Placental and Cord Blood Markers Associated With Premature Birth and Disorders of Premature Birth in Newborn Infants

Premature Birth Clinical Trial

Official title:

Study of Environmental Toxicants and Inflammatory Markers in Prematurity and Diseases of Prematurity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01439048
• Other study ID #: CHW 09/102, GC 900
• Status: Completed
• Phase: N/A
• First received: September 21, 2011
• Last updated: August 27, 2015
• Start date: June 2009
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to determine if changes in specific gene products in the placenta or cord/infant blood affect a baby's birth weight, increase the risk of premature birth, or increase the risk of developing diseases of prematurity. We would also like to characterize whether placental epigenetic changes or placental markers of environmental exposures are associated with premature birth.

Description:

Prematurity, diseases of prematurity and growth-disorders of newborn infants contribute significantly to morbidity and mortality seen in newborn infants [1,2,3]. One out of eight newborn infants in the USA is born premature (gestational age less than 37 completed weeks). In 2004, of the 27,860 infants dying within the first year of life, greater than 16,000 were born premature [2]. Moreover, premature infants who survive the neonatal period are at increased risk of cerebral palsy, developmental delays, growth impairment and long-term respiratory disability [3-5]. Additionally, fetal growth restriction and fetal growth excess results in infants being delivered as small for gestational age infants or large for gestational age infants, respectively. Infants born with such growth-disorders are at increased risk of perinatal morbidity and mortality and as adults are at significant risk of obesity, type II diabetes and heart disease [6,7].

While the etiology of preterm birth and growth-disorders can be ascribed to maternal conditions, chromosomal defects or specific maternal environmental exposures in some newborn infants, for a majority the etiology remains unknown [8,9]. There is increasing evidence pointing to the role of genetic susceptibility factors in the causation of prematurity and growth-disorders of the newborn infant [8, 10-12]. Further, epigenetic changes in growth regulating or inflammatory genes in the placenta can program the fetus for premature birth, growth-disorders and other diseases in the postnatal period.

The overall objective of this application is four-fold.

1. To determine whether altered placental or fetal expression of imprinted genes is associated with disorders of growth, prematurity or other postnatal diseases in newborn infants.

2. To determine whether altered placental expression of genes that regulate the innate immune response is associated with premature birth or other postnatal diseases in newborn infants.

3. To determine whether placental markers of environmental exposure (such as Polycyclic Aromatic Hydrocarbons or PAH) or epigenetic changes in placental inflammatory genes or growth genes are associated with prematurity or postnatal diseases in newborn infants.

4. To determine whether cord blood immune responses and markers of immune-cell function are different between preterm and term infants and are associated with postnatal diseases in preterm infants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 3 Months

Eligibility

Inclusion Criteria:

• all infants born alive

Exclusion Criteria:

• infants who are born with no signs of life

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Premature Birth

Locations

Country	Name	City	State
United States	Froedtert Memorial Lutheran Hospital	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (12)

Adams KM, Eschenbach DA. The genetic contribution towards preterm delivery. Semin Fetal Neonatal Med. 2004 Dec;9(6):445-52. Review. — View Citation

Chakraborty S, Joseph DV, Bankart MJ, Petersen SA, Wailoo MP. Fetal growth restriction: relation to growth and obesity at the age of 9 years. Arch Dis Child Fetal Neonatal Ed. 2007 Nov;92(6):F479-83. Epub 2007 Feb 14. — View Citation

Clausson B, Lichtenstein P, Cnattingius S. Genetic influence on birthweight and gestational length determined by studies in offspring of twins. BJOG. 2000 Mar;107(3):375-81. — View Citation

Guyer B, Martin JA, MacDorman MF, Anderson RN, Strobino DM. Annual summary of vital statistics--1996. Pediatrics. 1997 Dec;100(6):905-18. — View Citation

Hao K, Wang X, Niu T, Xu X, Li A, Chang W, Wang L, Li G, Laird N, Xu X. A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods. Hum Mol Genet. 2004 Apr 1;13(7):683-91. Epub 2004 Feb 19. — View Citation

Kramer MS. Intrauterine growth and gestational duration determinants. Pediatrics. 1987 Oct;80(4):502-11. — View Citation

Mathews TJ, MacDorman MF. Infant mortality statistics from the 2003 period linked birth/infant death data set. Natl Vital Stat Rep. 2006 May 3;54(16):1-29. — View Citation

Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002 Aug;110(2 Pt 1):285-91. — View Citation

Stoll BJ, Hansen N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol. 2003 Aug;27(4):293-301. Review. — View Citation

Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, Higgins RD; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004 Nov 17;292(19):2357-65. — View Citation

Treloar SA, Macones GA, Mitchell LE, Martin NG. Genetic influences on premature parturition in an Australian twin sample. Twin Res. 2000 Jun;3(2):80-2. — View Citation

Valsamakis G, Kanaka-Gantenbein C, Malamitsi-Puchner A, Mastorakos G. Causes of intrauterine growth restriction and the postnatal development of the metabolic syndrome. Ann N Y Acad Sci. 2006 Dec;1092:138-47. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparisons of placental gene expression and cord blood immune markers	Placental gene expression and cord-blood immune markers/function will be compared between 50 term infants and 150 preterm infants. Further, among preterm infants it will be determined whether certain patterns of gene expression and immune marker distribution are associated with specific diseases/condition and growth outcomes. Similarly, epigenetic changes in the immune genes and markers of environmental exposure will be compared between preterm infants and term infants. Associations between environment exposures and epigenetic changes and diseases of prematurity will also be determined.	through hospital discharge	No