Correlation between prenatal ultrasound and postmortem findings in 1029 fetuses following termination of pregnancy.

OBJECTIVE: A prenatal ultrasound examination and a postmortem examination provide the basis for correct diagnosis in fetuses terminated due to congenital anomalies. The aim of this study was to correlate fetal anomalies detected by ultrasound examination with those identified at autopsy following termination of pregnancy (TOP) over a 30-year period, and to evaluate the correlation between findings at different gestational ages and assess these trends over time. METHODS: The study group consisted of 1029 TOPs performed over a 30-year period, from 1985 to 2014. The gestational age ranged between 11 and 33 weeks. Prenatal ultrasound examinations were performed at the National Center for Fetal Medicine, St Olavs Hospital, Trondheim, Norway. Autopsies were performed at the Department of Pathology and Medical Genetics at the same hospital or a collaborating hospital. RESULTS: There was full agreement between ultrasound and autopsy findings in 88.1% (907/1029) of TOPs, and the main diagnosis was correct in 97.9% (1007/1029). When comparing the 15-year period of 2000-2014 with that of 1985-1999, the difference in the rates of full agreement and agreement in the main diagnosis was statistically significant. In 1.3% (13/1029) of cases, ultrasound findings were not confirmed at autopsy. There were no false-positive diagnoses leading to TOP. Throughout the 30-year period, there was an increase in early TOPs, whereas late TOPs declined. CONCLUSIONS: Our study demonstrates that there is a clear correlation between ultrasound and autopsy findings, which is continuously improving. Despite this high correlation, there is reason to continue the practice of validation to ensure the safety of the diagnostic process leading to TOP. The trend towards an earlier termination emphasizes the necessity of such a practice. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Risk assessment for preeclampsia in nulliparous women at 11-13 weeks gestational age: prospective evaluation of two algorithms.

OBJECTIVE: To evaluate two algorithms for prediction of preeclampsia in a population of nulliparous women in Norway. DESIGN: Prospective screening study. SETTING: National Centre for Fetal Medicine in Trondheim, Norway. POPULATION: Five hundred and forty-one nulliparous women. METHODS: The women were examined between 11(+0) and 13(+6) weeks with interviews for maternal characteristics and measurements of mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A and placental growth factor. The First Trimester Screening Program version 2.8 by The Fetal Medicine Foundation (FMF) was compared with the Preeclampsia Predictor TM version 1 revision 2 by Perkin Elmer (PREDICTOR). MAIN OUTCOME MEASURES: Prediction of preeclampsia requiring delivery before 37 weeks, before 42 weeks and late preeclampsia (delivery after 34 weeks). RESULTS: The performance of the two algorithms was similar, but quite poor, for prediction of preeclampsia requiring delivery before 42 weeks with an area under the curve of 0.77 (0.67-0.87) and sensitivity 40% (95% CI 19.1-63.9) at a fixed 10% false positive rate for FMF and 0.74 (0.63-0.84) and sensitivity 30% (95% CI 11.9-54.3) at a fixed 10% false positive rate for PREDICTOR. The FMF algorithm for preeclampsia requiring delivery <37 weeks had an area under the curve of 0.94 (0.86-1.0) and sensitivity of 80% (95% CI 28.4-99.5) at a 10% fixed false positive rate. CONCLUSIONS: Fetal Medicine Foundation and PREDICTOR algorithms had similar and only modest performance in predicting preeclampsia. The results indicate that the FMF algorithm is suitable for prediction of preterm preeclampsia.

Abnormal gyration of the temporal lobe and megalencephaly are typical features of thanatophoric dysplasia and can be visualized prenatally by ultrasound.

Autopsies of fetuses with thanatophoric dysplasia (TD) have shown abnormal gyration of the temporal lobes. In addition, the head is relatively large compared with the abdomen. We evaluated by ultrasound six consecutive cases of TD at 19 + 0 to 19 + 6 gestational weeks based on last menstrual period. We observed abnormal and deep transverse sulci in the temporal lobes in all cases; these features were confirmed at autopsy. We performed biometric assessment, including biparietal diameter (BPD) and mean abdominal diameter (MAD). For each MAD value in the TD fetuses, we computed mean and SD of the corresponding BPD values from a population-based registry in the relevant age range, and used them to calculate Z-scores for each BPD/MAD ratio. In the general population, the average BPD/MAD ratio was 1.05. In the TD fetuses, the mean BPD was 51.5 (range, 49-54) mm, the MAD was 45 (range, 41-47) mm and the BPD/MAD ratio was 1.15 (range, 1.09-1.20). The average Z-score of the ratios for TD fetuses was 2.44 (range, 1.05-3.39). The ratios for the TD fetuses were significantly higher than were the population ratios (P = 0.016). At autopsy, the mean brain-to-body weight ratio was 20.6% (range, 15.4-24.1%), which was greater than the corresponding mean ratio of 14.9% in normal fetuses. We conclude that abnormal and deep transverse gyration of the temporal lobes can be visualized by ultrasound in mid-second-trimester fetuses with TD. Due to megalencephaly, fetuses with TD have significantly different body proportions, with a larger BPD compared with normal fetuses.

Comparison between prenatal ultrasound and postmortem findings in fetuses and infants with developmental anomalies.

OBJECTIVE: To determine if postmortem examinations of fetuses and infants change the diagnosis obtained at prenatal ultrasound and affect counseling of future pregnancies, and if there has been a change over recent years in the accuracy of prenatal ultrasound diagnosis. METHODS: This was a retrospective review of 455 autopsies of fetuses and infants with developmental anomalies performed at Trondheim University Hospital between 1995 and 2004 and with a prenatal ultrasound examination performed at a tertiary referral center. The routine ultrasound examinations were performed by specially trained midwives and obstetricians, referral scans by fetal medicine experts and autopsies by consultant pathologists with experience in perinatal pathology. The results of this study were also compared with those of a previous similar study performed between 1985 and 1995, with fetuses and infants coming from the same population and diagnosed at the same center. RESULTS: Of all cases analyzed during the study period, there was complete agreement between prenatal ultrasound and postmortem findings in 84% (384/455), i.e. prenatal ultrasound diagnoses were supplemented by postmortem examinations in 16% (71/455). Autopsy findings in four of these cases influenced further counseling. There was agreement regarding the main diagnosis in 98% (445/455) of cases. In the previous 10-year period, there was complete agreement in 75% and the main diagnosis was correct in 90% of cases. These differences between the two time periods were statistically significant (P = 0.0004 and P < 0.0001, respectively). The most frequent defects involved the central nervous system, heart and urinary tract. For these defects, detection rates for the main diagnoses were significantly better in 1995-2004 compared with in the previous 10-year period (P = 0.0125, P = 0.0111 and P = 0.0241, respectively). CONCLUSION: The accuracy of prenatal sonographic detection of developmental anomalies has increased in recent years. However, postmortem examination is still necessary to verify or improve the prenatal diagnosis and may influence future counseling.

Prenatal sonographic assessment and perinatal course of ichthyosis prematurity syndrome.

All cases of ichthyosis prematurity syndrome (IPS), registered at the National Center for Fetal Medicine in Trondheim, Norway between 1987 and 2010 were identified and the findings analyzed. Five fetuses with IPS were identified between 1988 and 2000. All five developed polyhydramnios between 28 and 31 weeks. The fetal stomach appeared to be empty in four cases, and was not described in one case. The fetal skin was described as 'uneven' at ultrasound examination in two cases. Separation of chorionic and amniotic membranes with a peculiar appearance of echo-free fluid in the chorionic cavity and echogenic sediment in the amniotic cavity were observed between 28 + 5 and 32 + 3 weeks in all cases. All fetuses were delivered prematurely between 30 and 34 weeks. All neonates had difficulties in breathing, two developed aspiration pneumonia, and one had bilateral pneumothorax after intubation and died at 6 months because of pulmonary and cardiac sequelae. Prenatal sonographic signs of IPS are separation of the membranes, echogenic amniotic fluid and echo-free chorionic fluid occurring between 28 and 32 weeks' gestation. Delivery occurs at 30-34 weeks and, as there is a high risk of asphyxia, an experienced neonatal intensive care unit team should be present at delivery.

Sonoembryology and early prenatal diagnosis of neural anomalies.

In the following review, the early development of the central nervous system (CNS), as described by embryologists and anatomists in modern embryological textbooks, is compared with sonoanatomic descriptions from two-dimensional (2D) and three-dimensional (3D) ultrasound studies, week by week in the first trimester. The anatomic descriptions are limited to details that are of interest for the understanding of ultrasound examinations. Further, the detection of main CNS anomalies including spina bifida during the first trimester are presented and discussed. Empty or enlarged brain cavities, or abnormal contours of the head and spine are important diagnostic markers for the detection of CNS anomalies in the very early pregnancy.

Prenatal detection of trisomy 21 by second-trimester ultrasound examination and maternal age in a non-selected population of 49 314 births in Norway.

OBJECTIVES: To assess the contribution of the second-trimester routine ultrasound examination and maternal age (>or= 38 years) to the prenatal detection of trisomy 21 in a large non-selected population in which no other screening methods were carried out. METHODS: A prospective follow-up study was carried out in a non-selected Norwegian population from 1987 to 2004, including a total of 49 314 births. Data from all cases of trisomy 21, detected prenatally by karyotyping following amniocentesis performed for abnormal ultrasound findings or because of maternal age >or= 38 years, or postnatally after delivery, were registered. The study period was divided into three 6-year periods. RESULTS: Eighty-eight cases of trisomy 21 were registered. The prenatal detection rate was 43% (38/88). No significant change in the detection rate was observed over the 18 years. Fourteen percent (12/88) of cases were detected as a result of advanced maternal age and 30% (26/88) by prenatal ultrasound examination. Of all women with a trisomy 21 fetus, 72% (63/88) were under 38 years of age. The percentage of women >or= 38 years opting for karyotyping during the three time periods decreased significantly from 51% to 50% and 36%, respectively. The termination rate of trisomy 21 fetuses was 84%, with no significant change over time. CONCLUSIONS: Our data can be considered as a reference standard for population screening for trisomy 21 based solely on maternal age and second-trimester ultrasound imaging. The prenatal detection rate of trisomy 21 cases was poor and remained unchanged throughout the 18-year study period. If improvement in detection rates is desired, additional programs are necessary.

Prenatal ultrasound detection of facial clefts: a prospective study of 49,314 deliveries in a non-selected population in Norway.

OBJECTIVES: To evaluate prenatal detection of facial clefts by ultrasound examination in a large non-selected population, and to study trends in detection rates over 18 years, as well as the prevalence of isolated cases and those with associated anomalies. METHODS: This prospective follow-up study from January 1987 to December 2004 was divided into two 9-year periods. The study included all registered cases of prenatally or postnatally diagnosed facial clefts in a non-selected population in Norway. RESULTS: A total of 101 fetuses or newborns with facial clefts in a population of 49 314 deliveries were registered. The distribution of clefts was: 25 (25%) cleft lip, 52 (51%) cleft lip and palate, and 24 (24%) cleft palate (CP). No CP was detected prenatally. Cleft lip with or without cleft palate (CL(P)) was detected prenatally in 35/77 (45%) cases, with a significant increase in the detection rate from 34% to 58% between the two 9-year periods (P = 0.03). Over the whole study period CL(P) was detected at a median of 19 + 2 gestational weeks, with no change over time; altogether 24/35 (69%) cases were detected at the routine second-trimester ultrasound examination. Thirty-three of 77 (43%) cases of CL(P) and 14/24 (58%) cases of CP had associated anomalies; 12/101 (12%) had chromosomal aberrations. In 18/101 (18%) the clefts were part of a syndrome or sequence. CONCLUSIONS: The detection rate for CL(P) improved significantly over time. Detection of CL(P) is important because nearly half the cases have associated anomalies.

Prenatal ultrasound detection of talipes equinovarus in a non-selected population of 49 314 deliveries in Norway.

OBJECTIVES: To evaluate prenatal ultrasound detection of talipes equinovarus (TEV) in a large non-selected population and to study trends in detection rates over time, as well as the prevalence and outcome of isolated TEV and TEV with associated anomalies. METHODS: All cases of pre- or postnatally diagnosed TEV between 1987 and 2004 within a non-selected population of 49 314 deliveries were investigated. The study period was divided into three 6-year periods to shed light on changes in detection rates and other aspects of the anomaly over time. RESULTS: A total of 113 cases of TEV were registered during the 18-year period, of which 49% had isolated TEV and 51% had associated anomalies. During the three 6-year periods, there was a significant improvement (P = 0.006) in the overall detection of TEV from 43% to 67% and 77%, respectively. The detection rate for isolated TEV increased over time. Isolated bilateral TEV cases were detected more than twice as often as isolated unilateral TEV. The three largest groups of associated anomalies were syndromes/sequences (26%), chromosome aberrations (26%), and musculoskeletal disorders (24%). Pregnancies were terminated in 23% of the cases, all with severe additional anomalies. Treatment of TEV included surgery in 86% of the cases. CONCLUSION: The overall detection rate of TEV improved significantly over time. Prenatal detection was higher when TEV was bilateral and when other associated anomalies were present. Parents should be informed that, in suspected isolated TEV, associated anomalies might remain undetected prenatally.

Esophageal obstruction-prenatal detection rate and outcome.

OBJECTIVE: Prenatal diagnosis of esophageal obstruction is believed to improve the outcome for the affected newborn. However, the prenatal detection rate is only 10-40%, the diagnosis is usually not made before the third trimester and the false-positive rate has been high. This study investigated the prenatal detection rate and time of prenatal diagnosis at our center and its influence on outcome. In addition, incidence, detection rate and accuracy of the diagnosis in a large non-selected population were determined. METHODS: All cases diagnosed pre- or postnatally with esophageal obstruction and examined prenatally by ultrasound at the National Center for Fetal Medicine in Norway during 1987-2004 were evaluated. RESULTS: Of 48 cases with esophageal obstruction, 21 (44%) were diagnosed prenatally (median, 32 + 0 weeks). All 21 had a small or empty stomach, 20/21 (95%) had polyhydramnios and 9/21 (43%) had a visible esophageal pouch. Associated anomalies were present in 38/48 cases (79%). The karyotype was abnormal in 11/48 cases (23%). Ten (21%) pregnancies with lethal fetal conditions were terminated. Two fetuses died in utero. Ten infants with associated anomalies died within 3 months after birth. The 26/48 (54%) survivors included 16/21 cases with a prenatal diagnosis of esophageal obstruction and 9/10 cases with isolated esophageal obstruction. CONCLUSIONS: The clinical signs of polyhydramnios were the most important factors for prenatal detection of esophageal obstruction. Consequently, the time of diagnosis was late and the detection rate was low (44%). An increased awareness of the possibility of esophageal obstruction, leading to targeted examinations whenever the suspicion is raised during pregnancy, might improve the prenatal detection rate and thereby provide a possibility to improve the outcome. Of the cases with isolated esophageal obstruction, 90% survived, irrespective of prenatal diagnosis.

Imperforate anus: A relatively common anomaly rarely diagnosed prenatally.

OBJECTIVE: Despite the relatively common occurrence of imperforate anus, prenatal diagnosis is rarely reported. In this study, we investigated the presence and diagnosis of imperforate anus along with strategies for improving prenatal diagnosis of the condition. PATIENTS AND METHODS: Fetuses and infants with imperforate anus who had been examined prenatally by ultrasound at the National Center for Fetal Medicine (NCFM) from 1987 to 2004, were evaluated. RESULTS: Of 69 cases with imperforate anus, only 11 (15.9%) were diagnosed prenatally, at a median gestation of 18 + 4 (range, 15 + 6 to 35 + 6) weeks. In all 11, dilatations of the rectum or lower part of the bowel were seen. Additional anomalies, most of them diagnosed prenatally, were present in 59/69 (85.5%) of the cases. The most frequent additional anomalies were urogenital (53.6%). The karyotype was abnormal in nine cases (13.0%). A retrospective evaluation of available videotapes of 22 cases of imperforate anus that were not diagnosed prenatally revealed that it was possible to suspect the diagnosis in 11/22 (50%) cases. Sixteen infants were born with imperforate anus without prenatal diagnosis of any abnormality. In total, 31/69 (44.9%) cases were terminated, two (2.9%) died in utero and 12 (17.4%) died postnatally. Twenty-four (34.8%) infants survived, including all 10 with isolated imperforate anus and seven of eight cases with only one additional anomaly. CONCLUSIONS: The prenatal detection rate of imperforate anus was only 15.9%. Imperforate anus is often associated with other anomalies; in this study, 85.5% had additional anomalies. Prenatal diagnosis makes prenatal counseling possible and facilitates optimized postnatal care. We believe that the prenatal detection rate of imperforate anus could be improved. Examiners should intensify their search for typical findings of imperforate anus especially when other anomalies that frequently accompany this condition are present.

Three-dimensional ultrasound volume calculations of human embryos and young fetuses: a study on the volumetry of compound structures and its reproducibility.

OBJECTIVE: To evaluate volumetry with three-dimensional (3D) ultrasonography in the assessment of the size of human embryos and fetuses. METHODS: Forty-four healthy embryos/fetuses with crown-rump length (CRL) ranging from 9 mm to 58 mm were studied using a 7.5-MHz annular array transvaginal 3D probe. EchoPAC 3D software was used to calculate the volumes of the head, body and limbs in the same data set by two observers working independently of each other. Regression analysis was used to assess the relationship between estimated volumes and CRL. RESULTS: The embryonic and fetal volume estimates of both observers ranged from a mean of 93 mm3 at 10 mm CRL to a mean of 11 169 mm3 at 55 mm CRL. The volume of the limbs as a proportion of the mean whole-body volume increased from 4.7% at a CRL of 15 mm to 9.3% at a CRL of 55 mm. Limits of agreement between the observers were calculated to be -0.12 +/- 9.2%. CONCLUSION: It is possible to reconstruct complex small anatomic structures and calculate the volumes of human embryos and fetuses in vivo by using dedicated 3D ultrasound equipment. The reproducibility of whole-body volume estimates seems to be high. The limbs represent a significant proportion of the size of the embryonic/fetal body.

Prenatal detection of heart defects in a non-selected population of 30,149 fetuses--detection rates and outcome.

OBJECTIVES: To evaluate the detection rate of congenital heart defects (CHD) in a non-selected population and to follow outcome after diagnosis. METHODS: All 30,149 fetuses/newborns that were scheduled to deliver at our hospital between February 1991 and December 2001 were registered prospectively. Of these, 29,460 (98%) fetuses had a prenatal ultrasound scan at our center. The routine fetal examination at approximately 18 weeks' gestation included the four-chamber view and the great arteries of the fetal heart. The follow-up period was 2-13 years. RESULTS: Of 97 major CHDs, 55 (57%) were detected prenatally, 16% (9/55) prior to, 66% (36/55) at and 18% (10/55) after the routine scan. Forty-four percent (19/43) of the isolated CHDs, 67% (36/54) of those with associated malformations and 48% (11/23) of the isolated ductal-dependent CHDs were detected. Thirty-eight percent (37/97) had an abnormal karyotype. Of the 55 major CHDs detected, 44% (24) of the pregnancies with lethal/serious fetal malformations were terminated, 15% (8) died in utero, 42% (23) were born alive and 27% (15) were still alive after 2 years. Of the 42 CHDs detected postnatally, 2% (1) were terminated for other reasons, 98% (41) were born alive and 81% (34) were still alive after 2 years. CONCLUSIONS: Prenatal detection of CHD is still a challenge, with a 57% detection rate only. Isolated defects are detected less frequently. The overall outcome suggests that the most severe defects are detected with the present screening setting; only 27% of the babies with major CHDs detected were still alive after 2 years. Data from long-term follow-up will be of importance for the counseling process.

Characteristics and outcome of 90 cases of fetal omphalocele.

OBJECTIVE: The aim of this study was to describe the outcome of a case series of fetuses with omphalocele. METHODS: Ninety fetuses with omphalocele at the National Center for Fetal Medicine (NCFM) between January 1985 and January 2004 were followed from the time of prenatal diagnosis. Follow-up times ranged from 6 months to 17 years. Omphaloceles were subdivided into epigastric, central and hypogastric types based on their location on the abdominal wall. RESULTS: There were 58 central and 32 epigastric omphaloceles. Abnormal karyotype was found in 40/58 (69%) of the central and in 4/32 (12.5%) of the epigastric omphaloceles. Trisomy 18 was the most frequent abnormality associated with omphalocele. Among the fetuses with normal karyotype, 89% of the central and 71% of the epigastric cases had other anomalies. 38 (66%) of the fetuses with central omphalocele were terminated and 12 (21%) died during pregnancy or after delivery. 11 (34%) of the fetuses with epigastric omphalocele were terminated and eight (25%) died during pregnancy or after delivery. Of the 90 cases followed from the time of diagnosis there were 21 (23%) survivals. Of eight survivals with central omphalocele, only two were considered healthy while six had other anomalies and/or substantially impaired development. Of 13 survivals with epigastric omphalocele, six were considered healthy and seven had other anomalies and/or substantial impairment. CONCLUSIONS: Fetal central and epigastric omphaloceles may be different entities: central omphaloceles are more strongly associated with abnormal karyotype (69%) than are epigastric omphaloceles (12.5%). The outcome of fetuses with omphalocele is poor irrespective of the type of omphalocele, with only eight of the 90 (9%) being alive and healthy at present. The results emphasize the importance of identifying both those fetuses with a potentially good prognosis and favorable outcome and those which are likely to have a fatal outcome.