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Objectives: The purpose of this study was to test the relationship between adenovirus genetic material in the amniotic fluid and adverse pregnancy outcome.Study Design: This was a prospective, observational study of women who were referred in the second trimester of gestation for either genetic amniocentesis or evaluation of fetal malformation. A 2-mL aliquot of amniotic fluid was subjected to multiplex polymerase chain reaction for a panel of viruses that included adenovirus and human genome controls. Fetuses with an abnormal karyotype were excluded from analysis.Results: The prevalence of adenovirus was similar in normal (39/652) and anomalous fetuses (23/364; chi(2) test, P=.376). There was significant seasonal variation in the prevalence in both normal and anomalous fetuses (chi(2) exact test, P<.001), but no significant difference between groups. The monthly proportion of patients who underwent amniocentesis remained constant throughout the year (mean, 8.3%; chi(2) test, P=.67). Central nervous system anomalies and echogenic liver foci were significantly more common among fetuses with positive amniotic fluid polymerase chain reaction results for adenovirus (P<.005, respectively).Conclusion: Adenovirus is found in a similar prevalence and seasonal variation in sonographically normal and abnormal pregnancies. Although a specific fetal presentation was not identified, echogenic liver lesions with or without hydrops and neural tube defects were significantly more common in the presence of adenovirus. The significance of these findings deserves further study. [ABSTRACT FROM AUTHOR]

Objective: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR)., Methods: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR., Results: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05)., Conclusion: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To evaluate whether fetal epicardial fat thickness (EFT) differs in diabetic and nondiabetic pregnant women., Methods: Retrospective case-control study of pregnancies between 24 and 36 weeks complicated by preexisting (PDM) or gestational (GDM) diabetes mellitus, matched one to one with controls for body mass index and gestational age (GA). Epicardial fat was identified as the hypoechogenic area between myocardium and visceral pericardium over the right ventricle and its thickness was measured by a single observer blinded to clinical condition and outcomes. A linear regression analysis was performed to assess the relationship between GA and EFT, and regression lines were compared between diabetics and controls., Results: 53 PDM and 53 GDM pregnant women were matched with controls. With the exception of maternal age, the demographics were similar among groups. EFT increased significantly with advancing gestation in both diabetics and controls (P < 0.0001) and was significantly greater in diabetics than in controls (P < 0.0001). The best fit lines were different between diabetics (EFT = 0.05 × GA + 0.07 mm; R 2  = 0.70) and controls (EFT = 0.07 × GA + 0.04 mm; R 2  = 0.93) (P < 0.0001)., Conclusion: Fetal EFT was greater in diabetics than in nondiabetics, and even greater in pregestational diabetics. EFT maybe an additional and/or earlier marker to identify early changes in fetal metabolism before accelerated fetal growth and polyhydramnios is apparent., (© 2018 Wiley Periodicals, Inc.)

Maternal pregestational diabetes mellitus (PGDM) induces congenital heart defects (CHDs). The molecular mechanism underlying PGDM-induced CHDs is unknown. microRNAs (miRNAs), small non-coding RNAs, repress gene expression at the posttranscriptional level and play important roles in heart development. We performed a global miRNA profiling study to assist in revealing potential miRNAs modulated by PGDM and possible developmental pathways regulated by miRNAs during heart development. A total of 149 mapped miRNAs in the developing heart were significantly altered by PGDM. Bioinformatics analysis showed that the majority of the 2111 potential miRNA target genes were associated with cardiac development-related pathways including STAT3 and IGF-1 and transcription factors (Cited2, Zeb2, Mef2c, Smad4 and Ets1). Overexpression of the antioxidant enzyme, superoxide dismutase 1, reversed PGDM-altered miRNAs, suggesting that oxidative stress is responsible for dysregulation of miRNAs. Thus, our study provides the foundation for further investigation of a miRNA-dependent mechanism underlying PGDM-induced CHDs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown., Objective: We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects., Study Design: A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination., Results: Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene expression; and XBP1 messenger RNA splicing, as well as increased cleaved caspase 3 and 8 in embryonic hearts. Furthermore, maternal type 2 diabetes mellitus triggered excessive apoptosis in ventricular myocardium, endocardial cushion, and outflow tract of the embryonic heart., Conclusion: Similar to those observations in type 1 diabetic embryopathy, maternal type 2 diabetes mellitus causes heart defects in the developing embryo manifested with oxidative stress, endoplasmic reticulum stress, and excessive apoptosis in heart cells., Competing Interests: The authors report no conflict of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Platelet Endothelial Aggregation Receptor 1 (PEAR1) is a newly identified membrane protein reported to be involved in multiple vascular and thrombotic processes. While most studies to date have focused on the effects of this receptor in platelets, PEAR1 is located in multiple tissues including the endothelium, where it is most highly expressed. Our first objective was to evaluate the role of PEAR1 in endothelial function by examining flow-mediated dilation of the brachial artery in 641 participants from the Heredity and Phenotype Intervention Heart Study. Our second objective was to further define the impact of PEAR1 on cardiovascular disease computationally through meta-analysis of 75,000 microarrays, yielding insights regarding PEAR1 function, and predictions of phenotypes and diseases affected by PEAR1 dysregulation. Based on the results of this meta-analysis we examined whether genetic variation in PEAR1 influences endothelial function using an ex vivo assay of endothelial cell migration. We observed a significant association between rs12041331 and flow-mediated dilation in participants of the Heredity and Phenotype Intervention Heart Study (P = 0.02). Meta-analysis results revealed that PEAR1 expression is highly correlated with several genes (e.g. ANG2, ACVRL1, ENG) and phenotypes (e.g. endothelial cell migration, angiogenesis) that are integral to endothelial function. Functional validation of these results revealed that PEAR1 rs12041331 is significantly associated with endothelial migration (P = 0.04). Our results suggest for the first time that genetic variation of PEAR1 is a significant determinant of endothelial function through pathways implicated in cardiovascular disease.

Owing to vascular connections within a single placenta, monochorionic gestations present distinctive prenatal management challenges. Complications that can arise as a result of unbalanced hemodynamic exchange (twin-twin transfusion syndrome and twin anemia polycythemia sequence) and unequal placental sharing (selective fetal growth restriction) should be kept in mind while prenatal management is being planned. Because of unique monochorionic angioarchitecture, what happens to one twin can directly affect the other. Death of one twin can result in death or permanent disability of the co-twin. Early detection of these unique disease processes through frequent ultrasonographic surveillance may allow the opportunity for earlier referral, intervention, or both and potentially better outcomes. Therefore, monochorionic gestations should be managed differently than dichorionic gestations or singletons. The purpose of this document is to present in detail methods for monitoring and management of uncomplicated monochorionic gestations and to review the evidence for the roles of these methods for detection of complications in clinical practice. Finally, we present evidence-based and expert opinion-supported recommendations developed by the North American Fetal Therapy Network for the diagnosis, surveillance, and delivery of uncomplicated monochorionic gestations.

Objective: A four-dimensional (4D) fetal echocardiographic technique utilizing spatiotemporal image correlation, tomographic ultrasound imaging display (STIC-TUI echo) and color Doppler has previously been shown to be effective in displaying the examination planes constituting the extended cardiac examination. The aim of this study was to evaluate the performance of this first-trimester STIC-TUI echo technique in identifying complex congenital heart disease (CHD) in high-risk pregnancies., Methods: This was a prospective study of patients presenting at first-trimester screening who were at high risk for CHD owing to pregestational diabetes, in-vitro fertilization (IVF), increased nuchal translucency (NT) thickness, first-trimester tricuspid regurgitation or reversed ductus venosus (DV) a-wave, a previous child with CHD or who were on anticonvulsant medication. First-trimester STIC-TUI echo was performed, and the findings were correlated with second-trimester echocardiography and post-delivery echo findings in survivors., Results: One hundred and sixty-four fetuses from 152 patients were enrolled (77 diabetics, 38 IVF, 14 with increased NT, 23 cases of tricuspid regurgitation or reversed a-wave in the DV, 22 with prior CHD and two on anticonvulsants). STIC-TUI echo was abnormal in 20 (12%), showing atrioventricular canal defect (n = 9), hypoplastic left heart (n = 2), pulmonary stenosis (n = 2), right aortic arch (n = 1), interrupted aortic arch (n = 1), tricuspid atresia (n = 1), heterotaxy (n = 1), persistent truncus arteriosus (n = 1), double outlet right ventricle and ventricular septal defect (n = 1) and double inlet ventricle with transposition of the great arteries (n = 1). 85% of these anomalies were evident in the four-chamber view plane of the TUI display, and the remainder were diagnosed in the outflow tract planes with color Doppler imaging. In 13, CHD was isolated while seven had extracardiac anomalies. Thirteen fetuses had aneuploidy and all 13 underwent first-trimester termination of pregnancy. In the remaining seven, second-trimester echocardiography and neonatal echo/postmortem examination confirmed anomalies (two stillborn neonates, one neonatal death, four live births). Two cases of CHD missed by first-trimester STIC-TUI echo were diagnosed on second-trimester echo. Accordingly, first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD., Conclusions: First-trimester 4D echocardiography using a standardized application of STIC, TUI and color Doppler imaging is effective in displaying the imaging planes that are necessary for achieving the diagnosis of complex cardiac anomalies in high-risk patients. Optimal imaging of the four-chamber view with two-dimensional ultrasound is the major determinant of successful volume acquisition., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the impact of prior preeclampsia on first trimester assessment in subsequent pregnancy., Methods: A total of 1283 parous patients were prospectively enrolled at 9-14 weeks of gestation. Maternal biophysical characteristics, ultrasound parameters and placental analytes were compared between women with and without prior preeclampsia., Results: There is no association between prior preeclampsia and the first trimester ultrasound parameters or placental analytes studied. The effects of prior preeclampsia in subsequent pregnancy are exaggerated by increasing parity and are predominantly blood pressure-related, independent of other cardiovascular risk factors., Conclusion: There is a potential role for lifestyle modification and stricter pregnancy blood pressure control in patients with prior preeclampsia.

Objectives: The purpose of this study was to establish reference ranges for ductus venosus velocity ratios., Methods: Singleton pregnancies from 11 to 38 weeks with exactly established gestational ages (GAs) were recruited for the study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical complications, stillbirth, birth weight below the 10th or above the 90th percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a, where S indicates ventricular systole [s-wave], v, ventricular end-systolic relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a, active ventricular filling during atrial systole [a-wave]) were calculated. Separate regression models were fitted to estimate the mean and standard deviation at each GA for each ratio., Results: A total of 902 velocity wave ratios and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a ratios were reduced with GA (P < .0001 for all). Significant reductions in the means and standard deviations of the PIV and S/a, v/a, and D/a ratios were observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately created between 11 and 17 weeks and 18 and 38 weeks., Conclusions: We created reference ranges for ductus venosus velocity ratios between 11 and 38 weeks' gestation in normal pregnancies. These reference ranges may prove beneficial for evaluation of fetal conditions that are associated with cardiovascular abnormalities.

Objective: The objective of the study was to compare the outcome in women with twin-twin transfusion syndrome (TTTS) who were managed by selective laser ablation of placental anastomoses (S-LASER) vs equatorial dichorionization of the anastomoses and chorionic plate (ED-LASER)., Study Design: We conducted an analysis of 2 consecutive cohorts with TTTS treated with S-LASER and ED-LASER. Preoperative, procedural, delivery, and outcome details were compared between treatment groups., Results: A total of 147 twin pregnancies had laser (S-LASER, n = 71; ED-LASER, n = 76). Obstetric history, Quintero stage, placental location, individual arterial and venous Doppler parameters, and gestational age at laser and delivery did not differ. Use of lens fetoscope (96.1% vs 50.7%), coagulated anastomosis count (11 vs 15, P < .001), complete equatorial plate visualization (77.5% vs 92.1%, P = .019), and amniotic fluid transparency (80.3% vs 94.7%, P = .011) was greater during ED-LASER. Procedure-related complications, gestational age at delivery, and perinatal details were comparable between groups. ED-LASER was associated with significantly lower recurrence of TTTS (3.9% vs 8.5%), twin anemia polycythemia sequence (2.6% vs 4.2%), and amniotic fluid abnormalities (0% vs 5.6%, P < .05 for all comparisons). Logistic regression identified complete visualization of the equator as the primary determinant for successful TTTS treatment and coagulation of the chorionic plate as an independent cofactor. Double survival at age 6 months was significantly higher after ED-LASER (68.4% vs 50.7%, P < .05), attributable to a lower postlaser and neonatal mortality rates., Conclusion: In patients with TTTS, photocoagulation of causative anastomoses and the chorionic plate along the vascular equator decreases recurrence without increasing adverse outcome and improves survival compared with the selective technique., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Aims: To test if an isolated finding of low-normal amniotic fluid index (AFI) in the early third trimester in low-risk patients is associated with adverse perinatal outcomes., Methods: Retrospective cohort study with uncomplicated singleton pregnancies that had ultrasound studies between 28.0 and 31.9 weeks' gestation. Two cohorts with AFI 8.0-11.9 cm (low-normal, LN) and AFI 12.0-19.9 cm (mid-normal, MN) were compared., Results: Patients with LN-AFI (n=99) were more likely to have early (<34 weeks) and late (<37 weeks) preterm birth (PTB) (relative risk 4.2 and 2.4, respectively) and a small for gestational age (SGA) infant (relative risk 1.8) than MN-AFI (n=834), corresponding to a higher NICU admission rate (relative risk 2.5). The risk of "spontaneous" PTB (preterm labor and rupture of membranes) did not differ between the cohorts, whereas the risk of "indicated" PTB (maternal or fetal indications) was significantly increased in LN-AFI. The incidence of abnormal antepartum testing, stillbirth, preeclampsia, placental abruption, fetal intolerance to labor, emergency cesarean delivery, umbilical artery pH <7.0, Apgar scores <7 at 5 min, and neonatal death was not increased in patients with LN-AFI., Conclusion: Low-normal AFI in the early third trimester increases the risk for subsequent delivery of an SGA infant and indicated PTB.

Objectives: To test if emergence of third-trimester (T3) placental dysfunction is related to the impedance change in uterine artery blood flow resistance between the first trimester (T1) and T3., Study Design: Mean T1 and T3 uterine artery (mUtA) pulsatility index (PI) was measured in 1098 singletons. Each patient's individual mUtA-PI change was calculated ([(T3 PI - T1 PI/interval in days)] × 100; ΔmUtA-PI). This parameter and T1 and T3 mUtA-PI z-scores were related to placenta-related disease (PRD) and to constitutionally small neonates (CS)., Results: Forty-seven (5%) women had PRD and 83 (8.7%) delivered a CS neonate. T1 and T3 mUtA-PI z-scores were higher with PRD (0.418 versus -0.097 and 1.06 versus -0.13, p < 0.001 for all). Change in mUtA-PI (ΔmUtA PI) was similar for patients with PRD. However, the prevalence of PRD doubled with rising ΔmUtA-PI (11.1% versus 5.2%, p = 0.041)., Conclusion: T3 uterine artery Doppler performs significantly better in detecting patients at risk for late-onset PRD than T1 or the gestational age change in uterine artery Doppler resistance This suggests that a proportion of late emerging PRD is not amenable to early screening by uterine artery Doppler. Further research is essential to identify the optimal screening strategy for late-onset placental dysfunction., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The frequency of fetal anomalies in women with pregestational diabetes correlates with their glycemic control. This study aimed to assess the predictive performance of first-trimester fetal nuchal translucency (NT), ductus venosus (DV) Doppler, and hemoglobin A1c (HbA1c) to predict fetal anomalies in women with pregestational diabetes., Study Design: This was a prospective observational study of patients undergoing first-trimester NT with DV Doppler. Screening performance was tested for first-trimester parameters to detect fetal anomalies., Results: Of 293 patients, 17 had fetal anomalies (11 cardiac, 7 major, 3 multisystem). All anomalous fetuses were suspected prenatally. One had NT >95th centile, 2 had reversed DV a-wave, and 13 had HbA1c >7.0%. The HbA1c was the primary determinant of anomalies (r(2), 0.15; P < .001) and >8.35% was the optimal cutoff for prediction of anomalies with an area under the curve of 0.72 (95% confidence interval, 0.57-0.88). Therefore, first-trimester prediction of anomalies was best in women with increased NT or HbA1c >8.3% (sensitivity 70.6%, specificity 77.4%, positive predictive value 16.2%, negative predictive value 97.7%, P < .001)., Conclusion: In women with pregestational diabetes and poor glycemic control, an increased NT increases risks for major fetal anomalies. Second-trimester follow-up is required to achieve accurate prenatal diagnosis., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To examine the relationship between hematologic parameters at birth and prenatal progression of Doppler abnormalities in fetal growth restriction (FGR)., Methods: The study was a secondary analysis of FGR patients (abdominal circumference < 5th percentile and umbilical artery pulsatility index (UA-PI) elevation) with at least three examinations prior to delivery. Prenatal progression was classified as rapid, moderate or slow based on the interval between diagnosis and delivery and the extent of UA, middle cerebral artery and ductus venosus Doppler abnormalities. Associations between diagnosis-to-delivery interval, Doppler Z-scores, progression and hematologic parameters at birth were examined., Results: Of 130 patients, 54 (41.5%) had rapid, 51 (39.2%) moderate and 25 (19.2%) slow deterioration, delivering within 4, 6 and 9 weeks of diagnosis, respectively. The strongest association of moderate and rapid deterioration was with a low platelet count (r2  = 0.37 and 0.70, respectively; P < 0.0001). In patients with moderate deterioration, platelet count correlated inversely with UA-PI (ρ = -0.44, P = 0.001) and was lowest when end-diastolic velocity was absent. With rapid progression, platelet count correlated inversely with nucleated red blood cell count (ρ = -0.51, P < 0.001) but no longer with UA-PI., Conclusion: Our observations suggest a relationship between prenatal clinical progression of FGR and hematologic abnormalities at birth. Accelerating cardiovascular deterioration is associated with decreased platelet count, which can be explained by placental consumption or dysfunctional erythropoiesis and thrombopoiesis., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: Cardiovascular status in fetal growth restriction (FGR) can be classified by the severity of individual Doppler abnormalities (early and late) or by the rate of clinical progression. We tested the hypothesis that aspects of the fetal cardiovascular status in FGR affect neonatal cardiovascular findings., Study Design: FGR cases [abdominal circumference <5th percentile and an elevated umbilical (MCA) artery (UA) pulsatility index] had UA, middle cerebral artery and ductus venosus (DV) Doppler. Positive UA end-diastolic velocity and/or a low MCA pulsatility index denoted early and absent/reversed UA end-diastolic velocity, whereas an increased DV pulsatility index for veins denoted late responses. The rate of progression was classified into mild, progressive and severe. After delivery, shunt dynamics and blood flow across the patent ductus arteriosus (PDA), foramen ovale and atriaventricular valves, myocardial contractility and pharmacologic pressor requirement were noted at neonatal echocardiography. These findings were related to prenatal Doppler parameters., Results: In 94 patients, only individual Doppler parameters related to neonatal echocardiographic findings. Absent/reversed UA DV significantly predicted PDA with right to left shunt (p = 0.016). The pressor need for cardiovascular instability was observed in neonates with abnormal prenatal DV Doppler and with lower birth weights delivered at earlier gestational age (p < 0.0001 for both). Pressor need was significantly related to neonatal death (Nagelkerke R² = 0.35, p = 0.002)., Conclusion: A markedly abnormal UA Doppler predisposes growth-restricted neonates to persistence of fetal circulation associated with right to left shunting. Abnormal venous Doppler is a risk factor for cardiovascular instability which in turn significantly contributes to neonatal mortality. Further clarification of the neonatal cardiovascular transition may be helpful in guiding early neonatal assessment and management., (Copyright © 2012 S. Karger AG, Basel.)

Objective: We aim to test the hypothesis that two-dimensional (2-D) fetal adrenal gland volume (AGV) measurements offer similar volume estimates as volume calculations based on 3-D technique., Methods: Fetal AGV was estimated by three-dimensional (3-D) ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2-D measurements of the same blocks (0.523 × length × width × depth). Comparisons were performed by intraclass correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The corrected AGV (cAGV; AGV/fetal weight) was calculated for both methods and compared for prediction of preterm birth (PTB) within 7 days., Results: Among 168 volumes, there was a significant correlation between 3-D and 2-D methods (ICC = 0.979; 95% confidence interval [CI]: 0.971 to 0.984). The coefficient of repeatability for the 3-D was superior to the 2-D method (intraobserver 3-D: 30.8, 2-D:57.6; interobserver 3-D:12.2, 2-D: 15.6). Based on 2-D calculations, cAGV ≥ 433 mm3/kg was best for prediction of PTB (sensitivity: 75%, 95% CI = 59 to 87; specificity: 89%, 95% CI = 82 to 94). Sensitivity and specificity for the 3-D cAGV (cutoff ≥ 420 mm3/kg) was 85% (95% CI = 70 to 94) and 95% (95% CI = 90 to 98), respectively. In receiver-operating-curve curve analysis, 3-D cAGV was superior to 2-D cAGV for prediction of PTB (z = 1.99, p = 0.047)., Conclusion: 2-D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3-D AGV calculations for prediction of PTB., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The present study was conducted to determine the impact of suppressing trophoblast remodeling of the uterine spiral arteries by prematurely elevating estrogen levels in the first trimester of baboon pregnancy on uterine and umbilical blood flow dynamics. Uteroplacental blood flow was assessed by Doppler ultrasonography after acute administration of saline (basal state) and serotonin on days 60, 100, and 160 of gestation (term: 184 days) to baboons in which uterine spiral artery remodeling had been suppressed by the administration of estradiol on days 25-59 of gestation. Maternal blood pressure in the basal state was increased (P < 0.01), and uterine artery diastolic notching and the umbilical artery pulsatility index and systolic-to-diastolic ratio, reflecting downstream flow impedance, were increased (P < 0.01) after serotonin administration on day 160, but not earlier, in baboons treated with estradiol in early gestation. These changes in uteroplacental flow dynamics in serotonin-infused, estradiol-treated animals were accompanied by a decrease (P < 0.05) in uterine and umbilical artery volume flow and fetal bradycardia. The results of this study show that suppression of uterine artery remodeling by advancing the rise in estrogen from the second trimester to the first trimester disrupted uteroplacental blood flow dynamics and fetal homeostasis after vasochallenge late in primate pregnancy.

Objective: To determine which prenatal ultrasound findings indicate the need to also obtain PCR studies for viral genome in women undergoing midtrimester amniocentesis., Methods: This was a retrospective observational study on women that underwent amniotic fluid karyotyping and viral PCR testing for history or ultrasound based indication. Amniotic fluid was tested for adenovirus, cytomegalovirus, respiratory syncytial virus, enterovirus, Epstein-Barr virus, and parvovirus B19 using multiplex PCR study with multiple appropriate controls. Ultrasound findings were coded as normal or abnormal with 34 categories of ultrasound abnormality stratified into 18 subgroups. Relationships between these subgroups and karyotype/PCR results were tested by Pearson chi-square method or Fisher's exact test and overall logistic regression analysis., Results: Amniotic fluid samples from 1191 patients were obtained for the study. Abnormal karyotype was detected in 5.4% of cases (64/1191), and PCR was positive in 6.5% of cases (77/1191). Abnormal fetal ultrasonographic findings were observed in 28.4% of cases (338/1191). There was an association between intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies or neural tube defects (NTDs), and PCR positivity. NTDs were associated with PCR positivity in fetuses with normal karyotype and nuchal thickening, cardiac or ventral wall defects were specifically associated with aneuploidy., Conclusion: Amniotic fluid viral PCR testing should be considered for fetuses with intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies, or NTDs. After aneuploidy is excluded, NTDs are associated with PCR positivity., (© 2012 John Wiley & Sons, Ltd.)

Objective: To study if the duration of individual Doppler abnormalities is an independent predictor of adverse outcome in fetal growth restriction (FGR) caused by placental dysfunction., Methods: This was a secondary analysis of patients with FGR (abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index (PI) elevation) who had at least three examinations before delivery. Days of duration of absent/reversed UA end-diastolic velocity (UA-AREDV), low middle cerebral artery PI (brain sparing), ductus venosus (DV) and umbilical vein Doppler abnormalities were related to stillbirth, major neonatal morbidity and intact survival., Results: One hundred and seventy-seven study participants underwent a total of 1069 examinations. The duration of an absent/reversed a-wave in the DV (DV-RAV) was significantly higher in stillbirths (median, 6 days) compared with intact survivors and those with major morbidity (median, 0 days for both; P = 0.006 and P = 0.001, respectively). Duration of brain sparing was also longer in stillbirth cases compared with intact survivors (median, 19 days vs. 9 days, P = 0.02). Stepwise multinomial logistic regression showed that gestational age at delivery was a significant codeterminant of outcome for all arterial Doppler abnormalities when the DV a-wave was antegrade. However, when present, the duration of DV-RAV was the only contributor to stillbirth (probability of stillbirth = 1/(1 + exp - (interval to delivery × 1.03 - 2.28)), r2 = 0.73). Receiver-operating characteristics curve statistics showed that a DV-RAV for > 7 days predicted stillbirth (100% sensitivity, 80% specificity, likelihood ratio = 5.0, P < 0.0001). In contrast, neither neonatal death nor neonatal morbidity was predicted by the days of persistent DV-RAV., Conclusions: The duration of absent or reversed flow during atrial systole in the DV is a strong predictor of stillbirth that is independent of gestational age. While prematurity remains the strongest predictor of neonatal risks it is unlikely that pregnancy can be prolonged by more than 1 week in this setting., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: The objective of the study was to test whether ultrasound-measured fetal adrenal gland volume (AGV) and fetal zone enlargement (FZE) predicts preterm birth (PTB) better than cervical length (CL)., Study Design: Three-dimensional and 2-dimensional ultrasound were used prospectively to measure fetal AGV, FZE, and CL in women with preterm labor symptoms. We corrected AGV for fetal weight (cAGV). The ratio between whole gland depth (D) and central fetal zone depth (d) (d/D) was used to measure FZE. Ability of cAGV, d/D, and CL to predict PTB 7 days or less was compared., Results: Twenty-seven of 74 women (36.5%) presenting between 21 and 34 weeks had PTB of 7 days or less. FZE greater than 49.5% was the single best predictor for PTB (sensitivity/specificity 100%/89%) compared with cAGV (81%/87%) and CL (56%/60%; P < .05). Prediction was independent of obstetrics history and tocolytic use., Conclusion: The 2-dimensional measurement of the adrenal gland FZE is highly effective performing superior to CL in identifying women at risk for PTB within 7 days., (Published by Mosby, Inc.)

Although estrogen regulates important aspects of maternal cardiovascular physiology, the role of estrogen on uteroplacental and fetal blood flow is incompletely understood. This study tested the hypothesis that chronically suppressing endogenous estrogen production during the second half of baboon pregnancy alters uterine and fetal blood flow dynamics assessed by ultrasonography. Pregnant baboons were untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus estradiol on days 100-160 of gestation (term = 184 days). Blood flow dynamics were determined by Doppler ultrasonography on day 60 and longitudinally between days 110 and 160 of gestation. Letrozole decreased maternal serum estradiol and estrone concentrations by 95% (P < 0.001). Fetal growth biometrical parameters increased (P < 0.001) between days 110 and 160 of gestation and were similar in untreated and letrozole-treated animals. Uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index declined (P < 0.01) by 30-50% and uterine artery volume flow increased sixfold (P < 0.001) between days 60 and 160, but values were similar in untreated, letrozole-treated, and letrozole plus estradiol-treated baboons. Thus uterine and fetal artery blood flow indexes, uterine artery volume flow, and fetal growth were maintained at normal levels despite chronic estrogen suppression in the second half of baboon pregnancy. This suggests that elevated levels of endogenous estrogen are not required to maintain low impedance blood flow within the uteroplacental vascular bed during the second half of nonhuman primate pregnancy.

Objective: Pentraxin (PTX)-3 is an inflammatory molecule that may be increased in the first trimester in pregnancies with subsequent preeclampsia. We measured first-trimester serum PTX-3 and correlated levels with maternal/placental factors related to placental development., Study Design: Prospectively enrolled women had ultrasound, physical examination, and blood draw at 11-14 weeks. PTX-3 determined by enzyme-linked immunosorbent assay was related to maternal age, parity, race, body mass index (BMI), mean arterial blood pressure (MAP), smoking/caffeine, and uterine/umbilical artery Doppler pulsatility index (PI)., Results: In 111 patients PTX-3 levels ranged from 0.2-13.8 ng/mL. Spearman correlation between PTX-3 and gestational age (rho = 0.096), maternal age (rho = -0.049), BMI (rho = -0.07), MAP (rho = -0.085), mean uterine artery PI (rho = 0.150), and umbilical artery PI (rho = -0.021) was nonsignificant (all P > .05). Similarly, PTX-3 distribution was unaffected by smoking/caffeine use, BMI >30, MAP >100 mm Hg, or uterine artery notching (P > .05 for all)., Conclusion: First-trimester PTX-3 is unrelated to maternal characteristics and placental Doppler.

Purpose: To assess the added value of 3-dimensional (3D) echocardiography with spatiotemporal image correlation (STIC) in the diagnosis of aortic arch abnormalities in fetuses with isolated abnormal upper thoracic 3-vessel view (3VV)., Method: A total of 3,420 women underwent a targeted anatomic survey at 18-22 weeks' gestation in a 1-year period. An isolated abnormal upper thoracic 3VV detected on 2-dimensional (2D) imaging was followed up by conventional 2D echocardiography and 3D fetal echocardiography with STIC. Offline reconstruction by a second operator blinded to the suspected diagnosis was performed. Neonatal echocardiography and MRI with 3D reconstruction were performed to verify the prenatal diagnosis., Result: Of the 3,420 patients referred, 4 had an isolated abnormal 3VV (0.09%). A right-sided aortic arch (RAA, n = 3) and double aortic arch (DAA, n = 1) were suspected. In all aortic arch abnormalities, 3D fetal echocardiography and STIC correctly identified RAA with aberrant left subclavian artery in 3 cases and DAA in 1 case with a degree of definition that was equal to the confirmatory postnatal echocardiography and 3D MRI., Conclusion: Although the 2D upper 3VV is a powerful screening tool for isolated aortic arch abnormalities, 3D fetal echocardiography with STIC allows an accurate prenatal characterization of the abnormality to a degree that is typically attainable only by post partum imaging.

Objective: The challenges of the first-trimester examination of the fetal heart may in part be overcome by technical advances in three-dimensional (3D) ultrasound techniques. Our aim was to standardize the first-trimester 3D imaging approach to the cardiac examination to provide the most consistent and accurate display of anatomy., Methods: Low-risk women with normal findings on first-trimester screening at 11 to 13 + 6 weeks had cardiac ultrasound using the following sequence: (1) identification of the four-chamber view; (2) four-dimensional (4D) volume acquisition with spatiotemporal image correlation (STIC) and color Doppler imaging (angle = 20 degrees, sweep 10 s); (3) offline, tomographic ultrasound imaging (TUI) analysis with standardized starting plane (four-chamber view), slice number and thickness; (4) assessment of fetal cardiac anatomy (four-chamber view, cardiac axis, size and symmetry, atrioventricular valves, great arteries and descending aorta) with and without color Doppler., Results: 107 consecutive women (age, 16-42 years, body mass index 17.2-50.2 kg/m(2)) were studied. A minimum of three 3D volumes were obtained for each patient, transabdominally in 91.6%. Fetal motion artifact required acquisition of more than three volumes in 20%. The median time for TUI offline analysis was 100 (range, 60-240) s. Individual anatomic landmarks were identified in 89.7-99.1%. Visualization of all structures in one panel was observed in 91 patients (85%)., Conclusion: Starting from a simple two-dimensional cardiac landmark-the four-chamber view-the standardized STIC-TUI technique enables detailed segmental cardiac evaluation of the normal fetal heart in the first trimester., ((c) 2009 ISUOG.)

We applied the concept of umbilical arterial and venous (A-V) blood gas difference in evaluating placental respiratory function to establish normative values for these relationships. Umbilical A-V cord blood gas samples were obtained in standardized fashion in uncomplicated singleton pregnancies. A-V pO (2) and A-V pCO (2) differences were related to obstetric factors, placental weight, and gestational age. Mean absolute differences in uncomplicated vaginal deliveries between umbilical artery and umbilical vein were: pO (2) 11.4 +/- 7.0 mm Hg and pCO (2) 11.9 +/- 6.8 mm Hg. Values in nonlabor cesarean section cases did not differ significantly from those of cases delivered vaginally. A-V pO (2) differences did not vary significantly across gestation (Pearson's R = 0.05, P = 0.43) and did not correlate with birth weight ( R = 0.06, P = 0.30). A-V pCO (2) differences showed increases with gestational age ( R = 0.15, P = 0.008) and with birth weight ( R = 0.18, P = 0.002). Results similar to those of women delivered vaginally were seen in nonlabor cesarean deliveries. Duration of labor did not impact the A-V blood gas relationship. Umbilical A-V oxygen differences reflect placental respiratory function independent of gestational age, birth weight, duration of labor, and mode of delivery. They are easy to collect and represent a potentially valuable resource for assessment of placental function.

Objective: We have previously described placental oxygenation capacity as an index of placental function. The aim of this study was to utilize this test to evaluate placental gas exchange capacity in pre-eclampsia and fetal growth restriction (FGR)., Study Design: Two nested case-control studies were conducted between: (i) pre-eclamptic appropriate-for-gestational-age fetus (AGA) and non-pre-eclamptic AGA; and (ii) pre-eclamptic FGR and non-pre-eclamptic FGR based on gestational age match. Umbilical A-V gas differences were compared between groups., Results: Pre-eclamptic AGA was associated with smaller A-V pO(2) and A-V pCO(2) differences compared to non-pre-eclampsia (A-V pO(2), 7.1+/-3.8 mm Hg vs. 11.3+/-5.9 mm Hg, P=0.001; A-V pCO(2), 7.8+/-5.7 mm Hg vs. 10.7+/- 5.9 mm Hg, P=0.01). Pre-eclamptic FGR was associated with smaller A-V pO(2) and A-V pCO(2) differences compared to non-pre-eclampsia (A-V pO(2), 6.6+/-3.1 mm Hg vs. 10.8+/-8.1 mm Hg, P<0.001; 6.7+/-4.5 mm Hg vs. 10.9+/-10.3 mm Hg, P=0.044). Pre-eclamptic FGR also had significantly lower venous pO(2) but not arterial pO(2) (Venous pO(2), 20.3+/-6.3 mm Hg vs. 25.4+/-11.9 mm Hg, P=0.003)., Conclusion: Pre-eclampsia decreases the placental oxygenation capacity as measured by the umbilical arterial-venous oxygen difference.

The complex nature of amniotic fluid reflects contributions from many fetal systems, many functional roles, and multiple interactions with fetal maturation, obstetric, and maternal factors. Simple ultrasound measurement, probably done best with the maximum vertical pocket method, has a clinical role in fetal surveillance, substantiated by extensive level II and some level I evidence. Interventions (amnioinfusion for oligohydramnios, amnioreduction for polyhydramnios) have not been studied effectively in controlled fashion, with the exception of intrapartum applications, where effective reduction of cesarean delivery for fetal distress and perinatal impacts of meconium aspiration may follow amnioinfusion. A wealth of research opportunities exists into regulation of amniotic fluid constituents and their relation to preterm delivery.

Objective: To identify the sequence of progression of arterial and venous Doppler abnormalities from the onset of placental insufficiency in intrauterine growth restriction (IUGR)., Methods: Prospective observational study of singletons with IUGR (abdominal circumference < 5(th) percentile) who underwent serial standardized umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV) Doppler surveillance. Time intervals between progressive Doppler abnormalities and patterns of deterioration were related to UA Doppler status and gestational age., Results: Six hundred and sixty-eight longitudinal examinations were performed in 104 fetuses, identifying three patterns of progression: (1) Mild placental dysfunction (n = 34) that remained confined to the UA/MCA. The UA became abnormal at a median of 32 weeks' gestation but the pulsatility index never exceeded 3 SD above normal. Progression took a median of 33 days, requiring delivery at a median of 35 weeks. (2) Progressive placental dysfunction (n = 49). Initially normal UA Doppler PI at 29 weeks' gestation increased beyond 3 SD, progressing to abnormal MCA, absent/reversed UA diastolic flow, abnormal DV, UV pulsations in 9-day intervals requiring delivery by 33 weeks. (3) Severe early-onset placental dysfunction (n = 21). Markedly elevated UA PI established by 27 weeks' gestation was associated with rapid (7-day intervals) progression to abnormal venous Doppler with median delivery at 30.6 weeks. Gestational age at onset, time to delivery and progression intervals were different between patterns (all P < 0.05)., Conclusion: The characteristics of cardiovascular manifestations in IUGR are determined by the gestational age at onset and the severity of placental disease. Recognition of these factors is critical for planning fetal surveillance in IUGR., ((c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: The purpose of this study was to test the hypothesis that multivessel fetal Doppler imaging provides enhanced prediction of necrotizing enterocolitis (NEC) in preterm placental insufficiency., Study Design: Placental-based growth-restricted fetuses (abdominal circumference <5%, abnormal umbilical artery [UA] Doppler imaging) were examined. UA, middle cerebral artery, ductus venosus, and umbilical vein (UV) were evaluated prenatally and were assessed for their ability to predict NEC in neonates who were delivered at <37 weeks of gestation., Results: Thirty-nine of 404 neonates (9.7%) experienced NEC. Among these, the mortality rate was 15.4% (6/39 neonates; odds ratio, 2.7; 95% CI, 1.03-7.11). NEC cases had higher UA Doppler indices prenatally (P = .023), lower gestational ages and birthweight at delivery (P < .0001, respectively), 5-minute Apgar scores of <7, and higher umbilical cord artery base deficit (P < .01, respectively). NEC was more likely after prenatal UV pulsations (odds ratio, 2.4; 95% CI, 1.13-5.14; P = .028) and severe cardiovascular abnormality (composite variable incorporating UA- absent or reversed end diastolic velocity, absent or reversed ductus venosus a-wave, or UV pulsations; odds ratio, 2.1; 95% CI, 1.06-4.05; P = .029) Logistic regression revealed birthweight and base deficit as the main contributors of NEC (r(2) = 0.20; P < .0001). Receiver operating characteristic analyses revealed birthweight of <790 g (sensitivity, 74.4%; specificity, 72.9%; P < .0001) and gestational age of < or =32.2 weeks (sensitivity, 94.9%; specificity, 45.8%; P < .0001) as optimal cut-offs that provide an odds ratio for NEC of 8.2 (95% CI, 3.9-17.6; P < .0001)., Conclusion: Placental disease predisposes the severely growth-restricted neonate to necrotizing enterocolitis. Even when arterial and venous Doppler variables are taken into consideration, birthweight remains the predominant risk factor for NEC. Further research should focus on the critical transition to neonatal life to identify relevant triggers in predisposed neonates.

Background: The most common significant complication of total thyroidectomy is hypoparathyroidism. Intraoperative prediction of which patients are likely to be affected would allow both intraoperative and postoperative interventions to be utilised in these patients. Selection of these patients is essential if we are to be successful at discharging total thyroidectomy patients on the first postoperative day. We investigated the utility of intraoperative parathormone measurement from the internal jugular vein at predicting postoperative hypocalcaemia., Materials and Methods: Prospective collection of data was done on 45 consecutive total thyroidectomy patients. Preoperative calcium, intraoperative parathormone and postoperative calcium and parathormone were collected. The accuracy of intraoperative parathormone in predicting those with postoperative hypocalcaemia was assessed., Results: Intraoperative parathormone of less than 2 pmol l(-1) had a sensitivity of 100% and a specificity of 95% in predicting those with postoperative hypocalcaemia. An intraoperative sample less than 2 pmol l(-1) was a highly significant predictor (p < 0.0001) of postoperative hypocalcaemia., Conclusion: Intraoperative assessment of parathormone is an accurate predictor of those patients who will become hypoparathyroid in the postoperative period. Intraoperative prediction allows for targeted autotransplantation of glands in those at risk and selected early institution of postoperative supplementation in these patients. Patients not identified as at risk can be safely discharged.

Objective: The purpose of this study was to identify physiologic determinants of the peak systolic blood flow velocity (PSV) of the middle cerebral artery (MCA) in the human fetus., Study Design: MCA PSV was measured with pulsed wave Doppler ultrasound in human fetuses who underwent cordocentesis. Hemoglobin, hematocrit, and blood gas values were analyzed from umbilical venous blood, and the data were normalized for gestational age. Total oxygen content of fetal venous blood was calculated from oxygen saturation, hemoglobin value, and pO2. Correlation and logistic regression analyses were performed to identify primary physiologic determinants of MCA PSV., Results: In 136 fetuses who underwent cordocentesis (predominantly for alloimmune disease), hematocrit, hemoglobin, and blood oxygen content correlated significantly with the MCA PSV (P < .01). Logistic regression modeling demonstrated that fetal hemoglobin content (odds ratio, 7.1; 95% CI, 3.71-13.7) and pCO2, but not pO2 or fetal blood oxygen content, accounted for increases in MCA PSV., Conclusion: Under physiologic circumstances, fetal hemoglobin, and not fetal oxygenation, primarily determines the middle cerebral artery peak systolic velocity.

Objective: Nucleated red blood cells (NRBC) are fetal hematologic markers for placental dysfunction, hypoxemia, and asphyxia. NRBC count elevation at birth or persistence is linked statistically to adverse outcome, but clinical predictive value is variable. We studied novel indices to better define overall magnitude of NRBC response., Study Design: Peripheral NRBC count was obtained from preterm (<34 weeks of gestation) growth-restricted neonates within 2 hours of life. Daily counts and duration of NRBC count >30/100 white blood cells were determined. Mean counts (NRBC-mean), area under the curve (NRBC-AUC), and declination (NRBC-slope) were analyzed over week 1. NRBC parameters were related to major morbidity (bronchopulmonary dysplasia, grade III/IV intraventricular hemorrhage, necrotizing enterocolitis included) and neonatal death (NND)., Results: Twenty-two of 176 patients (12.5%) had acidosis. Complications included bronchopulmonary dysplasia (n = 36; 20.5%), intraventricular hemorrhage (n = 18; 10.2%), necrotizing enterocolitis (n = 18; 10.2%), NND (n = 18; 10.2%). NRBC-AUC and NRBC-mean correlated most strongly with pH, birthweight, and gestational age (Pearson coefficient -0.45 to -0.18; all P < .001). NRBC-AUC varied most between nonmorbid and morbid; NRBC-mean varied most between survivors and NND (all P < .001). NRBC persistence strongly predicted NND: clearance by day 4 was achieved by 80% of survivors and only 35% of NNDs. Logistic regression identified prematurity and persistent NRBC counts as primary morbidity determinants (r2 = 0.56; P < .01). Although the importance of individual NRBC counts varied, day-4 NRBC counts of >70 predicted morbidity best (sensitivity, 82%; specificity, 96%). Presence of morbidity and birthweight were prime determinants of death (r2 = 0.42; P < .01)., Conclusion: Simple daily NRBC counts provide clinical information that is equivalent to more complicated methods. The importance of prematurity and growth are emphasized, but elevated NRBC counts beyond day 3 are relevant independent predictors of adverse outcome.

Fetoscopic laser ablation of placental vascular anastomoses is an intrauterine therapy targeting the source of twin-to-twin transfusion syndrome (TTTS). Our patient had successful laser treatment, with resolution of stage II TTTS, suggesting closure of all significant anastomoses. After an uneventful pregnancy course, she elected a trial of labor. Following spontaneous onset of labor, acute intrapartum twin-to-twin transfusion was suspected, suggested by sinusoidal heart rate changes, confirmed postdelivery by twins' complete blood counts. The potential risks of labor with prior fetoscopic laser ablation are reviewed in the context of current knowledge about placental architecture in TTTS.

Objective: To evaluate the relationship between umbilical artery end diastolic velocity in growth restricted fetuses and neonatal hematologic parameters., Study Design: Growth restricted fetuses were studied with ultrasound and Doppler evaluations. Neonates were analyzed in two groups based on umbilical artery Doppler status: positive end-diastolic velocities (PEDV) and absent or reversed end-diastolic velocities (AEDV). At birth and throughout the first week of life, groups were compared for anemia and thrombocytopenia; transfusion of red blood cells, platelets, and fresh frozen plasma; and intraventricular hemorrhage (IVH)., Results: Seventy-three neonates met inclusion criteria, 38 with PEDV, 35 with AEDV. Those with AEDV were delivered 3 weeks earlier, were 450 g smaller, had lower cord arterial pH values, and greater cord artery base deficits (p<0.05, respectively). AEDV neonates were twice as likely to be anemic and thrombocytopenic at birth and remain so during the first week, requiring more red blood cell and platelet transfusions. There was no difference in occurrence of severe IVH between groups., Conclusion: Hematological alterations associated with intrauterine growth restriction appear to continue into the first week of neonatal life. These are proportional to the degree of placental dysfunction and are predicted by fetal Doppler status., Summary: Abnormal development of the placental vascular tree is the primary step in a cascade of fetal compromises leading to intrauterine growth restriction (IUGR). Doppler ultrasound evaluation of fetal and placental blood flows provides a non-invasive assessment of the fetal condition which reflects the impact of placental vascular abnormalities. The degree of placental dysfunction determines the severity of fetal disease, which can affect many fetal organ systems. In addition to disturbances in placental respiratory function, abnormal umbilical artery Doppler status is also indicative of hematologic abnormalities during fetal life and at birth. Neonates who had more severe placental dysfunction, as depicted by absent umbilical artery end diastolic velocity, were more likely to be anemic and thrombocytopenic at birth and remain so during the first week of life, and required more transfusions than those with positive end diastolic velocities. The severity of hematologic alterations during the first week of life in growth restricted neonates was proportional to and predicted by the antenatal umbilical artery end diastolic velocity Doppler status.