Neurodevelopmental Outcomes Among Infants Born Preterm Fed With Mother's Own Milk: A Comparison of Singletons and Twins.

OBJECTIVE: To examine associations between early exposure to mother's own milk (MOM) and neurodevelopmental outcomes among preterm infants, and to compare these associations between singletons and twins. STUDY DESIGN: Retrospective cohort study that included low-risk infants born at <32 weeks gestational age. Nutrition was documented over a 3-day period at mean ages of 14 and 28 days of life; an average of the 3 days was calculated. The Griffiths Mental Development Scales (GMDS) were administered at 12 months corrected age. RESULTS: Preterm infants (n = 131) with median gestational age of 30.6 weeks were included; 56 (42.7%) were singletons. On days 14 and 28 of life, 80.9% and 77.1% were exposed to MOM, respectively. Exposure rate was comparable, but MOM intake (mL/kg/day) was higher among singletons than among twins (P < .05). At both time points, MOM-exposed infants scored higher on personal-social, hearing-language, and total GMDS assessments than nonexposed infants. These differences were significant for the entire cohort and for twins (P < .05). MOM intake correlated with total GMDS score for both singletons and twins. Any exposure to MOM was associated with additional 6-7 points on total GMDS score or 2-3 additional points for every 50 mL/kg/day of MOM. CONCLUSIONS: The study supports the positive association between early MOM exposure among low-risk preterm infants and neurodevelopmental outcomes at 12 months corrected age. The differential effects of MOM exposure on singletons vs twins need further exploration.

Early exposures and inherent factors in premature newborns are associated with type 1 diabetes.

BACKGROUND: Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. METHODS: This is a multicenter, matched case-control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. RESULTS: Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92-9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69-14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. -0.27 ± 0.97, OR = 2.03 (1.19-3.49), p = 0.01), longer duration of glucose infusion (3 (1-5) days vs. 2 (0-4), OR = 1.23 (1.03-1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32-20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11-0.88), p = 0.027). CONCLUSIONS: A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. IMPACT: Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters. Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors. Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.

Neurobiological perspective on the development of executive functions.

Executive functions are a set of top-down cognitive processes necessary for emotional self-regulation and goal-directed behaviour supporting, among others, academic abilities. Premature infants are at high risk for subsequent cognitive, psychosocial, or behavioural problems even in the absence of medical complications and in spite of normal brain imaging. Given that this is a sensitive period of brain growth and maturation, these factors may place preterm infants at high risk for executive function dysfunction, disrupted long-term development, and lower academic achievements. Therefore, careful attention to interventions at this age is essential for intact executive functions and academic development.

The role of orotic acid measurement in routine newborn screening for urea cycle disorders.

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.

B4GALT1-congenital disorders of glycosylation: Expansion of the phenotypic and molecular spectrum and review of the literature.

A congenital disorder of glycosylation due to biallelic mutations in B4GALT1 has been previously reported in only three patients with two different mutations. Through homozygosity mapping followed by segregation analysis in an extended pedigree, we identified three additional patients homozygous for a novel mutation in B4GALT1, expanding the phenotypic spectrum of the disease. The patients showed a uniform clinical presentation with intellectual disability, marked pancytopenia requiring chronic management, and novel features including pulmonary hypertension and nephrotic syndrome. Notably, affected individuals exhibited a moderate elevation of Man3GlcNAc4Fuc1 on serum N-glycan analysis, yet two of the patients had a normal pattern of transferrin glycosylation in repeated analysis. The novel mutation is the third disease-causing variant described in B4GALT1, and the first one within its transmembrane domain.

Increased risk for early hypertriglyceridemia in small for gestational age preterm infants.

Small for gestational age preterm are at increased risk for future metabolic syndrome. Early indication for the disrupted metabolism may be found in the perinatal period. We aimed to evaluate whether small for gestational age preterm infants are at increased risk for hypertriglyceridemia when treated with lipid emulsions, and to investigate the association between triglyceride levels and morbidity. Small for gestational age infants ≤ 34 weeks' gestation age born during 2013-2016 were matched and compared with appropriate for gestational age counterparts. Triglyceride concentration > 250 mg/dL during treatment with parenteral nutrition was considered high. The study included 71 pairs of preterm infants. Hypertriglyceridemia was documented among 22.5% of the small for gestational age infants vs. 5.6% of the appropriate for gestational age infants (p = 0.007). Mean triglyceride levels were 194.4 ± 192.3 mg/dL and 99.9 ± 82.8 mg/dL, respectively (p < 0.001). Small for gestational age was predictive of hypertriglyceridemia (OR = 6.41; 95% CI 1.8-22.9). No significant association was found between triglyceride levels and morbidities in multivariate analysis.Conclusion: Small for gestational age preterm infants receiving lipid emulsions might be at a higher risk for hypertriglyceridemia. Routine monitoring of triglyceride levels will enable identification of the necessity for a slower increase in lipid emulsion therapy. What is Known: • Moderate and very preterm infants are routinely treated with lipid emulsions. • Small for gestational age (SGA) infants may have different metabolism, as they demonstrate higher risk for metabolic syndrome. What is New: • • SGA infants had a higher mean triglyceride level and more commonly had early hypertriglyceridemia (triglycerides > 250 mg/dL) compared with appropriate for gestational age infants treated with the same intravenous lipid dose. Small for gestational age was predictive of hypertriglyceridemia. • No significant association was found between triglyceride levels and morbidities in multivariate analysis.

Factors associated with early phosphate levels in preterm infants.

To investigate perinatal factors and early morbidities associated with early serum phosphate (sPhos) levels in a cohort of preterm infants. Retrospective data were obtained from the medical records of a cohort of 454 infants born at < 32 weeks gestational age. Serum phosphate levels were directly associated with gestational age, body weight z-score, and Apgar scores and inversely associated with timing of enteral nutrition initiation and diet consisting of mostly breast milk. Maternal hypertension, lactate levels, early symptomatic hypotension, and total protein supplemented on days 1 to 3 were also inversely associated with sPhos. Morbidities that were found to be associated with sPhos did not persist after adjustment for confounding factors.Conclusions: We report a novel association between early sPhos and timing and content of enteral nutrition, as well as with the early neonatal hemodynamic condition of preterm infants. This information may help identify infants at risk for low sPhos and aid in the nutritional strategy utilized in these patients. This study did not identify early morbidities associated with sPhos. What is Known: • High initial amino acid intake is associated with increased risk of Refeeding like syndrome and hypophosphatemia, among preterm infants. What is New: • Early enteral nutrition, starting within the first 72 h of life, is associated with higher serum phosphate (sPhos) compared to nothing per os (NPO). • sPhos was not associated with early adverse neonatal outcomes.

Intergenerational relations, circumstances, and changes in mothers' marital quality during two years following childbirth.

In this study, the researchers examined, from an attachment theory perspective, changes in mothers' (n = 707) perception of the marital relationship over the course of the two years following childbirth. We found a decline in perceived quality of mothers' marital relationship over time, as well as several significant associations between birth circumstances (assisted reproductive technology, first/non-first baby), insecure attachment, and certain forms of support from the grandmothers on the one hand, and marital quality immediately after childbirth and over time on the other. Some forms of support served as partial mediators between attachment orientation and marital quality. We believe that the current findings can assist in designing interventions aimed at improving the spousal relationship after childbirth and decreasing potential stressors for both parents and newborns.

Short-Term Neonatal Outcome among Term Infants after In-Utero Exposure to Beta Blockers.

BACKGROUND: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined. OBJECTIVES: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring. METHODS: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%), cardiomyopathy 11 (7.2%) and migraine 4 (2.6%). The controls were infants of mothers with hypertension not exposed to BBs who were born at the same gestational age and born closest (before or after) to the matched infant in the study group. RESULTS: Compared to the control group, the infants in the study group had a higher prevalence of early asymptomatic hypoglycemia (study 30.7% vs. control 18.3%, P = 0.016), short symptomatic bradycardia events, other cardiac manifestations (P = 0.016), and longer hospitalization (P < 0.001). No life-threatening medical conditions were documented. The birth weight was significantly lower for the high-dose subgroup compared to the low-dose subgroup (P = 0.03), and the high-dose subgroup had a higher incidence of small-for-gestational-age (P = 0.02). CONCLUSIONS: No alarming or life-threatening medical conditions were observed among term infants born to BB treated mothers. These infants can be safely observed for 48 hours after birth close to their mothers in the maternity ward. Glucose follow-up is needed, especially in the first hours of life.

Pre-term delivery, optimism and initial personal growth as predictors of mothers' long-term personal growth.

Introduction: Positive outcomes in the aftermath of childbirth have increasingly been studied in the last decade. However, most of the studies concentrate on short-term outcomes. The current study examined the perceived personal growth of mothers four years after childbirth, investigating the contribution of the event characteristics (full-term/pre-term birth), internal resources (optimism, self-esteem) and personal growth as measured one year after the birth. Methods: Mothers (n=259) participated in the study by completing a set of self-report questionnaires one and four years following the birth of their child/ren. Results: Personal growth after four years was found to be higher among mothers of pre-terms than of full-terms, and higher four years after the birth than it had been three years earlier. Furthermore, regression analysis indicated the significant contributions of being a mother to pre-term baby/ies, optimism and personal growth one year after the birth to women's personal growth three years later. Discussion: The results highlight the potential long-term effects of giving birth to a pre-term baby on personal growth, as well as the contribution of optimism as an important internal resource. They also indicate the development of personal growth over time. Explanations for the findings are offered and their practical implications are discussed.

A Proposed Role of Surfactant in Platelet Function and Treatment of Pulmonary Hemorrhage in Preterm and Term Infants.

BACKGROUND: We evaluated the effect of surfactant on platelet function as a potential contributing mechanism to the pathogenesis of pulmonary hemorrhage (PHEM) in term and preterm infants. METHODS: Cord blood samples were collected from neonates following delivery. Complete blood count and platelet function were measured using a cone and platelet analyzer (CPA). Increasing surfactant concentrations were added to platelets in vitro, and the adhesion molecule P-selectin and the monoclonal antibody PAC-1 were evaluated following platelet activation by flow cytometry. RESULTS: Forty-one infants (11 preterm and 30 term) were studied. CPA revealed a significant decrease in the average size of the aggregates and in platelet adhesion when surfactant was added. In term infants, the addition of surfactant to native platelets yielded an increased binding capacity of PAC-1 but did not affect P-selectin expression. In preterm infants, platelet activation with adenosine diphosphate in the presence of a high surfactant concentration (0.5 mg/mL) resulted in increased PAC-1 binding and no change in P-selectin expression. CONCLUSIONS: The platelets of preterm infants are less active (hyporesponsive) than those of term infants, both in their native state as well as after stimulation with various agonists. Surfactant may play an important role in treating PHEM in preterm infants.

Feeding Imprinting: The Extreme Test Case of Premature Infants Born With Very Low Birth Weight.

Feeding imprinting, considered a survival-enabling process, is not well understood. Infants born very preterm, who first feed passively, are an effective model for studying feeding imprinting. Retrospective analysis of neonatal intensive care unit (NICU) records of 255 infants (Mgestational age  = 29.98 ± 1.64) enabled exploring the notion that direct breastfeeding (DBF) during NICU stay leads to consumption of more mother's milk and earlier NICU discharge. Results showed that DBF before the first bottle feeding is related to shorter transition into oral feeding, a younger age of full oral feeding accomplishment and earlier discharge. Furthermore, the number of DBF meals before first bottle feeding predicts more maternal milk consumption and improved NICU outcomes. Improved performance in response to initial exposure to DBF at the age of budding feeding abilities supports a feeding imprinting hypothesis.

Maternal mental health over the course of 4 years following childbirth: The contribution of birth circumstances and psycho-social factors.

The aim of this study is to identify mothers at risk for poorer maternal mental health (MMH) 1 month post-partum and to determine changes in MMH over 4 years in relation to birth circumstances (singleton/twins, full-term/pre-term infant/s, first/non-first child), internal resources (adult attachment styles), and external resources (marital quality and maternal grandmother's support) at 1 month post-partum. The mediating effects of external resources were also investigated. Questionnaires were completed between 2001 and 2012 by 561 Israeli mothers. Shortly after birth, mothers at risk for poorer MMH were those who gave birth prematurely or were characterized by insecure attachment styles, lower marital quality, younger age, or a higher level of education. The mothers with a good prognosis for improvement in MMH were those who had given birth prematurely or were younger, more highly educated, or multiparous. Women with insecure attachment or lower marital quality reported lower MMH one month after delivery that did not improve over time, and the MMH of older or less educated mothers deteriorated over time. Marital quality mitigated or exacerbated the effects of birth circumstances and insecure attachment style on MMH shortly after giving birth. Findings suggested that early interventions may be important to help identify women at risk.

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography.

BACKGROUND: The fibrinolytic system in newborns is immature and probably impaired. The aim of this study was to prospectively evaluate functional fibrinolytic capacity of newborn's cord blood using a new thromboelastometry (rotational thromboelastogram, ROTEM®) test. METHODS: Infants born at Sheba Medical Center were studied prospectively. Cord blood was obtained immediately after clumping, and ROTEM parameters were assessed applying non-activated TEM (NATEM) assay with increasing concentration of tissue plasminogen activator (tPA, 0-200 U/ml). Baseline clotting time (CT), clot formation time (CFT), alpha angle, and maximum clot firmness (MCF) were compared among infants versus adults. Each infant's demographic information was prospectively followed up until discharge. RESULTS: One hundred one newborns were tested. CT and CFT values were lower and alpha angles were higher among neonate's cord blood compared to adults (n = 23; P = 0.001, 0.03, and 0.02, respectively). The addition of tPA significantly shortened CT and CFT, and reduced alpha angles and MCF in both groups. The lysis index at 30 min (LI30) and lysis onset time (LOT) decreased significantly, and fibrinolysis was more rapid in the newborns. Hematocrit and platelet counts in neonates correlated with LI30 (P = 0.035 and 0.037, respectively) and LOT (P = 0.02) when higher tPA concentrations were used. ROTEM values were unrelated to the occurrence of postnatal complications. CONCLUSIONS: This first report of functional fibrinolysis in cord blood demonstrated that neonatal fibrinolysis may be augmented as compared to adult values. Further studies are required to validate this test and assess its predictive value and clinical relevance.

Cycled light in the intensive care unit for preterm and low birth weight infants.

BACKGROUND: Potential benefits and harms of different lighting in neonatal units have not been quantified. OBJECTIVES: • To determine effectiveness and safety of cycled light (CL) (approximately 12 hours of light on and 12 hours of light off) for growth in preterm infants at three and six months' corrected age (CA).• In separate analyses, to compare effects of CL with those of irregularly dimmed light (DL) or near darkness (ND), and effects of CL with those of continuous bright light (CBL), on growth in preterm infants at three and six months' CA.• To assess, in subgroup analyses, the effectiveness and safety of CL (vs control interventions (DL, ND and CBL)) introduced at different postmenstrual ages (PMAs) - before 32 weeks', at 32 weeks' and from 36 weeks' PMA - and to compare effectiveness and safety of CL for small for gestational age (GA) infants versus appropriately grown infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE via PubMed (1966 to January 2016), Embase (1980 to January 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 2016). We searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised trials of CL versus ND or CBL in preterm and low birth weight infants. DATA COLLECTION AND ANALYSIS: We performed data collection and analyses according to the methods of the Cochrane Neonatal Review Group. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: We identified one additional study enrolling 38 participants for inclusion in this update, for a total of nine studies reporting on 544 infants. In general, the quality of the studies was low, mainly owing to lack of blinding and small sample sizes.Six studies enrolling 424 infants compared CL versus ND. No study reported on weight at three or six months. One study (n = 40) found no statistically significant difference in weight at four months between CL and ND groups. In another study (n = 62), the ratio of day-night activity before discharge favoured the CL group (mean difference (MD) 0.18, 95% confidence interval (CI) 0.17 to 0.19), indicating 18% more activity during the day than during the night in the CL group compared with the ND group. Two studies (n = 189) reported on retinopathy of prematurity (stage ≥ 3) and reported no statistically significant differences between CL and ND groups (typical risk ratio (RR) 0.53, 95% CI 0.25 to 1.11, I(2) = 0%; typical risk difference (RD) -0.09, 95% CI -0.19 to 0.01, I(2) = 0%). Two studies (n = 77) reported length of hospital stay (days) and noted a significant reduction in length of stay between CL and ND groups favouring the CL group (weighted mean difference (WMD) -13 days, 95% CI -23 to -2, I(2) = 0%; no heterogeneity). The quality of the evidence according to GRADE was low for this outcome. One study (n = 37) reported less crying at 11 weeks' corrected age (CA) in the CL group compared with the ND group (MD -0.57 hours/24 h, 95% CI -1.09 to -0.05). Tests for heterogeneity were not applicable.Three studies enrolling 120 infants compared CL versus CBL. Two studies (n = 79) reported significantly shorter length of stay in the CL group compared with the CBL group (WMD -16.5 days, 95% CI -26.2 to -6.8, I(2) = 0%; no heterogeneity). The quality of the evidence according to GRADE was low for this outcome. One study (n = 41) reported higher mean weight at three months' CA among infants cared for in the CL nursery (P value < 0.02) and a lower mean number of hours spent awake in 24 hours at three months of age (P value < 0.005). Data could not be entered into RevMan or GRADE. One study (n = 41) reported shorter time on the ventilator in the CL compared with the CBL group (MD -18.2 days, 95% CI -31.40 to -5.0). One study (n = 41) reported a shorter time to first oral feeding in the CL group (MD -6.8 days, 95% CI -13.29 to -0.31). We identified no safety issues. AUTHORS' CONCLUSIONS: Trials assessing the effects of CL have enrolled 544 infants. No study reported on our primary outcome of weight at three or six months. Results from one additional study strengthen our findings that CL versus CBL shortens length of stay, as does CL versus ND. The quality of the evidence on both comparisons for this outcome according to GRADE was low. Future research should focus on comparing CL versus ND.

Short-term morbidities and neurodevelopmental outcomes in preterm infants exposed to magnesium sulphate treatment.

AIM: The aim of the study is to examine whether baseline serum Mg concentration has an impact on short-term and long-term outcomes in preterm infants exposed antenatally to MgSO4. METHODS: Participants included all infants admitted to the neonatal intensive care unit at <32 weeks of gestational age. Infant serum Mg concentration (iMgC) was examined immediately after birth in those exposed to maternal MgSO4. Data for short-term outcomes were collected from the infants' computerised charts. Neurodevelopmental outcomes at 6-12 months corrected age were assessed using the Griffiths Mental Developmental Scales. RESULTS: Of 197 eligible infants, 145 were exposed to MgSO4. Baseline iMgC was available for 88 infants. Mean iMgC was 3.5 ± 0.88 mg/dL (1.6-5.7 mg/dL). Baseline iMgC was not associated with an increased risk for neither early morbidities nor adverse long-term outcome. However, iMgC above the mean (>3.5 mg/dL) was associated with significantly lower scores on locomotor (P = 0.016) and personal-social (0.041) scales in the first year of life. CONCLUSIONS: In a cohort of preterm infants antenatally exposed to MgSO4, elevated baseline iMgC (>3.5 mg/dL) was associated with lower locomotor scores. Further research is needed in order to study the relationship between supra-physiologic iMgC and its effect on the developing brain.

Neonatal morbidities and need for intervention in twins and singletons born at 34-35 weeks of gestation.

OBJECTIVE: To compare indications for delivery and neonatal morbidities between twins and singletons born between 34 and 35 weeks of gestation. STUDY DESIGN: A prospective observational study was performed in which all infants born between January and August 2008, at Sheba Medical Center at 34 0/7-35 6/7 weeks of gestational age were included. Indications for delivery, infants' morbidities and medical interventions were documented. Twins and singletons were compared for antenatal maternal characteristics, risks of short-term neonatal complications and interventions. RESULTS: One hundred and seventy-three mothers and 229 neonates (114 twins and 115 singletons) were included. Background maternal characteristics as well as the use of antenatal steroids and MgSO4 were similar between the groups. Only 44% of all deliveries were spontaneous, while the rest were indicated deliveries. Twins were born lighter and 31.9% of them were SGA. Nevertheless, singletons were significantly more likely to receive medical interventions such as prolonged oxygen use (>1 day) and phototherapy. All late preterm infants (n=5) needing surfactant administration were singletons. Overall, the risk of needing any medical intervention was significantly higher for singletons compared with twins (OR 1.8, 95% CI 1.02-3.2). CONCLUSIONS: A significant proportion of late preterm births is iatrogenic. Twins and singletons are dissimilar with regards to risks of short-term complications. Despite being born smaller and more SGA, twins are at lower risk of requiring medical intervention in the immediate neonatal period compared with singletons.

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.