High inter-rater reliability between physicians and nurses utilising modified Downes' scores in preterm respiratory distress.

AIM: To assess the inter-rater reliability of modified Downes' scores assigned by physicians and nurses in the Ethiopian Neonatal Network and to calculate the concordance of score-based treatment for preterm infants with respiratory distress. METHODS: We included preterm infants admitted from June 2020 to July 2021 to four tertiary neonatal intensive care units (NICUs) of the Ethiopian Neonatal Network that presented with respiratory distress. We calculated the kappa statistic to determine the nurse and physician correlation for each component of the modified Downes' score and total score on admission and evaluated the concordance of scores above and below the treatment threshold of 4. RESULTS: Of the 1151 eligible infants admitted, 817 infants (71%) had scores reported concurrently and independently by nurse and physician. The kappa statistic for modified Downes' score components ranged from 0.88 to 0.92 and was 0.89 for the total score. There was 98% concordance for score-based treatment. CONCLUSION: Incorporation of the modified Downes' score on admission for preterm infants with respiratory distress was feasible in tertiary NICUs in Ethiopia. The kappa statistics showed near-perfect agreement between nurse and physician assessments, translating to a very high degree of concordance in score-based treatment recommendations. These results highlight an opportunity for task-shifting assessments and empowering nurses.

Impact of an Online Program of Bubble Continuous Positive Airway Pressure Education in a Resource-Constrained Setting.

Background: Respiratory distress is a leading cause of preterm infant mortality in sub-Saharan Africa. Bubble continuous positive airway pressure (CPAP) is emerging as a potentially safe, cost-effective way of delivering noninvasive respiratory support in low-income and middle-income countries. However, without healthcare providers who are knowledgeable and skilled in the use of this technology, suboptimal neonatal care and related health disparities are likely to persist. Objective: We hypothesized that an Internet-based, blended curriculum on bubble CPAP for bedside providers in low-resource mother-baby units (MBUs) could be developed and implemented and lead to improvements in clinical knowledge, reasoning, and learner confidence in bubble CPAP. Methods: Clinical educators from Israel, Ghana, and the United States used the analysis, design, development, implementation, and evaluation (ADDIE) design framework to create an online curriculum for two MBUs in Kumasi, in the Ashanti Region of Ghana. Participants completed pre and post curriculum knowledge tests and completed surveys on their perspectives. Results: Fifty-four interdisciplinary health professionals from the MBUs participated in the curriculum. Median knowledge test scores improved from 64% (interquartile range [IQR] = 50-72%) to 81% (IQR = 71-89%) after participation in the curriculum (P < 0.001). Learners reported high levels of confidence with bubble CPAP after participating in the curriculum and evaluated the curricular components highly. Conclusion: An online curriculum was successfully implemented and led to changes in healthcare worker knowledge in bubble CPAP. This may be an effective way to deliver education to healthcare professionals in resource-constrained countries and warrants further study.

The impact of the early onset neonatal sepsis calculator on antibiotic initiation: a single center study in Israel.

To evaluate the effect of implementation of the Kaiser Permanente (KP) early onset sepsis (EOS) calculator in infants born at 34 week's gestation or more on antibiotic utilization and length of hospitalization. A single center, retrospective cohort study included all neonates born in Soroka Medical Center at 34 weeks gestation or more between January 1st, 2015, and January 1st, 2019, with a predefined maternal risk factor for EOS. Two cohorts of neonates were compared during two time periods, before and after the implementation of the KP calculator. Multivariable logistic and linear regressions were performed to assess the effect of the KP calculator on antibiotic treatment and length of hospitalization. Also, an interrupted time series (ITS) analysis was used to assess the time trends of the two periods. The study included 3858 neonates in the pre-implementation period and 3081 neonates in the post-implementation cohort. The use of the calculator resulted in a significant reduction (46%) in antibiotics treatment for suspected EOS (5.1 vs. 9.4%, P < 0.001). The ITS analysis demonstrated a sharp decline in the slope of antibiotic treatment in the post intervention period: (b = -0.14, p-value = 0.08). The length of hospitalization was significantly reduced in the post-implementation cohort from 62 to 60 h (p-value < 0.001) with no clinical significance. The incidence of EOS was similar in both groups.    Conclusion: A significant reduction in antibiotic treatment was demonstrated after the implementation of the KP calculator without an increase incidence of EOS. The calculator is a powerful accessory decision-making tool that can be used safely in combination with, but not replacing, thorough clinical assessment. What is Known: • The EOS calculator is a useful tool that leads to a significant reduction in preemptive antibiotic utilization. What is New: • The EOS calculator is sensitive when applied to the whole-nursery. • The calculator is useful in different populations, also when women are not routinely screened for GBS.

Early versus late-onset necrotizing enterocolitis in very low birth infants in the neonatal intensive care unit.

BACKGROUND: Necrotizing enterocolitis (NEC), one of the most severe emergencies in neonates, is a multifactorial disease with diverse risk factors. OBJECTIVES: To compare between the clinical and laboratory characteristics of premature infants diagnosed with early-onset NEC (EO-NEC) and those with late-onset NEC (LO-NEC). PATIENTS AND METHODS: Enrolled infants were identified from prospective local data collected for the Israel National very low birth weight (VLBW, < 1500 g) infant database and from the local electronic patient files data base for the period 1996-2017. RESULTS: Overall, 95 VLBW infants (61, 64.21% EO-NEC and 34, 35.87% LO-NEC) were enrolled. EO-NEC infants had higher rate of IVH grade 3 and 4 (26.2% vs 2.9%, p = 0.005) and were more likely to undergo surgery (49.2% vs 26.5%, p = 0.031). LO-NEC infants had a higher incidence of previous bloodstream infections (35.3% vs 8.2%, p = 0.002) compared to EO-NEC. In multivariable analysis models, surgical intervention was associated with EO-NEC (OR: 4.627, p = 0.013) as well as PDA and positive blood culture prior to the NEC episode. CONCLUSIONS: Our data support the hypothesis that EO-NEC has significant different clinical and microbiological attributes compared to LO-NEC.

Neonatal SARS-CoV-2 Infections in Breastfeeding Mothers.

OBJECTIVES: To assess infection rates predischarge and postdischarge in breast milk-fed newborns with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers who were separated postdelivery from their mothers and discharged from the hospital. Also, we aim to evaluate breastfeeding rates predischarge and postdischarge. METHODS: Nasopharyngeal swabs for SARS-CoV-2 were obtained from symptomatic and high-risk women in the delivery room. Mothers with positive SARS-CoV-2 test results were separated from the newborns. Newborns were screened within 48 hours of delivery, and anti-infectious guidelines were imparted to the mothers before discharge. Rescreening took place ≥14 days postdischarge. Data regarding SARS-CoV-2-positive household members and breastfeeding were obtained by follow-up phone calls. RESULTS: A total of 73 newborns of SARS-CoV-2-positive mothers were born in Israel during the ∼3-month period under study. Overall, 55 participated in this study. All neonates tested negative for the virus postdelivery. A total 74.5% of the neonates were fed unpasteurized expressed breast milk during the postpartum separation until discharge. Eighty-nine percent of the neonates were discharged from the hospital after their mothers were instructed in anti-infection measures. In 40% of the households, there were additional SARS-CoV-2-positive residents. A total of 85% of the newborns were breastfed postdischarge. Results for all 60% of the newborns retested for SARS-CoV-2 postdischarge were negative. CONCLUSIONS: No viral infection was identified in neonates born to and separated from their SARS-CoV-2-positive mothers at birth and subsequently fed unpasteurized breast milk. All infants breastfed at home remained SARS-CoV-2 negative. These findings may provide insights regarding the redundancy of postpartum mother-newborn separation in SARS-CoV-2-positive women and, assuming precautions are adhered to, support the safety of breast milk.

Clinical Application of Postmortem Magnetic Resonance Imaging in Neonates.

BACKGROUND: Recent reports advocate the use of MRI either as a substitute for postmortem examinations or for a more targeted autopsy. METHODS: A full-body postmortem MRI (pMRI) of infants was performed as early as possible after death, and findings were compared to clinical premortem diagnoses. RESULTS: Thirty-one infants were scanned during the study period. Median gestation at birth was 34 weeks (ranges: 24-43). In 3 (10%) cases, no new findings were detected. In 2 (6%), new minor findings not related to the cause of death were detected, and in 17 (55%), new minor findings related to the cause of death were detected. New major findings related to the cause of death were detected in 4 (13%) cases, and new major findings not related to the cause of death were detected in 5 (16%) cases. In 3 (10%), findings thought to alter the perceived cause of death were detected. Overall, in 23 (74%) cases, pMRI findings reinforced the clinical premortem diagnoses. CONCLUSIONS: pMRI is a culturally accepted alternative when autopsy is not performed and can either reinforce, refute, or add to premortem clinical diagnoses.

Implementing a Practical Global Health Curriculum: The Benefits and Challenges of Patient-Based Learning in the Community.

Background: A growing number of medical schools across the world have incorporated global health (GH) into their curricula. While several schools focus GH education on lecture-based courses, our premise is that global health education should embody a holistic approach to patient care and medical education in local communities. Medical students may learn global health by focusing on real patients, their families and communities as part of a practical curriculum. Aims and Objectives: A unique GH curriculum was devised to compare student learning outcomes on a practical vs. lecture-based course. The premise was that learning from patients would result in a greater breadth of coverage of the global health syllabus as compared to that from a lecture-based course. Methods: A teaching and learning program was developed over 3 years to provide medical students interaction with real patients in the community on a first-preclinical-year Introduction to Global Health and Medical Anthropology course. Learning outcomes on the practical vs. lecture-based course were compared using thematic analysis of the written assignments of both courses: global health case reports and literature reviews, respectively. All members of three cohorts of students undertaking the course in successive academic years were compared (Group A: literature review; Groups B and C: case reports; n = 87). Results: Case reports provided evidence of a greater breadth of learning outcomes when compared to the literature review (p < 0.001). The writing of the case report was enhanced by completion of a field journal and family health needs assessment tool (p < 0.001). Students demonstrated a closeness to their patients that added depth, understanding and motivation to assist patients in health activities and advocate for their needs. Discussion: Placements with patients in the community provided students with a rich learning environment and facilitated the formation of relationships with patients to better understand the social determinants of health and advocate for improvements in their living and working conditions and access to healthcare. Conclusions: Global health may be better learned experientially by following patients rather than from frontal lectures. Patient-based learning inspires a commitment to the individual and facilitates medical schools in meeting their obligations to the communities they serve.

Predictive Value of Early Amplitude Integrated EEG in Extremely Premature Infants.

Amplitude integrated EEG (aEEG) is increasingly utilized in preterm infants. The aim of the study was to evaluate whether semiquantitative visual assessment of aEEG background during the first 72 hours of life is associated with long-term outcome in a group of premature infants born less than 28 weeks' gestation. Infants were prospectively enrolled and monitored in the first 72 hours after birth. aEEG was classified daily according to background activity, appearance of cyclical activity and presence of seizures activity. Log-rank and multivariable cox analysis were used to explore associations of background aEEG activity with short and long-term outcome. Overall, 51 infants were enrolled into the study. Depressed aEEG background on the third day of life was associated with poor outcome (P = .028). Similarly, absence of cycling on the third day of life was associated with death or poor outcome (P = .004 and .012, respectively). In different multivariable models adjusted for gestational age, severe intraventricular hemorrhage or use of sedative medication, neither background nor cycling activities were associated with outcome. Depressed aEEG background and absence of aEEG cycling on the third day of life are associated with poor outcome in univariable analysis. Although continuous aEEG monitoring of premature infants can provide real-time assessment of cerebral function, its use as a predictive tool for long-term outcome using visual analysis requires caution as its predictive power is not greater than that of gestational age or intraventricular hemorrhage.

Impact of maternal depression on perinatal outcomes in hospitalized women-a prospective study.

Scarce data exists regarding the prevalence of antenatal depression in hospitalized pregnant women, and its effect on perinatal outcome. We aimed to estimate the risk of maternal depression among women hospitalized in a high-risk pregnancy department, and to evaluate its potential association with adverse perinatal outcome. A depression screening self-questionnaire-based prospective study was performed, in which hospitalized pregnant women who screened positive for depression were compared to those who screened negative. The Edinburgh Postnatal Depression Scale (EPDS) was used for antenatal depression screening. Pregnancy course and perinatal outcome were compared between the groups. A multivariate logistic regression model was constructed to control for clinically relevant confounders. During the study period, 279 women met the inclusion criteria. Among them, 28.3% (n = 79) screened positive for depression (≥ 10 points on the EPDS). In the univariate analysis, a significantly higher incidence of preterm delivery (< 37 weeks), low birthweight (< 2500 g), low Apgar scores (at 1 and 5 min), and neonatal intensive care unit (NICU) admissions were noted among the screen positive group. In the multivariate regression model, controlled for maternal age, ethnicity, gestational diabetes mellitus, preeclampsia, past preterm delivery, and gestational age upon admission, maternal antenatal depression during hospitalization was noted as an independent risk factor for preterm delivery (adjusted OR 3.32, 95%CI 1.16-9.52, p = 0.026). Maternal antenatal depression during hospitalization is very common and appears to play a significant and independent role in the prediction of preterm delivery.

Risk Factors for the Development of Delayed TSH Elevation in Neonatal Intensive Care Unit Newborns.

Context: Delayed thyrotropin (TSH) elevation (dTSH) is defined as elevated TSH at the second neonatal screening (after normal TSH levels at the initial screening) in premature, low-birth-weight, and ill newborns, mostly in the neonatal intensive care unit (NICU) setting. The pathogenesis of dTSH is elusive. Objective: To identify the risk factors for dTSH development among newborns in the NICU. Design, Setting, and Patients: A retrospective medical record review of neonates with dTSH was conducted in eight university-affiliated NICUs. Two controls were selected for each patient, matched for sex and birth weight. The risk factors for dTSH were identified by univariate analysis, followed by multivariate analysis. Main Outcome Measures: Maternal variables, types of NICU treatments and procedures, syndromes, and various medical conditions were compared between dTSH patients and their matched controls. Results: We enrolled 100 dTSH patients and 200 matched controls and 46 variables were compared between the two groups. Twelve risk factors for dTSH were identified on univariate analysis: cesarean section, mechanical ventilation, patent ductus arteriosus (PDA), pneumothorax, and administration of cefotaxime, vancomycin, fluconazole, dopamine, ibuprofen, furosemide, insulin, and packed red blood cells. On multivariate analysis, four risk factors were identified: PDA and vancomycin, insulin, and furosemide administration. In 26 twin pairs, in which one twin had dTSH, all variables presented similarly in both twins. Conclusions: Although some variables had direct effects on pituitary-thyroid axis dysfunction, these variables, altogether, reflect the severity of the clinical conditions in the NICU, which is the common basis for dTSH.

Comparison of Amplitude-Integrated EEG and Conventional EEG in a Cohort of Premature Infants.

OBJECTIVE: To compare amplitude-integrated EEG (aEEG) and conventional EEG (EEG) activity in premature neonates. METHODS: Biweekly aEEG and EEG were simultaneously recorded in a cohort of infants born less than 34 weeks gestation. aEEG recordings were visually assessed for lower and upper border amplitude and bandwidth. EEG recordings were compressed for visual evaluation of continuity and assessed using a signal processing software for interburst intervals (IBI) and frequencies' amplitude. Ten-minute segments of aEEG and EEG indices were compared using regression analysis. RESULTS: A total of 189 recordings from 67 infants were made, from which 1697 aEEG/EEG pairs of 10-minute segments were assessed. Good concordance was found for visual assessment of continuity between the 2 methods. EEG IBI, alpha and theta frequencies' amplitudes were negatively correlated to the aEEG lower border while conceptional age (CA) was positively correlated to aEEG lower border ( P < .001). IBI and all frequencies' amplitude were positively correlated to the upper aEEG border ( P ≤ .001). CA was negatively correlated to aEEG span while IBI, alpha, beta, and theta frequencies' amplitude were positively correlated to the aEEG span. CONCLUSIONS: Important information is retained and integrated in the transformation of premature neonatal EEG to aEEG. SIGNIFICANCE: aEEG recordings in high-risk premature neonates reflect reliably EEG background information related to continuity and amplitude.

Social variables predict gains in cognitive scores across the preschool years in children with birth weights 500 to 1250 grams.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

Antenatal diagnosis and treatment of hypothyroid fetal goiter in an euthyroid mother: a case report and review of literature.

Fetal goiter is an extremely rare complication of pregnancy. Its incidence is 1 in 40,000 deliveries. Antithyroid maternal therapy is responsible for 10-15% of fetal congenital hypothyroidism and can be considered as the most frequent underlying cause for this condition. The frequency of fetal goiter that is associated with fetal hypothyroidism and normal maternal thyroid function, as in our case, is even less frequent. Fetal goiter is associated with increased rate of perinatal complications and long-term morbidity, due to peripartum complications including labor dystocia due to its mass effect, as well as neonatal airway obstruction that may lead to hypoxic-ischemic brain injury and death. We present, in this study, a case report of late antenatal fetal goiter in an euthyroid woman and a literature review of the diagnosis and treatment of these cases.

In and ex utero maturation of premature infants electroencephalographic indices.

OBJECTIVES: To assess the effect of extra uterine life on continuity and amplitude of premature infants' cerebral activity at different gestational age as compared to soon after birth. METHODS: Stable infants less than 34weeks gestation were prospectively recruited and EEG was recorded bi-weekly. Interburst interval and different wavelength amplitudes were digitally measured during the most discontinuous and most continuous (periods with longest and shortest interburst intervals, respectively) parts of the tracings. Linear regression was used to assess conceptional age prediction of interburst interval and wavelength amplitudes. Significant regression results were compared to the group of babies recorded close to delivery (newborn group). RESULTS: 144 EEG tracings from 59 infants were analyzed. Interburst intervals were significantly predicted by conceptional age in the newborn group only (p⩽0.002). Delta and theta amplitudes were significantly predicted by conceptional age in the newborn group and most of the other conceptional age groups (p<0.004). No significant differences were detected between the different groups. CONCLUSIONS: Our data reiterates the normal maturation of cerebral activity in the premature infant and support the concept of similar in and ex-utero maturation of cerebral activity in stable premature infants. SIGNIFICANCE: The effect of ex-utero maturation on the brain of stable premature infant is not readily discernible when using specific neonatal EEG indices.

A prospective study of the patterns and dynamics of colonization with Candida spp. in very low birth weight neonates.

BACKGROUND: Knowledge of fungal colonization patterns in very low birth weight infants (VLBWI) admitted to the neonatal intensive care unit (NICU) is essential in understanding the process of fungal infections in neonates. We analyzed prospectively, during 2009-2010, the patterns and dynamics of fungal colonization in VLBWI, including timing, colonization sites, and species involved. METHODS: Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis. RESULTS: Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed < 1000 g; 68 were delivered by cesarean section. Candida albicans (57/104, 55%) and Candida parapsilosis (26/104, 25%) were the main fungi isolated. Eight (24%) VLBWI were colonized during the first week and 23 (68%) during the second week. No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI. The colonization risk at least once during the first 10 weeks was 23% for skin, 14% for oropharynx, 27% for rectum/stool, and 38% for any anatomic site sampled. Persistent colonization was recorded in 5/34 (15%), while transient colonization was found in 14/34 (41%) VLBWI; 16/34 (47%) were discharged or died colonized with Candida spp. Candidemia was diagnosed in 4 (3%) VLBWI and previous/simultaneous colonization was found in 3/4. CONCLUSIONS: The cumulative risk of colonization, at any sampled site and at least once during follow-up, was high. Initial colonization occurred most often during the first 2 weeks of life. Colonization dynamics were characterized by various persistence, disappearance, and recolonization patterns. Candidemia was rare.

Proactive approach to containment of enterovirus infection in the nursery.

Administration of prophylactic intravenous immunoglobulins to contacts of infants actively shedding enterovirus during a hospital nursery outbreak may attenuate severity of disease in those contacts and aid in containment of the outbreak. Four cases of neonatal enteroviral disease were treated in our hospital nursery in July and August 2011; 3 were presumed or proven vertical transmission cases and 1 was a presumed horizontal transmission. We aimed to prevent development of severe illness in contacts of affected neonates following a ministry of health advisory during the summer of 2011 warning of increased neonatal enteroviral morbidity and mortality in Israel. Strict infection control measures were implemented, including meticulous decontamination of the nursery environment and administration of intravenous immunoglobulin prophylaxis to contacts. No further horizontal transmission occurred after infection control interventions. Immunoglobulin prophylaxis to control enteroviral infection in the nursery should be considered as an auxiliary infection control intervention during a nursery outbreak.

The physician's relationship with the pharmaceutical industry: caveat emptor...buyer beware!

Historically physicians have had close relationships with the pharmaceutical or other medically related industry. This has come under close scrutiny by the public, with articles appearing in medical journals and the lay press. The reality is that physicians depend on industry to bring products to market as well as to assist in research and education, leaving physicians questioning what their relationship with industry should be. This review deals with this complex relationship, identifying ways that industry might affect decision making in the clinical context. We will highlight areas of potential concern in this relationship, identify attendant moral dilemmas, and provide some recommendations. Our intention in raising the consciousness of physicians and medical institutions to these potential areas of concern is to aid physicians in their efforts to provide the best medical care for patients and to practice with integrity.

Imaging in the newborn: infant immobilizer obviates the need for anesthesia.

BACKGROUND: Neonatal cerebral imaging is a sensitive technique for evaluating brain injury in the neonatal period. When performing computed tomography or magnetic resonance imaging, sedation is needed to prevent motion artifacts. However, general anesthesia in neonates carries significant risks and requires a complex logistic approach that often limits the use of these modalities. The development of infant immobilizers now enables imaging without general anesthesia and significantly increases clinical and research investigational opportunities. OBJECTIVES: To assess the efficacy of the infant immobilizer instead of general anesthesia for infants undergoing imaging. METHODS: The study group comprised all infants born over a 1 year period at Soroka University Medical Center who required imaging such as MRI, CT or bone scans. A MedVac Vacuum Splint infant immobilizer was used in all infants to prevent motion during imaging. The success rate of a single scan and the need for general anesthesia were assessed. RESULTS: Forty infants were examined during 1 year. The studies included 15 CT scans, 25 MRIs and 1 bone scan. The infants' gestational age at birth was 27-40 weeks and the examinations were performed at ages ranging from delivery to 6 months old. All imaging was successful and none of the infants required general anesthesia. CONCLUSIONS: An infant immobilizer should be used for imaging of newborns. Since this method carries a low risk and has a high success rate, general anesthesia in newborns is justified only when this non-invasive procedure fails.

Fatal familial lung disease caused by ABCA3 deficiency without identified ABCA3 mutations.

OBJECTIVE: To test the hypothesis that some functionally significant variants in the gene encoding member A3 of the ATP Binding Cassette family (ABCA3) are not detected using exon-based sequencing approaches. STUDY DESIGN: The first of 2 female siblings who died from neonatal respiratory failure was examined for mutations with sequence analysis of all ABCA3 exons and known regulatory elements within the 5' untranslated region. Lung tissue from both siblings was immunostained for ABCA3 and examined with electron microscopy. Segregation of ABCA3 alleles was determined with analysis of polymorphisms in the parents and all children. RESULTS: No mutations were identified with ABCA3 sequence analysis in the first affected infant. Affected siblings were concordant for their ABCA3 alleles, but discordant from those of their unaffected siblings. ABCA3 protein was not detectable with immunostaining in lung tissue samples from both affected infants. Electron microscopy demonstrated small, dense lamellar bodies, characteristically seen with ABCA3 mutations. CONCLUSIONS: The segregation of ABCA3 alleles, absence of ABCA3 immunostaining, lung pathology, and ultrastructural findings support genetic ABCA3 deficiency as the cause of lung disease in these 2 infants, despite the lack of an identified genetic variant.