Background-The lysyl oxidases are extracellular copper enzymes that initiate the crosslinking of collagens and elastin, 5 human isoenzymes having been characterized so far. The crosslinks formed provide the tensile strength and elastic properties for various extracellular matrices, including vascular walls. We studied the role of the first described isoenzyme Lox by inactivating its gene in mice. Methods and Results-Murine Lox gene was disrupted by routine methods. Lox Ϫ/Ϫ mice died at the end of gestation or as neonates, necropsy of the live-born pups revealing large aortic aneurysms. In light microscopy, hazy and unruffled elastic lamellae in the Lox Ϫ/Ϫ aortas were observed, and electron microscopy of the aortic walls of the Lox Ϫ/Ϫ fetuses showed highly fragmented elastic fibers and discontinuity in the smooth muscle cell layers in Lox Ϫ/Ϫ fetuses. The wall of the aorta in the Lox Ϫ/Ϫ fetuses was significantly thicker, and the diameter of the aortic lumen was significantly smaller than that in the Lox ϩ/ϩ aortas. In Lox Ϫ/Ϫ fetuses, Doppler ultrasonography revealed increased impedance in the umbilical artery, descending aorta, and intracranial artery blood velocity waveforms, decreased mean velocities across cardiac inflow and outflow regions, and increased pulsatility in ductus venosus blood velocity waveforms. Conclusions-Lox

Background-Fetal aortic valvuloplasty may prevent progression of aortic stenosis (AS) to hypoplastic left heart syndrome (HLHS). Predicting which fetuses with AS will develop HLHS is essential to optimize patient selection for fetal intervention. The aim of this study was to define echocardiographic features associated with progression of midgestation fetal AS to HLHS. Methods and Results-Fetal echocardiograms were reviewed from 43 fetuses diagnosed with AS and normal left ventricular (LV) length at Յ30 weeks' gestation. Of 23 live-born patients with available follow-up data, 17 had HLHS and 6 had a biventricular circulation. At the time of diagnosis, LV length, mitral valve, aortic valve, and ascending aortic diameter Z-scores did not differ between fetuses that ultimately developed HLHS and those that maintained a biventricular circulation postnatally. However, all of the fetuses that progressed to HLHS had retrograde flow in the transverse aortic arch (TAA), 88% had left-to-right flow across the foramen ovale, 91% had monophasic mitral inflow, and 94% had significant LV dysfunction. In contrast, all 6 fetuses with a biventricular circulation postnatally had antegrade flow in the TAA, biphasic mitral inflow, and normal LV function. With advancing gestation, growth arrest of left heart structures became evident in fetuses developing HLHS. Conclusions-In midgestation fetuses with AS and normal LV length, reversed flow in the TAA and foramen ovale, monophasic mitral inflow, and LV dysfunction are predictive of progression to HLHS. These physiological features may help refine patient selection for fetal intervention to prevent the progression of AS to HLHS.

Objective To examine whether intrapartum monitoring by means of automatic ST analysis (STAN) of fetal electrocardiography could reduce the rate of neonatal acidemia and the rate of operative intervention during labour, compared with monitoring by means of cardiotocography (CTG).Design Randomised controlled trial.Setting Labour ward in tertiary-level university hospital.Sample A total of 1483 women in active labour with singleton term fetus in cephalic presentation.Methods Women were randomly assigned to be monitored either by STAN or by CTG. Fetal blood sampling (FBS) was optional in both groups.Main outcome measures Neonatal acidemia (umbilical artery pH <7.10), neonatal metabolic acidosis (umbilical artery pH <7.05 and base excess <-12 mmol/l) and operative interventions: caesarean section rate, vacuum outlet (VO) rate and FBS rate.Results There were no statistically significant differences between the STAN group and CTG group in the incidence of neonatal acidemia (5.8 versus 4.7%) or metabolic acidosis (1.7 versus 0.7%). The caesarean section rate (6.4 versus 4.7%) and the VO rate (9.5 versus 10.7%) were also similar in the STAN and CTG groups. The incidence of FBS was lower (P < 0.001) in the STAN group (7.0%) than in the CTG group (15.6%).Conclusions Intrapartum fetal monitoring by means of automatic STAN did not improve the neonatal outcome or decrease the caesarean section rate. However, the need for FBS during labour was lower in the STAN group.

Background-Placental insufficiency may lead to fetal cardiovascular compromise. We sought to determine whether ultrasonographic parameters of fetal cardiovascular function correlate with umbilical arterial levels of biochemical markers of myocardial dysfunction and damage in placental insufficiency. Methods and Results-In 48 fetuses with placental insufficiency, umbilical artery blood was obtained at delivery for assessment of N-terminal peptide of proatrial natriuretic peptide (NT-proANP) and cardiac troponin-T (cTnT). Group 1 fetuses (nϭ12) had normal NT-proANP and cTnT serum concentrations. Group 2 fetuses (nϭ25) showed increased NT-proANP (Ͼ1145 pmol/L) and normal cTnT values. Group 3 fetuses (nϭ11) had increased NT-proANP and cTnT (Ͼ0.10 ng/mL) levels. The ultrasonographic parameters of fetal cardiovascular function were compared between the groups. Pulsatility indices for veins of the ductus venosus, left hepatic vein, and inferior vena cava correlated significantly with NT-proANP levels. In group 3, ductus venosus, left hepatic vein, and inferior vena cava pulsatility indices for veins were higher (PϽ0.01) than in groups 1 and 2. The proportion of left ventricular cardiac output of combined cardiac output was greater (PϽ0.05) and that of right ventricle was smaller (PϽ0.05) in group 3 than in group 2. In group 3, tricuspid regurgitation was noted most often (PϽ0.05), and right ventricular fractional shortening was less (PϽ0.01) than in group 2. Conclusions-Pulsatility in human fetal systemic veins correlated significantly with the cardiac secretion of ANP. Fetuses with myocardial damage demonstrate increased systemic venous pressure, a change in the distribution of cardiac output toward the left ventricle, and a rise in right ventricular afterload.