Postmortem Assessment of Isolated Congenital Heart Defects Remains Essential Following Termination of Pregnancy.

OBJECTIVES: To investigate the correlation between prenatal ultrasound (US) and autopsy findings in pregnancies terminated due to isolated congenital heart defects (CHDs), including CHDs associated with heterotaxy syndrome. MATERIALS AND METHODS: The material consists of 67 fetuses with prenatally detected isolated CHDs or CHDs associated with heterotaxy syndrome at a tertiary center in Norway between 1985 and 2014. The main CHDs were categorized into subdiagnoses of CHDs in accordance with ICD-10. The US and autopsy findings were categorized according to degree of concordance. RESULTS: Gestational age at termination was 12 + 0-22 + 6 weeks. Hypoplastic left heart syndrome was the most common main diagnosis among the 67 fetuses (32.8%). There was full agreement between US and autopsy findings in 97.4% (222/228) of all subdiagnoses. The discrepant findings in three fetuses had no influence on the decision to terminate the pregnancy. CONCLUSIONS: The correlation was high between prenatal US and postmortem findings in fetuses with isolated CHDs. Meticulous assessment of cardiac anatomy is particularly necessary when the decision to terminate relies on isolated CHDs. The trend of earlier termination challenges verification of diagnoses at autopsy. Consequently, the fetus should be examined at a tertiary center with fetal medicine specialists, pediatric cardiologists and perinatal pathologists.

Prenatal examination and postmortem findings in fetuses with gastroschisis and omphalocele.

OBJECTIVE: This study compares prenatal ultrasound examination and autopsy findings in fetuses and infants with gastroschisis and omphalocele. METHOD: Criteria for inclusion in the study were an autopsy of fetuses/infants with gastroschisis or omphalocele performed between January 1985 and December 2009 and a prenatal ultrasound examination performed in a tertiary referral center. The results were organized into five categories depending on the degree of agreement. RESULTS: Of 11 cases with gastroschisis, only one was not detected at the prenatal ultrasound examination, and the rest had full agreement. Of 70 fetuses with omphalocele, two were not diagnosed at the prenatal ultrasound examination. Four (15%) had major autopsy findings not detected prenatally. The main diagnosis was correct in 64/70 (91%) and improved from 85% to 95% during this study period. The number of cases with major and minor autopsy findings not detected by ultrasound examination was reduced from 48% to 21%. Full agreement occurred in 46/70 (66%). CONCLUSION: This study shows that the correlation between prenatal ultrasound findings and postmortem examination is good and has improved over time. Comparing full agreement during the first 10 years with the last 15 years showed an improvement (p = 0.05) for fetuses with omphalocele.

A prospective study of screening for hypertensive disorders of pregnancy at 11-13 weeks in a Scandinavian population.

OBJECTIVE: To investigate the prediction of preeclampsia and gestational hypertension using maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at gestational weeks 11-13 in a Scandinavian population with a medium to high prior risk for developing hypertensive disorders of pregnancy. DESIGN: Prospective screening study. SETTING: National Center for Fetal Medicine, Trondheim, Norway. POPULATION: 579 women who were nulliparous or had a previous history of preeclampsia or gestational hypertension. METHODS: Women were examined between 11(+0) and 13(+6) weeks, with interviews for maternal characteristics and measurements of MAP, UtAPI, PAPP-A and PlGF. The tests were evaluated separately and in combined models with receiver operating characteristics (ROC) curves. MAIN OUTCOME MEASURES: Prediction of preeclampsia, severe preeclampsia and gestational hypertension. RESULTS: The best model for severe preeclampsia (MAP+UtAPI+PlGF+PAPP-A) achieved an area under the ROC curve of 0.866 [95% confidence interval (95% CI) 0.756-0.976]. The best models for preeclampsia (MAP+UtAPI+age) achieved 0.738 (0.634-0.841), gestational hypertension (MAP) 0.820 (0.727-0.913) and hypertensive disorders in pregnancy overall (MAP+PlGF+age) 0.783 (0.709-0.856). Using the best model we could identify 61.5% (95% CI 31.6-86.1) of severe preeclampsia, 38.5% (95% CI 20.2-59.4) of preeclampsia and 42.9% (95% CI 21.8-66) of gestational hypertension at a fixed 10% false-positive rate. CONCLUSIONS: Maternal characteristics, MAP, UtAPI, PAPP-A and PlGF showed limited value as screening tests. Further research on biochemical and biophysical tests and algorithms combining these parameters is needed before first trimester screening for hypertensive disorders of pregnancy is included in antenatal care in Scandinavia.

A randomized controlled trial of third-trimester routine ultrasound in a non-selected population.

OBJECTIVE: To compare detection rates of small-for-gestational-age fetuses, large-for-gestational-age fetuses, congenital anomalies and adverse perinatal outcomes in pregnancies randomized to third-trimester routine ultrasound or ultrasound on clinical indication. DESIGN: Randomized controlled trial. SETTING: National Center for Fetal Medicine in Norway between 1989 and 1992. POPULATION: A total of 6780 pregnancies from a non-selected population. METHODS: Two routine ultrasound examinations at 18 and 33 weeks were compared with routine ultrasound at 18 weeks and ultrasound on clinical indication. Suspected small-for-gestational-age fetuses were followed with serial scans and cardiotocography. Doppler ultrasound was not used. MAIN OUTCOME MEASURES: Detection rates of small-for-gestational-age and large-for-gestational-age fetuses, congenital anomalies and adverse perinatal outcomes. RESULTS: Third trimester routine ultrasound improved detection rates of small-for-gestational-age fetuses from 46 to 80%, but overall perinatal morbidity and mortality remained unchanged. Detection of large-for-gestational-age fetuses increased from 36 to 91%. There was a significant increase of induction of labor and elective cesarean sections due to suspected small-for-gestational-age and a significant decrease of induction of labor and elective cesarean sections due to suspected large-for-gestational-age in the study group; there were no other differences regarding intervention. The detection rate of congenital anomalies was 56%, with no significant difference between the groups. CONCLUSIONS: Routine use of third-trimester routine ultrasound increased detection rates of small-for-gestational-age and large-for-gestational-age fetuses. This did not alter perinatal outcomes. Third-trimester ultrasound screening should not be rejected before a policy of adding Doppler surveillance to the high-risk group identified has been investigated further.

Ichthyosis prematurity syndrome: clinical evaluation of 17 families with a rare disorder of lipid metabolism.

BACKGROUND: Ichthyosis prematurity syndrome (IPS) is classified as a syndromic congenital ichthyosis based on the presence of skin changes at birth, ultrastructural abnormalities in the epidermis, and extracutaneous manifestations. Recently, mutations in the fatty acid transporter protein 4 gene have been identified in patients with IPS. OBJECTIVE: We sought to perform a detailed clinical evaluation of patients with IPS identified in Norway. METHODS: Clinical examination and follow-up of all patients (n = 23) and light and electron microscopic examination of skin biopsy specimens were performed. RESULTS: IPS was characterized prenatally by ultrasound findings of polyhydramnios, separation of membranes, echogenic amniotic fluid, and clear chorionic fluid. All patients were born prematurely with sometimes life-threatening neonatal asphyxia; this was likely caused by aspiration of corneocyte-containing amniotic fluid as postmortem examination of lung tissue in two patients revealed keratin debris filling the bronchial tree and alveoli. The skin appeared erythrodermic, swollen, and covered by a greasy, thick vernix caseosa-like "scale" at birth, and evolved rapidly to a mild chronic ichthyosis. Many patients subsequently had chronic, severe pruritus. Histopathologic and ultrastructural examination of skin biopsy specimens showed hyperkeratosis, acanthosis, dermal inflammation, and characteristic aggregates of curved lamellar structures in the upper epidermis. Peripheral blood eosinophilia was invariably present and most patients had increased serum immunoglobulin E levels. Over 70% of the patients had a history of respiratory allergy and/or food allergy. LIMITATIONS: The study included only 23 patients because of the rarity of the disease. CONCLUSION: IPS is characterized by defined genetic mutations, typical ultrastructural skin abnormalities, and distinct prenatal and postnatal clinical features.

Thanatophoric dysplasia: autopsy findings over a 25-year period.

The aim of our study was to retrospectively assess morphological findings in thanatophoric dysplasia, particularly, in how many cases were cerebral manifestations with temporal lobe dysplasia identified. We also wanted to register and analyze the proportions between lung, brain, and body weight. Criteria for inclusion were an autopsy performed during the period ranging from 1985 to 2009 with a diagnosis of thanatophoric dysplasia. During a 25-year period 25 cases of thanatophoric dysplasia were registered. Temporal lobe dysplasia was recognized in 52% of the cases, and after 1998 temporal lobe dysplasia was described in all cases. In 19 cases the brain/body weight ratio was increased, and in all cases the lung/body weight ratio was below the corresponding ratio calculated according to standard measurements. In all but one case the ratio of brain to lung weight was increased. This study focuses on morphological findings, stressing the importance of temporal lobe dysplasia in confirming a diagnosis of thanatophoric dysplasia. Lung/body, brain/body, and brain/lung weight ratios confirm macrocephaly and lung hypoplasia, which are constant findings in cases involving thanatophoric dysplasia. Femur and brain morphology inclusive histology remains the ultimate tool for confirmation of this lethal condition, although it has to be seen in a context inclusive of radiological examination.

Impact of thyrotropin receptor antibody levels on fetal development in two successive pregnancies in a woman with Graves' disease.

BACKGROUND: Treatment with radioiodine for Graves' disease regularly increases the level of antithyroid antibodies, and transplacental passage of stimulating thyrotropin receptor antibodies (TRAb) may cause fetal hyperthyroidism. CASE PRESENTATION: A 21-year-old woman with Graves' disease received radioiodine treatment to avoid use of antithyroid drugs in pregnancy. She became pregnant 4 months later and was euthyroid during pregnancy. In gestational week (GW) 33, she was admitted with an increased fetal heart rate of 176-180 beats/min. Fetal echocardiography indicated cardiac decompensation. The neonate had severe hyperthyroidism (free thyroxine >100 pmol/l, nv 12.0-22.0), cardiac insufficiency, insufficient weight gain, goiter and considerably accelerated skeletal age. In the mother and neonate, TRAb was >40 IU/l (nv <1.0), indicating transplacental passage of stimulating antibodies. After delivery, TRAb remained >40 IU/l in the woman, and 18 months later she underwent total thyroidectomy with subsequent decline in TRAb. In her next pregnancy, TRAb fluctuated between 38 and 17 IU/l, and repeated fetal ultrasound showed no goiter or sign of hyperthyroidism. In cord blood, TRAb was 10.9 IU/l, and the neonate had normal thyroid hormone levels. CONCLUSION: This case report illustrates the impact of maternal TRAb level for neonatal outcome in two successive pregnancies.

Sonographic development of the normal foetal thorax and abdomen across gestation.

In the following review, the development of the thorax and abdomen, as described by embryologists and anatomists in modern embryological text books, is compared with sonoanatomic descriptions from 2D and 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. For the second and third trimester, the description of the sonographic development of the thorax and abdomen is divided into thoracic skeleton, diaphragm, lungs, oesophagus, stomach, liver, spleen, bowel and gall bladder. The review is restricted to the normal development, appearance and biometric assessment of these organs; and discusses topical literature.