ABSTRACT
Background: COVID-19 trials took <1 year to identify therapies reducing death in >30,000 patients but the Australian Placental Transfusion Study took >12 years to show that delaying cord clamping reduced death or major disability (cerebral palsy, severe visual loss, deafness, or cognitive delay) in 1,531 preterm infants. What can this teach us? Further, as composite outcomes of death or major disability can be inconclusive if each is unequally affected (as in the NeOProM Collaboration1) 2 important aims are (i) global co-operation (https://www.alphacollaboration.com/) to identify core Participant-Intervention-Comparator-Outcome questions for trials assessing mortality, a key outcome, and (ii) to answer those questions in much larger, faster trials. Such trials will also yield much more precise estimates of disability in survivors than was previously typical - a major benefit. Method: To inform these aims we compared enrolment in 2 COVID-19 trials and in 10 trials by IMPACT collaborators with samples >1,500 in high- or low-or-middle-income countries (HIC/LMIC). Results: The COVID-19 trials took 3-9 months, enrolling 13 - 219 per-site-per-year. Perinatal trials took 16-86 months, enrolling 5 - 1,700 per site per year. Trials in pregnant women or LMIC (n = 53,092) enrolled 5 times more than trials in newborns or restricted to HIC (n = 9,014). (Table) Conclusions: Greater international collaboration could resolve questions of shared relevance and priority more rapidly. Megatrials addressing mortality may benefit from highly streamlined processes for enrolment and minimal data collection, e.g., RECOVERY's one-page outcome form.
ABSTRACT
BACKGROUND: Early reports of COVID-19 in pregnancy described management by caesarean, strict isolation of the neonate and formula feeding. Is this practice justified? OBJECTIVE: To estimate the risk of the neonate becoming infected with SARS-CoV-2 by mode of delivery, type of infant feeding and mother-infant interaction. SEARCH STRATEGY: Two biomedical databases were searched between September 2019 and June 2020. SELECTION CRITERIA: Case reports or case series of pregnant women with confirmed COVID-19, where neonatal outcomes were reported. DATA COLLECTION AND ANALYSIS: Data were extracted on mode of delivery, infant infection status, infant feeding and mother-infant interaction. For reported infant infection, a critical analysis was performed to evaluate the likelihood of vertical transmission. MAIN RESULTS: Forty nine studies included information on mode of delivery and infant infection status for 655 women and 666 neonates. In all, 28/666 (4%) tested positive postnatally. Of babies born vaginally, 8/292 (2.7%) tested positivecompared with 20/374 (5.3%) born by Caesarean. Information on feeding and baby separation were often missing, but of reported breastfed babies 7/148 (4.7%) tested positive compared with 3/56 (5.3%) for reported formula fed ones. Of babies reported as nursed with their mother 4/107 (3.7%) tested positive, compared with 6/46 (13%) for those who were reported as isolated. CONCLUSIONS: Neonatal COVID-19 infection is uncommon, rarely symptomatic, and the rate of infection is no greater when the baby is born vaginally, breastfed or remains with the mother. TWEETABLE ABSTRACT: Risk of neonatal infection with COVID-19 by delivery route, infant feeding and mother-baby interaction.