Tag Archives: Children

What Do You Think When You Hear ‘Scientist’?

If you have spent much time in universities you may have seen various stickers or leaflets raising awareness of campaigns that support women in STEM fields (science, technology, engineering and mathematics). There has been a push in recent years to get more girls and women into STEM subjects. Fifty-two percent of those who graduated in STEM disciplines in 2014 were female.[1] This varies widely between disciplines though, with females making up around 80% of graduates in subjects allied to medicine or veterinary sciences, but only around 15% in computer science or engineering and technology. While the gender balance of all STEM graduates are roughly equal, this is not reflected in employment however, with figures suggesting around 23% of employees in UK STEM industries are female,[1] while data from the UNESCO Institute for Statistics less than 30% of scientific researchers worldwide are female.[2]

Does the future hold more promise? A meta-analysis by Miller and colleagues looked at fifty years worth of studies where school children were asked to draw a scientist and examined the genders depicted.[3] They found that over time the percentage showing female scientists has increased – from 0.6% in data collected in 1966-77 to around 40% in 2015. However, when looking at the age of children (in studies since the 1980s) they found that while there was roughly equal representation of male and female scientists among 5 and 6 year olds, by the age of 7-8 years significantly more men were drawn. In the drawings made by girls only, the switch from predominantly female to male depictions happened around 10-11 years. Perhaps with an increase in female representation in STEM roles, especially in public, then young girls might be more likely to see themselves in such a field and thus increase the proportion in the workplace. Equally more needs to be done to emphasise gender equality at these key developmental milestones.

— Peter Chilton, Research Fellow

References:

  1. WISE Campaign for Gender Balance in Science, Technology & Engineering. Women in STEM workforce 2017. 24 October 2017.
  2. UNESCO Institute for Statistics. Women in Science. Fact Sheet No. 43. March 2017.
  3. Miller DI, Nolla KM, Eagly AH, Uttal DH. The Development of Children’s Gender-Science Stereotypes: A Meta-analysis of 5 Decades of U.S. Draw-A-Scientist Studies. Child Development. 2018.
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Immunisation Against Rotavirus: At What Age Should it be Given?

A three way RCT [1] from Thailand shows that rotavirus vaccine is effective in reducing the incidence of diarrhoea in children (which we know), and that a neonatal schedule is no less effective and probably more effective than an infant schedule. Giving the vaccine early may reduce the risk of intussusception – apparently a risk with the infant schedule.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Bines JE, At Thobari J, Satria CD, et al. Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth. New Engl J Med. 2018; 378(8): 719-30.

The Health Economics of Infertility Treatment

Recently I found myself holding forth on the above topic in a plenary talk at the International Federation of Fertility Societies combined meeting with the African Fertility Society in Kampala. I made the point that the health economics of infertility raises a number of issues that are not generally considered in the standard canon for health economic assessment of health technology assessments (HTA).[1] Four issues stand out:

  1. The benefits of infertility treatment are more difficult to capture on a single quality of life (QoL) scale than in the case for standard HTA.
  2. The standard practice of discounting benefits can be questioned.
  3. The beneficiaries are more diverse, potentially extending to many family members.
  4. The issue of whether the lifelong utility of the potential child should be include is controversial.

I shall briefly consider these in turn.

  1. Benefit – generic quality of life (QoL) scales do not seem up to the job. First, it is very difficult to capture the benefits over a lifetime. The ‘area under the curve’ is the important relevant quantity and this is not well captured in cross-sectional studies. Second, QoL deteriorates when a sub-fertile couple have a baby, as it does for fertile people. I discovered this many years ago in a collaborative study with the Health Economics department at the University of York (unpublished). This finding reinforces the importance of a lifetime perspective. Third, it is doubtful that maximisation of the dimensions captured in a generic QoL scale are the things that people wish to maximise when they decide to have children – there is a deeper purpose in play. So, a utility function based on a direct trade-off would be preferable to a standard generic QoL scale, such as the SF-12 or EQ-5D. This way, the respondent can take a lifetime perspective and factor in all the valued benefits and disbenefits of treatment. Torrance used a standard gamble on a large study of US citizens and measured a disutility of 0.07 (utility 0.93).[2] That is to say, the average respondent would run up to a 7% risk of death to enable them to have a first child. Such a standard gamble method would likely underestimate the utility loss for those who actually experience infertility for reasons David Arnold and I explicated elsewhere.[3] A perhaps better method to capture the benefit over a lifetime would be willingness-to-pay studies and here, in addition to studies at the population level (say using discrete choice methods), studies of revealed preferences are possible. This is because much IVF takes place in an entirely private market. This enables the ‘market clearing’ price for infertility services to be observed (ideally in relation to disposable income). The high proportions of disposable incomes infertile people allocate to infertility treatment, sometimes amounting to catastrophic losses,[4] provides some evidence that Torrance’s study underestimates the trade-offs people will make in order to have children.
  2. Choice of discount rate – The fact that benefits continue to accrue, and may increase, over time, suggests that discounting may not be normative. Given that disbenefits generally precede benefits, it makes little sense to discount from the point of intervention. That said, it is important to factor disbenefits of treatment and downstream costs into the analysis. Disbenefits include the cost and discomfort of treatment and knock-on costs, for example, resulting from an increased risk of prematurity. Conversely, there may be hidden benefits beyond the joys of parenthood – for example, in reduced Intimate Partner Violence.[5]
  3. Diverse beneficiaries – In ‘normal’ health economics, benefits are hypotheticated on the affected person, even though loved ones also stand to benefit. Loved ones benefit through the improved health of the affected person. Ignoring third party benefits can be condoned on the ‘level playing field’ principle – in a comparison across diseases of middle-age, beneficiaries of various alternative treatments are in a roughly similar position – they have similar numbers of loved ones on average. On this basis, the decision tree can be ‘pruned’. It could be argued that this argument breaks down when comparisons are made across generational lines. In the particular case of infertility, mothers and fathers get direct benefits, as do grandparents and others, not only through the ‘affected’ person, but directly from the child that results from the treatment. For instance, the father is just as much a beneficiary as the mother. Grandparents are not far behind – I can attest to that. On the other hand, factoring these beneficiaries into the equation seems to tilt the playing field too far the other way, i.e. towards infertility services. Factoring the benefits that accrue to all these people would weight services for children in general, and infertility services in particular, very strongly. This is a topic requiring more philosophical analysis and, perhaps, empirical investigation.
  4. What about the child who would otherwise not have existed – the question of the utility of the hypothetical lives is vexed. Certainty, no-one counts the utility loss from contraception, even when no later ‘replacement child’ is envisaged. On the other hand, the utility of neonatal survival is included in standard economic practice. My preference is not to include this utility, but I am hard-pressed to defend this on a bottom-up, philosophical basis. Richard Hare, the famous Oxford philosopher, did attempt such an analysis and his conclusions support my instinct. Certainly, including the lifetime utility of the child massively improves the cost-benefit ratio of infertility services,[6-8] and if the tax return from the child is included, then a treatment such as IVF becomes a ‘no-brainer’ since it ‘dominates’ – it saves money and yields benefit down to a very low success rate (<6% of so).[9]

What would happen if we:

  1. Accepted a utility function of 0.9 (close to that of Torrance).
  2. Ignored other beneficiaries, including the child?

We present such an analysis below. Even under these relatively conservative constraints, IVF is cost-effective in most countries, and could be cost-effective in LMICs if some new idea, such as incubation within the vagina, were used.

Say we gave infertility a disutility of 0.1 over 50 years, undiscounted.
Then, the utility in an infertile couple successfully treated = 5 QALYs undiscounted and 1.1 discounted at 3%.
Let’s say society will pay $100 per QALY.
Then a treatment with a 25% success rate can have a net cost of up to $125 undiscounted, but less than $28 discounted.

— Richard Lilford, CLAHRC WM Director

I thank Sheryl van der Poel for sending some of the references quoted in this article.

References:

  1. Drummond MF. Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press. 2005.
  2. Torrance GW. Measurement of Health State Utilities for Economic Appraisal. J Health Econ. 1986; 5: 1-30.
  3. Arnold D, Girling A, Stevens A, Lilford R. Comparison of direct and indirect methods of estimating health state utilities for resource allocation: review and empirical analysis. BMJ; 2009; 339: b2688.
  4. Wu AK, Odisho AY, Washington III SL, Katz PP, Smith JF. Out-of-Pocket Fertility Patient Expense: Data from a Multicenter Prospective Infertility Cohort. J Urology. 2014; 191(2): 427-32.
  5. Stellar C, Garcia-Moreno C, Temmerman M, van der Poel S. A systematic review and narrative report of the relationship between infertility, subfertility, and intimate partner violence. Int J Gynecol Obstet, 2016; 133: 3-8.
  6. Connolly MP, Pollard MS, Hoorens S, Kaplan BR, Oskowitz SP, Silber SJ. Long-term Economic Benefits Attributed to IVF-conceived Children: A Lifetime Tax Calculation. Am J Manag Care. 2008; 14(9): 598-604.
  7. Svensson A, Connolly M, Gallo F, Hägglund L. Long-term fiscal implications of subsidizing in-vitro fertilization in Sweden: A lifetime tax perspective. Scand J Pub Health. 2008; 36: 841-9.
  8. Fragoulakis V & Maniadakis N. Estimating the long-term effects of in vitro fertilization in Greece: an analysis based on a lifetime-investment model. Clinicoecon Outcomes Res. 2013; 5: 247-55.
  9. Baird DT, Collins J, Egozcue J, et al. Fertility and Ageing. Hum Reprod Update. 2005; 11(3): 261-76.

Involving Families in Neonatal Care

It is an unfortunate fact that some children need to be admitted into a neonatal intensive care unit (NICU) soon after birth, and this physical separation can often impact on the physical, psychological and emotional health of both the parents and the babies. In many NICUs the parents are expected to take a step back, with NICU staff providing the great majority of day-to-day care of the baby. An alternative approach, that is not widely used, is the Family Integrated Care (FICare) programme, which facilitates collaboration between parents and the NICU staff. Parents become involved in all aspects of their baby’s care, such as feeding, changing, bathing, as well as decision-making and taking part in medical rounds. A recent paper in the Lancet Child and Adolescent Health looked at the effectiveness of an FICare programme in 26 NICUs in Canada, Australia and New Zealand.[1] Premature babies (born at 33 weeks or earlier) were randomly assigned to receive standard NICU care (n=891), or be provided with FICare (n=895). Parents in the FICare group had to commit to be present for at least six hours each day, attend educational sessions, and provide active care for their baby. At 21 day follow-up the babies in the FICare group had significantly greater weight gain and an average daily weight gain of 26.7g (vs. 24.8g) (both p<0.0001). Mothers in the FICare group also had significantly higher rates of exclusive breastmilk feeding (p=0.016).  Further, parents had significantly lower scores on mean levels of stress (p<0.00043) and anxiety (p=0.0045). There were no significant differences in mortality, major morbidity, oxygen therapy duration, or length of hospital stay.

— Peter Chilton, Research Fellow

Reference:

  1. O’Brien K, Robson K, Bracht M, et al. Effectiveness of Family Integrated Care in neonatal intensive care units on infant and parent outcomes: a multicentre, multinational, cluster-randomised controlled trial. Lancet Child & Adol Health. 2018.

Risks of Children Using Technology Before Bed

We live in an increasingly technologically connected society, which even extends to children – for example, 74% of children (9-16 years old) in the UK use a mobile phone, with most receiving their first phone at the age of 10 years old;[1] while around half have a television in their bedroom at age 7.[2] For many it can be difficult to switch off at the end of the day – the allure of one more video, or another scan of social media can be strong. As such, many children use technology at bedtime, which may impact on their sleep as the light emitted by these devices has a higher concentration of ‘blue light’, which affects the levels of melatonin, a sleep-inducing hormone.[3] Previous research has shown the importance of sleep on children’s health and behaviour, and so Fuller and colleagues conducted a study looking at use of technology at bedtime and its effects on various health outcomes.[4] They surveyed 207 parents of 8-17 year olds and found that children who watched television at bedtime were significantly more likely to be overweight or obese than those who did not (odds ratio 2.4, 95% CI 1.35-4.18). Similar results were found for children who used a phone at bedtime (OR=2.3, 95% CI 1.31-4.05). There were no significant differences seen with computer or video game use. The authors also looked at sleeping behaviour and found a significant relationship between average hours of sleep and bedtime use of television (P=0.025), phone (P<0.001), computer (P<0.001), and video games (P=0.02). Further analysis showed that children who used various technologies were also more likely to be tired in the morning, less likely to eat breakfast, and more likely to text during the middle of the night. The authors recommend setting up ‘tech-free’ zones and making sure that devices are charged outside of the child’s bedroom.

Of course, this study only shows an association – it may be that some children have difficulty getting to sleep and so turn to technology in order to help them drift off. Meanwhile, the study is subject to reporting bias from the self-reported surveys of the parents, and so further studies are needed.

— Peter Chilton, Research Fellow

References:

  1. GSMA report. https://www.gsma.com/publicpolicy/wp-content/uploads/2012/03/GSMA_Childrens_use_of_mobile_phones_2014.pdf. 2014.
  2. Heilmann A, Rouxel P, Fitzsimons E, Kelly Y, Watt RG. Longitudinal associations between television in the bedroom and body fatness in a UK cohort study. Int J Obes. 2017; 41: 1503-9.
  3. Fuller C, Lehman E, Hicks S, Novick MB. Bedtime Use of Technology and Associated Sleep Problems in Children. Glob Pediatr Health. 2017.
  4. Schmerler J. Q&A: Why Is Blue Light before Bedtime Bad for Sleep? Scientific American. 01 September 2015.

Breastfeeding and SIDS

Over the years many studies have shown an association between breastfeeding and decreased risk of sudden infant death syndrome (SIDS), with a previous meta-analysis showing an adjusted odds ratio of 0.55 (95% CI 0.44-0.69), which increased to 0.27 (95% CI 0.24-0.31) with exclusive breastfeeding.[1] However, it has been difficult to identify just how long breastfeeding needs to continue to realise this benefit. This is because duration of breastfeeding has not been correlated with reduction in risk. As a follow-up to their original meta-analysis, Thompson and colleagues worked in cooperation with the authors of the included studies to obtain individual-level data.[2] They were able to glean information on duration of breastfeeding so that the association between duration and effect could be examined. In total 9,104 infants were analysed from eight case-control studies. Although analysis showed some protection against SIDS associated with any breastfeeding up to 2 months, this was not statistically significant after controlling for potential confounders. When confounders were controlled for, analysis found that any breastfeeding for at least 2 months, compared to no breastfeeding, had an adjusted odds ratio (aOR) of 0.60 (95% CI 0.44-0.82), while it was a similar aOR of 0.61 (95% CI 0.42-0.87) for exclusive breastfeeding. The aOR for any amount of breastfeeding compared to none improved with increased duration – an aOR of 0.40 (95% CI 0.26-0.63) with 4-6 months breastfeeding, and 0.36 (95% CI 0.22-0.61) with at least 6 months breastfeeding. A similar improvement was seen with at least 4 months of exclusive breastfeeding (aOR 0.46, 95% CI 0.29-0.74).

In order to lower the incidence of SIDS it is important that new mothers are encouraged to breastfeed and to continue for at least 2 months, even if they are unable to do so exclusively, as any amount of breastfeeding seems to confer more protection than none.

— Peter Chilton, Research Fellow

References:

  1. Hauck FR, Thompson JM, Tanabe KO, Moon RY, Vennemann MM. Breastfeeding and reduced risk of sudden infant death syndrome: a meta-analysis. Pediatrics. 2011; 128(1): 103–10
  2. Thompson JMD, Tanabe K, Moon RY, Mitchell EA, McGarvey C, Tappin D, Blair PS, Hauck FR. Duration of Breastfeeding and Risk of SIDS: An Individual Participant Data Meta-analysis. Pediatrics. 2017: e20171324.

Autism and Allergies

The prevalence of autism spectrum disorder (ASD) is increasing, with the US Centers for Disease Control and Prevention estimating that 1 in 68 people have the disorder. While there is no single known cause of ASD, research has suggested that the immune system may have a role, and that activation of the maternal immune response during pregnancy may increase the risk of ASD developing in the unborn child. A recent paper in Nature investigated associations between the maternal immune activation (MIA) and the severity of ASD symptoms in their child.[1]

The authors analysed an existing cohort of 220 children diagnosed with autism spectrum disorder (ASD) and found that the children whose mothers had a history of allergies and/or asthma had significantly higher scores on the social responsiveness scale (SRS) (p=0.016), compared to those whose mothers did not. The SRS measures social interaction, language, and repetitive/restricted behaviours and interests in the child; a higher score is suggestive of a greater degree of social impairment symptoms. The association was not seen when looking at autoimmune conditions, but many of the mothers were diagnosed with autoimmune problems post-pregnancy, which may have affected the findings.

Although no causal relationship was shown, the study does suggest that the immune system may have a role in ASD.

— Peter Chilton, Research Fellow

Reference:

  1. Patel S, Masi A, Dale RC, Whitehouse AJO, Pokorski I, Alvares GA, Hickie IB, Breen E, Guastella AJ. Social impairments in autism spectrum disorder are related to maternal immune history profile. Mol Psychiatry. 2017.

Association Between Cigarette Price and Infant Mortality

In an effort to reduce smoking rates governments often increase the taxation levied on cigarettes. Previous research has shown that this is an effective strategy, including improvements in child health outcomes. However, tobacco companies often use differential pricing strategies to move the increased taxation on to their premium cigarettes. This lessens the effectiveness of increased taxes as it allows people to switch to the cheaper cigarettes instead. Researchers from Imperial College London set out to assess any associations between price rises, differential pricing (using data on the minimum and median cigarette prices) and infant mortality across 23 European countries.[1] This longitudinal study looked at more than 53.7m live births over a period of ten years. During this time the authors found that a median increase of €1 per pack of cigarettes was associated with 0.23 fewer deaths per 1000 live births in the year of the price hike (95% CI, -0.37 to -0.09), and a decline of 0.16 deaths per 1000 live births in the subsequent year (95% CI, -0.30 to -0.03). Using a counterfactual scenario, the authors estimated that, overall, cigarette price increases were associated with 9,208 fewer infant deaths (i.e. if cigarette prices had remained unchanged then there would have been 9,208 more deaths). Analysis of the price differentials showed that a 10% increase in the differential between the minimum and median priced cigarettes was associated with 0.07 more deaths per 1,000 live births the following year. Further, had there been no cost differential, they estimated that 3,195 infant deaths could have been avoided.

So, while increasing cigarette taxation can have a positive effect, there needs to be more of an effort to try to eliminate budget cigarettes. This is especially true in low-income countries where price differentials tend to be significantly higher than in high-income countries.

— Peter Chilton, Research Fellow

Reference:

  1. Filippidis FT, Laverty AA, Hone T, Been JV, Millett C. Association of Cigarette Price Differentials With Infant Mortality in 23 European Union Countries. JAMA Pediatr. 2017.

A Drug Treatment for Autism

Autism affects 1-2% of children. These children may have problems with social interaction, adhere to strict routines, have repetitive behaviours, restricted interests, poor self-care, and/or heightened sensory experiences. A very wide array of genetic mutations and environmental exposures interact to produce the phenotype. It is a neurological disease and one theory, the “cell danger hypothesis”, holds that certain neurological pathways are prone to become over-activated and respond as though they were under ‘threat’. Purines released from mitochondria leech through the cell membrane where they play a role in activating microglia and affecting synaptic remodelling – a topic covered in other News Blogs.[1][2] A drug called suramin inhibits the action of purines such as ATP. It is used in high doses to control trypanosomiasis (sleeping sickness). It is toxic at high dose, but might it be effective at a lower dose for autism? A very small, double-blind trial has been carried out in which five matched pairs of autistic children were randomised to a single intravenous dose of suramin or saline.[3] Metabolic pathways were affected as expected, and the treatment was associated with improvement on a standard score two days after the infusion. It is early days, but it is just possible that we are entering a period where autism will be added to the growing list of neuro/psychiatric disorders that can be mitigated by pharmacological therapy based on an improved understanding of molecular pathogenesis.

— Richard Lilford, CLAHRC WM Director

References:

  1. Lilford RJ. Okay Then, There is a Fourth Period of Whole-Scale Synaptic Pruning in the Grey Matter of the Brain. NIHR CLAHRC West Midlands News Blog. 13 January 2017.
  2. Lilford RJ. A Fascinating Account of the Opening up of an Area of Scientific Enquiry. NIHR CLAHRC West Midlands News Blog. 11 November 2016.
  3. Naviaux RK, Curtis B, Li K, et al. Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Ann Clin Transl Neurol. 2017.

Nodding Syndrome: Autoimmune Reaction to the Parasitic Worms That Cause River Blindness?

We have described the above enigmatic disorder of young children in East Africa before; a degenerative brain disease characterised by repetitive nodding movement, an inability to swallow, and eventually global brain failure.[1] Authors of a recent study hypothesised that the disease may be caused by an autoimmune response to the river blindness parasite.[2] They detected auto-antibodies to the parasite more often in cases than age-matched controls from the same village. The antibody attacks various cell markers in the mouse brain among neural networks that are affected in nodding syndrome. But only about half the patients with nodding syndrome exhibited the antibodies. The authors speculate that a number of yet to be identified antibodies may also be involved. I wonder why the disease does not map onto the geography of river blindness, which appears to be much broader than that of nodding syndrome.

So, here is my hypothesis. Remember, a few News Blogs ago,[3] I articulated a ‘three hits hypothesis’ as the cause of many diseases. One example was cytomegalovirus infection, which in the presence of the malaria parasite, and along with genetic predisposition, leads to Burkitt’s lymphoma. So I suspect that exposure to river blindness may be a sensitising event, and propose a search for a further exposure that is more specific to the ‘nodding syndrome belt’ extending from South Sudan, through Uganda to North Tanzania (see Figure).

Map of African countries showing where River Blindness is endemic and where outbreaks of Nodding Disease have occurred.

Data on River Blindness taken from the World Health Organization.

— Richard Lilford, CLAHRC WM Director

References:

  1. Chilton PJ. A Mysterious Disease with Unknown Cause. NIHR CLAHRC West Midlands News Blog. 27 June 2014.
  2. Johnson TP, Tyagi R, Lee PR, et al. Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus. Sci Transl Med. 2017; 9.
  3. Lilford RJ. Three Hits Hypothesis. NIHR CLAHRC West Midlands News Blog. 7 April 2017.