Obstetric risk factors and persistent increases in brain parenchymal echogenicity in preterm infants

Abstract

Objective To assess the risk of persistent ( > 7 days) increases in brain parenchymal echogenicity in preterm infants and their association with known obstetric risk factors. Design Case -control study of prospectively collected data.Setting A University hospital in Northern Italy.Population Eighty-five singleton infants between 24 and 34 weeks of gestation with a cranial ultrasonographic diagnosis of persistently increased parenchymal echogenicity without development of cystic degeneration, and 170 control infants with negative cranial ultrasonographic findings. Methods A comparison of the prevalence of selected obstetric risk factors between infants with persistent echo-dense lesions and negative controls. Main outcome measures Odds ratios of persistent echo-dense lesions including first-degree interactions between variables. Results After adjusting for birthweight, logistic regression analysis showed that the only factor associated with an increased risk of persistent brain echo-dense lesions in infants was multiple courses of antenatal steroids (OR ¼ 2.14, 95% CI ¼ 1.11 -4.15, P ¼ 0.024). In this group, the risk of persistent echo-dense lesions was particularly high in: (i) mothers receiving dexamethasone rather than betamethasone (P value for interaction ¼ 0.015) and (ii) after expectant management of pre-eclampsia or intrauterine growth retardation (P value for interaction ¼ 0.03). Conclusions Multiple doses of antenatal steroids, especially dexamethasone, could influence the prevalence of persistent increases in brain parenchymal echogenicity in preterm infants.

Toxicity of corticosteroids and catecholamines for mice neuronal cell cultures: Role of preservatives

“…More recently, Spinillo et al demonstrated that multiple doses of antenatal steroids, and especially of dexamethasone, were significantly associated with the occurrence of infant cerebral echo-dense lesions in preterm infants [27]. This association was more frequent when mothers were treated with dexamethasone than with betamethasone (p ¼ 0.018) [27]. These papers agree with other reports demonstrating that dexamethasone increases the risk of brain lesions or neuromotor deficits in preterm infants treated for bronchopulmonary dysplasia [4,5].…”

“…Furthermore, some clinical trials evaluating the effects of antenatal exposure to dexamethasone in preterm infants, suggest that it is dangerous for the neurodevelopment of preterm infants [26,27]. Baud et al found that maternal treatment with dexamethasone was associated with an increased risk of neonatal periventricular leukomalacia, although the increment was not statistically significant (p ¼ 0.20) [26].…”

“…Baud et al found that maternal treatment with dexamethasone was associated with an increased risk of neonatal periventricular leukomalacia, although the increment was not statistically significant (p ¼ 0.20) [26]. More recently, Spinillo et al demonstrated that multiple doses of antenatal steroids, and especially of dexamethasone, were significantly associated with the occurrence of infant cerebral echo-dense lesions in preterm infants [27]. This association was more frequent when mothers were treated with dexamethasone than with betamethasone (p ¼ 0.018) [27].…”

“…But it is noteworthy that the structure of betamethasone, which is neuroprotective in vitro and in vivo [8,26,27], differs from that of dexamethasone in the configuration of the methyl group at position 16. In addition, the presence of sulfiting agents in the dexamethasone preparation (the majority of intravenous dexamethasone preparations throughout the world, such as Soludecadron, contain 0.155 mg of sulfite per milligram of dexamethasone) may account for its detrimental effect.…”

Systemic prenatal insults disrupt telencephalon development: Implications for potential interventions

“…Some studies have shown antenatal steroids may be of long term neurologic benefit (236), others showed they are not necessarily harmful, with no increase in WML on ultrasound (233). More recent studies have found an association of antenatal steroid use with ultrasound WML (237). The differences in formulation of dexamethasone and betamethasone may play a role (232,237).…”