Neonatal Research

Jiang ZD, Ping LL, Chen C, Wilkinson AR: Brainstem auditory response findings in preterm infants after necrotizing enterocolitis. Acta Paediatrica 2012, 101(12):e531-e534. Auditory brainstem response latencies were longer in preterm infants who had had NEC (when they reached term) compared to term infants. This may be a sign of brainstem dysfunction in this group of infants.

Ivars K, Nelson N, Finnström O, Mörelius E: Nasopharyngeal suctioning does not produce a salivary cortisol reaction in preterm infants. Acta Paediatrica 2012, 101(12):1206-1210. Salivary cortisol did not increase with nasopharyngeal suctioning, whether or not you gave glucose before the intervention, also pain scores did not increase.

van der Laan ME, Verhagen EA, Bos AF, Berger RM, Kooi EM: Effect of balloon atrial septostomy on cerebral oxygenation in neonates with transposition of the great arteries. Pediatr Res 2012. Cerebral oxygen saturations were very low prior to the Rashkind procedure in newborns with transposition. This is not too surprising as systemic oxygenation is poor also. The systemic saturations increased from 72% to 85% within 2 hours, cerebral saturations increased from 42 to 48% in that period, and then continued to increase to 64% 24 hours afterward.

Whitelaw A: Periventricular hemorrhage: A problem still today. Early Human Development 2012, 88(12):965-969. Good review of the state of the art.

Brown SD, Donelan K, Martins Y, Burmeister K, Buchmiller TL, Sayeed SA, Mitchell C, Ecker JL: Differing attitudes toward fetal care by pediatric and maternal-fetal medicine specialists. Pediatrics 2012. This questionnaire study compared the attitudes of obstetric maternal fetal medicine specialists and pediatricians who are involved in fetal counseling. They asked whether and when pregnant women should be seen by pediatricians when the fetus was affected by (1) maternal alcohol abuse, (2) maternal cocaine abuse, (3) maternal use of seizure medications, and (4) maternal diabetes. We asked whether such counseling should occur (1) before a decision about continuing or terminating the pregnancy, (2) only if the decision has been made to continue the pregnancy, (3) only after delivery, or (4) never. MFMs and the pediatricians had very different opinions, 40 to 50% of the MFMs didn’t think that a pediatric consultation was ever necessary for each of these indications, and when they did think they were necessary, it was mostly after the woman had decided to continue the pregnancy. Pediatricians in contrast thought that most women should be seen by a pediatrician before they make any decision. The also asked the respondents about the appropriateness of seeking court intervention to compel adherence when a pregnant woman has decided to continue a pregnancy but refused to comply with recommendations regarding the following: (1) a program to discontinue cocaine use at 25 weeks; (2) azidothymidine (AZT) therapy to prevent perinatal transmission of HIV at term; and (3) percutaneous transfusion for fetal anemia secondary to Rh isoimmunization at 25 weeks. Pediatricians were far more likely to want court orders than the MFMs.

This is an innovative Randomized Controlled Trial.

Hofmann J, Zotter H, Kerbl R: How to dress as a paediatrician? Acta Paediatrica 2012, 101(12):1260-1264.
“One hundred and seven children and 72 parents were visited by a paediatrician randomly wearing one of the three different outfits (casual, semiformal, formal) during a hospital stay.” They were then asked what they thought.

Parents and children preferred the casual style, and parents trusted the doctor just as much regardless of dress.

This is the figure from the article showing the different styles.

Yay! Its T-shirt time. Now I know why I never wear a tie.

When I started this blog I intended it mostly for my own trainees, with the hope that others might find it useful, and that the energy expended for my fellows (and colleagues) could help others struggling like me to stay on top of the literature. As well as giving my own idiosyncratic interpretations of published articles, and trying to evaluate research in the context of previous published research.

Since the first posts on the 5th of May, I have written 101 posts, and the blog has just passed 20,000 page views from 105 countries.

Thanks everyone for their positive comments, I hope I can maintain the effort for another 6 months, and fill in the rest of the world map.

The grey areas on the map below are those countries that have not yet benefited from neonatalresearch.org!

This is the title of a live webinar debate, Nov 29^th, 12-1pm

Organized by the Children’s mercy Hospital, Kansas City.

The Information for the Webinar is as follows:

Every NICU or PICU doctor has faced the following situation:  A baby is dying, slowly, of multisystem organ failure.  The family insists that everything be done and will not agree to a DNR order.  The doctors, nurses, chaplains and social workers have tried explaining the situation.  The disagreement has become intractable.

In such situations, doctors usually respond in one of three ways: 1) they sometimes continue discussions and try to convince the patient or family to agree to a DNR order; 2) they sometimes accede to the family wishes and do the CPR, even though they find it reprehensible to do so; and 3) they sometimes refuse to do CPR, explain this to the patient or family and, if disagreement persists, seek legal sanction to override family’s choices.

We have brought together two national experts in neonatal bioethics to discuss these situations.  Children’s Mercy Bioethics Director John Lantos, MD, will moderate and our special guests will be:

–          William Meadow, MD, PhD, Professor of Pediatrics and Assistant Director of the MacLean Center for Clinical Medical Ethics at The University of Chicago, who argues that, in some situations, there is a fourth possible response – one that allows for less than vigorous resuscitation – a “slow code” – without any explicit authorization from the family.

–          Annie Janvier, MD, PhD, Associate Professor of Pediatrics and Co-director of Pediatric Clinical Ethics at the University of Montreal, who argues that “…all resuscitations need to be taken seriously and performed in a consistent fashion every time…. performances and rituals are best left to priests, ministers and mullahs.”

They will debate and discuss different approaches to these difficult cases.  The webinar will be free, but you must register at: https://cmhbioethics.webex.com/cmhbioethics/onstage/g.php?d=660663559&t=a.  For more information on the CMH Bioethics Center and their debate series, visit their website – www.cmh.edu/cmbc.

Tin W, Brunskill G, Kelly T, Fritz S. 15-Year Follow-Up of Recurrent “Hypoglycemia” in Preterm Infants. Pediatrics. 2012. A very long term follow up of a study by my friend Win Tin in the North East of England. They were unable to show an effect, no matter how they divided up the numbers, of recurrent hypoglycemia among preterm infants.

Grigsby PL, Novy MJ, Sadowsky DW, Morgan TK, Long M, Acosta E, et al. Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol. 2012(0). If you inject Ureaplasma into the amniotic fluid of rhesus monkeys they go into premature labour. If you treat them with azithromycin, premature delivery is prevented.

Miedema M, van der Burg PS, Beuger S, de Jongh FH, Frerichs I, van Kaam AH. Effect of Nasal Continuous and Biphasic Positive Airway Pressure on Lung Volume in Preterm Infants. J Pediatr. 2012(0). Increasing CPAP from 2 to 4 to 6 cmH2O increased lung volumes, and also increased tidal volumes in preterm infants, as measured by electrical impedance tomography. When infants on CPAP of 6 had BiPAP added (all this was using the InfantFlow SyPAP system) which was at an additional pressure of 3 cmH2O 50 times per minute for 0.5 seconds (non-synchromized) there was a very small further increase in lung volume, and no further increase in tidal volume. The authors were unable to consistently synchronise the device using the synchronisation module. In many parts of the world, medical devices, or new modes of ventilation can be introduced without any evidence that they are effective in improving clinical outcomes. BiPAP for preterm infants is one of those modes, this study suggests that clinical effects are unlikely with these settings.

Nyp M, Sandritter T, Poppinga N, Simon C, Truog WE. Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits? J Perinatol. 2012;32(1):64-9. The authors gave sildenafil to 21 infants with BPD who also had pulmonary hypertension. They showed that according to the echocardiogram there was a reduction in pulmonary artery pressure, but there was no improvement in gas exchange after 48 hours of treatment. To be honest I don’t think that is the point; what we need to know is whether sildenafil improves survival and the long term. If the O2 needs don’t improve acutely, so what? There are may unknowns for these babies concerning the use of sildenafil, we need other good studies with clinical outcomes.

Stein H, Alosh H, Ethington P, White DB. Prospective crossover comparison between NAVA and pressure control ventilation in premature neonates less than 1500 grams. J Perinatol. 2012. This study only had 5 infants. They ventilated them with NAVA (where the ventilator is controlled by the diaphragmatic EMG) and with pressure control. The NAVA led to lower peak pressures but higher tidal volumes. Really who cares?We really need to know the comparisons between NAVA and volume ventilation, and whether there are clinically important differences.

Vento M, Cubells E, Escobar JJ, Escrig R, Aguar M, Brugada M, et al. Oxygen saturation after birth in preterm infants treated with continuous positive airway pressure and air: assessment of gender differences and comparison with a published nomogram. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2012. Max Vento and his colleagues compared the pulse oximeter profiles of preterm infants who received CPAP in 21% oxygen to the published nomograms from infants who mostly did not receive CPAP. They showed that babies who get CPAP saturate higher, more quickly than published standards, especially the girls.

Ricci Z, Garisto C, Favia I, Vitale V, Di Chiara L, Cogo P. Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial. Intensive Care Medicine. 2012;38(7):1198-204. If you haven’t heard about levosimendan, you probably will…. It is an agent that sensitizes the myocardium to calcium, which has some theoretical value in the newborn who have reduced calcium sensitivity. It causes vasodilation and inotropism. This study randomized 63 babies to receive levosimendan or “standard post-op inotrope therapy”, which was as follows “… for CPB weaning consisted of milrinone (0.75 μg/kg/min) and dopamine (5 μg/kg/min) started at the end of cross clamp. If MAP was below 45 mmHg and filling pressures did not indicate the need for fluid replacement, dopamine was increased to 10 μg/kg/min. If such targets were not achieved, adrenaline (0.05–0.3 μg/kg/min) was added. Clinicians were allowed to decrease milrinone dose if MAP was lower than the selected cutoff after the addition of adrenaline.” The primary outcome of teh study was the development of Low Cardiac Output Syndrome, which is defined by them as “clinical signs and symptoms of the syndrome such as tachycardia (heart rate > 170 beats/min), oliguria (urine output < 0.5 mL/kg/h), cold extremities (peripheral temperature < 27 °C) with or without at least 30 % difference in arterial-mixed venous oxygen saturation or metabolic acidosis (an increase in the base deficit of greater than 4 or an increase in the lactate of more than 2 mg/dL) on two successive blood gas measurements. Postoperative cardiac arrest or the need for extracorporeal membrane oxygenation (ECMO) was also considered LCOS” Now that isn’t very clear to me, it looks like you could have LCOS just on the basis of tachycardia, or cool toes. In an unblinded study that is a bit of  a problem. the incidence of LCOS dropped from 61% to 37%, but it looks like none of the individual parts of the LCOS were different, in particular the mixed venous O2 was the same. The controls received more other inotropes than the Levosimendan group.

So I don’t know if this study really shows much effect of levosimendan, but it may be coming to an NICU near you, my colleague Po-Yin Cheung has published a few studies of levosimendan in newborn piglets, and showed that it has inotropic effects, in a hypoxia re-oxygenation model, with variable effects on regional perfusion. More work is needed before we start giving this widely in the NICU.