700 e-Letters

  • 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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  • Bubble CPAP for neonates :Is it really better than others!

    CPAP is the standard method of respiratory support in preterm neonates. BCPAP is the most widely used type of CPAP in low- and middle-income countries due to its simplicity of design, ease of use and low cost.[1] Efficacy of BCPAP has been compared against other pressure generating devices in many small RCTs and is the topic of interest amongst neonatologists. Latest systematic review involving 12 eligible studies including 1194 subjects shows a significant reduction of CPAP failure in BCPAP group [RR 0.75 ,95% CI (0.57-0.98)] without any significant impact on mortality, BPD and air leak.[2] However, we want to identify few issues with the review which if addressed, may shift the pooled treatment effect towards ‘null’.
    First, authors have used the random-effects meta-analysis (REM) to calculate the pooled effect size. A fixed-effects meta-analysis assumes that all individual studies are trying to estimate a single true effect of the intervention and the pooled estimate is the ‘typical’ intervention effect.[3] However, the REM assumes that different studies are estimating different (but related) treatment effect which have a distribution (assumed to be a normal distribution). The pooled estimate obtained with REM is hence an ‘average’ intervention effect based on the assumption that intervention effects seen in all the individual studies are available for pooling. Therefore, before conducting a REM, publication bias needs to be excluded. If a publication bias exists,...

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  • School-age outcomes following intraventricular haemorrhage in infants born extremely preterm – Is it right to blame the IVH?

    Hollebrandse et al are to be congratulated on achieving such a high follow-up rate at 8 years in a large cohort of preterm infants with intraventricular haemorrhage (IVH). Long-term outcomes related to specific cUS findings are increasingly important as many significant if more subtle neurodevelopmental problems are not detected at earlier follow-up.

    It is reassuring that children with the milder grades of IVH had intellectual outcomes similar to the no-IVH group but of concern is the report of significant motor deficits and cerebral palsy (CP) following grades 1 and 2 IVH. However the outcomes given may not solely be related to IVH but to other pathologies notably cystic periventricular leukomalacia (cPVL) a well-known predictor of motor deficits and CP.[1,2] cPVL was found in 6% and 4% of the children with grades 1 and 2 IVH and 13% and 25% of those with grades 3 and 4 IVH. The authors neither adjust for this pathology, saying that “cPVL may lie along the causal pathway between IVH and adverse outcomes”, nor do they give evidence to support this statement. Indeed the contribution of cPVL to outcomes is not discussed or mentioned in the abstract. We are not aware of evidence that low grade IVH is in a causal pathway to cPVL, and suggested associations between cPVL and higher grades of IVH were based on studies using infrequent ultrasound protocols and without MRI scanning at term equivalent age. [3,4] We are aware of preterm infants who develop late-onset c-PVL no...

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  • Breastfeeding and CMV infection -risks and benefits for the very premature babies

    CMV exposure of breast milk fed infants from seropositive mothers is a well known phenomenon. Patel et al. excellent research has shed a very important and troubling consequence of this infection on very low birth premature babies. Yet, some of the information needed for decision making and recommendations is lacking from the published data. From the data we see that 17% (76 of 457 infants) of seropositive mothers decided not to give there babies any breast milk in contrast to 0% ! of seronegative mothers. I think that in order to make a proper decision we need to compare the incidence of Necrotizing Enterocolitis and other complications of prematurity between this group of exclusively formula fed babies and CMV infected babies. Although the numbers may not be sufficient for statistical analysis we might benefit as caregivers from this important information.

  • Randomized controlled trials on therapeutic hypothermia for mild neonatal encephalopathy are very fragile

    Dear Editor,
    We read with great interest the systematic review and meta-analysis by Kariholu et al on the evaluation of therapeutic hypothermia as a tool to decrease composite outcome like death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE). [1]. The authors, including 5 randomized controlled trials (RCTs) reporting the considered outcome, found insufficient evidence to recommend routine therapeutic hypothermia for NE [1]. We agree with this statement and we’d like to support it evaluating the fragility index of the RCTs included in this meta-analysis.
    The fragility index (FI), an intuitive measure of the robustness of RCTs, was introduced in critical care medicine [2]. The studies with larger FI have more robust findings compared with the studies with poor FI [2]. Recently the FI was applied to different meta-analyses in order to confirm or not the results by including in the analysis the studies with FI greater than zero [3, 4, 5]. We evaluated the FI of the RCTs included in this meta-analysis using a two-by-two contingency table and p-value produced by Fisher exact test [2]. In line with the high risk of bias of the included RCTs, we found no studies with FI more than zero for death or moderate/severe disability (Battin FI=0 p= 0,455, Gluckman FI=0 p=1, Jacobs FI=0 p= 0,729, Thayyil FI=0 p=0.350, Zhou FI=0 p=1) [1].
    Since all the included studies are fragile, we strongly support the author’s conclusion that...

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