OBJECTIVES: To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy.

SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials.

SELECTION CRITERIA: We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation).

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO2) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.

MAIN RESULTS: We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO2 range (MD 13.54%, 95% CI 11.69 to 15.39; I2 = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO2 range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I2 = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO2 range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO2 Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis.

METHODS: This cross-sectional, randomized, double-masked clinical trial compared cyclopentolate 1% + phenylephrine 2.5%, tropicamide 1% + phenylephrine 2.5%, and a prepared combination of cyclopentolate 0.2% with phenylephrine 1% for pupillary dilation in preterm infants with dark irides. Thirteen infants were randomized to each regimen. Outcomes measured were pupillary dilation, heart rate, blood pressure, abdominal girth, and intolerance to feeds.

RESULTS: All three mydriatic regimens provided adequate pupillary dilation at 45 minutes, with dilation sustained at 60 minutes. There was a significant increase in mean blood pressure in the cyclopentolate 1% + phenylephrine 2.5% and the tropicamide 1% + phenylephrine 2.5% groups. Although there was no significant change of abdominal girth in any of the three groups, a total of eight patients developed intolerance to feeds; four (50%) of these infants were from the cyclopentolate 1% + phenylephrine 2.5% group.

Methods and analysis: This retrospective, comparative study of prospectively collected data in an ROP screening programme included infants indicated by gestational age ≤32 weeks, birth weight <1501 g, ventilation for 7 days or requiring oxygen >1 month, who underwent dilated fundoscopic examination from age 4 weeks, every 2 weeks until full retinal vascularisation. Infants with ROP were examined weekly and treated where indicated. Data were divided into two epochs. Epoch 1 oxygen saturation targets were [88-92%], epoch 2 targets [90-95% (99%)] with allowance of increase to 20% for several hours after procedures. Outcome measures included development of ROP, treatment, mortality, sepsis and intraventricular haemorrhage.

Results: A total of 651 infants underwent examination between 2003 and 2016. The incidence of ROP in epoch 1 was 29.1% and epoch 2 was 29.3% (p=0.24). ROP progression doubled in epoch 2 (5 vs 11%, p=0.006), proportion of cases treated halved (14% vs 6%, p=0.0005), sepsis was halved (78.5% vs 41.2%, p<0.0001) and intraventricular haemorrhage doubled (20.2% vs 43.8%, p=0.0001) in epoch 2. Mortality was 4% and 0% in epochs 1 and 2, respectively.

Participants: This was a retrospective study involving premature infants with gestational age less than 32 weeks treated from September 2016 to March 2019 in Hospital Universiti Sains Malaysia. Clinical diagnosis was made based on Early Treatment Retinopathy of Prematurity study. Participants' weekly weight gain since birth was entered in the website (http://winrop.com), along with date of birth, gestational age and final clinical examination outcome. WINROP software signals an alarm if an infant is at high risk of developing ROP requiring treatment during weight data entry. By using the alarm status, the sensitivity and specificity of this algorithm for predicting ROP requiring treatment were obtained.

Results: Ninety-two infants were included in this study. An alarm was detected in 67 infants (72.8%). There were a total of 53 infants (54.6%) with no ROP, 15 (16.3%) of whom developed stage 1 ROP, 10 (10.8%) who developed stage 2 ROP and 14 infants (15.2%) who developed stage 3 ROP. In our study, WINROP sensitivity was 95.2% and specificity was 33.8%.

Methods: A comparative cross-sectional study involving 86 Malay premature babies (ROP = 41 and non-ROP = 45) was performed from September 2012 to December 2014. Mutation analyses in (FEVR)-causing genes (NDP, FZD4, LRP5, and TSPAN12) were performed using DNA from premature babies using polymerase chain reaction (PCR) and direct sequencing. Sequencing results were confirmed with PCR-Restriction Fragment Length Polymorphism (RFLP).

Results: We found variants of FZD4, LRP5, and TSPAN12 in this study. One patient from each group showed a non-synonymous alteration in FZD4, c.502C>T (p.P168S). A synonymous variant of LRP5 [c.3357G>A (p.V1119V)] was found in 30 ROP and 28 non-ROP patients. Two variants of TSPAN12, c.765G>T (p.P255P) and c.*39C>T (3'UTR), were also recorded (29 and 21 in ROP, 33 and 26 in non-ROP, respectively). Gestational age and birth weight were found to be significantly associated with ROP (P value < 0.001 and 0.001, respectively).