Fetal megacystis: a lot more than LUTO.

OBJECTIVE: Fetal megacystis presents a challenge in terms of counseling and management because of its varied etiology and evolution. The aim of this study was to present a comprehensive overview of the underlying etiologies and structural anomalies associated with fetal megacystis. METHODS: This was a retrospective multicenter study of cases referred to the fetal medicine unit of one of the eight academic hospitals in The Netherlands with a diagnosis of fetal megacystis. For each case, data on and measurements of fetal urinary tract and associated structural anomalies were collected. All available postmortem examinations and postnatal investigations were reviewed in order to establish the final diagnosis. In the first trimester, fetal megacystis was defined as longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during an extended ultrasound examination lasting at least 40 min. RESULTS: Of the 541 pregnancies with fetal megacystis, it was isolated (or solely accompanied by other signs of lower urinary tract obstruction (LUTO)) in 360 (67%) cases and associated with other abnormal ultrasound findings in 181 (33%) cases. The most common associated ultrasound anomaly was an increased nuchal translucency thickness (22%), followed by single umbilical artery (10%) and cardiac defect (10%). A final diagnosis was established in 418 cases, including 222 (53%) cases with isolated LUTO and 60 (14%) infants with normal micturition or minor isolated urological anomalies. In the remaining 136 (33%) cases, concomitant developmental or chromosomal abnormality or genetic syndrome was diagnosed. Overall, 40 chromosomal abnormalities were diagnosed, including trisomy 18 (n = 24), trisomy 21 (n = 5), Turner syndrome (n = 5), trisomy 13 (n = 3) and 22q11 deletion (n = 3). Thirty-two cases presented with anorectal malformations involving the anus, rectum and urogenital tract. In cases with confirmed urethral and anal atresia, megacystis occurred early in pregnancy and the bladder appeared severely distended (the LBD (in mm) was equal to or greater than twice the gestational age (in weeks)). Fetal macrosomia was detected in six cases and an overgrowth syndrome was detected in four cases, comprising two infants with Beckwith-Wiedemann syndrome and two with Sotos syndrome. Megacystis-microcolon-intestinal hypoperistalsis syndrome was diagnosed in five (1%) cases and prenatally suspected only in one case. CONCLUSIONS: Although the main cause of fetal megacystis is LUTO, an enlarged fetal bladder can also be present as a concomitant finding of miscellaneous genetic syndromes, developmental disturbances and chromosomal abnormalities. We provide an overview of the structural anomalies and congenital disorders associated with fetal megacystis and propose a practical guide for the differential diagnosis of genetic syndromes and chromosomal and developmental abnormalities in pregnancies presenting with fetal megacystis, focusing on the morphological examination of the fetus. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis of LUTO: improving diagnostic accuracy.

OBJECTIVE: To propose a clinical score for the optimal antenatal diagnosis of fetal lower urinary tract obstruction (LUTO) in the second and third trimesters of pregnancy, as an alternative to the commonly used ultrasound triad of megacystis, keyhole sign and hydronephrosis. METHODS: This was a national retrospective study carried out at the eight tertiary fetal medicine units (FMUs) in The Netherlands. Only cases referred for megacystis from the second trimester onwards and with a clear postnatal diagnosis were included in the study. At referral, data were collected on amniotic fluid volume, renal cortical appearance, bladder volume, hydronephrosis, fetal ascites, ureteral size, keyhole sign, fetal sex and gestational age. Multivariate analysis was performed, starting by including all antenatal variables, and then excluding the weakest predictors using the backward stepwise strategy. RESULTS: Over a 7-year period, 312 fetuses with a diagnosis of megacystis were referred to the eight Dutch tertiary FMUs. A final diagnosis was achieved in 143 cases, including 124 of LUTO and 19 reclassified after birth as non-obstructive megacystis. The optimal bladder volume cut-off for prediction of LUTO was 35 cm3 (area under the curve (AUC) = 0.7, P = 0.03). The clinical score formulated on the basis of the multivariate analysis included fetal sex, degree of bladder distension, ureteral size, oligo- or anhydramnios and gestational age at referral. The combination of these five variables demonstrated good accuracy in discriminating LUTO from non-obstructive megacystis (AUC = 0.84, P < 0.001), compared with the poor performance of the ultrasound triad (AUC = 0.63, P = 0.07). CONCLUSIONS: We propose a clinical score that combines five antenatal variables for the prospective diagnosis of congenital LUTO. This score showed good discriminative capacity in predicting LUTO, and better diagnostic accuracy compared with that of the classic ultrasound triad. Future studies to validate these results should be carried out in order to refine antenatal management of LUTO and prevent inappropriate fetal interventions. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Fetal megacystis: prediction of spontaneous resolution and outcome.

OBJECTIVES: To investigate the natural history of fetal megacystis from diagnosis in utero to postnatal outcome, and to identify prognostic indicators of spontaneous resolution and postnatal outcome after resolution. METHODS: This was a national retrospective cohort study. Fetal megacystis was defined in the first trimester as a longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during the entire extended ultrasound examination. LBD and gestational age (GA) at resolution were investigated with respect to likelihood of resolution and postnatal outcome, respectively. Sensitivity, specificity and area under the receiver-operating characteristics curve (AUC) were calculated. RESULTS: In total, 284 cases of fetal megacystis (93 early megacystis, identified before the 18th week, and 191 late megacystis, identified at or after the 18th week) were available for analysis. Spontaneous resolution occurred before birth in 58 (20%) cases. In cases with early megacystis, LBD was predictive of the likelihood of spontaneous resolution (sensitivity, 80%; specificity, 79%; AUC, 0.84), and, in the whole population, GA at regression was predictive of postnatal outcome, with an optimal cut-off at 23 weeks (sensitivity, 100%; specificity, 82%; AUC, 0.91). In the group with early megacystis, the outcome was invariably good when resolution occurred before the 23rd week of gestation, whereas urological sequelae requiring postnatal surgery were diagnosed in 3/8 (38%) cases with resolution after 23 weeks. In the group with late megacystis, spontaneous resolution was associated with urological complications after birth, ranging from mild postnatal hydronephrosis in infants with resolution before 23 weeks, to more severe urological anomalies requiring postnatal surgery in those with resolution later in pregnancy. This supports the hypothesis that an early resolution of megacystis is often related to a paraphysiological bladder enlargement that resolves early in pregnancy without consequences, while antenatal resolution occurring later in pregnancy (after the 23rd week of gestation) should suggest a pathological condition with urological sequelae. CONCLUSIONS: In fetal megacystis, LBD and GA at regression can be used as predictors of resolution and outcome, respectively. These parameters could help in fine-tuning the prognosis and optimizing the frequency of follow-up scans. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fluid shift from intravascular compartment during fetal red blood cell transfusion.

OBJECTIVES: Intrauterine transfusion imposes a considerable burden on the fetal circulation by increasing volume and pressure, and a fluid shift from the fetal circulation occurs even during the procedure. The aim of this study was to quantify the intraprocedural fluid shift and to investigate the effect of procedural and fetal characteristics on this fluid shift. METHODS: In 95 alloimmunized pregnancies, we calculated fluid shift at the first intrauterine transfusion by determining initial and final blood volumes. We evaluated the association of the fluid shift with the speed and volume of the transfusion, the severity of anemia and the presence of hydrops. RESULTS: Of the included fetuses, 11 were mildly hydropic and four were severely hydropic. A mean fluid shift of 36% of the transfused volume was found. Fluid shift related positively to transfused volume (P < 0.001). The percentage fluid shift of transfused volume was inversely related to the speed of transfusion (mL/kg/min) (P < 0.041) and was not related to the severity of anemia (P = 0.55) or to hydrops (P = 0.66). It was found that younger fetuses had been unintentionally subject to high volumes and speeds of transfusion relative to their size. CONCLUSIONS: Around one-third of the transfused volume is lost from the intravascular compartment during the procedure of intrauterine transfusion. There is a large variation between fetuses, partly explained by the volume and speed of the transfusion. Neither severity of anemia nor hydrops plays a clear-cut role, and thus other factors may explain the variation in fluid shift. The probability that hematocrit will still increase after transfusion, as a result of a continuing fluid shift, should be considered in transfusion policy. Advice is given on gestational age-adjusted speed of transfusion.

Fetal stress hormone changes during intrauterine transfusions.

OBJECTIVE: To document fetal stress hormone and Doppler changes after intrauterine transfusions (IUTs) in either the intrahepatic portion of the umbilical vein (IHV) or the placental cord insertion (PCI). METHOD: Pregnant women scheduled for IUT for fetal anemia (N = 25) were included prospectively. Cortisol, ß-endorphin and noradrenalin concentrations in fetal plasma and middle cerebral artery pulsatility index before and after transfusion were compared. Transfusions were performed through the (IHV), thus puncturing the fetus, or at the PCI. RESULTS: There were no measurable differences between the transfusion sites. CONCLUSION: In anemic fetuses undergoing transfusion, Doppler changes and fetal stress hormone changes were unrelated to the site of needle insertion.

Randomised experimental comparison of 23G versus 22G needle for ultrasound guided invasive fetal procedures.

OBJECTIVES: To experimentally compare the standard 22G spinal needle with a newer 23G needle with specific ultrasound visualisation tip (Cook echotip®, Spencer, Indiana, USA) in the setting of ultrasound-guided invasive intrauterine procedures. MATERIALS AND METHODS: We first determined the size of the defects created in human fetal membranes using light microscopy and adapted area calculating software by both needles in an in vitro model performing 20 paired experiments on 4 term membrane specimens. Secondly, we determined the performance of 3 groups of operators, with different levels of experience in invasive intrauterine procedures during cordocentesis on a simulator model, using either a 22G or 23G needle. For each procedure, we measured the time required to successfully obtaining 2 ml of artificial blood in 24 paired experiments. RESULTS: The mean ±â€ˆSD defect sizes created was 0.66 ±â€ˆ0.12 mm(2) with the 22G needle and 0.59 ±â€ˆ0.13 mm(2) with the 23G needle (P = 0.11). The mean duration of sampling was 144 ±â€ˆ188 sec with the 22G needle versus 140 ±â€ˆ120 sec with the 23G needle (P = 0.99) for all operators pooled but four out of six operators showed shorter sampling times with a 22G needle. CONCLUSION: This experimental study shows that the use of a 23G needle compared to a 22G needle was not associated with significantly different procedure duration or defect size.

Total blood volume is maintained in nonhydropic fetuses with severe hemolytic anemia.

OBJECTIVE: Fetal alloimmune anemia is associated with increased blood flow velocities and cardiomegaly. In severe cases, hydrops can develop. We investigated whether the decrease of red blood cell volume is associated with a reduction or expansion of plasma volume. METHODS: In 86 alloimmunized fetuses that received a first intrauterine transfusion, we calculated fetal total blood volumes (i.e. fetoplacental blood volumes) using a dilutional principle of fetal hemoglobin with adult hemoglobin. The relation between total blood volume and estimated fetal weight, severity of anemia and hydrops was analyzed. RESULTS: Gestational age ranged from 17 to 35 weeks. Mean hemoglobin deficit was 6.8 standard deviations (range 2.1-11.7) below the normal mean. Fetal total blood volume was significantly related to estimated fetal weight (p < 0.001). Mean total blood volume in nonhydropic fetuses was 123 ml/kg (n = 74) and in hydropic fetuses 144 ml/kg (n = 12). There was a significant relation between total blood volume per kg body weight and hydrops (p = 0.035); however, there was no relation with severity of anemia (p = 0.94). CONCLUSION: In the human nonhydropic fetus with severe hemolytic anemia, total blood volume is maintained: the decrease in red blood cell volume is thus compensated by an increase in plasma volume. In hydropic fetuses, however, total blood volume seems to be increased. This is in accordance with the hypothesis that congestive heart failure plays a role in the pathophysiology of hydrops in anemic fetuses.

Fetal brain hemodynamic changes in intrauterine transfusion: influence of needle puncture site.

OBJECTIVES: Previous research has suggested that hemodynamic changes after in utero transfusion may be related to fetal stress. We tested the hypothesis that these hemodynamic changes are more pronounced when the needle is inserted in the fetal abdomen compared with the umbilical cord root. METHODS: Most intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI) or in the intrahepatic portion of the umbilical vein (IHV). We analyzed prospectively collected data of all intrauterine blood transfusions (IUT) for fetal alloimmune anemia (from 2000 to 2003), for which complete data were available on needling site and middle cerebral artery (MCA) Doppler flow velocity measurements before and immediately after the procedure. RESULTS: Data of 57 IUTs were included. In 32 patients, the transfusion was performed through the PCI and in 25 patients through the IHV. Mean pulsatility index (PI) in the PCI group was 2.0 before and 1.7 after IUT (p = 0.011), and in the IHV group 1.9 before and 1.5 after IUT (p = 0.001). In both groups, MCA PI decreased significantly, but there was no difference in decrease between the two groups (p = 0.99). CONCLUSIONS: In anemic fetuses undergoing transfusion, the observed fetal brain hemodynamic changes were independent of the site of needle insertion. The decrease in fetal MCA PI is therefore likely to be caused by the volume expansion.

[Sonomarkers: subtle ultrasound findings in the 20-week ultrasound examination, which have a low association with some chromosomal and non-chromosomal abnormalities in the fetus]. / Sonomarkers: subtiele echoscopische bevindingen op de 20-wekenecho, die zwak correleren met enkele chromosomale en niet-chromosomale afwijkingen bij de foetus.

Currently all pregnant women residing in the Netherlands are offered second trimester ultrasound screening for the detection of fetal congenital structural abnormalities. This routine ultrasound examination takes place at 18 to 22 weeks' gestation. The ultrasound examination may yield soft markers, which are characterized by subtle morphological changes that are often transient and have little or no pathological significance. Soft markers are of interest because of their association with fetal congenital anomalies, in particular aneuploidy. This may create uncertainty for the pregnant woman and the care provider. Information can be found in the literature about the strength of the association of soft markers, when detected as an isolated finding, and the presence of fetal abnormalities. One or more soft markers are detected during routine ultrasound in approximately 5% of pregnant women. 4 markers (echogenic intracardiac focus, echogenic bowel, mild ventriculomegaly and shortened femur) are associated with Down syndrome. Given the low prevalence of Down syndrome in the general population and the relatively low strength of association with the syndrome, the positive predictive value of these markers is very low. The same is true for choroid plexus cysts, which are associated with trisomy 18. Apart from chromosomal abnormalities, some soft markers (echogenic bowel, mild ventriculomegaly and shortened femur) are also associated with non-chromosomal fetal abnormalities. Renal pyelectasis and the 2-vessel (instead of 3-vessel) umbilical cord are associated with non-chromosomal abnormalities only. It is recommended that pregnant women be informed about the nature and implications of these findings before the examination.

Biochemical composition of fluids for amnioinfusion during fetoscopy.

OBJECTIVE: To evaluate which of the commercially available solutions is best suited for amnioinfusion during fetoscopy, based on resemblance with the biochemical properties of amniotic fluid. MATERIALS AND METHODS: Amniotic fluid samples from 10 pregnancies were studied. Specimens were obtained from 5 pathologic pregnancies (of which 3 were complicated by polyhydramnios) and 5 uncomplicated pregnancies. The concentrations of sodium, potassium, chloride, bicarbonate, calcium, glucose, osmolality, pH, total protein content and albumin were determined in each sample. A literature search (PubMed, Embase) was performed to identify commercially available fluids used for amnioinfusion in clinical practice. The composition of these infusion solutions was compared to the amniotic fluid samples mentioned above. RESULTS: We identified two different electrolyte solutions used in clinical practice for amnioinfusion. We identified four additional commercially available solutions that could potentially be used for amnioinfusion. Most of these infusion solutions differ considerably from midtrimester amniotic fluid samples both in electrolyte composition and pH, with the most striking difference in the latter. CONCLUSION: Lactated Ringer's solution approximates amniotic fluid the closest for both electrolyte composition and pH. This infusion solution seems to be the most suitable choice for amnioinfusion during fetoscopy.

Amnioinfusion to facilitate external cephalic version after initial failure.

OBJECTIVE: To evaluate the effectiveness of antepartum transabdominal amnioinfusion to facilitate external cephalic version after initial failure. METHODS: Women with a structurally normal fetus in breech lie at term, with a failed external cephalic version and an amniotic fluid index (AFI) less than 15 cm, were asked to participate in our study. After tocolysis with indomethacin, a transabdominal amnioinfusion was performed with an 18G spinal needle. Lactated Ringers solution was infused until the AFI reached 15 cm, with a maximum of 1 L. External cephalic version was performed directly afterward. RESULTS: Seven women participated in the study. The gestational age of the women was between 36(+4) and 38(+3) weeks, and three women were primiparous. The AFI ranged from 4 cm to 13 cm. A median amount of 1,000 mL Ringers solution (range 700-1,000 mL) was infused per procedure. The repeat external cephalic versions after amnioinfusion were not successful in any of the patients. CONCLUSION: In our experience, amnioinfusion does not facilitate external cephalic version.

Biochemical composition of amniotic fluid in pregnancies complicated with twin-twin transfusion syndrome.

OBJECTIVE: To compare the electrolyte composition of pregnancies complicated with twin-twin transfusion syndrome (TTTS) with that of physiologic pregnancies. MATERIALS AND METHODS: Amniotic fluid samples from 16 pregnancies were studied. Specimens were obtained from recipient sacs in 10 pregnancies undergoing fetoscopy for severe midtrimester TTTS. Additionally, 6 amniotic fluid samples were obtained transcervically from legal second-trimester pregnancy terminations. The concentrations of sodium, potassium, chloride, bicarbonate, calcium, glucose, osmolality, pH, total protein content and albumin were determined in each sample. RESULTS: The mean gestational age at sampling was 20.2 weeks (range 17.2-27.1) in the TTTS group and 18.4 (range 16.0-22.0) in the control group (p = NS). We found significant lower levels of albumin (0.22 +/- 0.04 vs. 0.39 +/- 0.11, p = 0.01) and total protein (0.19 +/- 0.08 vs. 0.51 +/- 0.17, p < 0.001) and higher levels of bicarbonate (16.90 +/- 1.45 vs. 14.50 +/- 2.17, p = 0.02) in amniotic fluid samples taken from recipient sacs of TTTS pregnancies. CONCLUSION: Amniotic fluid from the receptor in severe midtrimester TTTS differs significantly from control amniotic fluid samples in bicarbonate concentration, total protein content and albumin concentration. These findings may help to understand the pathophysiology of TTTS and to optimise therapeutic modalities.

Outcome of children with prenatally diagnosed central nervous system malformations.

OBJECTIVE: To study the outcome of pregnancies with a prenatally diagnosed central nervous system (CNS) malformation. METHODS: Leiden University Medical Centre is a tertiary referral center for fetal ultrasound and invasive prenatal diagnosis. Maternal and neonatal records of prenatally diagnosed CNS malformations were retrospectively reviewed over a 6-year period (1993-1998). Information on current development of surviving children was obtained by contacting the care-giving pediatric neurologist. RESULTS: During the study period 124 fetuses were diagnosed with a CNS malformation. Data on pregnancy and delivery were available for 118 pregnancies. Additional malformations were present in 47% of fetuses (55/118). A total of 46% of pregnancies (54/118) were terminated, and 15% (18/118) ended in spontaneous intrauterine death. A total of 39% of pregnancies (46/118) resulted in live birth, and 29 of the infants were still alive at the age of 3 months. One child was lost to follow-up, one infant died at the age of 4 months, and two children died at the age of 3 years. Psychomotor development of the remaining 25 children was normal for five, slightly disabled for seven, moderately disabled for five and severely disabled for eight. CONCLUSION: Due to the high rate of termination of pregnancy and to the frequent association with other anomalies, the survival rate of pregnancies in which a CNS defect had been diagnosed prenatally was only 25%. More than 50% of surviving children were moderately or severely disabled.