First-trimester screening: lessons from clinical trials and implementation.
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Adult↗
Biomedical subjects
Brian J Koos
Publications and source records attributed to Brian J Koos.
Too much information or not enough? Editorial review.
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Congenital Abnormalities↗
Ultrasound and fetal diagnosis.
PURPOSE OF REVIEW: The purpose of this review is to highlight publications from the last year that have advanced the use of ultrasound in obstetrics. RECENT FINDINGS: Anatomic examination of the fetus in the first trimester has been emphasized because it allows for early diagnosis of many conditions. The prevalence of absent nasal bone, a marker for trisomy 21, in euploid fetuses depends on ethnicity. Nasal bone hypoplasia is another marker for Down syndrome. Studies on genetic screening in the first trimester have involved various serum analytes, adjustments in timing and calculations, use in multiple gestations, and the association of extreme measurements with adverse outcomes. A first-trimester integrated screening approach, which incorporates nuchal translucency, nasal bone, crown-rump length, pregnancy-associated plasma protein-A, and free beta-human chorionic gonadotropin, has the potential to maximize detection rates of Down syndrome and trisomy 18 and minimizes the screen-positive rate. The value of combining first and second-trimester results in sequential, contingent, or integrated screening protocols has been assessed. Isolated mild ventriculomegaly (10-12 mm) may prove to be a normal variant, and the role of 'soft' ultrasound markers in genetic counseling continues to be debated. Anomaly or high-risk status detection in the second trimester has been enhanced by the use of Doppler, 3D/4D ultrasound, and magnetic resonance imaging. SUMMARY: Imaging techniques have been critical in the development of screening methods for Down syndrome or trisomy 18 and for euploid fetuses at high risk for adverse outcomes.
Aneuploidy↗
Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs.
Adenosine (ADO) receptor antagonists (aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7-16 days of age breathed via face mask a gas mixture with a fraction of inspired O2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n=8), ZM-241385 (ADO A2A-receptor antagonist, n=7), or vehicle. Ventilation was measured at 20 degrees C by a turbine transducer flowmeter. In normoxia [arterial Po2 (PaO2) of approximately 83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (PaO2 of approximately 31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of approximately 2.5 times control within the first 3 min, which was followed by a significant (P<0.05) decline to approximately 50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (PaO2 of approximately 31 Torr, 10 min). It is concluded that 1) ADO A2A receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A1 receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression.
Adenosine A2 Receptor Antagonists↗
Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan.
Previous fetal studies have indicated depressor responses of intravenous (i.v.) administration of angiotensin antagonists. However, little is known of central effects of angiotensin blockers on fetal cardiovascular controlling. The cardiovascular effects of central administration of the angiotensin-1 (AT(1)) and angiotensin-2 (AT(2)) receptor antagonists, losartan and PD123319, were investigated in the chronically catheterized near-term ovine fetuses. Intravenous losartan produced within 1.5 min a significant and persistent depressor response [maximum Delta mean arterial pressure (MAP)=9 mm Hg] without altering fetal heart rate. Intracerebroventricular (i.c.v.) administration of losartan (1-5 mg/kg) increased fetal arterial pressures (Delta MAP=9-14 mm Hg). Central application of losartan (1 mg/kg) also increased fetal heart rate (maximum Delta heart rate=33 beat per minute). Losartan increased c-fos expression in the median preoptic nucleus and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, the lateral parabrachial nuclei, and the ventrolateral medullabrain. These brain sectors are with abundant AT(1) receptors and have been demonstrated in the involvement in cardiovascular regulation. In contrast, intracerebroventricular injection of the AT(2) receptor antagonist PD123319 had no effect on fetal arterial pressure and heart rate. The results demonstrate strikingly functional differences of losartan on the fetal cardiovascular regulation in central and peripheral sides.
Angiotensin II↗
Electrical stimulation of the posteromedial thalamus modulates breathing in unanesthetized fetal sheep.
Having previously shown that lesions in the posteromedial group of thalamic nuclei abolish hypoxic inhibition of fetal breathing, we devised this study to identify thalamic loci that depress breathing by focal stimulation of specific sectors of the caudal thalamus and adjacent structures. Multipolar electrode arrays consisting of a series of eight stimulation contacts at 1.25-mm intervals were implanted vertically through guide cannulae into the caudal diencephalon of 12 chronically catheterized fetal sheep (>0.8 term), and central neural tissue was stimulated between adjacent contacts. Each site was stimulated repeatedly with increasing current searching for spatial and stimulus strength parameters for a reliable alteration in respiratory rate. Respiratory period increased when stimulation involved areas of the parafascicular nuclear complex (Pf), which more than doubled the mean period compared with the baseline of 0.90 +/- 0.19 s. The change in respiratory period was due to an increase in expiratory time, whereas inspiratory time and breath amplitude were not significantly affected. Breathing period and expiratory time were also increased when the stimulations involved the intralaminar wing surrounding the mediodorsal nucleus, the rostral central gray, zona incerta, and ventral tegmental area. Reductions in respiratory frequency occurred less consistently, with stimulation involving surrounding zones including the sub-Pf, ventromedial nucleus, and ventrobasal nuclear complex. These findings support the hypothesis that a restricted area of the posteromedial thalamus (principally Pf) constitutes part of a neuronal circuitry that modulates respiratory motoneurons.
Animals↗
Adenosine A(2A) receptors mediate hypoxic inhibition of fetal breathing in sheep.
OBJECTIVE: Hypoxia inhibits fetal breathing through activation of central adenosine (ADO) receptors that modulate fetal behavioral state. This study was designed to determine whether adenosine A(1) and/or A(2A)receptor subtypes mediate the depressant effects of hypoxia. STUDY DESIGN: In 14 chronically catheterized fetal sheep (>0.8 term), hypoxemia was induced by having the ewe breathe a gas mixture of 9% oxygen for 1 hour. During hypoxia, the fetus was infused intra-arterially with a vehicle or an antagonist for adenosine A(1) or A(2A) receptors. Statistical analysis was performed by using analysis of variance with Tukey's least significant difference criterion. RESULTS: Fetal isocapnic hypoxemia (PaO(2): control, approximately 24 mm Hg; hypoxia, approximately 14 mm Hg) virtually eliminated rapid eye movements and breathing when the fetus was infused with vehicle or the A(1) receptor antagonist. In contrast, adenosine A(2A) receptor blockade abolished the hypoxia-induced arrest of rapid eye movements and breathing. CONCLUSION: Hypoxic inhibition of rapid eye movements and breathing is critically dependent on activation of adenosine A(2A) receptors.
Animals↗