Discussion

Over the last 10 years, epidemiological studies showed higher incidence of severe ROP and higher need for treatment among ELBW babies. These patients have been showing decreasing mortality rate in the last years in developed countries, as well as in some developing countries like Brazil [1,5,6].

Brazilian guidelines state treatable ROP when disease reach ROP zone I, any stage with plus disease; ROP in zone I, stage 3 with no-plus; or ROP in zone II, stages 2 or 3 with plus disease or at least, at threshold ROP [13]. In more recent years the indications for ROP treatment in most of the developed countries are at type 1 ROP, defined according to the ET-ROP, from 2003, but in many of the middle-income countries, and especially those in South America, the treatment continues to be performed at threshold ROP, as defined according to the Cryo-ROP [10].

In this way, all of the patients of our study were treated at threshold ROP and the assessments were repeated periodically, according to the Brazilian guidelines [13].

In this study it was observed that both groups were different in terms of BW and GA. Babies in group 2 had statically lower mean BW and lower mean GA when compared to babies in group 1, meaning that in the period from 2016-2024 the survived treated ELBW preterm babies were smaller and more immature babies when compared with the survived treated ELBW infants from the period between years 2002 to 2015. This situation could have been influenced by better prenatal and neonatal care during the last decades. Some centres show that survival rates among 27-28 weeks preterm babies is up to 90% and among 32 weeks or more preterm infants is above 95% in more recent years, although this number vary widely across centres [1,2]. Among better prenatal care are administration of corticoids and programs to develop strategies to reduce the incidence of preterm labour. Advances in neonatal care include modern incubators with better control thermal environment, development of better mechanical ventilators, including the high frequency ones, the early use of nasal CPAP (continuous positive airway pressure) immediately or shortly after birth, use of drugs like surfactant, erythropoietin and indomethacin, besides sophisticated ultrasonography and X-ray devices to identify associated morbidities in this highly susceptible population of patients [14].

Nowadays, especially in more developed countries, the incidence and severity of ROP are described as having an inverse relationship to BW and GA, with few cases of severe ROP being diagnosed in babies with BW higher than 1,500g or older than 32 weeks of GA [5], but over the last 10 years, epidemiological studies showed higher incidence and higher need for treatment among ELBW babies related to the decreasing mortality rate in the last years [16].

From 2002 to 2024, our institutional team in HCPA improved neonatal intensive care with the best possible technologies considering:

1) Optimization of oxygen therapy since birth at delivery room with the use of pulse oximetry in all VLBW and ELBW preterm babies with recommended saturation pressure between 88 and 94%.

2) Keeping strict control over the main risk factors for severe ROP.

3) Adopting the use of total parenteral nutrition optimization for babies with BW<1,250g.

4) Adopting an institutional ophthalmological screening program to detect and to treat ROP in the best moment.

5) Recommending the use of the ROPScore as a tool in order to help ophthalmologists to minimize unnecessary ophthalmological examinations in these vulnerable preterm infants once repeated eye examinations can cause stress and physical debilitation in the preterm babies.

6) Performing treatment for severe ROP always around the 37^th week of PCA, as recommended since the Cryo-ROP study [10].

ROPScore, as previously reported [15], is a score system which allow for a reduction in the number of ophthalmological examinations performed in the same patient during the screening for ROP. ROPScore is a robust predictor of ROP onset including risk factors for ROP that are easy to record. It is more accurate than BW and GA to predict the occurrence of ROP in preterm infants and reduce the excessive number of eye examinations performed in VLBW and in ELBW preterm infants in order to detect severe cases of ROP needing treatment. ROPScore is simple enough to be routinely used by ophthalmologists or by the NICU staff during screening examination to detect ROP [15].

At HCPA, to accomplish tighter control of oxygen therapy, strict guidelines are applied. All neonates in critical condition are permanently controlled by the use of pulse oximetry with a recommended oxygen saturation pressure between 88 and 94%, when babies are in oxygen therapy [16]. This kind of postnatal care is of crucial importance to avoid fluctuations during oxygen therapy to minimize the risk for severe ROP, as were achieved in our institution during the period from 2008 to 2015, when our incidence of treatable ROP dropped to 0% during 7 consecutive years among ELBW, but after 2016 the incidence of treatment among ELBW preterm infants raised again in the institution despite all of the staff care in the oxygen therapy.

Question is why this? After observing an increase in the need for treatments that occurred after 2015, we arbitrarily decided to divide the entire cohort of treated ELBW during the entire observational period of the study (2002-2024) into 2 groups: group 1 referring to the period between 2002 and 2015 and group 2 between 2016 and 2024, and it was hypothesised that we have now a smaller and more immature group of babies developing severe ROP despite all of the recent improvements of the intensive care achieved in our institution in order to minimize ROP. In one previous article we published about the influence of GA on the dynamic behaviour of the risk factors associated with ROP [17] where smaller preterm babies are surviving longer and very immature babies will develop ROP per se meaning that just for the immaturity itself the smaller babies have higher chance to develop severe ROP, despite the optimization in all of the clinical parameters in the ELBW preterm care, as well as in the nursery neonatal practices. In our institution, the NICU staff is regularly trained on the relationship between hyperoxemia and ROP. This training is helpful because it is possible to control and to prevent the occurrence of severe ROP in most cases only by carefully monitoring hyperoxia and avoiding fluctuations.

In this study it was clinically observed and statistically analysed that in the period from 2016-2024 the survived and treated for ROP ELBW preterm babies were smaller and more immature babies when compared with the survived and treated ELBW infants from the period between years 2002 to 2015. This situation can explain the recent increase for ROP treatment among smaller and more immature ELBW preterm infants who develop severe ROP despite all of the neonatal improvements used in our institution.

Our results drove attention that ROP in Zone 1 or Aggressive Posterior ROP (AP-ROP) was detected in only 3 patients during the entire observational period and, in our opinion, all of the institutional improvements in the neonatal practices contributed for this.

Finally, all of the 41 ELBW treated during the entire observational period, from 2002 to 2024, achieved regression of ROP avoiding blindness in this cohort of patients.

Conclusions

This study was carried out during the past 22 years, and many practices of neonatal care may have improved worldwide, or even achieved local improvement such as better control over the oxygen use since birth, better ventilation techniques, widespread use of pulse oximetry avoiding fluctuations during oxygen therapy, Improvements were also obtained in parenteral feeding for ELBW and routinely less use of vascular endothelial growth factor drugs, as erythropoietin, for example [4].

The higher survival rate, higher incidence of ROP and greater need of treatment in ELBW preterm babies indicate that this group of patients (born with BW under 1,000g) should receive special attention by ophthalmologists during the screening for ROP.

Is important to note that this study was conducted in only one institution, where guidelines for treating high risk premature infants are applied without exceptions. This is not a populationbased study and it was not conducted in a multicentre way, so our observations should only be applied to patients who are cared in the same conditions as the ones at HCPA. 

Acknowledgements

Authors acknowledge Professor Renato Soibelmann Procianoy MD, PhD and Professor Rita de Cássia Silveira MD, PhD, both heads of the NICU at HCPA in Porto Alegre (Brazil), where the data of all the included patients were obtained by the authors. Authors also acknowledge Statist Mayara M. Garcia from BioStats (Brazil) for carrying out the statistical analyzes in the present study.

Contribution of the Authors

All the authors participated in the writing of the manuscript. All authors have read and approved the final version of the manuscript.

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