Prenatal and postnatal screening and treatment of critical monosaccharide deficiencies for neurologic and immunologic function

• US 20110053889A1
• Filed: 09/02/2008
• Published: 03/03/2011
• Est. Priority Date: 09/02/2008
• Status: Abandoned Application

• Current Assignee: Joanne Szabo
• Original Assignee: Joanne Szabo
• Inventors: Szabo, Joanne
• Application Number:
  US12/231,383
• Publication Number:
  US 20110053889A1
• Time in Patent Office: Days
• US Class Current: 514/62
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23L 33/30 Dietetic or nutritional methods, e.g. for losing weight A23L33/10 takes precedence
• CPC Class Codes: A23L 33/40 Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals

Abstract

A method for determining the effect of critical glyconutrient dietary supplements in premature and term infants on growth, health, and brain function during early childhood development is described. The method comprises determining a critical target nutrient profile in typical samples of preterm and mother'"'"'s milk, developing a supplement of the missing critical target nutrients to simulate mother'"'"'s milk, performing an evaluation of early child development by correlating physiologic brain function with cognitive/behavioral brain function in low birth weight premature and term infants, assessing family influence and home environment on developmental outcome on infants under treatment, and comparing term siblings of low birth weight premature vs. term babies. A composition having the critical nutrients, an algorithm for screening and treatment, and a useful kit for employing the above are also described.

Claims

1. A method for determining the effect of critical nutrient dietary supplements in premature and term infants on growth, health, physiologic and cognitive/behavioral brain function during early childhood development, said method comprising:

determining a critical target nutrient content profile in typical samples of preterm and term mother'"'"'s milk (MM);

developing a supplement comprising missing critical target nutrients (MS);

adding the supplement to an infant'"'"'s diet, in order to simulate mother'"'"'s milk;

performing a longitudinal physical evaluation of early child development;

correlating physiologic brain function with cognitive/behavioral brain function in low birth weight (LBW) premature and term infants assigned to MM, F, or MS+F during infancy, from birth through 3 years;

assessing influence of family and home environment on developmental outcome of premature and term infants assigned to MM, F, or MS+F in order to determine the role of environment vs. nutrition on growth, health, physiologic and cognitive/behavioral brain functioning; and

comparing term siblings of LBW premature vs. term babies at age 3 years in order to provide preliminary complementary information about heritability influencing the nutrition-development relationship.

2. A method for determining effectiveness of critical monosaccharide dietary supplements on growth, health, physiologic and cognitive/behavioral brain function in premature and term infants during early childhood development, said method comprising:

determining a monosaccharide content profile in typical samples of preterm and term mother'"'"'s milk (MM);

developing supplements for missing critical monosaccharides (MS);

adding the supplements to preterm and term mothers'"'"' milk (MM) or formulas (F) in order to simulate their composition in mother'"'"'s milk (MS+F);

performing a longitudinal physical evaluation of early child development;

correlating physiologic brain function with cognitive/behavioral brain function in premature and term infants assigned to diet groups MM, F, or MS+F during infancy;

assessing influence of family and home environment on developmental outcome of premature and term infants assigned to said MM, F, or MS+F groups in order to determine the role of environment vs. nutrition on growth, health, physiologic and cognitive/behavioral brain functioning from birth through 3 years; and

comparing term siblings of the low birth weight (LBW) premature vs. term babies at age 3 years

in order to provide preliminary complementary information about heritability influencing the nutrition-development relationship.

3. The method according to claim 2, wherein the developing comprises pharmaceutical compounding of one or more members of the group consisting of fucose, mannose, glutamic acid and sialic acid.

4. The method according to claim 2, wherein the adding is to MM and preterm and term infant F.

5. The method according to claim 2, wherein the adding is to intravenous fluids.

6. The method according to claim 2, wherein the adding is to enteral feeds.

7. The method according to claim 2, wherein the adding comprises an amount determined by bioavailability and safety in a pharmaceutically acceptable carrier.

8. The method according to claim 2, wherein the adding is supplementing in Lewis recessive phenotype mothers.

9. The method according to claim 2, wherein the adding is through the first 6 months of infancy.

10. The method according to claim 2, wherein the performing comprises a period of 0-3 years.

11. The method according to claim 2, wherein the longitudinal evaluation comprises evaluation of

growth and body composition,

general health,

immunocompetence,

incidence of infection, and

morbidity.

12. The method according to claim 11, wherein the growth and body composition is evaluated by anthropometrics.

13. The method according to claim 12, wherein the anthropometrics comprises measurements of weight, length or height, head circumference and the like using standardized techniques.

14. The method according to claim 2, wherein the growth and body composition is further evaluated by BIA.

15. The method according to claim 2, wherein the growth and body composition is further evaluated by DEXA.

16. The method according to claim 11, wherein the immunocompetence is evaluated by examination of the development of natural and acquired immunity.

17. The method according to claim 16, wherein the analyses include Fluorescent in Situ Hybridization of gut microbiota, and Enzyme-linked Immunospit assay of circulating immunoglobulin-secreting cells.

18. The method according to claim 2, wherein the correlating physiologic brain function comprises electrophysiologic/behavioral assessments.

19. The method according to claim 18, wherein the electrophysiologic/behavioral assessments comprise heart rate, respiratory rate, and EEG recordings in response to paradigms designed to measure social and startle response, language discrimination, and visual attention.

20. The method according to claim 2, wherein the cognitive/behavioral brain function is assessed by one or more standardized tests comprising the group of intelligence, achievement, language, temperament and behavior.

21. The method according to claim 2, wherein the correlating is for a period of 0-3 years.

22. The method according to claim 2, wherein the assessing of influence of family and home environment comprises assessing maternal intelligence and psychopathology, family socioeconomic status, stability, adaptability and cohesion.

23. The method according to claim 2, wherein the comparing comprises:

grasp force data;

finger-length data;

resting state recordings;

heart rate analyses;

respiratory rate; and

to skin conductance.

24. The method according to claim 23, wherein the grasp force compares left-right hand strength isometric force differences.

25. The method according to claim 23, wherein the finger length comprises ratios of second to fourth finger lengths.

26. The method according to claim 23, wherein the resting state is based on EEG, EMG and EOG data coupled with quantitative analyses of EEG, autonomic activity and video recordings.

27. The method according to claim 23, wherein the heart rate analyses comprises measuring heart beat-to-beat intervals in resting periods and in association with stimuli.

28. A method to determine a genetic-dietary link of blood group phenotypes and monosaccharide deficiencies and premature birth, said method comprising:

determining mothers'"'"' blood type, and

comparing said blood type to blood type of mothers having monosaccharide deficiencies and premature birth whose infants are enrolled in longitudinal evaluations.

29. The method according to claim 28, wherein the blood-group phenotypes comprise ABO and Lewis b phenotypes.

30. The method according to claim 29, wherein the determination further comprises saliva tests for determination of Lewis secretor status.

31. A composition comprising a custom blend of critical monosaccharides in a formulation to supplement infant diets deficient in said monosaccharides, comprising:

adding critical monosaccarides to mothers'"'"' milk deficient in said monosaccharides and/or common commercial term and preterm formulas devoid of said monosaccharides in order to simulate their composition in normal term mothers'"'"' milk.

32. The composition according to claim 31, wherein the critical monossacharides comprise one or more members of the group comprising fucose, mannose, glutamic acid and sialic acid.

33. The composition according to claim 32, wherein the sialic acid is endogenous sialic acid produced from glucosamine by an epimerase enzyme.

34. The composition according to claim 32, wherein the critical monossacharides are pharmaceutically compounded in a powder form.

35. The composition according to claim 32, wherein the critical monossacharides are compounded in a pharmaceutically acceptable carrier for intravenous administration.

36. The composition according to claim 32, wherein the critical monossacharides are compounded in a pharmaceutically acceptable carrier for enteral feeding.

37. A method for determining a probability of adverse reproductive events in a woman of reproductive age, said method comprising:

determining the presence in a biological sample from said woman of one or more biomarker,

wherein said biomarker correlates with a known risk of adverse reproductive events.

38. The method according to claim 37, wherein the woman is in gestation.

39. The method according to claim 37, wherein said sample is selected from the group comprising a blood sample, a serum sample, a plasma sample, milk sample, saliva sample and fetal cord blood sample.

40. The method according to claim 37, wherein said biomarker is selected from the group comprising fucose, mannose, glutamic acid and sialic acid.

41. The method according to claim 37, wherein said biomarker is further selected from the group comprising ABO blood phenotypes and Lewis phenotypes.

42. The method according to claim 37, wherein said adverse reproductive events comprise premature birth and glyconutrient deficiencies leading to compromised growth, health, physiologic and cognitive/behavioral brain function in premature and term infants during early childhood development.

43. A method of predicting occurrence of adverse reproductive events, the method comprising:

obtaining a test sample from a subject;

analyzing the obtained test sample for

ABO phenotype or Lewis phenotype biomarkers, and

one or more additional biomarkers that are indicative of the probability of adverse reproductive events; and

correlating the presence or amount of said biomarkers, with a biomarker burden and clinicopathological data of adversely affected infants, in order to deduce a probability of having adverse reproductive events.

44. The method of claim 43, wherein said additional biomarkers are selected from one or more of the group consisting of fucose, mannose, glutamic acid and sialic acid.

45. The method according to claim 43, wherein the correlating step is made in accordance with an algorithm drawn from the group consisting essentially of:

linear or nonlinear regression algorithms;

linear or nonlinear classification algorithms;

ANOVA;

neural network algorithms; and

genetic algorithms.

46. The method according to claim 43, where the algorithm is a plurality of algorithms.

47. The method according to claim 46, wherein a tree algorithm, such as CART, MARS, or others, is trained to reproduce the performance of another machine-learning classifier or regressor.

48. The method according to claim 43, wherein said correlating step comprises:

determining level(s) of one or more biomarker(s) from a reproductive age or gestating woman;

comparing said levels values to women known to have had adverse reproductive events; and

training an algorithm to identify different patterns in said women that correlate with the presence or absence of said matched type of adverse reproductive events.

49. The method according to claim 47, wherein the training of said algorithm on characteristic biomarkers comprises the steps of:

obtaining numerous examples of

said biomarker data, and

historical clinical results corresponding to this biomarker data;

constructing an algorithm wherein

said biomarker levels and values are inputs to the algorithm, and

the historical clinical results are outputs of the algorithm; and

exercising the constructed algorithm to correlate said biomarker levels and values as inputs to the historical clinical results as outputs.

50. A kit useful for screening for monossacharide deficiencies and treatment in premature and term infants, comprising devices and reagents and an algorithm residing in a computer for measuring one or more of a group of biomarkers of a reproductive age woman and correlating with known adverse reproductive events.

51. The kit in accordance with claim 50, wherein said adverse reproductive events comprise premature birth, glyconutrient deficiencies leading to compromised growth, health, physiologic and cognitive/behavioral brain function in premature and term infants during early childhood development.

52. The kit in accordance with claim 50, wherein said group of biomarkers are comprised of a panel of fucose, mannose, glutamic acid, sialic acid, and ABO and Lewis phenotype markers.

53. A kit comprising devices and reagents and a computer algorithm installed on a computer for measuring one or more biomarkers in a biological sample from a woman of reproductive age and determining the probability in that woman for risk of adverse reproductive events by using the computer algorithm to correlate levels of said biomarkers,

wherein in response to the measured biomarkers, the algorithm determines for that woman a predictive value for adverse reproductive events and for treatment outcome.