Association of antenatal steroid use with cord blood immune biomarkers in preterm births

Objectives

To evaluate the effect of maternal administration of antenatal steroids (ANS) on cord blood cytokine levels at birth in preterm infants.

Methods

Cord blood cytokine concentrations were measured for pro-inflammatory cytokines (IL-1β, IL-6, and IL-8); anti-inflammatory cytokines (IL-4, IL-10 and TGF-β); and neurotrophic cytokines (BDNF, NT-3, and NT-4) in two hundred preterm infants. Data were analyzed using multivariable linear regression to model the independent and joint effects of ANS and inflammation on mean log cord blood cytokine concentrations adjusted for gestational age and Apgar scores.

Results

Exposure to ANS had no significant effect on the cord blood concentrations of cytokines measured in this study. All three pro-inflammatory cytokine levels and levels of IL-10 were significantly increased and cord blood levels of TGF-β and NT-3 were significantly decreased in infants with placental inflammation.

Conclusion

Although exposure to ANS did not have any significant effect on cord blood levels of cytokines, there was a trend toward the attenuation of inflammatory response and higher levels of neurotrophic cytokines in infants born to mothers with placental inflammation and exposure to ANS compared to infants born to mothers with placental inflammation and no ANS exposure.     

Soluble vascular endothelial growth factor receptor-1 in intrauterine growth restricted fetuses and neonates

BACKGROUND: Angiogenesis, a critical process for growth and development is altered in intrauterine growth restriction (IUGR). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, soluble (s) VEGFR-1 and VEGFR-2 represent a regulatory system, essential for both physiological and pathological angiogenesis. AIM: To study the implication of sVEGFR-1-a VEGF antagonist-in IUGR. STUDY DESIGN: Prospective study. METHODS: Twenty-five IUGR and 15 appropriate for gestational age (AGA) full-term fetuses and neonates with their mothers were included in the study. OUTCOME MEASURES: sVEGFR-1 levels were determined by enzyme immunoassay in the serum of: mothers (MS), umbilical cords (UC)-representing fetal state - and neonates on day 1 (N1) and 4 (N4) of life. RESULTS: MS, UC, N1 and N4 sVEGFR-1 levels in IUGR were significantly higher compared to respective AGA cases (p = 0.005, p = 0.026, p = 0.005 and p = 0.017, respectively). In IUGR and AGA groups, maternal sVEGFR-1 levels were significantly higher than fetal and neonatal levels (p in all cases < 0.001). The latter presented in both IUGR and AGA groups a significant decrease from UC to N4 (p in all cases < 0.01). MS, N1 and N4 sVEGFR-1 levels negatively correlated with the infants' customized centiles [(r = -0.489, p = 0.001), (r = -0.440, p = 0.004), (r = -0.431, p = 0.006), respectively]. CONCLUSIONS: Higher sVEGFR-1 levels in the IUGR as compared to the AGA group possibly reflect the predominance of antiangiogenic mechanisms present in IUGR. The decrease of sVEGFR-1 levels from UC to N4 may represent ex utero initiation of growth and development and therefore, prevalence of angiogenic mechanisms.     

Management of preterm infants with intrauterine growth restriction

Preterm intrauterine growth restriction (IUGR) is strongly associated with increased mortality and morbidity. In the management of these infants, complications of preterm birth can be amplified by the effect of suboptimal fetal growth. It is important that pregnancies with IUGR are detected before birth, so that delivery can be arranged in a high-risk maternity unit with the appropriate neonatal staff in attendance. The provision of full support for resuscitation and stabilisation of these infants is crucial to the short-term and long-term health of these infants, who have suffered chronic hypoxia and malnutrition in utero. The long term outcome studies of these infants are retrospective and they include SGA infants. The effects of prematurity affect the outcome of IUGR infants. IUGR is associated with cerebral palsy in those delivered more than 32 weeks gestation. Infants less than 32 weeks of gestation may have poor developmental outcome if the head growth is affected, these infants may have associated cognitive and behavioural problems. Children who fail to grow by 2-4 years are at risk of long term growth problems. This paper outlines the acute and long-term management of these infants.