A Retrospective Cohort Study to Evaluate a Swallow Study Use in the NICU Population to Optimize Feeding Support.

INTRODUCTION: Premature neonates demonstrate difficulties with swallowing due to neurological immaturity as well as a weaker suck reflex compared to full term infants. Swallowing starts to mature by 33-34 weeks of gestational age. In neonates, dysphagia is evaluated clinically by speech-language pathologists and a swallow study is ordered for infants with swallowing difficulties. However, leaving the NICU to undergo a swallow study puts infants under environmental stressors and a swallow study exposes infants to radiation. There is a concern that swallow studies are being over-utilized in the NICU. METHODS: All premature infants born before 36 weeks GA admitted to the Sanford Boekelheide NICU between January 2015 and December 2019 who underwent a swallow study were enrolled in data analysis. Deidentified data was collected retrospectively through electronic medical record review and RedCap was utilized for data storage. Infants were divided in two cohorts; those who underwent a feeding change (feeding thickening) following a swallow study vs those who continued with prior feedings. Infant demographics and characteristics were assessed to identify a group of infants who are at high risk of aspiration. RESULTS: A total of 179 infants were identified. DISCUSSION: A swallow study can identify infants at high risk for aspiration, however, many could potentially be avoided by allowing more time for infant maturation.

Origins of neonatal leptin deficiency in preterm infants.

BACKGROUND: Cord blood leptin increases with advancing gestation. Preterm delivery leads to premature separation from the maternal and placental leptin source predisposing infants to postnatal leptin deficiency, but this has not been fully described. METHOD: Blood leptin levels were measured for infants born before 33 weeks gestation daily for the first 2 days, then weekly until 36 weeks postmenstrual age (PMA). Cord blood was obtained to provide gestational age (GA)-specific standards. RESULTS: Cord blood leptin levels were positively associated with GA at birth, maternal body mass index (BMI) and pregnancy weight gain (all P < 0.05). Following birth, infant leptin levels decreased rapidly (74% decrease within 48 h). The extent of this decline correlated with GA (P < 0.05). Postnatal leptin began to increase by 33-36 weeks PMA, but remained below cord blood leptin levels (P < 0.01). At 36 weeks PMA, leptin levels were influenced by infant's weight and sex (P < 0.01), with females having higher leptin levels (1213 pg/ml vs. 984, P < 0.05). CONCLUSION: Cord blood leptin is influenced by maternal weight gain and BMI, suggesting an important role for trans-placental leptin delivery. Preterm delivery leads to sustained leptin deficiency through 36 weeks PMA, with the most premature male infants facing the longest and harshest deficiency.

Neonatal Leptin Levels Predict the Early Childhood Developmental Assessment Scores of Preterm Infants.

Preterm infants have low circulating levels of leptin, a key trophic hormone that influences growth and development. While the clinical importance of prematurity-associated leptin deficiency is undefined, recent preclinical and clinical investigations have shown that targeted enteral leptin supplementation can normalize neonatal leptin levels. We tested the hypothesis that, independent of growth velocity, prematurity-related neonatal leptin deficiency predicts adverse cardiovascular and neurodevelopmental outcomes. In a planned 2-year longitudinal follow-up of 83 preterm infants born at 22 to 32 weeks' gestation, we obtained blood pressures from 58 children and the Ages & Stages Questionnaire (ASQ-3) for 66 children. Based on univariate analysis, blood pressures correlated with gestational age at birth (R = 0.30, p < 0.05) and weight gain since discharge (R = 0.34, p < 0.01). ASQ-3 scores were significantly higher in female than male children. Utilizing best subset regression with Mallows' Cp as the criterion for model selection, higher systolic blood pressure was predicted by rapid postnatal weight gain, later gestation at delivery and male sex (Cp = 3.0, R = 0.48). Lower ASQ-3 was predicted by lower leptin levels at 35 weeks postmenstrual age, earlier gestation at delivery and male sex (Cp = 2.9, R = 0.45). Children that had leptin levels above 1500 pg/mL at 35 weeks postmenstrual age had the highest ASQ-3 scores at 2 years. In conclusion, independent of growth velocity, higher leptin levels at 35 weeks' gestation are associated with better developmental assessment scores in early childhood. While longer-term follow-up of a larger cohort is needed, these findings support investigations that have suggested that targeted neonatal leptin supplementation could improve the neurodevelopmental outcomes of preterm infants.

Inflammatory Biomarker Profiles in Very Preterm Infants within the Context of Preeclampsia, Chorioamnionitis, and Clinically Diagnosed Postnatal Infection.

Preterm delivery can be precipitated by preeclampsia or infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (clinical chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. Independent of gestational age, MCP-1 was significantly increased (p < 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (p < 0.01), and CRP was increased (p < 0.01) in the presence of chorioamnionitis with funisitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection, with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age, including over a 2-fold increase in MCP-1 among newborns of mothers with preeclampsia. Further, in those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants delivered for maternal indications.

Umbilical Cord Blood Leptin and IL-6 in the Presence of Maternal Diabetes or Chorioamnionitis.

Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.

Renal cell carcinoma trends in Latvia: incidence, mortality, and survival rates. Population-based study.

INTRODUCTION: Baltic States including Latvia are reported as having one of the highest renal cell carcinoma (RCC) incidence and mortality rates in the world. However, data are often presented without stage-specific stratification, making assessment of the overall RCC diagnosis and survival trends challenging. MATERIAL AND METHODS: We collected data on all newly diagnosed RCC patients from the national population-based cancer registry between 1997 and 2016. We analyzed RCC incidence, mortality and survival trends using Joinpoint analysis. Kaplan-Meier analysis was performed for 5- and 10-year cancer specific survival rate calculations. RESULTS: There were a total of 7893 patients with newly diagnosed RCC. The age standardized (AS) incidence rate (per 100,000) increased slightly from 8.9 in 1997 to 9.8 in 2016. There were no specific changes in the incidence rate trend. Detection of early stage RCC increased by 5.4% annually. The AS mortality rates (per 100,000) decreased from 4.9 in 1997 to 3.9 in 2016, however, it did not reach a statistically significant change. The mortality rates decreased significantly in females and in the age group of 60-69 years. The 5-year cancer specific survival (CSS) rate increased from 55.1% in 1997-2001 to 66.6% in years 2007-2011. The 10-year CSS rate increased from 49.1% in 1997-2001 to 56.5% in years 2002-2006. CONCLUSIONS: During the study period, RCC incidence rates increased and overall mortality rates did not change. Similar to the rest of the world, the incidence of RCC diagnosed at an earlier stage increased and 5- and 10-year survival rates improved.

Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure.

The risk of hypertension is increased by intrauterine growth restriction (IUGR) and preterm birth. In the search for modifiable etiologies for this life-threatening cardiovascular morbidity, a number of pathways have been investigated, including excessive glucocorticoid exposure, nutritional deficiency and aberration in sex hormone levels. As a neurotrophic hormone that is intimately involved in the cardiovascular regulation and whose levels are influenced by glucocorticoids, nutritional status and sex hormones, leptin has emerged as a putative etiologic and thus a therapeutic agent. As a product of maternal and late fetal adipocytes and the placenta, circulating leptin typically surges late in gestation and declines after delivery until the infant consumes sufficient leptin-containing breast milk or accrues sufficient leptin-secreting adipose tissue to reestablish the circulating levels. The leptin deficiency seen in IUGR infants is a multifactorial manifestation of placental insufficiency, exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant suffers from the same cascade of events, including separation from the placenta, antenatal steroid exposure and persistently underdeveloped adipose depots. Preterm infants remain leptin deficient beyond term gestation, rendering them susceptible to neurodevelopmental impairment and subsequent cardiovascular dysregulation. This pathologic pathway is efficiently modeled by placing neonatal mice into atypically large litters, thereby recapitulating the perinatal growth restriction-adult hypertension phenotype. In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension. Further pathway interrogation and clinical translation are needed to fully test the therapeutic potential of perinatal leptin supplementation.