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BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P

Objective This study aims to evaluate the utility of social media to distribute a patient survey on differences in management and outcomes of monochorionic–diamniotic (MCDA) pregnancies. Study Design A cross-sectional survey was posted to an English-language MCDA twins patient-centered support group within the social media site, Facebook from April 2, 2018 to June 26, 2018. Subjects were recruited through a technique called “snowballing,” whereby individuals shared the survey to assist with recruiting. Patient reported data were analyzed using Chi-square and Kruskal–Wallis's tests to explore characteristics associated with surveillance and outcomes as related to region and provider type. Results Over 3 months, the post “reached” 14,288 Facebook users, among which 5,653 (40%) clicked on the post. A total of 2,357 respondents with MCDA pregnancies completed the survey. Total 1,928 (82%) were from the United States (US) and 419 (18%) from other countries. Total 85% of patients had co-management with maternal–fetal medicine (MFM), more in the US compared with the rest of the world (87 vs. 74%, p Conclusion A survey distributed via social media can be effective in evaluating real-life management and outcomes of an uncommon obstetrical diagnosis. This survey elucidates wide international variation in adherence to guidelines, management, and outcomes.

Background During the early months of the coronavirus disease of 2019 (COVID-19) pandemic, risks to pregnant women of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were uncertain. Pregnant patients can serve as a model for the success of the clinical and public health response during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of SARS-CoV-2 infections in pregnancy are unknown due to incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early pandemic is poorly understood. Objective(s) To estimate the SARS-CoV-2 infection rate in pregnancy and examine disparities by race/ethnicity and English-language proficiency in Washington State. Study design Pregnant patients with a polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 1-June 30, 2020 were identified within 35 hospitals/clinic systems capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health (ACH) region and cross-sectionally compared to SARS-CoV-2 infection rates in similarly aged adults in Washington State. Race/ethnicity and language used for medical care among the pregnant patients were compared to recent data from Washington State. Results A total of 240 pregnant patients with SARS-CoV-2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study are: 1) The SARS-CoV-2 infection rate in pregnancy was 13.9/1,000 deliveries (95% confidence interval [CI], 8.3-23.2) compared to 7.3/1,000 (95%CI 7.2-7.4) in 20-39 year old adults in Washington State (Rate Ratio [RR] 1.7, 95%CI 1.3-2.3), 2) the SARS-CoV-2 infection rate reduced to 11.3/1000 (95%CI 6.3-20.3) when excluding 45 cases of SARS-CoV-2 detected through asymptomatic screening (RR 1.3, 95%CI 0.96-1.9), 3) the proportion of SARS-CoV-2 cases in pregnancy among most non-white racial/ethnic groups was 2-4 fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018, and 5) the proportion of SARS-CoV-2 infected pregnant patients receiving medical care in a non-English language was higher than estimates of limited English proficiency in Washington State (30.4% versus 7.6%). Conclusions The SARS-CoV-2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial/ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from COVID-19 in the early months of the pandemic with the greatest burden of infections occurring in nearly all racial/ethnic minority groups. This data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggests that pregnant people should be broadly prioritized for COVID-19 vaccine allocation in the U.S. similar to some states.

Background The impact of the coronavirus disease 2019 (Covid-19) on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease. Objective To describe maternal disease and obstetrical outcomes associated with Covid-19 disease in pregnancy to rapidly inform clinical care. Study Design Retrospective study of pregnant patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection from six hospital systems in Washington State between January 21, 2020 and April 17, 2020. Demographics, medical and obstetric history, and Covid-19 encounter data were abstracted from medical records. Results A total of 46 pregnant patients with a SARS-CoV-2 infection were identified from hospital systems capturing 40% of births in Washington State. Nearly all pregnant individuals with a SARS-CoV-2 infection were symptomatic (93.5%, n=43) and the majority were in their second or third trimester (43.5%, n=20 and 50.0%, n=23, respectively). Symptoms resolved in a median of 24 days (interquartile range 13-37). Seven women were hospitalized (16%) including one admitted to the intensive care unit. Six cases (15%) were categorized as severe Covid-19 disease with nearly all patients being either overweight or obese prior to pregnancy, asthma or other co-morbidities. Eight deliveries occurred during the study period, including a preterm birth at 33 weeks to improve pulmonary status in a woman with Class III obesity. One stillbirth occurred of unknown etiology. Conclusions Nearly 15% of pregnant patients developed severe Covid-19, which occurred primarily in overweight or obese women with underlying conditions. Obesity and Covid-19 may synergistically increase risk for a medically-indicated preterm birth to improve maternal pulmonary status in late pregnancy. Collectively, these findings support categorizing pregnant patients as a higher risk group, particularly for those with chronic co-morbidities.

Because they share a common placenta, monochorionic gestations are subject to unique pregnancy complications that can threaten the life and health of both fetuses and therefore impose a disproportionate disease burden on overall perinatal morbidity and mortality. Early detection of these unique disease processes may allow for prompt referral to a regional treatment center, comprehensive counseling, and better patient outcomes. The North American Fetal Therapy Network is a consortium of 30 medical institutions in the United States and Canada with established expertise in fetal surgery and other forms of multidisciplinary care for complex fetal disorders. The goal of this publication is to briefly describe complications of monochorionic gestations and to provide multidisciplinary, evidence-based, and consensus-driven recommendations for surveillance of uncomplicated monochorionic gestations.

BACKGROUND: Intrauterine transfusion for severe alloimmunization in pregnancy performed

Background The diagnosis of twin-to-twin transfusion syndrome (TTTS) usually relies the presence of polyhydramnios in one sac with concomitant oligohydramnios in the other sac in a monochorionic diamniotic twin pregnancy. However, TTTS does not always show a linear progression and may present with cardiac compromise or critically abnormal Doppler velocimetry in either fetus before fluid measurements meet the typically used cutoff. Objective The aim of this study was to investigate the prevalence of atypical presentations of TTTS in a population undergoing laser fetoscopy. Study Design We performed a retrospective review of our database of TTTS laser fetoscopy from 2003 to the present. Our center is the regional referral center in the Pacific Northwest for minimally invasive treatment of complicated monochorionic twin pregnancies. Cases were labeled as “atypical” if fluid discordance did not meet formal TTTS criteria (oligohydramnios defined as maximum vertical pocket [MVP] 8 before 20 weeks and >10 after 20 weeks). The rationale for consideration of laser fetoscopy was other evidence of severe TTTS such as significant cardiac compromise, evidence of twin anemia polycythemia sequence (TAPS), or persistent critically abnormal cord Dopplers. Results Three hundred seventy-nine cases of fetoscopic laser ablation for TTTS and its variants were available for review. Sixteen cases were excluded for a triplet pregnancy, 4 due to septostomy prior to referral to our center, 3 for monoamniotic pregnancy, and 11 for previous laser fetoscopy. Three hundred forty-five cases remained for evaluation. Among these, 25 cases were identified as “atypical,” equaling 7.24% of our population. Eleven of these were for stage 3 recipient disease, 3 were for stage 4 recipient disease, 4 were for stage 3 both in recipient and donor, 4 were for stage 3 donor disease, and 3 were for spontaneous TAPS. Conclusion In TTTS, severity of fetal compromise does not consistently correlate with fluid abnormalities meeting established criteria. This may be especially true in rapidly progressing cases. Attempts at rigid diagnostic amniotic fluid criteria may underestimate the severity and incidence of TTTS. This underscores the importance of careful surveillance, including arterial and venous Doppler velocimetry, of all monochorionic pregnancies.

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 High-order multifetal pregnancies carry a significant risk of obstetric complications and poor pregnancy outcome. Selective reduction has traditionally been performed using transabdominal and transvaginal ultrasound-guided intracardiac injection of potassium chloride. We have previously shown that high-intensity focused ultrasound (HIFU) can create a coagulative tissue necrosis in the sheep fetus. The objective of this study was to investigate the feasibility of non-invasive selective fetal reduction using HIFU in a rabbit model. Methods A protocol for HIFU-induced tissue coagulation was developed in the rabbit model. The fetal heart was targeted with ultrasound-guided tissue ablation by a HIFU beam. Five time-mated does between 20–29 days' gestation underwent transabdominal fetal cardiac ablation in a total of 11 fetuses. The HIFU system consisted of a 7-MHz high-power transducer, operated at 2000 W/cm2. The fetal heart rate was observed using real-time ultrasound with Doppler flow velocimetry. All lesions were assessed macroscopically and by histological analysis. Results Severe bradycardia leading to asystole was observed in all targeted fetuses with ultrasound examination. Dissection of fetuses demonstrated a necrotic intrathoracic lesion similar in size to the HIFU focus (approximately 1 × 9 mm). None of the surrounding fetuses was found to have bradycardia during the procedure or a macroscopic lesion on dissection. Conclusion In this pilot study HIFU seems promising to ablate even highly vascularized tissue in the fetus. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.

Objective The aim of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) ablation of fetal tissue in a sheep model. HIFU can deliver large amounts of thermal energy by using ultrasonic waves to induce tissue necrosis, without damaging intervening tissues. In contrast to diagnostic ultrasound where intensity levels are below 0.1 W/cm 2 , HIFU can deliver 1,000 to 10,000 W/cm 2 at the focal spot. Study design A protocol for HIFU-induced tissue coagulation in the fetus was developed in the ovine model. The fetal liver, lung, kidney, muscle, and placenta were targets for ultrasound-guided tissue ablation by a HIFU beam. All lesions were assessed macroscopically and by histologic analysis. Results In all animals, a necrotic lesion, similar in size to the HIFU focus (approximately 1×9 mm), was achieved. The fetal heart rate remained stable immediately after the procedure. Conclusion In conclusion, HIFU ablation seems to be an effective means to coagulate even highly vascularized tissues in the fetus. This procedure shows promise as a transcutaneous, minimally invasive technique to decrease blood flow through fetal tumors or vascular anastomoses. We are currently conducting further studies to refine the HIFU technique and assess safety for fetus and mother.

To determine whether fetal surgery in a fetus with myelomeningocele (MMC) allows normal development of rectal muscles and nerves, we analyzed the rectum after fetal surgery in a sheep model. An MMC lesion was surgically created in 13 fetal sheep at 75 days of gestation. One fetal sheep died after the lesion was created. Eight fetal sheep were repaired at 100 days of gestation; the others were not repaired, as a control (n=4). Three methods were used for fetal surgery of MMC: standard neurosurgical repair (4 fetal sheep), covering of the MMC lesion by Alloderm (2 fetal sheep), and covering of the MMC lesion by Gore-Tex (2 fetal sheep). At 140 days of gestation, fetal sheep were harvested and histo-pathological analysis was performed on the rectum using hematoxylin and eosin staining for muscles and S-100 protein staining for nerves. One fetal sheep treated by standard neurosurgical repair died before harvesting. The four untreated fetal sheep had hypoplastic longitudinal muscles of the rectum but well developed-circular muscles. In addition, the untreated fetuses had a hypoplastic submucosal nerve plexus but a well-developed intermuscular nerve plexus. In contrast, treated fetal sheep had well-developed longitudinal and circular muscles except for one sheep treated with standard neurosurgical repair. In addition, except for the same fetal sheep, treated fetal sheep had well-developed nerve plexuses. There was no difference in muscle and nerve development of the rectum among the three repair methods. Fetal surgery for repair of MMC allows normal development of rectal muscles and nerves.

Objectives To evaluate the reliability of sonographic lung-to-head ratio (LHR) measurement as a predictor of survival in fetuses with congenital diaphragmatic hernia (CDH) and to compare the probability of survival in those with temporary tracheal occlusion (TO) or standard care with respect to the LHR. Methods Fifty-six fetuses with left CDH with liver herniated into the thorax at complete prenatal evaluation were included in logistic regression analyses of antenatal predictors of survival to hospital discharge. Sixteen subjects underwent TO and 40 received standard care. Results LHR was a significant predictor of survival, with probability of survival increasing with increasing LHR (odds ratio (OR) 8.5, P = 0.04). When subjects with anomalies were excluded, the LHR effect was similar after adjustment for TO (OR 7.1, P = 0.11). Linear spline models suggested a plateau in survival at an LHR of 1.0 and all models suggested increased odds of survival with TO. Minimum LHR measurements had a high degree of inter- and intraobserver agreement (intraclass correlation coefficients of 0.70 and 0.80, respectively). Conclusions Calculation of the LHR in fetuses with CDH is a reliable and powerful predictor of survival to hospital discharge, although improving odds of survival may plateau at an LHR of 1.0. TO may have an independent benefit on survival to hospital discharge. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

The purpose of this case report is to demonstrate the importance of prenatal imaging for treatment management of fetal giant hepatic hemangiomas. Prenatal ultrasound revealed an abdominal mass with several cystic areas and punctate calcifications in a fetus at 29 weeks’ gestation. Doppler scans confirmed the highly vascular nature of the mass. In this case, ultrasound diagnosed the mass was of hepatic origin, while magnetic resonance imaging at 32 weeks’ gestation was more equivocal with respect to the anatomy source of the lesion. Imminent hydrops caused by a rapidly enlarged liver tumor was sonographically demonstrated at 34 weeks’ gestation. An elective C-section and immediate tumor resection was performed. At the age of 20 months the infant is thriving. This case supports the notion that the survival rates for giant hepatic hemangiomas improve when fetal hydrops is averted and specific pre- and postnatal treatment is applied based on correct prenatal imaging diagnostics.

Purpose: Multifetal pregnancy reduction is a widespread ‘therapy’ to diminish the risk of prematurity and adverse outcome for the survivors in higher order multiple gestation. The aim of our study was to determine the maternal and neonatal outcome of multifetal pregnancies under a conservative pregnancy management. Study Design: A retrospective review of 112 multifetal pregnancies is presented. All higher order multiple pregnancies delivered after 25 weeks of gestation and managed at a single institution between 1982 and 1999 are included. Results: Triplets, quadruplets and quintuplets were delivered at a mean gestational age of 31 + 5, 29 + 5 and 28 + 4 weeks, respectively. The perinatal mortality was 14 for triplets and 36 for quadruplets. No quintuplet died in the perinatal period. Respiratory distress syndrome occurred in 23% of triplets, 65% of quadruplets and 75% of quintuplets, intracranial hemorrhage was diagnosed in 14% of triplets, 15% of quadruplets and 10% of quintuplets and retinopathy of prematurity was found in 10% of triplets, 9% of quadruplets and 25% of quintuplets. Discussion: Despite a low neonatal mortality, morbidity of higher order multiple gestations remains significant. Mortality and morbidity are related to preterm delivery but do not exceed the rates of singletons or twins of an identical gestational age. Favorable prognostic landmarks are a gestational age >30 weeks and a number of fetuses per pregnancy ≤4. Conclusion: The risks of multifetal pregnancies are significant. Therefore, evidence-based counseling of couples seeking treatment for infertility and prevention of higher order multiple pregnancies through the prudent use of reproductive techniques attains paramount importance.

To determine the interobserver variability of prenatal magnetic resonance (MR) lung volumetry and to assess the value of MR lung volumetric findings as predictors of outcome in fetuses with congenital diaphragmatic hernia.Prenatal MR imaging was performed in 26 fetuses with unilateral congenital diaphragmatic hernia. Two independent observers performed planimetric measurement of lung volume. Relative lung volume was calculated as the observed total lung volume expressed as a percentage of the total lung volume predicted from fetal size. Relative lung volume was correlated with the ultrasonographic lung-head ratio in left-sided congenital diaphragmatic hernias evaluated before 27 weeks gestation (n = 21) and with pregnancy outcome in all cases of isolated left-sided congenital diaphragmatic hernia without prenatal intervention (n = 11).Observers demonstrated excellent agreement in total lung volume measurements at MR imaging, with an intraclass correlation coefficient of 0.95. Relative lung volume was positively correlated with lung-head ratio (r = 0.78, P.001). By using rank order analysis in the pregnancy outcome group, relative lung volume was predictive of prognosis (P.05) when adjusted for gestational age at delivery and birth weight. Three of four fetuses with a relative lung volume of less than 40% died.Interobserver agreement is high at MR lung volumetry, and its findings are predictive of outcome in fetuses with isolated left-sided congenital diaphragmatic hernia.

Objective: Fetuses with solid, highly vascularized sacrococcygeal teratomas can die as a result of the vascular steal syndrome. This is the first report in which a percutaneous technique, radiofrequency ablation, was used to interrupt blood flow to a sacrococcygeal teratoma in 4 human fetuses. Study Design: A radiofrequency ablation probe was percutaneously inserted into the fetal tumor under ultrasonographic guidance. In 2 fetuses a significant portion of the tumor mass was ablated, whereas in the other 2 fetuses only the major feeding vessels were targeted. Results: Two infants were delivered at 28 and 31 weeks' gestation, respectively, and are doing well. In 2 other cases hemorrhage into the tumor led to an unfavorable fetal outcome. Conclusion: Ablation of a majority of the tumor tissue in sacrococcygeal teratoma is not necessary and proved fatal in two instances. Targeted ablation of the feeding tumor vessels diminishes blood flow sufficiently to reverse high-output fetal heart failure. (Am J Obstet Gynecol 2001;184:503-7.)

Objective: The purpose of our study was to determine whether prenatal repair of myelomeningocele prevents or reverses hindbrain herniation in the sheep model. Study Design: A myelomeningocele was surgically created in fetal sheep. One group was repaired later in utero; the others were delivered without repair. After delivery, lambs were assessed for the presence of hindbrain herniation. Results: In all lambs that had not undergone repair of the myelomeningocele, severe hindbrain herniation developed, whereas the brains of all lambs that had undergone fetal repair were normal. Conclusion: Prenatal repair of myelomeningocele prevents or reverses development of hindbrain herniation in the fetal lamb model. (Am J Obstet Gynecol 2000;183:1119-23.)

CDH is a common congenital anomaly that occurs in 1 in 2000 to 5000 births. 1-5 In 90% of cases abdominal viscera herniate into the left hemithorax through the foramen of Bochdalek. 2 Less often, the abdominal viscera herniate into the right hemithorax. Rarely, defects in both hemidiaphragms or complete absence of the diaphragm occur. Prenatal diagnosis in these latter situations can be challenging but is important because the mass effect of bilateral lesions on the developing lungs leads to an extreme degree of pulmonary hypoplasia. Unfortunately, the usual findings used to detect fetuses with CDH may be absent, surprisingly subtle, or frankly confusing in this most extreme situation. We present two cases of prenatal sonography in fetuses with bilateral CDH. In the first case an erroneous diagnosis of unilateral CDH was made. The correct diagnosis was made in the second case. These cases illustrate the pitfalls leading to diagnostic error and the clues leading to a correct prenatal diagnosis.

Placental vascular communications can present a life-threatening problem in monochorionic twins when one fetus has a lethal anomaly. Although selective feticide is the best option for salvaging the normal twin, techniques normally employed (i.e. intracardiac potassium, air embolism) are not prudent given the common circulatory system. Furthermore, in monoamniotic, monochorionic twin gestations it is important to transect the umbilical cord completely to prevent entanglement of the dead fetus around the cord of the normal twin. We present two cases of monochorionic twins in which the cords were transected with a harmonic scalpel under ultrasonic guidance via one trocar. The harmonic scalpel is an instrument which can simultaneously coagulate and cut blood vessels or tissues. The cord ultrasonic transection procedure is a novel, minimally invasive technique which offers several advantages over the methods currently used for selective feticide in discordant monochorionic twin gestations.

One major problem for patients with myelomeningocele (MMC) is fecal incontinence. To prevent this problem, fetal surgery for repair of MMC has been recently undertaken. The strategy behind this surgery is to allow normal development of anal sphincter muscles. The purpose of this study was to determine whether fetal surgery for repair of MMC allows normal development of anal sphincter muscles. Myelomeningocele was surgically created in fetal sheep at 75 days of gestation. At 100 days of gestation, fetal surgery for repair of the MMC lesion was performed. Three repair methods were used: standard neurosurgical repair (4 fetal sheep), covering the MMC lesion with Alloderm (2 fetal sheep), and covering the MMC lesion with Gore-Tex (2 fetal sheep). After the sheep were delivered (140 days of gestation), external and internal anal sphincter muscles were analyzed histopathologically. In control fetal sheep (not repaired) anal sphincter muscles did not develop normally. In contrast, in fetal sheep that underwent repair of the MMC, the external and internal anal sphincter muscles developed normally. Histopathologically, in the external sphincter muscles, muscle fibers were dense. In the internal sphincter muscles, endomysial spaces were small, myofibrils were numerous, and fascicular units were larger than those in unrepaired fetal sheep. There was no difference in muscle development for the repair methods. Fetal surgery for repair of MMC allows normal development of anal sphincter muscles.

The purpose of this case report is to demonstrate the importance of prenatal imaging for treatment management of fetal giant hepatic hemangiomas. Prenatal ultrasound revealed an abdominal mass with several cystic areas and punctate calcifications in a fetus at 29 weeks' gestation. Doppler scans confirmed the highly vascular nature of the mass. In this case, ultrasound diagnosed the mass was of hepatic origin, while magnetic resonance imaging at 32 weeks' gestation was more equivocal with respect to the anatomy source of the lesion. Imminent hydrops caused by a rapidly enlarged liver tumor was sonographically demonstrated at 34 weeks' gestation. An elective C-section and immediate tumor resection was performed. At the age of 20 months the infant is thriving. This case supports the notion that the survival rates for giant hepatic hemangiomas improve when fetal hydrops is averted and specific pre- and postnatal treatment is applied based on correct prenatal imaging diagnostics.

Background/Purpose: In the last 10 years, the ability to diagnose fetal tumors in the prenatal period has improved greatly because of technical advances in imaging. Early diagnosis and determination of tumor may affect prognosis. Methods: The authors retrospectively reviewed the records of 1316 fetuses who underwent sonographic evaluation for congenital defects at University of California-San Francisco over a 6-year period. Of these, 16 had fetal tumors and were followed up at our institution. There were solid or predominately solid with small cystic component masses in one of 3 locations: cervical, mediastinal, or abdominal. Excluded from our study were those fetuses with either sacrococcygeal teratoma, congenital cystic adenomatoid malformation of the lung, or ovarian cyst, because these defects have been extensively reviewed elsewhere. In addition, masses that were primarily cystic also were excluded. Data collected included diagnosis, gestational age at diagnosis and at delivery, mode of delivery, fetal and neonatal survival, and disease confirmation. Results: Of the 16 fetuses, 4 had mediastinal tumors: 2 with pericardial teratomas (both of whom died in utero) and 2 with cardiac rhabdomyomas (1 died; the other presented tuberous sclerosis and is alive at 2 years of age). Four patients had cervical tumors (3 died; 1 survived and is alive and well), and 8 had abdominal tumors (3 with liver tumors, 4 with a left adrenal mass, and 1 with retroperitoneal teratoma). All eight patients with an abdominal tumor are alive and well. Conclusions: Fetal tumors are rare, and the prognosis seems to depend on their location and size. Although easier to detect, cervical and mediastinal tumors have a worse prognosis. Abdominal masses are more difficult to detect but have a better prognosis. J Pediatr Surg 36:1244-1247. Copyright © 2001 by W.B. Saunders Company.

Severe left congenital diaphragmatic hernia was diagnosed in a baby prenatally, and she underwent hernia repair on the sixth postnatal day of life. She was found to have a huge symptomatic gastroesophageal duplication cyst on day 24 of life. A thoracoabdominal dissection allowed successful cyst excision. J Pediatr Surg 36:626-628. Copyright © 2001 by W.B. Saunders Company.

Objective: Long-term access to the fetal circulation has the potential to open up new perspectives in the treatment of numerous fetal anomalies. The purpose of this study was to investigate the safety of long-term catheterization of fetal placental vessels. Methods: A midline laparotomy was performed in 4 time-mated pregnant ewes at 125 days’ gestation (term 145 days). Placental vessels were exposed by a small uterine incision. A specially designed catheter was inserted into a placental vessel over a length of 3 cm, the distal end of the catheter was tunneled underneath the maternal skin and attached to a subcutaneous port implanted in the maternal flank. All pregnancies were allowed to go to term. Results: Ewes and fetuses tolerated the placement of the catheter and port without complications. The catheter remained patent in all cases. All lambs were delivered vaginally at term and did not require resuscitation after birth. No fetal anomalies or growth restriction were noted. Conclusion: The ovine placental vessel can be accessed long term without complication.

The purpose of the present study was to determine the ability of lung-to-head ratio to predict survival and need for extracorporeal membrane oxygenation support in fetuses with left congenital diaphragmatic hernia without herniation of the liver into the chest. The perinatal records of 20 fetuses with isolated left congenital diaphragmatic hernia without herniation of the left lobe of the liver into the chest were reviewed. Fetuses were stratified into two groups depending on lung-to-head ratio: those with a ratio of less than 1.4 (historically a poor prognosis group) and those with a ratio of greater than 1.4. The outcome of both groups was compared with chi-square analysis. Eight of 11 fetuses with a lung-to-head ratio greater than 1.4 survived, whereas 8 of 9 fetuses with a ratio of less than 1.4 survived. No differences were noted in the need for extracorporeal membrane oxygenation support or survival between the two groups. Fetuses with a prenatally diagnosed left congenital diaphragmatic hernia without herniation of liver into the chest have a favorable prognosis even in the presence of a low lung-to-head ratio.

Objective The regulatory roles of a number of early-acting growth factors on the generation of natural killer (NK) cells and B cells from primitive progenitors were studied. Experiments focused on the contributions of granulocyte-macrophage colony-stimulates factor (GM-CSF) and interleukin-3 (IL-3) to the regulation of the early events of lymphopoiesis. Materials and Methods Two progenitor populations isolated from human fetal liver were studied, CD38 − CD34 ++ lineage − (Lin − ) cells (candidate hematopoietic stem cells [HSCs]) and the more mature CD38 + CD34 ++ Lin − cells. The effects of different cytokines on the generation of CD56 + CD3 − NK cells and CD19 + B cells were studied in serum-deprived cultures in the absence of stroma. Results NK cells generated in vitro were able to kill NK-sensitive target cells, expressed NK-associated marker CD161 (NKR-P1A), but exhibited little or no expression of CD2, CD8, CD16, CD94/NKG2A, or killer cell inhibitory receptors (KIRs). Among the cytokine combinations tested, kit ligand (KL) and IL-15 provided the best conditions for generating CD56 + NK cells from CD38 + CD34 ++ Lin − cells. However, either flk-2/flt3 ligand (FL), GM-CSF, IL-3, or IL-7 could partially substitute KL. All of these cytokines also supported the growth of NK-cell progenitors from candidate HSC, with the combination of IL-15, KL, GM-CSF, and FL generating the greatest number of CD56 + cells. B cells were generated from both progenitor populations in response to the combined effects of KL, FL, and IL-7. Both B and NK cells were generated with the further addition of IL-15 to these cultures. The in vitro generated B cells were CD10 + , CD19 + , HLA-DR + , HLA-DQ + , and some were CD20 + , but no cytoplasmic or surface immunoglobulin M expression was observed. In contrast with NK lymphopoiesis, GM-CSF, IL-3, and IL-15 had no effect on the generation of B cells from CD38 − CD34 ++ Lin − cells, and GM-CSF inhibited B-cell generation from CD38 + CD34 ++ Lin − progenitors. Conclusion These findings indicate a differential regulation of NK and B lymphopoiesis beginning in the early stages of hematopoiesis as exemplified by the distinctive roles of IL-7, IL-15, GM-CSF, and IL-3.

The amniotic band syndrome represents a prime example of exogenous disruption of an otherwise normal fetal development. It may be a sequel of invasive diagnostic procedures such as amniocentesis or fetal blood sampling. A 38-year-old gravida II, para II delivered a morphologically normal male stillborn at term. The pregnancy history had been unremarkable but for an early 2nd-trimester amniocentesis. Cause of the intra-uterine fetal demise was noted to be an amniotic band constricting the umbilical cord. An amniotic band is a rare but potentially fatal condition which may be induced by, e.g., invasive prenatal procedures. Such bands are not usually diagnosed prenatally; however, selected patients with augmented risk may profit from intensive ultrasound evaluation including Doppler studies.

DECREASES THE RISK OF METABOLIC SYNDROME BETTINA PAEK, KATHERINE EASTWOOD, KRISTINA UTZSCHNEIDER, JENNY TONG, FERNANDO GERCHMAN, DREW ROBILIO, WILFRED FUJIMOTO, STEVEN KAHN, DARCY CARR, University of Washington, Obstetrics and Gynecology, Seattle, Washington, University of Washington, Medicine, Seattle, Washington OBJECTIVE: Having a low weight at birth (LBW) or macrosomic weight (MBW) have been linked to cardiovascular risk factors and type 2 diabetes (T2D) later in life. We hypothesized that the risk of obesity, hypertension (HTN), the metabolic syndrome (MS), and T2D would be increased in subjects who weighed !2500g (LBW) or 4000g (MBW) at birth and had a first-degree relative with T2D. STUDY DESIGN: We performed a cross sectional analysis on 1148 motherchild pairs who participated in the GENetics of Non-Insulin dependent Diabetes (GENNID) to compare the frequencies of the MS and T2D in adult offspring with reported LBW (n=120) or MBW (n=122) compared to normal BW (NBW: n=906). The MS was defined by the revised National Cholesterol Education Program Adult Treatment Panel III. T2D was determined by medical history or fasting and 2 hour glucose values. RESULTS: The groups had similar age (meanGSE: LBW 45.2G1.12 vs NBW 44.2G0.39 vs MBW 43.4G1.07 years,p=0.5), sex distribution (female: 63 vs 59 vs 56%, p=0.6) and smoking status (48 vs 49 vs 57%, p=0.1). LBW subjects were more likely to be African American (25 vs 14 vs 9%, p=0.001). Adjusting for age, sex, smoking, and race, LBW were less obese than NBW (BMI 28.4G0.64 vs 31.3G0.28 kg/m, p!0.0001 and had lower waist circumference 92G2 cm vs 101G1 cm, p!0.0001), whereas MBW had higher BMI (33.6G0.87 vs 31.4G0.28 kg/m, p=0.02) and a trend to higher waist circumference (105G2 vs 101G1 cm, p=0.09). LBW also had lower blood pressures (systolic 119G2 vs. 123G1 mmHg, p=0.006) and insulin levels (13.9G1.3 vs 17.6G0.7 iU/ml, p=0.007). Consistent with this, LBW had a decreased risk of the MS (LBW 58 vs NBW 70%, OR .54, 95% CI .30-.95, p=0.03). However, the risk of T2D was not different (LBW 61 vs NBW 60 vs MBW 60%, p=0.9). CONCLUSION: Among individuals with a family history of T2D, having LBW decreased the risk of obesity, central adiposity, HTN, and the MS later in life. Thus, in this high-risk population, LBW appears protective for future metabolic risk; whereas MBW did not confer additional risk of MS or T2D over NBW.