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Immunologic responses of the bovine fetus to parvovirus infection.

Effects of bovine parvovirus (PBV) infection on the bovine fetal immune system were studied. Five fetuses obtained by cesarean section at 5, 10, 20, 40, and 60 days after they were inoculated and 2 control fetuses at 130 and 153 days of gestation were studied. Virus was recovered from the BPV-inoculated fetuses. between 5 and 10 days postinoculation (PI) fetal blood lymphocyte counts tripled, due primarily to an increase in E-rosetting lymphocytes. There were transient increases in fetal serum immunoglobulin (Ig) M (peaking at PI day 20), marked and gradual increase in IgG1, and minimal increase of IgG2. Serum-neutralizing antibodies were detected at PI day 10 and increased to a titer of 1:2056 by day 60. Peripheral blood lymphocytes of all fetuses responded well to the nonspecific mitogens phytohemagglutinin, concanavalin A, and pokeweed mitogen. Histopathologically, there was lymphoid hyperplasia, most evident in lymph nodes draining the site of PBV inoculation. There was no indication of lymphoid depletion or necrosis in lymph nodes, spleen, or thymus of PBV-inoculated fetuses. These data indicate that under the conditions of this study, inoculation of the isolate of PBV may stimulate an immune response in the fetus.

Animals↗

Diarrhea due to Campylobacter fetus subspecies jejuni. A clinical review of 63 cases.

Campylobacter fetus subspecies jejuni was isolated fom the feces of 63 (3.2%) of the 1,953 patients who had stools cultured at the Mayo Clinic in 1979. In contrast, Salmonella and Shigella combined were isolated from 31 (1.6%) patients. Two patients had double infections with Salmonella species and C. fetus subsp jejuni. Three patients had no diarrhea at the time of stool culture. One patient, who had chronic lymphocytic leukemia, had both blood and stool cultures positive for C. fetus subsp jejuni. There was a seasonal incidence that peaked in July when 7.8% of all patients who had stools cultured had C. fetus subsp jejuni isolated. Thirteen cases occurred in children 5 years of age and younger and 29 cases occurred between the ages of 15 and 30 years. Clinical features often included a prodrome of malaise, which preceded the onset of abdominal cramps, diarrhea, anorexia, fever, nausea, and vomiting. Grossly bloody diarrhea occurred in 33 patients, and massive intestinal bleeding occurred in 1 patient as a late complication after diarrhea had resolved. Transient splenomegaly was attributed to C. fetus subsp jejuni on one occasion. Proctoscopic findings may be similar to those seen in inflammatory bowel disease or pseudomembranous colitis. Three patients were referred to this institution with newly diagnosed chronic ulcerative colitis, and one patient was referred with newly diagnosed Crohn's disease. C. fetus subsp jejuni was isolated from their stools, and the diagnosis of inflammatory bowel disease was subsequently dropped. A selected review of cases illustrates the variety of gastrointestinal manifestations seen with this organism.

Adolescent↗

[Variability in occurrence, course and division into branches of renal arteries in human fetuses].

The existence and position of kidneys and suprarenal glands as well as the occurrence of the renal arteries were examined in 347 human fetuses between 3 and 9 months of age. The studies on the course and division variability of the right and left renal arteries were performed in 220 fetuses. The investigations consisted in filling arteries with resin, X-raying and preparing. No absence of a kidney, suprarenal body and renal artery was disclosed. In 2 cases an abnormal position of the right kidney was stated. The renal arteries, both right and left, were most frequently running off from the aorta as single branches, the right one in 190 (86.4%) cases, the left in 152 (69%) cases. Two branches on the right side were recorded in 24 (10.9%) fetuses, and on the left side in 56 (25.5%) fetuses. Three renal branches were stated in 6 (2.7%) on the right side and in 12 (5.5%) fetuses on the left side. In 50.9% of cases the renal arteries were leaving the aorta symmetrically on the same level. In 32.7% the right renal artery was higher and in 2.7%, it was lower than the left one. The horizontal course from the aorta to the kidney hilus of the right renal artery was observed in 83 (37.7%) and of the left one in 99 (45%) of fetuses. In others the renal arteries were running less or more obliquely and downwards. The way, in which the right and left renal arteries are divided into branches, and also the departure places of renal suprarenal ramifications were so different that it is not possible to work out their classifications.

Fetus↗

Value of standardized gestational age charts for fetuses of first-generation Oriental immigrants to Canada.

OBJECTIVE: to ascertain if standard gestational age charts can be used to accurately predict the gestational age of fetuses of first-generation Oriental immigrants to Canada. PATIENTS AND METHODS: Over a 3-year period, all patients presenting for obstetric ultrasound examinations were invited to participate in the study. The authors recorded biparietal diameter, head circumference, femur length and abdominal circumference for 139 fetuses in the second and third trimesters. A study performed in the first trimester was used as the baseline for gestational age. The data for 126 of the fetuses were complete, and these data were used for the analysis. RESULTS: For 77 of the fetuses, both parents were Oriental, and for 49, one or both parents were not Oriental; the latter constituted the control group. A total of 1008 individual measurements were obtained, and of these, all but 14 fell within two standard deviations of the norm, according to standard gestational age charts. Of the abnormal measurements, seven were obtained from five fetuses with Oriental parents, and seven were obtained from six fetuses in the control group. The difference between the two groups in the proportion of measurements falling either above or below two standard deviations from the norm was not statistically significant (Fisher's exact test, p = 0.41694). CONCLUSION: The authors conclude that standard gestational age charts can be used to determine gestational age in first-generation Oriental immigrants to Canada.

Anthropometry↗

Ontogeny of erythropoietin gene expression in the sheep fetus: effect of dexamethasone at 60 days of gestation.

We have used competitive reverse transcription and polymerase chain reaction (RT/PCR) to compare the levels of erythropoietin (Epo) mRNA in the liver and kidneys of the sheep fetus at 60, 80, 100, 130, and 140 days of gestation (term = 145 to 150 days). The effect of dexamethasone infusion in the ewe on Epo gene expression in the 60-day fetus was also investigated. Epo mRNA levels were highest at 60 days of gestation, the earliest age studied, in both liver and kidney. In the liver, Epo mRNA expression declined as gestation proceeded. Kidney Epo mRNA was maintained at a high level until 100 days of gestation, declining significantly in the 130-day fetus (P < .01). Treatment of ewes carrying 60-day fetuses with 0.76 mg/h dexamethasone for 48 hours resulted in a significant decrease in fetal plasma Epo values and Epo mRNA levels in both the liver and kidney. In the dexamethasone-treated fetuses, Epo mRNA in the liver was 52% of control values (P < .05), and in the kidney, 33% of control (P < .001). The results suggest that the kidney may play a more important role as a site of Epo synthesis in the early gestation sheep fetus than previously thought. Glucocorticoids may have a role in the regulation of Epo gene expression.

Animals↗

Chromosomal findings in fetuses with ultrasonographically diagnosed ventriculomegaly.

Out of 1101 fetuses with prenatally diagnosed malformations and/or growth retardation 166 (15.1%) revealed a ventriculomegaly. Out of these 18 fetuses (10.8%) demonstrated a chromosomal disorder. Within the group of 97 fetuses with isolated hydrocephalus 6 (6.2%) revealed a chromosomal abnormality. Two fetuses among 29 (6.9%) with hydrocephalus and spina bifida as the only additional sign showed pathologic karyotypes. Among fetuses with additional malformations, 10 out of 40 (25.0%) had a chromosomal disorder. Our data demonstrate that a prenatally diagnosed hydrocephalus should be regarded as an indication for a chromosomal analysis, with the highest amount of chromosomal disorders in fetuses with different additional malformations.

Cardiomegaly↗

Intra-uterine growth retardation and limb deformities produced by neuromuscular blocking agents in the rat fetus.

Intra-uterine growth retardation and limb deformities, resembling clubfoot, were produced by tubocuararine chloride, and by toxiferine, when administered to the rat fetus between the 16th and 19th day of gestation. These effects were associated in some fetuses, but were not sex-linked. Fetuses in the middle part of the uterine horn were observed to be more vulnerable. Placentae of the affected fetuses were smaller in size and weight at birth. Direct toxic effects of the drug on the fetus and/or on the placenta, along with immobilization of the fetus in utero due to the neuromuscular blocking action of the drugs, seem responsible for these effects. These finding warrant proper caution and care in administering such drugs to women, even as late as the third trimester of pregnancy.

Abnormalities, Drug-Induced↗

[Hepatic resection in the fetal rabbit. Histologic comparison of tissue regeneration in the fetus versus the adult].

Fetal tissues present peculiar features of repair after injury. Although the development of fetal hepatocytes have already been studied in vitro and in transplant models, an in vivo study of fetal liver regeneration is still missed in the literature, to the best of our knowledge. Eight time-dated pregnant California rabbits (23, 24, 25, 30 days of gestational age) and 2 adult male California rabbits were anesthetized following a standardized i.v. protocol (ketamine 50 mg/kg; xilazine 5 mg/kg; propiopromazine 0.75 mg/kg; spontaneous breathing; no anesthetic gas). All the pregnant does underwent a midline laparotomy and a minimal hysterotomy to approach a fetus per each animal. In 2 cases, 1 fetus was delivered and prior to sacrifice the fetal liver was sampled in toto (30 days of gestational age). These pregnancies were allowed to continue to term and were uneventful with a full-term spontaneous delivery of the remaining fetuses. In the other 6 pregnancies, after the hysterotomy, the fetal abdomen was entered through a right-sided longitudinal incision and the liver was partially resected by thermocauterization. Fetal abdomen was closed in 1 layer (non absorbable suture 7-0). The fetus was then returned in the uterus and, after amniotic fluid restoration with warmed saline, the hysterotomy was sutured in double layer (polyglycolic 5-0). Maternal abdomen was closed in 1 layer (polyglycolic 4-0) and the skin in a continuous overlying fashion (silk 3-0). The abdominal cavity of the 2 adult male rabbits was entered through a right subcostal incision. Partial liver resection was performed, and abdominal and skin closure followed the same techniques used for the pregnant does. The treated livers were then sampled in toto at 24, 48, 72 hrs and 4 days after surgery from the fetuses, and at 7 days from the adult rabbits. Histological stains were: H & E; Van Gieson; Masson; Alcian Bleu; PAS. Fetal histology showed a low inflammatory reaction poor in PMN cells with minimal deposition of collagen and a high amount of glycogen in the hepatocytes. The inflammatory response to resection was much more evident in the adult samples as much as the abundant intra and extra-cellular deposition of collagen associated to a minor amount of intracellular glycogen. The peculiar features of liver regeneration in the fetus, deserve further experimental studies.

Animals↗

Comparative stereological study on zonation and cellular composition of adrenal glands of normal and anencephalic human fetuses. I. Zonation of the gland.

Comparative stereological studies were performed on zonation of adrenal glands in 10 anencephalic and 11 normal fetuses, aged between 24 and 39 postovulatory weeks. The development of adrenal fetal zone (FZ) is the main factor responsible for normal adrenal gland growth during the intra-uterine life. At the end of fetal period volume of this zone attains over 8200 mm3 and constitutes 69-70% of the total gland volume, while respective values for zona glomerulosa (ZG), zona fasciculata (ZF) and medulla (M) are 1665 mm3 (14%), 833 mm3 (7%) and 1071 mm3 (9%). These data were in striking contrast with those found in adrenals of anencephalic fetuses, in which volume of the gland attained only ca 35% of that in normal fetuses. In the oldest anencephalic fetus studied (39 weeks) the volume of the fetal zone was 962 mm3 (ca 8-folds lower than in normal fetus) comprising only 25% of the total gland volume. For the remaining zones the values were: ZG-1501 mm3 (ca 90% of the normal value and 39% of the total gland volume); ZF-770 mm3 (ca 92% and 20% respectively), and M-539 mm3 (ca 50% and 14%, respectively). This stereological study provides the first systemic description of the development of adrenal gland of anencephalic fetuses in comparison with the normally developing gland. Moreover, evidence is given that the growth of adrenal medulla is also retarded in anencephaly while the growth of the zona glomerulosa remains rather unaffected.

Abnormalities, Multiple↗

State control in the substance-exposed fetus. I. The fetal neurobehavioral profile: an assessment of fetal state, arousal, and regulation competency.

Behavioral states are stable structures of behaviors that become more definable and coordinated with increasing age. With ultrasound we can see the fetus move, breathe, and react to changes in its environment. Ultrasound used in conjunction with Doppler fetal heart rate recording provides behavioral and neurophysiologic data useful in state determination. The Fetal Neurobehavioral Profile (FNP) was developed by our group as an assessment of fetal behaviors reflecting CNS integrity in the drug-exposed fetus. The FNP was designed to parallel methods of examining the newborn infant, especially in state-related behaviors. The FNP measures: fetal responsiveness and arousal after environmental perturbation with vibroacoustic stimulation (VAS); habituation to VAS; state recovery; and self-regulation post-VAS. From the behavioral and physiologic recordings, the constructs of state differentiation, organization, and regulation as well as fetal arousal and regulation competency can be measured. Previous work using the FNP showed that those fetuses with abnormal or suspect fetal state regulation demonstrated impaired performance on the NBAS (Am. J. Obstet. Gynecol. 161: 685, 1989). To expand these observations, three populations are currently being studied: prenatal nicotine-exposed, prenatal cocaine-exposed, and controls. Data are from 97 women/fetus dyads and a total of 236 FNP at ages 28-30 weeks gestational age, 31-34 weeks gestational age, and > 36 weeks gestational age. Although there are no group differences in the ability to achieve state by 36 weeks, interesting trends emerge: fetuses prenatally cocaine-exposed spend less time in 1F, more time in 4F and have fewer transitions. At FNP, fewer cocaine-exposed fetuses had an initial reaction to VAS, whereas fewer nicotine-exposed fetuses habituated. Although the ability to habituate to VAS did not discriminate the cocaine group from the control or nicotine groups, the number of stimuli required for habituation differed between groups: 7 for the cocaine-exposed, 3 for the nicotine, and 5 for the control groups. Thus latency, a measure of arousal, differs among the groups Preliminary data also suggest a correlation of prenatal data with postnatal outcome.

Arousal↗

Different patterns of obstetric complications in myotonic dystrophy in relation to the disease status of the fetus.

The obstetric histories of 26 women with myotonic dystrophy (DM), who had a total of 67 gestations, were reviewed retrospectively comparing gestations with affected (DM-fetuses) and unaffected fetuses (UA-fetuses). Second, the influence of gestation on the disease course and the personal attitude towards family planning in DM was assessed. Miscarriages and terminations occurred in 11 pregnancies. Of the 56 infants carried to term, 29 had or most likely had inherited the gene for DM from their affected mothers at the time of investigation; 18 (61%) in this series were affected by the congenital form of DM. Perinatal loss rate was 11% and associated with congenital DM. The rate of obstetric complications was significantly increased in all women. However, preterm labor was a major problem in gestations with DM-fetuses (55 vs. 20%), as was polyhydramnios (21% vs. none). While forceps deliveries or vacuum extractions were required in 21% of deliveries with DM-fetuses and only 5% of UA-fetuses, the frequency of Cesarean sections was similar in both groups (24 and 25%). Obstetric problems were inversely correlated with age at onset of maternal DM, while no effect of age at delivery or birth order on gestational outcome was seen. DNA analysis confirmed the diagnosis in 19 patients by the presence of enlarged CTG repeats (EcoRI-expansions) on chromosome 19. Of the 17 patients whose CTG repeat length was known, 59% were classified as E2 (corresponding to 500-1000 repeats), 24% as E1 (<500 repeats), while larger expansions (E3; 1000-1500 repeats, or E4; >1500 repeats) were seen in three patients (17%). Obstetric complications or congenitally affected children occurred in all maternal phenotypes and CTG repeat classes. Eight (31%) patients experienced a worsening of symptoms that was temporary, weight related in three cases, and persistent in five. With the exception of three patients, most new mothers were able to care for their families. To conclude, pregnant women with DM need constant obstetric monitoring and should be advised to deliver in centres with perinatal facilities.

Adult↗

Prenatal diagnosis of 30 fetuses at risk for fragile X syndrome.

The results of 30 prenatal diagnoses for fragile X syndrome are reported. Amniotic fluid cells were examined in 1 case, fetal blood in 4, and chorionic villi samples in the others. Of the 5 fetuses analyzed by cytogenetic methods, 1 had showed 4% of fraXq27.3 expression sites and the pregnancy was terminated. For 1 diagnosis, linkage analysis was used: the female fetus turned out to be normal. In 24 fetuses, the direct analysis of the mutation by StB12.3 probe was performed: 6 female and 3 male fetuses were found to carry a full mutation and 1 female fetus was found to carry a premutation. In 3 cases, the diagnoses were verified on fetal blood samples. Several tissues of 2 aborted male fetuses were analyzed for the fragile X mutation. The results are reported and discussed.

Chorionic Villi Sampling↗

Abnormalities of the heart and great arteries in first trimester chromosomally abnormal fetuses.

Pathological examination of the heart and great arteries was performed in 112 chromosomally abnormal fetuses after surgical termination of pregnancy at 11-16 weeks of gestation. The chromosomal abnormalities were diagnosed by chorion villus sampling which was carried out because screening of the pregnancies by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation identified them as being at increased risk. The group consisted of 60 fetuses with trisomy 21, 29 with trisomy 18, 17 with trisomy 13 and 6 with Ullrich-Turner syndrome. The most common cardiac lesion seen in trisomy 21 fetuses was an atrioventricular or ventricular septal defect. Trisomy 18 was associated with ventricular septal defects and/or polyvalvular abnormalities. In trisomy 13, there were atrioventricular or ventricular septal defects, valvular abnormalities, and either narrowing of the isthmus or truncus arteriosus. Ullrich-Turner syndrome was associated with severe narrowing of the whole aortic arch. In all four groups of chromosomally abnormal fetuses, the aortic isthmus was significantly narrower than in normal fetuses and the degree of narrowing was significantly greater in fetuses with high nuchal translucency thickness. It is postulated that narrowing of the aortic isthmus may be the basis of increased nuchal translucency thickness in all four chromosomal abnormalities.

Abnormalities, Multiple↗

Fetal breasts in normal and Down syndrome fetuses.

UNLABELLED: To assess the validity of fetal breast size measurement as a sonographic marker in fetuses with Down syndrome. METHODS: Fetal breasts were studied in 26 fetuses with trisomy 21 and 78 fetuses with normal chromosomes. Breasts were identified and measured in a cross-sectional plane of the fetal chest at the level of the four-chamber view of the heart. Normal fetuses had a mean breast size of 3.8 mm +/- 1.1 mm. Fetuses with Down syndrome had a mean breast size of 1.9 mm +/- 0.7 mm (p < or = 0.0001). Diminished breast size measured by ultrasound in the second trimester may be helpful in identifying fetuses with Down syndrome.

Breast↗

Doppler velocimetric indices from the abdominal and placental ends of the umbilical artery of growth-restricted fetuses.

PURPOSE: In normal pregnancies, as gestation advances, a progressive decrease is observed in the differences between Doppler indices recorded at the 2 extremities of the umbilical cord. The purpose of this study was to determine whether the same pattern is observed in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Forty-seven fetuses with sonographic diagnosis of IUGR underwent investigation by Doppler sonography. Blood flow velocities were measured at the abdominal and placental ends of the umbilical cord. The systolic-diastolic ratio, pulsatility index, and resistance index were calculated for each site. The differences in values between the 2 ends of the cord were calculated (abdominal end minus placental end) and then compared with the differences calculated for normal fetuses. RESULTS: In contrast to normal fetuses, IUGR fetuses with abnormal Doppler measurements had significant differences in the pulsatility and resistance indices between the 2 ends of the cord after 28 weeks of gestation. In addition, when compared with normal fetuses, the IUGR fetuses had a significantly greater difference in the values for the 2 ends of the cord for all indices. CONCLUSIONS: These results emphasize the importance of identifying the sampling site for serial Doppler investigations in IUGR-complicated pregnancies.

Abdomen↗

Prenatal sonographic findings in 187 fetuses with Down syndrome.

We determined the type and frequency of abnormal sonographic findings in 187 Down syndrome fetuses. Examinations were performed transvaginally or transabdominally between 9 and 28 weeks' gestation. Consecutive scans performed prior to knowledge of the fetal karyotype (n = 144) were analysed separately for one of the participating centres. In 93 fetuses (49.7 per cent), a total of 138 abnormalities were observed. The most commonly detected anomalies were cystic hygroma and increased nuchal fold thickness (30.5 per cent), hydrops (9.6 per cent), cardiac defects (7.5 per cent), pyelectasis or hydronephrosis (5.9 per cent), echogenic bowel (4.8 per cent), and a large variety of internal organ abnormalities (16.0 per cent) which are not typically associated with Down syndrome. Two anomalies or three anomalies in the same fetus were observed in 21 and 5 fetuses, respectively. No patterns of concurrent malformations were apparent among these fetuses. Sensitivity for Down syndrome detection by ultrasound scans performed without knowledge of the fetal karyotype was 24.1 and 42.6 per cent before 13 weeks and between 14 and 23 weeks, respectively. We conclude that structural abnormalities are frequently observed in Down syndrome fetuses, but many sonographic findings are not typically associated with this syndrome.

Abdomen↗

Signs of first-degree heart block occur in one-third of fetuses of pregnant women with anti-SSA/Ro 52-kd antibodies.

OBJECTIVE: To prospectively investigate the development of fetal heart block in anti-SSA/Ro 52-kd-positive women, and to evaluate the usefulness of serial Doppler echocardiography in detecting early signs of congenital heart block. METHODS: Twenty-four women with anti-SSA/Ro 52-kd antibodies and consequently increased risk for fetal heart block were followed up weekly, between 18 and 24 weeks of gestation, with two Doppler echocardiographic methods designed to estimate the time delay between hemodynamic events caused by atrial and ventricular depolarizations. Two hundred eighty-four women with normal pregnancies served as controls. Anti-Ro 52-kd, anti-Ro 60-kd, and anti-La antibodies were investigated by immunoblotting and enzyme-linked immunosorbent assay using recombinant proteins. RESULTS: In anti-Ro 52-kd-positive women, fetal atrioventricular (AV) time intervals were longer and heart rates were slightly lower compared with those in controls. Eight of 24 fetuses had signs of first-degree block. One of these fetuses had progression to complete block, and another showed recovery from second-degree block to first-degree block with betamethasone treatment. In the remaining 6 fetuses, spontaneous normalization occurred before or shortly after birth. Fetuses with normal AV time intervals at 18-24 weeks had normal electrocardiographic results at birth. CONCLUSION: Anti-Ro 52-kd-positive pregnant women frequently carry fetuses with Doppler echocardiographic signs of first-degree AV block. These blocks revert spontaneously in the majority of fetuses, but progression to a more severe degree of block may occur in some. Serial Doppler echocardiographic measurement of AV time intervals is suggested as a useful method for surveillance of these high-risk pregnancies.

Adult↗

Sonographic measurement of the fetal cerebellum, cisterna magna, and cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy.

PURPOSE: Absence of the cavum septum pellucidum (CSP), the cisterna magna (CM), or both, and enlargement of either or both structures are associated with various central nervous system malformations. In an effort to determine normal sizes and relationships between these cranial structures, we measured the CSP and CM in normal fetuses in the second and third trimesters of pregnancy using transabdominal sonography. METHODS: Women with uncomplicated pregnancies and normal singleton fetuses between 16 and 38 weeks' menstrual age were included in this prospective study. The width and anteroposterior (AP) diameters of the CSP were measured on the transverse transventricular plane, and the AP diameter of the CM was measured on the transcerebellar plane from the posterior aspect of the cerebellar vermis to the inner edge of the cranium. The transverse and AP diameters of the cerebellum were also measured. In addition, we measured the biparietal diameters (BPDs). RESULTS: In total, 130 women participated; 64 were examined in their second trimester and 66 in their third trimester. The mean age of the women was 27.4 +/- 4.8 years (range, 18-38 years), and the mean menstrual age of the fetuses was 26.9 +/- 6.7 weeks (range, 16-38 weeks). The mean BPD was 66.8 +/- 18.7 mm (range, 30-96 mm). The mean width and AP diameter of the CSP and the mean AP diameter of the CM differed significantly between the second and third trimesters (p < 0.001). All measured parameters correlated significantly with menstrual age and BPD. CONCLUSIONS: In normal fetuses, the CSP and CM should be visible on transabdominal sonography between 16 and 38 weeks' menstrual age. Because abnormalities in these cranial structures may be indicative of central nervous system malformations, the availability of mean sonographic measurements from normal fetuses should be helpful in determining the need for additional testing in fetuses with abnormal measurements.

Adult↗