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IMPORTANCE: Preterm infants screened for retinopathy of prematurity (ROP) are at risk for heterogenous neurodevelopment outcomes that are difficult to predict. OBJECTIVE: To characterize the potential association between socioeconomic and clinical risk factors and neurodevelopmental outcomes in a diverse, multicenter cohort of premature neonates screened for ROP. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study using electronic medical records and US Census Bureau income data. This study was performed at academic (University of California, Los Angeles [UCLA] Mattel Children’s Hospital and UCLA Santa Monica Hospital), community (Cedars-Sinai Medical Center), and LA county (Harbor-UCLA Medical Center) neonatal intensive care units. Participants included infants who met American Academy of Pediatrics guidelines for ROP screening and had records from at least 1 Bayley Scales of Infant and Toddler Development (BSID) neurodevelopment assessment between 0 and 36 months of adjusted age. Data analyses were conducted from January 1, 2011, to September 1, 2022. EXPOSURES: Demographic and clinical information, proxy household income, and health insurance type were collected as risk factors. MAIN OUTCOMES AND MEASURES: Neurodevelopmental outcomes in the cognitive, language, and motor domains measured via BSID were the primary outcomes. RESULTS: A total of 706 infants (mean [SD] age, 28.6 [2.4] weeks; 375 male [53.1%]) met inclusion criteria. In a multivariable model, which included adjustments for birth weight, sex, insurance type, intraventricular hemorrhage (IVH), and age at assessment, public health insurance was associated with a 4-fold increased risk of moderate to severe neurodevelopmental impairment (NDI) in cognitive and language domains (cognitive, odds ratio [OR], 3.65; 95% CI, 2.28-5.86; P = 8.1 × 10−8; language, OR, 3.96; 95% CI, 2.61-6.02; P = 1.0 × 10−10) and a 3-fold increased risk in the motor domain (motor, OR, 2.60; 95% CI, 1.59-4.24; P = 1.4 × 10−4). In this adjusted model, clinical factors that were associated with an increased risk of moderate to severe NDI included lower birth weight, diagnosis of IVH, male sex, and older age at time of Bayley assessment. In unadjusted analyses, infants who received either laser or anti-VEGF treatment, compared with infants without treatment-requiring ROP, had lower BSID scores in multiple domains at 0 to 12 months, 12 to 24 months, and 24 to 36 months (DATA). In the multivariable model, treatment type was no longer associated with worse neurodevelopmental outcomes in any domain. CONCLUSIONS AND RELEVANCE: Study results suggest an association between public insurance type and NDI in a diverse population screened for ROP, indicating the complexities of neurodevelopment. This study also supports the early neurodevelopmental safety of anti-VEGF treatment, as anti-VEGF therapy was not found to be independently associated with worse NDI in any domain.

This study examined the association between maternal variables and the development of any stage of retinopathy of prematurity. Our findings suggest that specific prenatal sociodemographic factors, social behaviors, and maternal comorbidities may affect the risk of retinopathy of prematurity in preterm infants.

Light‐sheet fluorescence microscopy (LSFM) introduces fast scanning of biological phenomena with deep photon penetration and minimal phototoxicity. This advancement represents a significant shift in 3‐D imaging of large‐scale biological tissues and 4‐D (space + time) imaging of small live animals. The large data associated with LSFM require efficient imaging acquisition and analysis with the use of artificial intelligence (AI)/machine learning (ML) algorithms. To this end, AI/ML‐directed LSFM is an emerging area for multiorgan imaging and tumor diagnostics. This review will present the development of LSFM and highlight various LSFM configurations and designs for multiscale imaging. Optical clearance techniques will be compared for effective reduction in light scattering and optimal deep‐tissue imaging. This review will further depict a diverse range of research and translational applications, from small live organisms to multiorgan imaging to tumor diagnosis. In addition, this review will address AI/ML‐directed imaging reconstruction, including the application of convolutional neural networks (CNNs) and generative adversarial networks (GANs). In summary, the advancements of LSFM have enabled effective and efficient post‐imaging reconstruction and data analyses, underscoring LSFM's contribution to advancing fundamental and translational research. The integration of artificial intelligence in light sheet imaging enhances the precision and efficiency of analyzing complex biological specimens, leading to more detailed and accurate insights into cellular and tissue structures.

IMPORTANCE: Previous studies suggest that race or ethnicity may be associated with risk for developing retinopathy of prematurity (ROP). Little is known about how socioeconomic factors mediate the relationship between race or ethnicity and ROP outcomes. OBJECTIVE: To evaluate how socioeconomic factors, in the context of race and ethnicity, are associated with ROP outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used US Census Bureau income data and electronic medical records from neonatal intensive care units at 4 hospitals, UCLA Mattel Children’s Hospital, UCLA Santa Monica Hospital, Cedars-Sinai Medical Center, and Harbor-UCLA Medical Center. Eligible participants included neonates born at a gestational age (GA) of 30 weeks or less, birth weight less than 1500 g, or a GA at birth greater than 30 weeks but with an unstable clinical course. Participants were screened for ROP between January 1, 2010, and December 31, 2020. EXPOSURES: Race and ethnicity data, GA, demographic and clinical information, proxy household income, and health insurance status were collected as risk factors. MAIN OUTCOMES AND MEASURES: Diagnosis and severity of ROP were the main study outcomes. Severity was determined according to a classification system developed by the Early Treatment for Retinopathy of Prematurity Cooperative Group. RESULTS: In a crude model, Hispanic neonates were more likely to be diagnosed with ROP (OR, 1.70; 95% CI, 1.20-2.42) and had more severe ROP (OR, 2.24; 95% CI, 1.21-4.15) compared with non-Hispanic White neonates; these associations were no longer found when adjusting for GA and socioeconomic factors (OR, 1.12; 95% CI, 0.68-1.82, and OR, 1.67; 95% CI, 0.80-3.52, for ROP diagnosis and severity, respectively). In a fully adjusted model, lower GA was the primary predictor of ROP incidence (OR, 0.52; 95% CI, 0.48-0.57; P < .001), and higher median household income was associated with higher GA (OR, 0.26; 95% CI, 0.09-0.43; P = .002). CONCLUSIONS AND RELEVANCE: In this cohort study, GA was the primary driver of disparities in ROP outcomes in a heterogeneous population of neonates in Los Angeles, California. When examined in the context of socioeconomic factors, GA did not differ between racial and ethnic groups. Studies of disparities associated with race and ethnicity should consider these constructs in conjunction with other sociodemographic factors and social determinants of health.

Cystoid macular edema (CME) has been reported in the neonatal period associated with preterm birth; however, its pathogenesis remains unclear and is likely multifactorial. The authors report the case of a preterm infant imaged using optical coherence tomography (OCT), which revealed severe CME that regressed after laser treatment. Because laser for retinopathy of prematurity aims to reduce vascular endothelial growth factor (VEGF) levels, this case considers the possibility of VEGF-mediated CME pathogenesis. Further, the authors provide additional evidence of the value of OCT for noninvasive visualization of the preterm retina; the modality provides an effective way to evaluate and monitor progression of CME.[[Ophthalmic Surg Lasers Imaging Retina. 2020;51:472–475.]

species (spp.) can be commensals or opportunistic pathogens of the urogenital tract, and they can be commonly isolated from amniotic fluid, placenta, and fetal/neonatal tissue or blood in mothers delivering prematurely or their preterm infants. Although the presence of Mycoplasmaspecies (spp.) can be commensals or opportunistic pathogens of the urogenital tract, and they can be commonly isolated from amniotic fluid, placenta, and fetal/neonatal tissue or blood in mothers delivering prematurely or their preterm infants. Although the presence of Mycoplasmaspp. has been associated with adverse maternal-fetal outcomes such as preterm birth and maternal chorioamnionitis, it is less clear whether vertical transmission to the neonate results in colonization or active infection/inflammation. Moreover, the presence of Mycoplasmaspp. in neonatal blood, cerebrospinal fluid, or tissue has been variably associated with increased risk of neonatal comorbidities, especially bronchopulmonary dysplasia (BPD). Although the treatment of the mother or neonate with antibiotics is effective in eradicating ureaplasma, it is not clear that the treatment is effective in reducing the incidence of major morbidities of the preterm neonate (eg, BPD). In this article, we review the animal and clinical data for ureaplasma-related complications and treatment strategies. [[Pediatr Ann. 2020;49(7):e305–e312.]

Arthrogryposis multiplex congenita (AMC) is a complex, etiologically diverse, clinical descriptor identified in a variety of diagnoses characterized by multiple congenital joint contractures. The root cause of AMC is decreased fetal movement in-utero, whether resulting from maternal or pregnancy influences, nervous system pathology, or an underlying genetic abnormality. Prenatal diagnosis via ultrasonography can be challenging and may require additional imaging techniques or studies. After birth, these infants may require assistance breathing and feeding depending on the underlying diagnosis. Physical therapy and surgical intervention of the contractures are the mainstays of therapy, and outcomes can be good when intervention is provided in a timely manner. Those infants with syndromic causes of arthrogryposis are more likely to have poor outcomes; therefore, determining the underlying etiology for AMC is important as this can influence counseling regarding individual prognosis as well as future pregnancies. Arthrogryposis multiplex congenita (AMC) is a complex, etiologically diverse, clinical descriptor identified in a variety of diagnoses characterized by multiple congenital joint contractures. The root cause of AMC is decreased fetal movement in-utero, whether resulting from maternal or pregnancy influences, nervous system pathology, or an underlying genetic abnormality. Prenatal diagnosis via ultrasonography can be challenging and may require additional imaging techniques or studies. After birth, these infants may require assistance breathing and feeding depending on the underlying diagnosis. Physical therapy and surgical intervention of the contractures are the mainstays of therapy, and outcomes can be good when intervention is provided in a timely manner. Those infants with syndromic causes of arthrogryposis are more likely to have poor outcomes; therefore, determining the underlying etiology for AMC is important as this can influence counseling regarding individual prognosis as well as future pregnancies. [[Pediatr Ann.2020;49(7):e299–e304.]

AbstractObjectives:To evaluate the utility of tracheal aspirates in suspected pneumonia in intubated neonates and to measure the burden of antibiotic use associated with a positive tracheal aspirate culture.Design:Retrospective cohort study between January 2016 and December 2017.Setting:A level IV neonatal intensive care unit (NICU).Patients:Intubated patients with a tracheal aspirate culture.Methods:Data on temporally associated clinical measures of illness, laboratory and radiographic testing, and clinical demographic information were analyzed.Results:Positive tracheal aspirate cultures were associated with lower birth weight and a normal immature to total neutrophil ratio (I/T ratio). Positive tracheal aspirates were not significantly associated with clinical, laboratory, or radiographic markers used in clinical practice to screen for infection. Despite the lack of positive clinical associations, a positive tracheal aspirate culture was associated with increased risk of prolonged antibiotic exposure.Conclusion:These findings suggest that positive tracheal aspirates do not always represent clinical infection and may result in unnecessary antibiotic exposure.

Congenital hyperinsulinism is a rare disorder that commonly presents in the immediate postnatal period as persistent hypoglycemia. The condition is frequently resistant to medical therapies, and the genetic mutations implicated in the disorder can be predictive of response to therapy. Evaluation of hypoglycemia in the illustrative case presented in this article led to genetic testing identifying recessive mutations in the potassium channel subunits of the beta-islet pancreatic cells. Potassium channel defects are often refractory to medical therapies, so near-total pancreatectomy is usually indicated; however, genetic mutations leading to metabolic dysregulation within the beta-islet pancreatic cells are usually responsive to medical therapy. Aggressive treatment of hypoglycemia in the setting of congenital hyperinsulinism is important to prevent long-term neurologic sequelae secondary to hypoglycemia-induced brain injury. Congenital hyperinsulinism is a rare disorder that commonly presents in the immediate postnatal period as persistent hypoglycemia. The condition is frequently resistant to medical therapies, and the genetic mutations implicated in the disorder can be predictive of response to therapy. Evaluation of hypoglycemia in the illustrative case presented in this article led to genetic testing identifying recessive mutations in the potassium channel subunits of the beta-islet pancreatic cells. Potassium channel defects are often refractory to medical therapies, so near-total pancreatectomy is usually indicated; however, genetic mutations leading to metabolic dysregulation within the beta-islet pancreatic cells are usually responsive to medical therapy. Aggressive treatment of hypoglycemia in the setting of congenital hyperinsulinism is important to prevent long-term neurologic sequelae secondary to hypoglycemia-induced brain injury. [[Pediatr Ann. 2017;46(11):e409–e414.]

Retinopathy of prematurity (ROP) is a condition seen in premature infants that is characterized by abnormal retinal blood vessel growth incited by relative hyperoxia and followed by hypoxia. It can have severe consequences ranging from high myopia to blindness. This article reviews recent “hot” topics related to ROP, specifically the changing incidence of ROP worldwide, the advent of predictive algorithms for screening for ROP, the emerging data behind efficacy of anti-vascular endothelial growth factor treatments for ROP, and advanced retinal imaging in children who were born premature. Retinopathy of prematurity (ROP) is a condition seen in premature infants that is characterized by abnormal retinal blood vessel growth incited by relative hyperoxia and followed by hypoxia. It can have severe consequences ranging from high myopia to blindness. This article reviews recent “hot” topics related to ROP, specifically the changing incidence of ROP worldwide, the advent of predictive algorithms for screening for ROP, the emerging data behind efficacy of anti-vascular endothelial growth factor treatments for ROP, and advanced retinal imaging in children who were born premature. [[Pediatr Ann. 2017;46(11):e415–e422.]

Background:Ex-premature infants are at higher risk for hypertension and cardiovascular disease as adults, although the mechanisms underlying such increased risks are unknown. We hypothesize that postnatal exposure to intermittent hypoxia (IH) leads to cardiovascular dysfunction in adulthood with alterations of the renin–angiotensin pathway.Methods:Neonatal mice were exposed to IH for 4?wk. At the age of 3 mo, various cardiovascular measurements were obtained.Results:IH-exposed mice exhibited higher systolic blood pressure, impaired baroreflex responses, and decreased heart rate variability. Furthermore, IH-exposed mice manifested evidence of endothelial dysfunction, as shown by reduced reperfusion indices after tail vessel occlusion and impaired vasodilatory responses to acetylcholine. CD31+endothelial cells isolated from mesenteric arteries of IH-exposed mice expressed higher levels of angiotensin-converting enzyme and reactive oxygen species; plasma angiotensin-II levels were also significantly higher in these animals. In addition, DNA methylation patterns of the Ace1 and the Agt genes in these cells were congruent with their expression patterns.Conclusion:Our results suggest that exposures to postnatal IH alter the normal development of the renin–angiotensin system and promote the occurrence of cardiovascular dysfunction during adulthood in mice.

Emerging infectious diseases including Ebola, Chikungunya, Zika, and dengue may have significant impacts on maternal-fetal dyads and neonatal outcomes. Pregnant women infected with Ebola demonstrate high mortality and very low evidence of neonatal survival. Maternal Chikungunya infection can result in high rates of perinatal transmission, and infected neonates demonstrate variable disease severity. Dengue can be transmitted to neonates via vertical transmission or perinatal transmission. Zika is characterized by mild disease in pregnant women, but congenital infection can be severe. Treatment is largely supportive for these diseases, and vaccine development remains underway, with promising recent advances notably for Ebola.

Introduction:The mouse retina is a robust tool to investigate vascular development or disease such as oxygen induced retinopathy (OIR). Light-sheet fluorescence microscopy (LSFM) can image the biological system with high-spatiotemporal resolution. We hereby integrate the dual-illumination LSFM and modified passive CLARITY for retina (MPCR) to reveal complete primary and deep capillary plexus in the intact 3-D retinal vascular system.Method:The dissected retinas from C57BL/6 mice at post-natal day 12 were fixed and transferred to monomer solution (4% Acrylamide (wt/vol), 0.05% Bis-Acrylamide (wt/vol), and 0.25% VA-044 initiator (wt/vol) in PBS). After thorough incubation, we placed the sample in 37?C incubator for hydrogel polymerization. The retinas were then placed into a clearing solution comprising 4% w/v sodium dodecyl sulfate (SDS) and 1.25% w/v boric acid (pH 8.5). After clearing, the retinas were immunostained with Isolectin (IB4) conjugated with Alexa-488 to complete the vascular staining. Filament tracing was applied to the entire 3-D vascular network for quantifying the vascular connectivity.Result:Our MPCR method optimized the tissue-hydrogel hybrids to support the intact hemispheric structure of the retina (Fig. 1A). We revealed the vascular network of the entire retina, including superficial capillary and deep vascular plexuses distributed from nerve fiber layer (NFL) to outer plexiform layer (OPL), bypassing the conventional flat-mount sample preparation (Fig. 1B). The two volumes of interest (VOI) were quantified to reveal the distinct vascular connectivity between two subvolumes; thus, demonstrating the feasibility to analyze the morphological and topological difference in vascular development and diseases (Fig. 1C).Conclusion:The integration of optical clearing and dual-illumination LSFM elucidate structural phenotypes otherwise optically challenging to advance the field of micro-vascular development and injury.