“Parenteral nutrition for preterm infants: Correcting for arachidonic and
docosahexaenoic acid may not suffice” by Bernard et al. regarding the publication:
Frazer LC, Martin CR. Parenteral lipid emulsions in the preterm infant: current issues
and controversies. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 29: fetalneonatal-
2020-319108. doi: 10.1136/archdischild-2020-319108. Epub ahead of print. PMID:
33514630.
Lauren C. Frazer1,2, Camilia R. Martin2,3,4
1Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA, USA 4Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence: cmartin1@bidmc.harvard.edu
We would like to thank Bernhard and colleagues for their thoughtful letter “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” written in response to our review. The authors of the letter raised important issues regarding the lack of data surrounding the optimal balance of arachidonic (ARA) and docosahexaenoic acid (DHA) that should be administered...
“Parenteral nutrition for preterm infants: Correcting for arachidonic and
docosahexaenoic acid may not suffice” by Bernard et al. regarding the publication:
Frazer LC, Martin CR. Parenteral lipid emulsions in the preterm infant: current issues
and controversies. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 29: fetalneonatal-
2020-319108. doi: 10.1136/archdischild-2020-319108. Epub ahead of print. PMID:
33514630.
Lauren C. Frazer1,2, Camilia R. Martin2,3,4
1Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA, USA 4Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence: cmartin1@bidmc.harvard.edu
We would like to thank Bernhard and colleagues for their thoughtful letter “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” written in response to our review. The authors of the letter raised important issues regarding the lack of data surrounding the optimal balance of arachidonic (ARA) and docosahexaenoic acid (DHA) that should be administered to preterm neonates by these emulsions as well as the inadequacy of current lipid emulsions in providing other components such as myristic acid and choline. While we focused on long chain polyunsaturated fatty acids in our review, we agree that lipid emulsions are a complex matrix of components beyond ARA and DHA and highlighted this in Table 3 under Formulation when discussing current research gaps. We chose to highlight the fatty acid balance in this concise review because, in our experience, this topic largely drives the motivation in selecting lipid emulsions by providers in the neonatal intensive care unit. Advanced analytical methods from detection to data analysis are now available to take a comprehensive approach in understanding the metabolic influence of complex lipid emulsions in neonatal development and disease risk. Such studies are a necessary step in developing nutritional products designed to meet the unique needs of preterm infants encompassing those highlighted by Bernhard and colleagues.
Thank you,
Lauren C. Frazer, MD PhD
Camilia R. Martin, MD MS
Dear Editor,
We read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on...
Dear Editor,
We read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on the occurrence of transient fluid retention, pulmonary edema, elevated pulmonary pressures, and brief oxygen dependency during and after the diazoxide treatment as side effects in neonates.
The authors have highlighted that seven (13%) out of fifty-five neonates developed NEC after diazoxide treatment. [1] And of the 7 patients, one patient was exposed to octreotide. [1] Octreotide has already been known to have proven hemodynamic side-effects on splanchnic circulation, thereby predisposing these vulnerable population leading to NEC. When the baby is receiving octreotide, there could have been a cascade of hemodynamic changes in the gut which could be monitored by NIRS or abdominal Doppler studies to assess gut blood flow. As the authors mention, Gray KD et al. reported 1066 neonates treated with diazoxide for hypoglycemia, less than 1% of neonates developed NEC. In our center, we decided to use diazoxide as a monotherapy in the treatment of neonatal hypoglycemia. Diazoxide did not cause any alterations in the intestinal blood flow which was monitored by near-infrared spectroscopy (NIRS). According to Table.3 in the paper, there were no significant difference between the diazoxide initial dose and maximum dose used between the NEC vs. no NEC group.
Thus, diazoxide has been used in our center successfully with no major side-effects. It also helped in shortening the duration of stay and cost of treatment substantially thereby reducing the burden on our provincial healthcare system.
Kaarthigeyan Kalaniti1, Veronica Samedi1, Neil Wonko1, Sibasis Daspal1
1Division of Neonatology, Dept. of Pediatrics,
Jim Pattison Children’s Hospital,
University of Saskatchewan, Saskatoon, SK, Canada
E-mail: vmsamedi@gmail.com
References:
1. Prado LA, Castro M, Weisz DE, et al. Arch Dis Child Fetal Neonatal Ed. 2020; 0: F1–F5.
We read with interest results from the Hypotension in Preterm Infants (HIP) trial by Dempsey et al.1 Unfortunately this multicentre randomised controlled trial (RCT) could not provide robust conclusions. Enrolment was limited to 58 of the planned 830 infants, 7% of those screened, attributed to strict inclusion criteria and recruitment challenges. This along with high inotropic usage in the restrictive group limits study power and generalisation.
Some clarification would be useful. The CONSORT diagram should label the two study arms, where imbalance in numbers not receiving the allocated intervention (6/29 vs 1/29) may warrant further analysis. The proportion with invasive lines seems low, exact reasons for exclusion/non-inclusion could be detailed, and maximum age at enrolment given.
In our published RCT 2, three blood pressure (BP) intervention protocols were compared (BP below gestational age as in HIP, more active, or less active). This single centre pilot study randomised 60 infants <29 weeks, 45% of those screened and 100% of target recruitment, with invasive BP acquired every 10 seconds for a week. The HIP trial suggests their hypotension rate of 25% is low but without BP acquisition details, comparison is difficult. Their figure showing BP following dopamine or placebo requires data variability measures.
In our study, we found higher BP was associated with lower EEG discontinuity.3 The HIP study4 did not stipulate commonly used end-organ p...
We read with interest results from the Hypotension in Preterm Infants (HIP) trial by Dempsey et al.1 Unfortunately this multicentre randomised controlled trial (RCT) could not provide robust conclusions. Enrolment was limited to 58 of the planned 830 infants, 7% of those screened, attributed to strict inclusion criteria and recruitment challenges. This along with high inotropic usage in the restrictive group limits study power and generalisation.
Some clarification would be useful. The CONSORT diagram should label the two study arms, where imbalance in numbers not receiving the allocated intervention (6/29 vs 1/29) may warrant further analysis. The proportion with invasive lines seems low, exact reasons for exclusion/non-inclusion could be detailed, and maximum age at enrolment given.
In our published RCT 2, three blood pressure (BP) intervention protocols were compared (BP below gestational age as in HIP, more active, or less active). This single centre pilot study randomised 60 infants <29 weeks, 45% of those screened and 100% of target recruitment, with invasive BP acquired every 10 seconds for a week. The HIP trial suggests their hypotension rate of 25% is low but without BP acquisition details, comparison is difficult. Their figure showing BP following dopamine or placebo requires data variability measures.
In our study, we found higher BP was associated with lower EEG discontinuity.3 The HIP study4 did not stipulate commonly used end-organ perfusion tests;5 they found abnormal cranial ultrasound (CrUSS) in 50%, but with timing unclear. Our study found lowest CrUSS abnormality rates (21%) in the active arm.
We agree that RCTs examining neonatal haemodynamics are difficult, particularly consenting parents during challenging times. None of our parents gave antenatal assent, preferring postnatal consent. Simple designs with safety-netting (echocardiography and other non-invasive measures) to detect cardiovascular compromise encourage parental and physician participation and should be considered for future trials.
References
1. Dempsey EM, Barrington KJ, Marlow N, et al. Hypotension in Preterm Infants (HIP) randomised trial. Arch Dis Chid Fetal Neonatal Ed 2021 doi: 10.1136/archdischild-2020-320241
2. Pereira SS, Sinha AK, Morris JK, et al. Blood pressure intervention levels in preterm infants: pilot randomised trial. Arch Dis Child Fetal Neonatal Ed 2018 doi: 10.1136/archdischild-2017-314159
3. Pereira SS, Kempley ST, Wertheim DF, et al. Investigation of EEG Activity Compared with Mean Arterial Blood Pressure in Extremely Preterm Infants. Frontiers in Neurology 2018;9 doi: 10.3389/fneur.2018.00087
4. Dempsey EM, Barrington KJ, Marlow N, et al. Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns. Neonatology 2014;105(4):275-81. doi: 10.1159/000357553
5. Stranak Z, Semberova J, Barrington K, et al. International survey on diagnosis and management of hypotension in extremely preterm babies. European journal of pediatrics 2014;173(6):793-8. doi: 10.1007/s00431-013-2251-9
The reported findings that some MRSOPA corrective steps actually made matters worse (1) should be a wake-up call to those teaching neonatal resuscitation (NRP), especially as many components of the algorithm are not evidence based and have never been validated.
I wish to briefly report on two adverse outcomes which occurred on Vancouver Island at separate sites and at separate times, both following the introduction of the MRSOPA algorithm. Both infants were delivered at term by C Section under maternal general anesthetic. One was a preplanned elective C Section, the other for failure to progress with no concerns with the fetal heart tracing. There was no meconium present in the amniotic fluid. Both infants were depressed at birth but with palpable heartbeat. For both infants, there was difficulty in establishing effective ventilation. When intubation was eventually achieved, there was no colour change with CO2 detector, resulting in removal and resumption of bag-mask ventilation. The Neopuff (Fisher & Paykel) T piece was used in both cases and pressures were initially set at 20/5cm H20, as per NRP guidelines. However pressure increases occurred late. One baby had completely normal arterial cord gases. The other had an arterial cord pH 7.17.
Following a prolonged but eventually successful resuscitation, both infants were cooled for 72hours. One infant required transport to a level 3 site and subsequently did well. The other child did poorly. That child now...
The reported findings that some MRSOPA corrective steps actually made matters worse (1) should be a wake-up call to those teaching neonatal resuscitation (NRP), especially as many components of the algorithm are not evidence based and have never been validated.
I wish to briefly report on two adverse outcomes which occurred on Vancouver Island at separate sites and at separate times, both following the introduction of the MRSOPA algorithm. Both infants were delivered at term by C Section under maternal general anesthetic. One was a preplanned elective C Section, the other for failure to progress with no concerns with the fetal heart tracing. There was no meconium present in the amniotic fluid. Both infants were depressed at birth but with palpable heartbeat. For both infants, there was difficulty in establishing effective ventilation. When intubation was eventually achieved, there was no colour change with CO2 detector, resulting in removal and resumption of bag-mask ventilation. The Neopuff (Fisher & Paykel) T piece was used in both cases and pressures were initially set at 20/5cm H20, as per NRP guidelines. However pressure increases occurred late. One baby had completely normal arterial cord gases. The other had an arterial cord pH 7.17.
Following a prolonged but eventually successful resuscitation, both infants were cooled for 72hours. One infant required transport to a level 3 site and subsequently did well. The other child did poorly. That child now has a profound permanent brain injury, attributed to perinatal hypoxic ischaemic encephalopathy.
I am concerned that these cases may not be isolated case reports but rather part of an emerging problem with infant resuscitation and the NRP MRSOPA algorithm. The P (for pressure increase) and the A (for alternative airway) are well down the pathway of interventions and follow useless and possibly counterproductive manoeuvers, such as opening the mouth and suctioning. Practitioners may also forget that there are now two “P”s (MR SOPPA), so may only increase pressures to 25cm (why do we start at pressures of 20cm for term babies?) before attempting an alternative airway. Further, since tracheal intubation for meconium was removed from the NRP algorithm, there has been a decrease in both confidence and skill when performing this procedure. Although a laryngeal mask airway is easy to insert, many practitioners have never used one.
If any readers are aware of similar cases, they are encouraged to contact (with patient identifiers removed) me in confidence. If we see any evidence of an emerging problem, we can share our findings with International Consensus on Cardiopulmonary Resuscitation Committee (ILCOR).
1. Corrective steps to enhance ventilation in the delivery room: Yang KC, Pas AB, Weinberg DD, et al. Arch Dis Child Fetal Neonatal Ed 2020;105:F605–F608
Dear Editor,
We read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on...
Dear Editor,
We read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on the occurrence of transient fluid retention, pulmonary edema, elevated pulmonary pressures, and brief oxygen dependency during and after the diazoxide treatment as side effects in neonates.
The authors have highlighted that seven (13%) out of fifty-five neonates developed NEC after diazoxide treatment. [1] And of the 7 patients, one patient was exposed to octreotide. [1] Octreotide has already been known to have proven hemodynamic side-effects on splanchnic circulation, thereby predisposing these vulnerable population leading to NEC. When the baby is receiving octreotide, there could have been a cascade of hemodynamic changes in the gut which could be monitored by NIRS or abdominal Doppler studies to assess gut blood flow. As the authors mention, Gray KD et al. reported 1066 neonates treated with diazoxide for hypoglycemia, less than 1% of neonates developed NEC. In our center, we decided to use diazoxide as a monotherapy in the treatment of neonatal hypoglycemia. Diazoxide did not cause any alterations in the intestinal blood flow which was monitored by near-infrared spectroscopy (NIRS). According to Table.3 in the paper, there were no significant difference between the diazoxide initial dose and maximum dose used between the NEC vs. no NEC group.
Thus, diazoxide has been used in our center successfully with no major side-effects. It also helped in shortening the duration of stay and cost of treatment substantially thereby reducing the burden on our provincial healthcare system.
Kaarthigeyan Kalaniti1, Veronica Samedi1, Neil Wonko1, Sibasis Daspal1
1Division of Neonatology, Dept. of Pediatrics,
Jim Pattison Children’s Hospital,
University of Saskatchewan, Saskatoon, SK, Canada
E-mail: vmsamedi@gmail.com
References:
1. Prado LA, Castro M, Weisz DE, et al. Arch Dis Child Fetal Neonatal Ed. 2020; 0: F1–F5.
2. Gray KD, Dudash K, Escobar C, et al. Prevalence and safety of diazoxide in the neonatal intensive care unit. J Perinatol 2018; 38: 1496-502.
Dear Sir or Madam!
Nasal CPAP is one of the most important therapies in neonatology. Accordingly, the manufacturers of such devices are very interested in gaining market share. Not all of their "sales arguments" correspond to clinical or physical reality. This is why studies comparing different devices are so extremely important.
The authors claim to have compared three CPAP systems that are referred to as "variable-flow" devices. This refers to CPAP systems that generate their CPAP through one or more jets, corresponding to jet ventilation as it is known in laryngeal surgery. But does the Miniflow CPAP belong in this category? The Miniflow has one inspiratory and one expiratory tube and does not have a jet. Pressure is generated through the expiratory valve of a ventilator. Such CPAP devices are actually called "constant-flow" devices.
Basically, the division into variable-flow and constant-flow devices is considered very confusing and, above all, physically questionable. However, the terms are very persistent. In any case, however, the statement of the study could be supplemented. It shows not only that there is no difference between variable flow devices, but equally no difference between variable and constant flow devices.
Yours sincerely,
Martin Wald
Ravaldi et al. in their letter raise two points of dispute. The first is linked to epidemiological data and the other to the fact that, according to them, a reduction in gynecological checks during pregnancy did not occur in the lockdown of spring 2020. I appreciate their engagement with the article but I disagree.
On the first point (epidemiological data), the difference between the data presented by Ravaldi and those indicated by us is linked to the fact that they mistakenly refer to older years. Ravaldi’s 2019 stillbirth is taken from the Italian Statistical Yearbook 2019, which refers to the entire 2016. Our data, obtained from the CEDAP (hospital discharge database, which records perinatal information on all newborns), are instead those of Mar-May 2019 and Mar-May 2020 (3 months of lockdown).
Furthermore, Ravaldi’s stillbirth data starting from 22 weeks were taken from the ISTAT Reproductive Health document published in 2018, which refers to 2015 data. The authors therefore cannot contest the difference in the results because they are using different data sources. A further analysis (to be published) on larger samples on all births in Lazio confirmed a significant difference between stillbirths in the period March-May 2020 compared to the same months in the years 2017-2019 (3.23 vs 1.83 per thousand, p value = 0.014) . The increase in stillbirths in the first half of 2020 was observed in numerous developed and developing countries as well as in Italy (1-...
Ravaldi et al. in their letter raise two points of dispute. The first is linked to epidemiological data and the other to the fact that, according to them, a reduction in gynecological checks during pregnancy did not occur in the lockdown of spring 2020. I appreciate their engagement with the article but I disagree.
On the first point (epidemiological data), the difference between the data presented by Ravaldi and those indicated by us is linked to the fact that they mistakenly refer to older years. Ravaldi’s 2019 stillbirth is taken from the Italian Statistical Yearbook 2019, which refers to the entire 2016. Our data, obtained from the CEDAP (hospital discharge database, which records perinatal information on all newborns), are instead those of Mar-May 2019 and Mar-May 2020 (3 months of lockdown).
Furthermore, Ravaldi’s stillbirth data starting from 22 weeks were taken from the ISTAT Reproductive Health document published in 2018, which refers to 2015 data. The authors therefore cannot contest the difference in the results because they are using different data sources. A further analysis (to be published) on larger samples on all births in Lazio confirmed a significant difference between stillbirths in the period March-May 2020 compared to the same months in the years 2017-2019 (3.23 vs 1.83 per thousand, p value = 0.014) . The increase in stillbirths in the first half of 2020 was observed in numerous developed and developing countries as well as in Italy (1-5).
On the second point, we had not indicated the precise causes of the increase in stillbirths as we did not have the data, but the most probable cause is the postponement of many medical checks that have affected all ages of life. It is true that all mothers love their children, but undoubtedly there has been a reduction in compulsory pediatric vaccinations and a postponement of many checks for fear of contracting coronavirus infection by going to hospitals and medical centers. For example, there was a reduction in emergency room activities and consequent delay in the diagnosis of various diseases, including serious ones (6-8). In the published article we never intended to blame women but we limited ourselves to observing a phenomenon.
In addition, in the study from Ravaldi et. al (9-10), the authors use a very limited sample and as they are aware there is also the risk of a sample selection bias: “Women likely to respond may have been better connected to health care and may have better access to internet and electronic facilities”.
Mario De Curtis, Leonardo Villani, Arianna Polo
References
1.Dell'Utri C, Manzoni E, Cipriani S et al. Effects of SARS Cov-2 epidemic on the obstetrical and gynecological emergency service accesses. What happened and what shall we expect now? Eur J Obstet Gynecol Reprod Biol .2020 Nov;254:64-68 July 10, 2020
2.A Khalil, von Dadelszen P, Draycott Tet al. Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic
3.Watson C. Stillbirth rate rises during coronavirus pandemic. Nature 2020, 585: 490
4.Mor M, Kugler N, Jauniaux E et al. Impact of the Covid-19 pandemic on excess perinatal mortality and morbidity in Israel. Am J Perinatol.2020 Dec 10, doi: 10.1055/s-0040-1721515
5. Kumari V, Mehta K, Choudhary R. Covid-19 outbreak and decreased hospitalisation of pregnant women in labour Lancet Glob Health 2020 Sep; 8(9): e1116-e1117. doi: 10.1016/S2214-109X(20)30319-3
6. Ciacchini B, Tonioli F, Marciano C et al., Reluctance to seek pediatric care during the COVID-19 pandemic and the risks of delayed diagnosis, in J. Pediatr., 2020 Jun, 29; 46(1):87, doi: 10.1186/s13052-020-00849-w;
7. Dopfer C, Wetzke M, Zychlinsky Scharff A et al., COVID-19 related reduction in pediatric emergency healthcare utilization – a concerning trend, in BMC Pediatr., 2020 Sep 7; 20(1):427, doi:10.1186/s12887-020-02303-6;
8. Lynn R. M, L Avis JL, Lenton S et al., Delayed access to care and late presentations in children during the COVID-19 pandemic: a snapshot survey of 4075 paediatricians in the UK and Ireland, in BMJ Arch. Dis. Child., 2020 Jun 25, doi: 10.1136/archdischild-2020-319848.
9. Ravaldi C, Vannacci A, The COVID-ASSESS dataset - COVID19 related anxiety and stress in prEgnancy, poSt-partum and breaStfeeding during lockdown in Italy. Data in Brief 2020 33, 106440 https://doi.org/10.1016/j.dib.2020.106440
10. Ravaldi C, Wilson A, Ricca V, Homer C, Vannacci A, Pregnant women voice their concerns and birth expectations during the COVID-19 pandemic in Italy, Women Birth (2020), doi: 10.1016/j.wombi.2020.07.002
I read with interest the economic evaluation of Speed of Increasing milk Feeds Trial (SIFT) in preterm infants presented by Tahir and colleagues.(1) While the clinical findings from the SIFT had shown short-term benefits such as lesser TPN days with faster feed increments, and was equivocal for the composite primary outcome of death and disability measured at 24 months, this analysis recommends against faster feed increments based on the cost-effectiveness analyses. The average total costs is shown to be marginally higher for subjects in this arm, with a mean difference of £267 (0.25%). I highlight below many issues that probably affect the conclusions, and the generalizability of the findings, of this economic evaluation.
First, the trial enrolled 1394 and 1399 patients in the two study arms. However, the cost data of initial hospitalization is presented for 1224 and 1246 patients in these arms. It seems that 170 and 153 patients from the two trial arms were lost to follow-up after the initial hospitalization;(2) however, the data for these subjects should not be excluded while calculating the average initial hospitalization costs per subject.
Second, more deaths during the initial hospitalization were reported in the slower increment arm and those probably lowered the average cost for this arm. It is well known that the hospitalization costs for very preterm infants that die during the neonatal period are substantially lower than those of the survivors....
I read with interest the economic evaluation of Speed of Increasing milk Feeds Trial (SIFT) in preterm infants presented by Tahir and colleagues.(1) While the clinical findings from the SIFT had shown short-term benefits such as lesser TPN days with faster feed increments, and was equivocal for the composite primary outcome of death and disability measured at 24 months, this analysis recommends against faster feed increments based on the cost-effectiveness analyses. The average total costs is shown to be marginally higher for subjects in this arm, with a mean difference of £267 (0.25%). I highlight below many issues that probably affect the conclusions, and the generalizability of the findings, of this economic evaluation.
First, the trial enrolled 1394 and 1399 patients in the two study arms. However, the cost data of initial hospitalization is presented for 1224 and 1246 patients in these arms. It seems that 170 and 153 patients from the two trial arms were lost to follow-up after the initial hospitalization;(2) however, the data for these subjects should not be excluded while calculating the average initial hospitalization costs per subject.
Second, more deaths during the initial hospitalization were reported in the slower increment arm and those probably lowered the average cost for this arm. It is well known that the hospitalization costs for very preterm infants that die during the neonatal period are substantially lower than those of the survivors.(3)
Third, health services costs for 2 years after the initial hospitalization was collected via a patient questionnaire, completed by 842 and 873 parents for the two trial arms. The missing data on a large percentage of study subjects could have resulted in biased estimates for these costs.
Fourth, unit cost of resource items presented in table 1, omit the parenteral nutrition costs that tend to be substantial.(4) Since the trial showed less parenteral nutrition use in the faster arm, the inclusion of these costs (as planned in the protocol), could have had a significant impact on the analyses.
Also, this economic evaluation lacks generalizability, in terms of its applicability to other jurisdictions, as no sensitivity analyses were conducted for a range of cost values for salient resource items that vary significantly across countries with similar economic development. For example, the costs listed for community paediatrician’s visit (£407 per visit) and donor breast milk (£335/litre) are 4 to 6 times higher than the typical costs for these items in the North America.
References
1. Tahir W, Monahan M, Dorling J, et al. Economic evaluation alongside the Speed of Increasing milk Feeds Trial (SIFT). Arch Dis Child Fetal Neonatal Ed. 2020 Nov;105(6):587-592. doi: 10.1136/archdischild-2019-318346.
2. Dorling J, Abbott J, Berrington J, et al; SIFT Investigators Group. Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants. N Engl J Med. 2019 Oct 10;381(15):1434-1443. doi: 10.1056/NEJMoa1816654.
3. Phibbs CS, Schmitt SK, Cooper M, et al. Birth Hospitalization Costs and Days of Care for Mothers and Neonates in California, 2009-2011. J Pediatr. 2019 Jan;204:118-125.e14. doi: 10.1016/j.jpeds.2018.08.041.
4. Walter E, Liu FX, Maton P, et al. Cost analysis of neonatal and pediatric parenteral nutrition in Europe: a multi-country study. Eur J Clin Nutr. 2012 May;66(5):639-44. doi: 10.1038/ejcn.2011.225.
Dear Editor,
we read with great interest the work by Balasubramanian H et al (1). Their systematic review and meta-analysis included 19 randomised controlled trials comparing umbilical cord milking (UCM) with delayed cord clamping (DCC, 5 studies, 922 newborns) and immediate cord clamping (ICC, 14 studies, 1092 newborns) in preterm infants. They concluded that “… cord milking, as compared to delayed cord clamping, significantly increased the risk of severe intraventricular haemorrhage (IVH) in preterm infants <34 weeks gestation”. We believe that this firm conclusion is not supported by the available data: 1) firstly, the gestational age of population in the four analyzed studies ranges from 23 to 31 weeks gestation in three studies (2-4) and from 24 to 32 weeks in one study with no severe IVH reported (5); 2) secondly, at least 20 of the 24 severe IVH events in the UCM group occurred in newborns less than 28 weeks’ gestation (3), while gestational age of newborns with the remaining 4 IVH events is not reported (thus, it actually might be even zero severe IVH in newborns above 27 weeks gestation). Therefore, the increased risk of severe IVH should be referred only to PREMOD 2 infants less than 28 weeks’ gestation (3), and not also extended to infants with 28-33 weeks’ gestation population.
This metanalysis confirms what we stated in our commentary to PREMOD 2 study (6): UCM procedure demonstrates advantages in comparison to routine practice of ICC at bir...
Dear Editor,
we read with great interest the work by Balasubramanian H et al (1). Their systematic review and meta-analysis included 19 randomised controlled trials comparing umbilical cord milking (UCM) with delayed cord clamping (DCC, 5 studies, 922 newborns) and immediate cord clamping (ICC, 14 studies, 1092 newborns) in preterm infants. They concluded that “… cord milking, as compared to delayed cord clamping, significantly increased the risk of severe intraventricular haemorrhage (IVH) in preterm infants <34 weeks gestation”. We believe that this firm conclusion is not supported by the available data: 1) firstly, the gestational age of population in the four analyzed studies ranges from 23 to 31 weeks gestation in three studies (2-4) and from 24 to 32 weeks in one study with no severe IVH reported (5); 2) secondly, at least 20 of the 24 severe IVH events in the UCM group occurred in newborns less than 28 weeks’ gestation (3), while gestational age of newborns with the remaining 4 IVH events is not reported (thus, it actually might be even zero severe IVH in newborns above 27 weeks gestation). Therefore, the increased risk of severe IVH should be referred only to PREMOD 2 infants less than 28 weeks’ gestation (3), and not also extended to infants with 28-33 weeks’ gestation population.
This metanalysis confirms what we stated in our commentary to PREMOD 2 study (6): UCM procedure demonstrates advantages in comparison to routine practice of ICC at birth in preterm infants, namely less need of RBC transfusions and a trend toward less IVH (both all grades and severe), but probably to delay cord clamping for at least 60 sec while assisting the baby bedside (with tactile stimulation, as in refs 3-4) is the right strategy to protect the newborn and respect the physiology of transition at birth.
1) Balasubramanian H, Ananthan A, Jain V et al. Umbilical cord milking in preterm infants: a systematic review and meta-analysis Arch Dis Child Fetal Neonatal Ed 2020 Nov;105(6):572-580
2) Katheria AC, Truong G, Cousins L, et al. Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 2015;136:61–9.
3) Katheria A, Reister F, Essers J, et al. Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 2019;322:1877–86
4) Finn D, Ryan DH, Pavel A, et al. Clamping the Umbilical Cord in Premature Deliveries (CUPiD): Neuromonitoring in the Immediate Newborn Period in a Randomized, Controlled Trial of Preterm Infants Born at <32 Weeks of Gestation. J Pediatr 2019;208:121–6
5) Rabe H, Jewison A, Alvarez RF, et al. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Obstet Gynecol 2011;117:205–11.
6) Pratesi S, Dani C. Commentary: Association of Umbilical Cord Milking vs. Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. Front Pediatr 2020 Apr 17;8:178. doi: 10.3389/fped.2020.00178
De Curtis et al reported some changes occurring in perinatal outcomes during lockdown in Lazio region, Italy. In particular, according to their data, preterm deliveries were reduced while stillbirth (SB) rate seems to be three-fold increased respect with the same period of 2019 (1).
We collected the same outcomes in Emilia-Romagna (ER), a northern Italian region with 4.47 million residents. Gestational age at delivery has been obtained by Birth Certificates (CedAP) while SB occurrence was collected from the Surveillance system of SB. This system is active since 2014. It records and audits, in a multidisciplinary way, each single case reported by every birth center of the Region. SB was defined according to WHO as published elsewhere together with other details of the Audit process (2).
In Emilia-Romagna, in the quarter March to May 2020, the one of the national lockdown, there were 22 SB (≥22+0 weeks) out of 6800 singletons births, for a rate of 3.24/1000. For the same quarter, in the previous 6 years, SB rate ranged from 2.86 (22/7687) in 2016 to 4.32 (31/7170) in 2019. According to one-way analysis of variance for 2014-2020 years, SB rate not changed significantly (p value >0.05 for each years of observation).
It has to be highlighted that a small number of events allow to a great variations in the rates, in a phenomenon such as SB that has a very low prevalence. For this reason, a comparison of only two points as previously done (1) could lead artif...
De Curtis et al reported some changes occurring in perinatal outcomes during lockdown in Lazio region, Italy. In particular, according to their data, preterm deliveries were reduced while stillbirth (SB) rate seems to be three-fold increased respect with the same period of 2019 (1).
We collected the same outcomes in Emilia-Romagna (ER), a northern Italian region with 4.47 million residents. Gestational age at delivery has been obtained by Birth Certificates (CedAP) while SB occurrence was collected from the Surveillance system of SB. This system is active since 2014. It records and audits, in a multidisciplinary way, each single case reported by every birth center of the Region. SB was defined according to WHO as published elsewhere together with other details of the Audit process (2).
In Emilia-Romagna, in the quarter March to May 2020, the one of the national lockdown, there were 22 SB (≥22+0 weeks) out of 6800 singletons births, for a rate of 3.24/1000. For the same quarter, in the previous 6 years, SB rate ranged from 2.86 (22/7687) in 2016 to 4.32 (31/7170) in 2019. According to one-way analysis of variance for 2014-2020 years, SB rate not changed significantly (p value >0.05 for each years of observation).
It has to be highlighted that a small number of events allow to a great variations in the rates, in a phenomenon such as SB that has a very low prevalence. For this reason, a comparison of only two points as previously done (1) could lead artifacts.
Moreover, another source of variation is represented by the Italian law which still defines any product of conception prior to 180 days of development (25 weeks and 5 days) as a miscarriage. We already reported that this underestimate SB rate when data collection is performed by using official statistical flow respect with a prospective recording in an active surveillance program (2).
Furthermore, the proportion of very premature births (<31+6 week) and moderate/late premature births (32+0-36+6) was not significantly different between the 2020 national lockdown period and the same calendar period from the previous 6 years (OR 0.88 – CI95% 0.67-1,16 and OR 0.91; CI 95% 0.80-1.03, respectively).
To understand differences with Lazio, it cannot be excluded that in 2020 there was an information bias (3) which led to a greater accuracy in the collection data and greater precision in the case definition in the pandemic than in the previous period. This hypothesis is supported by the very low rate of SB in 2019, much lower than reported in every European region.
Thus, we conclude from our findings that no changes occurred in SB during pandemic despite the rate of first Covid 19 spread in ER was 6.2/1000, almost five times higher than the one reported in Lazio (1.3/1000) (4).
During lockdown several emergency room accesses were significantly lesser requested by patients, including gynecological referrals (5). However, obstetric clinics of the National Health System did not change their offer and Obstetrics units never interrupted their perinatal cares.
In conclusion, statistical artifact or information bias could best explain the observed transitory increase of SB in Lazio rather a direct effect of infection or a supposed reduced utilization of NHS. We hope the findings here reported will be useful for larger data collection (entire set of data is available upon request) since only big databases could reliably conclude about perinatal outcomes.
References
1. De Curtis M, Villani L, Polo A. Increase of stillbirth and decrease of late preterm infants during the COVID-19 pandemic lockdown. Arch Dis Child Fetal Neonatal Ed. 2020 Oct 30:fetalneonatal-2020-320682. doi: 10.1136/archdischild-2020-320682. Epub ahead of print. PMID: 33127736.
2. Po' G, Monari F, Zanni F, Grandi G, Lupi C, Facchinetti F; Stillbirth Emilia-Romagna Audit Group. A regional audit system for stillbirth: a way to better understand the phenomenon. BMC Pregnancy Childbirth. 2019 Aug 5;19 (1):276. doi: 10.1186/s12884-019-2432-2. PMID: 31382995; PMCID: PMC6683556.
3. Kesmodel US. Information bias in epidemiological studies with a special focus on obstetrics and gynecology. Acta Obstet Gynecol Scand. 2018 Apr;97(4):417-423
4. Dipartimento della Protezione civile – Presidenza del Consiglio dei Ministri, accessed 13 Nov 2020. < http://www.protezionecivile.gov.it>
5. Grandi G, Del Savio MC, Caroli M, Capobianco G, Dessole F, Tupponi G, Petrillo M, Succu C, Paoletti AM, Facchinetti F. The impact of COVID-19 lockdown on admission to gynecological emergency departments: Results from a multicenter Italian study. Int J Gynaecol Obstet. 2020 Jun 30. doi: 10.1002/ijgo.13289. Epub ahead of print. PMID: 32602939.
A reply to:
“Parenteral nutrition for preterm infants: Correcting for arachidonic and
docosahexaenoic acid may not suffice” by Bernard et al. regarding the publication:
Frazer LC, Martin CR. Parenteral lipid emulsions in the preterm infant: current issues
and controversies. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 29: fetalneonatal-
2020-319108. doi: 10.1136/archdischild-2020-319108. Epub ahead of print. PMID:
33514630.
Lauren C. Frazer1,2, Camilia R. Martin2,3,4
1Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA, USA 4Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence: cmartin1@bidmc.harvard.edu
Word Count: 216
Keywords: arachidonic acid, docosahexaenoic acid, lipid emulsions, preterm infant
Dear Editor,
We would like to thank Bernhard and colleagues for their thoughtful letter “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” written in response to our review. The authors of the letter raised important issues regarding the lack of data surrounding the optimal balance of arachidonic (ARA) and docosahexaenoic acid (DHA) that should be administered...
Show MoreDear Editor,
Show MoreWe read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on...
We read with interest results from the Hypotension in Preterm Infants (HIP) trial by Dempsey et al.1 Unfortunately this multicentre randomised controlled trial (RCT) could not provide robust conclusions. Enrolment was limited to 58 of the planned 830 infants, 7% of those screened, attributed to strict inclusion criteria and recruitment challenges. This along with high inotropic usage in the restrictive group limits study power and generalisation.
Show MoreSome clarification would be useful. The CONSORT diagram should label the two study arms, where imbalance in numbers not receiving the allocated intervention (6/29 vs 1/29) may warrant further analysis. The proportion with invasive lines seems low, exact reasons for exclusion/non-inclusion could be detailed, and maximum age at enrolment given.
In our published RCT 2, three blood pressure (BP) intervention protocols were compared (BP below gestational age as in HIP, more active, or less active). This single centre pilot study randomised 60 infants <29 weeks, 45% of those screened and 100% of target recruitment, with invasive BP acquired every 10 seconds for a week. The HIP trial suggests their hypotension rate of 25% is low but without BP acquisition details, comparison is difficult. Their figure showing BP following dopamine or placebo requires data variability measures.
In our study, we found higher BP was associated with lower EEG discontinuity.3 The HIP study4 did not stipulate commonly used end-organ p...
The reported findings that some MRSOPA corrective steps actually made matters worse (1) should be a wake-up call to those teaching neonatal resuscitation (NRP), especially as many components of the algorithm are not evidence based and have never been validated.
Show MoreI wish to briefly report on two adverse outcomes which occurred on Vancouver Island at separate sites and at separate times, both following the introduction of the MRSOPA algorithm. Both infants were delivered at term by C Section under maternal general anesthetic. One was a preplanned elective C Section, the other for failure to progress with no concerns with the fetal heart tracing. There was no meconium present in the amniotic fluid. Both infants were depressed at birth but with palpable heartbeat. For both infants, there was difficulty in establishing effective ventilation. When intubation was eventually achieved, there was no colour change with CO2 detector, resulting in removal and resumption of bag-mask ventilation. The Neopuff (Fisher & Paykel) T piece was used in both cases and pressures were initially set at 20/5cm H20, as per NRP guidelines. However pressure increases occurred late. One baby had completely normal arterial cord gases. The other had an arterial cord pH 7.17.
Following a prolonged but eventually successful resuscitation, both infants were cooled for 72hours. One infant required transport to a level 3 site and subsequently did well. The other child did poorly. That child now...
Dear Editor,
Show MoreWe read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on...
Dear Sir or Madam!
Nasal CPAP is one of the most important therapies in neonatology. Accordingly, the manufacturers of such devices are very interested in gaining market share. Not all of their "sales arguments" correspond to clinical or physical reality. This is why studies comparing different devices are so extremely important.
The authors claim to have compared three CPAP systems that are referred to as "variable-flow" devices. This refers to CPAP systems that generate their CPAP through one or more jets, corresponding to jet ventilation as it is known in laryngeal surgery. But does the Miniflow CPAP belong in this category? The Miniflow has one inspiratory and one expiratory tube and does not have a jet. Pressure is generated through the expiratory valve of a ventilator. Such CPAP devices are actually called "constant-flow" devices.
Basically, the division into variable-flow and constant-flow devices is considered very confusing and, above all, physically questionable. However, the terms are very persistent. In any case, however, the statement of the study could be supplemented. It shows not only that there is no difference between variable flow devices, but equally no difference between variable and constant flow devices.
Yours sincerely,
Martin Wald
Ravaldi et al. in their letter raise two points of dispute. The first is linked to epidemiological data and the other to the fact that, according to them, a reduction in gynecological checks during pregnancy did not occur in the lockdown of spring 2020. I appreciate their engagement with the article but I disagree.
On the first point (epidemiological data), the difference between the data presented by Ravaldi and those indicated by us is linked to the fact that they mistakenly refer to older years. Ravaldi’s 2019 stillbirth is taken from the Italian Statistical Yearbook 2019, which refers to the entire 2016. Our data, obtained from the CEDAP (hospital discharge database, which records perinatal information on all newborns), are instead those of Mar-May 2019 and Mar-May 2020 (3 months of lockdown).
Show MoreFurthermore, Ravaldi’s stillbirth data starting from 22 weeks were taken from the ISTAT Reproductive Health document published in 2018, which refers to 2015 data. The authors therefore cannot contest the difference in the results because they are using different data sources. A further analysis (to be published) on larger samples on all births in Lazio confirmed a significant difference between stillbirths in the period March-May 2020 compared to the same months in the years 2017-2019 (3.23 vs 1.83 per thousand, p value = 0.014) . The increase in stillbirths in the first half of 2020 was observed in numerous developed and developing countries as well as in Italy (1-...
I read with interest the economic evaluation of Speed of Increasing milk Feeds Trial (SIFT) in preterm infants presented by Tahir and colleagues.(1) While the clinical findings from the SIFT had shown short-term benefits such as lesser TPN days with faster feed increments, and was equivocal for the composite primary outcome of death and disability measured at 24 months, this analysis recommends against faster feed increments based on the cost-effectiveness analyses. The average total costs is shown to be marginally higher for subjects in this arm, with a mean difference of £267 (0.25%). I highlight below many issues that probably affect the conclusions, and the generalizability of the findings, of this economic evaluation.
First, the trial enrolled 1394 and 1399 patients in the two study arms. However, the cost data of initial hospitalization is presented for 1224 and 1246 patients in these arms. It seems that 170 and 153 patients from the two trial arms were lost to follow-up after the initial hospitalization;(2) however, the data for these subjects should not be excluded while calculating the average initial hospitalization costs per subject.
Second, more deaths during the initial hospitalization were reported in the slower increment arm and those probably lowered the average cost for this arm. It is well known that the hospitalization costs for very preterm infants that die during the neonatal period are substantially lower than those of the survivors....
Show MoreDear Editor,
Show Morewe read with great interest the work by Balasubramanian H et al (1). Their systematic review and meta-analysis included 19 randomised controlled trials comparing umbilical cord milking (UCM) with delayed cord clamping (DCC, 5 studies, 922 newborns) and immediate cord clamping (ICC, 14 studies, 1092 newborns) in preterm infants. They concluded that “… cord milking, as compared to delayed cord clamping, significantly increased the risk of severe intraventricular haemorrhage (IVH) in preterm infants <34 weeks gestation”. We believe that this firm conclusion is not supported by the available data: 1) firstly, the gestational age of population in the four analyzed studies ranges from 23 to 31 weeks gestation in three studies (2-4) and from 24 to 32 weeks in one study with no severe IVH reported (5); 2) secondly, at least 20 of the 24 severe IVH events in the UCM group occurred in newborns less than 28 weeks’ gestation (3), while gestational age of newborns with the remaining 4 IVH events is not reported (thus, it actually might be even zero severe IVH in newborns above 27 weeks gestation). Therefore, the increased risk of severe IVH should be referred only to PREMOD 2 infants less than 28 weeks’ gestation (3), and not also extended to infants with 28-33 weeks’ gestation population.
This metanalysis confirms what we stated in our commentary to PREMOD 2 study (6): UCM procedure demonstrates advantages in comparison to routine practice of ICC at bir...
De Curtis et al reported some changes occurring in perinatal outcomes during lockdown in Lazio region, Italy. In particular, according to their data, preterm deliveries were reduced while stillbirth (SB) rate seems to be three-fold increased respect with the same period of 2019 (1).
Show MoreWe collected the same outcomes in Emilia-Romagna (ER), a northern Italian region with 4.47 million residents. Gestational age at delivery has been obtained by Birth Certificates (CedAP) while SB occurrence was collected from the Surveillance system of SB. This system is active since 2014. It records and audits, in a multidisciplinary way, each single case reported by every birth center of the Region. SB was defined according to WHO as published elsewhere together with other details of the Audit process (2).
In Emilia-Romagna, in the quarter March to May 2020, the one of the national lockdown, there were 22 SB (≥22+0 weeks) out of 6800 singletons births, for a rate of 3.24/1000. For the same quarter, in the previous 6 years, SB rate ranged from 2.86 (22/7687) in 2016 to 4.32 (31/7170) in 2019. According to one-way analysis of variance for 2014-2020 years, SB rate not changed significantly (p value >0.05 for each years of observation).
It has to be highlighted that a small number of events allow to a great variations in the rates, in a phenomenon such as SB that has a very low prevalence. For this reason, a comparison of only two points as previously done (1) could lead artif...
Pages