Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

Background: Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis. Methods: The study was conducted at the Erasmus University Medical Center–Sophia Children’s Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia). Results: A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64–3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70–5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68–2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support. Conclusions: Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy

Fetal and infant growth patterns and kidney function at school age

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Childhood kidney outcomes in relation to fetal blood flow and kidney size

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Infant feeding patterns are associated with cardiovascular structures and function in childhood

Nutrition in infancy seems to be associated with cardiovascular disease and its risk factors in adulthood. These associations may be explained by cardiovascular developmental adaptations in childhood in response to specific infant feeding patterns. The aim of this study was to assess whether duration and exclusivity of breastfeeding and timing of introduction of solid foods affect cardiovascular development in childhood. In a population-based prospective cohort study from fetal life onward, information about duration and exclusivity of breastfeeding and timing of introduction of solid foods was obtained from delivery reports and questionnaires. Blood pressure, carotid-femoral pulse wave velocity (PWV), left atrial diameter (LAD), aortic root diameter (AOD), left ventricular (LV) mass, and fractional shortening (FS) were measured at a median age of 6.0 y (95% range: 5.6-7.4 y). Analyses were based on 5003 children. Age at introduction of solid foods was negatively associated with systolic and diastolic blood pressure at the age of 6 y. Compared with children who had ever been breast-fed, never-breast-fed children had a higher carotid-femoral PWV (β: 0.13 m/s; 95% CI: 0.03, 0.24 m/s), a smaller LAD (β: 20.29 mm; 95% CI:20.55,20.03 mm), and less LV mass (b:21.46 g; 95% CI:22.41,20.52 g) at the age of 6 y. Among breast-fed children, duration and exclusivity were not associated with cardiovascular structures or function. Breastfeeding pattern and age at introduction of solid foods were not associated with AOD or FS. Feeding patterns in infancy may influence cardiovascular development in childhood. Further research is required to replicate these findings and to investigate whether these changes contribute to an increased risk of cardiovascular disease in later life

Parental smoking during pregnancy and total and abdominal fat distribution in school-age children: The Generation R Study

Objective: Fetal smoke exposure may influence growth and body composition later in life. We examined the associations of maternal and paternal smoking during pregnancy with total and abdominal fat distribution in school-age children. Methods: We performed a population-based prospective cohort study among 5243 children followed from early pregnancy onward in the Netherlands. Information about parental smoking was obtained by questionnaires during pregnancy. At the median age of 6.0 years (90% range: 5.7-7.4), we measured anthropometrics, total fat and android/gynoid fat ratio by dual-energy X-ray absorptiometry, and preperitoneal and subcutaneous abdominal fat were measured by ultrasound. Results: The associations of maternal smoking during pregnancy were only present among girls (P-value for sex interaction < 0.05). Compared with girls from mothers who did not smoke during pregnancy, those from mothers who smoked during the first trimester only had a higher android/gynoid fat ratio (difference 0.23 (95% confidence interval (CI): 0.09-0.37) s.d. scores (SDS). Girls from mothers who continued smoking throughout pregnancy had a higher body mass index (difference: 0.24 (95% CI: 0.14-0.35) SDS), total fat mass (difference: 0.23 (95% CI: 0.14-0.33) SDS), android/gynoid fat ratio (difference: 0.34 (95% CI: 0.22-0.46) SDS), subcutaneous abdominal fat (difference: 0.22 (95% CI: 0.11-0.33) SDS) and preperitoneal abdominal fat (difference: 0.20 (95% CI: 0.08-0.31) SDS). Similar associations with body fat distribution outcomes were observed for paternal smoking during pregnancy. Both continued maternal and paternal smoking during pregnancy may be associated with an increased risk of childhood overweight. The corresponding odds ratios were 1.19 (95% CI: 0.98-1.46) and 1.32 (1.10-1.58), respectively. Conclusions: Maternal and paternal smoking during pregnancy are associated with an adverse body and abdominal fat distribution and increased risk of overweight in children. Similar effects of maternal and paternal smoking suggest that direct intrauterine mechanisms and common family-based lifestyle-related factors explain the associations

Dietary Intake, FTO genetic variants, and adiposity: A combined analysis of over 16,000 children and adolescents

The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and mac

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation