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.
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...
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 gave birth during COVID-19 lockdown in Italy [3] show indeed the opposite: concern for their own health was quite low in Italian mothers, while wellbeing of their child and care of their pregnancy were considered the most important tasks during lockdown [4].
3. 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
4. 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
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...
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-grade IVH and cerebral palsy at 8 years remained after adjusting for cPVL [unadjusted OR 2.24 (95% confidence interval (CI) 1.21, 4.16); p=0.011; adjusted for cPVL OR 2.22 (95% CI 1.14, 4.29) p=0.018]. As brain magnetic resonance imaging was not widely available for the cohorts in this study, we are not able to confirm the possibility of other lesions explaining the rates of cerebral palsy observed in our low-grade IVH groups.
Our paper highlights the associations of all grades of IVH with adverse outcomes at school age. Regardless of whether the associations are explained by other brain lesions, the findings highlight the importance of long term follow up in all extremely preterm newborns in regard to risk of neurodevelopmental deficits, including those with low-grade IVH.
Jeanie Cheong, Alicia Spittle, Peter Anderson and Lex Doyle
References:
1) Hollebrandse NL, Spittle AJ, Burnett AC, et al. School-age outcomes following intraventricular haemorrhage in infants born extremely preterm. Arch Dis Child Fetal Neonatal Ed 2020 Jul 30:fetalneonatal-2020-318989. doi: 10.1136/archdischild-2020-318989.
2) Klebermass-Schrehof K, Czaba C, Olischar M, et al. Impact of low-grade intraventricular hemorrhage on long-term neurodevelopmental outcome in preterm infants. Childs Nerv Syst 2012;28:2085–92.
3) Bolisetty S, Dhawan A, Abdel-Latif M, et al. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 2014;133:55–62.
4) Beaino G, Khoshnood B, Kaminski M, et al. Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study. Dev Med Child Neurol 2010;52:e119–25.
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...
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 regular interaction of colleagues in a real-life setting.(4) This social interaction and kinaesthetic activity results in reflection, thus building on their previous knowledge of intubation as per situated learning theory.(5)
Videolaryngoscopy was felt to reduce anxiety levels, improving patient safety whilst learning. Some participants expressed concerns that gaining proficiency in videolaryngoscopy might place the trainee at a disadvantage at another hospital where videolaryngoscopes were not in common use. Videolaryngoscopy is a useful adjunct for intubation training but cannot completely replace direct laryngoscopy due to some differences in technique, equipment and the lack of availability across centres.
References
1 O’ Shea JE, Kirolos S, Thio M, et al. Neonatal videolaryngoscopy as a teaching aid: the trainees’ perspective. Arch Dis Child FetalNeonatal Ed. Published Online First: 22 September 2020. doi: 10.1136/archdischild-2020-319619.
2 Fleming ND, Mills C. Not another inventory, rather a catalyst for reflection. To Improve the Academy 1992;11,137-155.
3 Husmann PR, O’Loughlin VD. Another Nail in the Coffin for Learning Styles? Disparities among Undergraduate Anatomy Students' Study Strategies, Class Performance, and Reported VARK Learning Styles.Anat Sci Educ 2020;(12)1:6-19.
4 Wenger E. Communities of Practice. Learning, meaning and identity. Cambridge: Cambridge University Press 2000.
5 Lave J, Wenger E. Situated learning: Legitimate peripheral participation. Cambridge: Cambridge University Press 1991.
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...
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 births in 2020, and very premature births were 8.52/1000 live births in 2019 vs 8.89/1000 live births in 2020. Unlike the reports from Denmark, these preliminary data suggest that Brazil has not experienced a reduction in the prevalence of extremely premature birth during the early months of the COVID-19 pandemic and its associated interventions. It has been hypothesized that the association between the lockdowns and preterm birth rates may be attributed to underlying mechanisms, such as reduced pregnancy-associated stress, increased support systems, altered work practices, governmental financial assistance, and decreased incidence of infections during pregnancy3. In Brazil, it is plausible that the limited and heterogeneously implemented social distance measures and high incidence of SARS-CoV-2 combined with the pre-existing social inequities, substantial background burden of other infectious diseases, and current crises may have compromised the beneficial impact observed in Denmark1. Alternatively, the results observed in Denmark could be a spurious association due to small numbers or an increased number of pregnancies ending in intrauterine death, as highlighted by the authors1. We welcome the presentation of data from Hedermann and colleagues1, but the contrasting results from Brazil highlight the need for international comparisons to better interpret the impact of COVID-19 public health policies4.
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,...
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, some studies in the distribution of treatment effects are missing and REM should not be done. This systematic review includes more than 10 studies, the conventionally accepted threshold for assessing the publication bias. Yet, this important step is missed. Given small size of ‘positive’ studies favoring BCPAP, one cannot exclude absence of ‘negative’ unpublished studies.
Second, authors define time-point for the ‘CPAP failure’ at 7 days of use. No consensus exists on what time-point constitutes the ideal cut-off for defining the failure and many studies report 72 h (or other time-points) as the cutoff. We are not sure whether authors were able to obtain the 7-day failure data from all the included studies. In our assessment of the studies, we were able to retrieve the 7-day outcome in only 4 of 12 studies.
Third, it is not clear which risk of bias assessment (ROB) tool has been used by the authors. While the text mentions the use of ROB-2 tool,[4] the risk of bias figures uses the original Cochrane ROB framework.[3]As criteria of the assessment of risk of bias are different in these tools, same domain in a study can be classified to be at high- or low-risk of bias with these two ROB tools. Use of both the tools in a single review may confuse the readers.
Fourth, nasal injury, one of the review outcomes is reported to be twice [RR 2.04(95% CI 1.33-3.14)] more common with BCPAP. The authors have attributed the higher risk of nasal injury to oscillatory effect of BCPAP. But we tend to disagree with this as there is neither sufficient evidence nor biological rationale behind this plausibility. Rather the incidence of nasal injury is highly dependent on the type of nasal interface used.[5] Different CPAP devices use different types of nasal interfaces and individual trials may not have ensured the use of identical interface.
Finally, authors have used meta-regression to investigate the effect of co-variates on the success of CPAP device. However, the choice of co-variates used in the meta-regression (country of origin, type of CPAP used in control arm and risk of bias) seems to be driven by availability bias. Type of nasal interface, starting CPAP pressure, actual measurement and matching of airway pressure in the BCPAP arm of the trial are more important and unaddressed confounding factors.
Contributors SK(supreetkhurana85@gmail.com) and DC contributed to all steps of making this letter.
Funding None.
Competing interest None Declared.
Patient Consent for publication Not required.
References
1. Thukral A, Sankar MJ, Chandrasekaran A, et al. Efficacy and safety of CPAP in low- and middle-income countries. J Perinatol 2016;36(1):S21-S28.
2. Bharadwaj SK, Alonazi A, Banfield L, et al. Bubble versus other continuous positive airway pressure forms: A systematic review and meta-analysis. Arch Dis Child Fetal Neonatal 2020;105:526-531.
3. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 6.1 [updated September 2020].The Cochrane Collaboration, 2020. Available from training.cochrane.org/handbook/current.(accessed 20 Sep 2020)
4. Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.
5. Imbulana DI, Manley BJ, Dawson JA, et al. Nasal injury in preterm infants receiving non-invasive respiratory support: a systematic review. Arch Dis Child Fetal Neonatal Ed 2018 Jan;103(1):F29-F35.
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...
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 not related to an initial low grade IVH but following (Gram-negative) sepsis or necrotising enterocolitis occurring later in the neonatal period.
Compared to several other studies, a high percentage of infants in this study developed CP (8% with no IVH, and 15, 18, 26 and 75% with grades 1-4 IVH). The higher levels of CP than generally expected for grades 1 and 2 IVH [5,6] may partly be explained by the presence of cPVL. Additionally there may have been non-cystic white matter injury e.g. punctate white matter lesions, cerebellar lesions or strokes that were not detected with the imaging protocol used. The statement "Our study adds to a growing understanding of the negative impact of low grade IVH on motor development" fails to adjust the findings for other lesion(s) known to lead to impaired motor development.
We also find the rates of CP in children with grades 3 and 4 IVH high. These may in part be related to care pathways chosen and the timing of treatment of post-haemorrhagic ventricular dilatation but no information is given about this.[7] One might expect about 50-60% of preterm infants with grade 4 IVH to develop a hemiplegia whilst here it is 75% perhaps influenced by the fact that 25% also had cPVL.
Another unexpected and worrying finding is that the severity of CP was the same in children with lower and higher grades of IVH. This could be due to the inclusion of infants with co-existing c-PVL or other lesions. It is unfortunate that no MRI findings are reported to substantiate the cUS findings particularly in infants with CP following low-grade IVH.
This paper may well be used by neonatologists to give prognoses following IVH in the first week after birth. We are concerned that these data will worry parents unnecessarily, especially those of infants with isolated low-grade IVH. Whilst it is fair to tell parents that other lesions may become apparent or develop we need to distinguish between outcomes due to findings seen at the time of scanning and those related to a potential pathology not yet seen and perhaps developing following unrelated clinical problems.
Yours sincerely
Frances Cowan, Floris Groenendaal and Linda S de Vries
Author affiliations:
Prof Frances M Cowan PhD FRCPCH
Dept. of Paediatrics
Hammersmith Hospital
Imperial College London
W12 0HS, UK
Email f.cowan@imperial.ac.uk
Dr Floris Groenendaal MD PhD and Prof Linda S de Vries MD PhD
Wilhelmina Children’s Hospital,
University Medical Centre Utrecht,
KE 04.123.1, PO Box 85090,
3508 AB Utrecht, Netherlands
References
1. Martinez-Biarge M, Groenendaal F, Kersbergen KJ, Benders MJNL, Foti F, van Haastert IC, Cowan FM, de Vries LS. Neurodevelopmental Outcomes in Preterm Infants with White Matter Injury Using a New MRI Classification. Neonatology. 2019;116(3):227-235
2. van Haastert IC, Groenendaal F, Uiterwaal CS, Termote JU, van der Heide-Jalving M, Eijsermans MJ, Gorter JW, Helders PJ, Jongmans MJ, de Vries LS. Decreasing incidence and severity of cerebral palsy in prematurely born children. J Pediatr. 2011 Jul;159(1):86-91.e1
3. Kusters CDJ, Chen ML, Follett PL Dammann O. "Intraventricular" hemorrhage and cystic periventricular leukomalacia in preterm infants: How are they related? J Child Neurol 2009; 24:1158-1170.
4. Kuban K, Sanocka U, Leviton A, Allred EN, Pagano M, Dammann O, et al. White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. J Pediatr 1999; 134:539-546.
5. Payne AH, Hintz SR, Hibbs AM, Walsh MC, Vohr BR, Bann CM, Wilson-Costello DE; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network: Neurodevelopmental outcomes of extremely low-gestational age neonates with low-grade periventricular intraventricular hemorrhage. JAMA Pediatr 2013;167:451–459.
6. Reubsaet P, Brouwer AJ, van Haastert IC, Brouwer MJ, Koopman C, Groenendaal F, de Vries LS. The Impact of Low-Grade Germinal Matrix-Intraventricular Hemorrhage on Neurodevelopmental Outcome of Very Preterm Infants. Neonatology 2017;112(3):203-210.
7. Leijser LM, Miller SP, van Wezel-Meijler G, Brouwer AJ, Traubici J, van Haastert IC, Whyte HE, Groenendaal F, Kulkarni AV, Han KS, Woerdeman PA, Church PT, Kelly EN, van Straaten HLM, Ly LG, de Vries LS. Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene? Neurology. 2018;90(8):e698-e706
Footnotes
• Contributors: FMC, FD and LdeV contributed equally to the letter
• Funding: The authors have not declared a specific funding agency in the public, commercial or not-for-profit sectors.
• Competing interests: None declared.
• Provenance and peer review: Not commissioned.
• Patient consent for publication: Not required.
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.
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...
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.
Show More1. 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...
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...
Show MoreDr 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)
Show MoreIn 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...
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...
Show MoreCPAP 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’.
Show MoreFirst, 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,...
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...
Show MoreCMV 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.
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