Hideo Gotoh

Ultrasonographic prediction of lethal pulmonary hypoplasia: Comparison of eight different ultrasonographic parameters☆☆☆★

OBJECTIVE The aim of this study was to determine the usefulness of eight different ultrasonographic fetal parameters for predicting fetal pulmonary hypoplasia. STUDY DESIGN Nomograms of eight different ultrasonographic fetal parameters were evaluated by studying uncomplicated single fetus pregnancies with well-established dates between 18 and 40 weeks of gestation. The eight parameters, which could reflect fetal lung mass, were as follows: thoracic circumference, thoracic area, thoracic area minus heart area, lung area, thoracic circumference/abdominal circumference ratio, thoracic area/heart area ratio, thoracic area minus heart area/thoracic area ratio and lung area/thoracic area ratio. The relative efficacy of the eight parameters was determined by studying 21 fetuses at high risk for development of lethal pulmonary hypoplasia and 30 fetuses with premature rupture of membranes within 1 week. RESULTS The lung area (gestational age-dependent parameter) and the thoracic circumference/abdominal circumference (gestational age-independent parameter) ratio had the best diagnostic accuracy (sensitivity 81.3% and 90.5%, specificity 100% and 90.0%, positive predictive value 100% and 86.4%, negative predictive value 90.9% and 93.1%, respectively). There were significant linear relationships between lung weight and lung area and between the lung weight/body weight ratio and the thoracic circumference/abdominal circumference ratio. CONCLUSION These data suggested that the application of lung area and the thoracic circumference/abdominal circumference ratio are clinically useful for the evaluation of fetal pulmonary hypoplasia.

Diagnosis of fetal pulmonary hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler ultrasonography.

OBJECTIVE The aim of the study was to determine the utility of ultrasonographically recorded blood flow waveforms of the pulmonary artery in the diagnosis of pulmonary hypoplasia. STUDY DESIGN The normal values of the pulsatility index and peak systolic flow of pulmonary arterial blood velocity waveforms were determined in 300 uncomplicated single fetus pregnancies with well-established gestational ages between 24 and 40 weeks. We also measured the same parameters in 5 fetuses at high risk for development of severe pulmonary hypoplasia. We also determined the radial alveolar count and microvessel density, representing the extent of angiogenesis, in tissue specimens collected at autopsy from normal and hypoplastic lungs and stained both with hematoxylin and eosin and immunohistochemically for factor VIII. RESULTS In healthy fetuses the pulsatility index values of both the right and left pulmonary arteries diminished significantly with advancing gestation, whereas the peak systolic velocity increased significantly with advancing gestation. In fetuses with pulmonary hypoplasia pulsatility index values were high and the peak systolic flow was significantly lower than in healthy fetuses. Histologic examination showed a lower radial alveolar count and poorer angiogenesis in fetuses with pulmonary hypoplasia than in healthy fetuses. CONCLUSION Doppler ultrasonographic determination of pulmonary artery blood velocity waveforms is a useful tool for the diagnosis of pulmonary hypoplasia.

Management of prenatal ovarian cysts

OBJECTIVES The aim of the present study was to analyze the antenatal and postnatal outcome of fetal ovarian cysts in relation to their ultrasonographic pattern and size. METHODS Sixteen fetal ovarian cysts were diagnosed in 16 fetuses and followed with serial ultrasonograms in utero and after birth until spontaneous or surgical resolution. RESULTS Eleven fetal ovarian cysts were simple cysts at first prenatal scan but 3 of the 11 became complex cysts at last prenatal scan and required postnatal laparoscopic surgery. Seven of the 11 simple cysts (63%) disappeared on follow-up imaging by ultrasonograms or MRI during pregnancy or within 2 months after birth. The rate of spontaneous resolution of simple cysts was higher than that of complex cysts (40.0%). The mean maximum diameter of the ovarian cysts before delivery that were subsequently excised surgically at postnatal period (50+/-13.4 mm) was not different from that of ovarian cysts that resolved spontaneously (42.8+/-12.8 mm, P=0.2918). CONCLUSION In our study, cyst size did not predict the risk of ovarian loss. The opportunity of laparoscopic exploration versus conservative management needs to be investigated because some complex cysts resolved spontaneously in the postnatal period.

The effects of oligohydramnios and cervical cord transection on lung growth in experimental pulmonary hypoplasia in rabbits

OBJECTIVE Our goal was to examine the effects of oligohydramnios and cervical cord transection on fetal lung development, pulmonary surfactant, and lung mechanics in rabbits. STUDY DESIGN The amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits. In another group (n = 12) high cervical cord transection was performed at day 24 of gestation. Another 12 littermates not operated on served as the control group. Fetuses were delivered on day 30 of gestation by cesarean section and immediately put to death. The body weight and wet lung and liver weights were measured. To determine the extent of fetal lung growth, we measured the size of lung acini, the number of terminal airspaces, and the diameter of alveoli. We also measured the dynamic compliance of the lung, the concentration of phosphatidylcholine, and the lecithin/sphingomyelin ratio in lung lavage fluid at birth. RESULTS Amniotic fluid shunting produced a significant reduction in amniotic fluid volume. Amniotic shunt and cervical cord transection significantly decreased wet lung weight and fetal lung/body weight ratio compared with the control. The concentration of phosphatidylcholine and the lecithin/sphingomyelin ratio in lung fluid lavage from fetuses with amniotic shunt were significantly higher than the values for control and cord transection fetuses. Histopathologic examination of the lungs showed significant reductions in the size of acini, the number of terminal airspaces, and the diameter of alveoli in shunted and cord transection groups compared with the control group. The dynamic compliance of transection fetuses was significantly reduced compared with control and shunted fetuses. CONCLUSION Our results indicate that oligohydramnios or cervical cord transections cause pulmonary hypoplasia. However, oligohydramnios-induced pulmonary hypoplasia is associated with increased pulmonary surfactant compared with control and cord transection fetuses.

Fetal redistribution of blood flow and amniotic fluid volume in growth-retarded fetuses.

Our purpose was to assess the relationship between the fetal redistribution of blood flow and the amount of amniotic fluid in appropriate-for gestational-age fetuses and growth-retarded fetuses. Blood flow velocity waveforms of the umbilical artery, descending aorta, middle cerebral artery, renal artery and uterine artery were recorded using pulsed Doppler ultrasonography in 100 appropriate-for gestational age fetuses and 39 growth-retarded fetuses. The pulsatility index (PI) values and the amount of amniotic fluid were compared between the two groups. The PI values of the umbilical artery and renal artery were significantly higher in appropriate for gestational-age-fetuses with oligohydraminos than in fetuses with an adequate amount of amniotic fluid. The PI values of the umbilical artery and renal artery were significantly higher and the PI of the middle cerebral artery was significantly lower in growth-retarded fetuses with oligohydramnios than in fetuses with an adequate amount of amniotic fluid. Furthermore, there was a significant negative correlation between the PI value of the renal artery and the vertical diameter of amniotic fluid, and between the PI value of the renal artery and the amniotic fluid index. The PI value of the renal artery was related to the amount of amniotic fluid in growth-retarded fetuses, and the same relationship was demonstrated in appropriate-for gestational age fetuses.

Effect of epidermal growth factor on lung growth in experimental fetal pulmonary hypoplasia.

The purpose of this study was (1) to compare the expression of epithelial growth factor receptor (EGFR) in the lung tissues of human fetuses with or without pulmonary hypoplasia, and (2) to investigate the effects of EGF on lung growth in experimental pulmonary hypoplasia in rabbits. Firstly, we investigated the expression of EGFR in lung tissues of human fetuses with or without pulmonary hypoplasia by immunohistochemistry. Secondly, the amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits, another group (n = 12) received EGF injection (5 microg, i.p.) at day 25 of gestation. The third group (n = 12) was only treated with EGF while littermates not operated on served as the control group (n = 12). On day 29 of gestation, fetuses were delivered by Cesarean section and the lungs removed. The body weight and wet lung and liver weights were measured. As a measure of fetal lung growth, we determined the size of lung acini, the number of terminal airspaces, and diameter of alveoli (n = 6, each groups). We also measured the concentration of phosphatidylcholine (PC) and the lecithin/sphingomyelin (L/S) ratio in lung lavage fluid at birth in some fetuses (n = 6, each groups). In human fetuses with pulmonary hypoplasia, there was a significant decrease in radial alveolar count and expression of EGFR compared with fetuses without pulmonary hypoplasia. Amniotic shunt significantly decreased fetal lung/body weight ratio compared with control. Injection of EGF in the shunted group significantly increased lung/body weight ratio to the control level. The concentration of PC and L/S ratio in lung fluid lavage from rabbit fetuses with hypoplastic lungs was significantly higher than the other three groups. Histopathological examination of fetuses with hypoplastic lungs treated with EGF showed no significant change in the size of acini, number of terminal airspaces or the diameter of alveoli compared with the control group. Our results suggested that EGF was associated with lung growth and maturation of human lung and that treatment of rabbit fetuses with hypoplastic lungs with EGF facilitated lung growth and development.

Fetal blood flow redistribution in term intrauterine growth retardation (IUGR) and post-natal growth

Objective: The purpose of the present study was to evaluate the relationship between intrauterine growth retardation, represented by fetal blood flow redistribution and infantile growth. Methods: The blood flow velocity waveform of umbilical and middle cerebral arteries was recorded by Doppler ultrasonography in 77 growth‐retarded fetuses. We recorded the pulsatility index (PI) of the umbilical artery and middle cerebral and calculated the PI ratio of the middle cerebral to umbilical artery (C/U ratio). We selected a cutoff value of 1.0 to distinguish between normal and abnormal C/U ratios. To evaluate the development of infants, height, body weight and head circumference were measured serially at 3, 6 and 12 months of age. Results: Birth weight was significantly lower in newborns who had abnormal C/U ratios (2021 ± 295 g vs. 2294 ± 236 g). The number of cases admitted to NICU was higher and the duration of admission was longer in abnormal C/U ratio group (15/29 and 33.7 ± 13.5 days) than normal C/U ratio group (7/48 and 26.6 ± 5.6 days). Body weight was lower in infants of abnormal C/U ratio group at 3 months, but was not different at 6 and 12 months. The height was shorter in abnormal C/U ratio group at birth, there were no significant differences at 3, 6 and 12 months. The number of newborn infants with growth retardation was slightly higher in abnormal C/U ratio group, but the difference was not significant at 6 and 12 months. There was no relationship between C/U and growth variables recorded at birth and follow‐up in infants. Conclusion: Intrauterine growth‐retardation, represented by abnormal fetal blood redistribution was associated with adverse perinatal outcome, but the influence was not found at the first year of life.

Effect of experimentally induced urethral obstruction and surgical decompression in utero on renal development and function in rabbits

To investigate the effect of urethral obstruction during late fetal life on renal development and function, we developed a rabbit fetal model of obstructive nephropathy to examine the pathological and biochemical consequences of urethral obstruction and beneficial effects of early surgical decompression. Animals were divided into four groups, i.e., obstructed, early decompressed, late decompressed, and control. Fetal renal development was evaluated by histological examination and counting the number of glomeruli in the four groups. The number of renal glomeruli correlated with gestational age in the normal fetus (r = 0.90, P < 0.0001). Urethral ligation on gestational day 25 (full-term, 31 days) resulted in thinning of the renal cortex and significantly decreased the number of renal glomeruli. The concentration of urinary microalbumin was higher when urethral obstruction was maintained for 3 days than 1 day after urethral obstruction, although urinary beta2- microglobulin, Na, Cl, and osmotic pressure did not change during this period. Decompression of urethral obstruction 1 day after induction of urethral obstruction resulted in improvement in the severity glomerular hypoplasia compared with late decompression (P < 0.01). Our results suggest that the rabbit fetal model simulates fetal urethral obstruction in humans, and indicates that early surgical decompression may be effective in restoration of normal renal function.