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Highlights from the literature

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Developmental outcomes after neonatal surgery

Parents worry about the long-term effects of performing surgery on very young infants. Poorer developmental performance after cardiac surgery is well-documented, not surprising given the risk of cerebral hypoxia-ischaemia. But what about non-cardiac surgery? Authors from The Netherlands trawled the literature for studies where children with non-cardiac major congenital anomalies had been operated on up to 4 weeks post-term, and then had their development at 12 and 24 months assessed (Stolwijk L, et al. Pediatrics 2016. doi: 10.1542/peds.2015-1728). They found 23 studies involving almost 900 children. Those with known syndromic or chromosomal conditions were excluded. They were able to meta-analyse data on 500 children who had been assessed using Bayley Scales: cognitive delay was reported in 23%, with a significantly reduced mean developmental index of 92 (SD 13; p<0.001 compared to population norms). Factors increasing the risk included multiple anomalies, low birth weight and repeated surgery, but the risk remained when these were allowed for. Those with congenital diaphragmatic hernia did the worst. There was no difference between scores at 12 and 24 months, suggesting little recovery.

So is it the anaesthetic, the surgery or the condition itself? Or could it be that whatever went wrong in early intrauterine life produced not just the obvious anomaly but subtle brain defects as well?

Azithromycin—a treatment for asthma?

Things go in cycles. When I was training, my teachers frowned upon earlier generations of doctors who prescribed antibiotics for acute asthma episodes, preferring the then novel bronchodilator drugs. But now it seems those old physicians may have been right after all. There is evidence from various sources that macrolides have some anti-inflammatory properties. Researchers from Denmark also found in earlier studies that up to half of asthma episodes in young children may be triggered by bacteria, not just viruses. To investigate these observations, they recruited 160 children aged 1–3 years as part of the COPSAC cohort, all of whom had an asthma diagnosis (Stokholm J, et al. Lancet Respir Med 2016. doi.org/10.1016/ S2213-2600(15)00500-7). For each exacerbation they were randomised to Azithromycin (10mg/kg for 3 days) or placebo, and assessed using daily symptom-score diaries until resolution. Those with clear clinical signs of pneumonia, including C-reactive protein of >50 mg/l, were excluded. Pharyngeal aspirate specimens were collected for bacterial and viral analysis.

The results were striking: the treatment group had significantly shorter duration of illness (mean 3.4 vs 7.7 days; p<0.0001) and less beta-2 agonist use. Those treated early, on day one, did even better. So was the benefit due to an antibacterial or anti-inflammatory effect? This study doesn't give a clear answer. The 67% in whom bacteria were detected did no better overall, although the 24% with H. Influenzae, considered alone, did (p<0.0001).

If widespread use of antibiotics for this very common condition comes back into vogue there would be major implications for bacterial resistance rates, and this needs to be looked at carefully before recommendations are changed.

Obesity and PICU mortality

As paediatricians we tend to think of obesity as causing severe illness and mortality only when children reach adulthood, but if an obese child becomes critically ill for any reason, are they more likely to die? The adult literature is confusing: obesity is associated with more critical illness, particularly adult respiratory distress syndrome (ARDS), but not with increased mortality, perhaps because it protects in some way: the ‘obesity paradox’.

Researchers used the massive Virtual PICU Systems database to assess this (Ross P, et al. Pediatrics 2015. 10.1542/peds.2015-2035). They analysed data from 127 000 children admitted to intensive care units throughout the US, including age, weight, height where recorded and the PIM2 illness severity score. Diagnosis and reason for admission were not considered. Previous studies had looked only at weight-for-age: in this study they also analysed independently weight-for-height or body mass index (BMI). Only about a third had actually had their height or length measured (not surprising considering the obvious practical difficulties), but these did not differ from those where it had not. They computed meaningful mortality curves, adjusted for PIM2 severity scores. The curves for weight-for-age and for BMI were different: for both, as expected, mortality was higher for the very underweight children. But at the other end, the increase in mortality was much more pronounced when BMI was considered: the lowest mortality (2.0%) was around the mean (z-score +/− 0.5) while the highest (3.9%) was at BMI z-score >+3.5. Weight-for-age z-score of >+3.5, however, was associated with only a slight increase in mortality of 2.8%.

Thus if the correct measurements are considered, the ‘obesity paradox’ does not seem to apply to children, at least in the American population.

Fatty acids and tummy aches

When dealing with the many children we see in our clinics with recurrent abdominal pain (RAP), we tend to dichotomise them into a minority that have an organic cause, and a majority whom we label as ‘functional’ or stress-related. However the reality is far more complicated: increasingly, measurable physiological and biochemical abnormalities are being found in those labelled ‘functional’ in many contexts, although it is often difficult to distinguish cause and effect.

There is evidence that omega-6 FAs are ‘nocioceptive’, ie increase sensitivity to pain, while omega-3 FAs have the opposite effect. Researchers in Sweden took blood from 22 children aged 6-16 years who had a firm diagnosis of non-organic RAP, at a time when they were in pain, and compared them with 100 healthy controls (Alfven G, et al. Acta Paed 2016.doi: 10.1111/apa.13381). They found small, but statistically significant differences in the ratios (eg linoleic to alpha-linoleic ratios differed significantly p<0.001).

So does the ‘stress’ cause these abnormalities, or are these children somehow metabolically different, and hence more susceptible to experiencing pain? This study doesn't really answer this question. The numbers were small and there was no follow-up.

This work doesn't suggest any obvious treatment, but if confirmed by future studies, it may help to explain to these youngsters and their families how anxieties can cause real physical pain.

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