Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period.

BACKGROUND AND AIM: Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. METHODS: Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. RESULTS: Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. CONCLUSIONS: Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. IMPACT: This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.

Digit ratio (2D:4D) and maternal testosterone-to-estradiol ratio measured in early pregnancy.

The ratio of index to ring finger (2D:4D) has been hypothesised to indicate prenatal androgen exposure, yet evidence for its validity is lacking. We report the first pre-registered study to investigate mothers' early pregnancy sex hormone concentrations in relation to their children's digit ratios measured at 18-22-month follow-up. Although the testosterone (T) to estradiol (E) ratio correlated negatively with right hand digit ratio (R2D:4D) and directional asymmetry (right-minus-left) in digit ratio (D[R-L]), neither effect remained statistically significant once demographic and obstetric covariates were controlled for. Nevertheless, the multivariate level of analysis did reveal that T correlated positively with left hand digit ratio (L2D:4D) and negatively with D[R-L]. However, the first of these effects is in the opposite direction to that predicted by theory. Taken together, the results of our study suggest research with larger samples is required to determine whether digit ratios are valid proxies for maternal sex hormone exposure.

Free radicals and neonatal encephalopathy: mechanisms of injury, biomarkers, and antioxidant treatment perspectives.

Neonatal encephalopathy (NE), most commonly a result of the disruption of cerebral oxygen delivery, is the leading cause of neurologic disability in term neonates. Given the key role of free radicals in brain injury development following hypoxia-ischemia-reperfusion, several oxidative biomarkers have been explored in preclinical and clinical models of NE. Among these, antioxidant enzyme activity, uric acid excretion, nitric oxide, malondialdehyde, and non-protein-bound iron have shown promising results as possible predictors of NE severity and outcome. Owing to high costs and technical complexity, however, their routine use in clinical practice is still limited. Several strategies aimed at reducing free radical production or upregulating physiological scavengers have been proposed for NE. Room-air resuscitation has proved to reduce oxidative stress following perinatal asphyxia and is now universally adopted. A number of medications endowed with antioxidant properties, such as melatonin, erythropoietin, allopurinol, or N-acetylcysteine, have also shown potential neuroprotective effects in perinatal asphyxia; nevertheless, further evidence is needed before these antioxidant approaches could be implemented as standard care.

Introduction to neonatologist-performed echocardiography.

Cardiac ultrasound techniques are increasingly used in the neonatal intensive care unit to guide cardiorespiratory care of the sick newborn. This is the first in a series of eight review articles discussing the current status of "neonatologist-performed echocardiography" (NPE). The aim of this introductory review is to discuss four key elements of NPE. Indications for scanning are summarized to give the neonatologist with echocardiography skills a clear scope of practice. The fundamental physics of ultrasound are explained to allow for image optimization and avoid erroneous conclusions from artifacts. To ensure patient safety during echocardiography recommendations are given to prevent cardiorespiratory instability, hypothermia, infection, and skin lesions. A structured approach to echocardiography, with the same standard views acquired in the same sequence at each scan, is suggested in order to ensure that the neonatologist confirms normal structural anatomy or acquires the necessary images for a pediatric cardiologist to do so when reviewing the scan.

Infant subcortical cystic leucomalacia: a distinct pathological entity resulting from impaired fluid handling.

BACKGROUND: In the first months of life the subcortical white matter appears prone to fluid accumulation and cystic change. This condition has generally been considered to be due to hypoxic-ischaemic injury (HII) and is grouped with other forms of white matter disease including periventricular leucomalacia (PVL). AIMS: Our aim was to describe the sequential tissue changes in the formation of subcortical cystic leucomalacia in the infant brain and to delineate this from other forms of white matter disease in order to better understand its pathogenesis and aetiology. STUDY DESIGN: Standard samples of the frontal lobe, including subcortical white matter, were stained to demonstrate the cellular processes responsible for subcortical cyst formation in infants who had died from global hypoxic-ischaemic injury (HII) and brain swelling. Cases were of infants who had survived for known periods after collapse in order to determine the time course of the pathological changes. SUBJECTS: 20 infants under 5 months of age with global HII and no other primary brain pathology, and who had survived for between 2h and 13 days after collapse. OUTCOME MEASURES: The description of the sequential changes leading to subcortical cyst formation in infants after severe global HII. RESULTS: With increasing time of survival after global HII the subcortical white matter became more oedematous. Subcortical cysts were seen after one day but were most common in infants surviving more than 5 days. Cysts were not associated with cellular responses and seemed to be the result of fluid accumulation. The pathology was quite distinct from PVL which is due to tissue necrosis. CONCLUSIONS: Subcortical leucomalacia results from fluid accumulation and not necrosis. Predisposition to fluid accumulation may be age-related and due to impairment of fluid handling pathways which remain immature in this age group. Potential mechanisms are discussed.