#396 - [Journal Club] - 📌 The 6-Fold Risk of NEC in Growth Restricted Infants

In this episode of Journal Club, Ben and Daphna review a prospective cohort study from the Journal of Perinatology that examines the care of neonates following in-utero growth restriction. The hosts unpack the critical distinction between Fetal Growth Restriction (FGR) and Small for Gestational Age (SGA), highlighting how the "decay of information" in the NICU can lead clinicians to overlook early risk factors as babies grow. They discuss the study’s alarming findings regarding the six-fold increased risk of Necrotizing Enterocolitis (NEC) in SGA infants and the importance of maintaining a comprehensive medical history throughout a patient's stay.

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Care of neonates following in-utero growth restriction: A prospective cohort study exploring neonatal morbidity. Alda MG, Wood AG, MacDonald T, Charlton JK.J Perinatol. 2025 Sep;45(9):1219-1225. doi: 10.1038/s41372-025-02397-9. Epub 2025 Aug 21.PMID: 40841433 Free PMC article.

Transcript

[00:00.568] Ben Courchia MDHello everybody, welcome back to the Incubator Podcast. We're back today for another episode of Journal Club. Daphna, good morning, how are you?

[00:08.787] Daphna Yasova Barbeau MDYou keep saying good morning, but our listeners don't know we're recording in the evening this time.

[00:13.942] Ben Courchia MDIt's 7 p.m. at night. I know, it's released in the morning, so we are gonna assume that we just recorded this right before you guys refreshed your feed.

[00:22.205] Daphna Yasova Barbeau MDSometimes we let... what is it called? Pulling back the curtain.

[00:24.942] Ben Courchia MDPulling back the curtain. It is 7 p.m.. I am trying to eat some quick dinner because I haven't eaten all day. I am starving. And so if yesterday you heard some background noise, it's probably me eating my long overdue dinner in the freezing cold of Canada. You were loud? Good, thank you.

[00:42.375] Daphna Yasova Barbeau MDWe'll allow it. We'll allow it. Gabriel's really making it work hard up there in Montreal.

[00:49.98] Ben Courchia MDMy God, I mean it's not his fault, they're busy. And I'm busy by extension. Okay, so I'm just gonna go in order. I have a bunch of articles ready and they're all very interesting. The next article I wanna talk about is an article I saw in the Journal of Perinatology. It's called "Care of Neonates Following In-Utero Growth Restriction: A Prospective Cohort Study Exploring Neonatal Morbidity". The first author is M.G. Alda.

[00:49.98] Ben Courchia MDAnd what I really liked about this paper is that it really addresses something that we see every day. The background is a very interesting one if you're a young trainee, because it goes over some very basic principles of growth restriction. So when we talk about fetal growth restriction, it defines a fetus who does not reach their biological growth potential. It is a common pregnancy complication that increases the risk of neonatal mortality and morbidity in the short and long term.

[01:47.682] Ben Courchia MDAlthough we talk about growth restriction and we talk about small for gestational age, SGA, and we commonly use these terms interchangeably, not all growth restricted infants are born SGA and not all SGA babies are truly growth restricted. The small for gestational age label is just a measure of whether you are below the 10th percentile for your gestational age at birth, but you may still not have reached your full biological potential.

[01:47.682] Ben Courchia MDThe authors note that premature infants are more commonly growth restricted because preterm birth is often due to perinatal pathologies that affect fetal growth. Thus, when preterm infants' birth weights are used to derive growth curves, SGA infants are systematically underdiagnosed. Now granted, we have a whole episode about the release of the new Fenton growth curves. I think that this particular paper was conducted before these new growth curves came out, because this is precisely one of the pitfalls of the old Fenton growth curves that is addressed in this current edition.

[01:47.682] Ben Courchia MDSo in this study, the authors aimed to prospectively explore the trajectory of SGA preterm neonates admitted to a tertiary NICU, and they aimed to evaluate comorbidities occurring due to that growth restriction accounting for the impact of prematurity. It's very interesting how they did it. That's why I really like this paper.

[04:12.354] Ben Courchia MDThe study participants were basically any premature infant born between 24 and 36 weeks corrected at a hospital in Melbourne. The study ran from 2023 to 2024. The infants were enrolled as either SGA or AGA based on their birth weight percentile, using the GROW (Gestation Related Optimal Weight) chart. You can actually try to consult these growth charts. You have to request access, which I did not, but basically they have this link available for you to review. They say that these growth curves generate term optimal weight and then adjust for factors which influence fetal growth to produce a percentile according to the exact day of gestation known to be important to best detect pathological growth associated with poor outcomes.

[04:57.26] Ben Courchia MDThe SGA group included all enrolled preterm infants with a birth weight less than the 10th percentile on this particular growth chart that they've developed. The control group basically involved AGA preterm infants with a birth weight between the 10th and 90th percentile. Now, what they did is they had an intervention group of SGA babies, and then they had two control groups. They had a control group for gestational age. So basically we're comparing them based on their gestational age. And then they had a control group based on weight, which was very interesting. So if you are 29 weeks and you weigh 600 grams, you would have had two comparison groups for you. One, like a normally grown 29-weeker, and then a normally grown 600-gram baby, which would have probably been, I don't know, like 25 weeks or 26 weeks. So that I thought was very interesting.

[04:57.26] Ben Courchia MDThey had a bunch of exclusion criteria, which I'm not going to get into. In terms of outcome measure, they used the Fenton growth chart to assess neonatal growth during the hospital stay. They recorded weekly length, head circumference, and weight from birth to hospital discharge. They recorded baseline heart rate on day one and weekly until eight weeks of life or discharge. The authors also recorded blood gas measures in terms of pH, lactate, and blood sugar levels. The neonatal morbidities that they looked at included BPD (defined as oxygen requirement at 36 weeks), any grade of IVH, PVL, ROP, NEC, length of hospitalization, and death.

[07:22.766] Ben Courchia MDSo what they ended up having was about 150 patients: 54 in the SGA group, and then another 50 for each of the control groups. Maternal characteristics were similar between the SGA and control groups, though the SGA cohort had higher rates of ultrasound-diagnosed fetal growth restriction and preeclampsia. Among the SGA cohort, 37 bad antenatal Doppler assessments. Of these, 76% showed umbilical artery abnormalities. 46% showed middle cerebral artery abnormalities. No Doppler anomalies were noted in the controls. Of all included in the SGA cohort, 43 infants, or 80%, had a birth weight less than the third percentile on the GROW chart, which would categorize them as severely growth restricted.

[07:22.766] Ben Courchia MDSo what are some of the metabolic and physiological outcomes? In terms of neonatal outcomes, preterm SGA infants were more likely to have hypothermia on admission to the nursery. The rate was 44% for the SGA group compared to 15% for the ones matched by gestational age and 17.2% for the ones matched by birth weight. Infants in the SGA group were also at significantly higher risk of lower blood sugar levels at birth and in the first week of life compared to their cohort. The proportion of infants who had hypoglycemia was more common in the SGA group, especially in the first week of life compared with both groups. Additionally, the SGA infants had higher lactate levels on day one of life and between day two and day seven compared to both controls. No difference was seen, however, in the blood pH during the first week of life.

[07:22.766] Ben Courchia MDVery interesting, the respiratory and growth outcomes. Most infants in all groups required some form of respiratory support, not super surprising. There was no significant difference in the amount of steroids received. While it was not statistically significant, the incidence of BPD was higher in the lower gestational age group, 40.7%, compared to 30% in the SGA group. The requirements for inotropic support were the same. You know, we say that growth restriction accelerates your pulmonary development a little bit. That could very well be what manifested here. Regarding growth recovery, SGA infants recovered to their birth weight faster than both control groups who recovered at a slower pace. All groups had reduction in Z-scores of weight, length, and head circumference at discharge. That's extraordinary in growth restriction, which is the problem of this particular unit and not surprising, something that many of us struggle with.

[07:22.766] Ben Courchia MDIn terms of other morbidities and mortality, necrotizing enterocolitis was significantly increased in the SGA group. Are you ready for this, Daphna? The rates of NEC in the SGA group were 11% compared to 1.8% in the gestation matched control. Beware of these SGA babies. The authors state that the SGA had a six-fold higher risk of NEC in their study. All six cases of SGA infants who experienced NEC occurred in infants born at less than 28 weeks of gestation. It is important to mention that feeding practices within the SGA and the birth weight matched control were exactly the same.

[09:49.776] Ben Courchia MDIn terms of neurological outcome, IVH was significantly more prevalent in the birth weight matched control group at 39.5% compared with the SGA group at 15%. I think that you're going to start seeing that obviously there's no offsetting being born at 23 weeks, for example. If you are very immature, it's a big problem. No significant difference in PVL and ROP between the groups. Length of stay and post-menstrual age at discharge were similar between the groups. Regarding mortality, there were four deaths in the SGA group representing 7.4% compared to one control participant representing 1.8%. Again, not significant due to the low numbers.

[09:49.776] Ben Courchia MDThe discussion is interesting because of this particular form of control groups. The authors obviously mentioned in their conclusion the difference in the outcomes that we just discussed. They state that early iatrogenic delivery, which is performed to prevent stillbirth, must be weighed against the potential risks associated with prematurity and growth restriction, which I thought was interesting. Thoughts?

[11:10.194] Daphna Yasova Barbeau MDI mean, it feels right. It's supposed to look at data. I know, but we've definitely experienced this. We have a high rate of growth restricted infants. Sometimes you look at these babies and you're like, "Man, they're small". They're way smaller than they're supposed to be. And those are the ones that you just gotta keep a close eye on. They're always doing something.

[11:36.944] Ben Courchia MDI think what's tricky also is that there's a window for NEC that we talk about, like three weeks of life, 29 to 31 weeks, whatever. But if the baby is born very early, you forget their SGA status. And I think that it should now—when you read this paper, it sounds like it should be like a banner over the baby's isolette. Do not forget that I was growth restricted. Because when this baby is gonna do something interesting at three weeks of life, you might want to have all this information handy and not just assume that the patient is just doing well.

[12:04.493] Ben Courchia MDBecause like I said, there's all these things that we... there's a decay of information in the NICU. We have all this information at birth and then it rarely... I think that you've seen this, the presentation you get on day one is one thing from the team, from the resident, from the nurse. And then as the patient gets more complex and complex, you sort of start substituting some of the more recent issues for some of the more demographic type of issues. And maybe the maternal history gets a little bit more cloudy now because we're talking about the re-intubation and this and that. And then, that's how SGA just—poof—you forget about it.

[12:48.282] Daphna Yasova Barbeau MDYeah, you know, this occurred to me teaching in the med school with the first years. And I was like, man, we don't have all this previous medical history, but our babies do have a ton of previous medical history. Were they growth restricted? One. Were they chorioamnionitis? Two. What were the maternal problems during pregnancy? Three. And I mean, that changes your pre-test probability of when you come to the bedside and what could be wrong with them. We forget over time, or some interesting cases, like the fetal demise of a twin—what does that put babies at risk for? And just exactly like you said, their previous medical history has to follow them through the entire admission. And every time you go to the bedside to check a baby out, you have to say, what are this baby's additional risks to prematurity?

[13:52.419] Ben Courchia MDYeah, and I think that exactly like they say in the article, they regain weight pretty quickly. And so we forget, it's like, "No, this is so big, it's so big, so cute". It's like, no.

[14:00.474] Daphna Yasova Barbeau MDYeah, that's right. They're quadruple the size that they came in. It's interesting, especially, you know, obviously there are different causes for growth restriction, but when it's nutritional or it's placental insufficiency, once they're re-exposed to all of the nutrients and the flow, they grow like they're supposed to. Not all the babies, right? For different reasons, you know, genetic problems, things like that. There are lots of reasons babies don't grow, but yeah, sometimes they're doing so well. It seems to erase some of the history that was pretty dramatic on admission.

[14:44.079] Ben Courchia MD What is the sentence we hear commonly in the NICU? "Do you want the whole history? Or do you just want the updates?". And to everybody's credit and to everybody's blame, I often say, "I know this patient, just give me the highlights". And that's it. This is how you get, "All right, the kid has been stable overnight, he's tolerating feeds, and he had one emesis," and that's it.

[15:02.876] Daphna Yasova Barbeau MDAnd we're like, "Nah, nah, we know this baby".

[15:15.887] Ben Courchia MDCrazy. All right, on this note, we'll see you guys tomorrow.

[15:18.514] Daphna Yasova Barbeau MDAll right, buddy.