#410 - đ Journal Club - The Complete Episode from March 14th 2026
- Mickael Guigui
- 4 hours ago
- 37 min read
Hello friends đ
The PDA debate has a new data point. TREOCAPA, a phase 3 multicenter European RCT, tested prophylactic acetaminophen in infants born at 23 to 28 weeks. The ductus closed more reliably. Whether that translated into better survival without severe morbidity at 36 weeks is where the conversation gets interesting.
Also this week: a large multicenter cohort study puts real numbers on diazoxide use across US NICUs and the pulmonary hypertension risk that has driven so much practice variation. The NeoDry trial tests whether drying very preterm infants before plastic wrapping improves normothermia at admission, with results that are a good reminder of why we run trials. And a retrospective from NYU raises the question of whether standard caffeine dosing in the most premature infants is leaving something on the table.
The episode closes with Ben and Eli on Floridaâs infant formula heavy metal report and why publishing findings without methods may be as much a public health problem as the data itself.
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The articles covered on todayâs episode of the podcast can be found here đ
Prophylactic Treatment of Patent Ductus Arteriosus With Acetaminophen: A Randomized Clinical Trial. RozĂ© JC, Cambonie G, Flamant C, PatkaĂŻ J, MĂŒhlbacher T, Gascoin G, Rideau Batista Novais A, Tauzin M, Le Duc K, BeuchĂ©e A, Joye S, Babacheva E, Bouissou A, Ligi I, Tammela O, Plourde M, Dempsey E, Tosello B, Nguyen K, Vincent M, Andresson P, Binder C, Kruse C, Barcos Munoz F, Kuhn P, Proença E, Bartocci M, Kermorvant-Duchemin E, Nellis G, Lumia M, Giapros V, Rigo V, Sankilampi U, Mendes da Graça A, RĂžnnestad A, Soukka H, MondĂŹ V, Aikio O, Torre-Monmany N, RĂŒegger C, Baud O, Zeitlin J, Morgan AS, Baruteau AE, Ancel PY, Carbajal R, Bouazza N, Diallo A, Levoyer L, Kemper R, Hallman M, Alberti C, Ursino M; TREOCAPA Study Group.JAMA Pediatr. 2026 Feb 16:e256150. doi: 10.1001/jamapediatrics.2025.6150. Online ahead of print.PMID: 41697673
Prevalence and safety of diazoxide in the neonatal intensive care unit. Collins LC, Daniel KB, Tolia VN, Parikh P, Gray KD, Greenberg RG.J Perinatol. 2026 Feb 3. doi: 10.1038/s41372-026-02568-2. Online ahead of print.PMID: 41634357
Drying Very Preterm Infants Before Plastic Wrapping at Birth: A Randomized Clinical Trial. Cavallin F, Doglioni N, Risso FM, Monari CB, Aversa S, Troiani S, Battajon N, Moschella S, Villani PE, Vedovato S, Maiorca D, Frezza S, Lista G, Laforgia N, Mondello I, Sibona I, Staffler A, Pratesi S, Paviotti G, De Bernardo G, Lama S, Miselli F, Bua J, Gitto E, Pesce S, Baraldi E, Trevisanuto D; NEODRY Trial Group.JAMA Netw Open. 2026 Mar 2;9(3):e2556902. doi: 10.1001/jamanetworkopen.2025.56902.
Effects of higher caffeine dosing on rates of bronchopulmonary dysplasia and neurodevelopmental outcomes. Fleishaker S, Kazmi SH, Mavrogiannis N, Street H, Ravuri H, Moinuddin T, Pierce K, Verma S.J Perinatol. 2026 Feb 23. doi: 10.1038/s41372-026-02593-1. Online ahead of print.PMID: 41731043
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Watch this week's Journal Club on YouTube đ
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The transcript of today's episode can be found below đ
Ben Courchia MD (00:00) Hello everybody, welcome back to the incubator podcast. We're back today for an episode of journal club.
Daphna Yasova Barbeau MD (00:06) Good morning. I'm in my post-call snuggly here.
Ben Courchia MD (00:11) That's okay. The journals need to be read even when post-call. That's right, you're post-call. I forgot about that. Sorry. That's why you were asking for a late start this morning. I forgot you were post-call. You should have said that.
Daphna Yasova Barbeau MD (00:23) Yeah, but you keep us on such a strict schedule.
Ben Courchia MD (00:30) And here we are. Okay. We're going to start Journal Club. We have a bunch of very interesting articles that we can review. Is there anything that we need to announce? I don't really have any announcements, to be honest with you. We're going to soon go to the Cool Topics in Neonatology conference from the California Association of Neonatologists, which will be a lot of fun. And then we'll be at PAS in April. We'll be the official podcast partner of PAS this year. Very excited about that.
Daphna Yasova Barbeau MD (01:14) We've been doing a lot of traveling. I guess maybe to remind people if they haven't checked out our coverage from Neo Conference.
Ben Courchia MD (01:22) Yeah, the coverage from Neo Conference is on YouTube, on the main podcast channel, and we've had lots of very interesting interviews with lots of people. Did I have a favorite interview? I would say Mark Mercurio was my favorite interview for sure. I'm biased.
Daphna Yasova Barbeau MD (01:35) Did you have a favorite interview? Yeah, we've been really looking forward to having him on. I love chatting with Souvik Mitra.
Ben Courchia MD (01:50) Yeah, Souvik is always a good customer in these areas. But I also found that we spoke to a lot of people from Pediatrix, the company, which was very interesting to get the perspective of clinical neonatologists in private practice. And not just clinical neonatologists in private practice, but clinical neonatologists in private practice who are trying to do more than just clinical care, which is very hard to do.
Daphna Yasova Barbeau MD (01:53) Yeah. And Ariel Salas, those were my top two. Additionally, there are plenty of our colleagues in academia who are full-time clinical, right? And still trying to squeeze things into their FTE outside of that clinical work.
Ben Courchia MD (02:28) Yeah, absolutely. I hope that we've done this well to show that it's not easy to be in private practice and try to do more things, right? To do clinical research, to do quality improvement, to do education. It was interesting to hear from people who have been successful at doing it, how they've done it, and what they've leveraged. Because I think this is the reality for a lot of people. If you are an NIH-funded academic institution provider, good for you. You've reached the pinnacle of how to have your time protected.
Daphna Yasova Barbeau MD (03:12) But I think it was such a good reminder that so many institutions want to be engaged in research, and you may be neighbors to an academic center. When we talk about multi-site studies, sometimes it's people in your own community that we can be collaborating with. They're seeing a lot of babies every day, and hospitals want to be engaged; clinicians want to be engaged in research. So I think we have such a broader pool of colleagues and babies to be studied than we think.
Ben Courchia MD (03:54) Yeah, absolutely. But without further ado, I guess we can get into Journal Club?
Daphna Yasova Barbeau MD (04:02) It's time.
Ben Courchia MD (04:04) So I guess per tradition, I'm going to open the show today. You mentioned Souvik, so I was like, maybe this is going to be the right way to start this particular episode. And we're going to talk about the PDA. I will tell you about that in a second, because clearly we're not done.
Daphna Yasova Barbeau MD (04:18) Alright. Oof. I thought we were done talking about the PDA.
Ben Courchia MD (04:30) This article that I am reviewing today is called Prophylactic Treatment of Patent Ductus Arteriosus with Acetaminophen. It was published by first author Jean-Christophe Roze from France, who we're actively trying to get on the French podcast. The bottom line is that this is the result of the TREOCAPA study group, which if you were listening to Souvik Mitra's interview, he mentions the results. Now the problem that you run into, that's not something that I've seen being part of hemodynamics, is that people are very collaborative. So these guys have the results of some of these trials ahead of schedule. I've seen the results of the TREOCAPA trial a little bit early myself.
Daphna Yasova Barbeau MD (05:14) Look who's in the know now.
Ben Courchia MD (05:16) I was so surprised somebody brought them up at a private meeting, and I was like, very interesting. Anyway, the background is terrifying, right? When you read about this, I'm going to read the first sentence because I read it, paused, and you're going to see why. "Management of the PDA in extremely preterm infants remains a matter of debate, even though pharmacological constriction and closure of the ductus have been recognized for 50 years." And then I was like, five-zero. We've been at this for 50 years. "Experimental evidence and clinical cohort studies confirmed the association of the development of a symptomatic PDA with mortality and morbidity." "In contrast, meta-analyses and recent randomized controlled trials show that the prophylactic or early targeted treatment of a pre-symptomatic PDA by indomethacin or ibuprofen does not improve outcome, nor is expectant management inferior to early targeted ibuprofen treatment." "These observations could be related to the numerous adverse effects associated with these drugs." This is the other part of the history that got me. "Acetaminophen appeared as a new potential therapy in this debate since 2011." My God, it's been like 15 years. "Although its action on the constriction of the ductus arteriosus has been known since 1981."
Daphna Yasova Barbeau MD (05:48) Yeah, I know. That's as old as neonatology.
Ben Courchia MD (06:47) Man, it's just kind of like, jeez.
Daphna Yasova Barbeau MD (06:51) But it's interesting, because for pretty much our entire careers, acetaminophen has been on the landscape and on the rise. But it was basically just when we started.
Ben Courchia MD (07:02) Yeah, kind of, right? Mechanistically, they mentioned that it's postulated to inhibit the peroxidase enzyme, and this inhibition results in the downregulation of prostaglandin H2 synthase, which consequently decreases the production of prostaglandin E2, ultimately helping the closure of the ductus. Despite its promise, the authors have identified a few critical research gaps. First, the efficacy and safety of acetaminophen, specifically in extremely preterm infants, needed a closer look as these tiny babies were only included in a very small number in previous trials. Something that Souvik has mentioned on our interview is that obviously as we're resuscitating more 22, 23-weekers, these trials that were not including them suddenly now have to be revisited. Second, the optimal dose and duration of treatment to effectively constrict the ductus are unknown, meaning the pharmacokinetics and pharmacodynamics needed to be established. This is where the TREOCAPA project comes in. To fill these gaps, the trial, which stands for prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen, was a massive phase two and phase three study. The phase two portion of the study used a Bayesian approach to identify the minimum effective dose needed to close the ductus. We're talking about babies who are born at 26 weeks of gestation or less. The trial we're reviewing today represents the phase three of the project. The primary hypothesis of this randomized clinical trial was that prophylactic treatment with an appropriate dose of acetaminophen would increase survival without severe morbidity at a post-menstrual age of 36 weeks. They deliberately chose a prophylactic approach. Their goal was to intervene very early to rapidly reduce the left-to-right shunt, thereby preventing systemic under-circulation and pulmonary overflow. They hoped that this would improve survival without adding serious morbidity. I'm going to walk you through a little bit of the methods. They conducted a multicenter, double-blind, randomized, placebo-controlled superiority clinical trial. The patients were randomized into two arms in a one-to-one ratio. It took place in 43 neonatal intensive care units across 14 European countries. Enrollment ran from October 2020 to April 2024. Mentioning the phase two preceding the phase three trial, we're focusing on babies between 23 and 26 weeks of gestation. The patient population eligible for inclusion were babies whose gestational age at birth was between 23 weeks and zero days to 28 weeks and six days inclusive, and if their postnatal age was 12 hours or less. They had comprehensive exclusion criteria. They excluded babies who had congenital anomalies, severe twin-to-twin transfusion, or suspected pulmonary hypoplasia. They also excluded infants with hepatic impairment, which was suspected if there was a hemorrhagic syndrome or severe hypoxemia. Further exclusions included infants who exhibited extreme clinical instability with a high risk of rapid death, if the clinical team failed to start the treatment before 12 hours of life, if the parents were under judicial protection â which was a new exclusion criterion that I had not seen before in most studies â or if the infants were enrolled in another PDA trial. What kind of interventions are we looking at? I think this is where it gets really interesting. Based on the findings of the phase two trial, the intervention dosing was tailored by gestational age. For infants that had a gestational age between 27 and 28 weeks, they began with a 20 milligram per kilogram loading dose within 12 hours of birth, followed by 7.5 milligrams per kilo every six hours for five days, for a total of 20 doses. This specific regimen corresponded to the minimum effective dose identified in previous trials for closing the ductus in this particular age bracket. If you were more immature than that, 23 to 26 weeks, the dosage was a bit higher. They received a 25 milligram per kilo loading dose, followed by 10 milligrams per kilo every six hours for five days. I thought that was very interesting.
Daphna Yasova Barbeau MD (11:32) Yeah, it's interesting, because probably dose matters. You gotta pick something.
Ben Courchia MD (11:37) Yeah. But we usually do â I'm including you in this â we usually do 10 to 15 milligrams per kilo Q6 for a couple of doses, right? That's kind of what I've done before. I haven't done this sort of loading of the acetaminophen. They looked at specific outcomes. The primary outcome of the trial was survival without severe morbidity assessed at 36 weeks post-menstrual age or discharge home if this happened sooner. Severe morbidity was rigorously defined. It included BPD, specifically according to the 2018 NIH definition. It also included necrotizing enterocolitis, intraventricular hemorrhage grade three or four, and cystic periventricular leukomalacia observed at any time up to 36 weeks. They also had a bunch of exploratory secondary outcomes. They looked at successful rates of closure of the PDA, patients who required backup treatment, and whether they were in the intervention or the control group. To confirm the ductus status, echo assessment was performed to evaluate that. In terms of the statistical approach, when they did their sample size calculation, they were looking to assess a 10% difference in the primary outcome. By reaching 36 weeks, they were hoping to see survival without morbidity going from 50 to 60 percent. In terms of results, 778 infants were included in this trial in the modified intention-to-treat analysis. There were 391 infants in the acetaminophen group and 387 infants in the placebo group. The maternal and infant characteristics were not significantly different between the two groups. The overall cohort was quite premature with a median gestational age of 26 weeks and an interquartile range from 25 to 27. In terms of weight, the median weight was 850 grams. Looking at the primary outcome, survival at 36 weeks without severe morbidity was observed in 259 infants in the acetaminophen group compared to 246 in the control group. That meant there was 66.2% survival without severe morbidity in the intervention group with the acetaminophen compared to 63.6% in the control group. The absolute risk difference was a mere 2.7 percentage points, relative risk was 1.04, and a p-value of 0.43, meaning that the difference between these two numbers was not statistically significant. The researchers also noted that these primary outcome results were consistently similar across multiple sub-analyses. They found no significant difference when they looked specifically at infants that were either 23 to 26 weeks compared to babies who were 27 to 28 weeks. The one thing that's important to remember is that as you look at the number of patients in this trial, you clearly see a decay in the number of babies enrolled from 28 weeks to 23 weeks. For example, in the intervention arm of the trial, you have 101 infants at 28 weeks, 90 at 27 weeks, 87 at 26 weeks, and you go all the way down to 23 weeks, and there are only 10 babies at that point. Let's talk about some secondary analyses. Acetaminophen did what it was mechanistically supposed to do. Day seven after birth, the ductus was considered to be closed on echocardiography in 71.2% of the intervention group.
Daphna Yasova Barbeau MD (16:03) Wow. Yeah, that's one of the major arguments against closure, right?
Ben Courchia MD (16:24) What surprised me was that in the control group, it was reported to be closed as well in 52.2% of the group, which was more than I anticipated. The relative risk difference was 1.36. They found that difference to be consistent across all gestational age groups, meaning that you didn't see a difference appear to be wider when you looked at more immature babies. Looking at the need for additional intervention, at least one backup treatment to close the ductus was observed in 14% of the intervention group and 21% of the control group. Interestingly, despite the much earlier closure of the ductus in the acetaminophen group, there were no statistically significant differences in the ventilatory, hemodynamic, or nutritional support required between the two groups during that first week of life. In terms of safety outcomes, the medication was well tolerated. They saw no difference in the change in liver function. Both serious and non-serious adverse events were reported at rates that were not significantly different between the treatment and the placebo group. There was, however, one exception, which was cholestasis. It occurred significantly more frequently in the group receiving acetaminophen. It was observed in 6.4% of the intervention arm compared to 2.6% in the placebo group. The conclusion of the article is that the trial found that prophylactic treatment with acetaminophen did not increase survival without severe morbidity at 36 weeks, despite the fact that it was better at closing the PDA. So here we are. I would advise people to go and listen to our interview with Souvik, who mentioned some of these results and talks a little bit about the state of affairs when it comes to where we are at with the PDA.
Daphna Yasova Barbeau MD (19:09) So, what will you do with your next PDA?
Ben Courchia MD (19:17) I think I agree with what we discussed with Souvik. I think there should be an individualized approach to the PDA. I think the AAP statement about not treating the PDA in the first two weeks really makes it difficult for us to do much unless you have strong reasoning. But I think with hemodynamic assessment, and for babies that are quite immature, 22 to 26 weeks, I think you cannot really leave a PDA open for too long without causing some damage to the heart.
Daphna Yasova Barbeau MD (20:08) I am sticking with the medication theme this week. Most of my papers are regarding medications in the NICU. This is from the Journal of Perinatology. It is called The Prevalence and Safety of Diazoxide in the Neonatal Intensive Care Unit. Lead author Lucas Collins, senior author Rachel Greenberg. This is coming through the Pediatrix Center for Research using their data warehouse. This paper caught my eye because my sense is that our unit has had a real increase in hypoglycemic infants, and diazoxide has come up as a point of conversation for many of these babies. As a reminder for units who don't use a lot of diazoxide â which is a lot of units, as they'll talk about in this paper â it's a non-diuretic benzothiadiazide derivative. It's the only medication approved by the US FDA for infantile hyperinsulinism. It binds to the pancreatic islet cells where it finds the potassium ATP receptors. It hyperpolarizes the cell membrane and prevents the release. That's why it's a great medication for babies with hyperinsulinism. The FDA approval is limited to a very specific subset of conditions: symptomatic hyperinsulinemic hypoglycemia caused by leucine sensitivity, extrahepatic malignancies, islet cell hyperplasia, islet cell adenoma, and adenomatosis. It's frequently used as a first-line treatment for all types of infantile hyperinsulinemic hypoglycemia. Its most common use, however, is off-label for transient infantile hyperinsulinism. As part of its story, in 2015, the FDA issued a black box warning for the development of pulmonary hypertension in infants receiving diazoxide. Furthermore, the medication has a tendency to reduce free water clearance through sodium retention. It often requires diuretic therapy, which is another potential adverse effect. I think after that happened, units were even more concerned about initiating diazoxide. The study wanted to look at updated data regarding diazoxide use across NICUs, also looking at some of the demographic and clinical factors associated with diazoxide treatment. This is a cohort study. The infants were discharged from any of the 345 NICUs managed by PMG between 2017 and 2022. As I said, all data was extracted from the PMG clinical data warehouse. Let's talk about some definitions as we move in. For hypoglycemia status, I'm chuckling because a lot of it was based on clinician diagnosis. If you made the diagnosis, that's how it was defined. Hypoglycemia was determined based on clinician diagnosis in the EMR. The etiology of hypoglycemia â congenital or transient hyperinsulinism â was also based on clinician documentation. They used the Olsen definitions to classify infants as SGA or LGA. New exposure to diuretics, oxygen, or ventilators was defined as initiation after the start date of diazoxide. Only new exposures occurring at least one day after the initiation of diazoxide and before its discontinuation were included. They really wanted to distinguish babies who were needing new respiratory or medication support after the initiation of diazoxide. In terms of results, they had 545,065 infants admitted to the NICU between 2017 and 2022. Of these, 22% were diagnosed with hypoglycemia. Among all NICU admissions, 0.16% â so less than 0.5% â were exposed to diazoxide. Of those exposed to diazoxide, 95% were also diagnosed with hypoglycemia. The percentage of hypoglycemic infants exposed to diazoxide varied widely across the 272 centers that discharged at least 50 hypoglycemic infants during the study period. You can see that about 50% of units had 0% diazoxide use, going up to 16% in the units with the most use. The percentage of infants diagnosed with hypoglycemia and the percentage exposed to diazoxide slightly decreased from 2017 to 2022, but these changes were not statistically significant. There was a peak in 2020 and then a downtrend to 2021 and 2022, both for hypoglycemia diagnosis and diazoxide exposure.
Ben Courchia MD (26:32) I know you're describing the pattern of the curve, but these are very mild. Even based on the units on the x-axis. They haven't seen what we've seen. We feel like every kid's hypoglycemic. Maybe it's our machines.
Daphna Yasova Barbeau MD (26:40) Right. They're pretty flat. I feel like we've got a bunch right now that are out of proportion. It's not like we put them on a normal amount of D10 and they recover after one bad glucose. These kids are down and out.
Ben Courchia MD (27:04) One bolus, yeah.
Daphna Yasova Barbeau MD (27:09) Okay, so that's the overview. For the group of infants that were hypoglycemic, the median gestational age and birth weight in the group exposed to diazoxide were 36 weeks and 2.53 kilos, as compared to those babies who were not exposed, at 36 weeks and 2.62 kilos. The median postnatal age and PMA at diazoxide initiation was nine days and 38 weeks, with a median exposure duration of four days, which I thought was interesting. Documented hyperinsulinism diagnoses also differed between groups. Among the hypoglycemic infants who got diazoxide, 23% were reported to have congenital hyperinsulinism and 16% had transient hyperinsulinism, compared with less than 1% for both diagnoses among the non-exposed hypoglycemic infants. On univariable analysis, the median length of NICU stay was significantly longer for hypoglycemic infants exposed to diazoxide, 23 days compared to nine days. Significant differences were also observed between the two groups. The hypoglycemic infants exposed to diazoxide were more likely to be male (61% versus 56%), more likely to be growth restricted (SGA 30% versus 15%), or LGA (24% versus 19%) compared to those not exposed. There were no significant differences in prenatal steroid exposure or mortality rates between the two groups. Among the hypoglycemic infants treated with diazoxide, 1% were already receiving at least one diuretic prior to initiation, and 26% were started on a diuretic on the same day as diazoxide. It seemed like the clinical team started diazoxide and the diuretic at the same time, given the risk. Additionally, 17% had a pre-existing oxygen requirement and 4% were already on a ventilator at the time of initiation. Of the infants treated with diazoxide, 2% developed pulmonary hypertension at a median of six days during exposure. Another 2% were diagnosed after diazoxide had been discontinued. And 7% carried a diagnosis of pulmonary hypertension prior to diazoxide initiation. NEC was diagnosed in 2% and seizures occurred in only one infant (less than 1%) following diazoxide initiation. Among those infants exposed to diazoxide, 87% were discharged home, 11% were transferred, and 1% died.
Ben Courchia MD (30:45) So from the database standpoint, you're saying that they didn't really have that information â got it.
Daphna Yasova Barbeau MD (30:48) Correct. But there were nearly 500 infants discharged home with known end dates for diazoxide. 11% of those babies were still receiving diazoxide at discharge. 6% of these infants were also receiving diuretics at discharge. The median total duration of diazoxide exposure prior to discharge for those 53 infants was five days, with a range of four to seven days before the decision to discharge home on the medication. Infants discharged home while receiving diazoxide were more likely to have been born at greater than 36 weeks gestation (64% versus 40%), more likely to have a birth weight greater than 2,500 grams (77% versus 51%), and be of white race or ethnicity compared to those who had diazoxide discontinued prior to discharge. I think people are most comfortable with older, more mature babies going home on diazoxide. Their overall conclusion is that diazoxide use has been pretty stable across time in US NICUs, though there is much variability in use across centers. Some infants exposed to diazoxide did require additional therapies, most commonly diuretics. Most were able to wean off of diazoxide prior to discharge. And again, we need larger trials to better characterize the efficacy, specifically for the various types of hypoglycemia that we see.
Ben Courchia MD (32:44) Very interesting. I'm painfully aware of this data because since starting a hemodynamics fellowship, I get consulted when I'm in Montreal for kids on diazoxide for pulmonary hypertension rule-out. It's a pain because the babies that usually get started on diazoxide are the full-term ones. They're usually very cranky and it's a very hard echo to do. I know that when I see a former 35, 36 weeks, now two weeks old, needs an echo... It's like, oh man. My first reaction to all this was, diazoxide equals more hypertension. I don't know. I didn't know that. There it is.
Ben Courchia MD (33:38) I was very excited about this paper for a multitude of reasons. I'm going to tell you it's a paper I found in JAMA Network Open. The article is called "Drying Very Preterm Infants Before Plastic Wrapping at Birth, a Randomized Clinical Trial." This is coming from the NeoDry trial group. The senior author of the paper is none other than Daniele Trevisanotto, who we did a whole series with.
Daphna Yasova Barbeau MD (34:17) What a great name. It's probably two years. Yeah, November 2023 on thermoregulation of the neonate.
Ben Courchia MD (34:20) It feels like it was just yesterday, but it was a really great mini-series. We got a lot of good feedback on the mini-series. On thermoregulation. I know, right? I was going to say last year, but it was a great mini-series because thermoregulation is an important topic. It's an important marker of quality, and it's highly associated with mortality and other morbidities. So we should pay attention to thermoregulation, which is why I think the series was so good. We want to thank GE Healthcare, who helped with the production of that series. We can't do it without the help of our sponsors, so thank you to them.
Daphna Yasova Barbeau MD (35:18) For people who are looking, that's episodes 159 through 163, if you want to take a listen.
Ben Courchia MD (35:23) Right. And Daniele Trevisanotto, who is coming from Italy, was one of the featured guests on this series. I always enjoy talking to people, especially from abroad, because you can always learn about new ways of doing things. I was very excited to see this paper for that particular reason. I thought the question was very clever. The introduction is very important. The maintenance of thermal homeostasis is a critical milestone, as they call it in the paper, in neonatology. We know from extensive research that hypothermia at birth is clearly associated with adverse neonatal outcomes. Despite this awareness, the incidence of hypothermia in very preterm infants at the time of admission to the NICU remains stubbornly high.
Daphna Yasova Barbeau MD (36:09) Stubbornly. Who's stubborn? Us or the babies?
Ben Courchia MD (36:13) Well, listen to the series. Not you, Daphna. I know you were there. I think we don't realize that we're doing all these efforts to keep babies warm. But we're also doing interventions for neurodevelopment that are increasing the time the baby is not under the warmer, for example. As we delay cord clamping, how are we maintaining homeostasis and thermoregulation during that time?
Daphna Yasova Barbeau MD (36:53) Yeah, and temperature is so linked to IVH.
Ben Courchia MD (36:57) Yeah, absolutely. I think it's very interesting because it's something that is very difficult, that always falls by the wayside. Again, listen to the series; it's something that is often delegated to the nurses when it really is a team effort, truly. But it's true, when you're doing a minute of delayed cord clamping, how are you setting up your OR? What kind of temperature are we talking about? All these things are very important. International guidelines for neonatal resuscitation suggest several standard interventions to prevent thermal loss. They include ensuring adequate room temperature, infant warmers, applying polyethylene bags or wraps, using preheated mattresses, applying caps, and utilizing heated and humidified gases. Interestingly, while drying the infant is a highly recommended procedure for the thermal management of babies born at 32 weeks or greater, this intervention is explicitly not indicated for very preterm infants. Current practice dictates that these tiny vulnerable babies should be put directly into a plastic wrap immediately at birth without any prior drying. The authors point out that this specific recommendation to skip the drying portion is based on prior studies that compared wrapping the baby in the bag without drying against drying the baby without wrapping the baby. I'm going to say that again. The comparison made was whether we should just put the baby straight in the bag or whether we should dry the baby and not put the baby in the bag.
Daphna Yasova Barbeau MD (38:13) It's one of those things we've been doing all this time, thinking there was great evidence, when maybe there was a third group that got dried and put in a bag.
Ben Courchia MD (38:22) Yeah, right. What they're saying is, what if we combine the interventions? Meaning, what if we dried and put the baby in the bag? They said this had not really been fully explored. To the authors' knowledge, only one prior study had investigated the role of drying before wrapping. While that study found comparable temperatures between the two methods, it did not look at very preterm infants who are at significantly higher risk for heat loss due to evaporation. Based on this gap in the literature, they hypothesized that drying the infant before putting the bag on the baby could limit evaporative heat loss immediately after birth and then improve rates of normothermia at NICU admission. Let's talk a little bit about the methods. This was a multicenter, unblinded, randomized clinical trial performed across 21 Italian tertiary hospitals. Neonates were eligible to participate if they had an estimated birth weight of less than 1,500 grams, a gestational age of less than or equal to 30 weeks and six days, or both. They had to be inborn, get parental consent, and they excluded neonates with major congenital anomalies, cardiac disease, congenital diaphragmatic hernia, abdominal wall defect, and neural tube defects. Before the trial began, they randomized the babies one-to-one for each participating hospital. They were either going into the intervention arm, which involved drying the baby before wrapping in the delivery room, or the control arm, which involved just putting the baby in the bag without drying. In the delivery room, participants in both arms were managed according to current guidelines for neonatal resuscitation. Standard care included maintaining the room temperature of the delivery suite between 23 and 25 degrees Celsius, employing delayed cord clamping for more than 30 seconds in babies that were uncompromised or vigorous, placing the neonates under a radiant warmer set to maximum power, covering the infants with a plastic bag or wrap up to the shoulders, and covering the head with a cap. Importantly, pre-warmed mattresses and heated humidified gas were optional based on the clinician's preference. The critical difference was that participants in the treatment arm were intentionally dried with a pre-warmed towel before the plastic wrap was applied. When did they then measure the temperature? At the end of stabilization and resuscitation, each subject of the study was transferred to the NICU in an incubator set at 37 degrees Celsius. Once in the NICU, the plastic wrap was removed when the infant was placed into its incubator. Axillary temperature was measured using a digital thermometer at three distinct time points: at the end of stabilization in the delivery room, upon NICU admission, and finally one hour after admission. The primary outcome was the proportion of participants who were in the normothermal range, defined as between 36.5 degrees and 37.5 degrees Celsius at the time of admission. Secondary outcomes included proportions of participants with hypothermia, moderate to severe hypothermia, or hyperthermia. They also tracked some notable clinical morbidities: IVH, RDS, late-onset sepsis, BPD, and in-hospital mortality. Let's talk about the results. From 2023 to 2024, the study screened 458 neonates for eligibility. They were able to randomize 354, including 180 females and 174 males, with a mean gestational age of 28.6 weeks. 177 infants were randomized to the drying arm and 177 assigned to the control arm. When looking at the primary outcome, the intervention did not show an advantage. Upon NICU admission, normothermia was reached in 45.8% of neonates who were dried compared to 46.3% of neonates who were not dried.
Daphna Yasova Barbeau MD (43:37) Wow. We've got a long way to go. But I did think the drying would help.
Ben Courchia MD (44:00) I know. We'll see what it's not. We're not finished with the data, because you're going to see you definitely don't want to dry babies. The proportion was not statistically different between these two arms in the unadjusted and the adjusted analysis. In terms of secondary outcomes, for almost all of them, there was no evidence that the clinical outcome differed between the two arms. Looking at safety metrics, there were a few cases of severe hypothermia, but they were not statistically significant between the arms. There were also no cases of severe hyperthermia. In terms of mortality, there was a stark and unexpected difference. In-hospital mortality was observed in 14.7% of the drying arm.
Daphna Yasova Barbeau MD (45:16) I know, it's so disappointing. You wonder what the downward effects of skin integrity are.
Ben Courchia MD (45:28) This generated a relative risk of 2.7. As you can expect from a team of rigorous researchers, they went deep into the data and performed a rigorous post-hoc analysis, which confirmed that the drying arm was associated with increased mortality even after adjusting for clinically relevant confounders like sex, gestational age, multiple births, and intrauterine growth restriction. In terms of gestational age sub-analyses, they looked closely at 102 participants born between 23 and 27 weeks and six days. In this extremely preterm group, the drying arm had a significantly lower neonatal temperature at one hour of age and an alarming increased relative risk of mortality of 4.71. Conversely, for the 213 participants born between 28 and 31 weeks and six days, the outcomes were not significant between the two arms. In the discussion, the authors confront the surprising mortality head-on. They acknowledged that the higher mortality rate among the dried neonates was unexpected, particularly given the general safety of the procedure.
Daphna Yasova Barbeau MD (46:53) And because it's the mainstay of the initial steps of NRP, right?
Ben Courchia MD (46:58) Yeah, but not for these very small preemies. Because this mortality finding remained consistent across more than one sensitivity analysis, they emphasized that it required further clinical attention. They carefully reviewed the clinical records of each neonate that passed away. According to the authors, most of the deaths could be expected due to the "compromised clinical profile" of the neonates, saying that these babies were sick to begin with. Again, relating to the extreme prematurity, severe disease state, and so on. Furthermore, the stratified analysis suggested that the subgroup of the smallest infants was really what contributed to the mortality difference between the study arms. The authors noted that they could not completely exclude the possibility that the physical process of drying the infant immediately after birth could have triggered some degree of cardiovascular instability due to the manipulation of these very small, very fragile infants. But ultimately, they could not find a definitive pathophysiologic explanation related to the trial intervention itself, leading them to suggest that the mortality difference might just simply be a random finding. They also highlighted that while drying is formally recommended for the thermal management of older patients born after 32 weeks, their trial suggests that the procedure is not actively harmful in babies who are 28 to 32 weeks. Still, they warn that the importance of this critical mortality outcome cannot be understated and warrants further investigation. They also draw attention to the elephant in the room beyond the mortality, which is that less than half of the neonates arrive in the NICU in a normothermal range. To wrap up, I'm going to quote the conclusions from the study: "In this multicenter randomized clinical trial, drying before plastic wrapping provided no benefit to very preterm infants in maintaining normothermia at NICU admission." "Approximately half of the infants were outside the normal thermal range at NICU admission." "Most deaths could be expected due to the compromised profile of the neonates, and we could not reasonably find a pathophysiologic explanation related to the trial intervention." "Thermal management of such vulnerable infants is still a challenge and needs further investigation on suitable improvements of the current thermal intervention."
Daphna Yasova Barbeau MD (50:13) Now, I do think maybe they don't have that information, but not all the babies had the same thermal environment, right? They weren't all on thermal mattresses. That was different between babies.
Ben Courchia MD (50:34) You could potentially make the case for the mattress to basically improve the rates of normothermia on admission. But do you think that impacted... I mean, that could have an impact. And then mortality could be a downstream effect of that.
Daphna Yasova Barbeau MD (50:44) Maybe. Absolutely. Especially because, as we learned, there are so many ways thermoregulation works, right? Convection, et cetera. All those things that are also frequently tested on the board exams.
Ben Courchia MD (51:00) All the things. You're post-call, we're gonna excuse you. Evaporation, radiation, conduction, convection.
Daphna Yasova Barbeau MD (51:10) Radiation, convection, conduction! So that would be conduction, right? Direct skin to warmer, transwarmer.
Ben Courchia MD (51:21) Yeah, to the transwarmer. Exactly.
Daphna Yasova Barbeau MD (51:24) But I also think it highlights some low-hanging fruit where you're like, this is clearly a deficit for a lot of units. Let's work on thermoregulation. And that may look different for every unit, how you're able to tackle that.
Ben Courchia MD (51:44) Or just do the thing that they did. Just look at admission temperature, look at mortality. It's always an interesting thing to do when you're doing your stats for your unit.
Daphna Yasova Barbeau MD (51:23) I'm glad to hear that. Well, I know you're a fan of strong coffee and BPD papers, so this is one for you for sure. This is in the Journal of Perinatology. It's entitled "Effects of Higher Caffeine Dosing on Rates of Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes." Lead author Sarah Fleischacher and senior author Sourabh Verma. This is coming from NYU Hassenfeld Children's Hospital. The background is useful, and we've done a pretty good review of the CAP trial and caffeine for people who want to take a listen to that. We interviewed Dr. Barbara Schmidt on episode 136; she is one of our giants of neonatology. And we have a board review PowerPoint on caffeine for apnea of prematurity. The background states BPD is the most common complication associated with prematurity. Caffeine is one of the most common medications used in the NICU based on its utility in the CAP trial, the Caffeine Therapy for Apnea of Prematurity Study. In that study, they looked at infants between 500 and 1,250 grams who received a loading dose of 20 mgs per kilo, followed by a maintenance dose of five mgs per kilo of caffeine. Babies who were in the intervention arm had reduced rates of BPD compared to the placebo group. So it pretty much became the standard of care practice to give a caffeine bolus and continue on a maintenance dose to infants born less than 34 weeks until 34 weeks post-menstrual age. Notably, since the CAP trial, our definitions for BPD have changed a little bit. As we proceed through this conversation, it should be noted that the BPD criteria used is the Jensen criteria, the newest NICHD definition from 2019. Subsequently, other studies were done looking at high-dose caffeine compared to standard-dose caffeine in preterm newborns who are at risk of lung disease, which showed it was unclear if higher doses improve neurodevelopmental disability or duration of hospitalizations. But there was a signal that higher doses may reduce rates of BPD. Most of these studies were in large groups of babies that included more mature babies, kind of all babies less than 32 weeks gestation. So they really wanted to evaluate the efficacy and safety of using a higher maintenance caffeine dosing in infants born less than or equal to 28 weeks gestation. And again, its impact on neurodevelopmental outcomes and the outcome of BPD. This was a retrospective observational cohort study, a single-center study at New York University, which is a level four regional perinatal center. Eligible infants were born at less than or equal to 28 weeks gestation. They must have received caffeine between 2017 and 2023. They were excluded if they didn't receive caffeine in the first week of life, if they had congenital anomalies or congenital heart disease requiring surgical intervention that might affect respiratory drive, or if they had anomalies of lung development or anomalies that were felt to impact neurodevelopmental outcomes. Standard practice in their unit is to give that loading dose of 20 mgs per kilo for less than 34 weeks, followed by a maintenance dose of five mgs per kilo per day until 34 weeks. In the last five years of this cohort, there was a shift in practice to increase the maintenance dose to a range of 7.5 to 10 mgs per kilo per day for infants born at less than or equal to 28 weeks gestation. 62 infants were in the low-dose group. They considered low dose as an average daily dose of less than or equal to six mgs per kilo per day. High-dose infants were 111 of those babies that still got a 20 mgs per kilo bolus, but received an average daily dose of greater than six mgs per kilo per day. The primary objective was to compare rates and severity of BPD in the infants who received low versus high daily caffeine doses. A secondary objective was to compare neurodevelopmental outcomes using the Bayley scores. Most infants were followed up at their outpatient clinic at 6, 12, 18, and 24 months. There were some differences. Birth length and five-minute Apgars were lower in the low-dose group. Rates of maternal chorioamnionitis, which we know is linked to BPD, were higher in the low-dose group. The average daily dose of caffeine in the low-dose group was 5.15 mgs per kilo per day, while the average daily dose in the high-dose group was 8.18 mgs per kilo per day. There was no statistically significant difference in the duration of treatment or the need to decrease the dose secondary to adverse effects such as tachycardia. There were significantly higher rates of surgically treated PDA, number of packed red blood cell transfusions given prior to 36 weeks, duration of invasive ventilation, as well as patients discharged home on respiratory support seen in the low-dose group. When looking at the BPD outcomes, there was no significant difference between the rates of BPD overall. However, there was a statistically significant difference in the severity of BPD between the two groups. The low-dose caffeine group had grade one or mild BPD in 30% of patients compared to nearly 36% of patients in the high-dose group. Grade two or moderate BPD was 35% of patients in the low-dose group compared to 60% of patients in the high-dose caffeine group. Grade three was 35% in the low-dose caffeine group compared to 7% in the high-dose caffeine group. When evaluating the Bayley scores at 6, 12, 18, and 24 months, there was a difference in cognitive scores at six months. This was not seen at subsequent follow-up. They conclude that the study adds to the data that may support a higher maintenance dose in this population of less than or equal to 28 weeks. There was a significant reduction in the rate of severe BPD and an improvement in the Bayley cognitive score at six months. Importantly, there were no differences in adverse outcomes noted between the two groups, such that caffeine at higher doses may be safe and may confer some additional protection for these babies. Thoughts?
Ben Courchia MD (59:48) What are your thoughts? You love caffeine. It's interesting because I was going to mention the discussion we had after our On with VON episode with Dr. White. You are a neurodevelopmental expert, and you said, "Can we retime our caffeine to morning time caffeine?" Everybody was on board, and then the question came up: What if you give a loading dose too close to the morning dose of caffeine? Do you give it the next morning or do you wait another day? And you were like, "No, it's fine. More caffeine, there's no issue."
Daphna Yasova Barbeau MD (01:00:13) See, it's fine.
Ben Courchia MD (01:00:21) So I know you advocate for more caffeine. I'm just wondering what your thoughts are.
Daphna Yasova Barbeau MD (01:00:27) Well, I myself have experienced adverse effects of caffeine. So I know that I had to cut back on my caffeine. When I moved to South Florida, I realized that I was getting cafecitos five or six times a day passed in the unit. That is not something I had been drinking in Gainesville, Florida. Anyways, I think that caffeine is one of the few interventions that we have good data for in the NICU. Could we go higher on caffeine? I don't know. We have lots of babies in our unit where I feel like we are reducing caffeine quite a bit for tachycardia. Does it always fix the tachycardia? No, it usually doesn't in those babies that just stay tachycardic. But I think there's a lot of discussion about how we use caffeine. What's the timing for caffeine? In every unit that I've been in, we've done things differently. In one unit, we started a dose, we never checked it, and we never increased the dose. In one unit, we checked the levels and we increased the dose based on the levels. In our current unit, we weight-base the dose weekly. We don't really have good data for any of those practices. So I think for young early neonatal professionals, I think people think caffeine is solved, but I think there's still work to be done.
Ben Courchia MD (01:01:59) I was not very impressed with that particular paper from the standpoint that I don't know how much stake I place on a six months' Bayley.
Daphna Yasova Barbeau MD (01:02:10) Sure, yes. I mean, the CAP trial showed improvements at school age, but that didn't bear out into adolescence.
Ben Courchia MD (01:02:19) But the point of this paper is like, could I give more caffeine basically? It doesn't seem to be causing harm. That's first; I think that this is quite good. Am I going to be prompted to increase the dose of caffeine on babies because a retrospective study shows that at six months Bayley, the cognitive outcomes are marginally better? I don't know.
Daphna Yasova Barbeau MD (01:02:44) Yeah, I 100% agree with you, but a reduction in severe BPD is no small thing. That means, with this criteria, invasive mechanical ventilation at 36 weeks.
Ben Courchia MD (01:02:59) Yeah, it's a small group and it is... yeah, the BPD outcomes are...
Daphna Yasova Barbeau MD (01:03:10) It's a small group, obviously, but I also think the average caffeine doses weren't that different, six and eight overall. Most everywhere I've worked, we've been doing 10 per kilo.
Ben Courchia MD (01:03:21) Yeah.
Eli (01:04:14) One notable thing that we should talk about in the incubator world is we had the Delphi Conference since our last recording. We were talking about it before we came on air. You guys have been navigating the maddening curse of conferences. Every time you have a Delphi Conference, the ten plagues rain down upon you. How did it go?
Ben Courchia MD (01:04:39) I think it went well. The content of the conference was phenomenal. The speakers that came to the conference and the ideas they shared were quite exceptional. You're right. In 2024, when we did the conference, Hurricane Helene was on its way to the east coast of the US. People had to flee Florida on the last day of the conference. So we thought doing it in January would be a safe bet. Little did we know that 40 out of the 50 states in the US would be paralyzed by a polar vortex. We adapted. Online live streams and a lot of logistical juggling. I think it went okay. I'm almost eager to find out what the universe is going to throw at us for the next edition.
Eli (01:05:32) That is a sick interest. It's like Final Destination out there; I just gotta stay tuned. I'm delighted that it went well. Listeners, you are getting a post-Delphi, post-call Dr. Ben Courchia, and I am in Nepal. We're going to be unhinged this episode. We're going to see how it goes. This is our second go of this brave new experiment that we've been trying out in the new year. Basically, quick hitters, one article or one major topic, a deep dive. We're going to run them every week with Journal Club. Let us know what you think, what we're doing well, and what we can do better. We love your feedback. Our inboxes are open if you think there are ever articles that we should be covering. Without further ado, why don't we dive into the first article, or set of articles really. These focus on some interesting testing and announcements done by the state of Florida. Labs associated with the state tested 24 brands of infant formula for pesticides and four heavy metals: mercury, cadmium, arsenic, and lead. They found elevated levels of at least one heavy metal or pesticide in 16 â two-thirds â of the brands of formula, and they detected the most toxins in Similac Soy Isomil in particular. Testing lots of different formulas and finding heavy metals sounds deeply scary to me and probably most people. There's probably a little bit of context here that needs to be discussed in terms of heavy metal exposure in the general water supply and other things. Before we go much further, Ben, how did you interpret the state's decision to do this testing, release all this testing publicly, and the way they decided to announce it?
Ben Courchia MD (01:07:52) I think it was interesting because you didn't know this was going on. Then on the news, scrolling through articles, you find out the governor of Florida is announcing they've tested all these formulas and there are toxic levels of heavy metals. If you're a parent and you read this, you think, "Oh my God, what am I doing to my baby?" As a clinician, you wonder how this happened and what exactly was done. What's interesting is the fact that it was done. It's not exactly clear in what context. They created a website called exposingfoodtoxins.com where they show the reports from this testing. We don't really understand the results and how to interpret them because we know the presence of other elements in formula is helpful to increase shelf life or keep them safe. There's no information on that specifically. To me, it is very concerning because it leads parents to ask what they are supposed to do. Another aspect is that in testing 20 or so formulas, they are testing a lot of formulas that are not FDA approved. They may be FDA approved for distribution, but haven't gone through the FDA approval process. For example, one of the formulas I saw in this report is ByHeart. If you look at the ByHeart formula, it says there are no heavy metals, but it is under active recall. You wonder because of the presence of botulism, and there have been news articles about this formula and cases of botulism associated with its ingestion. It begs the question: what exactly is next for this type of information, and what are parents supposed to do about this? We're going to find out that the formula companies are probably going to give a little bit more context. If the state is doing the testing, they should be providing a preamble to why they're doing this and some guidance as to what will be done if they believe this is an issue.
Eli (01:11:57) We're already seeing some of the formula companies come out and criticize the state for not sharing methodology. In peer-reviewed scientific experiments, we would never forgive a study author group for leaving out methodology and just publishing results. Part of the challenge interpreting these data is the context. In the first section of any peer-reviewed article, there's a big introduction that gives context on the issue, and we don't have that here. The second section is the methods, and we also don't have that. This is like a research letter where all you got was the graph and the conclusion statement, without anything else. Even with that conclusion statement, I totally agree with you, Ben. The question is, what do we do with that? It's a little bit like when we get variants of unknown significance on a genome-wide association study. We found this, but what do we do? Heavy metals in formula sounds bad, and it is scientifically plausible that it is bad. But the question is how bad and what's the alternative? For families whose infants are on formula, what does this mean for how they use formula and what the alternative is? If the alternative is growth faltering bordering on malnutrition, are the risks of trace heavy metal exposure worth the benefits of preventing growth faltering? That's something I would have liked to know in the context of this study.
Ben Courchia MD (01:13:01) You've put your finger on the problem here. What exactly does that mean and translate into when it comes to infants? Does that translate into measurable levels of heavy metals in the blood of infants exposed to these formulas? We don't know any of that. It's a staple of this particular administration where we have to surmise and create the narrative for what to follow. That really is a dangerous game to play because families rely on these products to feed their baby. If this promotes breastfeeding, that's phenomenal. But it's concerning how parents are supposed to handle this information. As a clinician, I don't know about you in California, but in Florida, we're seeing a lot more parents coming into the newborn nursery and the NICU wishing to bring their formula from home. In our hospital, we don't have a contract with a specific company. The two FDA-approved companies in the US are Similac by Abbott and Enfamil. People in our unit can get both by preference. We don't have issues with either, but sometimes they'll ask to bring something else. Our institution does not allow parents to bring other formulas. It is tricky because reports lacking context lead people to steer away from the FDA-approved ones and go to ones produced in other countries. What kind of oversight are we looking at? There's a complete lack of transparency. Do you have these issues of parents wanting to bring other types of formulas, and how do you handle that in California?
Eli (01:15:17) I can't say I'm super familiar with our formula policies. What I think is interesting is what you brought up about regulatory agencies. This is an emerging trend where data or reports are released, often without transparent methods, bearing significant implications for families. The MAHA initiative seems aligned with the principle of people wanting to be more engaged in their health, going after big food and pharma. Theoretically, that's not bad. The challenge is the lack of transparency, methods, and context. The other challenge is the "so what" question. One way to think about finding trace metals in formulas is to say, don't use any of them â like breast is best.
Ben Courchia MD (01:18:55) That's exactly the mental leap they're hoping you make.
Eli (01:18:56) Right. The other option in a theoretical world is giving regulatory agencies more purview to continue these studies, so it's not dependent on one study from one state. Formula falls into a challenging regulatory loophole where some regulation is done by the EPA and some by the FDA. It's not clear who follows up when mixing sterile water. These agencies have lost capacity in different districts within them. This study coming out under the MAHA agenda while gutting these agencies of regulatory capacity strikes me as a challenge to understanding the report and knowing how to guide our families in the future. Normally you might say this was an initial finding and they'll follow up. Now the question is, we have this released into the universe, what happens next? We don't know.
Ben Courchia MD (01:19:16) We absolutely don't know. We'll find out how the community responds. That's not a great way of doing this type of public service. I think they're falling short.
Eli (01:19:37) I guess we will see. All we can do is continue to provide all the information we have with lots of caveats.
Ben Courchia MD (01:19:39) This was well covered in the news. People can search Google for "Florida testing of baby formula." Lots of outlets have covered this. I looked at the Miami Herald, but people will find it in different places.
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