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Cord blood immune biomarkers in small for gestational age births

Published online by Cambridge University Press:  27 January 2011

N. Matoba ,
F. Ouyang ,
K. K. L. Mestan ,
N. F. M. Porta ,
C. M. Pearson ,
K. M. Ortiz ,
H. C. Bauchner ,
B. S. Zuckerman  and
X. Wang
N. Matoba*
Affiliation:
Division of Neonatology, Children's Memorial Hospital, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
F. Ouyang
Affiliation:
Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
K. K. L. Mestan
Affiliation:
Division of Neonatology, Children's Memorial Hospital, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
N. F. M. Porta
Affiliation:
Division of Neonatology, Children's Memorial Hospital, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
C. M. Pearson
Affiliation:
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
K. M. Ortiz
Affiliation:
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
H. C. Bauchner
Affiliation:
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
B. S. Zuckerman
Affiliation:
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
X. Wang
Affiliation:
Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
*
*Address for correspondence: Dr N. Matoba, MD, Children's Memorial Hospital, Division of Neonatology, 2300 Children's Plaza, Box 45, Chicago, IL 60614, USA. (Email [email protected])
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Abstract

Fetal growth restriction is a risk factor for development of adulthood diseases, but the biological mechanism of this association remains unknown. Limited biomarkers have been studied in settings of preterm birth and maternal inflammation, but the relationship between a wide range of immune biomarkers and fetal growth has not been studied. The hypothesis of this study was that fetal growth restriction is associated with altered immune biomarker levels. We examined the relationship between small for gestational age (SGA) status and 27 umbilical cord blood immune biomarkers. This study was part of a large-scale cohort study of preterm birth and low birth weight conducted at Boston Medical Center, an inner city, predominantly minority patient population. Growth status was determined based on birth weight standardized to an internal reference. There were 74 SGA births and 319 appropriate for age (AGA) births with complete clinical and biomarker data. Adjusting for covariates and using AGA as reference, SGA births had lower levels of log IL-1β (ng/l; β −0.38, 95% CI −0.57, −0.19, P < 0.01), log BDNF (β −0.29, 95% CI −0.55, −0.03, P < 0.05) and log NT-3 (β −0.46, 95% CI −0.77, −0.15, P < 0.01). No associations were found between other biomarkers and SGA. In conclusion, three biomarkers were selectively associated with SGA status. Our results provide information that could be used to guide additional studied aimed at determining mechanisms that contribute to fetal growth.

Keywords

biological markersfetal bloodinfantsmall for gestational age
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 2 , April 2011 , pp. 89 - 98
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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References

1. Martinez, A, Simmons, R. Abnormalities of fetal growth. In Avery's Diseases of the Newborn (eds. Taeusch H, Ballard R, Gleason C), 8th edn, 2005; pp. 32–45. Elsevier Saunders: Philadelphia.CrossRefGoogle Scholar
2. Lenfant, C. Low birth weight and blood pressure. Metabolism. 2008; 57(Suppl. 2), S32–S35.CrossRefGoogle ScholarPubMed
3. Forsen, T, Eriksson, JG, Tuomilehto, J, Osmond, C, Barker, DJ. Growth in utero and during childhood among women who develop coronary heart disease: longitudinal study. BMJ (Clinical research edn). 1999; 319, 1403–1407.CrossRefGoogle ScholarPubMed
4. Barker, DJ, Hales, CN, Fall, CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993; 36, 62–67.CrossRefGoogle ScholarPubMed
5. Laitinen, J, Pietilainen, K, Wadsworth, M, Sovio, U, Jarvelin, MR. Predictors of abdominal obesity among 31-y-old men and women born in Northern Finland in 1966. Eur J Clin Nutr. 2004; 58, 180–190.CrossRefGoogle ScholarPubMed
6. Mohamed-Ali, V, Goodrick, S, Rawesh, A, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997; 82, 4196–4200.Google Scholar
7. Ridker, PM, Hennekens, CH, Buring, JE, Rifai, N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. The New England Journal of Medicine. 2000; 342, 836–843.CrossRefGoogle Scholar
8. Ridker, PM, Rifai, N, Stampfer, MJ, Hennekens, CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000; 101, 1767–1772.CrossRefGoogle ScholarPubMed
9. Tzoulaki, I, Murray, GD, Lee, AJ, et al. C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh artery study. Circulation. 2005; 112, 976–983.CrossRefGoogle ScholarPubMed
10. Yudkin, JS, Kumari, M, Humphries, SE, Mohamed-Ali, V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000; 148, 209–214.CrossRefGoogle ScholarPubMed
11. Yudkin, JS, Stehouwer, CD, Emeis, JJ, Coppack, SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arteriosclerosis, Thrombosis, and Vascular Biology. 1999; 19, 972–978.CrossRefGoogle ScholarPubMed
12. Tzoulaki, I, Jarvelin, MR, Hartikainen, AL, et al. Size at birth, weight gain over the life course, and low-grade inflammation in young adulthood: northern Finland 1966 Birth Cohort study. European Heart Journal. 2008; 29, 1049–1056.CrossRefGoogle ScholarPubMed
13. Pellanda, LC, Duncan, BB, Vigo, A, et al. Low birth weight and markers of inflammation and endothelial activation in adulthood: the ARIC study. Int J Cardiol. 2009; 134, 371–377.CrossRefGoogle Scholar
14. Sattar, N, McConnachie, A, O'Reilly, D, et al. Inverse association between birth weight and C-reactive protein concentrations in the MIDSPAN Family Study. Arterioscler Thromb Vasc Biol. 2004; 24, 583–587.CrossRefGoogle ScholarPubMed
15. Cook, DG, Mendall, MA, Whincup, PH, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000; 149, 139–150.CrossRefGoogle ScholarPubMed
16. Cook, DG, Whincup, PH, Miller, G, et al. Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10–11 years. Am J Epidemiol. 1999; 150, 727–736.CrossRefGoogle ScholarPubMed
17. Laskowska, M, Laskowska, K, Leszczynska-Gorzelak, B, Oleszczuk, J. Maternal and umbilical sTNF-R1 in preeclamptic pregnancies with intrauterine normal and growth retarded fetus. Hypertens Pregnancy. 2007; 26, 13–21.CrossRefGoogle ScholarPubMed
18. Nieto-Diaz, A, Villar, J, Matorras-Weinig, R, Valenzuela-Ruiz, P. Intrauterine growth retardation at term: association between anthropometric and endocrine parameters. Acta Obstet Gynecol Scand. 1996; 75, 127–131.CrossRefGoogle ScholarPubMed
19. Sasanow, SR, Spitzer, AR, Pereira, GR, Heaf, L, Watkins, JB. Effect of gestational age upon prealbumin and retinol binding protein in preterm and term infants. J Pediatr Gastroenterol Nutr. 1986; 5, 111–115.Google ScholarPubMed
20. Gicquel, C, Le Bouc, Y. Hormonal regulation of fetal growth. Horm Res. 2006; 65(Suppl. 3), 28–33.Google ScholarPubMed
21. Giudice, LC, de Zegher, F, Gargosky, SE, et al. Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth. J Clin Endocrinol Metab. 1995; 80, 1548–1555.Google ScholarPubMed
22. Holmes, R, Montemagno, R, Jones, J, et al. Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth. Early Hum Dev. 1997; 49, 7–17.CrossRefGoogle ScholarPubMed
23. Yildiz, L, Avci, B, Ingec, M. Umbilical cord and maternal blood leptin concentrations in intrauterine growth retardation. Clin Chem Lab Med. 2002; 40, 1114–1117.CrossRefGoogle ScholarPubMed
24. Chiesa, C, Osborn, JF, Haass, C, et al. Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry? Clin Chem. 2008; 54, 550–558.CrossRefGoogle Scholar
25. Strinic, T, Roje, D, Marusic, J, Capkun, V. Cord blood cortisol level is lower in growth-restricted newborns. J Obstet Gynaecol Res. 2007; 33, 144–150.CrossRefGoogle ScholarPubMed
26. Street, ME, Seghini, P, Fieni, S, et al. Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls. Eur J Endocrinol. 2006; 155, 567–574.CrossRefGoogle ScholarPubMed
27. Laskowska, M, Leszczynska-Gorzelak, B, Laskowska, K, Oleszczuk, J. Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus. J Matern Fetal Neonatal Med. 2006; 19, 347–351.CrossRefGoogle ScholarPubMed
28. Wang, X, Zuckerman, B, Pearson, C, et al. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA. 2002; 287, 195–202.CrossRefGoogle ScholarPubMed
29. Matoba, N, Yu, Y, Mestan, K, et al. Differential patterns of 27 cord blood immune biomarkers across gestational age. Pediatrics. 2009; 123, 1320–1328.CrossRefGoogle ScholarPubMed
30. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 30, September 2001 (replaces Technical Bulletin Number 200, December 1994). Gestational diabetes. Obstet Gynecol. 2001; 98, 525–538.Google Scholar
31. Gibbs, RS, Blanco, JD, St Clair, PJ, Castaneda, YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982; 145, 1–8.CrossRefGoogle ScholarPubMed
32. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000; 183, S1–S22.CrossRefGoogle Scholar
33. Zhang, J, Bowes, WA Jr. Birth-weight-for-gestational-age patterns by race, sex, and parity in the United States population. Obstet Gynecol. 1995; 86, 200–208.CrossRefGoogle ScholarPubMed
34. Wang, L, Wang, X, Laird, N, et al. Polymorphism in maternal LRP8 gene is associated with fetal growth. Am J Hum Genet. 2006; 78, 770–777.CrossRefGoogle ScholarPubMed
35. Kramer, MS, Platt, R, Yang, H, McNamara, H, Usher, RH. Are all growth-restricted newborns created equal(ly)? Pediatrics. 1999; 103, 599–602.CrossRefGoogle ScholarPubMed
36. Skogstrand, K, Thorsen, P, Norgaard-Pedersen, B, et al. Simultaneous measurement of 25 inflammatory markers and neurotrophins in neonatal dried blood spots by immunoassay with xMAP technology. Clin Chem. 2005; 51, 1854–1866.CrossRefGoogle ScholarPubMed
37. Mestan, K, Yu, Y, Thorsen, P, et al. Cord blood biomarkers of the fetal inflammatory response. J Matern Fetal Neonatal Med. 2009; 22, 379–387.CrossRefGoogle ScholarPubMed
38. Ekins, R, Edwards, P. On the meaning of “sensitivity”. Clin Chem. 1997; 43, 1824–1831.CrossRefGoogle ScholarPubMed
39. Duijts, L, Bakker-Jonges, LE, Labout, JA, et al. Fetal growth influences lymphocyte subset counts at birth: The Generation R Study. Neonatology. 2008; 95, 149–156.CrossRefGoogle ScholarPubMed
40. McDade, TW, Beck, MA, Kuzawa, C, Adair, LS. Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence. Am J Clin Nutr. 2001; 74, 543–548.CrossRefGoogle ScholarPubMed
41. Hotamisligil, GS, Erbay, E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev. 2008; 8, 923–934.Google ScholarPubMed
42. Chung, S, Lapoint, K, Martinez, K, et al. Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes. Endocrinology. 2006; 147, 5340–5351.CrossRefGoogle ScholarPubMed
43. Demas, GE, Chefer, V, Talan, MI, Nelson, RJ. Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice. Am J Physiol. 1997; 273(5 Pt 2), R1631–R1637.Google ScholarPubMed
44. Kajantie, E. Fetal origins of stress-related adult disease. Ann N Y Acad Sci. 2006; 1083, 11–27.CrossRefGoogle ScholarPubMed
45. Phillips, DI, Jones, A, Goulden, PA. Birth weight, stress, and the metabolic syndrome in adult life. Ann N Y Acad Sci. 2006; 1083, 28–36.CrossRefGoogle ScholarPubMed
46. Stallmach, T, Hebisch, G, Joller-Jemelka, HI, et al. Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease. Lab Invest. 1995; 73, 384–392.Google ScholarPubMed
47. Amu, S, Hahn-Zoric, M, Malik, A, et al. Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation. Pediatr Res. 2006; 59, 254–258.CrossRefGoogle ScholarPubMed
48. Lykissas, MG, Batistatou, AK, Charalabopoulos, KA, Beris, AE. The role of neurotrophins in axonal growth, guidance, and regeneration. Curr Neurovasc Res. 2007; 4, 143–151.CrossRefGoogle ScholarPubMed
49. Chouthai, NS, Sampers, J, Desai, N, Smith, GM. Changes in neurotrophin levels in umbilical cord blood from infants with different gestational ages and clinical conditions. Pediatr Res. 2003; 53, 965–969.CrossRefGoogle ScholarPubMed
50. Schulte-Herbruggen, O, Braun, A, Rochlitzer, S, Jockers-Scherubl, MC, Hellweg, R. Neurotrophic factors--a tool for therapeutic strategies in neurological, neuropsychiatric and neuroimmunological diseases? Curr Med Chem. 2007; 14, 2318–2329.CrossRefGoogle ScholarPubMed
51. Pan, W, Banks, WA, Kastin, AJ. Permeability of the blood-brain barrier to neurotrophins. Brain Res. 1998; 788, 87–94.CrossRefGoogle ScholarPubMed
52. Malamitsi-Puchner, A, Nikolaou, KE, Puchner, KP. Intrauterine growth restriction, brain-sparing effect, and neurotrophins. Ann N Y Acad Sci. 2006; 1092, 293–296.CrossRefGoogle ScholarPubMed
53. Conde-Agudelo, A, Althabe, F, Belizan, JM, Kafury-Goeta, AC. Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. Am Obstetr Gynecol. 1999; 181, 1026–1035.CrossRefGoogle ScholarPubMed
54. Jeyabalan, A, Powers, RW, Durica, AR, et al. Cigarette smoke exposure and angiogenic factors in pregnancy and preeclampsia. Am J Hypertens. 2008; 21, 943–947.CrossRefGoogle ScholarPubMed
55. Malamitsi-Puchner, A, Nikolaou, KE, Economou, E, et al. Intrauterine growth restriction and circulating neurotrophin levels at term. Early Hum Dev. 2007; 83, 465–469.CrossRefGoogle ScholarPubMed
56. Rich-Edwards, JW, Stampfer, MJ, Manson, JE, et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ (Clinical research edn) 1997; 315, 396–400.CrossRefGoogle Scholar
57. Forsen, T, Eriksson, JG, Tuomilehto, J, et al. Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. BMJ (Clinical research edn). 1997; 315, 837–840.CrossRefGoogle Scholar
58. Henry, OA, Guaran, RL, Petterson, CD, Walstab, JE. Obstetric and birthweight differences between Vietnam-born and Australian-born women. Med J Aust. 1992; 156, 321–324.CrossRefGoogle ScholarPubMed
59. Wang, X, Guyer, B, Paige, DM. Differences in gestational age-specific birthweight among Chinese, Japanese and white Americans. Int J Epidemiol. 1994; 23, 119–128.CrossRefGoogle ScholarPubMed
60. Davies, DP, Senior, N, Cole, G, Blass, D, Simpson, K. Size at birth of Asian and white Caucasian babies born in Leicester: implications for obstetric and paediatric practices. Early Hum Dev. 1982; 6, 257–263.CrossRefGoogle ScholarPubMed
61. Rizos, D, Protonotariou, E, Malamitsi-Puchner, A, et al. Cytokine concentrations during the first days of life. Eur J Obstet, Gynecol Reprod Biol. 2007; 131, 32–35.CrossRefGoogle ScholarPubMed
62. Meas, T, Deghmoun, S, Armoogum, P, Alberti, C, Levy-Marchal, C. Consequences of being born small for gestational age on body composition: an 8-year follow-up study. J Clin Endocrinol Metab. 2008; 93, 3804–3809.CrossRefGoogle ScholarPubMed
63. Hediger, ML, Overpeck, MD, Kuczmarski, RJ, et al. Muscularity and fatness of infants and young children born small- or large-for-gestational-age. Pediatrics. 1998; 102, E60.CrossRefGoogle ScholarPubMed