Median Reference Values Research Articles

Growth and micronutrient status parameters of Nigerian preterm infants consuming preterm formula or breastmilk.

Moderate-to-late preterm infants (32-34 weeks GA) have increased risk of neonatal morbidities compared to term infants, however dedicated nutritional guidelines are lacking. Moderate-to-late preterm infants received a preterm formula (n = 17) or breastmilk (n = 24) from age 2-10 weeks in a non-randomized, open-label observational study. Anthropometric measurements were assessed bi-weekly. Blood concentrations of hemoglobin, ferritin, serum retinol, and 25-hydroxy-vitamin D (25OHD) were analyzed at age 2 and 10 weeks. Average growth per day was 14.7 g/kg BW/day in formula-fed and 12.8 g/kg BW/day in breastmilk-fed infants but not different from each other. Length and head circumference in both groups were in line with the median reference values of the Fenton growth chart. At 10 weeks of age, hemoglobin tended to be higher in the formula-fed group (10.2 g/dL vs. 9.6 g/dL, p = 0.053). 25OHD increased in formula- and breastmilk-fed infants from 73.8 to 180.9 nmol/L and from 70.7 to 97.6 nmol/L, respectively. Serum retinol only increased in the formula-fed group (0.63 to 1.02 µmol/L, p < 0.001). Breastfeeding resulted in adequate growth in moderate-late preterm infants but was limiting in some micronutrients. The preterm formula provided adequate micronutrients, but weight gain velocity was higher than the Fenton reference value. Unfortified breastmilk resulted in adequate growth in weight, length and head circumference in Nigerian moderate to late preterm infants during an study period of 8 weeks, but status of vitamin D, vitamin A and iron needs to be monitored. The high-energy formula, developed for very preterm infants, resulted in higher growth in body weight in moderate to late preterm infants than the median of the Fenton preterm growth chart. This study supports the necessity of dedicated nutritional guidelines, and regular monitoring of growth and nutritional status of moderate to late preterm infants.

THU091 Hypopituitarism And The Finding Of Hyperprolactinemia Following Mild Traumatic Brain Injury In Female Athletes

Abstract Disclosure: L.Ó. Eggertsdóttir Claessen: None. H. Kristjánsdóttir: None. M.K. Jónsdóttir: None. S.H. Lund: Employee; Self; Amgen Inc. I.S. Kristensen: None. H.Á. Sigurjónsdóttir: None. Background Hypopituitarism (HP) following mild traumatic brain injury (mTBI) in sports can have serious consequences making prompt diagnosis and treatment essential. Studies have focused on male populations despite female athletes being more susceptible to mTBI. To the best of our knowledge, this study is the first all-female study reporting the prevalence of HP following mTBI. Subjects The study included 508 female athletes aged 18 to 45 years currently active in or retired from soccer, team handball, basketball, ice hockey, and martial arts who answered an online questionnaire regarding mTBI history. Women who reported one or more concussions (n = 308) were invited to participate in a medical interview and a physical examination with 151 accepting. Consequently, 133 women attended pituitary hormone screening blood tests (SBT). Methods SBT were taken at 8 a.m. and included S-IGF1, S-cortisol, S-prolactin, S-TSH, S-fT4, S-FSH, S-oestrogen, and S-progesterone measurements. When SBT were repeatedly outside reference value (O-RV), participants were referred to an endocrinologist for a medical interview and physical examination. Detailed endocrinological tests for possible HP were performed as indicated. When serum levels of TSH or fT4 were O-RV, anti-TPO antibodies were measured and when negative, an MRI was performed. If S-prolactin was repeatedly above reference value (RV) an MRI was performed. When S-cortisol was below 350 mmol/L, morning plasma ACTH was added and morning Synacthen test performed. When S-IGF1 was below median RV and clinical symptoms of GHD were present, a GHRH-arginine test was performed. An ITT was performed in one woman due to practical reasons and strong clinical symptoms indicating GHD. Results etailed endocrinological evaluation for possible HP was indicated in 86 women. Pituitary dysfunction (PD) was diagnosed in 16 women (12.0%). Six (4.5%) women had HP. One woman had GH measurements below RV in a GHRH-arginine test (peak GH levels ≤11.0 µg/L for BMI &amp;lt;25 kg/m2) and one had GH below &amp;lt;3µg/L in an ITT. Four women had low or normal TSH levels (reference range 0.270 - 4.20 mIU/L), low fT4 (reference range 12 - 22 pmol/L) and a negative anti-TPO measurement. Ten women (7.5%) had hyperprolactinemia (HPRL) (reference range 4.79 - 23.3 μg/L). Four of the 10 women with HPRL were diagnosed with a prolactinoma following an MRI. Medical treatment was initiated for 13 (9.8%) women as one woman had a prolactinoma but no clinical symptoms of HPRL. Conclusions PD is an important consideration in post-concussion care as 12.0% had PD following mTBI with 9.8% requiring medical treatment. Six women (4.5%) had HP following mTBI (GHD = 2 and central hypothyroidism n = 4). This is lower than previously reported and may be due to HP recovering with time. As six women had HPRL without a prolactinoma, HRPL may represent pituitary or hypothalamic injury following mTBI. Presentation: Thursday, June 15, 2023

Software tools for practical application of human nutrient requirements in food-based social science research

This article focuses on the use of human nutrition requirements for applied social science research by non-nutrition experts. Our motivation is to provide the data and default nutrient requirements to calculate the Cost of Nutrient Adequacy (CoNA) least-cost diet meeting specified nutrient requirements. The final format of the resulting datafile is ready for use in the CoNA protocol. However, we expect this article and associated software tools to be generally useful to social science researchers interested in nutrition-related research questions and the potential implications of food systems’ changes for nutrition. We provide readily usable data files (Supplement 1) containing the Dietary Reference Intakes (DRIs) and guide non-nutrition experts through appropriate use to establish the nutrient needs and assess the adequacy of diets for populations and groups. We complement the DRIs with companion data files (Supplement 2) containing the WHO Child Growth Standards and WHO Growth References for School-Aged Children and Adolescents percentiles tables of anthropometric measures, extract the median heights and weights, and calculate median reference values for the age-sex groups consistent with the DRIs nutrient requirements. We provide calculations of energy requirements using the DRIs Estimated Energy Requirement (EER) equation and WHO growth references for all age-sex groups and physical activity levels. We also calculate the protein Estimated Average Requirement (EAR) per kilogram body weight according to the WHO growth references. For children under two, we provide nutrient needs required from food in Supplement 3. We provide Stata code and R syntax (Supplements 4 and 5) to compile the single data files into usable datasets for statistical analysis. Finally, we also provide data files (Supplement 6) with the recently proposed harmonized average values and upper levels and briefly discuss their potential application.

Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy.

An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm. Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

Serum bile acids in term and preterm neonates: A case-control study determining reference values and the influence of early-onset sepsis.

Serum bile acids (BA) reference values are lacking for neonates. Therefore, this study aimed to determine serum BA reference values in term and preterm neonates. Furthermore, as serum BA concentrations are well-known to rise in septic adults, BA values were determined in early-onset neonatal sepsis (EOS), a common and serious disease in neonates.Using high-performance liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS), we profiled serum BA in 236 infants, including healthy term neonates (n = 84), premature infants (n = 101), and both term infants (n = 35) and preterm infants (n = 16) with EOS. We examined the impact of prematurity and EOS on BA concentrations.The median reference values of serum BA were 8.0 μmol/L, interquartile range (IQR): 4.6 to 12.9, in healthy term neonates and 10.1 μmol/L, IQR: 5.7 to 15.7, in preterm neonates. Neonates with EOS had significantly lower median BA values, term (4.7 μmol/L, IQR: 2.7–7.6; P < 0.01) as well as preterm (6.4 μmol/L, IQR: 3.5–8.4; P < 0.01). Furthermore, primary and conjugated BA were most abundant in all groups. Taurine-conjugated BA were predominant in all neonates; glycine-conjugated BA were significantly lower in term neonates with EOS than in controls (P < 0.05). Multivariate regression analysis results obtained for BA and inflammatory parameters revealed that BA are an independent factor associated with EOS.This is the first study to determine standard value ranges of serum BA in neonates using HPLC-HRMS. In contrast to adults with sepsis, neonates suffering from EOS exhibit significantly lower BA values than do controls of the same gestational age. These data suggest BA as a supplementary parameter within a panel of biomarkers for EOS in the future.

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition.

The Comprehensive Complication Index

To develop and validate a comprehensive complication index (CCI) that integrates all events with their respective severity. Reporting of surgical complications is inconsistent and often incomplete. Most studies fail to provide information about the severity of complications, or inform only on the most severe event, ignoring events of lesser severity. We used an established classification of complications, adopting methods from operation risk index analysis in marketing research to develop a formula that considers all complications that may occur in a patient. The weights of each grade of complication, defined as median reference values, were obtained from 472 participants, who rated 30 different complications. Validation to assess sensitivity to treatment effects and validity of the CCI was performed by 4 different approaches, based on 1299 patients. The CCI is calculated as the sum of all complications that are weighted for their severity (multiplication of the median reference values from patients and physicians). The final formula yields a continuous scale to rank the severity of any combination of complications from 0 to 100 in a single patient. The CCI was highly sensitive in detecting treatment effect differences in the context of a randomized trial (effect size detected by CCI vs conventional standardized morbidity outcomes). It also showed a negative correlation with postoperative health status (r = -0.24, P = 0.002), and high correlation with the results of patient-rated single and multiple complications on conjoint analysis (r = 0.94, P < 0.001). The CCI summarizes all postoperative complications and is more sensitive than existing morbidity endpoints. It may serve as a standardized and widely applicable primary endpoint in surgical trials and other interventional fields of medicine. The CCI can be readily computed on the basis of tabulated complications according to the Clavien-Dindo classification (available at www.assessurgery.com).

Perinatal drug exposure and renal function in very preterm infants

ObjectiveTo determine the impact on glomerular filtration rate (GFR) and tubular function of drugs prescribed to very preterm infants during the first week of life.DesignProspective multicentre cohort study of infants...

346 Neonatal Treatment Toxicity on Day 7 and Throughout the First Month of Life

Background and aims: Preterm infants are at high risk of drug-induced acute kidney injury. We aimed to determine the impact on GFR during the first month of life, of the drugs prescribed shortly after birth in the Neonatal Intensive Care Units. Methods: multicenter study nested in a cohort of 27-31 weeks GA infants. Infants parted into two groups: “Low GFR”: GFR day7< median GFR for GA; “High GFR”: GFR day7 ≥ median GFR for GA GFR was measured weekly for one month and analyzed with a logistic regression model and an ANOVA with repeated measures (drug and time effects throughout the first month). Results: 269 infants included. Nephrotoxic drugs prescribed before day7 were mainly aminoglucosides, glycopeptides, and Cox-inhibitors. Cox-inhibitors were far the most nephrotoxic drugs, and GFR remained low for the first month of life after Cox-inhibitor administration. Even high plasmatic levels of aminoglycosides or of glycopeptides did not reach the nephrotoxic effect of Cox-inhibitors: Table Conclusion: If GFR day7 < median reference value, and infants have received ibuprofen, blood levels of other potentialy nephrotoxic drugs should be closely monitored.

L/I‐5 Hemodynamics in adult‐to‐adult living donor liver transplantation: personal experience

Introduction: The interaction and modulation of inflow and outflow in adult living donor liver transplants (LDLTs) is very complex; small‐for‐size syndrome (SFSS) still represents the most dangerous complication in this regard.Methods: We measured the liver hemodynamics, in both donors and recipients, in 21 LDLTs.Measured parameters included hepatic artery flow (HAF) and portal vein flow (PVF) (ml/min/100 g ), PVF/HAF ratio (PAR) by means of transit time flowmeter, and portal vein pressure (PVP). For all recipients, we used a maximalized outflow with blanket technique (with MHV in 19). According to the results, in order to prevent SFSS, we performed either splenic artery ligation (SAL) or modified porto‐caval‐shunt (PCS) or intrarterial PGI2 + steroid infusion.Results: The median reference values in donors were as follows: HAF, 26.5 ml/min/100g; PVF, 78.5 ml/min/100g; and PAR, 2.5. At total of 5 patients underwent SAL because of GBWR ≤ 0.9; HAF decreased from 32% to 82% in 4; PVF increased from 300% to 400% in 3; PAR was &gt; 20 in 2. None of these patients developed SFSS. Two patients underwent intraarterial infusion of PGI2 + steroids over 14 days because of a PVF increase ≥ 300%, HAF decrease of 82% in 1, PAR 66 and 22, PVP &gt; 20 in 1, and impossibility of SAL. No SFSS was observed. One patient underwent a modified PCS because of PVF increase of 250%, HAF decrease of 70%, PAR 27. No complications occurred.Discusssion: Strength monitoring of liver hemodynamics at pre‐, intra‐, and posthepatic level allows specific management at the different levels in order to prevent SFSS and graft loss.

Obesity in children and young people: a crisis in public health.

Ten per cent of the world’s school-aged children are estimated to be carrying excess body fat (Fig. 1), with an increased risk for developing chronic disease. Of these overweight children, a quarter are obese, with a significant likelihood of some having multiple risk factors for type 2 diabetes, heart disease and a variety of other co-morbidities before or during early adulthood. The prevalence of overweight is dramatically higher in economically developed regions, but is rising significantly in most parts of the world. In many countries the problem of childhood obesity is worsening at a dramatic rate. Surveys during the 1990s show that in Brazil and the USA, an additional 0.5% of the entire child population became overweight each year. In Canada, Australia and parts of Europe the rates were higher, with an additional 1% of all children becoming overweight each year. The burden upon the health services cannot yet be estimated. Although childhood obesity brings a number of additional problems in its train – hyperinsulinaemia, poor glucose tolerance and a raised risk of type 2 diabetes, hypertension, sleep apnoea, social exclusion and depression – the greatest health problems will be seen in the next generation of adults as the present childhood obesity epidemic passes through to adulthood. Greatly increased rates of heart disease, diabetes, certain cancers, gall bladder disease, osteoarthritis, endocrine disorders and other obesityrelated conditions will be found in young adult populations, and their need for medical treatment may last for their remaining life-times. The costs to the health services, the losses to society and the burdens carried by the individuals involved will be great. The present report has been written to focus attention on the issue and to urge policy-makers to consider taking action before it is too late. Specifically, the report:

Immunological evaluation of 60 children with AIDS

OBJECTIVE: The immunologic defects that occur in children with HIV infection are important tests to both diagnosis and therapeutic response. The objective of this study was to verify the immunologic abnormalities in 60 children with AIDS, in Florianópolis, Santa Catarina State, Brazil. METHODS: Serum immunoglobulin levels were determined by nephelometry and compared to a normal pattern for Brazilian children. The lymphocyte T helper (CD4+) and the lymphocyte T suppressor (CD8+) count and percentage, and the ratio between them, determined by commercial flow cytometry, were compared to a pattern for healthy children of HIV-positive mothers. RESULTS: The mean serum IgG levels was higher in the children with AIDS (p<0.005). The mean serum IgM levels was higher in the children with AIDS in the age group between 13 and 108 months (p<0.005). The CD4+ lymphocytes count was below the inferior limit of the 95% confidence interval of the median reference values to each group of age in 50 (84.7%) of the 59 determinations. The CD4+ lymphocytes percentage was much lower than the percentages of reference. The graph curve of the medians of the ratio between lymphocytes CD4+ and CD8+ to each group of age was below the fifth percentile of the graph curve of the medians of reference. CONCLUSIONS: The hypergamaglobulinemia and the lymphocyte T CD4+ count and percentage are sensitive indicators of HIV infection, observed in the present study. Immunologic evaluation of the HIV-positive children is recommended, including those younger than 18 months of age.