704 e-Letters

  • Letter/Comments to Editor on paper “Necrotizing enterocolitis in newborns receiving Diazoxide” published in ADC Fetal Neonatal Ed 2020; 0: F1-F5.

    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...

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  • Constant or variable flow nCPAP devices.

    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

  • Increase of stillbirth and decrease of late preterm infants during the COVID-19 pandemic lockdown

    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-...

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  • Comments on the analyses and the generalizability of findings from the Economic Evaluation of SIFT

    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....

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  • Umbilical cord milking is probably better than immediate cord clamping at birth in preterm infants

    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...

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  • First wave SARS-CoV-2 pandemic did not affect stillbirth prevalence.

    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...

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  • Stillbirth rates should be carefully assessed, and women should not be blamed for adverse perinatal outcomes

    Stillbirths are tragic events with devastating consequences on women and couples: all efforts to better understand, manage and prevent their occurrence are welcome. Nevertheless, we have some concerns on what reported by De Curtis et al, who suggested an increase of stillbirth rate during the COVID-19 pandemic lockdown in Lazio, Italy.
    1. First, we do not believe that a crude comparison with the corresponding months of 2019 is a proper control. Stillbirths are rare events, with a variable incidence during the year and alternating phases of low incidence and clusters of cases. The assumption that in the period Mar-May 2020 their number in the Lazio region should have been the same as of Mar-May 2019 is unsubstantiated. Consistently, the incidence reported by the authors in Lazio for 2020 (3.23 ‰) is almost the same of what reported for the same region in 2019 yearly statistics (3.00 ‰) [1] in which stillbirth is defined as a loss after 180 days (25 wks + 5 days). Furthermore, when using the 22 wks definition, reported stillbirth rate for Italy is significantly higher (4.70 ‰) [2].
    2. Second, the authors suggest that the supposed increase could be due to reduced visits to hospitals due to the fear of contracting COVID-19. Unfortunately, this claim (that indeed blames women for the loss of their unborn child) is not at all supported by facts, as it wasn’t in the manuscript that the authors cite as a reference. Data from a sample of 2448 women who were pregnant or...

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  • Reply to Cowan et al

    We thank Drs Cowan, de Vries and Groenendaal for their interest in our study.(1) Their main concerns related to our findings that low-grade intraventricular haemorrhages (IVH) were associated with higher rates of cerebral palsy than experienced in their own centres and other published studies, and that other lesions apart from low-grade IVH may explain the higher rates of motor impairment and cerebral palsy noted in our cohorts.

    Our cerebral palsy rates were determined at age 8 years, by experienced developmental paediatricians blinded to group and clinical history. Thus we are confident of the robustness of clinical ascertainment. We accept that our reported rates of cerebral palsy in low-grade IVH may be higher than those in some other studies, highlighting that our findings are likely specific to our population rather than others. However, our finding of increased cerebral palsy in low-grade IVH is not isolated, as we identified several studies describing 1.5-2 times the baseline rates in preterm cohorts born <33 weeks’ with low-grade IVH compared with no IVH.(2-4) We acknowledge that our data supports an association between low-grade IVH and cerebral palsy, and at no point did we imply a causal relationship.

    We agree that cystic periventricular leukomalacia (cPVL) is a well-established cause of cerebral palsy. Co-existing cPVL in our low-grade IVH groups did not explain the associations with cerebral palsy. The independent relationships between low-gra...

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  • Response to Neonatal videolaryngoscopy as a teaching aid: the trainees’ perspective

    Dr O’Shea and colleagues provide useful trainee perspective on the use of videolaryngoscopy as a teaching aid and highlight the need for standardised training packages.

    We performed a qualitative study using semi-structured interviews of 22 consultants and trainees in a UK tertiary neonatal unit where videolaryngoscopy is commonly used. Interviews were recorded and transcribed verbatim. Data was analysed using attribute and descriptive coding methods. Framework Analysis was used to interpret the data obtained from interviews.

    In our study, videolaryngoscopy was felt to have largely positive effects on facilitating safer training in an era where intubation opportunities are lacking. As with O’Shea et al,(1) our participants felt that videolaryngoscopy allowed considerably easier demonstration of intubation techniques. Interviewees commented that looking at the monitor combined with the movements of the operator and coaching in real-time, assisted eye-hand co-ordination and made it easier to correct technique. Visual feedback would benefit kinaesthetic learning as per the VARK: Visual, Aural, Read/write, and Kinesthetic learning styles, although the existence of these styles is debated.(2,3)
    In our study, interviewees felt that use of videolaryngosopy allowed group teaching, and instilled confidence in those watching in what was occurring. This ‘team learning’ aligns with social cognitive theory, where learning experiences are active and social, with re...

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  • Preliminary data suggest that COVID-19 pandemic disruption has no impact on preterm births rates in Brazil: early nationwide estimates

    Hedermann and colleagues reported a decreased rate of extremely premature birth as a potential beneficial effect of nationwide COVID-19 lockdown in Denmark1. Although this study provides important new evidence that enhances our understanding of the aetiology of extreme prematurity, comparisons with other populations are vital for delineating the mechanisms underlying the observed beneficial effect. Moreover, uncertainty remains about the direct and indirect impacts of the COVID-19 pandemic and its associated lockdowns on live births globally. To begin to address these gaps in knowledge, we used preliminary administrative data from the Brazilian Live Births Information System (SINASC) to assess the effect of COVID-19 and its associated disruptions on prematurity rates in a middle-income country with a high incidence of SARS-CoV-2 infections. Similarly, to Hedermann and colleagues1, we included the months of most intensive social distance interventions (17th March to 31st May 2020)2 and excluded registrations with multiple births. However, to adapt for the Brazilian data, we also excluded congenital abnormalities and used as comparison the same period but only for the year of 2019, due to the Zika virus epidemic that occurred in previous years. We included 613,640 live births from 2019 and 560,691 from 2020. Overall, we observed similar rates of premature births in both years; the proportion of extremely preterm births was 4.57/1000 live births in 2019 vs 4.52/1000 live bi...

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