Does Having an Older Sibling Hinder Your Development?

Previous research has shown that birth order can affect a child in a number of ways, including verbal skills where there is a negative association between the number of older siblings a child has and their language skills. It has been hypothesised that this is due to parents having less time for one-to-one interactions with the younger child. A recent study looked at the language skills of a cohort of French children (n=1,154) at ages 2, 3, and 5-6 years.[1] Analysis showed that children with an older sibling scored significantly worse than children with no older siblings, but when separated by sex, children with an older sister had better language skills than children with an older brother, and were comparable to children with no older sibling. There was no significant impact associated with the age difference between children.

The authors conclude that the negative older sibling effect should be more accurately thought of as an older brother effect. A number of hypotheses are put forward for this difference, including that girls are more talkative or more willing to play with their younger siblings, and so can better contribute to language development, making up any lost parental interactions; or that girls require less parental attention, so parents can focus more on the younger child.

— Peter Chilton, Research Fellow

Reference:

1. Havron N, Ramus F, Heude B, et al. The Effect of Older Siblings on Language Development as a Function of Age Difference and Sex. Psychol Sci. 2019.

Chlamydia Vaccine

Chlamydia, is the most common bacterial sexually transmitted infection (STI), with around 218,000 new cases in the UK in 2018, accounting for 49% of all new STI diagnoses.[1] Worldwide it is estimated that there are 131 million new cases each year. Although it can be treated with antibiotics, around 75% of people with chlamydia do not show any signs of infection, and left untreated it can lead to infertility. Therefore there is a need for a preventive measure. The first ever clinical trial looking at a vaccine for genital chlamydia was recently published in Lancet Infectious Diseases.[2]

The authors conducted a phase 1 RCT in 35 women, randomly assigning them to receive one of two versions of a new chlamydia vaccine (CTH522:CAF01 or CTH522:AH) (N=15 in each arm) or a saline placebo (N=5). Thirty-two women completed the study, being given an injection at the start of the study and then again 1 and 4 months later. This was followed by intranasal administrations at 4.5 and 5 months. No serious adverse events were reported, and there was no significant differences in the incidence of reactions at the injection-site (P=0.0526), or in reactions to intranasal administration (P=1.000) when comparing either vaccine to placebo. Analyses showed that both versions of the vaccine induced an immune response in all participants, compared to none in the placebo group. When comparing the two vaccines, one (CTH522:CAF01) showed more promising results including antibodies detected earlier, higher levels of IgG antibodies, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile. With both vaccines appearing to be safe and tolerable, further clinical trials will hopefully be forthcoming.

— Peter Chilton, Research Fellow

References:

1. Public Health England. Sexually transmitted infections and screening for chlamydia in England, 2018. Health Protection Report. 2019; 13(19).
2. Abraham S, Juel HB, Bang P, et al. Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Infect Dis. 2019.

Another Very Interesting Paper on Molecular Analysis of Stool in Childhood Diarrhoea

We have previously summarised the results of a study using molecular analysis to examine samples from children with and without diarrhoea. Among many interesting findings, this showed that Shigella is one of the most common bacterial causes of childhood diarrhoea.[1][2] A further study by the same investigator team tested stool samples from 1,715 children from eight countries for presence of 29 entertopathogens.[3] This was a reanalysis of a previously published dataset (MAL-ED) using quantitative PCR methods in order to refine the aetiology estimates by increasing the pathogens tested for.

While the original study found that 32.8% of diarrhoea samples were attributable to an infectious aetiology, this new analysis found 64.9% attributable. Thus, the more rigorous method doubled the proportion of diarrhoea cases that could be attributed to a specific pathogen. Diarrhoea attributable to pathogens during the first year of life was lower (50.5%) than during the second year (82.8%). The study also found that viral diarrhoea was most common (36.4%), then bacterial (25.0%) and parasitic (3.5%). Ten pathogens accounted for 95.7% of attributable diarrhoea. Again, Shigella was shown to be the most common (26.1%), followed by sapovirus (22.8%) and rotavirus (20.7%).

The CLAHRC WM Director has questions:

1. What causes the unattributable cases, especially in the first year of life?
2. Did all cases really have diarrhoea? It is a diagnosis that is partly ‘in the eye of the beholder’.[4]
3. Contrary wise, how can we be sure that the agent detected was causal of the condition?

— Richard Lilford, CLAHRC WM Director
— Peter Chilton, Research Fellow

References:

1. Liu J, Platts-Mills JA, Juma J, et al. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet. 2016; 388: 1291-301.
2. Lilford RJ. Did You Ever Want to Know What Bugs Were Actually in Diarrhoea? NIHR CLAHRC West Midlands News Blog. 11 November 2016.
3. Platts-Mills JA, Liu J, Rogawski ET, et al. Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study. Lancet Glob Health. 2018; 6(12): e1309-18.
4. Lilford RJ. Childhood Diarrhoeal Diseases – Update of the Famous Wolf Review. NIHR CLAHRC West Midlands News Blog. 19 October 2018.

Use of a Menstrual Cup

There is a rising awareness of ‘Period Poverty’ [1] where girls and women simply cannot afford a constant supply of menstrual products. While this is a particular concern in low- and middle-income countries (LMICs), it also affects people in high-income countries, such as the UK where 10% of girls have reported being unable to afford menstrual products.[2] With choices limited, a lack of affordable and effective products can result in leakage, chaffing and increase the risk of urogenital infections, as well as lead to social stigma and a negative impact on schooling and employment. Many argue that reusable products would be a more effective alternative to single-use products currently favoured by agencies providing aid in LMICs settings.

A systematic review published in the Lancet Public Health looked at evidence from 43 studies on the effectiveness of using a menstrual cup.[3] Fifteen of these studies were conducted in low- and middle-income countries. Four studies looked at leakage compared to usual products, finding comparable results. Overall, the authors found that the use of menstrual cups were a safe option for managing menstruation, with very few serious adverse events reported. However, as menstrual cups need to be manually removed with clean hands and cleaned thoroughly before being used again, there may be a greater risk in areas with poor facilities.

Although the conclusions are promising, more good quality studies are needed, as only two of the quantitative studies analysed were of moderate-to-high quality. Furthermore, studies regarding cost-effectiveness and environmental effects are also required, though the authors estimated significant savings compared to both sanitary pads and tampons.

In light of this study there is also a need for information regarding menstrual cups to be made more prominent in educational materials, especially as participants reported using a menstrual cup required a period of familiarisation.

— Peter Chilton, Research Fellow

References:

1. George A. The Shame of Period Poverty is Keeping British Girls Out of School. Let’s Break the Silence. The Guardian. 19 December 2017.
2. Plan International UK. Research on Period Poverty and Stigma. 20 December 2017.
3. van Eijk AM, Zulaika G, Lenchner M, et al. Menstrual Cup Use, Leakage, Acceptability, Safety, and Availability: a Systematic Review and Meta-Analysis. Lancet Public Health. 2019.

Rotavirus Vaccine

Gastroenteritis as a result of rotavirus infection is a major cause of morbidity and mortality among children under 5 years old, with around 215,000 deaths in 2013.[1] Thankfully there is now a vaccine available, and hospital admissions and deaths have been shown to have declined significantly since its introduction. However, not all countries have incorporated the rotavirus vaccine into their national immunisation programmes. A recent paper in Lancet Global Health used data from the WHO-coordinated Global Rotavirus Surveillance Network to look at the impact the vaccine has had worldwide, as it had not previously been analysed using primary data.[2]

More than 400,000 children from 82 countries were admitted to hospital with acute gastroenteritis over the study period, with around one-third being tested positive for rotavirus. The impact analysis of the study looked at a subset of ~300,000 children and found that there was a decline of 39.6% (95% CI 35.4-43.8) in admissions in countries that had introduced the vaccine into their immunisation programme, compared to the years before, resulting in rotavirus being detected in around 23% of admissions. Meanwhile, in countries that did not include the vaccine there was no significant change in rotavirus detected over time, remaining stable at around 38% of admissions. Further, in countries that had introduced the vaccine, the age distribution of children that tested positive for rotavirus gastroenteritis was skewed towards older children, perhaps as a result of the improved protection.

References:

1. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD; World Health Organization-Coordinated Global Rotavirus Surveillance Network. Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000–2013. Clin Infect Dis. 2016; 62: S96-S105.
2. Aliabadi N, Antoni S, Mwenda JM, et al. Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008–16: findings from the Global Rotavirus Surveillance Network. Lancet Glob Health. 2019; 7(7): e893-903.

Nutritional Interventions for Childhood Stunting in Slums

For many people living in slums, getting sufficient food is a challenge, especially when children are involved. A lack of proper nutrition is one of many risk factors for stunting in children, which can lead to increased risk of infection, cognitive and behavioural problems, and lower work performance and earnings as an adult. Various interventions have been shown to successfully reduce the incidence of childhood stunting, including interventions focussed on nutrition. However, these have not been extensively assessed in urban slums.

A team of researchers from Loughborough University recently conducted a Cochrane systematic review looking at this, finding 15 studies that were conducted in slums or poor urban areas, primarily in Bangladesh, India and Peru.[1] Fourteen of the studies were RCTs, and all looked at nutrient supplementation or educational interventions. In total the studies included 9,261 infants and 3.664 pregnant women.

The studies did not take into account the unique challenges found in slums (such as high mobility, lack of social services, and high loss of participants to follow-up) in their design stages, which meant they had low to moderate reliability. Even so, the authors were able to conclude that nutritional interventions in slums had not been successful in decreasing childhood stunting as expected (based on evidence from non-slums). Future research will not only need to take into account the slum environment, but also combine multi-sectoral components, innovative targeting and have long-term follow-up.

— Peter Chilton, Research Fellow

Reference:

1. Goudet SM, Bogin BA, Madise NJ, Griffiths PL. Nutritional interventions for preventing stunting in children (birth to 59 months) living in urban slums in low‐ and middle‐income countries (LMIC). Cochrane Database Syst Rev. 2019: CD011695.

Physical Fitness, Obesity and Mortality

Although we know that poor physical fitness and being overweight may indicate an unhealthy lifestyle, and be predictive of an early death, there is debate about the relative importance of fitness and weight in relation to one another. For example, some meta-analyses have concluded that people who were overweight yet physically fit had no significant increase in mortality compared to those who were of normal weight.[1] [2]

A recent paper by researchers from the University of Leicester [3] used data from a UK Biobank prospective cohort study to look for any associations between physical fitness (as measured by walking pace and handgrip strength) and life expectancy, at various levels of BMI. They analysed data from 474,919 participants who had been followed-up for a median average of ~7 years. Those who had reported a brisk walking pace were found to have a significantly longer life expectancy than slow walkers (hazard ratios for mortality of 0.48 [95% CI 0.46-0.51] in males and 0.47 [95% CI 0.45-0.49] in females), and this was true at all levels of BMI. For 45 year olds who were brisk walkers, life expectancy across all levels of BMI ranged from 86.7-87.8 in females, and 85.2-86.8 in males. For slow walkers the range was 72.4-85.0 in females, and 64.8-81.2 in males. There were smaller, but still significant, differences in mortality when comparing handgrip strength between those with the highest and lowest results.

— Peter Chilton, Research Fellow

References:

1. Barry VW, Caputo JL, Kang M. The Joint Association of Fitness and Fatness on Cardiovascular Disease Mortality: a meta-analysis. Prog Cardiovasc Dis. 2018; 61: 136-41.
2. Ortega FB, Cadenas-Sanchez C, Migueles JH, et al. Role of physical activity and fitness in the characterization and prognosis of the metabolically healthy obesity phenotype: a systematic review and meta-analysis. Prog Cardiovasc Dis. 2018; 61: 190-205.
3. Zaccardi F, Davies MJ, Khunti K, Yates T. Comparative Relevance of Physical Fitness and Adiposity on Life Expectancy. Mayo Clin Proceed. 2019.

Using Machine Learning to Diagnose Childhood Depression

Although we may think of childhood as a care-free time, it is estimated that as many as one in five children develop depression or anxiety, with it even being seen in children as young as four years old. Unfortunately, due to the abstract nature of the emotions involved, children are often unable to clearly communicate their problems. Further, signs are not easily recognised by parents. This can lead to a lack of support, and eventually cause the child to internalise their disorders, something that is associated with long-term negative outcomes. Current diagnosis requires long interviews with trained clinicians, which can further hinder assessment. However, researchers at the universities of Vermont and Michigan have developed a new approach for identifying such children using machine learning.[1] This involves tasking the children with preparing and then presenting a three-minute speech that is then interrupted after 90 and 150 seconds by a buzzer. Caregivers were then interviewed for 1-2 hours using the gold standard technique (K-SADS-PL), and completed questionnaires in order for a standard diagnosis to be provided for the child. Subsequent machine analysis of the audio data was able to identify signs of depression and anxiety in the children’s speech patterns with 80% accuracy (54% sensitivity, 93% specificity). In comparison, identifying children with depression and anxiety using the Child Behaviour Checklist (a 15-minute, parent-reported questionnaire) was found to have a lower accuracy (67-77%), though with similar sensitivity and specificity.

This process is significantly quicker and easier than the current methods used, and can hopefully led to earlier diagnosis and ensure children get the help they need while they are still developing.

— Peter Chilton, Research Fellow

Reference:

1. McGinnis EW, Anderau SP, Hruschak J, et al. Giving Voice to Vulnerable Children: Machine Learning Analysis of Speech Detects Anxiety and Depression in Early Childhood. IEEE J Biomed Health Inform. 2019; 1.

How Many Cigarettes in a Bottle of Wine?

We have talked before about the effects alcohol has on health – ranging from studies showing protective effects against dementia and Alzheimer’s disease,[1] to increasing risk of structural brain changes and cognitive decline.[2] While there have been studies looking at association between alcohol and cancer rates,[3] the general public do not think of cancer when asked to list health risks of drinking (only 13% of adults surveyed were aware of the putative association between alcohol and cancer).[4] A recent paper in the BMC Public Health calculated the lifetime risk of developing alcohol-related cancers and equated this to the risk from smoking.[5]

The authors found that drinking one bottle of wine per week was associated with an increase in the absolute risk of developing cancer during a lifetime of 1.0% in non-smoking men, and 1.4% in non-smoking women. The gender difference was predominantly driven by an increased risk of developing breast cancer. They calculated that this was “equivalent” to a weekly smoking habit of five (for men) or ten (for women) cigarettes.

Although moderate alcohol intake is not equivalent to smoking, there is an argument to increase the level of public health awareness on the risk of cancer from drinking, especially among women. Using cigarettes as an equivalent may help communicate the message of risk more effectively.

— Peter Chilton, Research Fellow

References:

1. Lilford RJ. So Where Are We Up to With Alcohol And Health? NIHR CLAHRC West Midlands News Blog. 12 January 2018.
2. Lilford RJ. Alcohol and its Effects. NIHR CLAHRC West Midlands News Blog. 18 August 2017.
3. Lilford RJ. Oh Dear – Evidence Against Alcohol Accumulates. NIHR CLAHRC West Midlands News Blog. 7 December 2017.
4. Buykx P, Li J, Gavens L, et al. Public awareness of the link between alcohol and cancer in England in 2015: a population-based survey. BMC Public Health. 2016;16:1194.
5. Hydes TJ, Burton R, Inskip H, Bellis MA, Sheron N. A comparison of gender-linked population cancer risks between alcohol and tobacco: how many cigarettes are there in a bottle of wine? BMC Public Health. 2019.

Detecting the Smell of Parkinson’s Disease

Diagnosis of Parkinson’s disease is usually through a variety of physical exercises conducted with specialists, looking for two of three symptoms – a tremor at rest, slowness of movement, muscle stiffness. Diagnosis can also be aided if symptoms are improved after taking levodopa, or through brain scans. However, there is no diagnostic chemical test. At least, not yet. Recently, a team based at the University of Manchester detailed a specific odour found in the sebum from patients with Parkinson’s disease that can be detected.[1]

A few years ago a small study tested a member of the public who claimed to be able to detect a distinctive smell on patients with Parkinson’s disease.[2] Given clothing from 12 individuals (six with Parkinson’s disease, six without) she was correctly able to identify their diagnosis in 11 cases. Amazingly, however, the control subject that she misidentified was later diagnosed with Parkinson’s disease, giving her a 100% accuracy rate. On the basis of this, researchers began to investigate what could cause this distinctive odour, finding that it was present in the sebum (an oily secretion of the body that coats the skin) of patients’ upper backs.

The present study conducted mass spectrometry and olfactory analysis of sebum samples from 64 participants (43 with Parkinson’s disease), which were then combined, revealing a unique volatilome (odour profile) that was associated with Parkinson’s disease. This was then validated using an independent cohort of 31 participants. It is hoped that further studies can help further characterise this volatilome, and eventually led to a panel of biomarkers associated with Parkinson’s disease.

— Peter Chilton, Research Fellow

References:

1. Trivedi DK, Sinclair E, Xu Y, et al. Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum. ACS Cent Sci. 2019.
2. Morgan J. Joy of super smeller: sebum clues for PD diagnostics. Lancet Neurol. 2016; 15(2): 138-9.