Dataset Information

Association of Maternal Preeclampsia With Infant Risk of Premature Birth and Retinopathy of Prematurity.

ABSTRACT:

Importance

Studies report conflicting associations between preeclampsia and retinopathy of prematurity (ROP). This study provides explanations for the discrepancies to clarify the relationship between preeclampsia and ROP.

Objective

To evaluate the association of maternal preeclampsia and risk of ROP among infants in an unrestricted birth cohort and a restricted subcohort of preterm, very low birth weight (P-VLBW) infants.

Design, setting, and participants

A retrospective review of 290 992 live births within the Intermountain Healthcare System in Utah from January 1, 2001, through December 31, 2010, was performed. Generalized estimating equations for logistic regressions with covariate adjustment were applied to relate ROP to preeclampsia among the full cohort and in a subcohort of P-VLBW infants born at younger than 31 weeks' gestation and weighing less than 1500 g.

Main outcomes and measures

The occurrence of ROP was related to maternal preeclampsia in the full cohort and in a subcohort of P-VLBW infants.

Results

In the full cohort, 51% of the infants were male and the mean (SD) gestational age was 38.38 (1.87) weeks. In the P-VLBW cohort, 55% were male and the mean (SD) gestational age was 26.87 (2.40) weeks. In the full cohort, preeclampsia was associated with an increased risk of all ROP (adjusted odds ratio [aOR], 2.46; 95% CI, 2.17-2.79; P < .001), severe ROP (aOR, 5.21; 95% CI, 3.44-7.91; P < .001), infant death (aOR, 1.66; 95% CI, 1.16-2.38; P = .006), and giving birth to a P-VLBW infant (aOR, 7.74; 95% CI, 6.92-8.67; P < .001). In the P-VLBW subcohort, preeclampsia was inversely associated with the development of all ROP (aOR, 0.79; 95% CI, 0.68-0.92; P = .003), severe ROP (aOR, 0.62; 95% CI, 0.36-1.06; P = .08), and infant death (aOR, 0.19; 95% CI, 0.11-0.32; P < .001).

Conclusions and relevance

Preeclampsia was associated with an increased risk of developing ROP among an unrestricted cohort but with a reduced risk of ROP among a restricted subcohort of P-VLBW infants. Although the conflicting associations in the full and P-VLBW cohorts may reflect true differences, the association of a reduced risk of ROP among the P-VLBW subcohort also may reflect biases from restricting the cohort to prematurity, because prematurity is an outcome of preeclampsia.

SUBMITTER: Shulman JP

PROVIDER: S-EPMC5710540 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceMost premature infants will not develop retinopathy of prematurity (ROP) of clinical relevance, yet screening evaluations often continue beyond hospital discharge, even for those infants without ROP.ObjectivesTo identify the characteristics of infants at low risk for ROP, for whom further postdischarge screening may be of limited value.Design, setting, and participantsThis study took place in North American neonatal intensive care units where clinicians had expertise in ROP. Infants with birth weight less than 1251 g who were born at or transferred into an Telemedicine Approaches to Evaluating Acute-Phase ROP (e-ROP) study center were enrolled. The study included post hoc analysis of prospectively collected in-hospital ROP examination results among infants enrolled in the e-ROP study. We characterized infants without ROP and performed logistic regression on the subset of infants who were 27 to 33 weeks' gestational age to determine characteristics associated with the absence of ROP during all in-hospital examinations.Main outcomes and measuresThe main measure was the absence of ROP prior to hospital discharge; the main outcome was treatment for ROP.ResultsA total of 1257 infants born at 22 to 35 weeks' gestation (median [interquartile range (IQR)], 26 [25-28] weeks) with birth weights less than 1251 g (median [IQR], 860 [690-1040] g) underwent 4113 ROP examinations between 31 and 47 weeks' postmenstrual age. Overall, 1153 examinations (38%) showed no ROP, and 456 infants (36%) did not have ROP prior to study center discharge or study end point. Among infants without ROP during examinations at 32 and 33 weeks' postmenstrual age, 16 (9.4%) and 14 (5.3%) subsequently underwent ROP treatment, respectively. At hospital discharge, there was no ROP in 59% of infants of 27 to 33 weeks' gestational age, compared with 15% of those who were less than 27 weeks' gestational age (difference, 44% [95% CI, 38.5%-48.1%]; P ≤ .001). With more than 85% follow-up among infants without ROP by 37 weeks' postmenstrual age, none (95% CI, 0%-0.98%) were treated for ROP. In multivariate analysis of infants born at 27 to 33 weeks' gestation, larger birth weight (OR, 4.1 [95% CI, 1.6-10.3]) and higher gestational age (OR, 4.0 [95% CI, 1.5-10.8]) were significantly associated with absence of ROP.Conclusions and relevanceThese findings suggest that, for infants of 27 weeks' gestational age or greater and birth weights larger than 750 g, if no ROP has been detected by discharge at near-term postmenstrual age, then further ROP surveillance has limited value. Studies of all infants at risk are needed to develop more specific, objective criteria for termination of ROP surveillance and focus resources on infants at higher risk of ROP.Trial registrationClinicalTrials.gov Identifier: NCT01264276.

Project description:Importance:To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives:To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants:In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures:The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results:Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance:This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.

Project description:ImportanceEarly slow postnatal weight gain, a surrogate for low insulinlike growth factor 1 (IGF-1) levels, is predictive of retinopathy of prematurity (ROP). While low IGF-1 levels inhibit retinal vessel growth, a later rise theoretically activates vascular endothelial growth factor, causing neovascularization. Rate of rise of IGF-1 level is represented by weight gain acceleration (WGA) and may be used to evaluate risk of ROP.ObjectiveTo evaluate whether faster WGA during a later postnatal period is associated with a higher, rather than lower, risk of severe ROP.Design, setting, and participantsThis secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) study included 6835 infants undergoing ROP examinations from 29 hospitals in North America from January 2006 to June 2012. Data were analyzed from September to December 2016.Main outcomes and measuresEarly weight gain rate (WGR) during 29 to 33 weeks' postmenstrual age and late WGA during 34 to 38 weeks' postmenstrual age were determined using linear regression of daily weight measurements and changes in daily weight measurements, respectively. The primary outcome was the association of late WGA with severe ROP.ResultsOf the 6835 included infants, the mean (SD) birth weight was 1086 (357) g, and the mean (SD) gestational age was 27.9 (2.5) weeks. Risk of severe ROP increased with increasing late WGA up to about the 80th percentile of WGA. After adjusting for birth weight and gestational age, among infants in the lowest early WGR tertile, there was no association of late WGA with severe ROP, and among infants in the moderate and highest early WGR tertiles, the moderate WGA tertiles had the highest risk of ROP (moderate early WGR tertile: adjusted odds ratio, 1.38; 95% CI, 0.98-1.94; highest early WGR tertile: adjusted odds ratio, 1.63; 95% CI, 1.02-2.60).Conclusions and relevanceAlthough much attention has been paid to the association of slow weight gain with ROP, the association may be more complex than appreciated. These findings suggest that low early WGR is associated with severe ROP regardless of subsequent WGA, but if early WGR is moderate or high, subsequent rapid rises in WGR are associated with increasing risk of severe ROP. If validated in additional cohorts, this finding may affect potential therapies, such as the timing of IGF-1 supplementation.