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.

Ultrasound assessment of endotracheal tube depth in neonates: a prospective feasibility study.

OBJECTIVE: To examine the reliability of a novel ultrasound (US) method for assessment of endotracheal tube (ETT) position in neonates. DESIGN: Prospective, observational, single-centre, feasibility study. SETTING: Level III neonatal intensive care unit. PATIENTS: Term and preterm neonates requiring endotracheal intubation. INTERVENTION: US measurement of the ETT tip to right pulmonary artery (RPA) distance was used to determine ETT position according to one-fourth to three-fourths estimated tracheal length for weight. US demonstration of pleural sliding and diaphragmatic movement was also assessed. Chest radiography (CXR) was performed following each intubation. MAIN OUTCOME MEASURES: Agreement between US assessment of ETT tip position and CXR served as the gold standard. Sensitivity, specificity, positive and negative predictive values for each US method and correlation between ETT tip to RPA distance on US, and ETT tip to carina distance on CXR were assessed. RESULTS: Forty-two US studies were performed on 33 intubated neonates. US evaluation of ETT-RPA distance identified 100% of ETTs positioned correctly: 77% deep and 80% high, demonstrating strong agreement with CXR (kappa=0.822). Sensitivity was 78%, specificity 100%, positive predictive value 100% and negative predictive value 86%. US ETT-RPA distance strongly correlated with CXR ETT-carina distance (r=0.826). No significant agreement was found between CXR and US assessment of pleural sliding and diaphragmatic movement. No adverse events were encountered during US scans. CONCLUSION: US evaluation of ETT-RPA distance demonstrated excellent accuracy for determining ETT position in neonates compared with CXR. More research is needed to support its feasibility in clinical settings.

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.

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.

Early Enteral Feeding of the Preterm Infant-Delay until Own Mother's Breastmilk Becomes Available? (Israel, 2012-2017).

AIM: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother's breastmilk or to wait for breastmilk to be available. METHODS: A retrospective study of infants born prior to 32 weeks of gestation during the period 2012-2017 at a single tertiary center in Tel Aviv, Israel. Three TF groups were defined: exclusive breastmilk, mixed, and exclusive formula. Univariate and multivariate analyses were conducted. Logistic regression was used, and adjusted odds ratio and 95% interval were reported. RESULTS: Univariate analysis demonstrated that infants in the exclusive breastmilk group were born earlier, had lower birth weights and lower Apgar scores, were given lower volumes of TF, and were more likely to have a longer hospital stay. Poor composite outcome was more common among the exclusive breastmilk group. Multivariate regression analysis revealed no differences in incidence of early neonatal morbidities between the groups, except for longer duration of parenteral nutrition in the exclusive breastmilk group. CONCLUSION: In our cohort, exclusive formula TF was not associated with increased risk of any of the studied morbidities. Clinicians should consider this finding in deciding between early TF or fasting while waiting for own mother's breastmilk.

Neurodevelopmental outcomes of preterm infants born to preeclamptic mothers - A case-control study.

OBJECTIVE: Preeclampsia during pregnancy is associated with an increased risk for various neonatal morbidities. We aimed to investigate the association between prematurity due to maternal preeclampsia and developmental outcomes. STUDY DESIGN: This retrospective matched case-control study included 39 preterm infants (<32 weeks gestation) born to preeclamptic mothers between 2012 and 2016, compared with 39 infants born to mothers without preeclampsia. The two groups were matched for gestational age (±1 week), gender and plurality. Neurodevelopmental outcome was assessed using the Griffith's Mental Developmental Scales at 6, 12 and 24 months corrected age. RESULTS: The groups were comparable in terms of gestational age (30.2 weeks vs 29.8, P = 0.6), exposure to antenatal glucocorticosteroids and magnesium sulfate. The two groups differed significantly in birthweight so that cases had significantly lower birthweight, 1100 (IQR 844.5-1316.5) vs. 1370 (IQR 1174-1604.5) grams. 19/39 (48.7%) cases were small for gestational age compared with only 4/39 (10.3%) controls (P < 0.01). 16/39 of cases were born less than 1000 g, compared with only 5/39 controls (41% vs 12.8%, P < 0.01). Early complications were similar. Compared with controls, an overall trend for better neurodevelopmental performance on Griffith's score was found for cases, especially for early (6 months) non-motor performance. All severely disabled infants (Griffith's score < 55) at 24 months assessment were among controls. CONCLUSION: Although significantly smaller and smaller for gestational age, neurodevelopmental assessment by Griffiths' Mental Development Scales was similar for cases and controls with a trend towards better performance of cases at 6 months. Further studies are needed to determine whether the trend for better performance implies a developmental advantage.

Predictors of Developmental and Respiratory Outcomes Among Preterm Infants With Bronchopulmonary Dysplasia.

Objectives: To examine the importance of perinatal and postnatal environmental factors on developmental and respiratory outcomes among preterm infants with bronchopulmonary dysplasia (BPD). Methods: Preterm infants (<32 weeks of gestation) born at a single tertiary medical center between 2012 and 2015 were included. Development was assessed at 12 months corrected age. Parents retrospectively completed a health and lifestyle questionnaire reviewing their child's health during the first 2 years of life. A linear regression model was applied to assess the effect of various perinatal and postnatal factors on development. A machine-learning algorithm was trained to assess factors affecting inhaler use. Results: Of 398 infants meeting the inclusion criteria, 208 qualified for the study: 152 (73.1%) with no BPD, 40 (19.2%) with mild BPD, and 16 (7.7%) with moderate-severe BPD. Those in the moderate-severe group were more likely to be male, have mothers who were less educated, and require longer ventilation periods and less time to regain birth weight. They were also more likely to have mothers with asthma/allergies and to have a parent who smoked. Those in the moderate-severe BPD group exhibited significantly lower developmental scores (85.2 ± 16.4) than the no-BPD group (99.3 ± 10.9) and the mild BPD group (97.8 ± 11.7, p < 0.008) as well as more frequent inhaler use (p = 0.0014) than those with no or mild BPD. In addition to perinatal factors, exposure to breast milk, income level and daycare attendance positively affected development. Exposure to cigarette smoke, allergies among family members and daycare attendance proved to be important factors in inhaler use frequency. Conclusions: Postnatal environmental factors are important in predicting and modifying early childhood outcomes among preterm infants.

Early-onset preeclampsia - The impact of antiphospholipid antibodies on disease severity.

OBJECTIVES: Antiphospholipid antibodies have been associated with various obstetric complications, including recurrent pregnancy loss, preeclampsia, intrauterine growth restriction, placental insufficiency, and late fetal loss. Despite the amassed body of evidence emphasizing the association between antiphospholipid antibodies and preeclampsia, the severity of preeclampsia with regard to antiphospholipid antibodies status has not been elucidated. This study aimed to evaluate whether early-onset preeclampsia with severe features before 34 weeks' gestation is clinically different when associated with antiphospholipid antibodies. STUDY DESIGN: In this retrospective case-control study, we collected data on pregnancy outcomes of 101 women with singleton pregnancies who delivered prior to 34 weeks of gestation due to preeclampsia with severe features. The antiphospholipid antibodies status of 55 of these women was available for analysis. The study group comprised 20 women with positive antiphospholipid antibodies (positive-aPL group), while the control group comprised 35 women without antiphospholipid antibodies (negative-aPL group). Obstetric and neonatal outcomes, laboratory results and pregnancy complications were extracted from medical records. RESULTS: In the clinical setting of early-onset preeclampsia with severe features necessitating delivery before 34 weeks gestation, positive-aPL women were hospitalized earlier (29, IQR 26.3-32, vs. 32, IQR 28-33 weeks gestation, P = 0.05), gave birth at a significantly earlier gestational age (30, IQR 28.3-32.8 vs. 33, IQR 30-34, P = 0.02) with a lower mean birth-weight (1266.7 ±â€¯579.6 vs. 1567.3 ±â€¯539.7 g, P = 0.058) compared with negative-aPL women. Furthermore, platelet nadir was significantly lower for positive-aPL compared with negative-aPL women (97 ±â€¯49×103/µL vs. 141 ±â€¯61×103/µL, P < 0.001) and maximal serum creatinine was higher (1.0 ±â€¯0.3 mg/dL vs. 0.9 ±â€¯0.1 mg/dL, P = 0.03). Rates of neonatal complications were low and comparable between groups, except for higher rates of retinopathy of prematurity requiring treatment in the study group (30.0% vs. 5.7%, p = 0.02), and there was a trend for higher perinatal mortality among study group infants. CONCLUSIONS: The presence of antiphospholipid antibodies in women with early-onset preeclampsia with severe features is associated with earlier, more severe disease course. Expedited screening for antiphospholipid antibodies in cases of early-onset severe preeclampsia may be considered, along with close monitoring for pregnant women with positive antibodies.

Hyper-Reactivity to Salience Limits Social Interaction Among Infants Born Pre-term and Infant Siblings of Children With ASD.

The ability to engage attention with selected stimuli is essential for infants to explore the world and process information relating to their surroundings. There are two main populations with a higher risk to develop attentional and social deficits whose deficits may arise from difficulties in regulating attention to salient cues: (1) siblings of children diagnosed with Autism; and (2) infants who were born pre-term. This study investigated infants' (N = 97) attention-engagement and pupil-dilation (PD) at 9 months of age, using a gaze-contingent paradigm and a structured social interaction. Specifically, we explored attention to stimuli with simple salient features (e.g., clear defined shapes, colors, and motions) vs. more complex non-social cues (amorphous shapes, colors, and motions) and social interaction in typically developing infants (TD, N = 25) and among two groups of infants at-risk to develop social difficulties (pre-terms, N = 56; siblings of children with Autism, N = 16). Findings show that the two risk groups preferred stimuli with simple features (F = 11.306, p < 0.001), accompanied by increased PD (F = 6.6, p < 0.001). Specifically, pre-term infants showed increased PD toward simple vs. complex stimuli (p < 0.001), while siblings showed a pervasive hyper-arousal to both simple and complex stimuli. Infants in the TD group preferred complex stimuli with no change in PD. Finally, the preference for the simple stimulus mediated the relationship between increased risk for social difficulties and decreased engagement duration in face-to-face interaction with the experimenter. Results suggest that activation of the attention-salience network shapes social abilities at infancy. Further, hyper-reactivity to salient stimuli limits social interaction among infants born pre-term and siblings of children with ASD.

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.

Using sensor-fusion and machine-learning algorithms to assess acute pain in non-verbal infants: a study protocol.

INTRODUCTION: Objective pain assessment in non-verbal populations is clinically challenging due to their inability to express their pain via self-report. Repetitive exposures to acute or prolonged pain lead to clinical instability, with long-term behavioural and cognitive sequelae in newborn infants. Strong analgesics are also associated with medical complications, potential neurotoxicity and altered brain development. Pain scores performed by bedside nurses provide subjective, observer-dependent assessments rather than objective data for infant pain management; the required observations are labour intensive, difficult to perform by a nurse who is concurrently performing the procedure and increase the nursing workload. Multimodal pain assessment, using sensor-fusion and machine-learning algorithms, can provide a patient-centred, context-dependent, observer-independent and objective pain measure. METHODS AND ANALYSIS: In newborns undergoing painful procedures, we use facial electromyography to record facial muscle activity-related infant pain, ECG to examine heart rate (HR) changes and HR variability, electrodermal activity (skin conductance) to measure catecholamine-induced palmar sweating, changes in oxygen saturations and skin perfusion, and electroencephalography using active electrodes to assess brain activity in real time. This multimodal approach has the potential to improve the accuracy of pain assessment in non-verbal infants and may even allow continuous pain monitoring at the bedside. The feasibility of this approach will be evaluated in an observational prospective study of clinically required painful procedures in 60 preterm and term newborns, and infants aged 6 months or less. ETHICS AND DISSEMINATION: The Institutional Review Board of the Stanford University approved the protocol. Study findings will be published in peer-reviewed journals, presented at scientific meetings, taught via webinars, podcasts and video tutorials, and listed on academic/scientific websites. Future studies will validate and refine this approach using the minimum number of sensors required to assess neonatal/infant pain. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03330496).

Oral glucose tolerance test for suspected late onset gestational diabetes.

BACKGROUND: Oral glucose tolerance test is used for the diagnosis of gestational diabetes at the second trimester, however, its use at term has been questioned. OBJECTIVE: To compare obstetric outcomes in women with and without abnormal oral glucose tolerance test (OGTT) conducted at term due to large for gestational age (LGA) fetuses or polyhydramnios. METHODS: A retrospective cohort study including all women ≥37 weeks of gestation, with normal glucose challenge test (GCT), who performed 100 g OGTT at term, due to LGA fetus or polyhydramnios between January 2012 and January 2017. Abnormal OGTT was considered according to Carpenter and Coustan criteria. Data are presented as median and inter-quadrantile range (IQR). RESULTS: Database included 34,897 women, of them, 1131 (3.2%) met inclusion criteria. A total of 150 (13.2%) and 981 (86.7%) women were included in the abnormal and the normal OGTT groups, respectively. Women in the abnormal OGTT group had higher glucose levels on GCT [126 (IQR 107-137) versus 110 (IQR 91-132) mg/dL; p = .001]. The rate of cesarean deliveries was twice as high in the abnormal OGTT group [37 (24.7%) versus 103 (10.5%); p = .001]. No difference in the rate of shoulder dystocia, postpartum hemorrhage (PPH) or third and fourth-degree perineal tear was observed among women who delivered vaginally. CONCLUSIONS: Abnormal OGTT at term was related to a higher rate of cesarean deliveries, with no difference in obstetrical complications among women who delivered vaginally.

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.

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.

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.

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.