Relations between the fetal circulation and pituitary-thyroid function.

OBJECTIVE--To study the relation between changes in the fetal thyroid hormone and thyroid stimulating hormone (TSH) concentrations and alterations in the fetal circulation as assessed by Doppler ultrasound. DESIGN--A cross-sectional study of small for gestational age (SGA) and red-cell isoimmunized fetuses undergoing cordocentesis and Doppler studies for the assessment and determination of fetal karyotype, acid-base balance and haemoglobin concentration. SETTING--Harris Birthright Research Centre for Fetal Medicine, King's College, London. SUBJECTS--38 growth retarded and 38 red-cell isoimmunised fetuses. INTERVENTIONS--Cordocentesis. MAIN OUTCOME MEASURES--Serum TSH total and free thyroxine (T4, FT4) and total and free triiodothyronine (T3, FT3) concentrations; middle cerebral artery (MCAVm) and descending thoracic aorta (AoVm) mean blood velocities; fetal Po2 and haemoglobin concentration (Hb). RESULTS--Delta values (delta) calculated as the number of SDs from the respective normal mean for gestation were used to compare the results with those from a previous study of normal fetuses. Mean AoVm was increased in the isoimmunized fetuses (P less than 0.001) but decreased in the SGA fetuses (P less than 0.001). Mean MCAVm was increased in both groups (P less than 0.01; P less than 0.001). There were significant associations between the gestational age adjusted values for TSH and MCAVm (r = 0.23, P less than 0.05) and between T4, FT4 or FT3 and AoVm (r = 0.41, P less than 0.01; r = 0.50, P less than 0.01; r = 0.36, P less than 0.01 respectively). In addition, T4 and FT4 were associated with delta Po2 and delta Hb. CONCLUSION--In the hypoxaemic hypoxia of growth retardation and the anaemic hypoxia of rhesus disease there are significant associations between changes in fetal thyroid hormone concentrations and changes in fetal blood flow as assessed by Doppler. Irrespective of whether altered blood flow is the cause or effect of changes in thyroid hormone concentrations, the observed changes could have beneficial effects for fetal survival, in the presence of a hostile intrauterine environment.     

The fetal circulation

Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.     

正常孕妇垂体-甲状腺轴功能变化的研究

目的了解正常孕妇妊娠各期及产后垂体-甲状腺轴功能的变化;探讨妊娠期人绒毛膜促性腺激素(hCG)对垂体-甲状腺轴的调节作用.方法采用放射免疫法,测定正常孕妇妊娠早、中、晚期及产后甲状腺功能参数[血清总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)、血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)]、hCG及甲状腺结合球蛋白(TBG)的水平.结果(1)血清TT3、TT4水平在妊娠各期均较产后显著升高,其中TT4在妊娠早期最高为(170.00±40.28)nmol/L,TT3在妊娠中期最高为(2.64±0.53)mmol/L.(2)血清FT3水平在妊娠早期[(4.37±0.78)pmol/L]和中期[(4.75±0.90)pmol/L]显著升高,晚期[(3.94±0.75)pmol/L]下降,产后最低(2.96±0.84)pmol/L];血清FT4妊娠早期最高[(14.07±1.44)pmol/L],中期[(12.86±0.84)pmol/L]和晚期(11.29±1.00)pmol/L]逐渐下降,产后[(10.45±1.45)pmol/L]最低.(3)血清TSH水平在妊娠早期最低为(0.88±0.83)mU/L,妊娠中期[(1.86±1.04)mU/L]和晚期[(1.48±0.90)mU/L]上升,产后(2.82±1.42)mU/L]达最高峰.(4)血清hCG水平在妊娠早期最高为(309.05±320.02)μg/L,中期(69.11±19.18)μg/L]和晚期[(86.25±44.60)μg/L]下降,产后[(29.95±20.91)μg/L]最低.(5)hCG与TSH呈负相关,而与FT4、TT4呈正相关.结论(1)hCG可能在整个妊娠期及产后一定时间内,对垂体-甲状腺轴功能有一定的调节作用.(2)产后部分孕妇处于一过性甲状腺功能低减状态.     

An update on the fetal circulation

The fetal circulation has been an exciting area of study for centuries. The principles which grew from the period of hypotheses have been demonstrated in several animal models. These experiments have shaped the major concept of fetal circulation. More recently, the improvement in ultrasound technology has allowed a non invasive study of the fetal circulation in humans. Although the general schema of the fetal circulation has been confirmed in humans, in some aspects some substantial differences have been demonstrated. They may not only reflect some inter-species differences, but also underscore the limitation of chronically instrumented animal studies.     

Doppler investigation of the fetal circulation

Doppler ultrasound provides a non-invasive method for the study of fetal haemodynamics. Animal studies on effects of hypoxia have provided evidence of a redistribution of cardiac output to favour perfusion of the fetal heart, adrenals and brain, at the expense of the carcass, gut and kidneys. This paper summarises the changes in fetal Doppler parameters with advancing gestation. Furthermore, it examines the alterations in fetal haemodynamics in relation to fetal blood oxygen tension in samples obtained by cordocentesis from small for gestational age (SGA) fetuses. In SGA fetuses increased downstream impedence to flow in the umbilical artery, as demonstrated by the absence of end-diastolic frequencies in the flow velocity waveforms (FVW), is associated with fetal hypoxia. This presumably reflects the underlying derangement of placental structure and function. The impedence to flow and mean blood velocity were also measured in FVWs from the descending thoracic aorta and common carotid artery, obtained by pulsed Doppler ultrasound, and from the middle cerebral and renal arteries obtained by colour flow imaging. There were significant correlations between the degree of fetal hypoxia and alterations in Doppler parameters, which were compatible with the brain sparing effect. Thus, in fetal hypoxia impedence to flow in the common carotid and middle cerebral arteries was decreased, whereas impedence in the aorta and renal artery was increased. There were simultaneous alterations in the mean blood velocity in the opposite direction to those in impedence.     

Doppler sonography of the fetal venous circulation

Venous Doppler sonography has been used for assessment of the fetal hemodynamics in the last 15 years. The velocimetries of the central fetal veins — umbilical vein (UV), ductus venosus (DV), hepatic veins (HV) and inferior vena cava (IVC) — reflect the cardiac function and its impairment due to changes in cardiac preload or afterload, and due to changes in the cardiac rhythm. It is possible to see the severity of the disturbance in cardiac function and venous Doppler is broadly used in the surveillance of pregnancies, which are disturbed by severe placental insufficiency, cardiac defects, arrhythmias, anemia, hydrops fetalis and hyper- or hypovolemia as in twin-to-twin transfusion syndrome. Herein we summarize the past, present and eventual future developments of venous Doppler sonography, reflecting the physiology and pathophysiology of the fetal venous circulation and describing the state of the art of its clinical application.     

Regulation of fetal placental circulation

The development and the reactivity of fetoplacental circulation appear to be extremely well coordinated phenomena which follow a precise chronology and are regulated by numerous angiogenic and vasoactive factors. The endothelium of the villous vessels, due to its capacity to release vasodilatating substances, would appear to play a crucial role in the gradual decrease in the vascular resistance of the placenta, thereby enabling it to meet the growing needs of the fetus right up until the end of pregnancy. In the endothelium, as in the smooth muscle of the placental vessels, control of production and mechanisms of action of the signal modulators of placental tone--endothelin 1, nitric oxide, prostanoids, etc.--as well as their dependence on oxygen, are far from being entirely elucidated. The study of their interactions could contribute to better evaluating the relative importance of each of them in the particular balances which are established at different stages of normal pregnancy, as well as during pathological situations (pre-eclampsia, intrauterine growth retardation, etc.) when placental blood flow and fetal development are at risk of being compromised.     

Pulmonary hypertension and persistent fetal circulation in the newborn

Despite these infants' very significant medical instabilities, which require vigorous therapeutic intervention, we have seen a population of infants with little in the way of persistent residual problems. Although many of their pulmonary complications persist after hospital discharge, most resolve within the first year of life. In addition, there are few neurodevelopmental disabilities encountered in such a high-risk population of children.     

Transvaginal Doppler assessment of the fetal cerebral circulation

Blood flow velocity waveforms were recorded by pulsed Doppler examination of the fetal internal carotid and middle cerebral arteries using the established transabdominal route as well as a new transvaginal approach. Fourteen normal controls and 11 pregnancies complicated by intrauterine growth retardation were studied. Satisfactory recordings were obtained in all 25 cases. There was a good correlation (R2 = 0.98) between pulsatility index (PI) values obtained transabdominally and transvaginally. The PI in the middle cerebral artery was significantly higher than in the internal carotid artery in both normal and growth-retarded fetuses. Pulsatility in both cerebral vessels was significantly decreased in growth-retarded fetuses when compared with normal controls. The transvaginal route, which produces a coronal section of the fetal brain, allows better distinction between the internal carotid and middle cerebral arteries. Furthermore, signals of equal quality are obtained from vessels in both cerebral hemispheres. Transvaginal scanning of the fetal cerebral arteries is a feasible technique offering an alternative to transabdominal scanning when the latter is hampered by technical difficulties.