Connie Jørgensen

New treatment of early fetal chylothorax.

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. LEVEL OF EVIDENCE: II

MULTISCAN ‐ A Scandinavian multicenter second trimester obstetric ultrasound and serum screening study

AIMnTo study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Downs 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).nnnSTUDY DESIGNnProspective multicenter study with a three year inclusion period: 1/1/1989-31/12/1991.nnnSUBJECTSn27,844 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.nnnMETHODSnAn 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.nnnRESULTSnIn 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.nnnCONCLUSIONnSecond 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.

Ultrasound screening for fetal anomalies in Southern Sweden: a population-based study

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.

Insulin-Like Factor 3 Levels in Second-Trimester Amniotic Fluid

BACKGROUNDnAccording 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.nnnMETHODSnAmniotic 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).nnnRESULTSnINSL3 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).nnnCONCLUSIONSnINSL3 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.

Book Review and Announcements

This excellent guide armed at assisting the pediatric house officer and neonatology fellow in day-to-day practice issues in neonatal intensive care is a second edition of the first one written in 1979. Each section was carefully updated and new and expanded sections have been added to take into account the changes in neonatal practice. New chapters include percutaneous central venous catheters, congenital epidermolysis bullosa, neonatal neoplasms, major vessel thrombosis, fetomaternal hemorrhage, fetal and neonatal arrhythmias, the effects of maternal drugs on the fetus/newborn and lactation, high-frequency ventilation, neonatal pain, the neonatal airway, neonatal anesthesia, and inhalational nitric oxide therapy. The role of the neonatal nurse practitioner is also addressed. The chapters on neonatal surgery and respiratory care have been expanded, as has the section on neonatal infection, which includes guidelines for intrapartum and neonatal management of group B streptococcal disease. Serge Uzan, Paris

Long-Term Neurodevelopmental Outcome of Monochorionic Twins after Laser Therapy or Umbilical Cord Occlusion for Twin-Twin Transfusion Syndrome

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.

OK-432 Treatment of Early Fetal Chylothorax: Pregnancy Outcome and Long-Term Follow-Up of 14 Cases

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.

Ultrasound-Guided Bipolar Umbilical Cord Occlusion in Complicated Monochorionic Pregnancies: Is There a Learning Curve

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.