Optimal timing of fetal reduction from twins to singleton: earlier the better or later the better?

OBJECTIVES: To determine the rate of pregnancy complications and adverse obstetric and neonatal outcomes of twin pregnancies that were reduced to singleton at an early compared with a later gestational age. METHODS: This was a historical cohort study of dichorionic diamniotic twin pregnancies that underwent fetal reduction to singletons in a single tertiary referral center between January 2005 and February 2017. The study population was divided into two groups according to gestational age at fetal reduction: those performed at 11-14 weeks' gestation, mainly at the patient's request or as a result of a complicated medical or obstetric history; and selective reductions performed at 15-23 weeks for structural or genetic anomalies. The main outcome measures compared between pregnancies that underwent early reduction and those that underwent late reduction included rates of pregnancy complications, pregnancy loss, preterm delivery and adverse neonatal outcome. RESULTS: In total, 248 dichorionic diamniotic twin pregnancies were included, of which 172 underwent early reduction and 76 underwent late reduction. Although gestational age at delivery was not significantly different between the late- and early-reduction groups (38 weeks, (interquartile range (IQR), 36-40 weeks) vs 39 weeks (IQR, 38-40 weeks); P = 0.2), the rates of preterm delivery < 37 weeks (28.0% vs 14.0%; P = 0.01), < 34 weeks (12.0% vs 1.8%; P = 0.002) and < 32 weeks (8.0% vs 1.8%; P = 0.026) were significantly higher in pregnancies that underwent late reduction. Regression analysis revealed that late reduction of twins was an independent risk factor for preterm delivery, after adjustment for maternal age, parity, body mass index and the location of the reduced sac. Rates of early complications linked to the reduction procedure itself, such as infection, vaginal bleeding and leakage of fluids, were comparable between the groups (7.0% for early reduction vs 9.2% for late reduction; P = 0.53). There was no significant difference in the rate of pregnancy loss before 24 weeks (0.6% for early reduction vs 1.3% for late reduction; P = 0.52), and no cases of intrauterine fetal death at or after 24 weeks were documented. There was no significant difference in the prevalence of gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm prelabor rupture of membranes or small-for-gestational age. The rates of respiratory distress syndrome (6.7% vs 0%; P = 0.002), need for mechanical ventilation (6.7% vs 0.6%; P = 0.01) and composite neonatal morbidity (defined as one or more of respiratory distress syndrome, sepsis, necrotizing enterocolitis, intraventricular hemorrhage, need for respiratory support or neonatal death) (10.7% vs 2.9%; P = 0.025) were higher in the late- than in the early-reduction group. Other neonatal outcomes were comparable between the groups. CONCLUSIONS: Compared with late first-trimester reduction of twins, second-trimester reduction is associated with an increased rate of prematurity and adverse neonatal outcome, without increasing the rate of procedure-related complications. Technological advances in sonographic diagnosis and more frequent use of chorionic villus sampling have enabled earlier detection of fetal anatomic and chromosomal abnormalities. Therefore, efforts should be made to complete early fetal assessment to allow reduction during the first trimester. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Perinatal outcome of monochorionic diamniotic twin pregnancy complicated by selective intrauterine growth restriction according to umbilical artery Doppler flow pattern: single-center study using strict fetal surveillance protocol.

OBJECTIVE: To determine the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective intrauterine growth restriction (sIUGR), which were classified according to the umbilical artery (UA) Doppler flow pattern of the IUGR twin. METHODS: This was a retrospective cohort study of all MCDA twin pregnancies diagnosed with sIUGR and managed at a single tertiary referral center between 2012 and 2018. Cases were classified according to the UA Doppler flow pattern of the IUGR twin as Type I (positive end-diastolic flow), Type II (persistently absent/reversed end-diastolic flow) or Type III (intermittently absent/reversed end-diastolic flow). Patients with Type-II or -III sIUGR were hospitalized at 26-28 weeks of gestation for increased fetal surveillance. Perinatal and immediate and long-term neurodevelopmental outcomes were stratified according to the UA Doppler flow pattern at the final examination. Intact survival rate was defined as the number of infants surviving without neurological impairment, divided by the total number of fetuses. Composite adverse outcome, defined as any mortality, presence of severe brain lesions on postnatal transcranial ultrasound or severe neurological morbidity, was also assessed. RESULTS: Of 88 MCDA twin pregnancies with sIUGR included in the study, 28 underwent selective termination by cord occlusion using radiofrequency ablation, resulting in a perinatal survival rate of 89.3% and a median gestational age (GA) at delivery of 33.8 (interquartile range (IQR), 28.8-38.2) weeks for the large cotwin. Expectant management was employed in 60 cases. In 26 (43.3%) cases in the expectant-management group, the classification according to the UA Doppler flow pattern changed during gestation, resulting in 26 (43.3%) cases of Type-I, 22 (36.7%) cases of Type-II and 12 (20.0%) cases of Type-III sIUGR at the final examination. The perinatal survival rate of both twins with sIUGR Types I, II and III at the final examination was 100%, 81.8% and 75.0%, respectively (P = 0.04). Two cases of double fetal death and one case of single fetal death occurred 1-4 weeks after the Doppler pattern had changed from Type I or Type II to Type III. The median GA at delivery was 34.8 (IQR, 33.1-35.7) weeks in Type I, 30.3 (IQR, 28.6-32.1) weeks in Type II and 32.0 (IQR, 31.3-32.6) weeks in Type III (P < 0.01). The total intact survival rate was 100% for Type I, 77.3% for Type II and 75.0% for Type III (P < 0.001). Multivariate analysis demonstrated that early GA at diagnosis (odds ratio (OR), 0.83 (95% CI, 0.69-0.99); P = 0.04) and the presence of Type II or III vs Type I at the last examination (OR, 13.16 (95% CI, 1.53-113.32); P = 0.02) were associated with preterm birth < 32 weeks' gestation. Early GA at diagnosis was also associated with the composite adverse outcome (OR, 0.60 (95% CI, 0.36-0.99); P = 0.04). CONCLUSIONS: The classification system of MCDA pregnancy complicated by sIUGR, according to the UA Doppler flow pattern of the IUGR twin at final examination, is associated with perinatal outcome. Importantly, the UA Doppler flow pattern can change during gestation, which has an impact on the risk of fetal death. Nevertheless, under strict fetal surveillance, the perinatal outcome of these pregnancies is favorable. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Revisiting short- and long-term outcome after fetal first-trimester primary cytomegalovirus infection in relation to prenatal imaging findings.

OBJECTIVE: To determine the short- and long-term outcome of pregnancies with proven first-trimester fetal cytomegalovirus (CMV) infection in a large prospective cohort. METHODS: This was a prospective cohort study of pregnancies with documented primary maternal CMV infection in the first trimester and evidence of fetal infection, referred for further evaluation between January 2011 and January 2018. Maternal serological diagnosis of primary CMV infection was documented by seroconversion. Vertical CMV transmission was identified by amniocentesis with polymerase chain reaction (PCR) for the CMV genome. After birth, fetal infection was re-tested by PCR in neonatal urine or saliva samples. All patients underwent serial prenatal ultrasound scans and fetal magnetic resonance imaging (MRI) at 32-33 weeks' gestation. All neonates underwent ocular fundus examination, an ultrasound brain scan and hearing evaluation, and were followed periodically for a median of 2 years (range, 6 months to 10 years). Follow-up information was obtained from hospital charts and by telephone interviews with parents. The CMV-associated outcomes assessed were sensorineural hearing loss (SNHL), neurodevelopmental abnormality, composite clinical outcome (including SNHL and neurodevelopmental abnormality) and composite outcome (additionally including termination of pregnancy (TOP)). The association between prenatal ultrasound or MRI findings and abnormal outcome was assessed. RESULTS: Primary CMV infection in the first trimester occurred in 123 patients. The rate of an abnormal ultrasound finding was 30.9%, and the rate of an abnormal MRI finding was 30.1% overall and 14.1% in the subgroup of patients with normal ultrasound. Of the 85 patients with normal ultrasound, 12 had an abnormal MRI finding, of whom five (5.9%) had true anatomical findings. Fifteen patients decided to terminate the pregnancy owing to abnormal prenatal findings on either ultrasound or MRI. Overall, the rate of CMV-associated postnatal and childhood sequelae was 27.8%, with a rate of 16.7% for SNHL and 11.1% for neurodevelopmental abnormalities, mostly slight motor or verbal delay. Approximately half of the cases with CMV-associated sequelae did not have any abnormal prenatal imaging findings. Abnormal prenatal findings on ultrasound were not associated significantly with SNHL, neurodevelopmental delay or composite clinical outcome (P = 0.084, 0.109 and 0.176, respectively), but they were associated with the composite outcome including TOP (P < 0.001). We identified a non-significant trend for a higher rate of SNHL in the group with abnormal ultrasound than in those with normal ultrasound. For abnormal MRI findings, we found a correlation only with neurodevelopmental abnormality and composite outcome (P = 0.014 and P < 0.001, respectively). CONCLUSIONS: The risk of childhood sequelae after first-trimester fetal CMV infection is most often associated with abnormal prenatal imaging findings. However, normal imaging does not rule out the development of SNHL and minor neurodevelopmental abnormalities. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Volumetric MRI Study of the Brain in Fetuses with Intrauterine Cytomegalovirus Infection and Its Correlation to Neurodevelopmental Outcome.

BACKGROUND AND PURPOSE: In recent years, effort has been made to study 3D biometry as a method for fetal brain assessment. In this study, we aimed to compare brain volumes of fetuses with cytomegalovirus infection and noninfected controls. Also, we wanted to assess whether there is a correlation to their neurodevelopmental outcome as observed after several years. MATERIALS AND METHODS: A retrospective cohort study examined MR imaging brain scans of 42 fetuses (at 30-34 weeks' gestational age) that were diagnosed with intrauterine cytomegalovirus infection. Volumetric measurements of 6 structures were assessed using a semiautomated designated program and were compared with a control group of 50 fetuses. Data collected included prenatal history and MR imaging and sonographic and neurodevelopmental follow-up. RESULTS: We found that all brain volumes measured were smaller in the cytomegalovirus-infected group and that there was a correlation between smaller cerebellar volume and lower Vineland II Adaptive Behavior Scales questionnaire scores, especially in the fields of daily living and communication skills. CONCLUSIONS: In this study, we found that brain volumes are affected by intrauterine cytomegalovirus infection and that it has a developmental prognostic meaning. Such information, which should be supported by further research, may help clinicians further analyze imaging data to treat and make a better assessment of these fetuses.

Can middle cerebral artery peak systolic velocity predict polycythemia in monochorionic-diamniotic twins? Evidence from a prospective cohort study.

OBJECTIVE: The antenatal diagnosis of twin anemia-polycythemia sequence (TAPS) in monochorionic-diamniotic (MCDA) twin pregnancies is based on elevated peak systolic velocity in the middle cerebral artery (MCA-PSV) in the donor twin and decreased MCA-PSV in the recipient twin. However, the association between these parameters and polycythemia has not yet been established. The aim of this study was to determine whether MCA-PSV can predict polycythemia in MCDA pregnancies. METHODS: This was a prospective cohort study of MCDA pregnancies recruited at 14-18 weeks' gestation from a single tertiary care center between January 2011 and June 2014. Fetal MCA Doppler waveforms were recorded every 2 weeks from 18 weeks' gestation until delivery. Only those with an MCA-PSV measurement within 1 week of delivery were included in the analysis. Neonatal hematocrit level was determined in all twins from venous blood obtained within 4 h of delivery. Polycythemia was defined as a hematocrit of > 65%, and anemia as a hematocrit of < 45%. TAPS was diagnosed when an intertwin hemoglobin difference of > 8 g/dL and reticulocyte count ratio of > 1.7 were observed. RESULTS: Of 162 MCDA pregnancies followed during the study period, 69 had an MCA-PSV measurement within 1 week of delivery and were included in the study. Twenty-five neonates were diagnosed with polycythemia and nine twin pairs met the criteria for TAPS. In a pooled analysis, MCA-PSV was negatively correlated with neonatal hematocrit (P = 0.017, r = -0.215) and was significantly higher in anemic fetuses than in normal controls (1.15 multiples of the median (MoM) vs 1.02 MoM, respectively; P = 0.001). However, MCA-PSV was similar among polycythemic and normal fetuses (0.95 MoM vs 1.02 MoM, respectively; P = 0.47). Intertwin difference in MCA-PSV (delta MCA-PSV) was positively correlated with intertwin hematocrit difference (P = 0.002, r = 0.394). Moreover, twin pregnancies with an intertwin hematocrit difference of > 24% had a significantly greater delta MCA-PSV than did those with an intertwin hematocrit difference of ≤ 24% (delta MCA-PSV, 19 vs 5 cm/s; P < 0.001). CONCLUSIONS: MCA-PSV is not significantly decreased in polycythemic MCDA twins. However, delta MCA-PSV is associated with a large intertwin difference in hematocrit, and its use may be better than conventional methods for the risk assessment of TAPS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Region-specific reductions in brain apparent diffusion coefficient in cytomegalovirus-infected fetuses.

OBJECTIVE: To evaluate the effects of cytomegalovirus (CMV) infection on apparent diffusion coefficient (ADC) values of the fetal brain in utero. METHODS: In this retrospective analysis we compared 58 fetal head magnetic resonance imaging (fhMRI) scans of PCR-verified CMV-infected fetuses, obtained in 2008-2012, with those of a normal control group of 36 gestational age (GA)-matched uninfected fetuses scanned between 2006 and 2012. Estimated GA at infection ranged from 1 to 32 weeks, and fhMRI was performed at 24 to 38 weeks. The frontal, parietal, temporal and occipital lobes (mainly white matter), basal ganglia, thalamus, pons and cerebellum were analyzed by assessing ADC values. Two pregnancies were terminated and postmortem confirmation was available in these cases. RESULTS: ADC values of CMV-infected fetuses correlated significantly and negatively with GA in all brain regions except the basal ganglia. The cerebellum had the greatest reduction (r = -0.52, P < 0.0001). Maternal age correlated positively with ADC in the frontal lobe (P < 0.05). GA at infection and overt pathological changes did not affect ADC significantly. Compared with non-infected fetuses, ADC values of affected fetuses were significantly reduced in the frontal (P < 0.0001), parietal (P < 0.0001), occipital (P = 0.0005) and temporal (P = 0.001) lobes and thalamus (P = 0.006). CONCLUSION: CMV infection of the fetal brain results in a highly significant, region-dependent reduction of ADC values in the frontal, parietal, occipital and temporal lobes and thalamus, probably reflecting hypercellularity and inclusion bodies in damaged areas. Further studies are needed to determine if reduction in ADC values may serve as a prognostic factor in CMV-infected fetuses. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Selective reduction in complicated monochorionic twins: prediction of obstetric outcome and comparison of techniques.

OBJECTIVES: To compare the outcomes of radiofrequency ablation (RFA) and bipolar cord coagulation (BPC) methods for selective feticide in complicated monochorionic (MC) twin gestations and to determine risk factors for adverse pregnancy outcome. METHODS: This was a retrospective cohort study of all patients with complicated MC twin pregnancy who underwent selective reduction in a single tertiary care center between 2000 and 2014. We compared the two methods with respect to various demographic, obstetric and perinatal outcome variables. RESULTS: Fifty-three selective terminations in complicated MC twin gestations were performed, 36 by RFA and 17 by BPC. Each technique resulted in a similar overall survival rate of the remaining twin (88.9% vs 76.5%, P = 0.25). Likewise, the mean procedure-to-delivery interval, the rate of spontaneous preterm delivery < 37, < 34, < 32 and < 28 weeks and the rate of preterm prelabor rupture of the membranes did not differ between the groups. However, among patients in the BPC group, there was a trend towards earlier gestational age at delivery (31.3 vs 35.0 weeks, P = 0.09) compared with in the RFA group. There was selective reduction by RFA due to selective intrauterine growth restriction (sIUGR) in 19 cases, 17 (89.5%) of which survived perinatally, with delivery at a median gestational age of 37 weeks. There were no significant differences in perinatal outcome, irrespective of whether the procedure was performed pre- or post-viability. All post-viability reductions, most of which were by RFA, resulted in perinatal survival. CONCLUSIONS: Perinatal outcome of complicated MC twin gestations undergoing selective feticide seems to be similar regardless of whether termination is by BPC or RFA. Nevertheless, RFA appears to be particularly useful in MC twins complicated by sIUGR and in cases requiring selective reduction beyond the age of viability.

Low molecular weight heparin therapy during pregnancy is associated with elevated circulatory levels of placental growth factor.

INTRODUCTION: Low molecular weight heparin (LMWH) has been shown to be effective in decreasing the recurrence of placenta-mediated complications of pregnant women. The aim of this study was to determine the effect of LMWH on circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PLGF) in pregnant women who required anticoagulation therapy. METHODS: A longitudinal prospective cohort study was performed including pregnant women in whom anticoagulation therapy by LMWH during pregnancy was clinically indicated (n = 33). Healthy pregnant women, matched for gestational age, who did not require thromboprophylaxis served as controls (n = 29). Maternal plasma samples were obtained throughout gestation every 4 weeks and stored at -70 °C. Maternal plasma concentrations of sFlt-1, sEng and PLGF were determined by ELISA and compared between the two groups. RESULTS: Patients treated with LMWH had significantly increased circulatory levels of PLGF during the third trimester compared with controls (28-34 weeks: 719.2 pg/ml vs 558.6 pg/ml at, p < 0.01; 35-40 weeks: 975.6 pg/ml vs 511.2 pg/ml, p < 0.01, respectively). In contrast, circulatory levels of sFlt-1 and sEng were similar between the LMWH treatment group and controls throughout gestation. Consistent with these findings, the ratio of sFlt-1/PLGF was lower in patients treated with LMWH compared to controls (28-34 weeks: 1.9 vs 7.2, p < 0.05; 35-40 weeks: 5 vs 12.9, p < 0.05, respectively). DISCUSSION: Anticoagulation treatment of pregnant women with LMWH is associated with a pro-angiogenic state. These findings may explain the effectiveness of LMWH in the prevention of placenta-mediated complications of pregnancy.

Early detection by diffusion-weighted sequence magnetic resonance imaging of severe brain lesions after fetoscopic laser coagulation for twin-twin transfusion syndrome.

OBJECTIVE: Monochorionic twins treated by fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS) are at increased risk of neurodevelopmental impairment. Our aim was to evaluate the additional value of diffusion-weighted imaging (DWI) over fetal sonography and T2 magnetic resonance imaging (MRI) in the detection of acute ischemic cerebral lesions shortly following FLC. METHODS: This was a prospective cohort study of fetuses with TTTS treated by FLC. All fetuses underwent brain DWI and T2-MRI within 24-96 h after the procedure and a follow-up MRI at 30-32 weeks' gestation. All fetuses also had frequent ultrasound evaluation until delivery. RESULTS: Thirty pregnancies with TTTS were included in the study. Eight resulted in survival of only one twin after the procedure (Group A), while the other 22 pregnancies resulted in the survival of both twins (Group B), as assessed at the time of initial MRI. Two fetuses in Group A and four in Group B had evidence of transient bleeding in the germinal matrix. Three fetuses in Group B and none in Group A had diffuse ischemic changes in the white matter. One fetus died in utero 24 h after MRI. The other two fetuses in Group B demonstrated an acute infarct 24-48 h after the procedure. Subsequent scans at 28-29 and 32 weeks showed brain atrophy compatible with an old infarct. CONCLUSIONS: DWI can demonstrate cerebral damage immediately after FLC. Larger cohorts are needed to determine the role of fetal MRI in the prenatal assessment and follow-up of patients with TTTS.

Late diagnosis of fetal central nervous system anomalies following a normal second trimester anatomy scan.

OBJECTIVE: The aim of this study was to describe the nature of central nervous system (CNS) anomalies diagnosed during the third trimester following a normal anatomy scan at 21-24 weeks of gestation. METHODS: Retrospective cohort study of all pregnant women referred to the fetal medicine unit at Sheba Medical Center between 2005 and 2011 due to fetal CNS anomalies detected at the late second and third trimesters following a normal anatomy scan at 21-24 weeks of gestation. RESULTS: During the study period, 47 patients were diagnosed with fetal CNS anomalies at a median gestational age of 31.1 weeks (range 24-38). The four most common anomalies found included intracranial cysts (19%), mild ventriculomegaly (15%), absence or dysgenesis of the corpus callosum (10%), and intracerebral hemorrhage (10%). Other CNS anomalies detected in this group of patients included hydrocephalus, Dandy walker malformation, large cysterna magna, microcephalus with lissencephaly, craniosynestosis, periventricular pseudocysts, global brain ischemia, cerebellar hypoplasia, and sub-ependymal nodule. CONCLUSIONS: Fetal brain continues to evolve throughout gestation, and therefore, some of the CNS anomalies can be diagnosed only during late second and third trimesters of pregnancy. Consequently, in patients who have a third trimester scan for any reason, assessment of the fetal CNS should be considered.

Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging.

OBJECTIVE: To determine the outcome of pregnancies with documented fetal cytomegalovirus (CMV) infection with and without abnormal findings on ultrasound examination and magnetic resonance imaging (MRI). METHODS: In this prospective cohort study of pregnant women with documented fetal CMV infection, vertical CMV transmission occurred during the first and second trimesters following primary maternal infection. Patients underwent serial prenatal ultrasound scans and fetal MRI. All neonates underwent ocular fundus examination, ultrasound brain scan and hearing evaluation, and were then followed periodically by a pediatrician. RESULTS: Primary CMV infection occurred during the first and second trimesters of pregnancy in 71 and 74 patients, respectively. Seven patients (4.8%) decided to terminate pregnancy because of prenatal findings and one neonate died because of CMV complications. Patients with first-trimester infection had infants with significantly more associated sequelae (either auditory damage or neurodevelopmental disabilities) than did patients with second-trimester infection (19.7% vs 5.6%, respectively; P = 0.01). Abnormal prenatal findings on ultrasound examination were associated with increased risk of sequelae. When both ultrasound and MRI findings were normal, the rate of sequelae was decreased to 15.6% for first-trimester infections and to 2.0% for second-trimester infections, partial hearing loss being the sequela in most cases. In the presence of abnormal ultrasound and/or MRI findings the risk was 25% and 16%, respectively, and in most cases the sequelae were deafness and neurodevelopmental delay. The rate of intrauterine growth restriction (IUGR) in the study group was 11.7% and was not affected by the time of onset of maternal infection. Isolated IUGR was not associated with increased risk of sequelae. CONCLUSION: The risk of sequelae is higher following first-than second-trimester CMV infection. However, the risk of severe sequelae is significantly reduced in the presence of normal prenatal ultrasound and MRI findings.

Diffusion MRI findings in monochorionic twin pregnancies after intrauterine fetal death.

BACKGROUND AND PURPOSE: Monochorionic twin pregnancies complicated by the IUFD of 1 twin are associated with substantial morbidity to the survivor twin. The aim of this study was to determine whether fetal sonography, T2 MR imaging, and DWI can diagnose acute cerebral lesions in the survivor of an MC twin pregnancy shortly after fetal death of the co-twin. MATERIALS AND METHODS: During the study period (2007-2010) 34 cases of single IUFD were evaluated. Group A included 6 cases complicated by spontaneous IUFD. Group B had 10 cases of fetal death shortly after treatment of severe TTTS. These were compared with group C, with 18 pregnancies treated by selective termination due to severe complications in MC pregnancies. RESULTS: Altogether 9/34 patients had abnormal prenatal cerebral findings. In group A, in 2/6 of pregnancies with spontaneous death, MR imaging showed findings of severe cerebral infarct, while cerebral damage was not evident by sonography. In another case, the surviving fetus was found to be hydropic on sonography, while MR imaging findings were normal. In group B, in 1/10 cases, cerebral infarct was demonstrated only by DWI. In 2 other cases, sonographic findings were normal, but MR imaging showed germinal matrix bleeding. In group C, in 1/18 cases, only DWI showed bilateral cerebral ischemia. In 2 other cases, MR imaging findings suggested germinal matrix bleeding and focal changes in the basal ganglia. In both cases, fetal sonographic findings were normal. CONCLUSIONS: In our study, early manifestations of cerebral ischemia in monochorionic twin pregnancies were better diagnosed with MR imaging, especially with DWI.

Value of prenatal ultrasound and magnetic resonance imaging in assessment of congenital primary cytomegalovirus infection.

OBJECTIVE: To evaluate the outcome of pregnancies with proven and well-dated primary cytomegalovirus (CMV) infection with and without abnormal fetal ultrasound and magnetic resonance imaging (MRI) findings. METHODS: This was a prospective study of 38 singleton pregnancies with proven vertical transmission of CMV and prenatal ultrasound and MRI examinations. Entry requirements included precise dating of the pregnancy and known time of maternal infection. Neonatal follow-up was a strict requirement, all neonates having eye fundus examination, a brain ultrasound scan and a hearing evaluation. All children were followed up by specialists in child development. RESULTS: Primary CMV infection occurred during the first trimester in 10 patients, the second trimester in 19 and the third trimester in nine. Twenty-four of 29 patients with first- or second-trimester infections delivered; the other five underwent termination of pregnancy (TOP). Three patients had abnormal sonographic findings with normal MRI. Of these, two had damage to the auditory system. In both cases, infection occurred during the first trimester. In 16 patients with first- or second-trimester infection, both ultrasound and MRI exams were normal; there was one TOP but all other cases had favorable outcome, with normal hearing and developmental evaluations. The outcome of five pregnancies with subtle MRI findings and normal ultrasound exam was also favorable. None of the children infected during the third trimester was affected. CONCLUSION: The outcome of congenital primary CMV infection with normal prenatal ultrasound and MRI exams is favorable. The prognostic value of subtle MRI findings is limited and when such findings are isolated, termination of pregnancy is unlikely to be justified.

Outcome of severely anaemic fetuses treated by intrauterine transfusions.

BACKGROUND: Fetal anaemia is a well-known complication of pregnancy, which might have an ominous effect on the course of pregnancy, labour and the child's development. OBJECTIVE: To assess the effect of the severity of fetal anaemia on the child's outcome. METHODS: A retrospective cohort study. Pregnancies treated by intrauterine transfusions for fetal anaemia at Sheba Medical Center (1996-2004) were divided into two groups: mild to moderate anaemia (fetal haematocrit >0.50 multiples of the median (MoM)) and severe anaemia (hydrops fetalis or fetal haematocrit < or =0.50 MoM). Data were retrieved from relevant obstetric and fetal medicine files. RESULTS: During the study period, 54 fetuses were treated by 154 (median 3; range 1-7) intrauterine transfusions for red cell alloimmunisation. The sensitising antigen was D in 70% of cases; 18/54 patients were sensitised to more than one antigen. Thirty-three of the 54 fetuses (61%) were in the severely anaemic category (haematocrit range 3-20%); six were hydropic. Twenty-one of the 54 fetuses (39%) were in the mild-moderate anaemic category (haematocrit range 20-37%). On prenatal evaluation, there were no sonographic markers of central nervous system abnormalities or intraventricular haemorrhage. There were no differences in the neonatal outcome between the two groups. Developmental outcome was available in 14/18 (78%) mild-moderate cases and 26/29 (89%) severe cases. There were no significant differences in motor development score, percentage of abnormal cognitive development, and percentage of children needing supportive therapy between the mild-moderate and severe cases. CONCLUSION: Neonatal and developmental outcome of fetuses treated for severe anaemia is comparable to cases of mild anaemia.

Three- and four-dimensional ultrasound: new methods for evaluating fetal thoracic anomalies.

OBJECTIVE: To study three- (3D) and four-dimensional (4D) ultrasound applications for the evaluation of fetal thoracic anomalies. METHODS: Volume datasets of 23 fetuses with thoracic anomalies were acquired with static 3D and cine 4D ultrasound, i.e. spatiotemporal image correlation (STIC) mode. The volumes were analyzed and displayed by multiplanar and tomographic ultrasound imaging (TUI) modes and static volume contrast imaging (VCI). Color Doppler was added to the volumes acquired, and various rendering modes were used to display the volume datasets. RESULTS: The mean gestational age at evaluation was 22 (range, 14-34) weeks. The anomalies were identified as: diaphragmatic hernia (n = 5), lung dysplasia (n = 11), skeletal dysplasia with small thorax/thanatophoric dysplasia (n = 2), abnormal situs (n = 2), hydrothorax (n = 2) and esophageal atresia (n = 1). The TUI mode achieved optimal display of the thorax, thereby aiding the diagnosis of diaphragmatic hernia and lung dysplasia. In right diaphragmatic hernias, the VCI mode proved invaluable as it distinguished liver from lung tissue. High-definition color Doppler with glass-body rendering significantly contributed to the detection of abnormal vascularization in lung dysplasia. Maximal transparent mode with a transvaginal transducer provided accurate diagnosis of skeletal dysplasia in the first trimester. Situs abnormalities were best viewed with a minimal transparent mode, in which abnormal organs and positions of vessels were clearly identified. Pleuroamniotic shunt localization was monitored precisely by 3D in a fetus with hydrothorax, and inversion mode added important information regarding the size of an esophageal pouch in a fetus with esophageal atresia. CONCLUSION: The 3D-4D technique is a novel, useful sonographic tool for evaluating the fetal thorax. It enhances precise diagnosis and provides better spatial visualization of the anomalies involved.

Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia.

OBJECTIVE: To assess the value of antenatally determined observed to expected fetal lung area to head circumference ratio (LHR) in the prediction of postnatal survival in isolated, congenital diaphragmatic hernia (CDH). METHODS: Two groups of fetuses were examined. The first group included 650 normal fetuses at 12-32 weeks' gestation, and the data collected were used to establish a normal range of observed to expected LHR with gestational age. The second group included the data of a retrospective multicenter study of 354 fetuses with isolated CDH in which the LHR was measured on one occasion at 18-38 weeks' gestation. The patients were divided into those with left-sided CDH with and without intrathoracic herniation of the liver and right-sided CDH. Regression analysis was used to determine the significant predictors of postnatal survival. RESULTS: In both the normal fetuses and those with CDH the LHR increased but the observed to expected LHR did not change significantly with gestational age. In normal fetuses the mean observed to expected LHR in the left lung was 100% (95% CI, 61-139%) and in the right lung it was 100% (95% CI, 67-133%). In fetuses with CDH the mean observed to expected LHR was 39% (range 7-79%). Regression analysis demonstrated that significant predictors of survival were the observed to expected LHR (odds ratio (OR) 1.09, 95% CI, 1.06-1.12), side of CDH (left side OR 11.14, 95% CI, 3.41-36.39) and gestational age at delivery (OR 1.18, 95% CI, 1.02-1.36). CONCLUSION: In CDH, the LHR increases while observed to expected LHR is independent of gestational age. In fetuses with both left- and right-sided CDH, measurement of the observed to expected LHR provides a useful prediction of subsequent survival.

Management of Kell isoimmunization--evaluation of a Doppler-guided approach.

OBJECTIVE: To assess the role of peak systolic velocity in the middle cerebral artery (MCA-PSV) in the management of pregnancies complicated by Kell isoimmunization. METHODS: Sixteen fetuses were monitored by conventional protocol (Group 1) and eight fetuses by an MCA-PSV-guided protocol (Group 2). The conventional protocol included a weekly ultrasound evaluation and measurement of maternal anti-Kell titers every 4-6 weeks. In Group 2 Doppler assessment of the MCA-PSV was performed at intervals of 4 to 7 days and MCA-PSV>1.5 multiples of the median (MoM) was considered as an indication for fetal blood sampling (FBS). RESULTS: No parameter emerged as a reliable predictor of isoimmunization severity in Group 1. In Group 2, no FBS was necessary in one case since the MCA-PSV values obtained during the follow-up were <1.29 MoM. In two cases the first FBS was already indicated after 1 week of follow-up, but five other fetuses were followed for 3-9 weeks before FBS was indicated. All fetuses with MCA-PSV>1.5 MoM prior to intrauterine transfusion (IUT) had severe fetal anemia on FBS. In fetuses with severe anemia on the first FBS, the MCA-PSV values 7 days before the first FBS were <1.29 MoM (four cases), between 1.29 and 1.5 MoM (two cases) and >1.55 MoM (one case). CONCLUSIONS: In the management of Kell isoimmunization invasive procedures may be avoided by implementing MCA-PSV measurements. Delineation of appropriate intervals between reassessments, the reliability of MCA-PSV following repeated IUTs, and cut-off values for FBS await further study.

Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies.

OBJECTIVE: To study the outcome of 20 twin pregnancies with evidence of primary or recurrent cytomegalovirus (CMV) infection during pregnancy. DESIGN: Observational study. SETTING: Two tertiary perinatal departments in Israel. POPULATION: Twenty women with twin pregnancies who were referred because of serologic investigation indicating CMV infection. Seventeen women had evidence of primary CMV infection, and three women appeared to have recurrent CMV infection. METHODS: Prenatal diagnosis was made by amniocentesis of both sacs after 21 weeks of gestation. CMV isolation was performed by culture on fibroblasts, shell vial technique and polymerase chain reaction (PCR) amplification of CMV DNA. After birth, the neonatal urine and saliva were cultured for CMV. MAIN OUTCOME MEASURES: Intrauterine CMV infection defined as positive PCR at amniotic fluid analysis and congenital CMV infection defined as positive CMV cultures after birth. RESULTS: Except for one, all women underwent amniocentesis of both gestational sacs. In 14 (70%) women, no evidence of vertical transmission to any of the 28 fetuses was found and none of the newborns had evidence of congenital CMV infection. Intrauterine infection was detected by amniocentesis in five women and by ultrasound findings with positive maternal serology in one. In three women, CMV was detected in only one amniotic sac. In five of our six total cases, both twins were found to have congenital CMV infection at birth, all of whom had dichorionic-diamniotic placentation, three fused and two separate. CONCLUSIONS: In twin gestations, as in singletons, intrauterine and congenital CMV infection occurs in about 30% of women with primary or recurrent infection. The placenta type did not predict if one or both twins would be infected. Our data do not exclude the possibility that intrauterine transmission of the virus from one fetus to the other can occur.

Development of the human fetal pons: in utero ultrasonographic study.

OBJECTIVES: To examine the ultrasonographic feasibility of imaging the fetal pons and to construct a reference chart for its normal development during gestation. METHODS: A cross-sectional, prospective study on 293 healthy fetuses of low-risk pregnancies between 19 and 34 weeks was performed. The transfontanel approach, via the abdominal or vaginal routes, was used to evaluate the fetal metencephalon (pons and cerebellum). The anteroposterior diameter of the fetal pons was measured in a mid-sagittal plane. The longitudinal diameter of the cerebellar vermis was measured at the same plane and the vermis-pons ratio (VPR) was established. RESULTS: One hundred and forty-four fetuses were in vertex position. In 140 (97.2%) satisfactory visualization and measurements of the pons and cerebellar vermis were obtained. One hundred and forty-nine fetuses were breech presentations and measurements were successfully performed in 147 (98.6%). The pons anteroposterior and vermis longitudinal diameters showed a linear correlation with gestational age (GA) (r = 0.95 for both measurements; P < 0.001). The mean VPR was 1.5 (+/-0.1 SD) and did not change in the gestational interval that was considered. CONCLUSION: By using the transfontanel approach, evaluation of the fetal pons is feasible via the mid-sagittal plane. The nomograms developed and the ratio to fetal vermis provides reference data that may be helpful when evaluating anomalies of the brainstem.