Unveiling triglyceride levels in preterm neonates: a study to guide targeted monitoring.

BACKGROUND: Mixed lipid emulsion (MLE), most commonly soybean, medium chain triglycerides, olive, and fish oils (SMOF), has replaced soybean-based lipid emulsions in many neonatal intensive care units. Only a few studies report the triglyceride (TG) trajectory in neonates receiving MLE. We designed a study to compare TG levels in neonates receiving MLE stratified by gestational age (GA), birth weight (BW), and growth restriction status. METHODS: We included neonates born at <32 weeks GA or with BW <1500 gm. SMOF is started on admission, and plasma TG levels are measured 24 hours after 2 gm/kg/day and 24 hours after 3 gm/kg/day. TG levels were compared across groups defined by GA (<28 weeks vs. 328 weeks), BW (<1000 gm vs. 31000 gm), and small for GA (SGA) vs. appropriate plus large for GA groups using the Wilcoxon rank sum test. RESULTS: From 2018 to 2021, 427 infants met the inclusion criteria. TG levels were significantly higher in neonates with GA <28 weeks, BW <1000 grams, and SGA with a notable broad distribution of TG levels. Logistic regression analysis confirmed SGA and BW as significant independent predictors of hypertriglyceridemia after SMOF at 2 gm/kg/day and 3 gm/kg/day, respectively. CONCLUSIONS: The study emphasizes the importance of TG monitoring for neonates with GA <28 weeks, BW <1000 grams, and SGA. Conversely, it is advisable to individualize TG monitoring for infants with GA>28 weeks, BW>1000 grams, and non-SGA status. Prospective studies with larger sample sizes are warranted to validate our findings.

Novel TTN Mutation Causing Severe Congenital Myopathy and Uncertain Association with Infantile Hydrocephalus.

Arthrogryposis multiplex congenita (AMC) is characterized by nonprogressive symmetric contractures of multiple joints with normal intellect and normal systemic examination. AMC is often due to fetal akinesia, which has neurologic, muscular, and connective tissue etiologies. We present a case of AMC due to a variant in the titin (TTN) gene in a term neonate. The infant is homozygous for this variant, c.38442dup, which is predicted to result in a truncated protein (p.Pro12815Thr fs∗37, NM_001267550.2). A literature search (PubMed) failed to find reports of this TTN variant. The variant was classified as pathogenic and submitted to ClinVar. Titin is the body's largest protein, expressed in skeletal and cardiac muscles and encoded by the TTN gene. Due to its large size (364 exons), the TTN gene has been difficult to sequence; the number of variants in the TTN gene and the spectrum of titinopathies are probably underestimated.

Educational Perspectives: Palliative Care Education in Neonatal-Perinatal Medicine Fellowship.

The neonatal period from birth to less than or equal to 28 days is one of increased risk of death. Congenital anomalies and prematurity are 2 of the most common risk factors for death at this early age. Many of these neonates will die in an intensive care unit, some with full resuscitative efforts being undertaken despite the understanding that these actions are highly unlikely to yield an outcome different from death. Palliative care allows curative therapies to be provided alongside supportive techniques such as enhanced family communication, attention to spirituality and the psychosocial health of the family, management of symptoms other than those specific to the underlying disease process, and enhancing comfort. The American Academy of Pediatrics has set forth recommendations related to pediatric palliative care for the various pediatric subspecialties; however, much of the focus is on disease processes and curing or mitigating various illnesses. Given the high preponderance of death in the neonatal period, neonatal-perinatal medicine training programs should be tasked with generating formal palliative care training. Such training should be geared to providing better care for neonatal patients with a life-limiting or life-altering illness, and better equipping future neonatologists with the tools needed to provide truly comprehensive care for their sickest patients at risk for death and disability. This article serves to review the concept of palliative care in neonates, discuss the paucity of formal education in palliative care, explore the general trend in palliative care education, review various ways in which palliative care education can be formalized, and define metrics of a successful educational program.

Thromboelastography in term neonates: an alternative approach to evaluating coagulopathy.

OBJECTIVE: To develop normative ranges for citrate-modified and heparinase-modified thromboelastography (TEG) in term neonates. DESIGN: Prospective observational study. SETTING: An outborn neonatal and cardiac intensive care unit in a free-standing academic children's hospital. PATIENTS: Thirty term neonates were enrolled as control subjects. Seventeen infants with clinically documented bleeding requiring blood transfusion were enrolled in the comparison group. MAIN OUTCOME MEASURES: Citrate-modified and heparinase-modified TEG parameters were calculated from blood specimens drawn via peripheral arterial stick or arterial line. RESULTS: TEG in neonates differs from older children and adults; clotting time (R) and clot kinetics (K) values are generally lower while fibrinolysis or rate of clot breakdown (LY30) and coagulation index (CI) are often higher in neonates. TEG values in term neonates calculated as median (Q1-Q3) are as follows: R 4.150 (3.200-6.200), K 1.550 (1.200-1.800), α angle (α) 70.100 (66.000-72.900), maximum amplitude (MA) 61.850 (59.400-66.000), LY30 1.050 (0.100-1.600) and CI 1.950 (0.100 to 2.900). Cut points selected for optimal predictive value for bleeding using receiver operating curve analyses were R>6.3 (sensitivity 82.4%, specificity 80%); K>2.5 (sensitivity 82.4%, specificity 96.7%); α<59 (sensitivity 82.4%, specificity 96.7%); MA<57 (sensitivity 82.4%, specificity 86.7%); CI<-0.15 (sensitivity 88.2%, specificity 83.3%). CONCLUSIONS: The reference ranges and cut points for citrate-modified and heparinase-modified TEG can be used to diagnose and evaluate coagulopathy in term neonates.

Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: a retrospective case-control study.

BACKGROUND: Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormality that predicts bleeding is unclear, leading to varying transfusion therapy practices. METHODS: HIE infants treated with TH between 2008-2012 were included in this retrospective study. Initial, minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined as clinically significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24 hours, 2) transfusion of blood products for hemostasis, or 3) involvement of a critical organ system. Laboratory data between the bleeding group (BG) and non-bleeding group (NBG) were compared. Variables that differed significantly between groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses to determine cut-points to predict bleeding. RESULTS: Laboratory and bleeding data were collected from a total of 76 HIE infants with a mean (±SD) birthweight of 3.34 ± 0.67 kg and gestational age of 38.6 ± 1.9 wks. BG included 41 infants. Bleeding sites were intracranial (n = 13), gastrointestinal (n = 19), pulmonary (n = 18), hematuria (n = 11) or other (n = 1). There were no differences between BG and NBG in baseline characteristics (p > 0.05). Both groups demonstrated INR and aPTT values beyond the acceptable reference ranges utilized for full tem newborns. BG had higher initial and max INR, initial aPTT, and lower min PLT and min Fib compared to NBG. ROC analyses revealed that platelet count <130 × 109/L, fib level <1.5 g/L, and INR >2 discriminated BG from NBG. CONCLUSIONS: Laboratory evidence of coagulopathy is universal in HIE babies undergoing TH. Transfusion strategies to maintain PLT counts >130 × 109/L, fib level >1.5 g/L, and INR <2 may prevent clinical bleeding in this high risk population.

Effect of temperature on thromboelastography and implications for clinical use in newborns undergoing therapeutic hypothermia.

BACKGROUND: Encephalopathic neonates undergoing therapeutic hypothermia have increased risk for coagulopathy secondary to perinatal asphyxia and effects of cooling on the coagulation enzyme cascade. Thromboelastography (TEG) allows for a comprehensive assessment of coagulation that can be regulated for temperature. TEG has not been previously evaluated in newborns undergoing hypothermia treatment. METHODS: Encephalopathic neonates treated with systemic hypothermia were enrolled in this prospective observational study. Daily blood specimens were collected for standard coagulation tests and platelet counts during hypothermia and after rewarming. Concurrent TEG assays were performed at 33.5 and 37.0 °C for comparison. RESULTS: A total of 48 paired TEGs from 24 subjects were performed. Forty percent of the subjects were males, the mean (± SD) birth weight was 3.2 ± 0.7 kg, and the mean gestational age was 38.4 ± 1.4 wk. TEG results differed significantly between assays performed at 37.0 vs. 33.5 °C, indicating more impaired coagulation at 33.5 °C. TEG parameters clot kinetics, angle, maximum amplitude (MA), and coagulation index were significantly associated with clinical bleeding (P < 0.05). These remained significant (except for MA) after controlling for transfusion therapy. CONCLUSION: TEG results are affected by temperature, consistent with the known association of hypothermia with coagulopathy. Several TEG parameters are predictive of clinical bleeding in newborns undergoing hypothermia. Selected cutpoints to predict bleeding risk are temperature dependent.