The sensory neuropeptide calcitonin gene-related peptide (CGRP) regulates inflammatory and immune responses and mediates vascular functions at sites of inflammation. In adults, CGRP levels in blood are elevated during sepsis and/or shock. In these studies, we examined their potential role in neonatal and maternal inflammatory and immune dysfunction. A total of 168 samples (86 from cord blood and 82 from neonates) were collected within 12 hours of birth. The patients' gestational ages ranged from 24 to 43 weeks and the birth weights ranged from 520 grams to 4445 grams. CGRP levels were measured by radioimmunoassay (RIA). Reverse phase-HPLC analysis of the immunoreactive CGRP present in adult and infant human blood revealed that it coelutes with synthetic CGRP, confirming that the RIA is measuring authentic CGRP in human blood.

There is a developmental correlation of CGRP levels with a rise with gestational age and weight. The cord blood CGRP levels at term gestation are significantly higher than those in the patient blood at term (p<0.01), whereas there is not a significant difference between cord and patient blood in preterm neonates. Infants with and without certain complications were grouped according to gestational age (4 week intervals) or birth weights (500 gram intervals). CGRP levels in cord blood were significantly elevated where certain stressful situations existed in the mother (22 of 86 samples, p<0.001). These included culture positive chorioamnionitis, thick meconium staining of amniotic fluid with low Apgar scores at birth (less than 3 at 1 minute and less than 5 at 5 minutes), placental abruption, severe oligohydramnios or severe pregnancy induced hypertension. There was a similar elevation in CGRP in patient blood (21 of 82 samples, p<0.001) in infants with certain stressful conditions. These included culture positive sepsis/urinary tract infection, shock with blood pressure < 2 SD from the mean for corresponding gestation or congenital cyanotic heart disease. These results suggest that stress and inflammation lead to an increase in CGRP levels in the circulation in neonates. This study was supported by grants from Wyeth Pediatrics and Children's Miracle Network.