[Show abstract][Hide abstract] ABSTRACT: Objective. Monochorionic twin pregnancies are associated with increased risk of severe complications. Umbilical cord occlusion (UCO) and fetoscopic selective laser coagulation (FSLC) are used as invasive treatment. The study aim was to document treatment indications and pregnancy outcome where UCO and FSLC were used for treating fetal discrepancies and twin-to-twin transfusion syndrome (TTTS). Design. Cohort study of all consecutively treated monochorionic twin pregnancies 2004-2010. Setting. Tertiary care center. Population. One hundred and twenty pregnancies treated by FSLC (55) or UCO (65). Umbilical cord occlusion was undertaken in 49 TTTS cases, in four cases with fetal abnormality and TTTS and in 12 cases because of fetal anomaly only. Main outcome measures. Overall survival per fetus, survival per pregnancy of at least one fetus and further survival according to the Quintero stages. Infant survival until at least one week after birth. Results. Of the pregnancies studied, 84% had TTTS, 13% had a fetal malformation and 3% had both. Of TTTS cases, 69% were Quintero stage 3 and 4. In the UCO group with TTTS, 87% were in stage 3 and 4. Survival in the UCO group was 82%. In the laser group, the survival of at least one fetus was 85%. Overall survival per fetus was 60%. Conclusions. By far the most common indication for invasive treatment was TTTS in Quintero stage 3. Outcome by means of survival after FSLC and UCO were similar to what has been reported elsewhere. Cord occlusion was an acceptable treatment alternative to fetoscopic selective laser coagulation in severe TTTS cases.
[Show abstract][Hide abstract] ABSTRACT: To present normative data on prenatal mandibular morphology and growth.
Fifty-four normal fetuses (Danish Caucasian) were included in the study (gestational age: 11-26 weeks). Fetuses were scanned using a GE Voluson 730 Expert 3D scanner. Scans were visualized and analyzed using GE 4DVIEW software. Mandibular dimensions [base length (B), ramus height (H), and total length (L)] and the mandibular angle (phi) were measured, and the mandibular index was calculated. Method error was estimated by duplicate measurements. Growth was calculated by regressing measured variables on age.
Mandibular measurements were found to be reliable [precision: 0.5-1.2 mm (1SD)]. Mean mandibular variable values at week 11: B = 5.2 +/- 2.5 mm; H = 2.7 +/- 1.3 mm; L = 7.7 +/- 3.2 mm; phi = 149 +/- 6.0 degrees; and at week 26: B = 22.6 +/- 2.5 mm; H = 12.3 +/- 1.3 mm; L = 33.1 +/- 3.2 mm; phi = 135 +/- 6.0 degrees. A linear model described growth (B(g)/H(g)/L(g)/phi(g)) giving B(g) = 1.2; H(g) = 0.64; L = 1.7 mm/week; phi(g) = - 0.9 degrees/week.
Normative 3D data values for the human mandible in 11- to 26-week-old fetuses were presented. All measured mandibular parameters could be described using a linear increasing model from 11 to 26 weeks. All linear dimensions increased in size, while the mandibular angle decreased steadily during the observation period.
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether high-resolution comparative genomic hybridization (HR-CGH) and subtelomeric and syndrome-specific multiplex ligation-dependent probe amplification (MLPA) would detect minor chromosomal aberrations in fetuses with increased nuchal translucency thickness (NT) and normal karyotype on conventional karyotyping.
Chorionic villus samples from 100 fetuses with NT > or = 99(th) percentile and normal G-banding analysis and MLPA for detection of aneuploidies for chromosomes 13, 18, 21, X and Y were included. Examinations were supplemented by HR-CGH and MLPA for syndromes and subtelomeric regions. Pregnancy outcome was followed up.
Among 80 liveborn children who were followed up, three (4%) had syndromes involving mental retardation, including a case of Sotos syndrome caused by a de novo mutation. 15% of fetuses were lost during pregnancy due to abnormalities and termination. The rate of adverse outcome overall was 18%. HR-CGH and MLPA did not detect any chromosomal aberrations associated with the syndromes.
The rate of adverse outcome was similar to levels recorded in the literature. Using CGH and MLPA did not increase the detection rate of genetic disease, which supports the current approach of repeated ultrasound examinations in these high-risk pregnancies.
Ultrasound in Obstetrics and Gynecology 12/2009; 34(6):618-22. DOI:10.1002/uog.7468 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 34-year-old Caucasian woman with cleidocranial dysplasia (CCD) and a known family history of CCD was referred for an ultrasound examination in the first trimester of her second pregnancy. Molecular genetic analysis of the RUNX2 gene was non-informative. A routine 2D ultrasound examination carried out at a local hospital at gestational age 12 weeks showed no signs of CCD. A 3D ultrasound examination in week 15+4 showed a fetus with typical CCD features including large fontanelles, lack of nasal bones, clavicles without the typical S-form, as well as severe delay in calvarial ossification, especially in the midline. Serial 3D ultrasound examinations during pregnancy confirmed the diagnosis, and over time the manifestations became even more distinct. The diagnosis was clinically confirmed at birth. This case suggests that the typical craniofacial CCD traits, including wide unmineralized areas in the calvarial midline and missing nasal bones, are easily recognizable using 3D ultrasound as early as in week 15.
[Show abstract][Hide abstract] ABSTRACT: According to animal studies, the testicular Leydig cell hormone insulin-like factor 3 (Insl3) exerts a fundamental role in abdominal testis translocation, which occurs in the beginning of the second trimester in humans. Despite this, human prenatal INSL3 production has been poorly investigated.
Amniotic fluid from 91 pregnant women undergoing amniocentesis was analyzed for INSL3 and testosterone (T) levels. Data were related to gestational age (15-25 wk) at amniocentesis and to sex (45 males and 48 females).
INSL3 was present in amniotic fluid from all but one of the investigated male fetuses (range: <0.02-0.36 ng/ml; mean +/- sd: 0.12 +/- 0.07), whereas the hormone was undetectable in the female fetuses. T was significantly higher in male (range: 0.54-1.71 nmol/liter; mean +/- sd: 1.04 +/- 0.30) as compared with in female amniotic fluid (range: 0.19-0.50 nmol/liter; mean +/- sd: 0.34 +/- 0.06) (P < 0.001). In males there was no correlation between INSL3 and T. A statistically borderline negative association was found between INSL3 and gestational age (P = 0.07), whereas the corresponding association was not significant for T (P = 0.12). In contrast, T in females correlated positively with gestational age (P = 0.02).
INSL3 is clearly present in human male amniotic fluid in the second trimester, where abdominal testis translocation takes place. In contrast, the hormone is undetectable in female amniotic fluid. The prenatal presence of INSL3 supports the hypothesis that this hormone is essential for testicular descent in humans.
[Show abstract][Hide abstract] ABSTRACT: Early prenatal diagnosis of cleidocranial dysplasia (CCD) in a case in which molecular genetic analysis of the RUNX2 gene was non-informative.
2D ultrasound examination.
At week 13+6, a 2D ultrasound examination revealed a fetus with severely delayed ossification of the vertebral spine. The clavicles were barely seen and the calvarial bones were significantly less ossified than expected for gestational age. The fetus had otherwise normal anatomy and biometry. Serial ultrasound examinations during pregnancy confirmed the diagnosis, but the manifestations became less distinct. The diagnosis was confirmed clinically at birth.
This case illustrates an early easily recognizable pattern of severely delayed ossification of the vertebral spine, which is probably a characteristic of CCD.
[Show abstract][Hide abstract] ABSTRACT: To evaluate OK-432, a preparation of Streptococcus pyogenes, in the treatment of early fetal chylothorax.
A prospective study of all fetuses (n=7) with persistent early chylothorax (gestational ages 16-21 weeks) referred to the tertiary center of fetal medicine in Denmark in 2003-2005. Fetuses were injected with 0.2-1.0 mg of OK-432 into the pleural cavity. The treatment was repeated if there were persistent or increasing pleural effusions after 1-3 weeks. The main outcome measures included remission of pleural effusions and fetal and infant morbidity and mortality.
Total remission of pleural effusions was obtained in all fetuses after one or two intrapleural injections of OK-432. No adverse effects of the treatment were observed. No fetus developed hydrops, and all experienced an uncomplicated third trimester. All children were born healthy without pleural effusions, lung hypoplasia, or hydrops.
Persistent early chylothorax is a condition with a high mortality rate and no established treatment option. Use of OK-432 is a promising therapy for selected fetuses with persistent chylothorax early in the second trimester.
Obstetrics and Gynecology 06/2007; 109(5):1088-92. DOI:10.1097/01.AOG.0000259907.91973.69 · 5.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation.
Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex.
Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS.
Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies.
Ultrasound in Obstetrics and Gynecology 05/2007; 29(5):517-26. DOI:10.1002/uog.3918 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal outcome. This is a case report describing a 34-year-old woman presenting with acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory drugs (NSAID) and therapeutic amniocenteses was initiated immediately and resulted in a decreased amniotic fluid production from 30 weeks' gestation. Even after the discontinuation of NSAID treatment, the amniotic fluid production normalized, and the woman delivered a healthy boy at 39 weeks 2 days' gestation. Amniotic prolactin was measured at three occasions using an enzyme-linked immunosorbent assay. As in normal pregnancies, amniotic prolactin levels decreased by 80% from highest to lowest value in this case of resolving acute recurrent polyhydramnios.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception.
In a prospective multicenter observational study women with a twin pregnancy had an ultrasound scan before 14 + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the perinatal, neonatal and infant mortality rates and the frequency of very preterm labor were estimated for the different types of twin.
Among the 495 pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%) by assisted reproduction (AR). Outcome data for 945 liveborn babies were obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9% (7/64) among naturally conceived MC compared to 3.0% (5/165) for naturally conceived DC twins (P < 0.05). For twins conceived by AR the corresponding figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm birth-before 28 weeks' gestation-was 4.2 for MC twins compared to DC twins. The relative risk of fetal loss or death among DC twins was 20% of the risk for MC twins.
The risk of fetal loss, very preterm delivery and neonatal/infant death is significantly higher among twins with MC compared to DC placentation. Twins conceived by AR have a much lower risk of MC placentation. The risk of losing one or both twins seems higher among naturally conceived twins compared to twins conceived by AR, despite the fact that the maternal age was higher among the mothers of the AR twins.
Ultrasound in Obstetrics and Gynecology 10/2006; 28(5):644-52. DOI:10.1002/uog.3820 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate transvaginal sonographic assessment of cervical length at 23 weeks as a screening test for spontaneous preterm delivery in order to define a cut-off value that could be used to select twin pregnancies at low risk of spontaneous preterm delivery.
In a prospective multicenter study of 383 twin pregnancies included before 14 + 6 weeks a cervical scan with measurement of the cervical length was performed at 23 weeks' gestation. The results were blinded for the clinicians if the cervical length was > or = 15 mm. The rates of spontaneous delivery at different cut-off levels of cervical length were determined.
Eighty-nine percent of the twins had dichorionic placentation and 58% were conceived after assisted reproduction. The rate of spontaneous preterm delivery was 2.3% (1.5% for dichorionic (DC) and 9.1% for (MC) monochorionic twins) before 28 weeks and 18.5% (17.1% for DC and 29.5% for MC twins) before 35 weeks. The screen-positive rate was 5% for a cervical length < or = 20, 7-8% at < or = 25, 16-17% at < or = 30 and 34-48% at < or = 35 mm depending on chorionicity. The false-negative rate (1 - negative predictive value) ranged from 1.2% at 28 weeks to 18.6% at 35 weeks for all twins. Receiver-operating characteristics curves showed that the sensitivity increased with declining gestational age with cut-off levels of highest accuracy at 21 mm for 28 weeks and 29 mm for 33 weeks.
Cervical length measurement at 23 weeks of gestation is a good screening test for predicting twins at low risk of preterm and very preterm delivery, especially in DC twins. The present results suggest that a cut-off of 25 mm should be recommended.
Ultrasound in Obstetrics and Gynecology 08/2005; 26(2):138-44. DOI:10.1002/uog.1938 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim. To study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Down's syndrome (DS) in low risk populations at tertiary centers, and to compare the ultrasound screening detection rates with those that were obtainable by biochemical serum screening (double test: alpha-fetoprotein/human chorion gonadotrophin/age test). Study design. Prospective multicenter study with a three year inclusion period: 1/1/1989-31/12/1991. Subjects. 27,844 low-risk women at 18-34 years of age who had a second trimester ultrasound screening examination. Of these, 10,264 also had a serum test. Methods. An ultrasound malformation scan and a serum test were carried out at 17-19 weeks of gestation. Risk calculations regarding DS were based on alpha-fetoprotein, human chorion gonadotrophin and maternal age; performed retrospectively for the first two years. Results. In total 73 cases were identified in the study population: NTD (n=34), AWD (n=7) and DS (n=32). The detection rates, (% with 95% confidence interval) for ultrasound screening were: NTD: 79.4 (62.1-91.3); AWD: 85.7 (42.1-99.6); DS: 6.3 (0.8-20.8). In the subgroup of women who had both tests, the detection rates for ultrasound screening vs double test were: NTD: 62.5 (24.5-91.5) vs 75.0 (34.9-96.8); AWD: 66.7 (9.4-99.2) vs 100 (29.2-100.0); DS: 7.7 (0.2-36.0) vs 46.2 (19.2-74.9). The false positive rates (%) for ultrasound screening vs double test were: NTD: 0.01/3.3; AWD: 0.01/3.3; DS: 0.1/4.0. Conclusion. Second trimester ultrasound screening in a low risk population gave a low detection rate for fetal DS (6.3%) and an acceptable detection rate for NTD (79.4%) and AWD (85.7%). In the subgroup of women who had both tests, serum screening performed better than ultrasound as applied in the present study, especially regarding DS.
[Show abstract][Hide abstract] ABSTRACT: We describe a case of a 25-week fetus with severe bilateral pleural effusion, marked ascites, skin edema, an anterior thick (hydropic) placenta and polyhydramnios in which the most probable diagnosis was congenital chylothorax. Treatment with a pleuroamniotic shunt was planned, however the location of the fetus just below the anterior placenta made the placement of the shunt too dangerous. We therefore decided to use intrapleural injection of OK-432. From week 29, the lungs looked normal, the pleural effusion had resolved and the thoracic circumference was within normal limits. The severe ascites persisted throughout the pregnancy and a total volume of 3680 mL was removed on several occasions. A Cesarean section was performed at 38 weeks and a normal male was delivered. Continuous positive airway pressure was needed on the first 4 days but after a week the situation was stable. On day 8, an X-ray showed normally developed lungs. OK-432 appears to have prevented pulmonary hypoplasia in our patient.
Ultrasound in Obstetrics and Gynecology 02/2003; 21(1):66-9. DOI:10.1002/uog.23 · 3.85 Impact Factor