Humberto Azpurua

Metabolic Assessment of the Brain Using Proton Magnetic Resonance Spectroscopy in a Growth-Restricted Human Fetus: Case Report

Proton magnetic resonance spectroscopy (MRS) is a noninvasive method to assess concentrations of different metabolites in tissues, including the brain. We evaluated a fetus with growth restriction using Doppler ultrasound and proton MRS. Doppler assessment revealed absent end diastolic flow in the umbilical artery. Diastolic flow was increased in the middle cerebral artery. Proton MRS of the fetal brain showed lactate and a low N-acetylaspartate/choline index, metabolic markers of starvation/hypoxia. Proton MRS gave us in vivo metabolic information of the brain of a fetus under starvation/hypoxic conditions. It is potentially a new tool for fetal surveillance. To our knowledge, this is the first report of cerebral lactate detection using proton MRS in a growth-restricted human fetus with no associated malformations in the English literature. Further experimental and clinical longitudinal investigations are needed to evaluate its efficacy in the clinical setting.

Determination of placental weight using two-dimensional sonography and volumetric mathematic modeling.

An abnormally decreased placental weight has been linked to increased perinatal complications, including intrauterine fetal demise (IUFD) and fetal growth restriction (IUGR). Despite its promise, determining placental weight prenatally using three-dimensional systems is time-consuming and requires expensive technology and expertise. We propose a novel method using two-dimensional sonography that provides an immediate estimation of placental volume. Placental volume was calculated in 29 third-trimester pregnancies using linear measurements of placental width, height, and thickness to calculate the convex-concave shell volume within 24 hours of birth. Data were analyzed to calculate Spearmans rho (r (s)) and significance. There was a significant correlation between estimated placental volume (EPV) and actual placental weight (r (s) = 0.80, P < 0.001). Subgroup analysis of preterm gestations ( N = 14) revealed an even more significant correlation of EPV to actual placental weight (r (s) = 0.89, P < 0.001). Placental weight can be accurately predicted by two-dimensional ultrasound with volumetric calculations. This method is simple, rapid, and accurate, making it practical for routine prenatal care, as well as for high-risk cases with decreased fetal movement and IUGR. Routine EPV surveillance may decrease the rates of perinatal complications and unexpected IUFD.

Fetal Adrenal Gland Volume and Cortisol/ Dehydroepiandrosterone Sulfate Ratio in Inflammation-Associated Preterm Birth

OBJECTIVE: Fetal adaptation to stress is regulated in part by the pituitary-adrenocortical system. The stress hormones dehydroepiandrosterone sulfate (DHEAS) and cortisol have opposing effects: cortisol suppresses while DHEAS enhances immune functions. We sought to estimate the impact of intraamniotic inflammation on fetal adrenal gland volume and cortisol-to-dehydroepiandrosterone sulfate ratio (fetal stress ratio) in pregnancies complicated by preterm birth. METHODS: Fifty-one consecutive singleton fetuses of mothers who had an indicated amniocentesis to rule out infection were analyzed. Intraamniotic inflammation was assessed by proteomic profiling of amniotic fluid for the biomarkers of the Mass Restricted score. The Mass Restricted score ranges from 0 (biomarkers absent) to 4 (all biomarkers present), with Mass Restricted scores of 3 or 4 indicating severe intraamniotic inflammation. Fetal adrenal gland volume was assessed by three-dimensional ultrasonography and corrected for estimated fetal weight. Interleukin-6 (IL-6), cortisol, and DHEAS were measured by immunoassay. RESULTS: Women with intraamniotic inflammation delivered earlier (27.8±3.4 weeks, n=16, compared with 32.3±3.0 weeks, n=35, P<.001), and their fetuses had higher cord blood IL-6 (P=.011) and higher corrected adrenal gland volumes (P=.027). Cord blood IL-6 levels were in direct relationship with corrected adrenal volume (r=0.372, P=.019), fetal cortisol (r=0.428, P=.010), and DHEAS (r=0.521, P<.001). However, fetuses exposed to intraamniotic inflammation had an overall lower fetal stress ratio (P=.034). These results maintained after adjusting for gestational age, uterine contractions, and steroid exposure. CONCLUSION: Fetuses exposed to intraamniotic inflammation have higher adrenal gland volumes and lower cortisol-to-DHEAS ratios, suggesting that the fetal adrenocortical axis plays a role in the intrauterine adaptation to inflammation. LEVEL OF EVIDENCE: II

Acceleration/ejection time ratio in the fetal pulmonary artery predicts fetal lung maturity

OBJECTIVE The aim of this study was to determine whether sonographic fetal pulmonary artery flow velocity waveforms correlate with amniotic fluid biomarkers of fetal lung maturity. STUDY DESIGN We studied women with singleton pregnancies undergoing clinically indicated amniocentesis for fetal lung maturity at Yale-New Haven Hospital. Fetal pulmonary artery flow velocity measurements, including systolic/diastolic ratio, pulsatility index, resistance index, and acceleration-time/ejection-time ratio were obtained using spectral Doppler ultrasound. Pearsons correlation coefficient was used to determine the association between fetal pulmonary artery flow velocity parameters and the lecithin/sphingomyelin ratio. RESULTS Twenty-nine subjects met study criteria. The acceleration-time/ejection-time ratio was inversely correlated with the lecithin/sphingomyelin ratio (r = -0.76; P < or = .001). This relationship was maintained after controlling for potential confounders. Other fetal pulmonary artery flow velocity measurements were not associated with the lecithin/sphingomyelin ratio. CONCLUSION There is an inverse correlation between the acceleration-time/ejection-time ratio in the fetal pulmonary artery and the amniotic fluid lecithin/sphingomyelin ratio. This suggests that ultrasound evaluation of fetal pulmonary artery blood flow may be a promising new noninvasive technique to evaluate fetal lung maturity.

Fetal renal artery impedance as assessed by Doppler ultrasound in pregnancies complicated by intraamniotic inflammation and preterm birth

OBJECTIVE The objective of the study was to evaluate the fetal renal artery impedance in the context of inflammation-associated preterm birth. STUDY DESIGN We conducted a prospective Doppler assessment of the fetal renal artery impedance in 70 singleton fetuses. The study group consisted of 56 premature fetuses (median, 28.1 [interquartile range, 25.3-30.6] weeks at enrollment). Gestational age (GA) reference ranges were generated based on fetuses with uncomplicated pregnancies (n = 14). Doppler studies included renal artery pulsatility index (PI), resistance index (RI), systolic/diastolic (S/D) ratio, and presence or absence of end-diastolic blood flow. Proteomic profiling (surface-enhanced laser desorption ionization time-of-flight) was used for assessment of intraamniotic inflammation and biomarker peak corresponding to beta2-microglubin. Data were interpreted in relationship to amniotic fluid index (AFI), cord blood interleukin (IL)-6 and erythropoietin (EPO) levels. The cardiovascular and metabolic profiles of the neonates were investigated in the first 24 hours of life. RESULTS Fetuses delivered by mothers with intraamniotic inflammation had higher cord blood IL-6 but not EPO levels. Fetal inflammation did not affect either renal artery PI, RI, S/D ratio, or end-diastolic blood flow. Neonates delivered in the context of intraamniotic inflammation had higher serum blood urea nitrogen levels, which correlated significantly with AF IL-6 levels. The renal artery RI and SD ratio were inversely correlated with the AFI independent of GA, cord blood IL-6, and status of the membranes. CONCLUSION The fetus is capable of sustaining normal renal artery impedance despite inflammation. Resistance in the renal vascular bed affects urine output independent of inflammation.