Neonatal Surgery and Long Term Outcomes

A study from a group in Australia provides new data about the developmental outcomes of babies having surgery, in the medium long term. It is already clear that babies who need neonatal cardiac surgery have poorer developmental outcomes than control infants. Some of this is probably due to pre-existing abnormalities of cerebral development, but some is also probably due to peri-operative phenomena, and may be amenable to improvement by changing surgical or anesthetic techniques. In this new study more information about non-cardiac surgery outcomes is provided. Walker K, Badawi N, Halliday R, Stewart J, Sholler GF, Winlaw DS, et al. Early Developmental Outcomes following Major Noncardiac and Cardiac Surgery in Term Infants: A Population-Based Study. J Pediatr. 2012(0). Epub 2012/05/15

This was a very large regional cohort, and included a control group of infants who did not have surgery; this feature is very important as the authors performed the Bayley 3 scores for infant development on all of the babies. This was a major undertaking, and the authors are to be congratulated. Particularly for having a comparable control group; it is clear that we should not rely on the standardized scores of the Bayley 3 to determine whether an infant has developmental delay; scores (especially in Australia, where I guess they are smarter than average) in controls are usually substantially higher than the standardization would lead you to expect. Also the testing was done at 1 year, which is too early to have much predictive value for the very long term, but does on the other hand point out developmental delays at that time. Major non-cardiac surgery included thoracotomies, laparotomies and sclerotherapy for lymphatic abnormalities. So it excluded inguinal hernia repairs but included a lot of children who had pyloromyotomy for pyloric stenosis, which we often think of as being relatively minor surgery, but does involve opening the peritoneum.

The authors showed that there were many more infants with developmental delay after cardiac surgery than the controls, and a smaller increase in developmental delay after non-cardiac surgery. Now don’t panic if your baby had surgery, the delays were relatively minor, babies were a couple of months behind in their development. But the delays were seen in many areas of development, cognition, language and motor.

Now why should this be? If we assume that the large majority of the non-cardiac surgery babies, and most of the cardiac surgery babies, had a lesion that did not affect cerebral development before birth, then we are left to ask: is the cause of these problems the surgery and the hemodynamic and other physiologic changes that occur around surgery? Is the cause the drugs that are used for anesthesia? Or does the pain and discomfort of pain itself cause long term cerebral changes?

I think the answer to these questions is likely to be yes!

The Boston Circulatory Arrest Trial showed that being randomized to deep hypothermic circulatory arrest gave poorer developmental outcomes among a group of children with a single diagnosis (d-transposition), than the comparison group who had low-flow cardiopulmonary bypass. These infants were much less variable than most groups of children with congenital heart disease who have been studied, and the study gave strong evidence that the details of how the circulation is managed can affect brain development, with effects that last until school age. Bellinger DC, Wypij D, duPlessis AJ, Rappaport LA, Jonas RA, Wernovsky G, et al. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: The Boston Circulatory Arrest Trial. The Journal of Thoracic and Cardiovascular Surgery. 2003;126(5):1385-96. This is a pretty extreme example, but many babies during surgery have periods of low cardiac output, hypo- or hyper-ventilation, they may have a lung deflated to enabled access to particular structure or have gas insufflated into the abdomen to allow laporoscopic access to an organ, which changes hemodynamics and increases IVC resistance.  They may become dehydrated by having huge insensible fluid losses while the abdomen is open, or become fluid overloaded because guessing how much fluid has been lost is a very inexact science. So it is quite conceivable that these changes and the endocrine stress responses that accompany surgery, and the systemic inflammation that we see also, could cause brain injuries, inflammatory, ischemic, embolic or other, and long term effects.

In animal models just the administration of drugs that are commonly used in neonatal anesthesia can lead to neuronal apoptosis and long term adverse effects. How important this is in babies is unclear: obviously you cannot do surgery without anesthesia, so studies to find the most effective, and least harmful anesthetics are needed, if indeed anesthesia has the same effects in humans as in the animal models.

A study from a north american cohort (Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, et al. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011;128(5):e1053-61. Epub 2011/10/05 compared the effects of having surgery before the age of 2 on whether or not children were classified as having a learning disability later on.

The differences between this study design and the previous one should be noted. Randall Flick and his coworkers examined data in 2 large and quite complete regional databases. Children were classified as having a learning disability based on results on standardised educational testing, performed as a routine in the educational system in Minnesota. In this study children who had a surgery before the age of 2 (not before 90 days as in the previous study) had no increased risk of being below this specific threshold, unless they had 2 or more surgeries. In which case learning disabilities were more frequent. Now using a threshold to classify children as having a problem or not, is less powerful than comparing average scores on a test. Also we could presume that surgery in the first 90 days is more likely to be followed by problems than surgery in larger older children up to 2 years.

Finally another study which looked at the number of painful procedures that children experience and how it might affect brain development. (Brummelte S, Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, et al. Procedural pain and brain development in premature newborns. Annals of Neurology. 2012;71(3):385-96 )

I’m not sure you can really statistically correct for all of the potential confounders and there probably was some residual confounding, so it is hard to ascribe the effects that were shown just to the painful procedures,but nevertheless, children who had more painful procedures had differences in white matter MRI features (fractional inosotropy) and grey matter metabolism both early in life and at term.

Having surgery is bad for your brain, in general the effects are relatively small, but surgery, anesthesia and pain may all contribute to the adverse effects.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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