We read the letter from Noureldein and colleagues with interest. As former members of the NICE guideline committee on neonatal jaundice and individuals who have advised on many medico-legal claims involving kernicterus, we retain our interest in the topic. Thirty years after discussions about a “kinder, gentler” approach (1), the choice of threshold values for phototherapy remains contentious. The Birmingham group question whether the decision to treat babies born at 37 weeks gestation differently from those born at 38-42 weeks was justified. It took many years to appreciate that there was a significant difference regarding the risk of transient tachypnoea of the newborn between babies born at 37 weeks compared with more mature babies (2). Similar information about the risk of kernicterus is never likely to be forthcoming.
The rationale for treating 37 week gestation babies differently from those born at >38 weeks was based in part on the observation that the less mature group were over-represented in the US kernicterus registry of 1992-2004 (3). Denominator numbers are not available but there were 24 cases at 37 weeks, and a total of 71 at >37 weeks. The new AAP guideline notes that the risk of neurotoxicity from hyperbilirubinaemia is higher at <38 weeks, and with an albumin <3 g/dL (4). The evidence examined for the NICE 2010 guideline consistently showed that a gestational age <38 weeks was associated with an increased risk of hyperbi...
We read the letter from Noureldein and colleagues with interest. As former members of the NICE guideline committee on neonatal jaundice and individuals who have advised on many medico-legal claims involving kernicterus, we retain our interest in the topic. Thirty years after discussions about a “kinder, gentler” approach (1), the choice of threshold values for phototherapy remains contentious. The Birmingham group question whether the decision to treat babies born at 37 weeks gestation differently from those born at 38-42 weeks was justified. It took many years to appreciate that there was a significant difference regarding the risk of transient tachypnoea of the newborn between babies born at 37 weeks compared with more mature babies (2). Similar information about the risk of kernicterus is never likely to be forthcoming.
The rationale for treating 37 week gestation babies differently from those born at >38 weeks was based in part on the observation that the less mature group were over-represented in the US kernicterus registry of 1992-2004 (3). Denominator numbers are not available but there were 24 cases at 37 weeks, and a total of 71 at >37 weeks. The new AAP guideline notes that the risk of neurotoxicity from hyperbilirubinaemia is higher at <38 weeks, and with an albumin <3 g/dL (4). The evidence examined for the NICE 2010 guideline consistently showed that a gestational age <38 weeks was associated with an increased risk of hyperbilirubinaemia (section 3.1, internal page 45). Noureldein et al propose a “risk factor based” approach, but do not specify which risk factors should be used if that of gestation <38 weeks is dropped. There are no plans to screen for glucose-6-phosphatase deficiency, and the bilirubin:albumin ratio was not shown to be useful when evaluated by NICE. From legal cases, we have noted kernicterus occurring at lower than expected serum bilirubin levels in the context of low serum albumin and co-existent anaemia.
Phototherapy thresholds are chosen with a large margin of safety, given that the level of bilirubin which is likely to prove neurotoxic in an individual baby is variable, and free bilirubin cannot be measured routinely. The main downside of a cautious approach is separation, which could be avoided or minimised with suitable home phototherapy programmes that are currently being developed in the UK. In our view, caution regarding threshold level for phototherapy at 37 weeks is justified, and the way forward is to minimise the disruption of treatment.
Janet Rennie, Honorary Consultant Neonatologist, UCLH London
Kevin Ives, Consultant Neonatologist, John Radcliffe Hospital, Oxford
Reference List
1. Ives NK. Kernicterus in preterm infants; lest we forget (to turn on the lights). Pediatrics. 1992;90:757-9.
2. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. British Journal of Obstetrics and Gynaecology. 1995;102:101-6.
3. Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA kernicterus registry (1992 to 2004). Journal of Perinatology. 2009;29:S25-S45.
4. Kemper AR, Newman TB, Slaughter JL, Maisels MJ. Clinical Practice Guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022;150(3):e2022058859.
The data in the study [1] support the clinician in practicing heated humidified high-flow nasal cannula (nHF) as a viable alternative method for weaning preterm infants with a median gestational age of 28 weeks. The benefits of nHF include ease of application, earlier introductions of suck feeds, and parents’ satisfaction. While looking at the data, the nasal continuous positive airway pressure (nCPAP) group had more chronic lung disease (CLD) (OR of 0.42, favoring nHF). The question is: why nCPAP group have a significantly higher CLD despite receiving higher antenatal steroids (ANS)? The data is contradictory. ANS should be protective against the development of CLD. The nCPAP group received higher antenatal corticosteroids 48/61 (78%) compared to the nHF group 34/59 (57%). The difference in ANS use was statistically significant (as per online stats (https://www.socscistatistics.com/tests/chisquare2/default2.aspx), the chi-square statistic is 6.1481. The p-value is .013155).
The second question is regarding the use of nHF at 8 L/min as rescue instead of bubble CPAP of 6 cm. What was the rationale?
What is CHiPS stand for?
Reference: 1. Clements J, Christensen PM, Meyer M. A randomised trial comparing weaning from CPAP alone with weaning using heated humidified high flow nasal cannula in very preterm infants: the CHiPS study [published online ahead of print, 2022 Jul 18]. Arc...
The data in the study [1] support the clinician in practicing heated humidified high-flow nasal cannula (nHF) as a viable alternative method for weaning preterm infants with a median gestational age of 28 weeks. The benefits of nHF include ease of application, earlier introductions of suck feeds, and parents’ satisfaction. While looking at the data, the nasal continuous positive airway pressure (nCPAP) group had more chronic lung disease (CLD) (OR of 0.42, favoring nHF). The question is: why nCPAP group have a significantly higher CLD despite receiving higher antenatal steroids (ANS)? The data is contradictory. ANS should be protective against the development of CLD. The nCPAP group received higher antenatal corticosteroids 48/61 (78%) compared to the nHF group 34/59 (57%). The difference in ANS use was statistically significant (as per online stats (https://www.socscistatistics.com/tests/chisquare2/default2.aspx), the chi-square statistic is 6.1481. The p-value is .013155).
The second question is regarding the use of nHF at 8 L/min as rescue instead of bubble CPAP of 6 cm. What was the rationale?
What is CHiPS stand for?
Reference: 1. Clements J, Christensen PM, Meyer M. A randomised trial comparing weaning from CPAP alone with weaning using heated humidified high flow nasal cannula in very preterm infants: the CHiPS study [published online ahead of print, 2022 Jul 18]. Arch Dis Child Fetal Neonatal Ed. 2022;108(1):63-68. doi:10.1136/archdischild-2021-323636
In this study Selvanathan et al [1] showed small birth head circumference (HC) to be associated with poorer neurodevelopment outcome, independent of postnatal illness and white matter injury. They concluded that normalisation of HC during NICU care appears to moderate this risk.
It was interesting to note that normal/small group had the highest chorioamnionitis (40%), lowest ROP (0) and highest NEC (30%) rates. They also received the highest Energy (kcal/kg/day), median 80. What could be the reason for the HC to regress from normal to small?
We need to investigate other factors that affect the head growth. The individual factors such as parental bonding and availability, environmental exposure to noise, light and other stimuli may have some role in slowing the head growth.
Interestingly, in the same issue of ADC, Ni et al [2] have shown poor HC growth in EPICure2 that was unchanged from EPICure, which is alarming.
1. Selvanathan T, Guo T, Kwan E, et al. Head circumference, total cerebral volume and neurodevelopment in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):181-187. doi:10.1136/archdischild-2020-321397
2. Ni Y, Lancaster R, Suonpera E, et al. Growth in extremely preterm children born in England in 1995 and 2006: the EPICure studies. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):193-200. doi:10.1136/archdischild-2020-321107
We have read with interest the response by Dr. Shabih Manzar on our article. The Thompson score is a clinical score consisting of nine items that are associated with neurologic dysfunction to assess the severity of neonatal encephalopathy (NE) in infants with perinatal asphyxia.[1] There are indeed important limitations that need to be considered; the assessment of infants by use of the Thompson score requires interpretation from the examiner, and the degree of NE may change over time.[2] It should be noted that these limitations are also applicable to other clinical grading tools, such as the modified Sarnat score, which is being widely applied to select infants for therapeutic hypothermia.[2,3] We would like to emphasize that the majority of the infants described in this study was born in a level-II-hospital. Amplitude-integrated electroencephalography (aEEG), another tool to select infants for therapeutic hypothermia, allows continuous monitoring, expert revision and the detection of subclinical seizures, but also requires well-trained staff for correct interpretation and is often not available in these hospitals. By design, the Thompson score did not require extensive training of the observer, which is why it is suitable to be used in smaller hospitals.[1] In a previous study, our study group demonstrated that the Thompson score and aEEG had a similar predictive value for an adverse outcome.[4] We however completely agree with Dr. Manzar that it is of concern that the...
We have read with interest the response by Dr. Shabih Manzar on our article. The Thompson score is a clinical score consisting of nine items that are associated with neurologic dysfunction to assess the severity of neonatal encephalopathy (NE) in infants with perinatal asphyxia.[1] There are indeed important limitations that need to be considered; the assessment of infants by use of the Thompson score requires interpretation from the examiner, and the degree of NE may change over time.[2] It should be noted that these limitations are also applicable to other clinical grading tools, such as the modified Sarnat score, which is being widely applied to select infants for therapeutic hypothermia.[2,3] We would like to emphasize that the majority of the infants described in this study was born in a level-II-hospital. Amplitude-integrated electroencephalography (aEEG), another tool to select infants for therapeutic hypothermia, allows continuous monitoring, expert revision and the detection of subclinical seizures, but also requires well-trained staff for correct interpretation and is often not available in these hospitals. By design, the Thompson score did not require extensive training of the observer, which is why it is suitable to be used in smaller hospitals.[1] In a previous study, our study group demonstrated that the Thompson score and aEEG had a similar predictive value for an adverse outcome.[4] We however completely agree with Dr. Manzar that it is of concern that the Thompson score was not available in more than half of our study population, although this could have been the result of a lack of documentation.
Seven infants in our study developed moderate NE <6 hours after birth, and therefore indeed qualified for therapeutic hypothermia.[5] Three of these infants showed a rapid cardiorespiratory recovery after birth, i.e. they were cardiorespiratory stable with a minimal amount of oxygen support after resuscitation and only a short period of ventilation. All three were born in a level-II-hospital without access to aEEG. Although one of these infants had a Thompson score of 13 at 1 hour after birth, hypothermia was not started because of a low Thompson score (1) at 3 hours after birth on arrival at the NICU. In the other two cases, the first signs of NE were recognized around 4-5 hours after birth, but hypothermia was not started because the infants arrived at respectively 8 hours and 11 hours after birth at the NICU.
As mentioned in our discussion, the large trials on therapeutic hypothermia used different eligibility criteria for this intervention, including various thresholds for Apgar scores and pH.[6] Some trials indeed included infants using a pH <7.0 and 10-minute Apgar score ≤5,[7,8] while others included infants with a pH <7.1 [9,10] or 5-minute Apgar score <7.[9] The systematic review by Jacobs et al. used a cord or arterial pH <7.1 within 60 minutes of birth as criterium for peripartum asphyxia.[6] We were interested whether the infants in our study population would have been eligible for hypothermia using different thresholds, and therefore separately reported the proportion of infants with and without a pH <7.0.
To conclude, we would like to emphasize that selection of infants for therapeutic hypothermia is difficult, especially as most infants are born in level-II-hospitals with different levels of clinical experience and often no access to aEEG. Even though seven infants in our study should have received hypothermia, the proportion of infants who developed an adverse outcome remains high (16/32, 50%) when these seven infants are excluded. Both clinical grading tools as well as aEEG have limitations in clinical practice, which is why further studies on optimizing the selection of infants for therapeutic hypothermia are needed. Until a better tool to select infants for therapeutic hypothermia becomes available, structural use of the Thompson score and early referral of infants with perinatal asphyxia for neuromonitoring, including those who seem to recover quickly from a perinatal insult, remains of great importance.
References
[1]. Thompson, CM, Outerman AS, Linley LL, Hann FM, van der Elst CW, Molteno CD, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997 Jul;86(7):757-61.
[2]. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976 Oct;33(10):696-705.
[3]. Mrelashvili A, Russ JB, Ferriero DM, Wusthoff CJ. The Sarnat score for neonatal encephalopathy: looking back and moving forward. Pediatr Res. 2020 Dec;88(6):824-825.
[4]. Weeke LC, Vilan A, Toet MC, van Haastert IC, de Vries LS, Groenendaal F. A Comparison of the Thompson encephalopathy score and amplitude-integrated electroencephalography in infants with perinatal asphyxia and therapeutic hypothermia. Neonatology. 2017;112(1):24–9.
[5]. Groenendaal F, Casaer A, Dijkman KP, Gavilanes AWD, de Haan TR, ter Horst HJ, et al. Introduction of Hypothermia for Neonates with Perinatal Asphyxia in the Netherlands and Flanders. Neonatology. 2013;104(1):15-21.
[6]. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD003311.
[7]. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365(9460):663‐70.
[8]. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Whole‐body hypothermia for term and near‐term newborns with hypoxic‐ischemic encephalopathy: a randomized controlled trial. Archives of Pediatrics and Adolescent Medicine 2011;165(8):692‐700.
[9]. Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 1998;102(4 Pt 1):885‐92.
[10]. Lin Z, Yu H, Lin J, Chen S, Liang Z, Zhang Z. Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit. Journal of Perinatology 2006;26(3):180‐4.
The article by Parmentier et al [1] highlights the role of Amplitude-integrated electroencephalography (aEEG) and early biomarkers in selecting infants for therapeutic hypothermia (TH). They also suggested the role of the Thompson score (TS) in asphyxiated infants. The problem with TS is that it is subjective. It consists of nine clinical signs: tone, level of consciousness, fits, posture, moro reflex, grasp, suck, respiration, and fontanelle, which could change over time [2]. Also, in the data presented by Parmentier et al [1], twenty-one (53%) infants did not have TS performed.
It was surprising to note that four cases that had moderate neonatal encephalopathy (NE) were not treated with TH despite having seizures within the first 6 hours. The reason for not treatment was rapid recovery. What was the definition of rapid recovery? According to the published flow diagram for NE, the onset of seizure within 6 hours warrants TH [3].
The definition of perinatal asphyxia used by Parmentier et al [1] was from a study in 2003 [4]. It was defined as an arterial cord blood pH <7.1, Apgar Score <7 at 5 min, or need for neonatal resuscitation. While the analysis was done with pH of < 7 and > 7 [(Table 1) 1]. A pH of 7.1 and Apgar of 7 at 5 min is higher than the definition/criteria used in the TH trial [5].
References:
1. Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants w...
The article by Parmentier et al [1] highlights the role of Amplitude-integrated electroencephalography (aEEG) and early biomarkers in selecting infants for therapeutic hypothermia (TH). They also suggested the role of the Thompson score (TS) in asphyxiated infants. The problem with TS is that it is subjective. It consists of nine clinical signs: tone, level of consciousness, fits, posture, moro reflex, grasp, suck, respiration, and fontanelle, which could change over time [2]. Also, in the data presented by Parmentier et al [1], twenty-one (53%) infants did not have TS performed.
It was surprising to note that four cases that had moderate neonatal encephalopathy (NE) were not treated with TH despite having seizures within the first 6 hours. The reason for not treatment was rapid recovery. What was the definition of rapid recovery? According to the published flow diagram for NE, the onset of seizure within 6 hours warrants TH [3].
The definition of perinatal asphyxia used by Parmentier et al [1] was from a study in 2003 [4]. It was defined as an arterial cord blood pH <7.1, Apgar Score <7 at 5 min, or need for neonatal resuscitation. While the analysis was done with pH of < 7 and > 7 [(Table 1) 1]. A pH of 7.1 and Apgar of 7 at 5 min is higher than the definition/criteria used in the TH trial [5].
References:
1. Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants with under-recognised or delayed-onset encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2022;107(4):364-370. doi:10.1136/archdischild-2020-321331
2. Thompson CM, Puterman AS, Linley LL, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86(7):757-761. doi:10.1111/j.1651-2227.1997.tb08581.x
3. Chiang MC, Jong YJ, Lin CH. Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy. Pediatr Neonatol. 2017;58(6):475-483. doi:10.1016/j.pedneo.2016.11.001
4. Cowan F, Rutherford M, Groenendaal F, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet. 2003;361(9359):736-742. doi:10.1016/S0140-6736(03)12658-X
5. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574-1584. doi:10.1056/NEJMcps050929
We read with great interest this article published by Chandran et al. However, we have some critical
reservations on implementation of low dose diazoxide. The target blood glucose thresholds used for
management have been taken from Pediatric endocrine society guidelines of 2015, which are based
on adult neuroglycopenic effects. However, AAP guidelines recommend a lower treatment target of
<2.2 mmol/l (40 mg/dl) for asymptomatic,<2.5 mmol/l (45 mg/dl) for symptomatic neonates
during first 48 hours and <3.3 mmol/l (60mg/dl) thereafter (1, 2) . Moreover, in a recent multi-centric
trial published by Kempen et al; it was concluded that low treatment threshold of <2 mmol/l (36
mg/dl) was non inferior in terms of neurodevelopmental outcomes at 18 months of age in healthy
asymptomatic neonates (3) . Hence it is still debatable whether all the neonates being managed for
hypoglycemia warranted an intravenous glucose infusion therapy and diazoxide.
Authors have used a combination of starting dose of diazoxide along with hydrochlorothiazide for
management of SGA neonates; which are known to have a synergistic effect on increasing blood
glucose levels, hence actual dose of diazoxide required if used alone could have been potentially
higher in these neonates.
In the study design the authors have mentioned that this was an observational cohort study,
however neither the absence of compar...
We read with great interest this article published by Chandran et al. However, we have some critical
reservations on implementation of low dose diazoxide. The target blood glucose thresholds used for
management have been taken from Pediatric endocrine society guidelines of 2015, which are based
on adult neuroglycopenic effects. However, AAP guidelines recommend a lower treatment target of
<2.2 mmol/l (40 mg/dl) for asymptomatic,<2.5 mmol/l (45 mg/dl) for symptomatic neonates
during first 48 hours and <3.3 mmol/l (60mg/dl) thereafter (1, 2) . Moreover, in a recent multi-centric
trial published by Kempen et al; it was concluded that low treatment threshold of <2 mmol/l (36
mg/dl) was non inferior in terms of neurodevelopmental outcomes at 18 months of age in healthy
asymptomatic neonates (3) . Hence it is still debatable whether all the neonates being managed for
hypoglycemia warranted an intravenous glucose infusion therapy and diazoxide.
Authors have used a combination of starting dose of diazoxide along with hydrochlorothiazide for
management of SGA neonates; which are known to have a synergistic effect on increasing blood
glucose levels, hence actual dose of diazoxide required if used alone could have been potentially
higher in these neonates.
In the study design the authors have mentioned that this was an observational cohort study,
however neither the absence of comparison group nor the retrospective nature of study been
clearly disclosed in the methodology (4) .
Finally, to make the study findings more generalizable; it shall be of greater interest to know the
long-term neurodevelopmental outcomes in this group of neonates.
References
1. Committee on F, Newborn, Adamkin DH. Postnatal glucose homeostasis in late-preterm and
term infants. Pediatrics. 2011;127(3):575-9.
2. Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, et al.
Recommendations from the Pediatric Endocrine Society for Evaluation and Management of
Persistent Hypoglycemia in Neonates, Infants, and Children. The Journal of pediatrics.
2015;167(2):238-45.
3. van Kempen A, Eskes PF, Nuytemans D, van der Lee JH, Dijksman LM, van Veenendaal NR, et
al. Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia. N Engl J Med.
2020;382(6):534-44.
4. Chandran S, R PR, Mei Chien C, Saffari SE, Rajadurai VS, Yap F. Safety and efficacy of low-
dose diazoxide in small-for-gestational-age infants with hyperinsulinaemic hypoglycemia.
2021:fetalneonatal-2021-322845.
I agree with Yieh et al [1] that there is an overuse of therapeutic hypothermia (TH) in mild HIE resulting in increased resource utilization. The two main reasons we see this practice are the fear of litigation and scare that infant would later have neurological problems. DuPont et al [2] reported abnormal short-term neurologic outcomes in 20% of newborns with perinatal acidemia and mild HIE not treated with TH. However, in the same study they had 14% of infants that did not receive TH despite the neurological examination consistent with moderate and severe HIE.
Mehta et al [3] have earlier described overutilization of TH in mild HIE, recommending a robust review of the eligibility criteria definitions, especially the 10-min Apgar score. The subjectivity of TH criteria put the practitioner in a decision dilemma. For example, out of five components of Apgar score, only heart rate assessment is objective. A color score of 1 or 2 can change the Apgar from 5 to 6. Similarly, a slight variation in observer examination in obtaining Sarnat score could change it from mild to moderate. Therefore, using a combination of factors in deciding about TH would be a better approach [4].
One of the most important criterion for TH is presence of perinatal academia. Recently, Blecharczyk et al [5] have shown the benefits of standardized screening pathway for evaluating abnormal cord gases in neonates at risk for HIE. Following a structured pathway resulted in minimizing unnecess...
I agree with Yieh et al [1] that there is an overuse of therapeutic hypothermia (TH) in mild HIE resulting in increased resource utilization. The two main reasons we see this practice are the fear of litigation and scare that infant would later have neurological problems. DuPont et al [2] reported abnormal short-term neurologic outcomes in 20% of newborns with perinatal acidemia and mild HIE not treated with TH. However, in the same study they had 14% of infants that did not receive TH despite the neurological examination consistent with moderate and severe HIE.
Mehta et al [3] have earlier described overutilization of TH in mild HIE, recommending a robust review of the eligibility criteria definitions, especially the 10-min Apgar score. The subjectivity of TH criteria put the practitioner in a decision dilemma. For example, out of five components of Apgar score, only heart rate assessment is objective. A color score of 1 or 2 can change the Apgar from 5 to 6. Similarly, a slight variation in observer examination in obtaining Sarnat score could change it from mild to moderate. Therefore, using a combination of factors in deciding about TH would be a better approach [4].
One of the most important criterion for TH is presence of perinatal academia. Recently, Blecharczyk et al [5] have shown the benefits of standardized screening pathway for evaluating abnormal cord gases in neonates at risk for HIE. Following a structured pathway resulted in minimizing unnecessary evaluations, admissions to NICU and disruption of neonate–mother bonding.
In conclusion, the role of TH in mild HIE in reference to the long-term neurodevelopmental outcomes remain unclear. When using TH in mild HIE, healthcare cost and resource utilization should be considered.
References:
1. Yieh L, Lee H, Lu T, et al. Neonates with mild hypoxic-ischaemic encephalopathy receiving supportive care versus therapeutic hypothermia in California. Arch Dis Child Fetal Neonatal Ed. 2022;107(3):324-328. doi:10.1136/archdischild-2021-322250
2. DuPont TL, Chalak LF, Morriss MC, Burchfield PJ, Christie L, Sánchez PJ. Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy. J Pediatr. 2013;162(1):35-41. doi: 10.1016/j.jpeds.2012.06.042
3. Mehta S, Joshi A, Bajuk B, Badawi N, McIntyre S, Lui K. Eligibility criteria for therapeutic hypothermia: From trials to clinical practice. J Paediatr Child Health. 2017;53(3):295-300. doi:10.1111/jpc.13378
4. Bonifacio SL, Hutson S. The Term Newborn: Evaluation for Hypoxic-Ischemic Encephalopathy. Clin Perinatol. 2021;48(3):681-695. doi: 10.1016/j.clp.2021.05.014
5. Blecharczyk E, Lee L, Birnie K, et al. Standardized Evaluation of Cord Gases in Neonates at Risk for Hypoxic Ischemic Encephalopathy. Hosp Pediatr. 2022;12(1):29-37. doi:10.1542/hpeds.2021-006135
Kamupira et al [1] presented a case of umbilical venous line extravasation that was confirmed by contrast study. To justify the contrast use they stated, “There is evidence routine contrast use in checking tip positions improves long line positioning (reference 3 on the paper) and British Association of Perinatal Medicine (BAPM) has included this in it's central access guidance (reference 4 on the paper)”. The caveats with this statement are that first umbilical lines are not synonymous to long lines and second that in BAPM executive summary statement there is no mention of contrast use, “The findings of the Working Group recommend that:
• Any clinical deterioration of a baby in whom a central venous catheter is present should raise the question of catheter-related complications, particularly infection, extravasation and tamponade.
• All central catheter tips should be positioned outside the cardiac silhouette.
• An umbilical venous catheter (UVC) tip should ideally be sited at T8-T9 (assuming this lies outside the cardiac silhouette). A UVC tip sited at or below T10 carries a significantly higher risk of extravasation. It may be necessary to use these catheters in the short term, but they should be replaced at the earliest opportunity”.
In fact, the use of contrast has been associated with hypothyroidism in neonates [2]. UVC misplacements happen either due to the wrong placement or due to the migration of UVC from a safe to wrong position. Th...
Kamupira et al [1] presented a case of umbilical venous line extravasation that was confirmed by contrast study. To justify the contrast use they stated, “There is evidence routine contrast use in checking tip positions improves long line positioning (reference 3 on the paper) and British Association of Perinatal Medicine (BAPM) has included this in it's central access guidance (reference 4 on the paper)”. The caveats with this statement are that first umbilical lines are not synonymous to long lines and second that in BAPM executive summary statement there is no mention of contrast use, “The findings of the Working Group recommend that:
• Any clinical deterioration of a baby in whom a central venous catheter is present should raise the question of catheter-related complications, particularly infection, extravasation and tamponade.
• All central catheter tips should be positioned outside the cardiac silhouette.
• An umbilical venous catheter (UVC) tip should ideally be sited at T8-T9 (assuming this lies outside the cardiac silhouette). A UVC tip sited at or below T10 carries a significantly higher risk of extravasation. It may be necessary to use these catheters in the short term, but they should be replaced at the earliest opportunity”.
In fact, the use of contrast has been associated with hypothyroidism in neonates [2]. UVC misplacements happen either due to the wrong placement or due to the migration of UVC from a safe to wrong position. The ways to confirm the UVC placement and monitor possible migration are x-rays and ultrasound. Contrast studies are rarely indicated. The radiographic landmarks used to detect UVC malposition include the vertebrae and the expected course of the UVC. A slight change in position in relation to vertebrae indicate migration (Figure 1) [3].
The other way of locating the tip of UVC is using real-time ultrasound using the inferior vena cava and right atrium as landmarks [4].
In conclusion, in the light of the emerging evidence and growing interest in the use of point of care ultrasound in neonatal care and proper use of radiological landmarks, UVC placement or migration could be easily monitored avoiding the use of contrast.
References:
1. Kamupira SR, Tarr JD, Kuruvilla M. Contrast study in umbilical venous line extravasation. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):120. doi:10.1136/archdischild-2020-321081
2. Piatek M, Schneider DJ, Smith WJ, Hanna M, Abu Jawdeh EG. Hypothyroidism after Percutaneous Patent Ductus Arteriosus Device Closure in an Extremely Preterm Infant: Possible Role of Iodinated IV Contrast. Neonatology. 2020;117(6):776-779. doi:10.1159/000512110
3. Patel BS, Walyat N, Manzar S. Catheter related ascites in a preterm Infant. Neonatology Today. 2021 (2); 37-40
4. Rubortone SA, Costa S, Perri A, D'Andrea V, Vento G, Barone G. Real-time ultrasound for tip location of umbilical venous catheter in neonates: a pre/post intervention study. Ital J Pediatr. 2021;47(1):68. Published 2021 Mar 18. doi:10.1186/s13052-021-01014-7
Legend to Figure:
Figure: Panel A and B showing migration of the UVC over time, adapted from Patel et al. Catheter related ascites in a preterm Infant. Neonatology Today. 2021 (2); 37-40
Wonderful work by Vyas et al on ROP and its incidence in different
cities of Britain. The statistically significant difference in the
incidence of ROP in different centres may be related to the differences in
the level of care provided. The advancements in neonatal care,
particularly the use of surfactant and the resultant reduction in the
requirements of O2 has greatly influenced outcome and possible development
of ROP (...
Wonderful work by Vyas et al on ROP and its incidence in different
cities of Britain. The statistically significant difference in the
incidence of ROP in different centres may be related to the differences in
the level of care provided. The advancements in neonatal care,
particularly the use of surfactant and the resultant reduction in the
requirements of O2 has greatly influenced outcome and possible development
of ROP (Hussain et al, Pediatrics 1999). Obviously all factors need to be
taken into account while comparing results at widely differing centres.
We read with great interest the consensus article on the
investigation and management of hyperinsulinism in infancy (1). The
authors discuss the value of the intra-arterial calcium stimulation test,
but speculate that there is a significant risk of bowel infarction.
Intra-arterial calcium stimulation for localisation of insulinomas in
adult patients has been described by several authors (2,3,4). To our
knowledge...
We read with great interest the consensus article on the
investigation and management of hyperinsulinism in infancy (1). The
authors discuss the value of the intra-arterial calcium stimulation test,
but speculate that there is a significant risk of bowel infarction.
Intra-arterial calcium stimulation for localisation of insulinomas in
adult patients has been described by several authors (2,3,4). To our
knowledge, bowel infarction has never been reported as a complication.
We have used the intra-arterial calcium stimulation test in infants
with hyperinsulinism to localise the site of hypersecretion of insulin,
and to determine whether it is focal or diffuse (5). In six procedures
performed on children (age range 2 months to 3 years) there has been no
clinical or radiological evidence of bowel ischaemia or infarction, and no
evidence of arterial spasm has been demonstrated on coeliac or mesenteric
arteriograms.
We conclude that this is a safe and valuable investigation, and we
believe that it is less invasive than the alternative technique of
transhepatic portal venous sampling.
L J Abernethy Consulatant Paediatric Radiologist
G L Lamont Consultant paediatric Surgeon
D C Davidson Consulatant Paediatrician
References:
1.
A Aynsley-Green, K Hussain, J Hall, J M Saudubray, C Nihoul-Fékété, P De
Lonlay-Debeney, F Brunelle, T Otonkoski, P Thornton, and K J Lindley
Practical management of hyperinsulinism in infancy
Arch. Dis. Child. Fetal Neonatal Ed. 2000; 82: F98-F107
2. Doppman JL, Miller DL, Chang R, Shawker TH, Gorden P, Norton JA.
Insulinomas: localization with selective intra-arterial injection of
calcium.
Radiology 178: 237 - 241.
3. O'Shea D, Rohrer-Theurs AW, Lynn JA, Jackson JE, Bloom SR
Localization of insulinomas by selective intaarterial calcium injection.
J Clin Endocrinol Metab 1996 81: 1623-7.
4. Pereira PL, Roche AJ, Maier GW, Huppert PE, Dammann F, Farsworth
CT, Duda SH, Claussen CD.
Insulinoma and islet cell hyperplasia: value of the calcium intarterial
stimulation test when finding of other preoperative studies are negative.
Radiology 1998: 206: 703-9.
5. Abernethy LJ,Davidson DC, Lamont G, Shepherd RM, Dunne MJ
Intra-arterial calcium stimulation test in the investigation of
hyperinsulinaemic hypoglycaemia.
Arch Dis Child 1998; 78:359-63
Sir,
We read the letter from Noureldein and colleagues with interest. As former members of the NICE guideline committee on neonatal jaundice and individuals who have advised on many medico-legal claims involving kernicterus, we retain our interest in the topic. Thirty years after discussions about a “kinder, gentler” approach (1), the choice of threshold values for phototherapy remains contentious. The Birmingham group question whether the decision to treat babies born at 37 weeks gestation differently from those born at 38-42 weeks was justified. It took many years to appreciate that there was a significant difference regarding the risk of transient tachypnoea of the newborn between babies born at 37 weeks compared with more mature babies (2). Similar information about the risk of kernicterus is never likely to be forthcoming.
The rationale for treating 37 week gestation babies differently from those born at >38 weeks was based in part on the observation that the less mature group were over-represented in the US kernicterus registry of 1992-2004 (3). Denominator numbers are not available but there were 24 cases at 37 weeks, and a total of 71 at >37 weeks. The new AAP guideline notes that the risk of neurotoxicity from hyperbilirubinaemia is higher at <38 weeks, and with an albumin <3 g/dL (4). The evidence examined for the NICE 2010 guideline consistently showed that a gestational age <38 weeks was associated with an increased risk of hyperbi...
Show MoreThe data in the study [1] support the clinician in practicing heated humidified high-flow nasal cannula (nHF) as a viable alternative method for weaning preterm infants with a median gestational age of 28 weeks. The benefits of nHF include ease of application, earlier introductions of suck feeds, and parents’ satisfaction. While looking at the data, the nasal continuous positive airway pressure (nCPAP) group had more chronic lung disease (CLD) (OR of 0.42, favoring nHF). The question is: why nCPAP group have a significantly higher CLD despite receiving higher antenatal steroids (ANS)? The data is contradictory. ANS should be protective against the development of CLD. The nCPAP group received higher antenatal corticosteroids 48/61 (78%) compared to the nHF group 34/59 (57%). The difference in ANS use was statistically significant (as per online stats (https://www.socscistatistics.com/tests/chisquare2/default2.aspx), the chi-square statistic is 6.1481. The p-value is .013155).
The second question is regarding the use of nHF at 8 L/min as rescue instead of bubble CPAP of 6 cm. What was the rationale?
What is CHiPS stand for?
Reference: 1. Clements J, Christensen PM, Meyer M. A randomised trial comparing weaning from CPAP alone with weaning using heated humidified high flow nasal cannula in very preterm infants: the CHiPS study [published online ahead of print, 2022 Jul 18]. Arc...
Show MoreIn this study Selvanathan et al [1] showed small birth head circumference (HC) to be associated with poorer neurodevelopment outcome, independent of postnatal illness and white matter injury. They concluded that normalisation of HC during NICU care appears to moderate this risk.
It was interesting to note that normal/small group had the highest chorioamnionitis (40%), lowest ROP (0) and highest NEC (30%) rates. They also received the highest Energy (kcal/kg/day), median 80. What could be the reason for the HC to regress from normal to small?
We need to investigate other factors that affect the head growth. The individual factors such as parental bonding and availability, environmental exposure to noise, light and other stimuli may have some role in slowing the head growth.
Interestingly, in the same issue of ADC, Ni et al [2] have shown poor HC growth in EPICure2 that was unchanged from EPICure, which is alarming.
1. Selvanathan T, Guo T, Kwan E, et al. Head circumference, total cerebral volume and neurodevelopment in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):181-187. doi:10.1136/archdischild-2020-321397
2. Ni Y, Lancaster R, Suonpera E, et al. Growth in extremely preterm children born in England in 1995 and 2006: the EPICure studies. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):193-200. doi:10.1136/archdischild-2020-321107
We have read with interest the response by Dr. Shabih Manzar on our article. The Thompson score is a clinical score consisting of nine items that are associated with neurologic dysfunction to assess the severity of neonatal encephalopathy (NE) in infants with perinatal asphyxia.[1] There are indeed important limitations that need to be considered; the assessment of infants by use of the Thompson score requires interpretation from the examiner, and the degree of NE may change over time.[2] It should be noted that these limitations are also applicable to other clinical grading tools, such as the modified Sarnat score, which is being widely applied to select infants for therapeutic hypothermia.[2,3] We would like to emphasize that the majority of the infants described in this study was born in a level-II-hospital. Amplitude-integrated electroencephalography (aEEG), another tool to select infants for therapeutic hypothermia, allows continuous monitoring, expert revision and the detection of subclinical seizures, but also requires well-trained staff for correct interpretation and is often not available in these hospitals. By design, the Thompson score did not require extensive training of the observer, which is why it is suitable to be used in smaller hospitals.[1] In a previous study, our study group demonstrated that the Thompson score and aEEG had a similar predictive value for an adverse outcome.[4] We however completely agree with Dr. Manzar that it is of concern that the...
Show MoreThe article by Parmentier et al [1] highlights the role of Amplitude-integrated electroencephalography (aEEG) and early biomarkers in selecting infants for therapeutic hypothermia (TH). They also suggested the role of the Thompson score (TS) in asphyxiated infants. The problem with TS is that it is subjective. It consists of nine clinical signs: tone, level of consciousness, fits, posture, moro reflex, grasp, suck, respiration, and fontanelle, which could change over time [2]. Also, in the data presented by Parmentier et al [1], twenty-one (53%) infants did not have TS performed.
It was surprising to note that four cases that had moderate neonatal encephalopathy (NE) were not treated with TH despite having seizures within the first 6 hours. The reason for not treatment was rapid recovery. What was the definition of rapid recovery? According to the published flow diagram for NE, the onset of seizure within 6 hours warrants TH [3].
The definition of perinatal asphyxia used by Parmentier et al [1] was from a study in 2003 [4]. It was defined as an arterial cord blood pH <7.1, Apgar Score <7 at 5 min, or need for neonatal resuscitation. While the analysis was done with pH of < 7 and > 7 [(Table 1) 1]. A pH of 7.1 and Apgar of 7 at 5 min is higher than the definition/criteria used in the TH trial [5].
References:
1. Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants w...
Show MoreWe read with great interest this article published by Chandran et al. However, we have some critical
Show Morereservations on implementation of low dose diazoxide. The target blood glucose thresholds used for
management have been taken from Pediatric endocrine society guidelines of 2015, which are based
on adult neuroglycopenic effects. However, AAP guidelines recommend a lower treatment target of
<2.2 mmol/l (40 mg/dl) for asymptomatic,<2.5 mmol/l (45 mg/dl) for symptomatic neonates
during first 48 hours and <3.3 mmol/l (60mg/dl) thereafter (1, 2) . Moreover, in a recent multi-centric
trial published by Kempen et al; it was concluded that low treatment threshold of <2 mmol/l (36
mg/dl) was non inferior in terms of neurodevelopmental outcomes at 18 months of age in healthy
asymptomatic neonates (3) . Hence it is still debatable whether all the neonates being managed for
hypoglycemia warranted an intravenous glucose infusion therapy and diazoxide.
Authors have used a combination of starting dose of diazoxide along with hydrochlorothiazide for
management of SGA neonates; which are known to have a synergistic effect on increasing blood
glucose levels, hence actual dose of diazoxide required if used alone could have been potentially
higher in these neonates.
In the study design the authors have mentioned that this was an observational cohort study,
however neither the absence of compar...
I agree with Yieh et al [1] that there is an overuse of therapeutic hypothermia (TH) in mild HIE resulting in increased resource utilization. The two main reasons we see this practice are the fear of litigation and scare that infant would later have neurological problems. DuPont et al [2] reported abnormal short-term neurologic outcomes in 20% of newborns with perinatal acidemia and mild HIE not treated with TH. However, in the same study they had 14% of infants that did not receive TH despite the neurological examination consistent with moderate and severe HIE.
Show MoreMehta et al [3] have earlier described overutilization of TH in mild HIE, recommending a robust review of the eligibility criteria definitions, especially the 10-min Apgar score. The subjectivity of TH criteria put the practitioner in a decision dilemma. For example, out of five components of Apgar score, only heart rate assessment is objective. A color score of 1 or 2 can change the Apgar from 5 to 6. Similarly, a slight variation in observer examination in obtaining Sarnat score could change it from mild to moderate. Therefore, using a combination of factors in deciding about TH would be a better approach [4].
One of the most important criterion for TH is presence of perinatal academia. Recently, Blecharczyk et al [5] have shown the benefits of standardized screening pathway for evaluating abnormal cord gases in neonates at risk for HIE. Following a structured pathway resulted in minimizing unnecess...
Kamupira et al [1] presented a case of umbilical venous line extravasation that was confirmed by contrast study. To justify the contrast use they stated, “There is evidence routine contrast use in checking tip positions improves long line positioning (reference 3 on the paper) and British Association of Perinatal Medicine (BAPM) has included this in it's central access guidance (reference 4 on the paper)”. The caveats with this statement are that first umbilical lines are not synonymous to long lines and second that in BAPM executive summary statement there is no mention of contrast use, “The findings of the Working Group recommend that:
Show More• Any clinical deterioration of a baby in whom a central venous catheter is present should raise the question of catheter-related complications, particularly infection, extravasation and tamponade.
• All central catheter tips should be positioned outside the cardiac silhouette.
• An umbilical venous catheter (UVC) tip should ideally be sited at T8-T9 (assuming this lies outside the cardiac silhouette). A UVC tip sited at or below T10 carries a significantly higher risk of extravasation. It may be necessary to use these catheters in the short term, but they should be replaced at the earliest opportunity”.
In fact, the use of contrast has been associated with hypothyroidism in neonates [2]. UVC misplacements happen either due to the wrong placement or due to the migration of UVC from a safe to wrong position. Th...
Wonderful work by Vyas et al on ROP and its incidence in different cities of Britain. The statistically significant difference in the incidence of ROP in different centres may be related to the differences in the level of care provided. The advancements in neonatal care, particularly the use of surfactant and the resultant reduction in the requirements of O2 has greatly influenced outcome and possible development of ROP (...
We read with great interest the consensus article on the investigation and management of hyperinsulinism in infancy (1). The authors discuss the value of the intra-arterial calcium stimulation test, but speculate that there is a significant risk of bowel infarction.
Intra-arterial calcium stimulation for localisation of insulinomas in adult patients has been described by several authors (2,3,4). To our knowledge...
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