Examination of fetuses after induced abortion for fetal abnormality—a follow-up study

In the North-Western Region we offer a service to examine fetuses aborted after the diagnosis of fetal abnormalities. Many obstetricians use this service. We examined 343 mid-trimester fetuses over the last 5 years: 215 following an abnormal scan and 128 abnormal amniotic fluid or villus findings. When necessary, investigations were performed. A post-mortem examination was always required. As a result of fetal investigation, the scan diagnosis was modified or refined in 91 cases (42·3 per cent). In three of these cases, no fetal abnormality was found. For the fetuses diagnosed as abnormal by amniocentesis or chorionic villus biopsy, in one (0·8 per cent) the pre-termination diagnosis was not confirmed. The results were similar to those of our previous 5-year study except (a) diagnosis of neural tube defects was rarely based on amniocentesis in the present study (2/62, 3·2 per cent) compared with the previous one (32/103, 31 per cent), and (b) renal abnormalities were more often diagnosed in the pre-termination scan in the present study. We conclude that the examination of aborted mid-trimester fetuses by dysmorphologists continues to improve diagnosis, allowing more accurate genetic counselling for the families.     

The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false-positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.     

The importance of late pregnancy scans for renal tract abnormalities

A 12-month prospective population study of antenatal patients was undertaken in a large district general hospital to assess ultrasound scanning in late pregnancy for the detection of non-lethal fetal renal abnormalities. The rate of false-negative antenatal scans during the study period was also assessed. Both 18–20 and 28–32 weeks' gestational scans were performed on 6497 pregnant women. Forty fetuses with a suspected abnormality were referred for postnatal examination and 29 neonates were found to have renal abnormalities. Of these, 21 were significant and eight were likely to be extrarenal pelves. In six, there was evidence of an abnormality at the early scan. Nine children, seven with reflux, presented within the study period, all with preceding normal antenatal scans. The incidence (0·46 per cent) of structural renal abnormalities is similar to that reported previously. A late scan is necessary for the antenatal detection of non-lethal renal abnormalities.     

Fetal surgery for severe lower urinary tract obstruction

Fetal interventions have been proposed for treatment of severe lower urinary tract obstruction (LUTO), as this condition is associated with high rates of perinatal mortality and postnatal renal impairment. The rationale for in utero treatment for those cases is based on the possibility of relieving the obstruction, improving the amniotic fluid volume, and preventing renal and bladder damage. Candidates for fetal intervention should be rigorously selected based on the confirmation of severe LUTO (dilated bladder and bilateral hydronephrosis), oligohydramnios or anyhydramnios and ‘favorable’ fetal urinalysis (dependent on gestational age). Nowadays there are two different therapeutic options with specific technical approaches. Vesico-amniotic shunting is an easier procedure, but with a higher frequency of related complications. Fetal cystoscopy can be used for diagnostic purpose and for treatment of posterior urethral valves, with suggestive advantage of allowing a more physiological release of the obstruction. According to the literature, estimated survival rates and postnatal normal renal function frequencies are approximately 40 and 50% after vesico-amniotic shunting and 75 and 65% after fetal cystoscopy, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

The making of fetal surgery

Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. Copyright © 2010 John Wiley & Sons, Ltd.     

In utero therapy for lower urinary tract obstruction

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico‒amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico‒amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal evaluation of fetal renal function based on serum beta2-microglobulin assessment

The relationship between fetal renal function (FRF) and fetal serum beta₂-microglobulin (B2MG) was investigated by comparing its value in 112 unaffected fetuses with that of 23 fetuses presenting with urinary tract malformations (UTM). Fetal serum level of B2MG was totally unrelated to gestational age; its value increased in cases of severe impairment of FRF but was similar to controls in all mild uropathies (p<0.05). Evaluating serum B2MG could be beneficial in fetuses with severe renal damage, but is of no use in unilateral UTM since only the global FRF is tested and not the function of each single kidney. Copyright © 2001 John Wiley & Sons, Ltd.     

Tertiary centre referral of small-for-gestational age pregnancies: A 10-year retrospective analysis

Between 1981 and 1991, 461 pregnant women between 15 and 40 weeks of gestation (mean 30 weeks) with completed follow-up were referred to our centre for prenatal diagnosis because of a small-for-gestational age (SGA) fetus or combined SGA and structural abnormality. The referral diagnosis was based either on biparietal diameter measurements or on measurement of the upper-abdominal circumference. SGA in our centre was defined as a fetal upper-abdominal circumference below the tenth centile. SGA was confirmed by ultrasound in 75 per cent of the fetuses, whilst combined SGA and fetal structural abnormality was substantiated in only 16 per cent of the fetuses. However, in our centre structural abnormality was detected in 34 fetuses who were referred because of SGA alone. Nearly half of the structurally normal SGA fetuses displayed a normal head-to-abdomen (H/A), ratio, whereas an increased H/A ratio was found in 13/15 fetuses with an abnormal karyotype. An abnormal karyotype was present in 20 fetuses, which is 7 per cent of the total SGA population. Nearly 50 per cent represented triploidy associated with oligohydramnios. SGA was confirmed by a birth weight below the tenth centile in 89 per cent, below the fifth centile in 77 per cent, and below the 2·3rd centile in 55 per cent of infants. Structural abnormality was confirmed in 65 per cent of infants, whereas in 19 per cent of infants the abnormality was missed or a misclassification was made. Perinatal mortality was 31 per cent for all SGA fetuses, 27 per cent for SGA fetuses without anomalies, and 64 per cent for SGA fetuses with structural abnormality.     

Maternal platelet size as a marker for fetal trisomies 18 and 13

Maternal and fetal platelet size and glycoprotein expression were measured in 14 pregnancies complicated by fetal aneuploidy between 20 and 24 weeks' gestation. Flow cytometry was used to determine platelet size and surface glycoprotein Ib (GPIb) and GPIIIa expression both before and after stimulation with adenosine diphosphate (ADP). The data were compared with results obtained from 35 normal paired maternal and fetal controls. In fetuses affected with trisomies 18 and 13, but not trisomy 21, the maternal and fetal platelet sizes were significantly higher than those of the normal controls. Furthermore, the increase in fetal platelet size was significantly associated with the increase in maternal platelet size. Increase in maternal platelet size may be of potential value as a marker for fetal trisomies 18 and 13.     

Detection of fetal structural abnormalities at the 11–14 week ultrasound scan

The aim of this study was to evaluate the detection of fetal structural abnormalities by the 11–14 week scan. 2853 pregnant women were submitted to a routine ultrasound scan between the 11th and 14th week and the fetal skull, brain, spine, abdominal wall, limbs, stomach and bladder were examined. Following the scans the patientes were examined in the second or third trimester of pregnancy. An isolated increased nuchal translucency was not considered an abnormality. However, these patients had an early echocardiography assessment. Fetal structural abnormalities were classified as major or minor and of early or late onset. A total of 130 (4.6%) defects were identified and 29 (22.3%) of these were diagnosed at the 11–14 week scan, including nine cardiac defects associated with increased nuchal translucency. The antenatal ultrasound detection rate was 71.5%, and 31.2% were detected in the first-trimester assessment. 78.8% of the major defects were diagnosed by the prenatal scan and 37.8% by the 11–14 week scan. Fetal structural abnormalities at the 11–14 week scan were detected in approximately 22.3% of the cases, therefore, a second-trimester anomaly scan is important in routine antenatal care to increase the prenatal detection of fetal defects. Copyright © 2002 John Wiley & Sons, Ltd.     

Successful intrauterine shunting of a sacrococcygeal teratoma (SCT) causing fetal bladder obstruction

We report a case of a sacrococcygeal teratoma (SCT) diagnosed at 22 weeks with a substantial intrapelvic cystic extension leading to bladder outlet obstruction and hydronephrosis at 27 weeks. Prenatal percutaneous shunting of the cystic teratoma was performed at 28 weeks to avoid prolonged fetal pelvic compression by the tumour that could have adverse effects by stretching the pelvic plexus and sacral nerves. Urinary dilatation resolved completely after shunting and a 3880 g baby girl was delivered at 39 weeks. The potential benefits of in utero shunting to avoid urological complications of SCTs with intrapelvic extension are discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal cholecystomegaly: A prenatal marker of aneuploidy

The fetal gall bladder can now be easily identified during the second and third trimesters using high-resolution ultrasonography. In this report we present eight fetuses with an enlarged gall bladder detected on prenatal ultrasonography at a mean gestational age of 24.6 weeks (range 19–31 weeks). Additional ultrasonographic findings were present in four cases: fetal anomalies and intrauterine growth retardation in three and polyhydramnios in one. Of those cases associated with fetal anomalies, one woman underwent amniocentesis at 21 weeks revealing trisomy 18. The other two declined prenatal karyotyping; neonatal karyotyping revealed trisomy 13 in one and trisomy 18 in the other. Although an enlarged fetal gall bladder can be a normal variant in the second and third trimesters, the prenatal detection of cholecystomegaly should prompt a search for associated anomalies and other markers of aneuploidy. If found, prenatal karyotyping should be considered.     

Derivated fetal haemoglobin as a marker for red cell age in the human fetus reflecting stimulated or impaired red blood cell production

We have determined whether derivated fetal haemoglobin (dHbF, consisting of glycated and acetylated HbF) can be used as a cell age marker for fetal red blood cells (RBCs). Cord blood was obtained between 19 and 39 weeks of gestation from 28 alloimmunised anaemic fetuses (23 RhD+ and 5 Kell) and from 20 non-anaemic fetuses and newborns (controls). Density gradient centrifugation was applied to 36 samples (20 RhD+, 15 controls and 1 Kell) to obtain fractions of increasing cell age. Blood samples were used for measurements of mean cellular volume (MCV), mean cell haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), pyruvate kinase activity (PK) and derivated fetal haemoglobin (dHbF) by cation-exchange HPLC. Reticulocytes were counted only in the whole blood samples. In all density gradient separated RBC fractions, the values for MCV, MCH and PK activity decreased and those of MCHC and dHbF increased with increasing density (equivalent to increasing cell age). The mean density was lower for RBCs of the anaemic RHD group (1.072±0.007 g/ml) than for the non-anaemic controls (1.077±0.005 g/ml) (p<0.05) The RBC density of the Kell sensitised fetus did not differ from those of the controls. In the control group, the values of the cell age markers in whole blood changed significantly with the gestational age, showing an increase of mean age of the erythrocyte population. The best linear relationship was found for dHbF (y=6.28+0.17*weeks; r=0.84; p<0.001). In the anaemic RhD+ fetuses, the RBC age markers did not change with gestational age; the dHbF percentages were lower, and the MCV, MCH, PK values and the reticulocyte counts were higher than in the controls (0.05<p<0.001). The dHbF values of the Kell sensitised fetuses were above (p<0.01) and the reticulocyte counts were below normal (p<0.05) for gestational age. For the anaemic fetuses, a significant number of the dHbF values (86%) and of the reticulocyte counts (78%) differed from the values of the controls (p<0.01). The dHbF percentages in RhD+ fetuses showed the best correlation with the Hb deficit, which is a measure for anaemia (r=−0.81, p<0.0001). We conclude that the percentage derivated HbF may indicate whether the RBC production is normal for gestational age. It may in that sense reflect stimulated or impaired erythropoiesis in alloimmunised haemolytic anaemia. Copyright © 2001 John Wiley & Sons, Ltd.     

Normal fetal growth in women with antiphospholipid syndrome treated with high-dose intravenous immunoglobulin (IVIG)

Antiphospholid antibodies are associated with fetal distress and fetal death. Although different therapeutic regimens have been used, the incidence of fetal growth retardation varies between 30 and 60 per cent of reported cases. We report the evolution of fetal growth in patients with antiphospholipid antibody syndrome treated with high-dose intravenous immunoglobulins (IVIG). Fourteen patients with a history of recurrent spontaneous abortion and immunological diagnosis of antiphospholipid syndrome were followed longitudinally. Intravenous immunoglobulin at a dose of 0.5 g/kg body weight for two consecutive days was started from the fifth week of pregnancy and repeated every 4 weeks until the 33rd week of gestation. Fetal biometry was evaluated longitudinally from the appearance of the gestational sac at 4 weekly intervals. In the period between 26 and 34 weeks, the frequency of evaluation was increased to every 14 days. Data obtained were compared with a control group of 70 fetuses with uneventful pregnancies matched for gestational age. Neonatal weight is shown in relation to the centiles for the normal population. One patient out of 14 (7.1 per cent) developed gestational hypertension and abruptio placentae. No other pregnancy complications were seen. No proteinuria was found. The mean maternal age was 31.2±3.8 years. Median birth weight was 3433 g±287. The median centile of the birth weight was 65.3±18.6. Mean gestational age at delivery was 1.3 weeks. No fetal or neonatal growth retardation was seen. No significant differences were found in the biometrical parameters investigated in the various gestational ages vs. the control group (Student's t-test not significant); a significant increase in head circumference (P< 0.001) and abdominal circumference (P< 0.05) was found at 36–37 weeks gestational age in the IVIG-treated fetuses. The presence of antiphospholipid antibodies is considered detrimental for pregnancy outcome because of their negative effects on placental vascular perfusion and fetal transfer of metabolites. The use of IVIG seems to avoid or inhibit the reduced availability of nutrients for the fetal anabolic functions, as the expected reduction in fetal growth was not seen in our series.     

Hyperechoic fetal bowel: The perinatal consequences

A number of publications have reported an association between the finding of hyperechoic fetal bowel on prenatal sonogram and disorders such as aneuploidy and cystic fibrosis. To define more precisely the significance of this finding, we systematically reviewed the published material on the subject. Based on a total of 357 reported cases, we documented a high prevalence of cystic fibrosis (25·6 per cent) and chromosome abnormality (12·4 per cent) associated with increased bowel echogenicity in the fetus. High rates of intrauterine growth retardation (14·9 per cent), fetal demise (9·0 per cent), and prematurity (15·3 per cent) were also found. The data were obtained from a population at high a priori risk for aneuploidy and included fetuses at 1 in 4 risk for cystic fibrosis reported in two studies. This increased the bias towards an adverse outcome. The rate of complications when a hyperechoic abdomen is noted in a low-risk fetal population has so far not been delineated. Although the high frequency of complications found is of concern and warrants investigation, extrapolation of these risk figures to a fetal population at low a priori risk may not be appropriate.     

Further predictors of renal dysplasia in fetal obstructive uropathy: Bladder pressure and biochemistry of ‘fresh’ urine

Urine was aspirated on two consecutive days from the dilated bladder of nine fetuses with lower urinary tract obstruction. Gestational age ranged from 17 to 35 weeks. Renal dysplasia was diagnosed histologically in four fetuses, whereas the other five had normal renal histology or only partial dysplasia. Urinary sodium (Na⁺) and osmolality (Osm) decreased significantly in the second urine sample 1 day after bladder emptying (median decrease: Na⁺ = −11.3 per cent; Osm= −13.3 per cent). Although there were no significant differences between fetuses with or without renal dysplasia, normalization of an initially raised urine Na ⁺ concentration occurred at the second sample in a fetus with partially normal renal histology, thus correcting a false-positive diagnosis of dysplasia. Bladder pressure was measured at the time of the first urine sampling in seven fetuses and in a further eight with bladder outlet obstruction undergoing a single urine aspiration at 18–28 weeks. Bladder pressure was increased above the reference range in 8 of 15 fetuses with urinary obstruction, but there was no correlation between pressure and the degree of impairment of renal function. Although no conclusive clinical guidelines can be drawn from this study for the evaluation of fetal renal function, these findings suggest that, in lower urinary tract obstruction, tubular reabsorption is impeded by the standing pressure in the urinary tract and that improvement of renal function may occur following relief of obstruction.     

Magnetic resonance spectroscopy of the fetal brain

Fetal magnetic resonance spectroscopy (MRS) is technically feasible in utero and demonstrates similar findings to those observed in neonatal populations. MRS can provide additional information to conventional T1- and T2-weighted imaging of the fetal brain. It is of particular use when subtle changes are present on conventional fetal MRI sequences, and when imaging fetuses at risk of brain injury and metabolic abnormalities. Copyright © 2009 John Wiley & Sons, Ltd.     

Successful early in utero management of fetal hydrothorax in a twin pregnancy

We present a case of dichorionic diamniotic twin pregnancy in which one of the fetuses was found to have a major pleural effusion at 15 weeks of gestation. A single-needle pleural fluid aspiration was performed at 15 and 16 weeks, but the fluid reaccumulated quickly after each procedure and at 16 weeks, the fetus was found to become progressively hydropic. A shunt was then successfully inserted at 17 weeks, which is the earliest gestation reported so far in the literature for such a procedure to treat isolated hydrothorax. Because we felt that the fetus would be too small for a classical double-pigtail pleuroamniotic shunt, we used a multilength double-pigtail bladder stent (Harrison drain; Cook; Spencer; Indiana; USA) via a 13-gauge echo tip trocar. This shunt could be used for both singleton and twin pregnancies presenting with fetal pleural effusion from as early as 16 to 17 weeks to prevent the development of fetal hydrops and polyhydramnios and subsequent premature delivery. Treatment at this stage of gestation would also minimize the risk of lung hypoplasia, which is the main clinical issue when shunts are inserted after 24 weeks. Copyright © 2003 John Wiley & Sons, Ltd.     

New technique using galactose-specific lectin for isolation of fetal cells from maternal blood

To isolate fetal cells from maternal blood, we developed a new method based on galactose-bearing conjugation. Nucleated red blood cells (NRBCs), which highly express galactose on their surface, were selectively attached to a substrate coated with a galactose-containing polymer via soybean agglutinin (SBA), a galactose-specific lectin. Cord blood samples were used to evaluate enrichment efficacy of NRBCs by this method. Blood samples were obtained from 131 pregnant women between 6 and 27 gestational weeks. After preliminary condensation of fetal cells by Ficoll gradient centrifugation, NRBCs were enriched using galactose-positive selection by adjusting SBA concentration. We isolated one to severalhundred NRBCs (mean±SD, 7.8±8.5) in 2.3 ml of peripheral blood samples from 96% of pregnantwomen. The isolated NRBCs were analyzed by a Y-chromosome FISH probe in eight cases carrying male fetuses. Y-signals were detected in all eight cases and more than half of the NRBCs wereoffetal origin. The study demonstrates that our new method using galactose-specific lectin provides effective enrichment of fetal NRBCs allowing non-invasive prenatal diagnosis. Copyright © 2002 John Wiley & Sons, Ltd.     

Failure to detect fetal obstructive uropathy by second trimester ultrasound

The prenatal diagnosis, management and outcome of an hereditary obstructive uropathy is presented. Serial ultrasonic assessment of the fetal urinary tract was carried out from the early second trimester onward. Slight bilateral hydronephrosis as a first sign of obstructive uropathy was only established as late as 30 weeks of gestation. On the basis of weekly ultrasound scans, a conservative approach was adopted. In view of fetal maturity, labour was induced at 36 weeks resulting in the vaginal delivery of a male infant with moderate bilateral hydronephrosis. Neonatally, anuria developed due to bilateral obstruction of the ureters as a result of increasing bladder wall hypertrophy due to urethral valves. A bilateral uretero-cutaneostomy was carried out. The infant so far develops normally, and renal function is normal for age. Women at risk for fetal obstructive uropathy should have ultrasonic monitoring throughout pregnancy.