index (BMI) ≥30 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance (HOMA-IR)) were defined. The relationships of baseline weight/health status with 20-year trajectories summarizing ~25,000 observations of systolic and diastolic blood pressures, HDL-C, triglycerides, glucose, and HOMA-IR were investigated using multilevel models. Relationships of baseline weight/health status with all-cause mortality up until July 2015 were investigated using Cox proportional hazards regression.ResultsTrajectories tended to be consistently worse for the MHO group compared to the healthy non-obese group (e.g., glucose by 0.21 (95% CI 0.09, 0.33; p < 0.001) mmol/L at 20-years of follow-up). Consequently, the MHO group had a greater risk of mortality (hazard ratio 2.11 (1.24, 3.58; p = 0.006)) when the referent group comprised a random sample of healthy non-obese individuals. This estimate, however, attenuated (1.34 (0.85, 2.13; p = 0.209)) when the referent group was matched to the MHO group on baseline risk factors.ConclusionsWorse baseline risk factors may explain any difference in mortality risk between obese and non-obese groups both labelled as healthy, further challenging the concept of MHO.

Do changing levels of maternal exercise during pregnancy affect neonatal adiposity? Secondary analysis of the babies after SCOPE: evaluating the longitudinal impact using neurological and nutritional endpoints (BASELINE) birth cohort (Cork, Ireland)

Objective To investigate whether changing levels of exercise during pregnancy are related to altered neonatal adiposity. Design Secondary analysis of data from a prospective cohort study. Setting Cork, Ireland. Participants 1200 mother–infant pairs recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). Main outcome measures Neonatal adiposity was assessed within several days of birth using air displacement plethysmography (PEAPOD). Per cent body fat (BF%) as a continuous outcome and a pair of dichotomous variables; high or low adiposity, representing BF% >90th or <10th centile, respectively. Multivariable linear and logistic regression models were used to investigate the relationship between exercise and the respective outcomes. Results Crude analysis revealed no association between a changing level of exercise (since becoming pregnant) at 15 weeks’ gestation and any of the outcomes (BF%, low adiposity and high adiposity). At 20 weeks’ gestation, analyses revealed that relative to women who do not change their exercise level up to 20 weeks, those women who decreased their exercise level were more likely to give birth to a neonate with adiposity above the 90th centile (OR 1.62, 95% CI 1.07 to 2.46). This association was maintained after adjustment for putative confounders (OR 1.62, 95% CI 1.06 to 2.47). Conclusions We observed a possible critical period for the association between changing exercise levels and neonatal adiposity, with no association observed with exercise recall for the first 15 weeks of gestation, but an association with a decreasing level of exercise between 15 and 20 weeks. These results should be interpreted in line with the limitations of the study and further studies utilising objectively measured estimates of exercise are required in order to replicate these findings. Trial registration number NCT01498965.

Updated birth weight centiles for England and Wales

Objectives Construct updated birth weight-for-gestational age centile charts for use in the UK and compare these to the currently used UK-WHO charts. Design Secondary analysis of national birth data. Participants Centiles were constructed using 1 269 403 singleton births occurring in England and Wales in 2013–2014 as part of the MBRRACE-UK national perinatal surveillance programme. These were then validated using 642 737 singleton births occurring in England and Wales in 2015. Main outcome measures Sex-specific birth weight-for-gestational age centiles. Centiles were created using the lambda-mu-sigma method via the GAMLSS package in R. This method transforms the skewed birth weight distribution to approximate a normal distribution, allowing any birth weight centile to be produced. Results The new centiles performed well in the validation sample, with the observed and expected proportion of births below a given centile in agreement. Overall, driven by the predominance of term births, the UK-WHO charts classify a smaller proportion of infants as below a given centile. For example, the UK-WHO estimates classified only 1.32% (8035/606 430) of term infants born in 2015 as below the second centile, compared with 1.97% (11 975/606 430) using the new MBRRACE-UK centiles. At the earliest gestational ages, however, the opposite is observed, with the UK-WHO classifying a larger proportion of infants as below a given centile, particularly at the lower end of the birthweight distribution. Conclusions We have constructed and validated updated birth weight-for-gestational age centiles using a contemporary sample of births occurring in England and Wales. The benefits of these updated centiles will be first to assist the national surveillance of perinatal mortality programme by improving the identification of the proportion of stillbirths and neonatal deaths affected by intrauterine growth restriction and, second, to aid clinicians by more accurately identifying babies who require increased monitoring in the period immediately following birth.

Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort

Objective/Background Sleep abnormalities are characteristic of chronic fatigue syndrome (CFS, also known as ‘ME’), however it is unknown whether sleep might be a causal risk factor for CFS/ME. Patients/Methods We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We describe sleep patterns of children aged 6 months to 11 years, who were subsequently classified as having (or not having) ‘chronic disabling fatigue’ (CDF, a proxy for CFS/ME) between the ages 13 and 18 years, and we investigated the associations of sleep duration at age nine years with CDF at age 13 years, as well as sleep duration at age 11 years with CDF at age 16 years. Results Children who had CDF during adolescence had shorter night-time sleep duration from 6 months to 11 years of age, and there was strong evidence that difficulties in going to sleep were more common in children who subsequently developed CDF. The odds of CDF at age 13 years were 39% lower (odds ratio (OR) = 0.61, 95% CI = 0.43, 0.88) for each additional hour of night-time sleep at age nine years, and the odds of CDF at age 16 years were 51% lower (OR = 0.49, 95% CI = 0.34, 0.70) for each additional hour of night-time sleep at age 11 years. Mean night-time sleep duration at age nine years was 13.9 (95% CI = 3.75, 24.0) minutes shorter among children who developed CDF at age 13 years, and sleep duration at age 11 years was 18.7 (95% CI = 9.08, 28.4) minutes shorter among children who developed CDF at age 16 (compared with children who did not develop CDF at 13 and 16 years, respectively). Conclusions Children who develop chronic disabling fatigue in adolescence have shorter night-time sleep duration throughout early childhood, suggesting that sleep abnormalities may have a causal role in CFS/ME or that sleep abnormalities and CFS/ME are associated with a common pathophysiological cause.

Factors associated with catch-up growth in early infancy in rural Pakistan: a longitudinal analysis of the Women's Work and Nutrition Study

Abstract The adverse health impacts of early infant stunting can be partially ameliorated by early catch‐up growth. Few studies have examined predictors of and barriers to catch‐up growth to identify intervention points for improving linear growth during infancy. This study aimed to estimate the prevalence of, and factors associated with, catch‐up growth among infants in Pakistan. A longitudinal study of mother–infant dyads (n = 1,161) was conducted in rural Sindh province, with enrolment between December 2015 and February 2016 (infants aged 0.5–3 months), and follow‐up (n = 1035) between November 2016 and January 2017 (infants aged 9–15 months). The outcome was catch‐up growth (change in conditional length‐for‐age z‐scores >0.67 between baseline and endline). Associated factors were examined using multivariable logistic regression analyses. The prevalence of stunting was 45.3% at baseline and 60.7% at follow‐up. 22.8% of infants exhibited catch‐up growth over this period. Factors positively associated with catch‐up growth included maternal height (odds ratio (OR) = 1.08 [1.05–1.11]), household wealth (OR = 3.61 [1.90–6.84]), maternal (OR = 2.43 [1.30–4.56]) or paternal (OR = 1.46 [1.05–2.03]) education, and households with two or more adult females (OR = 1.91 [1.26–2.88]). Factors negatively associated with catch‐up growth were two (OR = 0.64 [0.45–0.89]) or three or more (OR = 0.44 [0.29–0.66]) preschool children in the household and the infant being currently breastfed (OR = 0.59 [0.41–0.88]). Catch‐up growth was exhibited among approximately a quarter of infants despite living in challenging environments associated with extremely high rates of early infant stunting. Several modifiable factors were identified that might represent suitable programme intervention points to off‐set early infant stunting in rural Pakistan.

Investigating the relationship between fetal growth and academic attainment: secondary analysis of the Born in Bradford (BiB) cohort

Abstract Background The relationship between ultrasongraphically derived estimates of fetal growth and educational attainment in the postnatal period is unknown. Results from previous studies focusing on cognitive ability, however, suggest there may be gestation-specific associations. Our objective was to model growth in fetal weight (EFW) and head circumference (HC) and identify whether growth variation in different periods was related to academic attainment in middle childhood. Methods Data come from the Born in Bradford (BiB) cohort study, which has performed data linkage to both routine antenatal scans and national academic attainment tests at age 6–7 years. Multilevel linear spline models were used to model EFW and HC. Random effects from these were related to Key Stage 1 (KS1) results in reading, writing, mathematics, science and a composite of all four (age 6–7 years), using ordinal logistic and logistic regression. Associations were adjusted for potential confounders, facilitated by directed acyclic graphs. Missing covariate data were imputed using multiple imputation. Results In all, 6995 and 8438 children had complete KS1, and EFW and HC data, respectively. Positive associations were observed between both fetal weight in early pregnancy (14 weeks) and EFW growth in mid-pregnancy (14-26 weeks) and the individual KS1 outcomes. Furthermore, after adjustment for previous size and confounders, a 1-z score increase in growth in mid-pregnancy was associated with an 8% increased odds of achieving the expected standard for all KS1 outcomes [odds ratio (OR): 1.08, 95% confidence interval (CI): 1.02; 1.13]. Similar results were observed for HC, with generally larger effect sizes. Smaller associations were observed with growth in the early-third trimester, with no associations observed with growth in the later-third trimester. Conclusions We observed consistent positive associations between fetal size and growth in early and mid-gestation and academic attainment in childhood. The smaller and null associations with growth in the early-third and later-third trimester, respectively, suggests that early-mid gestation may be a sensitive period for future cognitive development.