Prenatal Diagnosis of Fetal Aqueductal Stenosis: A Multicenter Prospective Observational Study through the North American Fetal Therapy Network.

INTRODUCTION: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention. METHODS: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe central nervous system (CNS) ventriculomegaly (lateral ventricle diameter >15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and magnetic resonance imaging (MRI) were calculated, as was the mean gestational age at diagnosis. RESULTS: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives, rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7 weeks). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n = 35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average. CONCLUSION: The prenatal diagnosis of fetal AS can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience.

The Impact of Spontaneous versus Indicated Preterm Birth on Neonatal Outcomes among Extremely Premature Neonates.

OBJECTIVE: This study aimed to investigate whether neonatal morbidity differs in spontaneous compared with indicated preterm births in extremely premature neonates. STUDY DESIGN: This is a retrospective cohort study including births ≤28 weeks at a single institution from 2011 to 2020. Births were categorized as either medically indicated or spontaneous preterm deliveries. The primary outcome was inhospital mortality and serious morbidity in survivors. t-tests, Fisher's exact tests, chi-square tests, and logistic regression models were utilized as appropriate. p < 0.05 was significant. RESULTS: Two hundred and twenty-seven births were included, with two-thirds representing spontaneous births (65.6%, 149/227) and one-third categorized as medically indicated births (34.4%, 78/227). Inhospital mortality was more common in the spontaneous preterm birth group (p = 0.04), while inhospital morbidity did not significantly vary between the medically indicated and spontaneous birth groups (p = 0.32). There was no difference in inhospital morbidity or mortality by maternal race. In multivariate models of inhospital morbidity and mortality, gestational age was the only significant predictor of adverse outcomes. CONCLUSION: Despite inhospital mortality being more common in spontaneous preterm births, inhospital mortality and significant morbidity are best accounted for by gestational age alone. KEY POINTS: · Inhospital death is more common in spontaneous preterm births.. · Perinatal outcomes do not differ on the basis of racial/ethnic group.. · Gestational age is the best predictor of inhospital morbidity and mortality..

Timing of birth and adverse pregnancy outcomes in cases of prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa. DATA SOURCES: Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022. STUDY ELIGIBILITY CRITERIA: The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth. METHODS: Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions. RESULTS: The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from <32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score <7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score <7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation. CONCLUSION: Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa.

Umbilical Vein Pulse Wave Spectral Analysis: A Possible Method for Placental Assessment Through Evaluation of Maternal and Fetal Flow Components.

OBJECTIVES: Placental blood flow analysis is complicated by having both maternal and fetal flow components. Using the Fast Fourier Transform (FFT) of the umbilical venous pulse wave spectra (PW) envelope, we could simultaneously assess maternal/fetal blood flow in the placenta and investigate if normal and intrauterine growth restriction (IUGR)/pre-eclamptic pregnancies could be distinguished. METHODS: This retrospective study included normal gestations (N = 11) and gestations with IUGR, pre-eclampsia, or both (N = 13). Umbilical vein PW were acquired and spectral envelopes were identified as a function of time and analyzed by FFT. Base-10 logarithms of the ratios of the maternal/fetal spectral peaks (LRSP) were compared in normal and IUGR/pre-eclamptic populations (two-tailed t-test). Body mass index (BMI), gestational age at scan time, placental position, and weight-normalized umbilical vein blood volume flow (two-tailed t-test, analysis of variance [ANOVA] analysis) were tested. P < .05 was considered significant. RESULTS: The LRSP for normal and IUGR/pre-eclamptic pregnancies were 0.141 ± 0.180 and -0.072 ± 0.262 (mean ± standard deviation), respectively (P = .033). We detected differences between normal gestations and combinations of LRSP and weight-normalized umbilical venous blood flows. Placental effects based on LRSPs and blood flow may act synergistically in cases with both pre-eclampsia and IUGR (P = .014). No other significant associations were seen. CONCLUSIONS: In this preliminary study, we showed that umbilical venous flow contains markers related to placental maternal/fetal blood flow, which can be used to assess IUGR and pre-eclampsia. When coupled with umbilical cord blood flow, this new marker may potentially identify the primary causes of the two conditions.

Placental Location in Maternal-Fetal Surgery for Myelomeningocele.

INTRODUCTION: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes. OBJECTIVE: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure. METHODS: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations. RESULTS: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location. CONCLUSIONS: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes.

Comparison of Variations Between Spectral Doppler and Gaussian Surface Integration Methods for Umbilical Vein Blood Volume Flow.

OBJECTIVES: We are studying a new method for estimating blood volume flow that uses 3-dimensional ultrasound to measure the total integrated flux through an ultrasound-generated Gaussian surface that intersects the umbilical cord. This method makes none of the assumptions typically required with standard 1-dimensional spectral Doppler volume flow estimates. We compared the variations in volume flow estimates between techniques in the umbilical vein. METHODS: The study was Institutional Review Board approved, and all 12 patients gave informed consent. Because we had no reference standard for the true umbilical vein volume flow, we compared the variations of the measurements for the flow measurement techniques. At least 3 separate spectral Doppler and 3 separate Gaussian surface measurements were made along the umbilical vein. Means, standard deviations, and coefficients of variation (standard deviation/mean) for the flow estimation techniques were calculated for each patient. P < .05 was considered significant. RESULTS: The ranges of the mean volume flow estimates were 174 to 577 mL/min for the spectral Doppler method and 100 to 341 mL/min for the Gaussian surface integration (GSI) method. The mean standard deviations (mean ± SD) were 161 ± 95 and 45 ± 48 mL/min for the spectral Doppler and GSI methods, respectively (P < .003). The mean coefficients of variation were 0.46 ± 0.17 and 0.18 ± 0.14 for the spectral Doppler and GSI methods respectively (P < 0.002). CONCLUSIONS: The new volume flow estimation method using 3-dimensional ultrasound appears to have significantly less variation in estimates than the standard 1-dimensional spectral Doppler method.

Fetal Surgery in the Primate 4.0: A New Technique 30 Years Later.

INTRODUCTION: Open fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. For over 30 years, the standard of care for hysterotomy in the gravid uterus has been the AutoSuture Premium Poly CS*-57 stapler. OBJECTIVE: In this study, we sought to test the feasibility of hysterotomy in a rhesus monkey model with the Harmonic ACE®+7 Shears. METHODS: A gravid rhesus monkey underwent midgestation hysterotomy at approximately 90 days of gestation (2nd trimester; term = 165 ± 10 days) using the Harmonic ACE®+7 Shears. A two-layer uterine closure was completed and the dam was monitored by ultrasound intermittently throughout the pregnancy. At 58 days after hysterotomy (near term), a final surgery was performed to evaluate the uterus and hysterotomy site. RESULTS: A 3.5-cm hysterotomy was completed in 2 min 7 s. The opening was hemostatic and the membranes were sealed. Immediately after closure and throughout the pregnancy, ultrasound revealed intact membranes without separation and normal amniotic fluid levels. At term, the scar was well healed without signs of thinning or dehiscence. CONCLUSIONS: The Harmonic ACE®+7 Shears produced a hemostatic midgestation hysterotomy with membrane sealing in the rhesus monkey model. Importantly, healing was acceptable.

Calculating Observed-to-Expected Total Fetal Lung Volume in CDH Fetuses in Twin Gestation: Is There a Better Way?

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a potentially lethal birth defect, and identifying prenatal predictors of outcome is important. Observed-to-expected total fetal lung volume (o/e TFLV) has been shown to be a predictor of severity and useful in risk stratification but is variable due to different TFLV formulas. OBJECTIVES: To calculate o/e TFLV for CDH patients part of a twin gestation using the unaffected sibling as an internal control and comparing these values to those calculated using published formulas for TFLV. METHODS: Seven twin gestations with one fetus affected by CDH were identified between 2006 and 2017. The lung volume for each twin was calculated using magnetic resonance imaging (MRI), and o/e TFLV was calculated using the unaffected twin's TFLV. This percentage was then compared to the o/e TFLV calculated using published formulas. RESULTS: Lung volumes in the unaffected twins were within normal ranges at the lower end of the spectrum. No single TFLV formula was found to correlate perfectly. Intraclass correlation coefficient estimate was most consistent for o/e TFLV calculated with the Meyers formula and supported by Bland-Altman plots. CONCLUSIONS: O/e TFLV measured in CDH/non-CDH twin gestations using the unaffected sibling demonstrated agreement with o/e TFLV calculated using the Meyers formula. We urge the fetal community to standardize the method, use, and interpretation of fetal MRI in the prenatal evaluation of CDH.

Subsequent pregnancy outcomes after open maternal-fetal surgery for myelomeningocele.

BACKGROUND: Open maternal-fetal surgery for fetal myelomeningocele results in reduction in neonatal morbidity related to spina bifida but may be associated with fetal, neonatal, and maternal complications in subsequent pregnancies. OBJECTIVE: The objective of this study was to ascertain obstetric risk in subsequent pregnancies after open maternal-fetal surgery for fetal myelomeningocele closure. STUDY DESIGN: An international multicenter prospective observational registry created to track and report maternal, obstetric, fetal/neonatal, and subsequent pregnancy outcomes following open maternal-fetal surgery for fetal myelomeningocele was evaluated for subsequent pregnancy outcome variables. Institutional Review Board approval was obtained for the registry. RESULTS: From 693 cases of open maternal-fetal surgery for fetal myelomeningocele closure entered into the registry, 77 subsequent pregnancies in 60 women were identified. The overall live birth rate was 96.2%, with 52 pregnancies delivering beyond 20 weeks gestational age and median gestational age at delivery of 37 (36.3-37.1) weeks. The uterine rupture rate was 9.6% (n = 5), resulting in 2 fetal deaths. Maternal transfusion was required in 4 patients (7.7%). CONCLUSION: The risk of uterine rupture or dehiscence in subsequent pregnancies with associated fetal morbidity after open maternal-fetal surgery is significant, but is similar to that reported for subsequent pregnancies after classical cesarean deliveries. Future pregnancy considerations should be included in initial counseling for women contemplating open maternal-fetal surgery.

Prenatal Dilated Rectum: Do We Need to Worry?

BACKGROUND: Advances in prenatal imaging is increasing detection of abnormally dilated bowel. There is no literature to date defining the criteria for a dilated rectum or its association with postnatal pathology. The aim of this study is to investigate the clinical significance of a prenatally identified dilated rectum. METHODS: A retrospective review was performed of all cases of "dilated bowel" on prenatal ultrasound between January 2000 and December 2017 at a single institution. We excluded ventral wall defects from review and sought to include only cases of a prominent or dilated rectum. Collected data included prenatal bowel measurements, postnatal diagnoses, need for surgical intervention, and outcomes. Descriptive statistics were applied. RESULTS: One hundred and ninety-three cases of prenatal "dilated bowel" were identified in which 12 (6.2%) had specifically visualized a prominent or dilated rectum. Nine of these (75.0%) had no rectal or intestinal abnormality on postnatal evaluation and were discharged feeding and defecating normally. The remaining three cases exhibited clinical pathology necessitating additional management: (1) meconium plug, (2) jejunal atresia with cecal perforation, and (3) rectal perforation with retroperitoneal abscess. All three had rectal biopsies with identification of ganglionated submucosa. CONCLUSIONS: Although a prenatal dilated rectum is a normal variant in the vast majority of cases, it may be associated with a gastrointestinal abnormality requiring surgical intervention. Interestingly, there were no cases of Hirschsprung's disease or anorectal malformations in this cohort. These results, in conjunction with continued efforts to identify and define rectal dilation, are useful for prenatal counseling and postnatal evaluation.

An Early Investigation into Possible Alternatives to Stapled Hysterotomy in Open Fetal Surgery.

PURPOSE: We hypothesized that surgical energy could be used to create hysterotomies in open fetal surgery. STUDY DESIGN: Initial studies compared the LigaSure Impact and Harmonic ACE + 7 Shears in the efficiency of hysterotomy and thermal damage. Pregnant ewes at an estimated gestational age (EGA) of 116 to 120 days (term = 145; n = 7) underwent hysterotomy using either device. Hysterotomy edges were resected, and thermal injury extent was determined by histopathological assessment. Upon determining a superior device, subsequent studies compared this to the AutoSuture Premium Poly CS*-57 Stapler in uterine healing. Pregnant ewes (n = 6) at an EGA of 87 to 93 days underwent 6-cm hysterotomy in each gravid horn with either the stapler (n = 5) or Harmonic (n = 5) followed by closure and animal recovery. After 37 to 42 days, uterine healing was assessed by evaluating tensile strength and histopathology. RESULTS: Thermal damage was more extensive with the LigaSure (n = 11 hysterotomies) than with the Harmonic (n = 11; 5.6 ± 1 vs. 3.1 ± 0.6 mm; p < 0.0001);therefore, the Harmonic was selected for healing studies. Gross scar appearance and tensile strength were the same between the Harmonic and stapler. The stapler caused more fibrosis (4/7 samples with "moderate" fibrosis vs. 0/8 with the Harmonic; p = 0.02). CONCLUSION: The Harmonic ACE + 7 caused less thermal injury than the LigaSure Impact and performed similar to the CS*-57 Stapler in uterine healing with continued gestation.

Cutis Marmorata Telangiectatica Congenita Presenting as a Fetal Hemothorax.

We report a case of a fetus diagnosed at 28 weeks' gestation with a spontaneous prenatal hemothorax. Fetal intervention consisted of 2 thoracenteses with analysis of the pleural effusion. The pregnancy was further complicated by recurrence of the hemothorax, with subsequent mediastinal shift, hydrops, and nonreassuring antenatal testing requiring delivery at 31 weeks' gestation. Postnatal workup established the diagnoses of cutis marmorata telangiectatica congenita (CMTC) and pulmonary lymphangiectasia. The child is currently 4 years old and without any active medical issues or sequelae from the CMTC, pulmonary lymphangiectasia, or prenatal interventions.

Fetal Hydrops Secondary to in utero Pancytopenia.

Nonimmune hydrops remains a challenge in the prenatal setting with many cases not having a clear etiology determined prior to birth. We present an unusual case of one fetus of a dichorionic twin pair presenting at 24 weeks' gestation with hydrops and fetal pancytopenia with complete absence of white cells of unknown etiology, as revealed by cordocentesis. Serial red blood cell transfusions resulted in resolution of hydrops and continuation of the pregnancy until 35 weeks' gestation. Pancytopenia was noted throughout gestation and persisted in the newborn period. Moreover, the T-cell receptor excision circle (TREC) assay, a newborn screening test for severe T-cell deficiency, was abnormal at birth. Further evaluation revealed detectable TRECs and normal response to lymphocyte mitogens indicating some preserved thymic and lymphocyte function. The affected child had spontaneous resolution of the pancytopenia, including her severe T-cell deficiency, by 10 weeks of life. There has been no recurrence as of 24 months of age. The self-resolving nature of the pancytopenia is an important feature of this case of nonimmune hydrops. The abnormal TREC assay at birth in the affected infant may help explain the discordant prenatal findings.

Outcomes of fetuses with primary hydrothorax that undergo prenatal intervention (prenatal intervention for hydrothorax).

BACKGROUND: Primary hydrothorax is a congenital anomaly affecting 1 in 10,000-15,000 pregnancies. The natural history of this condition is variable with some fetuses having spontaneous resolution and others showing progression. The associated pulmonary hypoplasia leads to increased perinatal morbidity and mortality. Optimal prenatal intervention remains controversial. METHODS: After obtaining the Institutional Review Board approval, a retrospective review of all patients evaluated for a fetal pleural effusion in the Fetal Diagnosis and Treatment Center at The University of Michigan, between 2006 and 2016 was performed. Cases with secondary etiologies for an effusion or when families decided to pursue elective termination were excluded. RESULTS: Pleural effusions were identified in 175 patients. Primary hydrothorax was diagnosed in 15 patients (8%). The effusions were bilateral in 13/15 cases (86%) and 10/15 (66%) had hydrops at presentation. All 15 patients with primary hydrothorax underwent prenatal intervention. Thoracentesis was performed in 14/15 cases (93%). Shunt placement was performed in 10/15 cases (66%). Shunt migration was seen in four patients (40%) and all of these underwent prenatal shunt replacement. Overall survival was 76%. The rates of prematurity and preterm premature rupture of membranes were 69% and 35%, respectively. CONCLUSIONS: Fetal intervention for the treatment of primary hydrothorax is effective, and it appears to confer a survival advantage. Both the fetuses and the mothers tolerated the procedures well. Preterm labor and preterm premature rupture of membranes remain an unsolved problem. Further studies are needed to understand the mechanisms behind the development of fetal hydrothorax.

Associations of snoring frequency and intensity in pregnancy with time-to-delivery.

BACKGROUND: Sleep-disordered breathing (SDB) is linked to adverse pregnancy outcomes. However, little is known about the association of SDB with timing of delivery. We examined the association of snoring frequency, a key SDB marker, and snoring intensity, a correlate of SDB severity, with time-to-delivery among a cohort of pregnant women. METHODS: In this prospective cohort study, 1483 third trimester pregnant women were recruited from the University of Michigan prenatal clinics. Women completed a questionnaire about their sleep, and demographic and pregnancy information was abstracted from medical charts. After exclusion of those with hypertension or diabetes, 954 women were classified into two groups by their snoring onset timing, chronic or pregnancy-onset. Within each of these groups, women were divided into four groups based on their snoring frequency and intensity: non-snorers; infrequent-quiet; frequent-quiet; or frequent-loud snorers. Cox proportional hazard regression models were used to investigate the association between snoring frequency and intensity and time-to-delivery, adjusting for maternal characteristics. RESULTS: Chronic snoring was reported by half of the pregnant women, and of those, 7% were frequent-loud snorers. Deliveries before 38 weeks' gestation are completed occurred among 25% of women with chronic, frequent-loud snoring. Compared with pre-pregnancy non-snorers, women with chronic frequent-loud snoring had an increased hazard ratio for delivery (adjusted hazard ratio 1.60, 95% confidence interval 1.04, 2.45). CONCLUSIONS: Snoring frequency and intensity is associated with time-to-delivery in women absent of hypertension or diabetes. Frequent-loud snoring may have a clinical utility to identify otherwise low-risk women who are likely to deliver earlier.

Evaluation of Umbilical Vein Blood Volume Flow in Preeclampsia by Angle-Independent 3D Sonography.

OBJECTIVES: To investigate the association between umbilical vein blood volume flow and the condition of preeclampsia in an at-risk maternal patient cohort. Umbilical vein volume flow was quantified by a 3-dimensional (3D) sonographic technique that overcomes several limitations of standard sonographic flow measurement methods. METHODS: A total of 35 patients, each with a singleton pregnancy, were recruited to provide 5 patients with preeclampsia, derived as a subset from a 26-patient at-risk group, and 9 patients with normal pregnancies. An ultrasound system equipped with a 2.0-8.0-MHz transducer was used to acquire multivolume 3D color flow and power mode data sets to compute the mean umbilical vein volume flow in patients with normal pregnancies and preeclampsia. RESULTS: The gestational ages of the pregnancies ranged from 29.7 to 34.3 weeks in the patients with preeclampsia and from 25.9 to 34.7 weeks in the patients with normal pregnancies. Comparisons between patients with normal pregnancies and those with preeclampsia showed weight-normalized flow with a moderately high separation between groups (P = .11) and depth-corrected, weight-normalized flow with a statistically significant difference between groups (P = .035). Umbilical vein volume flow measurements were highly reproducible in the mean estimate, with an intrapatient relative SE of 12.1% ± 5.9% and an intrameasurement relative SE of 5.6% ± 1.9 %. In patients who developed pregnancy-induced hypertension or severe pregnancy-induced hypertension, umbilical vein volume flow suggested gestational hypertensive disorder before clinical diagnosis. CONCLUSIONS: Results indicate that mean depth-corrected, weight-normalized umbilical vein volume flow is reduced in pregnancies complicated by preeclampsia and that volume flow may indicate hypertensive disorder earlier in gestation. Volume flow measurements are highly reproducible, and further study in a larger clinical population is encouraged to determine whether 3D volume flow can complement the management of preeclampsia and, in general, at-risk pregnancy.

Early Delivery of Sacrococcygeal Teratoma with Intraspinal Extension.

Sacrococcygeal teratoma (SCT) with intraspinal extension is rare. There is a risk of paraplegia associated with prolonged spinal cord compression. We present the case of an infant with a prenatal diagnosis of an SCT with a large intraspinal component that was causing compression of the lower spinal cord. Ultrasound at 33 weeks showed bilateral lower extremity and foot movement without hydrops or cardiac failure. Multidisciplinary decision was made to administer betamethasone and proceed with Cesarean delivery at 34 weeks. A vigorous live-born female was delivered and a multilevel laminectomy was performed at day of life 4. The pelvic resection was performed at 4 months. Pathology revealed mature teratoma. She had an uncomplicated postoperative course, is ambulatory, continent of stool, and has no evidence of recurrence. We conclude that intraspinal extension of SCT should be evaluated prenatally with ultrasound and fetal MRI. If there is concern for spinal cord compression, early delivery and urgent decompressive laminectomy may diminish the neurologic sequelae of prolonged spinal cord compression. Since these cases are rare, risks of prematurity need to be weighed against the neurologic risks. These infants should be treated with a multidisciplinary approach.

In Utero Evidence of Impaired Somatic Growth in Hypoplastic Left Heart Syndrome.

We hypothesized that fetuses with hypoplastic left heart syndrome (HLHS) have impaired growth compared to expected growth for gestational age. This is a retrospective cohort study including singleton fetuses with isolated HLHS identified from a single, referral center's ultrasound database. To account for variable timing of ultrasounds, z-scores for gestational age were assigned for each biometric parameter. We identified 169 fetuses, of which 96 had more than one ultrasound. The median number of ultrasound evaluations per fetus was 2 (range 1-5). The mean gestational age at time of last ultrasound was 33.7 ± 4.3 weeks with a range of 20.4-39.6 weeks. While fetal growth restriction (11%) and microcephaly (3%) were relatively rare, mean z-scores at the time of last ultrasound for estimated fetal weight (mean difference z-score -0.20, p = 0.04) and head circumference (-0.28, p = 0.02) were lower than at the time of the initial ultrasound. Impaired somatic growth, defined as a decrement in z-score of 0.5 or more over time, was common (32%). There is a deceleration in somatic and head growth in fetuses with hypoplastic left heart syndrome that can be identified by routine ultrasound evaluation.

Effect of Glucose on 3D Cardiac Microtissues Derived from Human Induced Pluripotent Stem Cells.

Maternal hyperglycemia is a risk factor for fetal cardiac anomalies. This study aimed to assess the effect of high glucose on human induced pluripotent stem cell-derived cardiomyocyte self-assembly into 3D microtissues and their calcium handling. Stem cells were differentiated to beating cardiomyocytes using established protocols. On the final day of the differentiation process, cells were treated with control media, 12 mM glucose, or 12 mM mannitol (an osmolality control). Once beating, the cardiac cells were dissociated with trypsin, collected, mixed with collagen, and plated into custom-made silicone micro molds in order to generate 3D cardiac microtissues. A time-lapse microscope took pictures every 4 h to quantify the kinetics of cellular self-assembly of 3D cardiac tissues. Fiber widths were recorded at 4-h intervals and plotted over time to assess cardiomyocyte 3D fiber self-assembly. Microtissue calcium flux was recorded with optical mapping by pacing microtissues at 0.5 and 1.0 Hz. Exposure to high glucose impaired the ability of cardiomyocytes to self-assemble into compact microtissues, but not their ability to spontaneously contract. Glucose-exposed cardiomyocytes took longer to self-assemble and finished as thicker fibers. When cardiac microtissues were paced at 0.5 and 1.0 Hz, those exposed to high glucose had altered calcium handling with shorter calcium transient durations, but larger amplitudes of the calcium transient when compared to controls. Additional studies are needed to elucidate a potential mechanism for these findings. This model provides a novel method to assess the effects of exposures on the cardiomyocytes' intrinsic abilities for organogenesis in 3D.