Weight gain measured at 6 weeks after birth as a predictor for severe retinopathy of prematurity: study with 317 very low birth weight preterm babies

Our study showed that WG proportion under 51.2% from birth to 6 weeks of life was an important and independent risk factor for severe ROP, and was capable of predicting the development of severe ROP needing treatment in the group of VLBW preterm babies. Our results are also in accordance with the longitudinal growth curves for hospitalized VLBW described by Ehrenkranz et al. [13] in 1999, and widely used in modern neonatology, in which these patients are expected to regain weight, around 50% of their BW, after completed 6 weeks of life.

ROP pathogenesis is still incompletely understood. For many years, the high oxygen levels administered to neonates was considered the main risk factor for ROP development [14]; however, the disease kept occurring even after careful control in oxygen administration [15]. To date, no absolutely safe level for oxygen use has been demonstrated [16, 17]. In our institution, oxygen administration is always monitored by pulse oxymetry, with recommended saturation between 88-94%. The overall incidence of ROP in our study was similar to other published results [18‐20].

The presence of any stage intraventricular hemorrhage was significant as a risk factor for ROP in our cohort of patients. Procianoy et al. [21], in 1981, related a significant association between cicatricial ROP and intraventricular hemorrhage in 138 VLBW. Christiansen et al. [22], in 2002, published a significant association between intraventricular hemorrhage and ROP in 60 VLBW where neonates with more severe intraventricular hemorrhage grades reached severe ROP.

Low BW and GA have been implicated most directly in ROP development [23‐25], but low WG as an independent risk factor for ROP development was just recently described. Hall et al. [26], in 1995, related a low WG associated with severity of ROP in four survivors in a birth of quintuples with identical GA and similar BW. Homes and Düffner [27], in 1996, demonstrated that rats submitted to growth retardation developed retinal neovascularization more frequently and more severely.

A retrospective study by Wallace et al. [7], published in 2000, analyzed postnatal WG and another 11 risk factors in a group of 111 neonates. They suggested that WG under 50% of BW at 6 weeks of life indicated an important risk for severe forms of ROP. According to Wallace et al., the study results could not be explained by the difference in the average BW among the patients with severe ROP and those with less severe or no ROP, but by the difference in WG proportion in the 6-week period after premature birth, and they concluded that there was a significant difference in WG in infants with severe and discrete or no ROP. Shaffer et al. [28] previously claimed that the absolute ratio of WG in VLBW would be proportional to the neonate’s BW, and consequently, the expected proportion of WG should be the same for preterm infants with different BW in the same period of life.

Allegaert et al. [8], in 2003, in a prospective case-control study registered perinatal growth characteristics of 31 neonates with ROP threshold disease and in 31 neonates with the same GA who didn’t develop ROP. They concluded that small for GA preterm newborns and those with intrauterine growth restriction had an increased risk of developing ROP threshold disease. In contrast, the relative WG (grams/kg/day) was not significantly different in the group with ROP and in the control group.

Recently, some studies showed the relation between the insulin-like growth factor-I (IGF-I) and ROP development. Hellström et al. [29] reported that in preterm infants with the same GA, IGF-I serum levels during the postnatal period were significantly and proportionally lower in those that developed ROP than in the ones who did not. In 2006, Löfqvist et al. [9] showed that weekly measurements of postnatal WG together with a serum level of IGF-I were a useful marker for the risk of severe ROP. In this article, the authors disclosed some very important conclusions indicating the need to monitor the postnatal factors of weight, IGF-I level and IGF binding protein 3 level in order to enhance the clinician’s ability to identify patients who will require treatment for ROP. Unfortunately, this approach seems to have some difficulties of use among ophthalmologists during the screening sessions to detect ROP, mainly in the middle-income countries context; once-weekly laboratory measurements of IGF-I and IGF binding protein 3 serum levels are cost expensive for national health care systems, and also, these laboratory tools are not widely available in most of the Latin American countries.

Engström et al. [30] related the role of maternal factors, postnatal nutrition and the WG in regulation of serum IGF-I among preterm infants. IGF-I is present in the natural maternal milk, and so an adequate natural breast-feeding could help in the prevention of ROP.

A question beyond the scope of our study is about why these babies are poor at gaining weight. The most practical answer to this question could be because they are sicker babies; but once we know about low WG as a risk factor for ROP, it is possible to follow-up these babies closely before the development of treatable ROP, trying to improve their clinical conditions. According to Ehrenkranz et al. [13], the WG after the second week of life is related to the nutritional support, and healthier babies usually gain weight faster than sicker babies. The low WG in the postnatal period could be indicative for the development of general morbidities, some of them also related with ROP development, such as sepsis, intraventricular hemorrhage, bronchopulmonary dysplasia, or necrotizing enterocolitis.