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Supplemental Digital Content is available in the text Objectives: Prenatal substance exposure is associated with abnormal visual evoked potentials in offspring, but whether ocular abnormalities are present past infancy is unclear. We determined the association between prenatal substance exposure and hospitalizations for eye disorders in childhood. Methods: We conducted a longitudinal cohort study of 794,099 infants born between 2006 and 2016 in all hospital centers in Quebec, Canada. We identified infants prenatally exposed to opioids, cocaine, cannabis, and other illicit substances and followed them over time to assess eye disorders that required in-hospital treatment, including retinal detachment and breaks, strabismus, and other ocular pathologies. We calculated incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) for the association of prenatal substance exposure with risk of eye disorders, adjusted for patient characteristics. Results: Infants exposed to substances prenatally had a higher incidence of hospitalizations for eye disorders compared with unexposed infants (47.0 vs 32.0 per 10,000 person-years). Prenatal substance exposure was associated with 1.23 times the risk of hospital admission for any eye disorder during childhood compared with no exposure (95% CI 1.04–1.45). Risks were greatest for strabismus (HR 1.55, 95% CI 1.16–2.07) and binocular movement disorders (HR 1.96, 95% CI 1.00–3.83). Opioid use was strongly associated with the risk of ocular muscle disorders (HR 3.15, 95% CI 1.98–5.01). Conclusions: Prenatal substance exposure is significantly associated with future hospitalizations for eye disorders in childhood. Efforts to minimize substance use in women of reproductive age are needed in light of the current opioid epidemic. [ABSTRACT FROM AUTHOR]

Preterm birth incurs an increased risk of early cardiovascular events and death. In the general population, cardiovascular risk factors cluster in the context of inflammation and oxidative stress. Whether this also occurs in young adults born preterm is unknown. We analyzed 101 healthy young adults (ages 18-29) born preterm (≤29 weeks of gestation) and 105 full-term controls, predominantly (90%) white. They underwent a comprehensive clinical and biological evaluation, including measurement of blood pressure, lung function (spirometry), glucose metabolism (fasting glucose, glycated hemoglobin, and oral glucose tolerance test), as well as biomarkers of inflammation and oxidative stress. Individuals born preterm were at higher risk than those born full-term of stage ≥1 hypertension (adjusted odds ratio, 2.91 [95% CI, 1.51-5.75]), glucose intolerance (adjusted odds ratio, 2.22 [95% CI, 1.13-4.48]), and airflow limitation (adjusted odds ratio, 3.47 [95% CI, 1.76-7.12]). Hypertension was strongly associated with adiposity and with glucose intolerance in participants born full-term but not in those born preterm. We did not find any group difference in levels of biomarkers of inflammation and oxidative stress. In individuals born preterm, inflammation, and oxidative stress were not related to hypertension or glucose intolerance but were associated with adiposity. In those born preterm, cardiovascular risk factors were not related to each other suggesting different pathophysiological pathways leading to the development of cardiovascular risk following preterm birth. Clinicians should consider screening for these abnormalities irrespectively of other risk factors in this at-risk population. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03261609. [ABSTRACT FROM AUTHOR]

Preterm birth is associated with proinflammatory conditions and alterations in adult cardiac shape and function. Neonatal exposure to high oxygen, a rat model of prematurity-related conditions, leads to cardiac remodeling, fibrosis, and dysfunction. TLR (Toll-like receptor) 4 signaling is a critical link between oxidative stress, inflammation, and the pathogenesis of cardiovascular diseases. The current study sought to investigate the role of TLR4 signaling in neonatal oxygen-induced cardiomyopathy. Male Sprague-Dawley pups were kept in 80% oxygen or room air from day 3 to 10 of life and treated with TLR4 antagonist lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides(LPS-RS) or saline. Echocardiography was performed at 4, 7, and 12 weeks. At 12 weeks, intraarterial blood pressure was measured before euthanization for histological and biochemical analyses. At day 10, cardiac TLR4, Il (interleukin) 18, and Il1β expression were increased in oxygen-exposed compared with room air controls. At 4 weeks, compared with room air-saline, saline-, but not LPS-RS treated-, oxygen-exposed animals, exhibited increased left ventricle mass index, reduced ejection fraction, and cardiac output index. Findings were similar at 7 and 12 weeks. LPS-RS did not influence echocardiography in 12 weeks room air animals. Systolic blood pressure was higher in saline- but not LPS-RS treated-oxygen-exposed animals compared with room air-saline and -LPS-RS controls. LPS-RS prevented cardiac fibrosis and cardiomyocytes hypertrophy, the increased TLR4, Myd88, and Il18 gene expression, TRIF expression, and CD68+ macrophages infiltration associated with neonatal oxygen exposure, without impact in room air rats. This study indicates that neonatal exposure to high oxygen programs TLR4 activation, which contributes to cardiac remodeling and dysfunction. [ABSTRACT FROM AUTHOR]

Preterm birth incurs a higher risk for adult cardiovascular diseases, including hypertension. Because preterm birth may impact nephrogenesis, study objectives were to assess renal size and function of adults born preterm versus full term and to examine their relationship with blood pressure (BP; 24-hour ambulatory BP monitoring) and circulating renin-Ang (angiotensin) system peptides. The study included 92 young adults born (1987-1997) preterm (≤29 weeks of gestation) and term (n=92) matched for age, sex, and race. Young adults born preterm had smaller kidneys (80±17 versus 90±18 cm3/m2; P<0.001), higher urine albumin-to-creatinine ratio (0.70; interquartile range, 0.47-1.14 versus 0.58, interquartile range 0.42 to 0.78 mg/mmol, P=0.007), higher 24-hour systolic (121±9 versus 116±8 mm Hg; P=0.001) and diastolic (69±5 versus 66±6 mm Hg; P=0.004) BP, but similar estimated glomerular filtration rate. BP was inversely correlated with kidney size in preterm participants. Plasma Ang I was higher in preterm versus term participants (36.3; interquartile range, 13.2-62.3 versus 19.4; interquartile range, 9.9-28.1 pg/mL; P<0.001). There was no group difference in renin, Ang II, Ang (1-7), and alamandine. In the preterm, but not in the term group, higher BP was significantly associated with higher renin and alamandine and lower birth weight and gestational age with smaller adult kidney size. Young adults born preterm have smaller kidneys, higher urine albumin-to-creatinine ratio, higher BP, and higher circulating Ang I levels compared with term controls. Preterm young adults with smaller kidneys have higher BP. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03261609. [ABSTRACT FROM AUTHOR]

Background: We identified maternal and neonatal birth characteristics that were associated with organ or tissue transplants during childhood., Methods: We designed a retrospective cohort study of the population of children born between 2006 and 2019 in Quebec, Canada. The exposure included birth complications such as congenital anomaly, neonatal blood transfusion, and oligohydramnios. The main outcome measure was organ or tissue transplantation before 14 y of age. We categorized transplants according to type (major organs versus superficial tissues). To determine the association of birth characteristics with risk of pediatric transplant, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards models adjusted for potential confounders., Results: The cohort comprised 1 038 375 children with 7 712 678 person-years of follow-up, including 436 children who had transplants before 14 y of age. Birth complications were predominantly associated with major organ transplants. Congenital anomaly was associated with heart or lung (HR, 10.41; 95% CI, 5.33-20.33) and kidney transplants (HR, 13.69; 95% CI, 7.48-25.06), compared with no anomaly. Neonatal blood transfusion was associated with all major organ transplants, compared with no transfusion. Maternal complications were not as strongly associated with the risk of childhood transplant, although oligohydramnios was associated with 16.84 times (95% CI, 8.09-35.02) the risk of kidney transplant, compared with no oligohydramnios., Conclusions: Adverse birth outcomes such as congenital anomaly, neonatal blood transfusion, and maternal oligohydramnios are associated with a greater risk of transplantation before 14 y of age. Maternal and neonatal birth outcomes may be useful predictors of transplantation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)