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An International Classification of Retinopathy of Prematurity
Abstract
A central problem in medicine is the development of classification systems of disease adequate to describe the many manifestations by which a disease may present to the clinician. Such is the problem presented by retinopathy of prematurity (ROP). A group of 23 ophthalmologists, representing 11 countries, met over a period of two years to develop a new classification. This paper presents the classification (previously published) and the author's experience with its use in classifying the disease in 121 infants of birthweight less than or equal to 1300 grams over a 15-month period.
... These broad areas of avascular retina later stimulate aberrant growth from existing blood vessels, known as angiogenesis, into the vitreous that can lead to complex fibrovascular tractional retinal detachments. Detached retina, which occurs in late stages of ROP [16,17], is the most recognized cause of blindness in ROP [18]. However, other components of poor vision in premature infants include abnormalities in the central nervous system with cortical visual impairment and neurovascular interactions within the retina that potentially affect retinal function [19]. ...
... Phases of OIR describe the hypothesis of how ROP develops. Decades after the initial two-phase hypothesis by Ashton, the International Committee for the Classification of ROP (ICROP) published a classification of ROP [16,17]. The classification underwent revisions in 1987 [17] and most recently in 2005 [25] to include pre-plus disease and aggressive posterior ROP (APROP). ...
... Decades after the initial two-phase hypothesis by Ashton, the International Committee for the Classification of ROP (ICROP) published a classification of ROP [16,17]. The classification underwent revisions in 1987 [17] and most recently in 2005 [25] to include pre-plus disease and aggressive posterior ROP (APROP). The classification system delineates ROP by the location of disease (zone), the severity of disease (stage), extent, and plus disease. ...
Introduction: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide.
Areas covered: Recent methods to identify and manage treatment-warranted vascularly active ROP are recognized and being compared to standard care by laser treatment in prospective large-scale clinical studies. Pharmacologic anti-angiogenic (anti-VEGF) treatment has changed the natural history of vascularly active ROP by reducing stage 3 intravitreal neovascularization and extending physiologic retinal vascularization in many infants. Tractional retinal detachments in stage 4 ROP after treatment with anti-VEGF agents show additional fibrovascular complexity compared to eyes treated with laser only. We review current management and outcomes for vascularly active and fibrovascular retinal detachment in ROP (stages 3, 4, 5 ROP), highlighting the evidence from recent clinical studies. Included are technical details important in surgery for retinal detachment in ROP. Literature searches were employed through PubMed.
Expert opinion: Experimental studies in basic mechanisms, methods in pediatric imaging, safer pharmacologic treatments, and surgical techniques continue to advance to improve future ROP outcomes.
... The following morbidities were evaluated: Bronchopulmonary dysplasia (BPD) at 36wks PMA [7], major intraventricular hemorrhage (IVH) (grade III & IV) based on the Papile classification [8], retinopathy of prematurity (ROP) based on pediatric ophthalmologic examination using the international classification of ROP [9] that needed intervention with intravitreous injection, Necrotizing Enterocolitis (NEC) on the Bell's classification [10] that needed surgical intervention with insertion of intraabdominal drain or laparotomy, cystic or diffuse periventricular leukomalacia (PVL) by ultrasound and/or MRI [11] and culture positive sepsis of the blood, CSF or urine. In addition, the duration of mechanical ventilation to the successful extubation in days and the length of hospital stay to the point of home discharge were also determined. ...
Objective
This study aimed to investigate the association between admission hypothermia (AH), neonatal mortality and major neonatal morbidities in preterm infants <33 weeks’ gestation. An additional aim of the study was to examine changes in the prevalence of admission hypothermia after the initiation of a thermoregulation quality improvement (QI) project.
Method
This is a retrospective cohort study of preterm infants < 33 weeks’ gestation born at King Abdul-Aziz Medical City Riyadh (KAMC-R) between January 2017 to December 2020.
Results
Eight-hundred infants were born during the study period. Four hundred and one infants (50.1%) had an admission temperature <36.5 °C and a further 399 (49.9%) had an admission temperature >36.5 °C. The mortality before discharge was 15.7% in infants with AH compared to 4.8% among those with an admission temperature above 36.5 °C. This remained statistically significant after adjustments for gestational age and maternal PET status on a multivariate analysis (P = .001, OR 2.7,95%CI 1.5–4.7). Need for mechanical ventilation (P = .005) and incidence of surgical NEC (P = .030) were significantly different between the two temperature groups. Mean (SD) admission temperature increased from 36.3 °C to 36.6 °C following the thermoregulation intervention program (P<.001). Admission temperature <36 °C is associated with higher mortality in the first week (P = .001, OR 3.3,95% CI (1.7–6.6)) and increased incidence of cystic PVL (P = .04, OR 2.1, CI (1.03–4.3)).
Conclusion
Preterm infants AH suffered higher mortality and greater neonatal morbidities.
... Evaluations of ROP were judged as follows: none, immature, or mature vascularization. Staging of disease was performed in accordance with the International Classification of ROP [18,19]. ...
Purpose
Retinopathy of prematurity (ROP) is a disease that causes vision loss, vision impairment, and blindness, most frequently manifesting among preterm infants. ROPScore and CHOP ROP (Children’s Hospital of Philadelphia ROP) are similar scoring models to predict ROP using risk factors such as postnatal weight gain, birth weight (BW), and gestation age (GA). The purpose of this study was to compare the accuracy and difference between using ROPScore and CHOP ROP for the early prediction of ROP.
Methods
A retrospective study was conducted from January 2009 to December 2019 in China. Patients eligible for enrollment included infants admitted to NICU at ≤32 weeks GA or those with ≤1500 g BW. The sensitivity and specificity of ROPScore and CHOP ROP were analyzed, as well as its suitability as an independent predictor of ROP.
Results
Severe ROP was found in 5.0% of preterm infants. The sensitivity and specificity of the ROPScore test at any stage of ROP was 55.8 and 77.8%, respectively. For severe ROP, the sensitivity and specificity was 50 and 87.0%, respectively. The area under the receiver operating characteristic curve for the ROPScore for predicting severe ROP was 0.76. This value was significantly higher than the values for birth weight (0.60), gestational age (0.73), and duration of ventilation (0.63), when each was category measured separately. For the CHOP ROP, it correctly predicted infants who developed type 1 ROP (sensitivity, 100%, specificity, 21.4%).
Conclusions
The CHOP ROP model predicted infants who developed type 1 ROP at a sensitivity of 100% whereas ROPScore had a sensitivity of 55.8%. Therefore, the CHOP ROP model is more suitable for Chinese populations than the ROPScore test.
Clinical registration number and STROBE guidelines
This article was a retrospective cohort study and reported the results of the ROPScore and CHOP ROP algorithms. No results pertaining to interventions on human participants were reported. Thus, registration was not required and this study followed STROBE guidelines.
... Lastly, maternal characteristics and neonatal outcomes were compared between neonates diagnosed as EONS with or without maternal fever. Neonatal outcomes were defined by the following criteria: (1) IVH was defined as intraventricular haemorrhage with ventricular dilatation (grade 3) or parenchymal involvement (grade 4) based on the Papil grading system; 24 (2) periventricular leucomalacia (PVL) was diagnosed by brain ultrasonography or brain magnetic resonance imaging; (3) ROP was defined as grade 2 or 3 based on the international classification of retinopathy of prematurity; 25 (4) respiratory distress syndrome (RDS) was diagnosed as the presence of respiratory grunting and retracting, an increased oxygen requirement (FiO 2 >0.4) combined with ground-glass appearance, and air bronchograms on chest radiographs; (5) bronchopulmonary dysplasia (BPD) was defined as requiring oxygen 28 days after birth; (6) neonatal enterocolitis (NEC) was defined as NEC identified by surgical findings or abdominal distension with absent bowel sounds, abdominal tenderness (stage 2), peritonitis, or perforation (stage 3) based on modified Bell's criteria; 26 (7) persistent ductus arteriosus (PDA) was defined as a clinical diagnosis with medical or surgical treatment; (8) in this study, neonatal composite morbidity was defined as the presence of any complications among IVH, PVL, ROP, BPD and PDA. RDS was excluded from neonatal composite morbidity because it is the most prevalent morbidity in preterm births. ...
Objective
To re‐evaluate the utility of the conventional criteria for clinical chorioamnionitis in the prediction of early‐onset neonatal sepsis ( EONS ) in preterm birth.
Design
Retrospective cohort study.
Setting
Seoul, Republic of Korea.
Sample
A total of 1468 singleton births between 24 and 34 weeks due to preterm labour ( n = 713) or preterm prelabour rupture of membranes ( n = 755).
Method
We evaluated three diagnostic categories of clinical chorioamnionitis: Criteria 1, conventional criteria; Criteria 2, combination of any three conventional parameters without prerequisite fever; Criteria 3, Criteria 1 plus positive maternal C‐reactive protein and neutrophil left‐shift into minor criteria. EONS included proven or suspected sepsis within 7 days following birth. Neonatal morbidity and mortality of EONS were also reviewed.
Main outcome measures
Diagnostic performance of three combinations.
Results
The prevalence of EONS was 13.8%. Among 203 cases of EONS , maternal manifestation of clinical chorioamnionitis by criteria 1 was evident in only one out of seven, indicating 15.3% sensitivity for EONS prediction. However, with application of criteria 2, sensitivity significantly increased to 34.0%, while compromising specificity from 92.3% to 78.7%. Criteria 3 showed similar diagnostic performance compared with criteria 1 (sensitivity 16.7%, specificity 91.6%). Overall, neonatal mortality and neonatal composite morbidity in EONS were 14.9% and 67.8%, respectively, and there was no difference in neonatal morbidity and mortality between neonates whose mothers showed fever as a sign of clinical chorioamnionitis and those whose mothers did not.
Conclusion
The renouncement of fever as a prerequisite for the criteria of clinical chorioamnionitis could increase sensitivity for the identification of EONS , a serious outcome of preterm birth.
Tweetable abstract
The renouncement of fever as an essential can increase sensitivity for prediction of neonatal sepsis.
... Standard definitions from the literature were used to define chorioamnoitis, morbidities and complications. [14][15][16][17] Gestational age was determined from early ultrasound scans or calculated from the date of the last maternal menstrual period. ...
Objectives:
This study aimed to evaluate the changing survival rate and morbidities among infants born before 26 gestational weeks at the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman.
Methods:
This retrospective study assessed the mortality and morbidities of all premature infants born alive at 23-26 gestational weeks at SQUH between June 2006 and May 2013. Infants referred to SQUH within 72 hours of birth during this period were also included. Electronic records were reviewed for gestational age, gender, birth weight, maternal age, mode and place of delivery, antenatal steroid administration, morbidity and outcome. The survival rate was calculated and findings were then compared with those of a previous study conducted in the same hospital from 1991 to 1998. Rates of major morbidities were also calculated.
Results:
A total of 81 infants between 23-26 gestational weeks were admitted to the neonatal unit during the study period. Of these, 58.0% were male and 42.0% were female. Median gestational age was 25 weeks and mean birth weight was 770 ± 150 g. Of the 81 infants, 49 survived. The overall survival rate was 60.5% compared to 41% reported in the previous study. Respiratory distress syndrome (100.0%), retinopathy of prematurity (51.9%), bronchopulmonary dysplasia (34.6%), intraventricular haemorrhage (30.9%) and patent ductus arteriosus (28.4%) were the most common morbidities.
Conclusion:
The overall survival rate of infants between 23-26 gestational weeks during the study period had significantly improved in comparison to that found at the same hospital from 1991 to 1998. There is a need for the long-term neurodevelopmental follow-up of premature infants.
... Standard definitions from the literature were used to define chorioamnoitis, morbidities and complications. [14][15][16][17] Gestational age was determined from early ultrasound scans or calculated from the date of the last maternal menstrual period. ...
ABSTRACT: Objectives: This study aimed to evaluate the changing survival rate and morbidities among infants born before 26 gestational weeks at the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. Methods: This retrospective study assessed the mortality and morbidities of all premature infants born alive at 23–26 gestational weeks at SQUH between June 2006 and May 2013. Infants referred to SQUH within 72 hours of birth during this period were also included. Electronic records were reviewed for gestational age, gender, birth weight, maternal age, mode and place of delivery, antenatal steroid administration, morbidity and outcome. The survival rate was calculated and findings were then compared with those of a previous study conducted in the same hospital from 1991 to 1998. Rates of major morbidities were also calculated. Results: A total of 81 infants between 23–26 gestational weeks were admitted to the neonatal unit during the study period. Of these, 58.0% were male and 42.0% were female. Median gestational age was 25 weeks and mean birth weight was 770 ± 150 g. Of the 81 infants, 49 survived. The overall survival rate was 60.5% compared to 41% reported in the previous study. Respiratory distress syndrome (100.0%), retinopathy of prematurity (51.9%), bronchopulmonary dysplasia (34.6%), intraventricular haemorrhage (30.9%) and patent ductus arteriosus (28.4%) were the most common morbidities. Conclusion: The overall survival rate of infants between 23–26 gestational weeks during the study period had significantly improved in comparison to that found at the same hospital from 1991 to 1998. There is a need for the long-term neurodevelopmental follow-up of premature infants.
Keywords: Extremely Premature Infants; Neonates; Survival Rate; Morbidity; Oman.
... Intraventricular hemorrhage (IVH) grading was based on Papile classification [31] and necrotizing enterocolitis (NEC) was staged using the modified Bell Staging Criteria [32] . Retinopathy of prematurity (ROP) was defined as per the International Classification of ROP with a Stage of I–V assigned to positive cases [33]. ...
Abstract Objective: To compare two treatment strategies in preterm infants with or at risk of respiratory distress syndrome: early surfactant administration (within one hour of birth) vs. late surfactant administration, in a geographically defined population. Outcome: The primary outcome was chronic lung disease (CLD) and mortality before/at 36 weeks. Secondary outcomes included: duration of mechanical ventilation and continuous positive airway pressure (CPAP), post-natal steroids for CLD and major neonatal morbidities. Subjects: Premature infants born at 22 to 32 weeks' gestation between January 2006 and December 2009. Setting: Ten neonatal intensive care units (NICUs) in New South Wales (NSW) and Australian Capital Territory (ACT), Australia. Design: Retrospective analysis of prospectively collected data from the regional NICU database in NSW and ACT. Results: Of the 2170 infants who received surfactant, 1182 (54.5%) and 988 (45.5%) received early and late surfactant, respectively. The early surfactant group was less mature (27.1±2.1 vs. 29.4±2.1 weeks) and had more CLD and mortality (40.2% vs. 20.0%). The multivariable analysis showed early surfactant to be associated with less duration of ventilation, longer duration of CPAP and longer hospital stay but had little or no impact on CLD/mortality. Conclusion: Early surfactant administration is associated with shorter duration of ventilation but does not appear to be significantly protective against CLD/mortality among premature infants. This may support the growing evidence for consideration of CPAP as an alternative to routine intubation and early surfactant administration. Further investigation from large randomized clinical trials is warranted to confirm these results.
... Neonatal outcomes were defi ned by the following clinical criteria: (1) RDS was defi ned as respiratory insuffi ciency that required ventilator support for at least 24 h; (2) BPD was defi ned as requiring oxygen 28 days aft er birth; (3) IVH was defi ned as intraventricular hemorrhage with ventricular dilatation (grade 3) or parenchymal involvement (grade 4) based on the Papil grading system [22] ; (4) PVL was diagnosed by brain ultrasonography or brain MRI; (5) ROP was defi ned as grade 2 or 3 based on the international classifi cation of retinopathy of prematurity [5] ; (6) NEC was defi ned as NEC identifi ed by surgical fi ndings or abdominal distension with absent bowel sounds, abdominal tenderness (stage 2), peritonitis, or perforation (stage 3) based on modifi ed Bell ' s criteria [13] ; (7) EONS was defi ned as a positive blood culture result obtained during the fi rst 7 days aft er birth; and (8) in this study, neonatal composite morbidity was defi ned as the presence of any complications mentioned earlier. ...
To test if there is a stepwise difference in neonatal outcomes according to the stage (or grade) of histological inflammatory response in the chorioamniotic membranes and umbilical cords of preterm premature rupture of membranes (PPROM).
This retrospective study included singleton pregnancies diagnosed as PPROM and delivered prior to 34 weeks of gestation (n=339). Acute histological chorioamnionitis and funisitis were subdivided into stages (or grade) as defined by Redline et al. Neonatal composite morbidities and mortality were also monitored. Univariate and multivariate analyses were conducted.
Increasing stage (or grade) of acute histological chorioamnionitis and funisitis was significantly associated with an earlier gestational age at membrane rupture and delivery. Among neonatal outcomes, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, retinopathy of prematurity, and composite morbidity showed incremental incidence according to increased stage (or grade) of acute chorioamnionitis, while periventricular leukomalacia and necrotizing enterocolitis did not. Only RDS, BPD, and composite morbidity showed similar incremental incidences associated with severity of funisitis stage. However, the incremental trends of each neonatal outcome were found to be nonsignificant by multivariate analysis adjusting confounding variables including gestational age at delivery.
Higher incidences of neonatal morbidity according to increased stage (or grade) of either acute histological chorioamnionitis or funisitis were due to an earlier gestational age at delivery.
... Since the original descriptions of RLF, more widespread use of indirect ophthalmoscopy 16 and later efforts of the Committee for the International Classification of ROP have permitted ophthalmologists to screen for early forms of ROP before RLF. 17,18 Also, technology to regulate oxygen and methods to implement its use were developed. Restricting high, unregulated supplemental oxygen to preterm infants dramatically reduced RLF, although it also increased mortality and morbidity. ...
In 1942, when retinopathy of prematurity (ROP) first manifested as retrolental fibroplasia, the technology to monitor or regulate oxygen did not exist, and a fundus examination of preterm infants was not routinely performed. Supplemental, uncontrolled oxygen at birth has since been found to cause retrolental fibroplasia. At the same time, technological advances have made it possible to regulate oxygen and detect early forms of ROP. Nevertheless, despite our better understanding of ROP and ongoing investigations of supplemental therapeutic oxygen, including recent clinical trials (Surfactant, Positive Airway Pressure, Pulse Oximetry Randomized Trial [SUPPORT] and Benefits of Oxygen Saturation Targeting [BOOST]), the best oxygen profiles to reduce ROP risk while optimizing preterm infant health and development remain unknown. This article reviews major studies on oxygen use in preterm infants and the effects on the development of ROP.
... Recommendations are summarised in the International Classification of Retinopathy of Prematurity, first published in 1985 113 and revised in 2005. 115 The retina is divided into three zones and the extent or severity of disease in these zones is classified as stages (figure 3). 116 Stages 1 and 2 are mild and likely to regress spontaneously. ...
The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal-fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ω-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development.
... The criteria of Bell were used for the diagnosis and staging of necrotizing enterocolitis [18]. Staging of retinopathy of prematurity was done according to the International Classification [19,20]. ...
Survival and outcomes for preterm infants with respiratory distress syndrome (RDS) have improved over the past 30 years. We conducted a study to assess the changes in perinatal care and delivery room management and their impact on respiratory outcome of very low birth weight newborns, over the last 15 years. A comparison between two epochs was performed, the periods before and after 2005, when early nasal continuous positive airway pressure (NCPAP) and Intubation-SURfactant-Extubation (INSURE) were introduced in our center. Three hundred ninety-five clinical records were assessed, 198 (50.1%) females, gestational age 29.1 weeks (22-36), and birth weight 1130 g (360-1498). RDS was diagnosed in 247 (62.5%) newborns and exogenous surfactant was administered to 217 (54.9%). Thirty-three (8.4%) developed bronchopulmonary dysplasia (BPD), and 92 (23%) were deceased. With the introduction of early NCPAP and INSURE, there was a decrease on the endotracheal intubation need and invasive ventilation (P < 0.0001), oxygen therapy (P = 0.002), and mortality (P < 0.0001). The multivariate model revealed a nonsignificant reduction in BPD between the two epochs (OR = 0.86; 95% CI 0.074-9.95; P = 0.9). The changes in perinatal care over the last 15 years were associated to an improvement of respiratory outcome and survival, despite a nonsignificant decrease in BPD rate.
... IVH grading is based on Papile classification [13] and NEC is staged using the modified Bell Staging Criteria [14]. All premature neonates admitted to TCH NICU were assessed by an ophthalmologist for ROP, and the International Classification of ROP was used to assign a Stage of I-IV to positive cases [15]. ...
Background/Objective: Hyperglycaemia is common in very premature neonates and is associated with increased risk of intraventricular haemorrhage, necrotising enterocolitis, sepsis and death. Administration of insulin may risk hypoglycaemia and associated complications. To determine effects of insulin infusions in very premature infants on morbidity, mortality and long-term neurodevelopmental outcome. Methods: Retrospective audit of 97 infants delivered at <29 weeks gestation and admitted to The Canberra Hospital NICU. Data on insulin treatment, Blood Glucose Levels (BGL's) prior and during insulin therapy, episodes of significant hypoglycaemia and neurodevelopmental outcome at 12 months corrected age was collected. Results: 17 (17.5%) neonates received insulin. Episodes of hypoglycaemia were infrequent (1.3%, 95% CI 0.5-2.9). Multiple regression analysis showed that insulin treatment was not associated with an increased risk of retinopathy of prematurity (OR 3.6, 95% CI 0.4-32.3) or mortality (OR 1.2, 95% CI 0.29-5.0). No significant difference in 12 month neurodevelopmental or anthropometric outcomes was detected in infants who received insulin. Conclusion: Insulin infusions for hyperglycaemia appear to be safe with infrequent episodes of hypoglycaemia, no increased risk of morbidity or mortality and no adverse effect on long-term neurodevelopmental outcome.
... ROP was defined according to the International Classification of ROP with a stage of I to IV assigned to positive cases. 43 ...
To determine whether male gender has an effect on survival, early neonatal morbidity, and long-term outcome in neonates born extremely prematurely.
Retrospective review of the New South Wales and Australian Capital Territory Neonatal Intensive Care Unit Data Collection of all infants admitted to New South Wales and Australian Capital Territory neonatal intensive care units between January 1998 and December 2004. The primary outcome was hospital mortality and functional impairment at 2 to 3 years follow-up.
Included in the study were 2549 neonates; 54.7% were male. Risks of grade III/IV intraventricular hemorrhage, sepsis, and major surgery were found to be increased in male neonates. Hospital mortality (odds ratio 1.285, 95% confidence interval 1.035-1.595) and moderate to severe functional disability at 2 to 3 years of age (odds ratio 1.877, 95% confidence interval 1.398-2.521) were more likely in male infants. Gender differences for mortality and long-term neurologic outcome loses significance at 27 weeks gestation.
In the modern era of neonatal management, male infants still have higher mortality and poorer long-term neurologic outcome. Gender differences for mortality and long-term neurologic outcome appear to lose significance at 27 weeks gestation.
Objective. To compare mortality and major neonatal morbidities between singleton preterm infants and preterm infants of multiple gestations born <33 weeks’ gestation. Method. Case-control study of preterm multiples and singletons <33 weeks’ born at King Abdul-Aziz Medical City Riyadh (KAMC-R) between January 2017 and December 2020. Out-born infants and infants with lethal congenital abnormalities were excluded from the study. Mortality and major neonatal morbidities including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), sepsis and surgical necrotizing enterocolitis (NEC) were compared between preterm singletons and multiples. Results. A total of 803 preterm infants were included: 567 (70.6%) were singletons, 158 (19.6%) were twins and 36 (4.5%) infants were higher multiples. Adjusted mortality before hospital discharge was significantly higher among preterm infants of multiple gestations compared to preterm singletons (12.3% vs 7.9%; P = .003; AOR, 2.2; 95% CI, 1.3-3.7). Retinopathy of prematurity (ROP) needing treatment was significantly higher among preterm infants of multiple pregnancies compared to preterm singletons (11% vs 6.5%, P = .033, AOR 1.1, 95% CI, 1.04-2.99). In addition, the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks post menstrual age (PMA) (29.7% vs 20.5%; P = .003; AOR, 1.7; 95% CI, 1.2-2.5) and culture positive sepsis (24.2% vs 17.5%; P = .044; AOR, 1.5; 95% CI, 1.01-2.2) were significantly higher among preterm infants of multiple pregnancy. There were no differences in mortality and adverse neonatal outcomes between twins and higher multiples. Conclusion. Preterm infants of multiple gestations suffered higher mortality and neonatal morbidities compared to preterm singleton infants despite a higher utilization of maternal antenatal steroids and better antenatal care.
Purpose:
To report a series of fundus photographs taken for retinopathy of prematurity (ROP) screening that contain artifacts with imaging characteristics mimicking a notch, a recently refined classification metric in the International Classification of Retinopathy of Prematurity, third edition.
Design:
Retrospective case series.
Participants:
Infants requiring ROP screening in neonatal intensive care units from the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) and TeleROP telemedicine screening programs.
Methods:
Preterm infants meeting ROP examination criteria were screened with 130° wide-angle imaging systems. The images were taken by a trained nurse in the neonatal intensive care unit and transferred to an ROP specialist using a Health Insurance Portability and Accountability Act-compliant picture archiving and communication system for interpretation.
Main outcome measures:
Presence of an artifact that appeared consistent with a notch.
Results:
We identified a total of 17 cases in ROP screening with artifact findings that had imaging characteristics similar to a notch. The artifactual appearance of the pseudo-notch was created by the camera illumination system within the gel-lens interface when the lens was not well apposed to the cornea. In telemedicine screening for ROP, we present fundus images of eyes with a pseudo-notch appearance; review of overlapping images can help differentiate between notch and artifact.
Conclusions:
Pediatric retinal specialists need to be aware that artifacts play a confounding role in screening for ROP, that can be mitigated through the use of overlapping and redundant images.
Financial disclosure(s):
Proprietary or commercial disclosure may be found after the references.
The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056–14.055) and NEC (OR: 12.410, 95% CI: 1.290–119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess.
Objective
To compare mortality and major neonatal morbidities between singleton preterm infants and preterm infants of multiple gestations born between 23 + 0 to 32 + 6 weeks.
Method
This is a retrospective cohort study of preterm infants (23 + 0 to 32 + 6 weeks gestational age) born at King Abdul-Aziz Medical City Riyadh (KAMC-R) between January 2016 to December 2020.
Results
Total of 803 preterm infants were included: 567 (70.6%) were singletons, 158 (19.6%) were twins and 36 (4.5%) infants were triplets and higher multiples. The mortality was significantly higher in preterm infants of multiple gestations compared to singleton (12.3% vs. 7.9%; p = 0.003; OR, 2.2; CI, 1.3–3.7). Preterm infants of multiple gestations had an increased risk of ROP (11% vs. 6.5%; P = 0.033; OR, 1.1, CI, 1.04–2.99), BPD at 36 weeks PMA (29.7% vs. 20.5%; P = 0.003; OR, 1.7; CI, 1.2–2.5) and sepsis (24.2% vs 17.5%, P = 0.044; OR, 1.5; CI, 1.01–2.2) compared to preterm singletons. There were no differences in mortality and adverse neonatal outcomes between twins and higher multiples.
Conclusion
Preterm infants of multiple gestations suffered higher mortality and neonatal morbidities compared to preterm singleton infants despite a higher utilization of maternal antenatal steroids and better antenatal care.
Objective
There is an expectation among the public and within the profession that the performance and outcome of neonatal intensive care units (NICUs) should be comparable between centres with a similar setting. This study aims to benchmark and audit performance variation in a regional Australian network of eight NICUs.
Design
Cohort study using prospectively collected data.
Setting
All eight perinatal centres in New South Wales and the Australian Capital Territory, Australia.
Patients
All live-born infants born between 23 ⁺⁰ and 31 ⁺⁶ weeks gestation admitted to one of the tertiary perinatal centres from 2007 to 2020 (n=12 608).
Main outcome measures
Early and late confirmed sepsis, intraventricular haemorrhage, medically and surgically treated patent ductus arteriosus, chronic lung disease (CLD), postnatal steroid for CLD, necrotising enterocolitis, retinopathy of prematurity (ROP), surgery for ROP, hospital mortality and home oxygen.
Results
NICUs showed variations in maternal and neonatal characteristics and resources. The unadjusted funnel plots for neonatal outcomes showed apparent variation with multiple centres outside the 99.8% control limits of the network values. The hierarchical model-based risk-adjustment accounting for differences in patient characteristics showed that discharged home with oxygen is the only outcome above the 99.8% control limits.
Conclusions
Hierarchical model-based risk-adjusted estimates of morbidity rates plotted on funnel plots provide a robust and straightforward visual graphical tool for presenting variations in outcome performance to detect aberrations in healthcare delivery and guide timely intervention. We propose using hierarchical model-based risk adjustment and funnel plots in real or near real-time to detect aberrations and start timely intervention.
Objective
The purpose of this study was to check whether the impact of abnormal vaginal colonization on perinatal outcomes would be different in patients with preterm labor (PTL) and premature membrane rupture (PPROM). We also sought to determine the concordance rate of microorganisms isolated from the maternal vagina and neonatal blood in cases of early-onset neonatal sepsis (EONS) in PTL and PPROM.
Methods
This retrospective study included 996 singleton pregnancies who were admitted to the high risk care unit of our institution due to PTL (n = 519) or PPROM (n = 477) and underwent vaginal culture examination at admission between January 2005 and April 2019. Abnormal vaginal colonization was defined upon isolation of aerobic microorganisms. The maternal baseline characteristics, delivery, and neonatal outcomes were compared according to the presence or absence of abnormal vaginal flora, both in PTL and PPROM.
Results
The rate of abnormal vaginal colonization in PTL and PPROM was 17.0 and 21.4%, respectively. Both in PTL and PPROM, the gestational age at admission was lower in the abnormal vaginal colonization group (PTL, 27.2 ± 3.5 vs. 28.2 ± 3.5 weeks, p = .024; PPROM, 26.1 ± 5.3 vs. 27.5 ± 4.5 weeks, p = .007). Multivariable analysis demonstrated that the group with abnormal bacteria in PPROM but not in PTL had a significantly higher rate of EONS than the group without abnormal bacteria after adjustment for confounders including gestational age at admission (PPROM, odds ratio, OR [95% confidence interval, CI]: 4.172 [1.426–12.206]; PTL, OR [95% CI]: 0.661 [0.079–5.505]). Concordance analysis showed that the maternal vaginal bacteria colonization by Escherichia coli (5.9 vs. 0.5%, p = .033) and Staphylococcus aureus (14.3 vs. 0.2%, p = .032) in PPROM was significantly correlated with the microorganisms from the neonatal blood culture EONS cases. In PTL, no specific microorganisms showed concordance between maternal vaginal bacteria and microorganisms causing EONS.
Conclusion
Our data showed that maternal vaginal colonization in PPROM, but not in PTL, is an independent risk factor for EONS.
Type I retinopathy of prematurity is increasing in prevalence proportionate to the advancements of neonatal care and remains the most preventable and potentially devastating neonatal retinal disease worldwide. It is distinguished from standard ROP by its posterior location, aggressive tempo, and high vascular activity/VEGF burden. Current treatment for Type 1 retinopathy of prematurity is guided by landmark multicenter prospective studies (CRYO-ROP, STOP-ROP, ET-ROP, and BEAT-ROP) as well as clinical experience and practical considerations using the available treatment modalities; these include ablation with laser or cryotherapy, intravitreal anti-VEGF agents (Bevacizumab or Ranibizumab) and systemic modulation of hemoglobin and oxygen saturation. Ideal treatment is timed to allow maximum growth of the intrinsic retinal vasculature while preventing fibrovascular contraction or retinal detachment and minimizing complications; these include myopia, visual field constriction, and anterior segment ischemia. With anti-VEGF therapy, recurrences well after the due date and consequent smoldering ROP require vigilant and prolonged outpatient monitoring. Herein, a review of retinal vascular development and the role of VEGF in ROP precedes a discussion of the hallmark studies and a systematic strategy to prevent ROP-associated vision loss while minimizing unnecessary treatments and morbidity to the fragile preemie. We argue that laser is most appropriate for ROP anterior to the equator and smoldering ROP, while intravitreal bevacizumab is more appropriate for posterior disease, especially in highly fragile neonates and situations where follow-up will be reliable.
The postnatal age at which acute retinopathy of prematurity (ROP) develops appears to be negatively related to the gestational age of the infant (1). Thus, the very small premature infant develops ROP later postnatally than his larger, more mature counterpart. But, when the degree of prematurity is corrected for, the first ophthalmoscopically visible signs of acute ROP are seen over a relatively narrow postmenstrual age range. These findings suggest that the onset of acute ROP is governed predominantly by the postmenstrual age of the infant, rather than by events in the neonatal period. In other words, a certain stage of development, probably at a retinal level, has to be reached before ROP can develop.
D-penicillamine (DPA) was first recognized as a potential benefit for neonatal hyperbilirubinemia (NHBI). During this time there was a remarkedly low incidence of retinopathy of prematurity (ROP) in the infants treated with DPA. Later, our studies were replicated in other institutes in Hungary, Poland, the U.S. A., India and Mexico. It is important to note that there was no intolerance or short- or long-term toxicity of the medication, in spite of the fact that in the newborn period DPA was used 10-20 times higher doses than those in adult. On the basis of an American research work concerning the beneficial effects of DPA-therapy in adult AIDS-patients (although in these cases there were many unpleasant, adverse effects), it would be reasonable to treat neonatal HIV-positivity due to vertical transmission with short-term DPA therapy (300 - 400 mg/kg/bw/day for 5-7 days). Therefore, we have a moral obligation to help the fight against HIV with this inexpensive (~ 30 USD/baby) drug in the neonatal period.
Thyroid dysfunction is common in preterm infants. Congenital hypothyroidism causes neurodevelopmental impairment, which is preventable if properly treated. This study was conducted to describe the characteristics of thyroid dysfunction in very low birth weight infants (VLBWIs), evaluate risk factors of hypothyroidism, and suggest the reassessment of thyroid function with an initially normal thyroid-stimulating hormone (TSH) as part of a newborn screening test.
VLBWIs (January 2010 to December 2012) were divided into two groups according to dysfunction-specific thyroid hormone replacement therapy, and associated factors were evaluated.
Of VLBWIs, 246 survivors were enrolled. Only 12.2% (30/246) of enrolled subjects exhibited thyroid dysfunction requiring thyroid hormone replacement. Moreover, only one out of 30 subjects who required thyroid hormone treatment had abnormal thyroid function in the newborn screening test with measured TSH. Most of the subjects in the treatment group (22/30) exhibited delayed TSH elevation. Gestational age, Apgar score, antenatal steroids therapy, respiratory distress syndrome, patent ductus arteriosus, sepsis, intraventricular hemorrhage, postnatal steroids therapy, and duration of mechanical ventilation did not differ between the two groups. Birth weight was smaller and infants with small for gestational age were more frequent in the treatment group.
Physicians should not rule out suggested hypothyroidism, even when thyroid function of a newborn screening test is normal. We suggest retesting TSH and free thyroxine in high risk preterm infants with an initially normal TSH level using a newborn screening test.
This study aimed to determine the impact of maternal cervical incompetence (with or without McDonald cerclage) on mortality and morbidity of preterm infant with birth weight <2000g.
581 neonates were eligible for this study, 79 with cervical incompetence and 502 without it (control). Incidences of neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), neonatal necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), periventricular leukomalacia (PVL), severe asphyxia, small for gestational age (SGA), early-onset sepsis (EOS), and mortality were compared between the two groups.
Mean gestational age was earlier in cervical incompetence group than in control (30.2±2.1 vs 30.7±1.9, P<0.05). Except lower frequency of SGA, there were no significant differences in the incidences of RDS, BPD, ROP, PVL, IVH, NEC, EOS, severe asphyxia and mortality between the two groups. Infants with no cerclage had a higher prevalence of RDS (21/66 vs 9/13, P<0.05) compared to cerclage group due to lower mean gestational age (30.68±2.1 vs 28.6±1.4, P<0.01) and birth weight (1519.5±274.6 vs 1205.8±204.4, P<0.001), and clinical neonatal outcomes of the elective cerclage were similar to emergency cerclage in cervical incompetence groups.
Maternal cervical incompetence was not associated with postnatal adverse neonatal outcomes. Lower mean gestational age was a major risk associated with higher prevalence of RDS in preterm neonates with no McDonald cerclage, and emergency cerclage did not predict poor clinical neonatal outcomes.
Ethical dilemmas continue regarding resuscitation versus comfort care in extremely preterm infants. Counseling parents and making decisions regarding the care of these neonates should be based on reliable, unbiased and representative data drawn from geographically defined populations. We reviewed survival and morbidity data for our population at the edge of viability.
A retrospective review of our perinatal database was carried out to identify all infants born alive and admitted to the neonatal intensive care unit (NICU) with BW⩽500 g between 1989 and 2009. Data from the initial hospital stay and follow-up at 24 months were collected.
Out of 22 672 NICU admissions, 273 were eligible: 212 neonates were reviewed after excluding infants with comfort care. BW ranged from 285 to 500 g (mean 448 g) and gestational age range 22 to 28 weeks (median 24 week). Sixty-one (28.8%) survived until discharge. Only 13.8% males survived compared with 39.2% females (P<0.05). Half (49%) were discharged with home oxygen/monitor. Fifty (82%) patients' charts were available to review at the 24-month follow-up. Thirty-three percent of surviving infants had a normal neurodevelopmental assessment at 24 months. Forty-three percent had weight/head circumference<5th percentile at 24 months.
About a third of neonates admitted to NICU with ⩽500 g BW survived, with 33% of those surviving, demonstrating age-appropriate development at a 24-month follow-up visit.Journal of Perinatology advance online publication, 7 May 2015; doi:10.1038/jp.2015.44.
Purpose
To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa.
Materials and Methods
A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records.
Results
Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (≥grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (≥stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3.
Conclusion
Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.
Objective:
To determine whether chronic oxygen dependency at the time of discharge from the neonatal intensive care unit (NICU) in infants with bronchopulmonary dysplasia (BPD) predicts respiratory outcomes at 3 years.
Study design:
Preterm infants ⩽1250 g without BPD, BPD and BPD with chronic oxygen dependency were identified from the Southern Alberta Perinatal Follow-up clinic database (1995-2007). Respiratory outcomes at 4, 8, 18 and 36 months corrected age following NICU discharge were examined. Univariate analyses were done.
Results:
Out of 1563 infants admitted to the NICU, 1212 survived. Complete follow-up data at 36 months were available for 1030 (85%) children. Children with BPD with or without chronic oxygen dependency had significantly (P<0.001) lower birth weights and gestational ages, and greater post-natal steroid use, compared with those with no BPD. At 4, 8 and 18 months follow-up, the use of respiratory medications and supplemental oxygen were both significantly higher in the BPD infants with chronic oxygen dependency group compared with the no-BPD group and BPD group. At 36 months, children in the BPD with chronic oxygen dependency group were more likely to use respiratory medications and supplemental oxygen vs the no-BPD or the BPD groups. At 4, 8 and 36 months of age, more children in the BPD with chronic oxygen dependency group had post-neonatal chronic lung disease (PNCLD) than children in the other groups, but at 36 months the difference was significant only for the BPD with chronic oxygen dependency vs no-BPD group (P<0.001).
Conclusions:
At 36 months, children diagnosed with BPD with chronic oxygen dependency at NICU discharge were more likely to need respiratory medications and supplemental oxygen in the previous 12 months, as compared with no-BPD or BPD groups. They were also more likely to require frequent physician visits and have PNCLD at 3 years, as compared with the no-BPD group.
Background
The aim of this study was to screen for retinopathy of prematurity (ROP) in southwestern China and understand the prevalence and risk factors of ROP, which may provide evidence useful in the prevention and treatment of ROP.
Material/Methods
1864 preterm infants (gestational age of <37 weeks and birth weight of ≤2500 g) underwent ROP screening from January 2009 to November 2012 in Southwest China. The medical information of infants during perinatal period was reviewed, and risk factors of ROP were determined. A total of 1614 infants were recruited for final analysis.
Results
Incidence of ROP was 12.8%. The first, second, third, and fourth stage of ROP was found in 64.6%, 29.6%, 3.4%, and 0.5% of infants, respectively. No fifth stage of ROP was observed. In addition, 7.7% of infants required surgical intervention. In our Department of Neonatology, the incidence of ROP was 20.0%, which was significantly higher than in non-hospitalized patients (9.9%). The incidence of ROP remained unchanged over the years. Independent risk factors of ROP included low birth weight (p=0.049), low gestational age (p=0.008), days of oxygen supplementation (p=0.008), and myocardial injury after birth (p=0.001).
Conclusions
The prevalence of ROP in preterm infants is relatively high in Southwest China, and low birth weight, low gestational age, days of oxygen supplementation, and myocardial injury after birth are independent risk factors for ROP.
Background:
Nasal intermittent positive pressure ventilation (NIPPV) is becoming more important as a mode of ventilation in premature neonates predisposed to development of bronchopulmonary dysplasia (BPD). To the best of our knowledge, there have been no detailed studies characterizing neonates who fail NIPPV.
Objective:
To determine the differences between neonates who are successfully extubated to NIPPV and those who require re-intubation from NIPPV, and the impact of timing of NIPPV failure on BPD rates.
Study design:
This was a retrospective cohort study in which we included infants with gestational age (GA) ⩽ 28 weeks and birth weight ⩽ 1000 g. χ²-test, analysis of variance and multivariate logistic regression models were used.
Results:
Two hundred and forty infants were studied; 180 failed NIPPV and of those, 33 (18%), 39 (22%) and 108 (60%) failed NIPPV within 0 to 6 h, ⩾ 6 to 24 h and ⩾ 24 h, respectively. Female sex and increased weight were protective against NIPPV failure (adjusted odds ratio (95% confidence interval): 0.28 (0.14 to 0.58), 0.04 (0.01 to 0.22)). Increased GA at extubation and female sex were both associated with increased time to failure (P=0.008, <0.001, respectively). Apnea was more likely the cause for failure ⩾ 24 h (P=0.015), whereas increased work of breathing/fraction of inspired oxygen requirements were more significant when NIPPV failure occurred earlier (P=0.001). Neonates who failed NIPPV within 24 h did not have any association with likelihood of developing BPD or severity of BPD, after adjusting for confounding variables.
Conclusion:
Significant differences in neonatal characteristics may help identify which neonates are more likely to fail NIPPV, and their timing of failure.
Purpose
Study the ophthalmic morbidities for infants born prematurely at Tertiary care center in Riyadh city.
Methods
Retrospective, longitudinal cohort study at King Fahad Medical City for premature infants born at gestational age (GA) ⩽ 32wk or birth weight (BW) ⩽ 1500 g during the study period from January 1, 2007, until the end of December 2009. Short term outcome was diagnosis with Retinopathy of Prematurity (ROP) and long-term outcome was ophthalmic findings at age 18–24 months.
Results
The cumulative incidence of ROP was 30%. Infants diagnosed with ROP had a mean GA of 27 wk (23–35 wk) and mean BW of 907 g (530–1730 g). Risk factors other than GA and BW for ROP, identified in the predictive logistic regression model, were blood transfusion [odds ratio (OR) 1.27] and diagnosis with intraventricular hemorrhage (OR = 2.90). Strabismus was identified in 14% of the study cohort. Diagnosis of hyperopia (spherical equivalent ⩾+0.75 D) was equal in both ROP and no-ROP groups (p = 0.56). Myopia (spherical equivalent ⩾-0.75 D) and astigmatism ⩾1.00 D were diagnosed more frequently in the ROP group (p < 0.0001 and 0.04, respectively).
Conclusions
A higher incidence of ROP was observed in this cohort compared to some Saudi Arabian centers. It is recommended that the screening criteria be maintained and that the effects of further control of blood transfusion be assessed in a prospective study. The authors recommend an extra ophthalmic evaluation at the age of 18–24 months for all premature infants born with GA ⩽ 32 wk.
ROP is a common disorder among extremely low-birth-weight premature infant survivors and may cause total vision loss in as many as 2% to 4% of those weighing less than 2 lb (1 kg) at birth. Regular examinations begun in the intensive care unit permit early detection and treatment of progressive ROP, reducing visual impairment. Ongoing research into antioxidants, angiogenesis, light exposure, and newer surgical techniques may offer new approaches for preventing and treating established ROP. Infants who have had ROP that regressed should continue regular ophthalmologic follow-up to detect and treat myopia, strabismus, and if they have cicatricial sequelae, late retinal detachments as teens or adults. Infants who develop retinal detachments should be referred for early intervention and special education programs and remain in regular ophthalmologic follow-up for the detection and treatment of further ophthalmic complications.
Objective
To determine if current retinopathy of prematurity screening guidelines1 adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants.
Study Design
Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants 24 0/7 to 27 6/7 weeks gestational age with consent prior to delivery were enrolled in 2005-2009. Severe retinopathy of prematurity (Type 1 retinopathy of prematurity or treatment with laser, cryotherapy, or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed then current American Academy of Pediatrics (AAP) screening recommendations, beginning by 31-33 weeks postmenstrual age.2,3
Results
1316 infants were enrolled in the trial. 997 of the 1121 who survived to first eye exam had final retinopathy of prematurity outcome determined. 137 (14% of 997) met criteria for severe retinopathy of prematurity and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe retinopathy of prematurity. Postmenstrual age at onset was 32.1 to 53.1 wks. In this referral center cohort, 1.4% (14/997) developed severe retinopathy of prematurity after discharge.
Conclusion
Our contemporary data support the 2013 AAP screening guidelines for ROP for infants 24 0/7 to 27 6/7 weeks gestational age.1 Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.
Background: The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) has not been well established. Objective: To conduct a systematic review and meta-analysis of the association between CA and ROP in preterm infants. Data Sources: The authors searched MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and PubMed, reviewed reference lists of relevant articles, abstracts and conference proceedings (Society for Pediatric Research, European Society for Paediatric Research 1990-2012), sought results of unpublished trials, and contacted the primary authors of relevant studies. Study Selection: Studies were included if they had a comparison group, examined preterm infants, and reported primary data that could be used to measure the association between exposure to CA and the development of ROP. Data Extraction: Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality using the Newcastle-Ottawa Scale. One reviewer extracted data and a second reviewer checked data extraction. Summary relative risks (RRs) were calculated using a random effects model. Data Synthesis: We identified 1,249 potentially relevant studies from the electronic databases. Twenty-seven studies involving 10,590 preterm neonates with 2,562 cases of ROP were included. Taking into account all included studies without adjusting for gestational age (GA), CA was significantly associated with ROP (any stage) [summary RR 1.33 (95% CI 1.14-1.55, I(2) = 77%, pheterogeneity < 0.0001)], and a borderline significant association was observed for severe ROP (stage ≥3) [summary RR 1.27 (95% CI 0.99-1.63, I(2) = 74%, pheterogeneity < 0.0001)]. There was no publication bias with Begg's test. However, subgroup analysis of studies adjusting for GA showed no significant association on CA with ROP [summary RR 0.98 (95% CI 0.77-1.26, I(2) = 0%, pheterogeneity = 0.89)]. Conclusion: Unadjusted analyses showed that CA was significantly associated with ROP (any stage) as well as with severe ROP (stage ≥ 3). However, the association disappeared on analysis of studies adjusting for GA. Hence, CA cannot be definitively considered as a risk factor for ROP, and further studies should adjust for potential confounding factors and report results by stage to clarify the association with severe ROP. © 2014 S. Karger AG, Basel.
Preterm children are at risk of developing increased blood pressure (BP). We evaluated possible associations between BP, early insulin-like growth factor-1 (IGF-1) and IGF-binding protein-1 (IGFBP-1) levels and Retinopathy of Prematurity (ROP) in preterm children.
The study included 32 infants: median gestational age 28.1 weeks (range 24.6-31.3) and birth weight standard deviation scores (SDS) (±SD) 1.0±2.7. IGF-1 and IGFBP-1 at postnatal weeks 32.6-34.6 and ROP stages were established after birth. BP was measured at the age of four years. The ratio (IGF-1)(2) /IGFBP-1 was created to investigate the influence of both IGF-1 and IGFBP-1 to later BP.
Diastolic BP correlated with IGFBP-1, inversely correlated with IGF-1 and IGF-1(2) /IGFBP-1 (r=-0.71, P<0.0001) and positively correlated with catch-up growth velocity from lowest weight SDS to age 36.5 weeks (r=0.48, P<0.01), independent of gestational age. Children with moderate to severe ROP as neonates had higher mean arterial BP (78 [±95%CI 74-83] vs 71 [±95%CI 68-75] mm Hg, P<0.05) adjusted for gestational age and birth weight SDS compared to children diagnosed with no to mild ROP.
Low neonatal IGF-1(2) /IGFBP-1 and severe ROP were associated with higher BP in four-year-old children born very preterm and may thus predict future cardiovascular morbidity. This article is protected by copyright. All rights reserved.
Although survival of extremely low birth weight (ELBW) infants dramatically improved over last decades, bronchopulmonary dysplasia (BPD) rate has not changed. The use of indomethacin prophylaxis in ELBW infants results in improved short-term outcomes with no effect on long-term outcomes. The addition of fluid restriction to the indomethacin prophylaxis policy could result in a reduction of BPD and improve long-term survival without neurosensory impairment at 18 months corrected age. To determine the effect of a policy of fluid restriction compared with a policy of no fluid restriction on morbidity and mortality in ELBW infants receiving indomethacin prophylaxis. The standard search strategy for the Cochrane Neonatal Review Group was used. This included search of OVID MEDLINE-National Library of Medicine, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 8, 2011). Additional search included conference proceedings, references in articles, and unpublished data. All randomized or quasi-randomized trials that compared fluid restriction and indomethacin prophylaxis vs. indomethacin prophylaxis alone in ELBW infants were included. Standard methods of the Cochrane Neonatal Review Group were planned to assess the methodological quality of the trials. Review Manager 5 software was planned to be used for statistical analysis. We found no randomized controlled trials to investigate the possible interaction between fluid restriction and indomethacin prophylaxis vs. indomethacin prophylaxis alone in ELBW infants. A well-designed randomized trial is needed to address this question.
The aim of the study is the relationship between the morbility of very low birthweight newborns which required neonatal intensive care and their cognitive abilities during school. Material and method: this is a prospective cohort reconstruction study with a sample of 18 newborns whose birthweight was lower than 1.250 g. It was compared with a control group (term newborns with adequate birthweight), paired by their socioeconomic status. During the neonatal period in the intensive care unit morbility and neonatal severity were assessed using SNAP and NTISS from the first day with weekly controls, until delivery day. Two postnatal evaluations were done: pre-school assessment (between 3 and 4 years old) and at school age (between 8 and 9 years old). In the first evaluation the Denver scale was used to evaluate their neurodevelopment. A health classification system which can detect the health state of a child (MASH) was also used. During school-age the WISC-III scale which evaluates cognitive abilities was applied. In both periods weigth, height and craneal perimeter were measured. The relationship between the number of pathologies and cognitive scale was studied with a linear regression. Results: the average cognitive capacity (CIG) was 87,5±14,3 in the preterm group and 104,3±12,18 in the control group, showing a significant difference (p
To evaluate mortality and short-term outcomes in very low birth weight infants admitted to the tertiary neonatal intensive care unit, Istanbul, Turkey.
Study data were recorded prospectively from January 1, 2010, to December 31, 2010. The clinical findings in neonates with birth weights <1000g were compared with infants with birth weights of between 1000g and 1499g.
In the present study, survival rates were 40% and 86.2% for infants weighing <1000g and 1000g to 1499g, respectively. There was no difference between males and females with respect to mortality (P>0.05). The mean (±standard deviation) birth weight was 985.6±150.15 g and mean gestational age was 27.5±2.04 weeks. The antenatal steroid rate was 37.2%, and the Cesarean section rate was 73%. Respiratory distress syndrome was diagnosed in 89% of the infants, with a 69% surfactant administration rate. Severe intracranial hemorrhage (IVH) (grade >II) was 14%. Grade 4 periventricular leukomalacia was 10%. Twelve (24%) infants had evidence of bronchopulmonary dysplasia (BPD). Retinopathy of prematurity (stage >II) was 4%. The correlation between ROP rate and need for ventilation therapy was present (r=0.52). Proven necrotizing enterocolitis (stage >2) was not observed. Patent ductus arteriosus (PDA) was diagnosed in 67% of the neonates. BPD, IVH, and PDA were statistically higher in neonates with a birth weight <1000g.
Survival rate of VLBW infants increased with increasing BW. Sex was not a risk factor for mortality. The need for ventilatory therapy may be an important risk factor for ROP in infants <1500g.
This study aimed to identify the main risk factors for development of retinopathy of prematurity (ROP) in neonatal intensive care units in Alexandria, Egypt, from January 2010 to January 2012.
A prospective cohort study was undertaken in infants weighing < 1250 g and maternal postmenstrual age < 32 weeks if there was concern about prolonged exposure to oxygen. The main clinical outcomes were occurrence of any stage of ROP and in particular severe ROP. Perinatal variables considered were: birth weight, gestational age, gender, method of ventilation (nasal continuous airway pressure or intermittent mechanical ventilation), packed red blood cell and/or plasma transfusion, occurrence of sepsis, neonatal indirect hyperbilirubinemia, intraventricular hemorrhage, and patent ductus arteriosus. After obtaining informed consent from the parents, infants at risk were examined for ROP using indirect ophthalmoscopy, ie, RetCam II fundus photography.
The study included 152 infants of mean gestational age 31.02 weeks and mean birth weight 1.229 kg. Seventy-two cases (47.5%) were male and 80 cases (52.5%) were female. Of the cases screened, 100 (65.6%) had no ROP, 52 had ROP of any stage (34.4%), and 27 (18%) had stage 1, five (3.3%) had stage 2, 17 (11.5%) had stage 3, and three (1.6%) had stage 4 disease. No infants had stage 5 ROP. Of all our cases with ROP, 15 (28.6%) had prethreshold disease type 1 that required treatment, comprising 9.8% of all cases screened for ROP. Using stepwise logistic regression analysis, all risk factors studied were found to be significantly associated with the development of ROP, except for neonatal indirect hyperbilirubinemia. Severity of ROP was inversely proportional to birth weight and gestational age.
ROP occurred in 34.4% of all infants screened in the neonatal intensive care units at three obstetric hospitals in Alexandria. The main risk factors for development of threshold ROP by regression analysis were low birth weight, gestational age, method of ventilation, need for packed red blood cell and/or plasma transfusion, occurrence of sepsis, intraventricular hemorrhage, and patent ductus arteriosus but not neonatal indirect hyperbilirubinemia. We suggest that both immaturity and compromised pulmonary function are both important etiological factors in the development of ROP.
Objective:
To identify variables associated with early nasal continuous positive airway pressure (ENCPAP) failure in preterm neonates less than 30 weeks gestational age.
Study design:
Multicenter prospective study including 131 preterm newborns, over a period of 2 years. Patients and respiratory variables were assessed using univariate analysis.
Result:
Variables associated with ENCPAP failure were: the need of resuscitation with a FiO(2)>0.30; a CPAP pressure of 6.4±1.2 cm H(2)O; the need of a FiO(2) of 0.40 in the first 4 h of life; male gender maintaining the need of a FiO(2)>0.25 in the first 4 h of life; and respiratory distress syndrome with criteria for surfactant administration.
Conclusion:
The need for oxygen in resuscitation and maintained in first hours of life, male gender, a CPAP pressure over 5 cm H(2)O and surfactant need are predictors of ENCPAP failure in preterm neonates 26 to 30 weeks gestational age.
ABSTRACT An analysis of the ophthalmic recordings from the pre-term infants born 1991-93 considered at risk of developing retinopathy of prematurity is added to three previous 3-year clinical surveys from the same Danish county. Out of the 203 subjects of the recent study 34 showed evidence of retinopathy of prematurity. In 27 the maximum retinopathy of prematurity stage was 1 or 2 prior to regression. Out of the seven subjects with stage 3, one progressed to bilateral blindness in spite of the cryotherapy given in this single case. Comparing with the four retinopathy of prematurity-blind born 1982-84, the trend over the 12 years appears to be towards a better overall ophthalmic outcome. Along with an increasing number of survivors of the low GA/BW groups, the retinopathy of prematurity percentage has shown a decline, and apparently with less serious sequelae. Together with other Danish experience, eventually the present data may lead to lower screening limits for retinopathy of prematurity regarding GA/BW. Prior to this, however, there should be support from the case data currently collected in the compulsory Danish register of visually impaired children. Hence our present basic recommendation is that gestational ages up to (and including) 31 full weeks qualify for serial eye examination.
Background. To evaluate the effect of antenatal tocolytic administration of magnesium sulphate and ritodrine on the cerebral blood flow velocity and on the cerebral vascular resistance of preterm newborns in the first hours of life.
Methods. Cerebral blood flow velocity, resistance index and relative vascular resistance were studied in 27 preterm infants (<34 weeks gestation) with antenatal exposure to maternal magnesium sulphate treatment and in 27 preterm infants (<34 weeks gestation) with antenatal exposure to maternal ritodrine treatment. Both antenatal magnesium sulphate or ritodrine were used for tocolysis. Cerebral blood flow was measured, using Doppler ultrasonography, in the anterior cerebral artery, in the left middle cerebral artery and in the right middle cerebral artery.
Results. We did not find any significant difference in the blood flow velocity, resistance index or relative vascular resistance in the three cerebral arteries between the two treatment groups.
Conclusions. Our study shows that maternal antenatal administration of magnesium sulphate to delay preterm delivery, compared to antenatal administration of ritodrine, does not induce any significant differences either in cerebral blood flow velocity or in cerebral vascular resistance of preterm infants in the first hours of life.
Abstract This study reported the prevalence and severity of retinopathy of prematurity (ROP) in ≤28 weeks gestation or ≤1000g birthweight infants over a 12-year period. Among 328 survivors of ≤28 weeks gestation, 30% had ROP, 12% had severe ROP of Stage 3 or worse, 5% had at least one blind eye and 3% were bilaterally blind. Among 201 survivors of ≤1000g birthweight, the above abnormalities were found in 40, 16, 6 and 4% respectively. In both cohorts there was a significant increase in the prevalence of ROP and severe ROP between the period 1977-80 and 1981-84, but the lesser increase observed between the periods 1981-84 and 1985-88 was not statistically significant. The rates of ROP-induced blindness were not significantly different between the three 4-year periods. An inverse relationship was noted between the prevalence of ROP and gestational age. The results suggest a resurgence of ROP in ≤28 weeks or ≤1000g infants, the cause of which is uncertain. In view of this trend, continued surveillance of ROP is warranted.
The reported resurgence of retinoathy of prematurity prompted analysis of the prevalence of retinopathy among premature infants born at Christchurch Women's Hospital over a five-year period. Of the 129 surviving very-low-birth weight infants, 65 (50.4%) underwent ocular screening during the review period. Retinopathy was detected in 17.1% (22/129) of surviving infants, or 34% (22/65) of selected infants referred by paediatricians for ocular screening. Five infants had severe or blinding retinopathy and these premature infants were of significantly lower birthweight and born after shorter gestation periods than those found to have no retinopathy. Examination techniques for eyes of premature infants are discussed, and recommendations for screening for retinopathy of prematurity made.
Objective:
To determine factors associated with latency time to birth after preterm premature rupture of membranes (PPROM) and the impact on neonatal outcomes.
Study design:
Data on singleton pregnancies with PPROM (n=1535 infants) were prospectively collected in a computerized perinatal/neonatal database at a tertiary care perinatal center. Latency was characterized as ≤72h versus >72 h after PPROM.
Result:
The percentage of women with latency to birth >72 h decreased from 67% in very preterm (gestational age (GA) 25 to 28 weeks) to 10% in late preterm women (GA 33 to 36 weeks). PPROM women with latency ≤72 h were more likely to have pregnancy-induced hypertension and birth weight <3%; PPROM women with latency >72 h were more likely to have received steroids and develop clinical chorioamnionitis. PPROM <32 weeks GA with latency ≤72 h was associated with a two-fold higher incidence of severe neonatal morbidity, while PPROM between 29 to 34 weeks GA and latency ≤72 h was associated with a higher incidence of moderate neonatal morbidity.
Conclusion:
A latency period >72 h was associated with a decreased incidence of adverse neonatal outcomes up to 32 weeks GA for severe and 34 weeks GA for moderate morbidity indices.
Objective:
To compare clinical outcomes of premature infants on synchronized nasal intermittent positive pressure ventilation (SNIPPV) vs nasal intermittent positive pressure ventilation (NIPPV) in the neonatal intensive care unit. Use of NIPPV in the neonatal intensive care unit has shown promise with better clinical outcomes in premature neonates. It is not known if synchronization makes a significant clinical impact when using this technique.
Study design:
Retrospective data were obtained (1/04 to 12/09) of infants who received NIPPV anytime during their stay in the neonatal intensive care unit. SNIPPV (Infant Star with StarSync) was utilized from 2004 to 2006, whereas NIPPV (Bear Cub) was used from 2007 to 2009. Bronchopulmonary dysplasia (BPD) was defined using the NIH consensus definition. Unadjusted associations between potential risk factors and BPD/death were assessed using the χ (2) or Wilcoxon rank-sum test. Adjusted analyses were performed using generalized linear mixed models, taking into account correlation among infants of multiple gestation.
Result:
There was no significant difference in the mean gestational age and birth weight in the two groups: SNIPPV (n=172; 27.0w; 1016 g) and NIPPV (n=238; 27.7w; 1117 g). There were no significant differences in maternal demographics, use of antenatal steroids, gender, multiple births, small for gestational age or Apgar scores in the two groups. More infants in the NIPPV group were given resuscitation in the delivery room (SNIPPV vs NIPPV: 44.2 vs 63%, P<0.001). Use of surfactant (84.4 vs 70.2%; P<0.001) was significantly higher in the SNIPPV group. There were no differences in the rate of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and necrotizing enterocolitis in the two groups. After adjusting for the significant variables, use of NIPPV vs SNIPPV (odds ratio 0.74; 95% confidence interval: 0.42, 1.30) was not associated with BPD/death.
Conclusion:
These data suggest that use of SNIPPV vs NIPPV is not significantly associated with a differential impact on clinical outcomes.
Published data on short-term outcomes of very low birth weight infants from Saudi Arabia are limited. In the present study, our objective was to describe and analyze the outcomes of very low birth weight infants admitted to our neonatal intensive care unit and to compare the results with data published by the National Institute of Child Health and Development.
This study was a retrospective analysis of prospectively collected data from a single tertiary care center over a three years period.
Biodemographic data and data regarding multiple outcome measures were analyzed for infants with birth weight of 1500 g or less. Data were obtained from our neonatal intensive care unit database.
Our results included a total of 186 infants with birth weights of 1500 g or less. Of these infants, 154 (82.8%) survived to discharge. Seventy-six (40.9%) were male, and mean (SD) gestational age (GA) was 29 (2.9) weeks with a range of 21 weeks, 6 days to 36 weeks, 2 days. Mean (SD) birth weight was 1062 (302) g with a range of 420 to 1495 g. Fifty-seven (30.6%) infants were characterized as small for gestational age. Antenatal steroids were given to 74.2% of mothers. Eighty-five percent of infants were born by cesarean section. The rate of bronchopulmonary dysplasia was 17.7%, patent ductus arteriosus 31.2%, intraventricular hemorrhage 12.9%, periventricular leukomalacia 3.8%, necrotizing enterocolitis 7.5%, retinopathy of prematurity 28.3%, and late-onset sepsis was 21.9%.
In this population of very low birth weight infants, survival rates and complications of prematurity were comparable to international data.
Coagulation therapy has repeatedly been recommended in cases of progressive active stages of retinopathy of prematurity. However, follow-up studies of infants with both eyes treated are less conclusive because of the high incidence of spontaneous regression. In the present study only one eye of each of the twenty-one premature infants was treated for advanced retinal neovascularizations. A remission occurred in both eyes of most of these babies. In none, any major benefit of the treatment was recorded as compared to the untreated control eye. But there were also cases which progressed from seemingly benign retinopathy of prematurity towards advanced retrolental fibroplasia. Coagulation therapy (preferably cryotherapy) should be considered only in infants with overshooting neovascularization occurring within 2 weeks after incubation, and with the development of retino-vitreal proliferations, hemorrhages, and circumscribed retinal detachment within 1-2 months after incubation. In one out of two cases, a total retinal detachment was cured with an encircling procedure.
A joint committee of pediatricians, obstetricians and ophthalmologists has been organized by the Ministry of Health and Welfare in Japan for the study of retrolental fibroplasia (RLF). The report by the committee includes a new classification for active and cicatricial RLF, the recommended method of fundus examination of premature infants, and guidelines for the treatment of active RLF by photocoagulation. It is emphasized that the overall effect of photocoagulation on RLF has not yet been established, and extensive and cooperative studies in related fields will be necessary in dealing with this serious disease.
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Introduction
Administration of oxygen to premature infants had been implicated as an etiologic agent in the development of retrolental fibroplasia (RLF) prior to late 1952.* But because of the apparently capricious fluctuation in incidence of the disease observed in various communities and the insufficiency of controlled investigations concerning the possible role of oxygen in RLF the evidence was deemed inadequate to justify curtailment of oxygen for premature infants, particularly in the absence of knowledge of the effect on mortality of such a change in procedure.For these reasons a number of pediatricians and ophthalmologists agreed early in 1953 to pool their nursery facilities and interests and investigate cooperatively the question of whether oxygen was in fact an etiologic agent in RLF and at the same time to determine what effect restricting oxygen might have on infant mortality. This group of investigators, from 18 hospitals located
• Retinas of 142 eyes from 71 premature infants on whom autopsies had been done were studied by gross observation and by using PAS-stained whole mount, trypsin-digest, and conventional histological techniques. With these techniques, vascular pathologic condition was correlated with fluorescein angiograms in living infants with acute retrolental fibroplasia. The specific lesions seen in acute phase were a major arteriovenous shunt in the eye, microvascular changes including tufting, and obliteration of capillaries around arteries and veins. Regression occurred by vascular budding from the anterior edge of the shunt. Observations on vascularization in the normal indicated a variability of the level of maturation of the retinal vasculature, only roughly correlated with gestational age.
(Arch Ophthalmol 95:29-38, 1977)
We have developed a classification system for the acute phases of retinopathy of prematurity based on more than 13,000 ophthalmoscopic examinations of more than 3,400 premature infants between 1968 and 1982. Two forms of the active disease exist. Retinopathy of prematurity is a relatively common mild disease and retinopathy of prematurity plus is characterized by rapid progression and posterior pole vascular tortuosity and dilation. The five grades progress from peripheral vascular abnormalities (Grade 1) through a demarcation line (Grade 2) and extraretinal neovascularization (Grade 3) to partial (Grade 4) or total (Grade 5) retinal detachment. The persistence of abnormal retinal vessels during the first year of life is considered "transitional" retinopathy of prematurity unless unequivocal cicatricial changes with macular distortion develop.
Four hundred and ninety seven babies were screened for signs of developing RLF and definite changes were found in 31; of these only two developed severe cicatricial RLF, while the results of three are still in doubt. The early developing changes all occur at the retinal periphery and similarly the mild cicatricial changes are also found there, so a new classification is proposed for grading both the developing and cicatricial stages of RLF. This new grading has been found to be clinically useful and corresponds more closely with the observed changes than the classification of Reese, King and Owens (1953).
Infants with retrolental fibroplasia have been followed at the Bascom Palmer Eye Institute from August 1969 through December 1974. Changes occurring in acute proliferative RLF were documented with fundus photography and fluorescein angiography. These are presented and especially those that have prognostic significance are emphasized.Die akute, proliferative Phase der retrolentalen Fibroplasie konnte an 55 Kindern studiert werden. In den ersten Lebenstagen ist der Glaskrper gewhnlich zu trbe, um eine Untersuchung des Augenhintergrundes zu gestatten. Zum Teil trgt zu dieser Trbung auch die Hornhaut und die Tunica vasculosa lentis bei. Die Trbung dauert mehrere Tage und hat keinen Zusammenhang mit der RLF. Eine Demarkationslinie ist spter bei den Kindern zu sehen, die eine RLF entwickeln. Danach bilden sich neue Gefe auf der Netzhaut und Gefanomalien innerhalb der Netzhaut (aneurysmatische Geferweiterungen und eine capillarenfreie Zone entlang der greren Gefe). Wenn eine Rckbildung eintrat, wurde die Demarkationslinie rosa und von Gefen ersetzt. Alle diese Befunde konnten am Kleinkind mittels Fluorescein-Angiographie besser nachgewiesen und demonstriert werden.
The changes occurring in retrolental fibroplasia were studied in 97 premature infants with fundus photography and fluorescein angiography. The macrovascular lesion of proliferative retrolental fibroplasia was identified as a functioning arteriovenous shunt. The microvascular abnormalities were capillary tufts, collaterals, capillary-free zones, and neovascular membranes. Regression was signaled by the ingrowth of capillaries from the shunt into the avascular retina. Cicatrization was characterized by persistence of the vascular abnormalities of the proliferative phase and organization of the avascular retina into a contracting scar.
Three hundred eighty-four premature infants were examined by indirect ophthalmoscopy in a period of 38 months. Sixty-eight were found to have some degree of retrolental fibroplasia. Most pathologic changes resolved spontaneously to normal or near normal. A classification was formulated, based on peripheral vascular changes, to enable observers to interpret and quantitate the amount of disease present. The role of the ophtalmologist in the perinatal intensive care nursery is not to dictate the amount of oxygen administration during the acute phase of respiratory distress syndrome but to monitor peripheral fundus and posterior vascular changes of infants of low birth weight, or who have received oxygen, or both, at a time that is not detrimental to the health of the infant. To evaluate the possible indications and efficacy of surgical intervention, an understanding of the natural course of the disease process is mandatory.
Retinas of 142 eyes from 71 premature infants on whom autopsies had been done were studied by gross observation and by using PAS-stained whole mount, trypsin-digest, and conventional histological techniques. With these techniques, vascular pathologic condition was correlated with fluorescein angiograms in living infants with acute retrolental fibroplasia. The specific lesions seen in acute phase were a major arteriovenous shunt in the eye, microvascular changes including tufting, and obliteration of capillaries around arteries and veins. Regression occurred by vascular budding from the anterior edge of the shunt. Observations on vascularization in the normal indicated a variability of the level of maturation of the retinal vasculature, only roughly correlated with gestational age.
The relation between PaO2 and retrolental fibroplasia (RLF) was studied prospectively in 719 premature infants born in or treated in the intensive care units of a group of university hospitals. Blood gas studies were performed on 589 of these infants, 66 of whom had a diagnosis of RLF; in 27 of these 66, some grade of mostly nonblinding cicatricial disease developed. The frequency of RLF was highest among infants of lowest birth weight. A multivariate statistical method was used to analyze simultaneously the effect of possible etiologic factors associated with RLF.
The occurrence of RLF was found to be unrelated to PaO2, as determined by the limited information available from intermittent sampling. RLF is associated with concentration of oxygen administered in the lightest birth weight group, but the strongest association, aside from birth weight, was with time in oxygen. None of the other variables involving blood chemical values appeared to be associated with RLF. The severity of cicatricial RLF is clearly greater in infants weighing less than 1,200 g at birth.
Conservative administration of oxygen may have been responsible for failure to demonstrate quantitative association between Pao2 levels and disease. Agreement between the observed and predicted numbers of infants with RLF demonstrates the strength of the multivariate technique employed in making the statistical analyses.
The purpose of this monograph is to summarize our knowledge of oxygen-induced retinal disease in preterm infants and to look at the clinical manifestations as seen by one ophthalmologist working in one nursery on an almost daily basis for 71/2 years and then twice weekly for an additional 1 1/2 years. The exposition is designed primarily for pediatricians and others working with immature babies. I hope that ophthalmologists in training will also find it helpful.
It is almost impossible to review all the clinical, experimental, statistical and historical data relating to this fascinating disorder but reference to some of the data is necessary. I have attempted to avoid any distortion of fact in this summary.
The clinical material presented is anecdotal in the sense that the observations were made only by the author, without the use of established guidelines as to how the disorder is manifest clinically or how it progresses. I hope that I have achieved the merit of unbiased consistent observation.
A refined classification of the stages of the retinopathy of prematurity (RLF) based on the experience of over 7500 examinations during the past decade is presented. We have been using the basic elements of this classification since 1972 in order to evaluate the influence of vitamin E on retrolental fibroplasia (RLF). It is our impression that it provides a more accurate clinical method of following the course of the retinopathy and a tool for assessing the factors other than prematurity and hyperoxia that may play a subtle role in the development of RLF.
Acute proliferative retrolental fibroplasia (RLF) has been studied in premature infants employing a Zeiss fundus camera and fluorescein angiography. A total of 164 angiograms have been performed on 122 infants. At the present time, angiography is reserved for studying infants with peculiar or puzzling fundus pictures. A dose of 0.1-0.4 cc of 10% sodium fluoresceinate is employed, depending on the age and the weight of the baby. Fluorescein clearly outlines the major arteriovenous shunt in the retina, which is the hallmark of acute RLF. The shunt fills with fluorescein and leaks it profusely. On regression, a fine brush border of capillaries is seen in the region where the shunt previously had been located. Study of the population susceptible to RLF reveals it to be the smallest sickest babies in the premature nursery.
A pathologic analysis of 19 cases of acute retrolental fibroplasia in autopsy eyes from paranatal infants is presented.
The clinical profile of these subjects showed no clear-cut maternal factors. Infant factors included systemic congenital anomalies (14 eases); ocular congenital anomalies (1); birth weight—less than 1500 grams (12), more than 2000 grams (4); neonatal complications—“respiratory distress” (8), “apneic spells” (7), Erythroblastosis fetalis (3); oxygen therapy of varying amounts (14); periodic elevations of arterial oxygen (7); and varying survival times (intrauterine death, one case; less than 48 extrauterine hours, 9 cases).
Considering all cases, the lesions showed a progressive pattern—beginning with proliferation of primitive vascular mesenchyme in vanguard of advancing vasculature (four cases), formation of intraretinal band of endothelial cells in rear guard (10 cases), and finally, extraretinal neovascularization from rear guard zone (five cases).
Infants with retrolental fibroplasia have been followed at the Bascom Palmer Eye Institute from August 1969 through December 1974. Changes occurring acute proliferative RLF were documented with fundus photography and fluorescein angiography. These are presented and especially those that have prognostic significance are emphasized.
Daily ophthalmoscopic monitoring was performed on 102 premature infants to test the feasibility of such monitoring as a guide to oxygen therapy. This monitoring was unsuccessful because of hazy media and the extremely small caliber of the retinal vessels. Fundus photography and fluorescein angiography were performed on selected infants to demonstrate the acute lesion of retrolental fibroplasia.
We examined 1,849 consecutively admitted premature infants weighing 2000 gm or less at birth for retrolental fibroplasia (RLF). Proliferative RLF was diagnosed frequently in low birth weight infants who were more likely to survive with modern neonatal intensive care. Cicatricial RLF was more likely to result from proliferative RLF and to be more severe in lower birth weight infants, but most affected eyes retained useful vision. Comparison of cases diagnosed over the 20 years of this study suggest that cicatricial RLF in recent years is less likely to result in severe visual disability. Improving survival rates for lower birth weight infants mandate continued surveillance for RLF and study of improved oxygen monitoring techniques.
There is evidence that, owing to the increased rate of salvage of premature infants weighing less than 1500 g at birth, the incidence of both retinopathy of prematurity (acute retrolental fibroplasia) and cicatricial retrolental fibroplasia is increasing. Treatment of the acute process to prevent blindness is controversial. In order that adequate studies be conducted to settle this issue, an international classification of retrolental fibroplasia is proposed.
1. 1. The results of the first of a three-year controlled oxygen nursery study are cited. Seven of 28 infants receiving prolonged high oxygen levels progressed to Grades III and IV retrolental fibroplasia. Of 37 infants in the lower oxygen group none progressed beyond Grade II changes. 2. 2. Mechanisms by which prologed high oxygen administration might influence the premature retina are discussed.
Classification of retinopathy of prematurity as a predictive tool: a re-evaluation. Retinopathy of Prematurity Conference Syllabus
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Quinn GE, Schaffer DB, Johnson LH. Classification of retinopathy of prematurity as a predictive tool: a re-evaluation. Retinopathy of Prematurity Conference Syllabus. Washington DC, December 4-6, 1981; Vol1:303-17.
Acute retrolental fibroplasia: classification and objective evaluation of incidence, natural history and resolution by fundus photography and intravenous fluorescein angiography
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- Curran
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- Edwards
Cantolino SJ, Curran JS, Van Cader TC, Edwards WC. Acute retrolental fibroplasia: classification and objective evaluation of incidence, natural history and resolution by fundus photography and intravenous fluorescein angiography. Perspect Ophthalmol 1978; 2:175-87.
An international classification of retinopathy of prematurity
Acute retrolental fibroplasia: classification and objective evaluation of incidence, natural history and resolution by fundus photography and intravenous fluorescein angiography
- Cantolino
Notes on a classification of acute proliferative retrolental fibroplasia (retinopathy of prematurity)
- Flynn
Classification of retinopathy of prematurity as a predictive tool: a re-evaluation
- Quinn