Distinct protein patterns related to postnatal development in small for gestational age preterm infants.

BACKGROUND: Preterm infants, especially those born small for gestational age (SGA), are at risk of short-term and long-term health complications. Characterization of changes in circulating proteins postnatally in preterm infants may provide valuable fundamental insights into this population. Here, we investigated postnatal developmental patterns in preterm infants and explored protein signatures that deviate between SGA infants and appropriate for gestational age (AGA) infants using a mass spectrometry (MS)-based proteomics workflow. METHODS: Longitudinal serum samples obtained at postnatal days 0, 3, 7, 14, and 28 from 67 preterm infants were analyzed using unbiased MS-based proteomics. RESULTS: 314 out of 833 quantified serum proteins change postnatally, including previously described age-related changes in immunoglobulins, hemoglobin subunits, and new developmental patterns, e.g. apolipoproteins (APOA4) and terminal complement cascade (C9) proteins. Limited differences between SGA and AGA infants were found at birth while longitudinal monitoring revealed 69 deviating proteins, including insulin-sensitizing hormone adiponectin, platelet proteins, and 24 proteins with an annotated function in the immune response. CONCLUSIONS: This study shows the potential of MS-based serum profiling in defining circulating protein trajectories in the preterm infant population and its ability to identify longitudinal alterations in protein levels associated with SGA. IMPACT: Postnatal changes of circulating proteins in preterm infants have not fully been elucidated but may contribute to development of health complications. Mass spectrometry-based analysis is an attractive approach to study circulating proteins in preterm infants with limited material. Longitudinal plasma profiling reveals postnatal developmental-related patterns in preterm infants (314/833 proteins) including previously described changes, but also previously unreported proteins. Longitudinal monitoring revealed an immune response signature between SGA and AGA infants. This study highlights the importance of taking postnatal changes into account for translational studies in preterm infants.

Most major bleeds in preterm infants occur in the absence of severe thrombocytopenia: an observational cohort study.

OBJECTIVE: To describe the incidence of major bleeds according to different platelet counts in very preterm infants, and to explore whether this association is influenced by other risk factors for bleeding. DESIGN: Observational cohort study. SETTING: A Dutch tertiary care neonatal intensive care unit. PATIENTS: All consecutive infants with a gestational age at birth <32 weeks admitted between January 2004 and July 2022. EXPOSURE: Infants were stratified into nine groups based on their nadir platelet count (×109/L) during admission (<10, 10-24, 25-49, 50-99, 100-149, 150-199, 200-249, 250-299 and ≥300), measured before the diagnosis of a major bleed and before any platelet transfusion was administered. MAIN OUTCOME MEASURE: Incidence of major bleeds during admission. Logistic regression analysis was used to quantify the relationship between nadir platelet count and incidence of major bleeds. RESULTS: Among 2772 included infants, 224 (8%) developed a major bleed. Of the infants with a major bleed, 92% (206/224) had a nadir platelet count ≥50×109/L. The incidence of major bleeds was 8% among infants with and without severe thrombocytopenia (platelet count <50×109/L), 18/231 (95% CI 5 to 12) and 206/2541 (95% CI 7 to 9), respectively. Similarly, after adjustment for measured confounders, there was no notable association between nadir platelet counts below versus above 50×109/L and the occurrence of major bleeds (OR 1.09, 95% CI 0.61 to 1.94). CONCLUSION: In very preterm infants, the vast majority of major bleeds occur in infants without severe thrombocytopenia.

Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors.

OBJECTIVES: Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. STUDY DESIGN: A cohort study was carried out among all neonates with proven culture positive sepsis that were admitted to a tertiary NICU between 2006 and 2015 (n = 460). The occurrence, severity and duration of thrombocytopenia were recorded, as well as major bleedings and potential risk factors for mortality in neonatal sepsis. RESULTS: Sepsis was diagnosed in 460 of 6551 neonates (7%). Severe thrombocytopenia (platelets ≤50*109/L) occurred in 20% (92/460) of septic neonates. The median time for platelets to rise >100*109 was 6.0 days (interquartile range 4.0-7.0). On multivariate analysis, maternal hypertension, intravascular thrombosis and Gram negative (as opposed to Gram positive) sepsis were independently associated with thrombocytopenia in neonatal sepsis. In severe thrombocytopenia, 10% (9/92) suffered a severe IVH, compared to 5% (20/356) in neonates with platelets >50*109/L (p = 0.125). 10% (9/92) suffered a pulmonary hemorrhage, compared to 2% (9/368) in neonates with platelets >50*109/L (p = 0.001). On multivariate analysis, thrombocytopenia and Gram negative (as opposed to Gram positive) sepsis were independently associated with neonatal mortality. CONCLUSIONS: Thrombocytopenia is independently associated with maternal hypertension, intravascular thrombosis and Gram negative sepsis. Thrombocytopenia in neonatal sepsis increases the risk of mortality nearly four-fold, with another six-fold increase in mortality in case of Gram negative sepsis.

Loneliness in Children and Adolescents With Chronic Physical Conditions: A Meta-Analysis.

Objective: This meta-analysis examines loneliness in children and adolescents with chronic physical conditions as compared with their peers. Multilevel meta-analyses were performed on 43 studies (69 samples), published between 1987 and 2015. A total of 2,518 individuals with chronic physical conditions and 1,463 control peers were included in the analyses. Children and adolescents with chronic conditions are, on average, somewhat lonelier than their peers without such conditions. Moreover, the link between chronic conditions and loneliness varied according to the recruitment procedure used for participant selection. Stronger links were found for studies that recruited from patient organizations as compared with clinical registers. Findings support the link between loneliness and chronic conditions. To take into account the heterogeneity within patient groups, we advocate an alternative approach that cuts across diagnostic boundaries and focuses on illness-related variables such as illness duration and visibility of the condition.