Can screening for retinopathy of prematurity be reduced?

BACKGROUND: As screening for retinopathy of prematurity (ROP) is costly, time-consuming for the ophthalmologist and discomforting for the neonate, the minimum number of infants should be screened for ROP, without missing infants with severe ROP, at risk for threshold ROP. OBJECTIVES: To develop a diagnostic screening guideline for ROP that would safely reduce the number of ROP screening funduscopies in our department. METHODS: Data of 275 infants admitted between 1996 and 2000 and screened for ROP according to our Dutch National guideline were studied. Significant risk factors for ROP were calculated, using logistic regression analysis and used to develop a guideline. The discriminative power of the guideline was evaluated using the area under the curve for the receiver operating characteristic curve. RESULTS: Significant risk factors for ROP were: gestational age, birth weight and number of erythrocyte transfusions within the first 4 weeks of life. The combination of these 3 factors resulted in the highest area under the curve: 0.793. Using these 3 factors, a diagnostic screening guideline for ROP was developed: if birth weight + 2 x (gestational age - 20) - 6 x erythrocyte transfusion value within the first 4 weeks of life >or=34, no screening for ROP is necessary. Using this guideline, 22.2% of the infants of the study group could have been excluded from screening; 3.8% of the infants with ROP stages 1-2 would have been missed. CONCLUSION: In our department, ROP screening can be safely reduced using our diagnostic screening guideline.

[Retinopathy in premature infants]. / Retinopathie van de prematuur geborene.

Retinopathy of prematurity (ROP) is found in about 30% of premature infants with a birth weight < 1500 g and/or a gestational age < 32 weeks. Many risk factors are directly or indirectly involved in the development of ROP. The younger the child and therefore the more immature at birth, the greater the risk of ROP leading to short-sightedness or blindness. As a result of advances in obstetric and neonatal care, more immature and extremely low birth weight infants survive, and thorough ophthalmological screening for ROP is therefore essential. Timely detection (ROP stage 3) enables treatment with cryotherapy or laser therapy. Although the rate of success has increased with these forms of treatment, about 40% of the treated children retain a serious visual handicap. In the Netherlands, this involves about 10 children each year. At a later age, prematurely born children have a higher risk of developing other ophthalmologic problems such as strabismus, amblyopia and refractive errors. Again, timely detection and treatment reduces the risk of permanent visual disability.

Long term follow up of premature infants: detection of strabismus, amblyopia, and refractive errors.

AIM: To establish recommendations for long term ophthalmological follow up of prematurely born infants. METHODS: 130 infants with a gestational age (GA) <37 weeks and born between 1 November 1989 and 31 October 1990 were enrolled in a prospective study about the development of strabismus, amblyopia, and refractive errors. Infants were subdivided in three groups according to GA: A <28 weeks (n=32), B >/=28-32-<37 weeks (n=34). Ophthalmological assessment took place at the postconceptional age of 32 weeks, at term and at 3, 6, 12, and 30 months post term. At the age of 5 years parents received a questionnaire and a majority of the children was examined again (n=99). RESULTS: At the age of 5 years 46 infants were known to have strabismus (n=29) and/or amblyopia (n=22) and/or refractive errors (n=22). Statistical analysis showed that gestational age, duration of supplementary oxygen, and duration of hospitalisation were important predictive variables for the development of strabismus, amblyopia, or refractive errors (SAR) at the age of 5 years (p<0.05). Infants with a GA 32 weeks, who developed an incidence comparable with the normal population. Strabismus developed mainly in the first year of life and at the age of 5 years. Most infants with amblyopia were detected at the age of 2-3 years. Refractive errors were found in the first year of life and at the age of 2.5 and 5 years. CONCLUSION: Infants with a GA <32 weeks should be selected for long term ophthalmological follow up. These infants should be screened at the age of 1 year, in the third year of life (preferably at 30 months), and just before school age (including testing of visual acuity with optotypes).

New developments in neonatology: less severe retinopathy of prematurity?

PURPOSE: To determine the effects of surfactant replacement therapy (SRT), high-frequency oscillatory ventilation (HFOV), and general improvements in quality of care on the incidence of severe retinopathy of prematurity (ROP). METHODS: Retrospective comparison of the incidence and severity of ROP in two groups of preterm infants admitted to our neonatal intensive care unit (NICU) in two consecutive 5-year periods (1986-1995) and screened for ROP. During the second study period, natural surfactant was introduced in the treatment of respiratory distress syndrome (RDS) and HFOV was used for treatment of respiratory insufficiency of any origin. The effects of these developments and general improvements on the incidence of severe ROP were analyzed with stepwise logistic regression. RESULTS: The overall incidence of ROP from 1986-1990 was not significantly different from the incidence of ROP from 1991-1995. The incidence of severe ROP (ROP stage 3 or greater) was significantly lower in the second period (15.7% versus 6.4%, P=.015). For infants <1000 g, the incidence of overall ROP was increased significantly during the second study period (47.6% versus 60.1 %, P=.045), although the incidence of severe ROP remained unchanged. Only SRT was associated with a decreased risk for severe ROP; HFOV and general improvements in quality of care had no influence on the outcome. In patients with RDS, the incidence of severe ROP decreased significantly during the second period. CONCLUSION: Of the recent new developments in neonatology, only SRT was associated with a decreased risk for severe ROP.

Do postnatal glucocorticoids and retinopathy of prematurity relate?

To study a possible relation between the use of postnatal glucocorticoids and the incidence and severity of retinopathy of prematurity (ROP), we conducted a retrospective study over a 4-year period that compared data of 161 preterm infants treated with hydrocortisone for bronchopulmonary dysplasia (BPD) with the data of 253 controls. The incidence of overall ROP was 62.7% in the hydrocortisone group and 21.3% in the control group. The incidence of severe ROP (stages 3-5) was 5% in the treatment group and 0.4% in the control group. Using logistic regression, postnatal hydrocortisone therapy was not associated with an increased risk for ROP or severe ROP (OR 1.387, 95% confidence interval 0.773-2.489, p = 0.272 and OR 4.112, 95% C.I. 0.44-38.37, p = 0.16, respectively). Also, in a subgroup of extremely low-birth-weight infants (<1000 g), postnatal hydrocortisone had no influence on the incidence of (severe) ROP. In the infants with ROP (n = 155), only prolonged use of postnatal hydrocortisone was associated with an increased risk for severe ROP (OR 1.02, 95% C.I. 1.00-1.03, p = 0.03). In this study postnatal use of hydrocortisone was not associated with an increased risk for (severe) ROP. However, in infants already suffering from ROP, prolonged treatment with hydrocortisone concurred with an increased risk for severe ROP.

Altered immune function in human newborns after prenatal administration of betamethasone: enhanced natural killer cell activity and decreased T cell proliferation in cord blood.

During the course of human pregnancy, glucocorticoid (GC) treatment is given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, in animal studies, a number of side effects of perinatal GC treatment have been described. The aim of the present study was to evaluate in humans the effects of antenatal GC treatment on development of the immune system. In addition, we examined the development of immune reactivity in infants born preterm and at term who did not receive GC treatment antenatally. We tested mitogen-induced T cell proliferation, natural killer cell activity, and lipopolysaccharide-induced IL-6 production in cord blood samples. We found that there is a significant effect of gestational age on the capacity of T cells to proliferate and of natural killer cells to kill K562 tumor cells. The capacity to produce IL-6 does not change between gestational age 26 and 41 wk. Moreover, our results show that antenatal treatment with GC does have immunomodulatory effects: T cell proliferation is decreased in infants born very preterm (gestational age 26-31 wk) as well as in infants born between 32 and 36 wk of gestation. In contrast, the activity of natural killer cells is only increased in GC-treated infants born between 26 and 31 wk. We did not observe a significant effect of antenatal GC treatment on the capacity to produce IL-6.

Retinopathy of prematurity: the continuing threat to vision in preterm infants. Dutch survey from 1986 to 1994.

From January 1st 1986 until January 1st 1994, 82 infants were registered in The Netherlands as partially sighted or blind due to retinopathy of prematurity (ROP). Compared with the previous Dutch survey (1975-1987) an increasing number of registered infants had been screened for ROP during their initial hospitalization (95.1% vs. 54.1%) and had ophthalmic treatment in the acute stages of the disease (43.9% vs. 24.5%). Nevertheless, an increase in the annual incidence of partial sight or blindness due to ROP from 4.2/100,000 live births (1975-1987) to 5.1/100,000 live births (1986-1994) was found. This increase seemed to be associated with a higher number of surviving premature infants of less than 28 weeks gestational age.

Less severe retinopathy of prematurity induced by surfactant replacement therapy.

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797-2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.

Ontogency of the responses of human peripheral blood T cells to glucocorticoids.

The inhibitory effect of steroids such as dexamethasone on the immune response of adults has been widely documented. Little is known, however, about the effect of these agents on the developing immune system in newborns. The present study describes the ontogeny of the sensitivity of peripheral blood T cells to dexamethasone during the first year of life. Cord blood T cells of preterm or term infants appear to be extremely sensitive to inhibition of the proliferative response. This high sensitivity of cells to dexamethasone can still be observed in the first 2 weeks after birth. Subsequently, the sensitivity to dexamethasone inhibition of T-cell proliferation gradually decreases. At 1 year of age, the adult response pattern has been acquired.

Screening for retinopathy of prematurity: do former guidelines still apply?

Early detection of retinopathy of prematurity (ROP) in premature and very-low-birth-weight infants is crucial. In this retrospective study, 581 infants either with a birth weight below 1500 g or a gestational age of less than 32 weeks, or who did not fit these criteria but were judged to be at increased risk, were screened for ROP. ROP developed in 159 (27.4%). The incidence of ROP appeared to be inversely proportional to birth weight and gestational age. Infants with a birth weight below 750 g had a significantly higher risk of developing stage 3 and 4 ROP. The mean age at detection was 7.6 +/- 1.6 weeks. Nearly all of the ROP cases and all of the stage 3 and 4 cases were detected between the 5th and 10th week. Because screening should be focused on these vision-threatening stages, ophthalmic examinations should be concentrated in, but not limited to, the period between the 5th and the 10th postnatal week.

Towards a universal approach for screening of retinopathy of prematurity (ROP).

To improve the cost-benefit ratio of our current screening program for retinopathy of prematurity (ROP), the records of 312 infants who had been screened for ROP were studied retrospectively. Using a safety-index containing three well known risk factors (birthweight, gestational age, oxygen use), infants were classified to be at high risk or low risk for the development of ROP. When all high risk infants would have been screened extensively from the 5th postnatal week onwards and all low risk infants would have been screened once at the 7th postnatal week, a 9.8% reduction of ophthalmological examinations would have been obtained at the expense of missing 2.9% of non vision threatening ROP.

Surfactant replacement therapy: a new risk factor in developing retinopathy of prematurity?

We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46 infants suffering from a moderate or severe respiratory distress syndrome and treated with surfactant replacement therapy (SRT) and 61 controls admitted in the year prior to the institution of SRT. Mortality in the treatment group was lower than in the control group (15.5% versus 23.8; P = 0.29). The ROP prevalence in the treatment group was 47.8% and in the control group 27.9%. To analyse the contribution of SRT alone to the prevalence of ROP, multivariate analysis using logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95% confidence interval of 1.3-20.7, P = 0.02. The prevalence of severe ROP in the surfactant treated group was not increased compared to the control group. From our data we conclude that SRT increases the risk of developing ROP but is not associated with more severe forms of ROP.

Why is there an increase in ROP in recent years?

During a 12 year period (1975-1987) the incidence of blindness and partial sight due to ROP in the Netherlands was constant at approximately 3/100,000 live births. However the incidence appears to be rising since. Probable causes are an increasing number of twin and triplet births associated with assisted reproduction, an increasing mean maternal age, but the largest contribution is formed by the growing number of "relatively low risk" children not referred to university clinics due to screening problems.

Blindness and partial sight due to retinopathy of prematurity in The Netherlands: 1975-1987.

In 1975-1987 at least 84 children developed blindness or impaired vision due to retinopathy of prematurity (ROP) in the Netherlands. Neonatal data were obtained on 74 (86%). Unexpectedly most children (40 i.e. 54%) had been in level I and II hospitals after birth. Screening for ROP had been either insufficient or not timed according to present recommendations in 33 out of 40 children in level I and II hospitals and 25 out of 34 in level III hospitals. As the number of children with ROP has not changed appreciably over the last 40 years, while birth rates in the Netherlands have steadily decreased, the incidence of blindness/impaired vision due to ROP has probably increased. In the current population at risk of ROP which differs considerably from the one during the first epidemic, the disease may not be completely preventable. We conclude that improvements in screening procedures and timely treatment are crucial in order to improve the present situation.

[Feeding problems in infants with bronchopulmonary dysplasia and other chronic respiratory disorders]. / Voedingsproblemen bij zuigelingen met bronchopulmonale dysplasie en andere chronische respiratoire aandoeningen.

Long lasting feeding problems can occur in children who, in the neonatal period, needed intensive treatment for severe respiratory disease. In some of these children long-term (months) gavage feeding is needed. Retrospectively a group consisting of 16 children with extended feeding problems after neonatal respiratory disease was examined. The results are being described in this article.

[Premature retinopathy: recommendations for a screening policy]. / Prematuren retinopathie: aanbevelingen voor het screeningsbeleid.

Few data exist from which an optimal strategy for retinopathy of prematurity (ROP) screening can be deduced. This strategy should compromise between the dual purpose of screening, to wit monitoring the incidence of ROP and determining an optimal moment for therapeutic intervention. We recorded the timely incidence and course of ROP in all except four premature infants admitted during a 1-year period. The study results indicated that a single screening moment is not likely to detect more than 70% of all cases. When relying, however, on a single screening the investigation should be performed between the 7th and 9th week. The unpredictable course of ROP, varying between early starting, rapidly progressing forms and very late starting, usually benign forms, probably precludes the possibility of 100% ROP detection. Screening during the 4th to 5th, 8th and 11th week probably gives the best chances for determination of an optimal moment for treatment and approximation of the incidence.

Hydrops fetalis associated with red cell pyruvate kinase deficiency.

A hydrops fetalis and multicystic encephalomalacia were diagnosed in a neonate who was one of twins. The co-twin had died 5 weeks prior to delivery. The most likely explantation for both hydrops and multicystic encephalomalacia was fetal anemia caused by a red cell pyruvate kinase deficiency, and aggravated by an intrauterine disseminated intravascular coagulation.

Effects of a tactile stimulation/range-finding programme on the development of VLBW-neonates during the first year of life.

To investigate long-term effects of a hospital-based neonatal intervention programme, we performed a follow-up study on the development of very low birthweight neonates who were subjected to a tactile stimulation/range-finding programme. At corrected ages up to 1 year we evaluated weight-for-length gain, length, head circumference, psychomotor development, ankle mobility, tactile responses, motor behaviour and physical/neurological status. Significant differences between groups were found in weight-for-length gain in the girls and on items 'inspects own hands' and 'playing with feet to mouth' of the psychomotor development profile. These results suggest that our programme influences growth and enhances the infant's adaptive behaviour.

Prematures with and without regressed retinopathy of prematurity: comparison of long-term (6-10 years) ophthalmological morbidity.

Forty-two ex-prematures having had regressed forms of retinopathy of prematurity (ROP) during the neonatal period were compared with 42 matched non-ROP ex-premature controls at ages 6 to 10 years. The overall incidence of ophthalmologic problems was 55% in the ROP and 36% in the non-ROP group. Strabismus, amblyopia, and refraction anomalies occurred more frequently in the ROP group. In this group, a significantly greater number of children had decreased vision in one or both eyes compared to the non-ROP group. Although the incidence of ophthalmologic problems in the ROP group was considerably higher, the incidence in the non-ROP group still turned out unexpectedly high. this implicates that non-ROP very low birth weight neonates should also be considered to be at a greatly increased risk for later visual problems. Regular ocular examinations, mandatory for the ROP group, thus should be included in follow-up programs of non-ROP very low birthweight neonates as well.

Timely incidence of retinopathy of prematurity and its consequences for the screening strategy.

Few data exist from which an optimal strategy for retinopathy of prematurity (ROP) screening can be deduced. This strategy should compromise between the dual purpose of screening, to wit monitoring the incidence of ROP and determining an optimal moment for therapeutic intervention. We recorded the timely incidence and course of ROP in all except four premature infants admitted during a 1-year period. The study results indicate that a single screening moment is not likely to detect more than 70% of all cases. When relying, however, on a single screening, the investigation should be performed between the 7th and 9th weeks. The unpredictable course of ROP, varying between early starting, rapidly progressing forms and very late starting, usually benign forms probably precludes the possibility of 100% ROP detection. Screening during the 4th to 5th, 8th, and 11th weeks probably gives the best chances for determination of an optimal moment for treatment and approximation of the incidence.