The JAMA Pediatrics study gives us the most up-to-date epidemiology yet about this #1 diarrheal killer of children.Read More
A study appearing in JAMA Pediatrics suggests that children born late-term have better cognitive outcomes than children born full-term. As if pregnant women didn’t have enough to worry about. For the video version of this post, click here.
Let’s dig into the data a bit, but first some terms (sorry for the pun). “Early term” means birth at 37 or 38 weeks gestation, “full term” 39 or 40 weeks, and “late term” 41 weeks. In other words, this study is not looking at pre-term or post-term babies, all of the children here were born in a normal range.
Ok, here’s how the study was done. Researchers used birth records from the state of Florida and linked them to standardized test performance in grades 3 through 10. Compared to children born at 39 or 40 weeks of gestation, those born at 41 weeks got test scores that were, on average, about 5% of a standard deviation higher. To get a sense of what the means, if these were IQ tests (they weren’t) that would translate to a little less than 1 IQ point difference. Not huge, but the sample size of over one million births makes it statistically significant.
10.3% of those born at 41 weeks were designated as “gifted” in school, compared to 10.0% of those born at full-term.
Before I look at what might go wrong in a study like this – is the effect plausible? To be honest, I sort of doubt it. One week extra development in utero certainly will lead to some differences at or near birth, but I find it hard to believe that any intelligence signal wouldn’t simply be washed away amid all the other factors that affect developing young minds prior to age 8.
Now, the authors did their best to adjust for some of these things – race, sex, socioeconomic status, birth order, but it seems likely that there are unmeasured factors here that might lead to longer gestation and better cognitive outcomes – maternal nutrition comes to mind, for example.
We also need to worry about systematic measurement error. These gestation times came from birth certificate data – in other words, many of these measurements may have been some doctors best guess. If the dates were determined by ultrasound, larger babies might be misclassified as later term. Also, I suspect that if conception dates weren’t well known, a lot of doctors filling out the birth certificate may have just written “40 weeks” to put something in that box.
The authors attempted to look just at women where the likelihood of prenatal care was high, finding similar results, but again, with the tiny effect size, any small systematic measurement error could lead to results like this.
The authors state that this information is relevant to women who are considering a planned cesarean or induction of labor. Currently, the American College of Obstetrics and Gynecology recommends “targeting” labor to 39-40 weeks to avoid some physical complications of late-term birth. In my opinion, having this study change that recommendation at all would be premature.
For the video version of this post, click here. Here’s a secret for any non-clinicians watching this. Docs are terrified of fevers in very young infants - not because they turn out so horribly - most are benign viral infections - but because fever in an infant of less than 4 weeks requires a spinal tap to rule out meningitis. It would be great to have a test that could reliably and quickly tell us if a baby’s fever was due to a bacterial infection that needs prompt and aggressive treatment, or a virus, that can be managed at home.
Enter procalcitonin. It’s pretty much undetectable in the blood of healthy kids, but goes up in the setting of inflammation. Interestingly, it seems to go up much more in the setting of bacterial infection than viral infection. Could we use procalcitonin level to triage infants with fevers? Could we avoid blood cultures and spinal taps?
An article appearing in JAMA pediatrics suggests that we could, but I’m not sure the evidence is so clear. Here are the basics: researchers in France enrolled around 2000 babies from 7 - 91 days of life who presented to the emergency room with fever. The workup done was left to the discretion of the treating physician, but a blood sample for procalcitonin was taken and blindly measured later.
As you might expect, only about 10% of the babies had bacterial infections (which included urinary tract infections). Bacteremia or meningitis were found in less than 1%. I want to focus on that last group, as UTIs can be pretty easily diagnosed by urine dipstick. Could procalcitonin rule out blood or cerebrospinal fluid infection? Well, using a cut-off of 0.3 ng/ml, babies with high procalcitonin levels were 31 times more likely to have bacterial meningitis or bacteremia than kids without those levels. That sounds pretty good.
But to really evaluate this test, we have to look at the sensitivity, which was reported at 90%. That means that you’ll capture 90% of those terrible infections if you use a 0.3ng/ml cutoff. That’s good, but not great. And as a parent of a one month old myself, not a risk I’d be willing to take. Lowering the threshold to 0.12ng/ml apparently would capture all the bad infections, but at that point, the false-positive rate would be really high.
The manuscript did demonstrate that procalcitonin is better than some alternatives like c-reactive protein and white blood cell count. But one thing they don’t report? Clinician’s suspicion. They mention in the methods section that the treating physician classified each infant as well, minimally, moderately, or very ill. How did those assessments perform? We aren’t told.
It basically boils down to how many spinal taps we can avoid without missing any cases of meningitis. It may be reasonable to feel comfortable sending the baby home when the procalcitonin level is extremely low, but I suspect in those cases the physicians were pretty comfortable anyway. For me to push for the broad adoption of this test, I want to see that it tells us something physicians don’t already know - and this manuscript came up short on that front. But if that data does finally arrive, well, we’ll all be thankful.