Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matchingBMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5678 (Published 16 October 2019) Cite this as: BMJ 2019;367:l5678
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Helenius et al highlight the value of having extremely premature births in tertiary neonatal units and suggest an association of increased mortality and severe brain injury among those extremely preterm (EP) infants born in non-tertiary centres or transferred out within 48 hours after birth. Through a propensity analysis to match the retrospective cohorts from National Neonatal Research Database (NNRD) of UK, the authors rightly suggested the promotion of births of EP infants in tertiary perinatal facilities.
Perhaps due to the limitations inherent to the data source, the article lacks visibility of certain key variables pertinent to neonatal brain injury and early mortality. Presence and management of chorioamnionitis (Triple I) , presence and management of premature prolonged rupture of membranes (PPROM), uptake of antenatal magnesium sulphate for neonatal neuroprotection , extremely low birth weight (ELBW) deliveries following in-utero transfers (IUT) from non-tertiary centres, delayed clamping of umbilical cord after birth , could all influence the outcome. The authors conducted the propensity analysis without the above important variables in the matching and the collective or individual contributions of these unmeasured potentially significant confounders remain at large .
While complex antenatal cases tend to gravitate to tertiary perinatal centres and potentially could have added morbidities, the advanced and structured continuity of obstetric and neonatal care of such units aids in their better outcomes. Yet to be determined are the specific neonatal benefits of IUT of potential ELBW delivery presenting to a non-tertiary centre versus the early postnatal transfer by the skilled and established neonatal transport networks. Such premature births being more common than those from complex antenatal cases receiving ongoing care in tertiary units, this observational study by Helenius et al  hopefully will prompt researchers to address the challenges and benefits around IUT of threatened EP births.
Multiple logistical and often non-clinical reasons could delay the attempted IUT with threatened preterm labour (PTL) . Early diagnosis of genuine PTL could be difficult and waiting for regular uterine contractions / established changes to cervix could miss a transfer opportunity . As more non-tertiary units apply point-of-care markers to predict preterm delivery such as quantitative fetal fibronectin (fFN) / actim partus (AP), ability to identify the genuine PTL and timely IUT to the designated tertiary centre would improve. Standardization of perinatal and early neonatal care of imminent periviable births among the non-tertiary centres also would have significant bearing on the resultant adverse outcomes.
If the frequency of IUT increase, service users should be better informed about the process and the circumstances that necessitate their displacement and efforts to minimize the emotional and socio‐economic impact to women and their families need to be considered . Perhaps this population-based study would pave the way to establish standardized guidelines and networks for IUT of extreme PTL, similar to the establishment of neonatal transport systems in developed countries.
1. Helenius K, Longford N, Lehtonen L, Modi N, Gale C. Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants; observational cohort study with propensity score matching. BMJ 2019;367:15678.
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Competing interests: No competing interests
Cord clamping at birth is an intervention without an indication in both term and preterm babies (1,2). In an emergency, clamping may be performed immediately, even before the first gasp, enabling the baby to be transferred to a resuscitaire, rather than allowing or supporting cardiovascular transition (3) and bringing help to the patient (rather than vice versa). This separates the baby from its mother, deprives it of the vital placental transfusion and circulating stem cells (4), and causes cardiovascular instability that is hardly improved by any later ambulance transfer. Little wonder it has been shown to increase death and brain haemorrhage in the extremely premature infant (2).
Nearly a decade after calls for routine documentation of the timing by accoucheurs (5), NICE recommended against early cord clamping, supplemented by a Quality Standard (6), and yet implementation has not been checked. It would be a joke were it not so serious (7). Although the National Neonatal Data Set records time between delivery and umbilical cord clamping in seconds, this matter did not appear to feature in the study (8) and accompanying editorial (9) which speculated about the causes of differences in extremely premature baby outcomes born in and outwith tertiary centres. Can the authors explain this?
1. Rabe H, Gyte GML, Díaz-Rossello JL, Duley L. Does delaying cord clamping or using cord milking at birth improve the health of babies born too early? 17 Sept 2019 https://www.cochrane.org/CD003248/PREG_does-delaying-cord-clamping-or-us... [last accessed 18 October 2019]
2. McDonald SJ, Middleton P, Dowswell T, Morris PS Effect of timing of umbilical cord clamping of term infants on mother and baby outcomes. 11 July 2013 https://www.cochrane.org/CD004074/PREG_effect-timing-umbilical-cord-clam... [last accessed 18 October 2019]
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4. Bewley S, Dìaz‐Rossello JL, Mercer J. Natural stem cell transplantation: interventions, nuances and ethics. J Cellular & Molecular Medicine 2010 https://onlinelibrary.wiley.com/journal/15824934 https://doi.org/10.1111/j.1582-4934.2010.01199.x
5. Diaz Rosello J. Early umbilical cord clamping and cord-blood banking. Lancet 2006;368:840 DOI:https://doi.org/10.1016/S0140-6736(06)69323-9
6. NICE. Quality standardQuality standard [QS105] Published December 2015, last updated: February 2017 https://www.nice.org.uk/guidance/qs105/chapter/Quality-statement-6-Delay... [last accessed 18 October 2019]
7. Weeks S, Bewley S. Achieving routine prophylactic red cell reduction via premature cord clamping vs. neonatal venesection: A randomised controlled trial protocol, JRSM 2018;111(8): 270–275
8. Kjell Helenius K, Longford N, Lehtonen L, Modi N, Gale C. Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matching. BMJ 2019;367 doi: https://doi.org/10.1136/bmj.l5678
9. Travers CP. Hospital transfer of extremely preterm infants. Do it before not after birth BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5930
Competing interests: DOI: SB received a fee for chairing NICE Intrapartum Care Guideline CG190 and, along with others, gave away intellectual property rights to a bedside trolley (3)