|About Discussion Pages|
Cite this page: Hill, M.A. (2018, February 23) Embryology Neonatal Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Neonatal_Development
Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children
Clin Pharmacokinet. 2015 Dec;54(12):1183-204. doi: 10.1007/s40262-015-0298-7.
Rodieux F1, Wilbaux M2, van den Anker JN3,4,5, Pfister M2,6.
Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. 'Omics'-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children.
Microvillus inclusion disease
- (MVID) A postnatal gastrointestinal tract disease due to the shortening or absence of epithelial cell (enterocytes) apical microvilli. Infants have life-threatening watery diarrhoea and mutations in myosin VB gene (MYO5B). Other forms of congenital diarrhea include congenital secretory chloride diarrhoea, an autosomal recessive form of severe chronic diarrhoea. International Classification of Diseases - XVI Perinatal Period Noninfective neonatal diarrhoea Neonatal diarrhoea NOS Excl.: neonatal diarrhoea NOS in countries where the condition can be presumed to be of infectious origin (A09).
- (More? Neonatal Development | Gastrointestinal Tract Development | OMIM 251850 | OMIM MYO5B | PMID 20186687 | PMID 26830108)
Human renal function maturation: a quantitative description using weight and postmenstrual age
Pediatr Nephrol. 2009 Jan;24(1):67-76. Epub 2008 Oct 10.
Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, Chatelut E, Grubb A, Veal GJ, Keir MJ, Holford NH. Source Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.
This study pools published data to describe the increase in glomerular filtration rate (GFR) from very premature neonates to young adults. The data comprises measured GFR (using polyfructose, (51)Cr-EDTA, mannitol or iohexol) from eight studies (n = 923) and involved very premature neonates (22 weeks postmenstrual age) to adulthood (31 years). A nonlinear mixed effects approach (NONMEM) was used to examine the influences of size and maturation on renal function. Size was the primary covariate, and GFR was standardized for a body weight of 70 kg using an allometric power model. Postmenstrual age (PMA) was a better descriptor of maturational changes than postnatal age (PNA). A sigmoid hyperbolic model described the nonlinear relationship between GFR maturation and PMA. Assuming an allometric coefficient of 3/4, the fully mature (adult) GFR is predicted to be 121.2 mL/min per 70 kg [95% confidence interval (CI) 117-125]. Half of the adult value is reached at 47.7 post-menstrual weeks (95%CI 45.1-50.5), with a Hill coefficient of 3.40 (95%CI 3.03-3.80). At 1-year postnatal age, the GFR is predicted to be 90% of the adult GFR. Glomerular filtration rate can be predicted with a consistent relationship from early prematurity to adulthood. We propose that this offers a clinically useful definition of renal function in children and young adults that is independent of the predictable changes associated with age and size.
PMID 18846389 Malin M Rhodin, Brian J Anderson, A Michael Peters, Malcolm G Coulthard, Barry Wilkins, Michael Cole, Etienne Chatelut, Anders Grubb, Gareth J Veal, Michael J Keir, Nick H G Holford Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr. Nephrol.: 2009, 24(1);67-76 PubMed 18846389
NHMRC - NHMRC Infectious Diseases School Exclusion recommendations This table has been revoked, and no longer represents the advice of NHMRC. It is included here only for historical reference purposes.
- Innate immunity of the newborn: basic mechanisms and clinical correlates. Levy O. Nat Rev Immunol. 2007 May;7(5):379-90. Review. PMID: 17457344
- T cell recognition and immunity in the fetus and mother. Koch CA, Platt JL. Cell Immunol. 2007 Jul;248(1):12-7. Epub 2007 Oct 24. Review. PMID: 17920574
- Control of the immunological environment of the uterus. Robertson SA. Rev Reprod. 2000 Sep;5(3):164-74. Review. PMID: 11006166
- Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung. Sozo F, O'Day L, Maritz G, Kenna K, Stacy V, Brew N, Walker D, Bocking A, Brien J, Harding R. Am J Physiol Lung Cell Mol Physiol. 2009 Mar;296(3):L510-8. Epub 2008 Dec 26. PMID: 19112099
- Hyper innate responses in neonates lead to increased morbidity and mortality after infection. Zhao J, Kim KD, Yang X, Auh S, Fu YX, Tang H. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7528-33. Epub 2008 May 19. PMID: 18490660
- Neonatal innate immunity to infectious agents. Maródi L. Infect Immun. 2006 Apr;74(4):1999-2006. Review. No abstract available. PMID: 16552028
- Passive immunity to vaccinia in newborns. I. Placental transmission of antibodies. KEMPE CH. Yale J Biol Med. 1952 Feb;24(4):328-33. No abstract available. PMID: 14914000
Melamine is commonly used to manufacture strong and durable laminates, plastics, adhesives, and flame-resistant textiles. It also has been deliberately added to food and animal feed, sometimes in high amounts, to boost the appearance of protein content based on nitrogen analysis.