[Invasive fetal therapy]. / Invasiv fosterterapi utvecklas allt mer - Från intrauterin blodtransfusion till fetoskopisk kirurgi, shuntinläggning, laserbehandling och radiofrekvensablation.

Invasive fetal therapy  Invasive fetal therapy in Sweden consists of fetoscopic interventions to treat twin-to-twin transfusion syndrome (TTS) or twin anemia polycytemia sequence (TAPS) in monochorionic twin or triplet pregnancies and for selective reduction in monochorionic twins complicated by discordant anomalies or severe growth retardation in one fetus. Alternative methods, such as intrafetal laser ablation and radio frequency ablation, are also used for selective reduction and rarely to treat fetal tumors. Ultrasound guided intrauterine blood transfusions to treat fetal anemia have been performed for a long time with excellent results. Placement of thoraco-amniotic shunts and vesico-amniotic shunts is indicated in a few cases per year in Sweden. Since these rare interventions were centralized to one national center in 2013, the outcome of the fetal interventions has improved consistently.

Mesalazine as a cause of fetal anemia and hydrops fetalis: A case report.

RATIONALE: Mesalazine and its prodrug sulfasalazine are both used for inflammatory bowel disease. Sulfasalazine has been associated with hematological side-effects such as aplastic and hemolytic anemia in patients, but also in fetuses after intrauterine exposure. To our knowledge, we describe the first case of a fetus with severe anemia, and subsequent hydrops, where this drug was found at concentrations in the fetus corresponding to those in the mother and most likely responsible for the fetal condition. PATIENT CONCERNS: A uniparous woman was referred at 31 weeks of gestation due to a hydropic fetus with massive ascites and cardiomegaly. DIAGNOSES: The patient had Crohn's disease and was thus treated with 4 g mesalazine daily. The fetus had severe anemia with an initial hemoglobin level of 51 g/L. INTERVENTIONS: The maternal medication was discontinued and four intrauterine erythrocyte transfusions were given during three weeks. Plasma samples were drawn from mother and fetus during cordocentesis for later analysis of mesalazine. OUTCOMES: A healthy baby was born after 37 full weeks of gestation. Plasma levels of mesalazine were non-conspicuous in neither mother nor fetus. The mesalazine half-life in the fetus (37 h) was half that of the mother (80 h), both considerably longer than previously reported (about 19 h). LESSONS: A causal relationship must be suspected between the fetal anemia and the maternal use of mesalazine. This fetal side-effect should be considered in pregnant women on mesalazine (and its prodrug sulfasalazine).

Fetal CD103+ IL-17-Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid.

Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45+ cells in AF is represented by a subset of fetal CD103+ group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103+ ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103+ ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth.

Pregnancy outcome for fetuses with increased nuchal translucency but normal karyotype.

OBJECTIVE: To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥3.5 mm but normal karyotype in the Stockholm (Sweden) area. METHODS: A retrospective population-based cohort study. From 2006 to 2012, fetal NT was measured in 55123 singleton pregnancies. There were 341 pregnancies with NT thickness ≥3.5 mm; 139 had a normal karyotype, 164 had an abnormal karyotype and 38 were removed from the study. Pregnancy outcome was defined as adverse (termination of pregnancy [TOP], miscarriage [MC], intrauterine fetal death [IUFD], or delivery of a child with structural defects or genetic disorders), or favourable (delivery of a child without any structural defects or genetic disorders diagnosed before discharge). RESULTS: Of the 139 high NT pregnancies with normal karyotype, 110 (79.2%) resulted in live births, one (0.7%) IUFD, 23 (16.5%) TOP and five (3.6%) MC. The risk of an adverse pregnancy outcome increased with increasing NT. Structural fetal defects were found in 28 (19.5%) of pregnancies undergoing second trimester ultrasound screening, of which seven resulted in live births and 21 were terminated. The most common structural defect was cardiac defects. CONCLUSIONS: Adverse pregnancy outcome increased with increasing NT, even with normal karyotype, however, the prognosis is good if the second trimester ultrasound screening is normal.

Survival and neonatal outcome after fetoscopic guided laser occlusion (FLOC) of twin-to-twin transfusion syndrome (TTTS) in Sweden.

AIM: To determine infant survival and neonatal outcome after fetoscopic laser treatment of twin-to-twin transfusion syndrome (TTTS). RESULTS: In 53/71(75%) laser-treated TTTS cases, at least one twin was liveborn and in 42/71(59%) cases at least one twin survived infancy. Fetal survival did not differ between donors [41/71(58%)] and recipients [46/71(65%), P=0.36]. Among liveborns, infant survival was 29/41(71%) in donors and 36/46(78%) in recipients (P=0.12). Infant survival did not correlate to maternal characteristics (age, BMI, smoking or parity), gestational age at treatment or severity of TTTS (Quintero stage). No TTTS infant born before 25 weeks of gestation survived the first week. Among the 87 infant survivors, 26 (30%) had an Apgar score <7 at 5 min, 47 (54%) developed respiratory distress syndrome, 10 (11%) showed signs of severe brain damage, nine (10%) renal failure, eight (9%) bronchopulmonary dysplasia, and five (6%) infants developed retinopathy of prematurity ≥stage 3. There was no significant difference in neonatal morbidity between recipients and donors. CONCLUSIONS: Fetal survival after laser treatment was comparable to that reported by other international centers. There was no significant difference in survival or neonatal morbidity between donors and recipients. Major neonatal morbidity was common, and combined with extremely preterm delivery the prognosis of TTTS is poor.

Establishing a national program for fetoscopic guided laser occlusion for twin-to-twin transfusion syndrome in Sweden.

OBJECTIVE: To describe the establishment of the fetoscopic guided laser occlusion (FLOC) technique for treatment of twin-to-twin transfusion syndrome (TTTS) and the initial results in a Swedish national center. DESIGN: Retrospective, descriptive study. SETTING: Tertiary level university hospital. POPULATION: All referred and treated cases suffering significant TTTS. METHODS: The present study includes all cases of FLOC for TTTS at the Center of Fetal Medicine at Karolinska University Hospital, Stockholm, Sweden from October 2001 until December 2009. Patients were referred from all over Sweden and a few from other Nordic countries. The patients were evaluated with ultrasound examination between gestational ages of 18 and 26 weeks. Data from patients were extracted from our electronic medical record system and, in addition, families were contacted and medical records requested from referring hospitals. MAIN OUTCOME MEASURES: Pregnancies with one or more surviving infants after FLOC treatment categorized according to stage of TTTS. RESULTS: In 75% of pregnancies, one or more infant was born alive. At stage I, both infants survived in one pregnancy and one survived in the second. There was no significant difference between cases at stage II or III, i.e. 73 vs. 78% of pregnancies resulted in one or more surviving infant. At stage IV, 66% of pregnancies ended with one or more surviving infant. CONCLUSIONS: Treatment of TTTS is feasible in a rather small country like Sweden, with comparable results to other centers. There are strong arguments for centralization and further improvement of this kind of highly specialized treatment.

Procedure-related complications and perinatal outcome after intrauterine transfusions in red cell alloimmunization in Stockholm.

INTRODUCTION: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved. MATERIAL AND METHODS: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery. RESULTS: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34. DISCUSSION: Our study confirms previous studies demonstrating favorable results with intravascular transfusions.

Fetal hydronephrosis; prevalence, natural history and postnatal consequences in an unselected population.

BACKGROUND: The aim of this study was to estimate the incidence of fetal hydronephrosis, the antenatal development and the postnatal findings in a low risk population. METHODS: A 2-year retrospective study included almost 9,000 patients, and all cases found to have antenatal hydronephrosis, defined as an AP diameter > or = 5 mm, had a structuralised ante- and postnatal follow-up. RESULTS: Some 85 cases were found in the antenatal period, and 32 of these cases had a pathologic follow-up. Of these, 13 had an increase in severity of dilatation during pregnancy, 10 had stable findings, but no case where the dilatation decreased had any postnatal pathology. Furthermore, half of the cases found in the third trimester (18 of 32) also had an abnormal follow-up. Two cases of Down's syndrome were diagnosed after birth. CONCLUSION: Antenatal hydronephrosis was found in almost 1% (n=85) of the study population. There was an almost 2% risk of Down's syndrome in this group. The majority of cases had an increase in severity and some were stable in the antenatal period, but it was not possible to predict the individual postnatal outcome. In the group where the finding diminished in the antenatal period, no patient had an abnormal postnatal follow-up. Female fetuses with hydronephrosis seem to have an adverse postnatal outcome compared to male fetuses.

Is screening for vesicoureteral reflux mandatory in infants with antenatal renal pelvis dilatation?

AIM: To determine whether postnatal ultrasound (US) can guide the use of voiding cystourethrography (VCUG) in infants with antenatally detected renal pelvis dilatation (ARPD). METHODS: 14,000 pregnant women consecutively underwent routine US examination during the second trimester. US examinations later in pregnancy were performed as follow-up of previous anomalies or on obstetrical indications. One hundred and six fetuses with ARPD > or =5 mm were identified. Two postnatal US examinations were performed in the newborns: on the 5th to 7th day and during the 3rd week of life. The findings were considered normal when renal pelvis dilatation (RPD) was < or =7 mm on both US examinations, and no calyceal or ureteric dilatation or signs of renal dysplasia or other anomalies were present. VCUG was done 6 to 8 wk after birth. RESULTS: In 53 of 103 analysable infants, the postnatal ultrasonographic findings were normal. The VCUG was abnormal in three of these 53 infants, all with vesicoureteral reflux (VUR) grade I. Of 50 infants who had abnormal US examinations, six had VUR, four of which were grade IV and V reflux. CONCLUSION: In infants with ARPD who undergo two postnatal US examinations with RPD < or =7 mm and have no other abnormalities, VCUG is unnecessary.

Is fetal growth impaired after in vitro fertilization?

BACKGROUND: The objective was to study fetal growth parameters in in vitro fertilization (IVF) pregnancies and to investigate the relationship between fetal growth and maternal blood pressure. METHODS: We examined 64 women, pregnant after in vitro fertilization, with repeated ultrasound examinations measuring biparietal diameter, femur length, abdominal diameter and fetal weight at 24, 30, and 36 weeks of gestation. We calculated deviations in percent from expected values in regards to biparietal diameter, femur length, abdominal diameter, and fetal weight. Blood pressure was measured every second week. RESULTS: Biparietal diameter in the study group was significantly smaller at 24 (-3.3%, 95%CI -4.4 to -2.2) and 30 (-1.4%; 95%CI -2.5% to -0.3) weeks. Femur length differed significantly on all three occasions, at 24 (-6.3%; 95%CI -7.7 to -5.1), 30 (-6.6%; 95%CI -8.0 to -5.3), and 36 (-3.9%; 95%CI; -5.0 to -2.8) weeks. Abdominal diameter demonstrated a significant deviation at 24 weeks (-1.6%; 95%CI -2.8 to -0.4). Fetal weight did not reach significant deviations at any gestational age. There was no correlation between deviation of the individual growth parameters or estimated fetal weight and elevated blood pressure. CONCLUSION: The growth pattern of in vitro fertilization pregnancies does not seem to differ from spontaneously conceived pregnancies to any appreciable extent. In the present material, no relationship between fetal growth and maternal blood pressure could be observed. We could not show that an impaired fetal growth predates the development of hypertension.

Oligohydramnios in uncomplicated pregnancies beyond 40 completed weeks. A prospective, randomised, pilot study on maternal and neonatal outcomes.

OBJECTIVES: In low-risk pregnancies, the management of oligohydramnios is not clear. The aim of this study was to compare maternal and neonatal outcomes in cases of isolated oligohydramnios randomised to either induction of labour or expectant management. METHODS: 87 women pregnant beyond 40 completed weeks were asked to participate in the study. Fifty-four accepted and were randomised at 288 days of pregnancy. Twenty-six were randomised to expectant management and 28 to induction of labour. The primary maternal outcome was the mode of delivery and the primary neonatal outcomes were cord blood pH and Apgar score at delivery. RESULTS: No significant differences were found for any important maternal or neonatal outcome. CONCLUSION: Based on these results, the decisions about management could be individualised. Even though the number of patients included was small, these results are well in concordance with others.