Prenatal Predictions Research Articles

Predicting Cardiac Anatomy, Physiology, and Surgical Management Based on Fetal Echocardiography in Heterotaxy Syndrome.

Heterotaxy syndrome (HS) is often associated with complex congenital heart disease (CHD). While fetal echocardiography (FE) permits accurate prenatal identification of most CHD, the high level of disease complexity in HS may pose challenges in predicting postnatal findings and outcomes. This study aimed to define the accuracy of FE in predicting postnatal anatomy, physiology, and surgical management of CHD in the setting of HS. Retrospective single-center cohort study including all patients with a prenatal diagnosis of HS from 2003 to 2018. Anatomic diagnoses from FE reports were compared with postnatal echocardiogram, catheterization, and operative reports. Prenatal predictions were compared with postnatal outcomes with a focus on ductal dependence, time to first intervention (immediate, neonatal period, 1-6 months, or older than 6 months), and surgical approach (single or biventricular). There were 102 pregnancies with fetal HS resulting in 21 terminations, 5 fetal losses, and 76 live births. Of the live births, 55 had significant CHD and available postnatal data for review. Among this group, survival to 1 year was 62% and was no different comparing single versus biventricular surgical approach. FE diagnostic accuracy varied by anatomic feature and was the lowest for diagnosis of venous anatomy. Determination of postnatal care was most accurate for predicting single versus biventricular surgical approach (91%), followed by ductal dependence (75%). Accuracy for predicting time to first intervention was the lowest at 69%. The most common reason for an incorrect prediction was difficulty in assessing the severity of pulmonary stenosis. FE permits accurate predictions regarding surgical approach. Characterizing systemic and pulmonary veins is challenging, as is predicting ductal dependence and time to first intervention. These data suggest that despite the high diagnostic accuracy of CHD in HS, a circumspect approach may be reasonable with regard to predicting some anatomic details and postnatal management decisions. · In HS, FE was most accurate for intracardiac anatomy.. · Diagnostic accuracy of venous anatomy was less reliable.. · Predicting surgical approach (single ventricle vs. biventricular) was highly accurate.. · Predicting ductal dependence and time-to-intervention were more challenging in some instances..

Does prenatal counseling for pregnancies complicated by multiple fetal abnormalities concord with postnatal outcomes?

In pregnancies complicated by multiple fetal abnormalities, our objective was to determine the degree of concordance between prenatal prognosis and postnatal outcomes. Retrospective cohort study of pregnancies with multiple fetal abnormalities referred to the Fetal Concerns Center of Wisconsin (FCCW) from 2015 to 2018. We reviewed records for anomalies, given prognostic severity, and postnatal outcomes. Prognostic severity was categorized as "likely mortality," "severe impairment," "moderate," and "mild" based on predetermined criteria. In 85 pregnancies with multiple fetal abnormalities, 48% were given a prognosis of "likely mortality," and 19% were given a prognosis of "severe impairment." In pregnancies that were continued after being counseled as "likely mortality," this outcome was concordant in all but one case, despite medical interventions. In pregnancies counseled as "severe impairment," the more common outcome was mortality or severe impairment in 88% of cases and survival with severe impairment in 33% of cases. Postnatal outcomes were concordant with prenatal severity in 68% of the cases, more severe in 20% of the cases, and less severe in fewer than 5% of cases. Prenatal predictions about severe outcomes are usually true in pregnancies complicated by multiple abnormalities. In cases of outcome discordance, outcomes tend to be more severe than predicted.

Accuracy of sonographic fetal gender determination: predictions made by sonographers during routine obstetric ultrasound scans.

Objectives: The purpose of this study was to determine the accuracy of sonographer predictions of fetal gender during routine ultrasounds. Primarily, the study sought to investigate the accuracy of predictions made in the first trimester, as requests from parents wanting to know the gender of their fetus at this early scan are becoming increasingly common. Second and third trimester fetuses were included in the study to confirm the accuracy of later predictions. In addition, the mother's decision to know the gender was recorded to determine the prevalence of women wanting prenatal predictions. Methods: A prospective, cross sectional study was conducted in a specialist private obstetric practice in the Illawarra, NSW. A total of 640 fetuses across three trimesters were examined collectively by seven sonographers. Fetal gender was predicted using the sagittal plane only in the first trimester and either the sagittal or transverse plane in later trimesters. Phenotypic gender confirmation was obtained from hospital records or direct telephone contact with women postnatally. Results: Results confirmed 100% accuracy in predictions made after 14 weeks gestation. The overall success rate in the first trimester group (11–14 weeks) was 75%. When excluding those scans where a prediction could not be made, success rates increased to 91%. Results were less accurate for fetuses younger than 12 weeks, with an overall success rate of 54%. Male fetuses under 13 weeks were more likely to have gender incorrectly or unable to be assigned. After 13 weeks, success rates for correctly predicting males exceeded that of female fetuses. Statistical differences were noted in the success rates of individual sonographers. Sixty seven percent of women were in favour of knowing fetal gender from ultrasound. Publicly insured women were more likely to request gender disclosure than privately insured women. Conclusions: Sonographic gender determination provides high success rates in the first trimester. Results vary depending on sonographer experience, fetal age and fetal gender. Practice guidelines regarding gender disclosure should be developed. Predictions prior to 12 weeks should be discouraged.

Prenatal and postnatal diagnosis of cleft lip and palate

Orofacial clefts are one of the most common congenital malformations. The prevalence of cleft lip and palate (CLP) has been reported to be 0.48/1000 (Baumler M et al, 2011). The genetic risk of malformations is more elevated when the clefts of palate and lip are associated than with cleft lip is alone (BergE SJ et al, 2001). Prenatal ultrasound tecniques are used to display both the normal and the pathological fetal lip and palate (Platt L et al, 2006). It’s very important to verify the accuracy of ultrasound tecnique in predicting clefting of the fetal lip and hard palate and other congenital anomalies. In the current study we present a case report of a woman with prenatal diagnosis of cleft lip and palate: we compared the prenatal ultrasound predictions with postnatal clinical findings on examination of the newborn’s palate. A 33-year-old woman, with a family history of cleft lip and palate, was referred for routine ultrasonic examination during her second trimester of pregnancy. Ultrasonography (USG) showed a single live foetus of a gestational age of 20+4 weeks; biparietal diameter and head circumference were adequate for the week of gestation. In frontal view it was possible to identify a bilateral cleft of the upper lip. In median sagittal view was depicted also a cleft of hard palate. After genetic counseling, the patient decided for an elective termination of the pregnancy. A stillborn female fetus was delivered with a weight of 350 g. Infantogram and gross autopsy confirmed the lip and palate cleft, but the autopsy revealed also an hidden form of spina bifida. A detailed scan of fetal anatomy between 20 and 32 gestational weeks detect majority of cleft lip and palate, but a few of congenital abnormalities are still difficult to diagnose antenatally. It’s therefore necessary to improve the accuracy of ultrasonic examination in order to provide the correct informations for a possible termination of pregnancy. However, this last must be preceded by genetic counseling and diagnosis for recurrence risk.

Accuracy of prenatal three‐dimensional ultrasound in the diagnosis of cleft hard palate when cleft lip is present

To investigate the accuracy of prenatal axial three-dimensional (3D) ultrasound in predicting the absence or presence of cleft palate in the presence of cleft lip. Between March 2005 and January 2009, there were 81 cases with a prenatal two-dimensional (2D) ultrasound screening diagnosis of unilateral or bilateral cleft lip at 22-25 weeks of gestation referred to our tertiary care center. Of these, 79 fetuses were included in this prospective study and two were excluded. Axial 3D ultrasound imaging of the fetal palate was performed and the diagnoses were compared with clinical findings at delivery. The frequencies of intact and cleft palate, the degree of association between the prenatal predictions and postnatal findings and the probability of detection of cleft lip and palate were determined. Of 79 prenatal predictions, 77 (97%) were correct and the association between the prenatal predictions and postnatal findings was strong. The sensitivity for detection of cleft lip and palate within this high-risk population was 100% and the specificity was 90%. In one of the excluded cases, the palate could not be visualized due to a fetal prone position. There were chromosomal anomalies in 4% of cases and associated structural or growth anomalies in 23%, termination of pregnancy was carried out in 4% and intrauterine fetal demise occurred in 3%. Axial 3D ultrasound of the fetal palate has high accuracy in identifying prenatal cleft palate when cleft lip is diagnosed at mid-trimester 2D ultrasound screening.

Prenatal prediction of childhood-onset spinal muscular atrophy (SMA) in Turkish families.

Childhood-onset spinal muscular atrophy (SMA) is one of the most common neurodegenerative genetic disorders. SMN1 is the SMA-determining gene deleted or mutated in the majority of SMA cases. There is no effective cure or treatment for this disease yet. Thus, the availability of prenatal testing is important. Here we report prenatal prediction for 68 fetuses in 63 Turkish SMA families using direct deletion analysis of the SMN1 gene by restriction digestion. The genotype of the index case was known in 40 families (Group A) but unknown in the remaining 23 families (Group B). A total of ten fetuses were predicted to be affected. Eight of these fetuses were derived from Group A and two of these fetuses were from Group B families. Two fetuses from the same family in Group A had the SMNhyb1 gene in addition to homozygous deletion of the NAIP gene. One fetus from Group A was homozygously deleted for only exon 8 of the SMN2 gene, and further analysis showed the presence of both the SMN1 and SMNhyb1 genes but not the SMN2 gene. In addition, one carrier with a homozygous deletion of only exon 8 of the SMN1 gene was detected to have a SMNhyb2 gene, which was also found in the fetus. To our knowledge, these are the first prenatal cases with SMNhyb genes. Follow-up studies demonstrated that the prenatal predictions and the phenotype of the fetuses correlated well in 33 type I pregnancies demonstrating that a careful molecular analysis of the SMN genes is very useful in predicting the phenotype of the fetus in families at risk for SMA.

Prenatal Prediction of Spinal Muscular Atrophy

With the localisation of the gene for the autosomal recessive forms of proximal spinal muscular atrophies (SMA) to the chromosomal region 5q13 and the later detection of homozygous deletions of the SMN gene located in this region, prenatal prediction of SMA has become feasible and is widely applied now. In our experience with 77 prenatal predictions of SMA, follow-up of the 39 liveborn children from these pregnancies never led to a false-negative result. Application of SMN deletion analysis has consequences for prenatal prediction of SMA. When the index patient has a homozygously deleted exon 7 of the SMN gene, prenatal prediction and interpretation of results are straightforward. In families in which no DNA from the index patient is available, prenatal detection of a homozygous SMN deletion may be considered almost proof of SMA in the fetus. Absence of a deletion, however, will not guarantee an unaffected child. A real problem exists if the index patient does not show a homozygous deletion of SMN exon 7. In such cases with non-homozygous SMN deletions, one cannot be certain of 5q linkage and autosomal recessive inheritance until other SMN mutations are detected. This is an argument to abstain from prenatal diagnosis by linkage analysis in these families.

Potential prenatal predictions of Down syndrome: A statistical analysis

To determine the feasibility of combining several screening tests for the prenatal detection of Down syndrome, we evaluated the potential relationship among three proposed predictors. We determined the concentration of chorionic gonadotropin in frozen serum samples from women of known maternal age and weight, fetal biparietal diameter, and femur length, and a-fetoprotein concentration. When corrected for gestational age and maternal weight, the potential predictors were independent, except for a slight correlation (r = 0.10) between maternal serum a-fetoprotein and maternal serum human chorionic gonadotropin. Both maternal serum human chorionic gonadotropin and biparietal diameter/femur length demonstrated an approximately log-normal distribution similar to maternal serum oa-fetoprotein. Therefore it is scientifically sound to use any or all of these variables in combination for the identification of pregnancies at increased risk for Down syndrome.

HLA-A,B,C,DR typing and 17-OHP determination for second trimester prenatal diagnosis of 21-hydroxylase deficient CAH.

In 18 families at risk for the HLA-linked, 21-hydroxylase deficient form of autosomal recessive congenital adrenal hyperplasia (CAH), prenatal diagnosis (PD) was performed using two methods: (1) HLA-A,B,C typing and in the latter 11 cases also DR typing of cultured amniotic fluid cells (AFC) using the standard microcytotoxicity assay, and (2) measurement of second trimester amniotic fluid 17-hydroxyprogesterone (17-OHP) concentration using gel chromatography and radioimmunoassay. The accuracy of the prenatal predictions was confirmed by postnatal HLA typing of umbilical cord blood lymphocytes and by clinical evaluation. In 16/18 families, both HLA typing of AFC and 17-OHP measurements proved informative for PD. The predictions of both methods were concordant in 14/16 families (88 per cent). In ten of these families, a normal fetus was predicted, and in four, an affected fetus; all pregnancies were carried to term and all predictions were confirmed postnatally. In 2/16 cases (12 per cent), however, the predictions were discordant: the prenatal HLA typing indicated an affected fetus, whereas the 17-OHP values predicted a normal fetus. Both pregnancies were continued and two healthy boys were delivered. The discordance proved to be due to a 'missed' HLA antigen in one case and to serologically cross-reactive HLA antigens in the second. Finally, in 2/18 cases, prenatal assessment of fetal genotype had to rely on HLA typing alone as 17-OHP measurement was not performed in one family and in the second family the 17-OHP values obtained were not informative due to inadvertent continuation of hormone therapy to the date of amniocentesis. In both cases, the HLA typing data accurately predicted a normal fetus. In conclusion, a combination of HLA typing of cultured AFC and 17-OHP measurements of amniotic fluid permits accurate prenatal diagnosis of CAH in most cases (88 per cent). In addition, the supplementary use of HLA-DR typing of AFC as presented here for the first time proved helpful in families with HLA-A,B homozygosity due to parental sharing of antigens and can be informative for identifying HLA-B/21-OH recombinant haplotypes.

Genetic origin of mutations predisposing to retinoblastoma.

Retinoblastoma is one of several human tumors to which predisposition can be inherited. Molecular genetic analysis of several nonheritable cases has led to the hypothesis that this tumor develops after the occurrence of specific mitotic events involving human chromosome 13. These events reveal initial predisposing recessive mutations. Evidence is presented that similar chromosomal events occur in tumors from heritable cases. The chromosome 13 found in the tumors was the one carrying the predisposing germline mutation and not the homolog containing the wild-type allele at the Rb-1 locus. These results suggest a new approach for identifying recessive mutant genes that lead to cancer and a conceptual basis for accurate prenatal predictions of cancer predisposition.