Neonatal Research

Basic concept of using LC-MS/MS technology in the clinical domain 347 

Generally speaking, and from the mass spectrometry perspective, neonatal research is viewed mainly as newborn screening (NBS) which can be defined as the presymptomatic identification of the most commonly known inborn errors of metabolism (lEM). 

A lot of papers have recently appeared either as reviews (a very exhaustive one is in ref. [1]) or as chronicles [2] concerning the technical developments of NBS with tandem mass spectrometry (LC-MS/MS). 

If deeply interested in some specific details, the reader can refer to those papers. The present chapter would like to give the essential information to both chemists and medical professionals and make them able to leverage this incontrovertible opportunity in detecting metabolic disorders. 

The largest part of the present work is devoted to the original format of NBS methodology (centered on acyl-camitine (AC) profile and most of the amino acids (AA)) with particular attention to some practical issues. A second part will cover the characterization of very long chain fatty acids, steroids, bile acids (BA), and other markers which are gaining relevance in the NBS context. 

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Stark AR, Carlo WA, Tyson JE, Papile LA, Wright LL, Shankaran S, Donovan EF, Oh W, Bauer CR, Saha S, Poole WK, Stoll BJ. National Institute of Child Health and Human Development Neonatal Research Network. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 2001 344(2) 95-101. 

Until recently, the neonate has been a black box, an eminently valued patient, yet one that is difficult to study and treat effectively. Neonatal research, in particular, is often plagued by ethical problems of invasiveness of protocols, volume of blood to be drawn, inability of the patient to speak on his/her own behalf, etc. Even simple studies that try to address neonatal outcome often pose problems in these areas, requiring volumes of blood that subsequently need to be replaced by transfusion. Because the perceived benefit to both individual patients and to society as a whole is deemed to be highly valuable, such downsides to neonatal research are often accepted as inevitable. The introduction, however, of MS analysis, utilizing low volumes of blood for multiple biomarkers, appears to be a very attractive alternative with great potential. A number of critical areas have already begun to be addressed and include such diverse entities as hypoxic-ischemic brain injury, the infant of a diabetic mother, neonatal renal function, neonatal nutrition, neonatal sepsis, and pharmaceutical development. 

Fetal lung maturation can be accelerated with antenatal corticosteroids. The National Institutes of Health (NIH) consensus conference in 1994 concluded that all fetuses between 24 and 34 weeks gestation at risk for preterm delivery should receive corticosteroids regardless of gender, race, maternal infection, and availability of surfactant. A report by the National Institutes of Child Health and Development Neonatal Research Network noted that antenatal steroid use was associated with fewer pulmonary problems and mortality. Many women who are appropriate candidates are... 

St John EB, Carlo WA. Respiratory distress syndrome in VLBW infants Changes in management and outcomes observed by the NICHD Neonatal Research Network. Semin Perinatol 2003 27 288-292. 

Hoehn K S, Wernovsky, Rychik J, et al. (2005). What factors are important to parents making decisions about neonatal research Arch Dis Child Fetal Neonatal Ed 90 E267-269. 

Manning D T (2000). Presumed consent in emergency neonatal research. J Med Ethics 26 249-253. 

Stenson B J, Becher J C, McIntosh N (2004). Neonatal research the parental perspective. Arch Dis Child Petal Neonatal Ed 89 F321-F323. 

Vuong LT, Lohstroh P, Blood A, Vasquez H, Vogel JS. Applying AMS in neonatal research and care. J Isotope Labelled Comp Radiopharm. 2010 53 352-354. 

Hugo Lagercrantz, M.D., Ph.D. Professor, Neonatal Research Unit, Karolinska Institute, Astrid Lindgren Children s Hospital, Stockholm, Sweden... 

Julie Peyronnet, Ph.D. Neonatal Research Unit, Karolinska Institute, Astrid... 

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