Current Controversies in Prenatal Diagnosis 1: Should MRI be performed on all fetuses with mild ventriculomegaly?

A ventricular diameter of 10 mm correlates with more than two standard deviations of the normal and hence is qualified as ventriculomegaly. The relevance of this is dependent on whether there are associated infectious, genetic, or structural problems. The chance for neurodevelopmental delay in isolated ventriculomegaly less than 15 mm is 7.9% (4.7-11.1), and less if it is unilateral. It can be further divided in mild (10-12) or moderate (13-15), though this is not widely accepted. As part of the workup, structural assessment today may include ultrasound or magnetic resonance imaging, or both. Discussants agreed that the diagnostic performance of both methods is as good as the expertise with which the images are acquired and interpreted. Discussants agreed that when the initial neurosonogram is normal, the likelihood of finding significant findings on MRI is low. Nevertheless, some anomalies may only be picked up or better worked out by fetal MRI. In utero follow-up is advocated, as progression may indicate a poorer outcome, and some conditions are only obvious late in pregnancy. Most benefit for future patients is expected from appropriate training in prenatal neuroimaging.     

Transabdominal chorionic villus sampling and amniocentesis for prenatal diagnosis: 5 years' experience at a University Centre

The fetal loss rates and fetal congenital birth defects in 821 transabdominal (TA) chorionic villus sampling (CVS) and 771 amniocentesis (AC) cases were evaluated from a 5-year period (1987–1991) at the University Central Hospital of Turku. The parents were given the option of choosing between the two sampling procedures. CVS was performed, in most cases, at 11 weeks of gestation; and AC, at 15 weeks. The rate of total post-procedure loss was 6·7 per cent in the CVS group and 4·4 per cent in the AC group (p=0·08). The rate of spontaneous abortions was 1·9 per cent in the CVS group and 1·0 per cent in the AC group (p=0·10). The number of birth defects was low in both study groups. No limb reduction cases were observed. Mosaicism was noted in 14 CVS cases and in five AC cases. We conclude that TA-CVS is a safe and practical alternative to AC in prenatal fetal karyotyping.     

Calf circumferences in fetuses and neonates with and without talipes equinovares. A prospective cohort study

Objective

Children and adults with talipes equinovarus (TEV) have smaller calves and shorter feet compared to non-affected controls. Do these changes have a prenatal onset?

Methods

A prospective cohort study (January 2020–July 2021) was conducted with serial ultrasonographic measurements at 20 and 28 weeks gestation and measurements directly and 6 weeks after birth. Calf circumference and width, foot length and length of humerus, ulna, radius, femur, tibia and fibula were measured in TEV and were compared to a control population. Calculated sample size necessitated a minimal population of 10 cases with TEV and 50 controls.

Results

Twenty cases with TEV and 62 controls were included. Fetal calf circumference (p < 0.001) and width (p < 0.001) were smaller in the TEV group in comparison to the control group, which persisted after birth. Growth in foot length (p < 0.001) and calf width (p 0.003) declined prenatally over time. The bone lengths and upper leg circumference were not smaller or shorter in TEV compared to controls.

Conclusion

This prospective cohort study demonstrated the prenatal onset of reduced calf and foot size in fetuses with TEV from 20 weeks and onwards, which persists directly after birth. To investigate whether reduction in circumference initiates TEV or is caused by TEV, further examination is needed.     

Rapid and radical amniodrainage in the treatment of severe twin–twin transfusion syndrome†

We have evaluated the role of a rapid and radical method of amniodrainage in the treatment of severe twin–twin transfusion. The outcome of 15 patients with severe twin–twin transfusion for which a amniodrainage was performed by means of a vacuum bottle system was compared with the outcome of 15 patients with a similar condition, matched for gestational age at the time of the initial procedure and drained using a standard procedure. In the study group the amniodrainage ended when no amniotic fluid could be aspirated, whereas the women in the standard group were drained with a syringe system and the fluid was removed until the deepest amniotic fluid pool was <8 cm. At the initial procedure, the mean volume of amniotic fluid drained was significantly (p<0.05) higher (3252 vs 2153 ml) and the length of the procedure significantly (p<0.001) shorter (21 vs 41 min) in the study group than in the standard group. The mean post-procedure amniotic fluid index was significantly (p<0.001) smaller (2.9 vs 7.7 cm) after radical amniodrainage than after the standard amniodrainage. The mean number of procedures was significantly (p<0.001) lower (1.5 vs 5.6) in the study group compared to the standard group. In the study group the mean placental thickness increased significantly (p<0.001) from 9 mm before the procedure to 49 mm after, and the overall perinatal survival rate was 80% and the proportion of pregnancies with at least one survivor was 93%. The present data indicate that early, rapid and radical amniodrainage is an effective and low-cost therapy for severe twin–twin transfusion syndrome. Compared to the standard amniodrainage technique it also appears to reduce the need for multiple procedures. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal ultrasonographic diagnosis of fetal cerebral ventriculitis associated with asymptomatic maternal cytomegalovirus infection

Cytomegalovirus is the most common cause of congenital viral infection. In utero infection is usually suspected in patients with growth-retarded fetuses or when maternal illness precipitates serological investigations. A case is presented where routine ultrasound examination at 30 weeks' gestation in an asymptomatic patient demonstrated mild fetal ventriculomegaly. Transvaginal ultrasound enabled the visualization of intraventricular adhesions and small periventricular cysts. The suspected diagnosis of in utero cytomegalovirus infection was confirmed by the presence of IgM antibodies in fetal blood and subsequently by isolation of the virus from the infant's urine. The presence of mild fetal ventriculomegaly should prompt transvaginal brain imaging.     

Prenatal ultrasound finding of atypical genitalia: Counseling,genetic testing and outcomes

Objective

To report uptake of genetic counseling (GC) and prenatal genetic testing after the finding of atypical genitalia on prenatal ultrasound (US) and the clinical and genetic findings of these pregnancies.

Methods

A retrospective cohort study (2017–2019) of atypical fetal genitalia in a large expert center for disorders/differences of sex development. We describe counseling aspects, invasive prenatal testing, genetic and clinical outcome of fetuses apparently without [group 1, n = 22 (38%)] or with [group 2, n = 36 (62%)] additional anomalies on US.

Results

In group 1, 86% of parents opted for GC versus 72% in group 2, and respectively 58% and 15% of these parents refrained from invasive testing. Atypical genitalia were postnatally confirmed in 91% (group 1) and 64% (group 2), indicating a high rate of false positive US diagnosis of ambiguous genitalia. Four genetic diagnoses were established in group 1 (18%) and 10 in group 2 (28%). The total genetic diagnostic yield was 24%. No terminations of pregnancy occurred in group 1.

Conclusions

For optimal care, referral for an expert fetal US scan, GC and invasive diagnostics including broad testing should be offered after prenatal detection of isolated atypical genitalia.     

Mid-trimester amniocentesis and antibiotic prophylaxis

Objectives and Methods Assuming that the rate of fetal loss after amniocentesis may be reduced in patients receiving antibiotic prophylaxis, we conducted a retrospective study on untreated versus treated patients receiving prophylactic antibiotics (amoxicillin/clavulanic-acid or azithromycin) and evaluated the fetal loss rate within the 22nd week of gestation, also with respect to the risk of spontaneous abortion, both preexisting and related to mid-trimester amniocentesis. Results Spontaneous abortion occurred in 22 cases out of 1744 (1.26%). The incidence of spontaneous abortion was 1.3% among patients treated with antibiotic prophylaxis and 1.2% among untreated patients. Between patients with risk factors that predated amniocentesis, the spontaneous fetal loss rate was 9.2% in untreated patients versus 2.3% in patients treated (p = 0.10). In patients with procedure-related risk factors at amniocentesis, the spontaneous abortion rate was, respectively, 2.2 and 1.2% (p = 0.72). Conclusion Our data demonstrate that antibiotic prophylaxis does not reduce the risk of spontaneous abortion within the 22nd week of gestation. Compared with untreated patients, patients treated with amoxicillin showed the lower fetal loss rate (1.16 vs 0.31%), but the difference was not statistically significant (odds ratio (OR) = 3.68, p = 0.32). The same was true for patients with preexisting risks (OR = 4.25, p = 0.10). Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal evaluation and postnatal outcomes of fetal ovarian cysts

To evaluate the natural history and outcome of cases of fetal ovarian cyst under conservative prenatal treatment. A retrospective cohort study included patients diagnosed with fetal ovarian cysts was conducted between January 2008 to December 2016. Data including clinical data, sonographic feature and postnatal outcomes were obtained. One hundred and two cases were included for statistical analysis. The rate of spontaneous resolution was significantly higher among cases with simple than complex cysts (70/92 or 76.1% vs 2/10 or 20%, P < .01) and for cysts <4 cm than cysts ≥4 cm (50/56 or 89.3% vs 22/46 or 47.8%, P < .01). Ovarian torsion was confirmed in 5/102 (4.9%) cases; neither prenatal characteristics of cysts (complex: 2/10 or 20% vs simple: 3/92 or 3.3%, P = .07), nor their size ( ≥ 40 mm: 4/46 or 8.7% vs < 40 mm: 1/56 or 1.8%, P = .17) was predictive for ovarian torsion. 25/102 (24.5%) of cysts change in size or sonographic characteristics prenatally. Half of the complex cysts at the last prenatal scan are not ovarian in origin. 98/102 neonates (96.1%) were able to preserve both ovaries. Spontaneous resolution of ovarian cysts is predicted by cyst size and characteristics, whereas likelihood of torsion cannot be predicted.     

Apert syndrome: what prenatal radiographic findings should prompt its consideration?

Apert syndrome was diagnosed in a newborn with typical facial and digital features whose only detected prenatal abnormality had been agenesis of the corpus callosum. This prompted a review of the central nervous system findings in all cases of Apert syndrome treated at the Craniofacial Center Boston Children's Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had prenatal identification of mild dilatation of the lateral cerebral ventricles and complete agenesis of the corpus callosum (ACC) documented with both ultrasound and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital malformations typical of Apert were eventually seen in these fetuses in the third-trimester, even in retrospect, these were not detectable at mid second-trimester, ultrasound screening for congenital malformations. Hand malformations also went undetected in the second-trimester despite extensive imaging by experienced radiologists. We conclude that prenatal ultrasonographic identification of mild ventriculomegaly or ACC should stimulate a careful search for features of Apert syndrome and prompt follow-up imaging to look for bony abnormalities that have later onset. Prenatal molecular testing for Apert mutations should be considered in cases of mild ventriculomegaly and ACC. Copyright © 2006 John Wiley & Sons, Ltd.     

Presentation of ventriculomegaly at 11–14 weeks of gestation: An analysis of longitudinal data

Objectives

The aim of this study was to examine the value of the sonographic measurements of the choroid plexus and the lateral ventricles at 11–14 gestational weeks in fetuses that had the diagnosis of second-trimester ventriculomegaly (VM) as a clinical reference.

Methods

The standard axial plane used for biparietal diameter measurement from 2D stored images in the first trimester was used to calculate the ratio between the choroid plexus and lateral ventricle diameter (PDVDR), the choroid plexus and lateral ventricle length (PLVLR) and the choroid plexus and lateral ventricle area (PAVAR) in 100 normal and 15 fetuses diagnosed with second-trimester VM.

Results

In fetuses with VM, the measurements of PDVDR, PLVLR and PAVAR were all significantly smaller compared to normal fetuses (p = < 0.001, <0.001, <0.01). Four out of seven cases with mild VM had measurements below the 5th percentile (57%). 75% of cases with moderate or severe VM had at least one measurement below the 5th percentile.

Conclusions

Since the axial plane of the fetal head is obtained in all first-trimester routine screenings, the measurements of PDVDR, PLVLR and PAVAR could easily be integrated into routine examinations for an early detection of VM.     

Isolated mild fetal cerebral ventriculomegaly: a retrospective analysis of 26 cases

We retrospectively studied 26 fetuses with isolated mild cerebral ventriculomegaly diagnosed between 1992 and 1998 and defined by a lateral ventricular atrial diameter of 10–15 mm without any other cerebral anomaly. Our objectives were to determine maternal risk factors, to evaluate complementary investigations, to assess developmental prognosis and to propose possible management. During pregnancy 10/26 patients had regressive ventriculomegalies, ten remained borderline at birth and six were confirmed postnatally. No maternal risk factors were identified. Prenatal investigations were carried out in 69% of cases but in only a few cases supplied any information. Postnatal examinations revealed one case of Down syndrome and one of porencephaly. Four children were lost to follow-up. In the 22 other cases, four had developmental delay. Early and unexplained mild ventriculomegaly appears to have a good prognosis. If ventriculomegaly is persistent, prenatal management should be carried out to investigate chromosomal abnormalities, viral infection, and fetal cerebral parenchymal damage. A long postnatal clinical follow-up is required. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal urinary insulin-like growth factor I and binding protein 3 in bilateral obstructive uropathies

Fetal urinary concentrations of insulin-like growth factor I (UIGF-I) and binding protein 3 (UIGFBP-3) were determined in patients with prenatal diagnosis of bilateral obstructive uropathy. Patients were retrospectively assigned to three groups, on the basis of outcome: group 1, termination of pregnancies (n = 11) with sonographic evidence of severe oligohydramnios or renal dysplasia, confirmed at histological examination; group 2, patients (n = 10) with postnatal plasma creatinine > 50 μmol/1 at the age of 1 year (1 yr-pCreat); and group 3, patients (n = 16) with 1 yr-pCreat ≤ μmol/1. The results show a significant increase in UIGF-I and UIGFBP-3 in groups 1 (18 159 ± 9083 pg/ml; 2657 ± 669 ng/ml) and 2 (1574 ± 847 pg/ml; 176 ± 50 ng/ml) in comparison with group 3 (35 ± 6 pg/ml; 21 ± 2 ng/ml). UIGF-I and UIGFBP-3 were significantly correlated with postnatal plasma creatinine, and were both sensitive (90 per cent; 80 per cent) and specific (88 per cent; 88 per cent) for prediction of elevated 1 yr-pCreat (>50 μmol/1). Fetal urinary IGF-I and IGFBP-3 are increased in severe fetal bilateral obstructive uropathy, possibly reflecting tubular dysfunction or/and increased synthesis consequent upon fetal kidney injury. Their predictive value for postnatal renal function needs further assessment.     

Short communication the natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling: A case report

A patient in whom intrauterine fetal cytomegalovirus (CMV) infection was diagnosed at approximately 25 weeks' gestation is presented. The fetus was evaluated by serial fetal blood samplings and ultrasound examinations. The fetus manifested evidence of severe thrombocytopenia and hepatic inflammation, with recovery over a period of approximately 8 weeks. The initial sonographic findings of marked fetal ascites and cardiomegaly gradually resolved; ventriculomegaly developed during the third trimester. At delivery, the baby was morphologically normal with the exception of mild ventriculomegaly. Cord blood was negative for CMV IgM but urine was culture-positive for CMV. At age 3, the child has a severe but stable unilateral hearing deficit and is otherwise developmentally normal. This case demonstrates the utility of serial ultrasound and fetal blood sampling in the prenatal diagnosis and management of fetal CMV infection.     

Risk of amniocentesis in women screened positive for Down syndrome with second trimester maternal serum markers

In routine obstetrical practice, prior to offering invasive prenatal diagnosis, it is crucial to weigh the risks attendant on amniocentesis against the individual's risk of aneuploidy. We took advantage of a policy of follow-up of patients undergoing Down syndrome maternal serum screening to compare the rates of fetal loss before 24 weeks and of early premature delivery at 24–28 weeks between women who underwent amniocentesis and women who did not. A total of 54 902 patients entered the study, of whom 4039 (7.35%) were lost to follow-up and 387 were excluded because of a severe fetal abnormality. Of the 50 476 remaining patients, 3472 had an amniocentesis whereas 47 004 had not and served as controls. In the amniocentesis group, the fetal loss rate before 24 weeks was 1.12% (95% CI=1.08–1.15) and the 24–28 weeks premature delivery rate was 0.40% (95% CI=0.39–0.41) which was significantly higher than in controls (0.42% with 95% CI 0.41–0.43 and 0.24% with 95% CI 0.23–0.25, respectively). The 0.86% difference in adverse outcome rates between the amniocentesis and control groups may be attributable to amniocentesis and compares favourably with the positive predictive value of maternal serum markers (1.70%) observed in the present study. Copyright © 2002 John Wiley & Sons, Ltd.     

Mild fetal cerebral ventriculomegaly as a prenatal sonographic marker for Kartagener syndrome

Primary ciliary dyskinesia (PCD), also referred to as immotile-cilia syndrome or Kartagener syndrome, is a group of genetic disorders caused by defective cilia leading to chronic sinupulmonary infection, situs inversus and reduced fertility. Some PCD patients also have cerebral ventriculomegaly or hydrocephalus. We report here two fetuses and one newborn with mild cerebral ventriculomegaly and a suspected and/or confirmed diagnosis of PCD. These cases demonstrate that mild fetal cerebral ventriculomegaly can be a prenatal sonographic marker of PCD, certainly in fetuses with situs inversus or a history of a previous sib with PCD. Copyright © 2003 John Wiley & Sons, Ltd.     

Prenatal diagnosis and prenatal imaging features of fetal monosomy 1p36

Deletion of the distal end of the short arm of chromosome 1 (1p36) is thought to be a common terminal chromosomal deletion. However, few cases prospectively diagnosed prenatally have been reported. In this case, prenatal ultrasound at 21 weeks of gestation noted the fetus to have mild ventriculomegaly (Vhanterior = 11 mm and Vhposterior = 12 mm) and increased nuchal edema (6 mm). Maternal serum α-fetoprotein was normal unlike in a majority of previously described cases. The prenatal ultrasound features were further clarified with fetal MRI. Chromosome analysis following amniocentesis demonstrated a 1p36 deletion, which was confirmed by fluorescence in situ hybridization (FISH). The syndrome associated with 1p36 deletion is well described in infants and is characterized by typical facial features (prominent forehead, straight eyebrows. deep-set eyes, flat nasal bridge and a pointed chin). Other associated features are neurodevelopmental delay, seizures, cardiomyopathy and neurosensory hearing impairment. This case supplements our knowledge of the prenatal features of 1p36. Identification of this deletion by direct chromosomal analysis can be technically difficult and vigilance is required to improve diagnosis. FISH analysis is an important diagnostic adjunct where the diagnosis is suspected following classical G-banding techniques. However, in this chromosomal anomaly there remain few characteristic prenatal signs that are readily diagnosed with prenatal imaging. Copyright © 2007 John Wiley & Sons, Ltd.     

Ultrasonic placental localization in relation to spontaneous abortion after mid-trimester amniocentesis

This paper summarizes our experience with a series of 562 women referred for mid-trimester amniocentesis for prenatal diagnosis. Ultrasonography was utilized for placental localization. Follow-up revealed a fetal loss rate of 3.03 per cent with 1.96 per cent being spontaneous abortions. Patients with an anterior placenta had a fetal loss and spontaneous abortion rate of 4.06 per cent and 3·05 per cent, respectively. No significant difference in the incidence of fetal loss (p > 0·1) or spontaneous abortion (p > 0·5) was found in patients having an anterior versus a posterior placenta. Neither multiple insertions through an anterior placenta nor blood contaminated amniotic fluid from patients with an anterior placenta were associated with an increased incidence of fetal loss or spontaneous abortion.     

Effects of mid-trimester induced abortion on the subsequent pregnancy

The outcome of the pregnancy following (a) a mid-trimester termination of pregnancy (TOP) for fetal neural tube defect (NTD) (77 women=group 1); (b) mid-trimester TOP for fetal Down's syndrome (13 women=group 2); (c) delivery of a baby with NTD (119 women=group 3) was studied. The prenatal fetal loss was relatively high in all groups. In group 1 it was similar to that found in other studies after first trimester TOP, in group 2 it was associated with advanced maternal age and the unexpected finding in group 3 was not attributable to advanced maternal age. It is suggested that a previous NTD per se might increase the risk of fetal loss in the next pregnancy. A previous mid-trimester TOP for NTD was not associated with an increase in premature labour, small for dates babies or congenital abnormality in the next pregnancy, but there was a slight increase in the number of babies weighing less than 2500 g.     

Risk assessment of amniocentesis between 11 and 15 weeks: Comparison to later amniocentesis controls

We studied 693 consecutive early amniocenteses (prior to 15 weeks) and found a spontaneous abortion rate to 28 weeks' gestation of 1·5 per cent. A control group of women having standard amniocentesis (15–20 weeks) experienced a 0·6 per cent fetal loss in the same period. There were no other apparent differences between the two groups. Early amniocentesis results are generally available 4–6 weeks before standard amniocentesis and 1–3 weeks after chorionic villus sampling (CVS). Alpha-fetoprotein (AFP) can be accurately assayed in 11- to 15-week amniotic fluid samples but additional studies are necessary to determine the accuracy of neural tube defect (NTD) detection. Including the present study, over 5800 early amniocenteses have been reported and the results suggest that this is a relatively safe prenatal diagnostic test and an alternative to CVS and later amniocentesis.     

The effect of fetal gender on second-trimester maternal serum inhibin-A concentration

Second-trimester serum inhibin-A is increasingly used as a fourth marker in addition to the triple test to screen for Down syndrome. We investigated whether fetal gender had an effect on serum inhibin-A concentration. A retrospective analysis was done on 316 normal pregnancies and 48 Down syndrome pregnancies in which maternal serum inhibin-A assays were performed between 15 and 20 weeks of gestation and in which the fetal sex was known. The median inhibin-A MoM (95% CI) for normal pregnancies in the presence of a male fetus was 0.93 (range 0.88–1.03). This was significantly lower than that in the presence of a female fetus (median MoM=1.04). The gender difference was not observed in the Down syndrome pregnancies. The increased inhibin-A concentration would lead to a 2.3-fold higher false-positive rate in the presence of a female fetus (10.6% vs 4.6%; p<0.05, Chi-square test). Because of the small number of cases studied, the results need to be substantiated by a larger series. If the gender effect is confirmed, adjustment for fetal sex may be necessary when inhibin-A is used as a screening marker. Copyright © 2001 John Wiley & Sons, Ltd.