Dopamine is an indicator but not an independent risk factor for grade 3 retinopathy of prematurity in extreme low birthweight infants

Retinopathy of prematurity (ROP) is a multifactorial disease with numerous risk factors.¹ Indicators besides birth weight or gestational age might be used to further discriminate the relative risk of developing ROP associated with a given gestational age or birth weight. Dopamine might be such an indicator since Mizoguchi et al reported on the association of dopamine and the risk of developing ROP in survivors (n = 41) with a birth weight below 1000 g and suggested that this association might be causal.²

To document whether dopamine is an indicator or an independent risk factor for developing ROP, a retrospective chart review in extreme low birthweight (ELBW—that is, below 1000 g) infants in a single neonatal intensive care unit during a 2 year period (2000–1) was performed. Neonatal characteristics collected were birth weight, gestational age, and Apgar score. Respiratory characteristics were either markers of duration of respiratory disease (day at first extubation, last day of respiratory support, last day of supplemental oxygen) or markers of severity of respiratory disease in the first 72 hours of life: maximal mean airway pressure (MAP) and oxygenation index (MAP × 100 × fractional oxygen/arterial oxygen mm Hg) at maximal MAP. In addition, data on CRIB (Clinical Risk Index for Babies, a disease severity scoring system) score were collected. The CRIB score was originally developed to document risk for neonatal mortality but there are reports on its association with morbidity characteristics.^3,4 Finally, prescription characteristics of dopamine (prescribed or not, maximal dose, and total hours of administration in the first week of life) were recorded.

Ophthalmological screening was initiated at the postnatal age of 4 weeks by indirect funduscopy after dilation. Screening was continued until full vascularisation or until diode laser therapy for threshold disease was provided. Findings were classified according to the International Classification of Retinopathy of Prematurity.⁵ Clinical characteristics in infants who developed grade 3 ROP were compared with infants who did not (Mann-Whitney U or χ² tests). Characteristics of dopamine administration were entered in a multiple regression model (MedCalc) with other significant risk factors to document the potential independent effect of dopamine on the risk of developing grade 3 ROP.

Of 90 infants admitted with a birth weight below 1000 g, 69 survived until discharge.

Retinopathy (any grade) was documented in 45/69 (65%) survivors. Twenty seven (39%) survivors developed grade 3 ROP and 15 (22%) of these infants developed threshold ROP. In survivors (n = 69), gestational age (p<0.001) and birth weight (p<0.003) were significantly lower in infants who developed grade 3 ROP while CRIB (p<0.002), oxygenation index (p<0.02) but not MAP were significantly higher in grade 3 ROP cases. All markers of duration of respiratory disease (ventilation (p<0.02), respiratory support (p<0.001), supplemental oxygen (p<0.005)) were significantly higher in survivors who developed grade 3 ROP.

Forty seven (68%) survivors received dopamine. Incidence of any retinopathy, grade 3 ROP, and threshold ROP was higher in infants who received dopamine during the first week of life (table 1). Maximal dose (p<0.05) was significantly higher and duration (hours) (p<0.03) in the first week of life was significantly longer in infants who developed grade 3 ROP. When the strongest marker of cardiovascular instability—that is, duration (hours) of dopamine administration in the first week of life was entered in a multiple regression model with either maximal oxygenation index or maximal MAP or CRIB score, dopamine was no longer an independent risk factor to develop threshold ROP.

Table 1.

Dopamine use in survivors (n = 69) and its association with the incidence and severity of retinopathy in extreme low birthweight infants (p value calculated using χ² test)

	Dopamine	No dopamine	p Value
Number	47	22
No ROP	29%	45%	NS
Any ROP	70%	54%	NS
Grade 3 ROP	44%	27%	NS
Threshold ROP	30%	5%	<0.04

Comment

In line with Mizoguchi, an association of dopamine with an increased risk to develop ROP was found.² In addition, dopamine was no longer an independent risk factor of developing grade 3 ROP after correction for either CRIB score or oxygenation index in a multiple regression model.

Although it is hypothesised that a synergistic effect of hypoxia and dopamine might induce retinal vascular constriction in early neonatal life,^2,6,7 it is more likely that this risk factor is merely an indicator of cardiovascular instability and not an aetiological factor involved in the pathogenesis of ROP.