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BACKGROUND: The treatment options for fetal chylothorax include thoracocentesis, thoracoamniotic shunting, and pleurodesis using OK-432. Knowledge on the long-term outcomes after treatment with OK-432 is limited. OBJECTIVE: The aim of this study was to assess the long-term outcomes of children treated in utero with OK-432. METHODS: We performed follow-up on pregnancies and children treated in utero with OK-432 between 2003 and 2009 at Copenhagen University Hospital Rigshospitalet for pleural effusions at gestational age (GA) 16+0-21+6 weeks. Anamnestic information, physical examination, pulmonary function test, neuropediatric examination, and intelligence testing using the Wechsler Intelligence Scale were used for evaluation. RESULTS: Fourteen cases, all chylothorax, were treated with OK-432. None had preterm premature rupture of membranes (PPROM), and the median GA at delivery was 38+5 (24+4-41+5) weeks. Twelve children were eligible for follow-up. The median age at follow-up was 11.4 (7.8-13.8) years. Pulmonary function was normal in all children and the mean full-scale IQ did not differ from that of normal children. Four children had a diagnosed medical condition, attention deficit disorder, or genetic syndrome. The remaining children had normal follow-up. CONCLUSION: Children treated with OK-432 have comparable survival rates and long-term neurodevelopmental outcomes to those treated with thoracoamniotic shunts. There seems to be a lower risk of procedure-related PPROM.

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INTRODUCTION: We sought to assess the incidence of severe neurodevelopmental impairment (NDI) in monochorionic twins treated for twin-twin transfusion syndrome (TTTS) and compare it to the incidence in uncomplicated monochorionic twins. MATERIAL AND METHODS: We included TTTS pregnancies treated by fetoscopic selective laser coagulation (FSLC) or umbilical cord occlusion (UCO) in 2004-2015. Primary outcome was severe NDI defined as cerebral palsy, bilateral blindness or bilateral deafness (ICD-10 diagnoses), and severe cognitive and/or motor delay (assessed by the Ages and Stages Questionnaires [ASQ]). RESULTS: A total of 124 children after TTTS and 98 controls were followed up at 25 months of age (SD 11.4). Severe NDI was found in 8.9% of the TTTS children (10.5% [9/86] after FSLC; 5.3% [2/38] after UCO) compared to 3.1% in the control group (p = 0.10). The odds ratio for severe NDI was 1.8 in cases versus controls (p = 0.37). The total ASQ score was significantly lower in the TTTS group than in controls (p = 0.03) after FSLC (p = 0.03) and after UCO (p = 0.14). DISCUSSION: Children after TTTS appear to have a higher risk of severe NDI and score significantly lower on the ASQ compared to monochorionic twins from uncomplicated pregnancies.

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INTRODUCTION: Ultrasound-guided bipolar umbilical cord occlusion (UCO) is used in complicated monochorionic multiple pregnancies in Denmark. The aim of this study was to assess a learning curve in the procedure of UCO. MATERIALS AND METHODS: One hundred and two monochorionic pregnancies treated with UCO at Rigshospitalet, Denmark between 2004 and 2015 were included. The procedures were divided into period 1 (2004-2009) and period 2 (2010-2015) to determine a learning curve. Primary outcome measure was survival rate. Secondary outcome measures were time from operation to fetal loss and gestational age (GA) at delivery. RESULTS: Period 1 included 59 cases. The median GA at procedure was 19.9 weeks (range 16.7-25.9) and at delivery 34.7 weeks (range 24.3-40.3). Period 2 included 43 cases. The median GA at procedure was 20.7 weeks (range 16.7-27.6) and at delivery 37.3 weeks (range 29.1-40.3). Survival rate increased from 78% (period 1) to 95% (period 2) (p = 0.02). GA at delivery increased as well. Fetal death within 48 h after surgery decreased from 4 (period 1) to 0 (period 2). DISCUSSION: Our results suggest a learning curve in the procedure of UCO with improved outcome on all measures.

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OBJECTIVE: To investigate normal human placental growth longitudinally throughout the second and third trimesters using MRI. METHODS: Twenty normal, first-time singleton pregnancies were scanned 7 times between the 14th and 38th week of gestation, at 4-week intervals, using MRI. Placental volumes were measured in both sagittal and transversal slices. All placentas were weighed after delivery to make a comparative study. RESULTS: Sixteen of the 20 women had increasing placental volumes from the 14th to 38th week of gestation. The 6th and 7th scan showed that 4 women had placentas of the same size. The mean placental volume increases linearly from the 14th till the 38th week of gestation, with a constant mean growth rate of 29.97 ml/week. The median placental volume extrapolated to delivery was to 856 ml (range 602-1,050 ml). The median weight of the exsanguinated placenta after delivery was 640 g (range 500-787 g). All pregnancies were carried to term, resulting in the delivery of healthy infants with good correlation between placental size and birth weight (R = 0.56, p = 0.009). CONCLUSION: Placental growth was measured systematically in a longitudinal study through the second and third trimesters using MRI. MRI provides a safe and feasible method to measure placental growth. The mean placental growth was linear throughout the second and third trimesters.

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In-utero treatment of fetal aortic stenosis (AS) may prevent hypoplastic left heart syndrome. A girl was diagnosed prenatally with severe AS and was referred to the Women's and Children's Hospital in Linz, Austria, where she underwent an intrauterine valvuloplasty of the aortic valve. Postnatally, the girl was given prostaglandin and operated a.m. Ross-Konno. An echocardiography at the age of four months showed a neoaorta without stenosis and insufficiency and a normal systolic function of the left ventricle. This treatment must be carefully considered when dealing with fetuses with AS.

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OBJECTIVES: The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark. METHODS: Fetuses and infants diagnosed with CHD in the period 01.01.2008-31.12.2010 were assessed regarding prenatal detection rate and accuracy, as well as correlation with nuchal translucency (NT) thickness. RESULTS: Out of 86 121 infants, 831 were born with CHD (0.96%). The prenatal detection rate of 'all CHD' was 21.3%, of 'Major CHD' 47.4%. Full agreement between prenatal and postnatal/autopsy findings was found in 96% of prenatally detected diagnoses. An NT thickness >95(th) percentile was found in 15.0% fetuses with 'Major CHD'. Of 'Major CHDs' detected prenatally, 77% were picked up at the time of the malformation scan at weeks 18-21. CONCLUSIONS: Nearly half of 'Major CHDs' were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. Increased NT thickness as a screening tool for CHD performed moderately but is an important high risk group for specialist examination. A minority of the prenatally detected CHDs was identified because of extra scans performed in high risk pregnancies. © 2014 John Wiley & Sons, Ltd.

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Twin anaemia-polycythaemia sequence (TAPS) is a rare form of feto-fetal transfusion between monochorionic twins. It occurs spontaneously or after laser surgery for twin-twin transfusion syndrome. TAPS is characterized by a large inter-twin haemoglobin difference and can be detected both ante- and postnatally. This is a case report of TAPS, detected antenatally by a routine scanning of monochorionic twins in gestational week 29.

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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.

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OBJECTIVE: To present normative data on prenatal mandibular morphology and growth. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

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OBJECTIVE: To evaluate OK-432, a preparation of Streptococcus pyogenes, in the treatment of early fetal chylothorax. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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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.

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By renal ultrasound examination, urological anomalies may be demonstrated in 1-2% of fetuses and in about 0.5% of newborns. Boys have about twice the frequency of girls. Surgical treatment is indicated in about one fourth of these urological anomalies. If all pregnant women in Denmark were to have fetal ultrasound examination of the kidneys and the urinary tract, about 70 children would be born each year with a prenatally diagnosed urological anomaly for which surgical procedure is or will be indicated. This paper provides Danish guidelines for prenatal diagnosis, follow-up and intervention in cases of urological anomalies and guidelines for post-natal diagnosis, follow-up and treatment of these anomalies, especially hydronephrosis.

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BACKGROUND: The accuracy of ultrasound in the diagnosis of congenital malformations has been the subject of many studies. Most of these are hospital-based studies over a limited period of years presenting high detection rates and also relatively high incidence of major malformations. We present here a large population-based study over a long period of years. METHODS: The prenatal diagnoses are compared with the diagnoses of the newborns and aborted fetuses, including autopsy results. The detection rate of some common structural malformations is studied. RESULTS: The overall detection rate of malformations in our study was 28.4%. We noticed an improved detection rate of heart defects and cleft lip during the study period. The prevalence of malformations in the population was 2.6%. The false positive diagnoses were few, 54 cases, and mainly of a mild nature. CONCLUSIONS: Ultrasound screening of fetal malformations in our population has a low false positive rate and even though the overall sensitivity is low, 28.4%, the detection rate for many common structural malformations is relatively good.

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BACKGROUND: Different screening procedures are becoming an important part of health care. Information about screening and its consequences can be difficult to both impart and understand. This study examined women's theoretical acceptance of a new screening procedure, before its introduction. METHODS: A group of women (n = 823), who had made an informed choice about the form of foetal diagnosis they wished for, were also asked, in a questionnaire, about their opinion on the acceptability of serum screening for Down syndrome. The main purpose of the this was to ascertain their feelings when making a choice. RESULTS: Replies were received from 80.4%. The answers indicated that serum screening would be acceptable to 86% of the women who had chosen a second trimester ultrasound examination. Of the women who had chosen amniocentesis, 51% would consider the test acceptable as a first alternative. CONCLUSIONS: The ease with which the women were able to make their choice of prenatal diagnosis had bearing on their degree of acceptance of serum screening for Down syndrome.

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Ultrasound examination during pregnancy is now an essential part of modern obstetrical management. In many European countries women are offered 1-3 ultrasound examinations during their pregnancy. In Denmark a similar offer is available but only to a very limited extent. Ultrasound examinations are performed on medical reasons. Modern equipment, trained sonographers, and the increasing use of ultrasound scannings imply that a considerable number of fetal malformations are diagnosed. A very comprehensive literature is available describing the sensitivity of diagnosing a fetal malformation at different times during the pregnancy. In a number of studies the sensitivity within different organ systems has been given as well. Intrauterine treatment is afield with great development, in which the more invasive operative techniques are replaced by laparoscopic procedures.

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