Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Early Check: translational science at the intersection of public health and newborn screening.

BACKGROUND: Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. METHODS: To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. DISCUSSION: Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants.

This retrospective study of 68 premature infants examined whether there was a difference between male and female mixed-sex multiple gestation infants with regard to stage of retinopathy of prematurity (ROP) developed or need for ROP treatment. We found that among mixed-sex twin infants there was no statistically significant difference between sexes in most severe ROP stage developed or need for ROP treatment, but males were treated at an earlier postmenstrual age (PMA) than females, despite females having a lower mean birthweight and slower mean growth velocity compared to males.

Association of patent ductus arteriosus with extubation failure among preterm infants.

BACKGROUND: Mechanical ventilation is associated with mortality/morbidities in preterm infants. Nearly a third of these infants fail extubation, and this may increase morbidities. OBJECTIVE: To evaluate the association of moderate to large symptomatic patent ductus arteriosus (PDA) with failure of extubation among preterm infants. METHODS: This was a retrospective study on preterm infants (birth weight <1250 g and gestational age ≥23 weeks) born between January 2009 and December 2016, who were mechanically ventilated and extubated within the first 60 days of age. RESULTS: Three hundred and sixty infants were evaluated, of these, 26% failed, and 74% succeeded in the initial extubation attempt. On adjusted analysis, symptomatic PDA was associated with an increased risk of extubation failure. CONCLUSION: The presence of symptomatic patent ductus arteriosus was associated with extubation failure. Further investigations are needed to establish whether there is a causal relationship between PDA and extubation failure and whether proactive screening for presence of PDA and treatment of the same, before extubation among these infants, improves chances of successful extubation and cardiorespiratory outcomes.

Longitudinal medical needs for periviable NICU survivors.

OBJECTIVE: To evaluate the technologies required, medications needed, and early intervention services utilized from discharge to 12 months post-discharge for periviable infants (22 0/7 to 24 6/7 weeks gestational age) followed in a comprehensive NICU follow-up clinic. STUDY DESIGN: Information regarding medication use, technology requirement, and early intervention services was collected prospectively at one, six, and twelve months after discharge. Neurodevelopmental assessment was completed at 12 months corrected age. RESULT: 69 periviable infants were actively treated and survived to discharge during the study period. 54 infants were enrolled and followed in the comprehensive NICU follow-up clinic. Use of technology and prescribed medications decreased with a 46% reduction of infants requiring ≥1 technology device (74.1% vs. 40.4%, p < 0.01) and 64% reduction in infants requiring ≥1 medication (88.9% vs 31.9%, p < 0.01) 12 months post discharge. There was an increase in early intervention services with 83% of infants receiving services by 12 months post discharge. CONCLUSION: Technology and medication requirements were high at discharge but notably decreased in the first year after discharge concurrent with increased enrollment in early interventional services. Many periviable infants survive without severe short-term developmental delays.

Rapid Whole Genome Sequencing in Critically Ill Neonates Enables Precision Medicine Pipeline.

Rapid genome sequencing in critically ill infants is increasingly identified as a crucial test for providing targeted and informed patient care. We report the outcomes of a pilot study wherein eight critically ill neonates received rapid whole genome sequencing with parental samples in an effort to establish a prompt diagnosis. Our pilot study resulted in a 37.5% diagnostic rate by whole genome sequencing alone and an overall 50% diagnostic rate for the cohort. We describe how the diagnoses led to identification of additional affected relatives and a change in management, the limitations of rapid genome sequencing, and some of the challenges with sample collection. Alongside this pilot study, our site simultaneously established a research protocol pipeline that will allow us to conduct research-based genomic testing in the cases for which a diagnosis was not reached by rapid genome sequencing or other available clinical testing. Here we describe the benefits, limitations, challenges, and potential for rapid whole genome sequencing to be incorporated into routine clinical evaluation in the neonatal period.

Macular features from spectral-domain optical coherence tomography as an adjunct to indirect ophthalmoscopy in retinopathy of prematurity.

PURPOSE: To compare vitreoretinal pathology imaged with portable handheld spectral-domain optical coherence tomography (SD-OCT) to conventional indirect ophthalmoscopic examination in neonates undergoing screening for retinopathy of prematurity. METHODS: Spectral-domain optical coherence tomography images were collected from 76 eyes of 38 neonates during 118 routine retinopathy of prematurity examinations. Imaging sessions in the Neonatal Intensive Care Unit were performed immediately after the subjects underwent a standard ophthalmic examination with indirect ophthalmoscopic by a pediatric ophthalmologist. Masked certified SD-OCT graders evaluated scans for preretinal and retinal findings including material in the vitreous, epiretinal membrane, intraretinal cystoid structures and deposits, optic nerve and vascular features, and severity and location of retinopathy of prematurity. The frequency of detection of these features by clinical examination and evaluation of SD-OCT images was compared to determine potential clinical advantages for each modality. RESULTS: Portable SD-OCT imaging characterized macular features of retinal cystoid structures in 39% of examinations and epiretinal membrane in 32% of examinations. Neither feature was visualized by indirect ophthalmoscopy in any cases. The clinician using indirect ophthalmoscopy detected stage of retinopathy of prematurity and the presence or absence of Plus or pre-Plus disease. These were not visualized with SD-OCT. CONCLUSION: Spectral-domain optical coherence tomography provides new information about the premature infant retina that is of unknown importance relative to visual development and acuity. As used in this study, SD-OCT does not replace indirect ophthalmoscopy for evaluation of retinopathy of prematurity.

Transcript Assembly and Quantification by RNA-Seq Reveals Significant Differences in Gene Expression and Genetic Variants in Mosquitoes of the Culex pipiens (Diptera: Culicidae) Complex.

The taxonomy of Culex pipiens complex of mosquitoes is still debated, but in North America it is generally regarded to include Culex pipiens pipiens, Culex pipiens molestus, and Culex quinquefasciatus (or Culex pipiens quinquefasciatus). Although these mosquitoes have very similar morphometry, they each have unique life strategies specifically adapted to their ecological niche. Differences include the capability for overwintering diapause, bloodmeal preference, mating behaviors, and reliance on blood meals to produce eggs. Here, we used RNA-seq transcriptome analysis to investigate the differential gene expression and nucleotide polymorphisms that may link to the divergent traits specifically between Cx. pipiens pipiens and Cx. pipiens molestus.

Structure-Function Properties in Disordered Condensates.

Biomolecular condensates appear throughout the cell serving a wide variety of functions. Many condensates appear to form by the assembly of multivalent molecules, which produce phase-separated networks with liquidlike properties. These networks then recruit client molecules, with the total composition providing functionality. Here we use a model system of poly-SUMO and poly-SIM proteins to understand client-network interactions and find that the structure of the network plays a strong role in defining client recruitment and thus functionality. The basic unit of assembly in this system is a zipperlike filament composed of alternating poly-SUMO and poly-SIM molecules. These filaments have defects of unsatisfied bonds that allow for both the formation of a 3D network and the recruitment of clients. The filamentous structure constrains the scaffold stoichiometries and the distribution of client recruitment sites that the network can accommodate. This results in a nonmonotonic client binding response that can be tuned independently by the client valence and binding energy. These results show how the interactions within liquid states can be disordered yet still contain structural features that provide functionality to the condensate.

Respiratory setback associated with extubation failure in extremely preterm infants.

BACKGROUND AND OBJECTIVES: Extubation failure in preterm infants is associated with an increased risk of mortality and morbidity. There is limited evidence to suggest if the increased morbidities are due to inherent differences among infants who fail or succeed; or whether these are due to a true respiratory setback among those who fail extubation. The aim of this study was to evaluate the respiratory status of infants who fail extubation and to assess the time taken for these infants to achieve pre-extubation respiratory status. METHODS: This was a retrospective study of infants with birth weight ≤ 1250 g who were born between January 2009 and December 2016. Infants were eligible if they failed first elective extubation. Extubation failure was defined as need for re-intubation within 5 days of extubation. Ventilator settings, blood gas parameters, respiratory severity score (RSS), and ventilation index (VI) were used to assess the respiratory status of infants. RESULTS: Out of 384 infants, 76% were successful and 24% failed extubation. Among those who failed extubation 91%, 77%, and 56% infants remained intubated at 24 h, 72 h, and 7 days, respectively. Respiratory status was worse at 24 and 72 h after re-intubation when compared to pre-extubation levels. The median times for RSS and VI to reach pre-extubation levels were 4 and 7 days, respectively. CONCLUSION: Among preterm infants, failed elective extubation is associated with a significant setback in the respiratory status. Infants who fail an extubation attempt may not achieve pre-extubation respiratory status for many days after reintubation.

Systemic Factors Associated with a Thinner Choroid in Preterm Infants.

Purpose: To identify systemic health factors associated with a thinner choroid, which has been hypothesized as a cause of poor visual outcomes in low-birth weight infants. Design: The prospective, observational Study of Eye Imaging in Preterm Infants (BabySTEPS) enrolled infants recommended for retinopathy of prematurity screening based on the American Association of Pediatrics guidelines. Participants: Infants who underwent imaging with investigational handheld OCT at 36 ± 1 weeks' postmenstrual age (PMA) as part of BabySTEPS. Methods: Average choroidal thickness was measured across the central subfoveal 1 mm. We concurrently collected maternal and infant clinical health data. Univariate and multivariate linear regression analyses were performed to evaluate factors associated with choroidal thickness. The left and right eyes showed similar thicknesses, so their average was used for analysis. Main Outcomes Measures: Association between infant health factors and subfoveal choroidal thickness. Results: Subfoveal choroidal thickness was measurable in 82 of 85 infants and 94% of eyes. Mean choroidal thickness was 231 ± 78 µm. In the univariate analysis, a thinner choroid was associated with decreased growth velocity (P < 0.001), lower birth weight (P < 0.001), smaller head circumference (P < 0.001), younger gestational age (P = 0.01), the presence of patent ductus arteriosus (P = 0.05), sepsis or necrotizing enterocolitis (P = 0.03), bronchopulmonary dysplasia (P = 0.03), pulmonary interstitial emphysema (P = 0.002), more days on oxygen support (P < 0.001), and being on oxygen support at 36 weeks (P < 0.001) and at the time of imaging (P < 0.001). In the multivariate analysis, growth velocity (P = 0.002) and oxygen support at the time of OCT imaging (P = 0.004) remained associated with a thinner choroid. Conclusions: A thinner choroid is associated independently with growth velocity and receiving oxygen support at 36 ± 1 weeks PMA. This suggests that choroidal development in preterm infants may be related to growth rate in the first weeks of life and the prolonged use of supplemental oxygen. Longitudinal studies are needed to assess differences in choroidal thickness before 36 weeks PMA and to assess their impact on visual outcomes.

Randomized controlled trial of the "WISER" intervention to reduce healthcare worker burnout.

OBJECTIVE: Test web-based implementation for the science of enhancing resilience (WISER) intervention efficacy in reducing healthcare worker (HCW) burnout. DESIGN: RCT using two cohorts of HCWs of four NICUs each, to improve HCW well-being (primary outcome: burnout). Cohort 1 received WISER while Cohort 2 acted as a waitlist control. RESULTS: Cohorts were similar, mostly female (83%) and nurses (62%). In Cohorts 1 and 2 respectively, 182 and 299 initiated WISER, 100 and 176 completed 1-month follow-up, and 78 and 146 completed 6-month follow-up. Relative to control, WISER decreased burnout (-5.27 (95% CI: -10.44, -0.10), p = 0.046). Combined adjusted cohort results at 1-month showed that the percentage of HCWs reporting concerning outcomes was significantly decreased for burnout (-6.3% (95%CI: -11.6%, -1.0%); p = 0.008), and secondary outcomes depression (-5.2% (95%CI: -10.8, -0.4); p = 0.022) and work-life integration (-11.8% (95%CI: -17.9, -6.1); p < 0.001). Improvements endured at 6 months. CONCLUSION: WISER appears to durably improve HCW well-being. CLINICAL TRIALS NUMBER: NCT02603133; https://clinicaltrials.gov/ct2/show/NCT02603133.

A predictive model for extubation readiness in extremely preterm infants.

OBJECTIVE: To develop an estimator for predicting successful extubation for an individual preterm infant. STUDY DESIGN: This was a retrospective study that included infants with birth weights ≤1250 g, who were admitted to a tertiary NICU over a 7-year period, received mechanical ventilation and had an elective extubation attempt within 60 days of age. Perinatal and periextubation characteristics were compared in the successful and failed extubation groups. RESULTS: Of 621 screened infants, 312 were included. Extubation succeeded in 73% and failed in 27%. Adjusted factors associated with successful extubation included greater gestational age, chronologic age, pre-extubation pH and lower pre-extubation FiO2, along with lower "peak" respiratory severity score in the first 6 h of age. CONCLUSIONS: We used readily available demographic and clinical data to create an extubation readiness estimator that provides the probability of extubation success for an individual preterm infant (http://elasticbeanstalk-us-east-2-676799334712.s3-website.us-east-2.amazonaws.com/).

A structural approach to examining prostate cancer risk for rural southern African American men.

Physical, cultural, and social factors influence health risk and behavior, but few have explored how the environmental context affects African American men's prostate cancer screening and treatment. This paper describes a structural analysis of data from eight focus groups of rural, southern African American men (n=66). A structural approach highlights the interrelationships between individuals, the health service system, and community factors that directly and indirectly affect screening and treatment for prostate cancer. The availability of accurate and timely health information and health services, social norms regarding health and professional help-seeking, and the sociopolitical context shaped men's screening and treatment behaviors. These proximal and distal health factors affected men's prostate cancer knowledge, perceived risk, willingness to seek care and trust in the health service system. The findings suggest that prostate cancer screening and treatment occurs in a larger structural context that has important implications for help-seeking and health promotion.

Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study protocol, review of literature and survey of current practices.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is commonly associated with pulmonary hypoplasia and pulmonary hypertension (PH). PH associated with CDH (CDH-PH) is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO) possibly due to right and left ventricular dysfunction. Milrinone is an intravenous inotrope and lusitrope with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PH. We developed this pilot study to determine if milrinone infusion would improve oxygenation in neonates ≥36 weeks postmenstrual age (PMA) with CDH. METHODS/DESIGN: Data on pulmonary vasodilator management and outcome of CDH patients was collected from 18 university NICUs affiliated with the Neonatal Research Network (NRN) from 2011 to 2012. The proposed pilot will be a masked, placebo-controlled, multicenter, randomized trial of 66 infants with CDH with an oxygenation index (OI) ≥10 or oxygen saturation index (OSI) ≥5. The primary outcome is the oxygenation response, as determined by change in OI at 24 h after initiation of study drug. As secondary outcomes, we will determine oxygenation at 48 h and 72 h post-infusion, right ventricular pressures on echocardiogram and the incidence of systemic hypotension, arrhythmias, intracranial hemorrhage, survival without extracorporeal membrane oxygenation, and chronic lung disease (oxygen need at 28 days postnatal age). Finally, we will evaluate the pulmonary and nutritional status at 4, 8 and 12 months of age using a phone questionnaire. RESULTS: Three hundred thirty-seven infants with CDH were admitted to NRN NICUs in 2011 and 2012 of which 275 were ≥36 weeks PMA and were exposed to the following pulmonary vasodilators: iNO (39%), sildenafil (17%), milrinone (17%), inhaled epoprostenol (6%), intravenous epoprostenol (3%), and intravenous PGE1 (1%). ECMO was required in 36% of patients. Survival to discharge was 71%. DISCUSSION: CDH is an orphan disease with high mortality with few randomized trials evaluating postnatal management. Intravenous milrinone is a commonly used medication in neonatal/pediatric intensive care units and is currently used in 17% of patients with CDH within the NRN. This pilot study will provide data and enable further studies evaluating pulmonary vasodilator therapy in CDH. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02951130; registered 14 October 2016.

Recent controversies on comparative effectiveness research investigations: Challenges, opportunities, and pitfalls.

The purpose of comparative effectiveness research (CER) is to improve health outcomes by developing and disseminating evidence-based information about which currently available interventions and practices are most effective for patients. Randomized Controlled Trials (RCT) are the hallmark of scientific proof, and have been used to compare interventions used in variable ways by different clinicians (comparative effectiveness RCTs, CER-RCTs). But such CER-RCTs have at times generated controversy. Usually the background for the CER-RCT is a range of "standard therapy" or "standard of care." This may have been adopted on observational data alone, or pilot data. At times, such prior data may derive from populations that differ from the population in which the widely variable standard approach is being applied. We believe that controversies related to these CER-RCTs result from confusing "accepted" therapies and "rigorously evaluated therapies." We first define evidence-based medicine and consider how well neonatology conforms to that definition. We then contrast the approach of testing new therapies and those already existing and widely adopted, as in CER-RCTs. We next examine a central challenge in incorporating the control arm within CER-RCTs and aspects of the "titrated" trial. We finally briefly consider some ethical issues that have arisen, and discuss the wide range of neonatology practices that could be tested by CER-RCTs or alternative CER-based strategies that might inform practice. Throughout, we emphasize the lack of awareness of the lay community, and indeed many researchers or commentators, in appreciating the wide variation of standard of care. There is a corresponding need to identify the best uses of available resources that will lead to the best outcomes for our patients. We conclude that CER-RCTs are an essential methodology in modern neonatology to address many unanswered questions and test unproven therapies in newborn care.

Comparative Transcriptomics Reveals Key Gene Expression Differences between Diapausing and Non-Diapausing Adults of Culex pipiens.

Diapause is a critical eco-physiological adaptation for winter survival in the West Nile Virus vector, Culex pipiens, but little is known about the molecular mechanisms that distinguish diapause from non-diapause in this important mosquito species. We used Illumina RNA-seq to simultaneously identify and quantify relative transcript levels in diapausing and non-diapausing adult females. Among 65,623,095 read pairs, we identified 41 genes with significantly different transcript abundances between these two groups. Transcriptome divergences between these two phenotypes include genes related to juvenile hormone synthesis, anaerobic metabolism, innate immunity and cold tolerance.

Point-of-Care Quantitative Measure of Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency.

BACKGROUND AND OBJECTIVES: Widespread newborn screening on a point-of-care basis could prevent bilirubin neurotoxicity in newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We evaluated a quantitative G6PD assay on a digital microfluidic platform by comparing its performance with standard clinical methods. METHODS: G6PD activity was measured quantitatively by using digital microfluidic fluorescence and the gold standard fluorescence biochemical test on a convenience sample of 98 discarded blood samples. Twenty-four samples were designated as G6PD deficient. RESULTS: Mean ± SD G6PD activity for normal samples using the digital microfluidic method and the standard method, respectively, was 9.7 ± 2.8 and 11.1 ± 3.0 U/g hemoglobin (Hb), respectively; for G6PD-deficient samples, it was 0.8 ± 0.7 and 1.4 ± 0.9 U/g Hb. Bland-Altman analysis determined a mean difference of -0.96 ± 1.8 U/g Hb between the digital microfluidic fluorescence results and the standard biochemical test results. The lower and upper limits for the digital microfluidic platform were 4.5 to 19.5 U/g Hb for normal samples and 0.2 to 3.7 U/g Hb for G6PD-deficient samples. The lower and upper limits for the Stanford method were 5.5 to 20.7 U/g Hb for normal samples and 0.1 to 2.8 U/g Hb for G6PD-deficient samples. The measured activity discriminated between G6PD-deficient samples and normal samples with no overlap. CONCLUSIONS: Pending further validation, a digital microfluidics platform could be an accurate point-of-care screening tool for rapid newborn G6PD screening.

Spectral-domain optical coherence tomographic assessment of severity of cystoid macular edema in retinopathy of prematurity.

OBJECTIVE: To investigate whether the severity of cystoid macular edema (CME) in neonates who were 31 to 36 weeks' postmenstrual age, as viewed by spectral-domain optical coherence tomography (SD-OCT)imaging, predicts the severity of retinopathy of prematurity(ROP) or is related to systemic health. DESIGN: Of 62 prematurely born neonates in a prospective institutional review board-approved study, 42 met the following inclusion criteria: at least 1 SD-OCT imaging session prior to 37 weeks' postmenstrual age and prior to ROP laser treatment, if a laser treatment was performed,and an ophthalmic ROP examination at or after 41 weeks' postmenstrual age, evidence of complete retinal vascularization in zone III, or documentation through telephone report of such information after transfer of care.Measures of CME severity, including central foveal thickness,retinal layer thicknesses, and foveal-to-parafoveal thickness ratio in 1 eye per subject, were compared with ROP outcomes: laser treatment, maximum plus disease,and maximum ROP stage. Systemic health factors were also correlated. RESULTS: Cystoid macular edema was present in 50% of neonates. Multiple elongated cystoid structures within the inner nuclear layer were most common. The presence of CME was not associated with ROP outcomes. The central foveal thickness, the thickness of the inner retinal layers, and the foveal-to-parafoveal thickness ratio were higher in eyes that required laser treatment or that developed plus disease or ROP stage 3. Cystoid macular edema was not clearly associated with systemic factors. CONCLUSIONS: Cystoid macular edema is common in premature infants screened for ROP before 37 weeks' postmenstrual age, with the most common SD-OCT phenotype ofa bulging fovea from multiple elongated cystoid spaces. Detection of CME is not associated with ROP severity; however,tomographic thickness measurements could potentially predict a higher risk of requiring laser treatment or developing plus disease or ROP stage 3. Systemic health factors are probably not related to the development of CME.

Digital microfluidics: a future technology in the newborn screening laboratory?

Expansion of newborn screening for inherited metabolic disorders using tandem mass spectrometry has generated interest in screening for other treatable conditions, including lysosomal storage diseases. Limitations to expansion include labor and equipment costs. We describe a cost-effective new platform that reduces the time to result reporting and can perform multiplexing assays requiring different platforms. Immunoassays and enzyme activity assays currently used in newborn screening have been translated to a disposable microchip programmed to dispense, transport, mix, wash, and incubate individual microdroplets from specimens, including dried blood spot extracts, and reagents all under software control. The specimen and reagents consumed are approximately 1% of those required by equivalent bench assays. In addition to immunologic and enzymatic assays, DNA amplification, amplicon detection, and sequencing have been demonstrated using the same microchips and control equipment. Recently, the multiplexing of 4 different enzyme activities has also been demonstrated with negligible cross-contamination. We review assays relevant to newborn screening.