Neuregulin-1 high-producer genotype is associated with a decreased risk of admission to the neonatal intensive care unit

Pleickhardt, Elizabeth P.; Celandine, Andrew; Davis, Jonathan M.; Chen, Minghua; Schürmann, Peter; Dörk, Thilo; Dammann, Christiane E.L.; Dammann, Olaf

doi:10.1016/j.earlhumdev.2010.03.010

« Previous Next »Early Human Development
Volume 86, Issue 5 , Pages 299-304, May 2010

Neuregulin-1 high-producer genotype is associated with a decreased risk of admission to the neonatal intensive care unit

Elizabeth P. Pleickhardt
- Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
Andrew Celandine
- Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
Jonathan M. Davis
- Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
Minghua Chen
- Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
Peter Schürmann
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
Thilo Dörk
- Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany
Christiane E.L. Dammann
- Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
- Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany
Olaf Dammann
- Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
- Perinatal Neuroepidemiology Unit, Hannover Medical School, Hannover, Germany
- Neuroepidemiology Unit, Children's Hospital, Boston, MA, USA
- Corresponding Author. Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Box 854, 750 Washington St., Boston, MA 02111, USA. Tel.: +1 617 636 0240; fax: +1 617 636 3309.

Received 29 December 2009; received in revised form 12 March 2010; accepted 15 March 2010.

Abstract

Background

Neuregulin (NRG1) is a developmental growth factor and homozygous C allele carriers at the NRG221533 locus are at reduced risk for developmental disability.

Aims

To explore whether 1) the NRG221533 CC genotype is associated with a decreased likelihood of neonatal intensive care unit (NICU) admission; 2) NRG1 is present in the infant's systemic circulation; and 3) to comparatively investigate two additional proposed high-producer single nucleotide polymorphisms (SNPs) for the cytokines interleukin 6 (−572) and interleukin 10 (−1082), examining both gene product and the association for admission to the NICU.

Study design

IL6 and IL10 protein was measured in umbilical cord blood by a multiplex sandwich immunoassay and NRG1 by ELISA. Infants were screened for SNPs IL6 (−572), IL10 (−1082), and NRG221533. We defined IL6 (C), IL10 (G) and NRG1 (C) as high-producer alleles based on published data.

Subjects

Unselected single-center convenience sample of 97 newborns with a gestational age of 25–33weeks (N=18), 34–36weeks (N=17), 37–38weeks (N=28), and 39–41weeks (N=34).

Outcome measures

Prematurity (<37 completed weeks) and admission to NICU.

Results

The SNP NRG221533 CC genotype was associated with reduced admission to the NICU, even after adjustment for confounders. Adjustment for high IL6 levels reduced the protective effect. NRG1 levels tended to increase with advancing gestational age. Unexpectedly, we found lower IL6 and IL10 levels in infants homozygous for the IL6 (C) and IL10 (G) alleles, and no associations between IL10 (−1082) and IL6 (−572) genotype and prematurity or admission to NICU.