Tag Archives: Children

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.
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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.

Childhood Decline in Physical Activity

Previously we have seen evidence from a cohort of children and adolescents in Norfolk that the decline in physical activity among modern young people takes place after childhood and during adolescence.[1] However in the majority of studies, including that which we looked at, the estimates of activity are largely based on reports. Now comes a new paper from Farooq and colleagues using objective measurements based on an accelerometer.[2] This new study shows that the previous conclusion was probably wrong. The study shows that there is a decline in moderate to vigorous physical activity throughout childhood and adolescence. A further interesting finding is that this study, based on objective measurements of activity, did not replicate the prevailing view that energy expenditure declines more rapidly in girls than in boys. This paper has considerable implications for policy. I would like to thank Professor Jeremy Dale for bringing this important paper to my attention.

— Richard Lilford, CLAHRC WM Director

References:

  1. Corder K, van Sluijs EMF, Ekelund U, Jones AP, Griffin SJ. Change in children’s physical activity over 12 months; longitudinal results from the SPEEDY study. Pediatrics. 2010; 126(4): e926-35.
  2. Farooq MA, Parkinson KN, Adamson AJ, et al. Timing of the decline in physical activity in childhood and adolescence: Gateshead Millennium Cohort Study. Br J Sports Med. 2017.

Crying Infants – the Epidemiology of ‘Colic’

The period following childbirth is stressful for parents and uncontrollable crying is an important cause of this stress. Wolke and colleagues [1] have consolidated the results of studies across the world in a meta-analysis and show that:

  1. Crying peaks at around six weeks of age, and then declines sharply over the next three months.
  2. Bottle or mixed-fed babies cry less than those that are purely breastfed.
  3. Crying is much more common in some countries (Canada and UK) than others (Denmark and Japan), and this is a robust finding (i.e. replicated across many studies). I don’t suppose that this is the result of lower breastfeeding rates in Denmark and Japan than in Canada or the UK?

What the study does not show is how crying varies within families or by birth order. Nor does there seem to be an effective remedy for the problem. Pilgrim was right, it is not easy being a human, not at the beginning, not in the middle, and certainly not at the end.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Wolke D, Bilgin A, Samara M. Systematic Review and Meta-Analysis: Fussing and Crying Durations and Prevalence of Colic in Infants. J Pediatr. 2017.

 

Computer Interpretation of Foetal Heart Rates Does Not Help Distinguishing Babies That Need a Caesarean from Those That Do Not

In an earlier life I was involved in obtaining treatment costs for a pilot trial of computerised foetal heart monitoring versus standard foetal heart monitoring (CTG). The full trial, funded by NIHR, has now been published in the Lancet,[1] featuring Sara Kenyon from our CLAHRC WM theme 1. With over 46,000 participants the trial found no difference in a composite measure of foetal outcome or intervention rates. Perinatal mortality was only 3 per 10,000 women across both arms and the incidence of hypoxic encephalopathy was less than 1 per 1,000. Of course, the possibility of an educational effect from the computer decision support (‘contamination’) may have reduced the observed effect, but this could only be tested by a cluster trial. However, such a design would create its own set of problems, such as loss of precision and bias through interaction between method used and baseline risk across interventions and control sites. Also, the control group was not care as usual, but the visual display IT system shorn of its decision support (artificial intelligence) module.[2] Some support for the idea that control condition affected care in a positive direction, making any marginal effect of decision support hard to detect, comes from the low event rate across both study arms. Meanwhile, the lower than expected baseline event rates mean that any improvement in outcome will be hard to detect in future studies. So here is another topic that, like vitamin D given routinely to elderly people,[3] now sits below the “horizon of science” – the combination of low event rates and low plausible effect sizes mean that we can move on from this subject – at least in a high-income context. If you want to use the computerised method, and its costs are immaterial, then there is no reason not to; economics aside there appear to be no trade-offs here, since both benefits and harms were null.

— Richard Lilford, CLAHRC WM Director

References:

  1. The INFANT Collaborative Group. Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial. Lancet. 2017.
  2. Keith R. The INFANT study – a flawed design foreseen. Lancet. 2017.
  3. Lilford RJ. Effects of Vitamin D Supplements. NIHR CLAHRC West Midlands News Blog. 24 March 2017.

Worm Wars Continued

We have discussed results of deworming before and argued that it is important to treat at cluster level because of rapid re-infection from reservoirs in soil. A recent important meta-analysis compares deworming targeted at children versus a community-wide intervention.[1] It finds that community-wide approaches are more effective than treatment targeted at children for roundworms (Ascaris) and hookworms (Ancylostoma), but not whipworms (Trichuris). This finding is consistent with the much greater efficiency of the medicine in the former two worm types. The relative effect was greater in roundworms (odds ratio >16) than the more dangerous hookworms (OR >4), consistent with the shorter life-span of hookworm eggs than of roundworm eggs. These are important findings, but there is a worry that resistance may emerge with mass treatment. It would be interesting to see whether any studies have been done in slum populations specifically.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Clarke NE, Clements ACA, Doi SA, et al. Differential effect of mass deworming and targeted deworming for soil-transmitted helminth control in children: a systematic review and meta-analysis. Lancet. 2017; 389: 287-97.

Keeping a Child Back at School

We have often talked about Hattie’s work on evidence-based education.[1-4] Now we turn to retention (pages 97-99) – the act of keeping a child back and having them repeat a year of school on the grounds of poor performance.[5] Numerous papers, including a meta-analysis of 20 studies,[6] have shown retention to be associated with negative effects for the retained student. In subsequent years they have lower scores for a whole range of subjects: language, arts, reading, mathematics, work-study skills, and social studies, as well as social and emotional adjustment and behaviour, self-concept, and attitude to school. So a picture is starting to emerge – remember streaming is also unhelpful.[7] So any act that demeans a child or destroys her self-confidence is bad, while bright children are not held back by having less bright peers in the classroom. See also our News Blog on the Michelle Obama effect.[8]

— Richard Lilford, CLAHRC WM Director

References:

  1. Lilford RJ. Evidence-based Education. NIHR CLAHRC West Midlands News Blog. 24 February 2017.
  2. Lilford RJ. The School, the Teacher of the Pupil – Which is Most Important? NIHR CLAHRC West Midlands News Blog. 28 October 2016.
  3. Lilford RJ. Ask Not to Whether, But Why, Before the Bell Tolls. NIHR CLAHRC West Midlands News Blog. 29 July 2016.
  4. Lilford RJ. Education Update. NIHR CLAHRC West Midlands News Blog. 2 September 2016.
  5. Hattie J. Visible Learning: A Synthesis of Over 800 Meta-Analyses Relating to Achievement. Oxon, UK: Routledge, 2009.
  6. Jimerson SR. Meta-analysis of Grade Retention Research: Implications for Practice in the 21st Century. School Psychol Rev. 2001; 30(3): 420-37.
  7. Lilford RJ. Evidence-Based Education (or How Wrong the CLAHRC WM Director Was). NIHR CLAHRC West Midlands News Blog. 15 July 2016.
  8. Lilford RJ. More on Education. NIHR CLAHRC West Midlands News Blog. 16 September 2016.