Erythropoietin and retinopathy of prematurity: a retrospective cohort study in Japan, 2008-2018.

BACKGROUND: Erythropoietin has an angiogenic effect on the retina and might increase the risk of retinopathy of prematurity (ROP). METHODS: This retrospective cohort study included infants born at 22 to 27 weeks' gestation between 2008 and 2018 who were admitted to neonatal intensive care units (NICUs). We compared mortality and morbidities between infants who received erythropoietin and those who did not. RESULTS: Among 18,955 livebirth infants, this study included 16,031 infants, among which 14,373 infants received erythropoietin. The risk of ROP requiring treatment was significantly higher in the erythropoietin group than in the control group (33% vs. 26%; aOR 1.50 [95% CI 1.28-1.76]). On the other hand, the erythropoietin group had lower risks of death and necrotizing enterocolitis. CONCLUSIONS: This study with a large sample size found that erythropoietin use was associated with increased risk of ROP requiring treatment, while being associated with reductions in deaths and NEC.

Inhaled Nitric Oxide Therapy in the Post-Acute Phase in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: To determine the trends in inhaled nitric oxide (iNO) utilization in the late phase of hospitalization in a large Japanese cohort of extremely preterm infants and evaluate its benefit on long-term outcomes. STUDY DESIGN: This was a retrospective multicenter cohort study of 15 977 extremely preterm infants born at <28 weeks of gestational age between 2003 and 2016, in the Neonatal Research Network, Japan. Demographic characteristics, morbidity, and mortality were compared between extremely preterm infants with and without post-acute iNO therapy. Multivariable logistic analysis was performed to determine factors associated with post-acute iNO and its impact on neurodevelopmental outcomes at 3 years of age. RESULTS: Post-acute iNO utilization rates increased from 0.3% in 2009 to 1.9% in 2016, even under strict insurance coverage rules starting in 2009. Gestational age (1-week increment; aOR 0.82, 95% CI 0.76-0.88), small for gestational age (1.47, 1.08-1.99), histologic chorioamnionitis (1.50, 1.21-1.86), 5-minute Apgar score <4 (1.51, 1.10-2.07), air leak (1.92, 1.30-2.83), and bubbly/cystic appearance on chest X-Ray (1.68, 1.37-2.06) were associated with post-acute iNO. Post-acute iNO was not associated with neurodevelopmental outcomes at 3 years of age. CONCLUSIONS: The increasing post-acute iNO utilization rate among extremely preterm infants has been concurrent with improved survival rates of extremely preterm infants in Japan. Infants treated with post-acute iNO had more severe disease and complications than the comparison group, but there were no differences in neurodevelopmental outcome at 3 years. This suggests post-acute iNO may benefit extremely preterm infants.

Prognosis of 22- and 23-Gestational-Week-Old Infants at Our Facility: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to compare inborn infants aged 22 and 23 gestational weeks at our hospital to assess for differences in survival and long-term prognosis. STUDY DESIGN: We retrospectively analyzed 22- and 23-gestational-weeks-old infants born in our hospital between January 2011 and December 2018. The prognosis of inborn infants in Japan was also calculated using the Neonatal Research Network of Japan (NRNJ) data during the same period. RESULTS: The survival rates at our institution's neonatal intensive care unit discharge, including stillbirth, were 72 and 89% at 22 and 23 gestational weeks, respectively. The mortality rate and neurodevelopmental impairment (NDI) rate at 3 years of age, including stillbirth, were 58 and 32% at 22 and 23 weeks, respectively. Cerebral palsy, mental developmental retardation, visual impairment, and hearing impairment defined NDI. The prognosis at our hospital was better than the average calculated using NRNJ data. Survival rates varied among facilities, and some facilities had survival rates similar to that of our hospital. CONCLUSION: The prognosis of 22-gestational-week-old inborn infants was inferior to that of 23 gestational weeks in our institution but was better than previously reported. If aggressive treatment is provided, survival without sequelae can be fully expected even for 22-gestational-week-old infants. KEY POINTS: · We examined babies of gestation ages 22 and 23 weeks.. · We examined the survival and neurological prognoses.. · We compared our facility with that in entire Japan..

Association of low birthweight and premature birth with hypertensive disorders in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that women born preterm or small have an increased risk of experiencing hypertensive disorders during pregnancy; however, a quantitative summary of the evidence on this issue is unavailable. OBJECTIVE: We aimed to systematically review the literature to describe the association between being born preterm, low birthweight (LBW), or small for gestational age (SGA), and future gestational hypertension, preeclampsia, or eclampsia. METHODS: We searched the MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and ICTRP databases. We included all cohort and case-control studies examining the association between LBW, preterm birth, or SGA and hypertensive disorders in pregnancy. We pooled the odds ratios and 95% confidence intervals using the DerSimonian and Laird random-effects model. We assessed the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluation criteria. RESULTS: Eleven studies were identified, totalling 752 316 participants. Being born preterm, LBW, or SGA was associated with gestational hypertension [pooled odds ratio (OR), 1.31; 95% confidence interval (CI) 1.15-1.50; moderate certainty of evidence] and preeclampsia (pooled OR, 1.35; 95% CI 1.23-1.48; moderate certainty of evidence). No study measured eclampsia as an outcome. CONCLUSION: Women born preterm, LBW, or SGA have an increased risk of gestational hypertension and preeclampsia. The course of the mother's own birth might be used to identify women at risk of gestational hypertension and preeclampsia.

Gestational diabetes mellitus in women born small or preterm: Systematic review and meta-analysis.

PURPOSE: There is some evidence that women born preterm or with low birth weight (LBW) have an increased future risk of gestational diabetes mellitus (GDM) during pregnancy; however, a quantitative summary of evidence is lacking. In this systematic review and meta-analysis, we examined the published data to investigate whether being born preterm, with LBW or small for gestational age (SGA) are associated with GDM risk. METHODS: We searched the MEDLINE, Embase, and CINAHL databases and study registries, including ClinicalTrials.gov and ICTRP, from launch until 29 October 2020. Observational studies examining the association between birth weight or gestational age and GDM were eligible. We pooled the odds ratios and 95% confidence intervals using the DerSimonian and Laird random-effects model. RESULTS: Eighteen studies were included (N = 827,382). The meta-analysis showed that being born preterm, with LBW or SGA was associated with increased risk of GDM (pooled odds ratio = 1.84; 95% confidence interval: 1.54-2.20; I2 = 78.3%; τ2 = 0.07). Given a GDM prevalence of 2.0, 10, and 20%, the absolute risk differences were 1.6%, 7.0%, and 11.5%, respectively. The certainty of the evidence was low due to serious concerns of risk of bias and publication bias. CONCLUSIONS: Women born prematurely, with LBW or SGA status, may be at increased risk for GDM. However, whether this should be considered in clinical decision-making depends on the prevalence of GDM.

Non-invasive neurally adjusted ventilatory assist versus nasal intermittent positive-pressure ventilation in preterm infants born before 30 weeks' gestation.

BACKGROUND: Non-invasive neurally adjusted ventilatory assist (NIV-NAVA), a mode of non-invasive ventilation (NIV) controlled by diaphragmatic electrical activity, may be superior to other NIV as a respiratory support after extubation in preterm infants, but no report has compared NIV-NAVA with other NIV methods. We evaluated the effectiveness and adverse effects of NIV-NAVA after extubation in preterm infants <30 weeks of gestation. METHODS: This retrospective study involved patients who were born before 30 weeks of gestation. We mainly used NIV-NAVA or nasal intermittent positive-pressure ventilation (NIPPV) for preterm infants as the NIV after extubation and compared these two groups. The primary outcome was treatment failure. The secondary outcomes were extubation failure and adverse events. Treatment failure was defined as a change of NIV (NIPPV was switched to NIV-NAVA, or NIV-NAVA was switched to NIPPV) or reintubation ≤7 days after extubation. RESULTS: Fifteen patients were in the NIV-NAVA group, and 19 were in the NIPPV group. The gestational age of the NIV-NAVA group was younger than that of the NIPPV group (25.7 ± 2.4 weeks vs 27.3 ± 1.8 weeks). Treatment failure occurred in six cases (40%) in the NIV-NAVA group and in nine cases (47.4%) in the NIPPV group, and no significant difference was demonstrated. No significant difference in adverse events was noted. CONCLUSIONS: NIV-NAVA has advantages compared with NIPPV as the NIV for premature infants after extubation. NIV-NAVA can also be used safely without a significant difference in the rate of complications compared with NIPPV.

Human milk reduces the risk of retinal detachment in extremely low-birthweight infants.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of blindness in children. Because the use of oxygen is a known risk factor for development of ROP, supplemental oxygen is used carefully. However, it does not necessarily reduce the morbidity of ROP-induced blindness. The aim of the present study was to identify the possible risk factors for progression to retinal detachment, a most relevant cause of visual impairment, in extremely low-birthweight infants (ELBWI). METHODS: The medical records of the 42 ELBWI who were admitted to the neonatal intensive care unit in Asahikawa Kosei Hospital from April 1999 to March 2004 were retrospectively reviewed. Seven infants (16.7% of the ELBWI) developed retinal detachment and two of them became blind. Perinatal and postnatal variables in these infants with retinal detachment were compared with those in infants without retinal detachment. RESULTS: A striking difference in the daily intake of human milk was found between the infants with or without retinal detachment when their gestational ages at birth were matched. The infants without retinal detachment were fed more human milk (67-83% volume of total nutritional intake) as compared to those with retinal detachment (24-38% volume of total nutritional intake) at a specific postnatal period, 5-7 weeks postnatal age. CONCLUSIONS: Human milk may contain some beneficial factors to reduce the severity of ROP. Identifying these factors in human milk may contribute to development of a strategy to rescue premature infants from blindness.