The relationship between severe hypertensive diseases of pregnancy and moderate-severe bronchopulmonary dysplasia.

OBJECTIVE: Determine the association between severe hypertensive disease of pregnancy (HDP) with moderate-severe bronchopulmonary dysplasia (BPD) in preterm infants (< 31 weeks' gestation). STUDY DESIGN: Preterm birth cohort study of 693 mother-infant dyads. Severe HDP was defined as severe preeclampsia, HELLP syndrome or eclampsia. The outcome was moderate-severe BPD classified at 36 weeks corrected gestational age, per the NICHD Consensus statement. RESULTS: 225 (32%) mothers developed severe HDP and 234 (34%) infants had moderate-severe BPD. There was an interaction between severe HDP and gestational age (p = 0.03). Infants born at < 25 weeks gestation to mothers with HDP had increased odds for moderate-severe BPD compared to infants of normotensive mothers delivering at the same gestational age. Infants born > 28 weeks to mothers with severe HDP had decreased odds for the outcome, though not statistically significant. CONCLUSIONS: Severe HDP has a differential effect on the development of moderate-severe BPD based on gestational age.

The Relationship Between Severe Hypertensive Diseases of Pregnancy and Moderate-Severe Bronchopulmonary Dysplasia.

Objective: Determine the association between severe hypertensive disease of pregnancy (HDP) with moderate-severe bronchopulmonary dysplasia (BPD) in preterm infants (< 31 weeks' gestation). Study Design: Preterm birth cohort study of 693 mother-infant dyads. Severe HDPwas defined as severe preeclampsia, HELLP syndrome or eclampsia. The outcome was moderate-severe BPD classified at 36 weeks corrected gestational age, based on the NICHD Consensusstatement. Results: 225 (32%) mothers developed severe HDP and 234 (34%) infants hadmoderate-severe BPD. There was an interaction between severe HDP and gestational age (p=0.03). Infants born at earlier gestational ages to mothers with HDP had increased odds for moderate-severe BPD compared to infants of normotensive mothers delivering at the same gestational age. Infants born at later gestational ages to mothers with severe HDP had decreased odds for the outcome. Conclusions: Severe HDP has a differential effect on the development of moderate-severe BPD based on gestational age.

Comparison between weight gain and Fenton preterm growth z scores in assessing the risk of retinopathy of prematurity.

Several studies have shown that postnatal weight gain is a significant predictor for retinopathy of prematurity (ROP) in preterm infants. Using a cohort of 1,301 infants from a single-center ROP registry, we investigated whether incorporation of changes in Fenton preterm growth curve z scores (ie, deviation from the population average) provides improved predictive ability for developing ROP compared to weight gain alone. Three logistic regressions were fit to severe ROP: (1) baseline model that included gestational age and birth weight, (2) the baseline model adding weight gain, and (3) the baseline model adding change in z score. The area under the receiver operating characteristic curve (C index) was used to compare models. Both weight gain and change in z scores were significant predictors after adjusting for birth weight (P = 0.01) and gestational age (P < 0.01). The C indices were not significantly improved by including weight gain or z score to the baseline model; however, for a subset of subjects, change in weight z score may be a more useful measure compared to simple weight gain with regards to assessing risk for severe ROP.

Relationship between severe bronchopulmonary dysplasia and severe retinopathy of prematurity in premature newborns.

BACKGROUND: Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two adverse sequelae of preterm birth associated with abnormal vascular development. The purpose of this study was to characterize the relationship between these two outcomes at a single institution. METHODS: The medical records of infants screened for ROP at the University of Colorado Hospital between January 2012 and December 2017 were reviewed retrospectively. ROP was classified according to Early Treatment Retinopathy of Prematurity (ET-ROP) criteria; BPD, according to the 2010 Criteria from the National Institute for Child Health and Human Development. We examined the relationship between moderate-severe BPD and the development of severe ROP (type 1 or 2) using univariate analysis and multivariable logistic regression with the odds ratio as a measure of association. Covariates included gestational age and birth weight at delivery. RESULTS: A total of 625 cases were reviewed. Of these, 64 infants (10%) developed severe ROP and 176 (28%) infants developed moderate-severe BPD. We found a significant relationship between these two outcomes following adjustments for gestational age, birth weight, and multiparity (OR = 3.2; 95% CI, 1.6-6.5 [P < 0.01]). CONCLUSIONS: In our cohort of preterm infants, we found a significant relationship between moderate-severe BPD with severe ROP. We hypothesize that these two neonatal outcomes have links with a common pathogenesis.

Delayed resolution of retinopathy of prematurity.

PURPOSE: To compare the characteristics of infants whose retinopathy of prematurity (ROP) resolves in <50 weeks with those of infants whose ROP resolves in >50 weeks' postmenstrual age (PMA) in order to identify which infants are at risk for delayed resolution and to evaluate whether severe ROP developed after 50 weeks' PMA. METHODS: The medical records of infants screened for ROP from January 2008 to December 2016 at a tertiary care facility were reviewed retrospectively. Infants without follow-up prior to ROP resolution or complete retinal vascularization and those with retinal detachment were excluded. Delayed resolution of ROP was defined as presence of immature retinal vasculature at ≥50 weeks' PMA. The birth characteristics, neonatal complications, and ROP characteristics of infants with and without delayed resolution were compared. RESULTS: A total of 996 infants were included, of whom 136 (13.6%) showed delayed resolution. Increasing severity of ROP (higher stage, lower zone, plus/pre-plus disease) and type 2 ROP was associated with delayed resolution (P < 0.05). Other variables associated with delayed resolution included <28 weeks gestational age, ≤3rd percentile birth weight, positive blood culture sepsis, necrotizing enterocolitis, intraventricular hemorrhage, and bronchopulmonary dysplasia (P < 0.05). No infants developed type 1 after 50 weeks' PMA. After a prolonged follow-up course consistent with AAP guidelines, a single patient in our study cohort was treated at 81 weeks' PMA for persistent type 2 ROP. CONCLUSIONS: In our cohort, delayed resolution of ROP was more likely in infants with more severe ROP or a complex neonatal course. No patient with delayed resolution developed type 1 ROP after 50 weeks' PMA, supporting AAP guidelines.

The role of the maternal and fetal inflammatory response in retinopathy of prematurity.

PROBLEM: There is a paucity of research on the contribution of placental inflammation to severe retinopathy of prematurity (ROP). METHOD OF STUDY: A retrospective cohort study (n = 1217) was conducted of infants screened for ROP (2006-2016). The outcomes of the study were severe ROP (type 1 or type 2 ROP) and low grade ROP. We categorized the placental pathology as the presence of (i) maternal plus fetal inflammatory response, (ii) maternal inflammatory response only, (iii) fetal inflammatory response only and, (iv) no evidence of a maternal or fetal inflammatory response. The data were analyzed using univariate and multivariate logistic regression analyses (P < .05). RESULTS: In this cohort, the number of infants with the maternal plus fetal inflammatory response, the maternal inflammatory response only, the fetal inflammatory response only, and no maternal or fetal inflammatory response was 305 (25%), 82 (7%), 8 (1%), and 822 (67%), respectively. Adjusted for covariates, the maternal plus fetal inflammatory response was a significant risk factor for severe ROP (AOR = 2.6, 95% CI 1.1-5.9, P = .03). None of the categories of placental inflammation were significantly associated with low grade ROP. CONCLUSION: Placental pathology distinguished by the maternal plus fetal inflammatory response was a significant risk factor for severe ROP. Our study supports a link between intrauterine inflammatory events and the subsequent development of severe ROP.

The relationship of the subtypes of preterm birth with retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity is an adverse outcome of preterm birth and is a leading cause of childhood blindness. The relationship between the subtypes of preterm birth with retinopathy of prematurity is understudied. OBJECTIVE: To investigate whether there is a difference in the incidence of type 1 or type 2 retinopathy of prematurity in infants with preterm birth resulting from spontaneous preterm labor, a medical indication of preterm birth, or preterm premature rupture of the membranes. STUDY DESIGN: A retrospective cohort study was conducted of 827 infants screened for retinopathy of prematurity who were delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for retinopathy of prematurity defined as "infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for retinopathy of prematurity." Two independent reviewers masked to retinopathy of prematurity outcomes determined whether preterm birth resulted from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes. Discrepancies were resolved by a third reviewer. Data were analyzed with univariate and multivariable logistic regression. RESULTS: In our cohort, the frequency of preterm birth resulting from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes was 34%, 40%, and 26%, respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the preterm birth subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days - 36 weeks, 4 days); spontaneous preterm labor, 28 weeks 1 day ± 2 weeks, 3 days (23 weeks, 3 days - 33 weeks, 4 days); medical indication of preterm birth, 29 weeks, 1 day ± 2 weeks, 2 days (24-36 weeks, 4 days); preterm premature rupture of the membranes, 28 weeks, 4 days ± 2 weeks, 1 day (24-33 weeks, 1 day). Among infants with type 1, type 2, or no retinopathy of prematurity, the incidence of type 1 or type 2 retinopathy of prematurity in births from spontaneous preterm labor, medical indication of preterm birth, and preterm premature rupture of the membranes was 37 of 218 (17%), 27 of 272 (10%), and 10 of 164 (6%), respectively. Adjusted for gestational age, birth weight, and multiparity and compared with the preterm premature rupture of the membranes group, the odds ratios of spontaneous preterm labor and medical indication of preterm birth for type 1 or type 2 retinopathy of prematurity were 6.1 (95% confidence interval, 1.8 to 20, P = .003) and 5.5 (95% confidence interval, 1.4 to 21, P = .01), respectively. Among neonates born after preterm premature rupture of the membranes, the probability of developing type 1 or type 2 retinopathy of prematurity was greatest in infants with rupture of membrane duration of up to 24 hours. After 24 hours, the probability of developing type 1 or type 2 retinopathy of prematurity declined. The odds of developing type 1 or type 2 retinopathy of prematurity was 9.0 (95% confidence interval 2.3 to 34, P = .002) in infants who had preterm premature rupture of the membranes ≤ 24 hours compared with infants who had preterm premature rupture of the membranes > 24 hours. CONCLUSION: Type 1 or type 2 retinopathy of prematurity are adverse ocular outcomes linked with not only lower gestational age and birth weight at delivery but also with events in the intrauterine environment that trigger a preterm birth. The reduced incidence of type 1 or type 2 retinopathy of prematurity in the preterm premature rupture of the membranes group compared with other causes of preterm birth may be related to the perinatal therapies associated with preterm premature rupture of the membranes (such as corticosteroids, antibiotics, maternal-fetal surveillance), which may have an inhibitory effect on the development of retinopathy of prematurity. We suggest that the physiologic events that predispose infants to type 1 or type 2 retinopathy of prematurity begin before delivery.