Ultrasound Microvessel Imaging of the Human Placenta Demonstrates Altered Vessel Densities in Fetal Growth Restriction With Vascular and Immune Pathologies: A Pilot Case-Control Study.

OBJECTIVES: Fetal growth restriction (FGR) is commonly associated with placental dysfunction, increasing perinatal morbidity and mortality. Visualizing placental vessels in utero would be advantageous for identifying functional FGR cause and determining proper management strategies. We aimed to utilize high-sensitivity ultrasound microvessel imaging (HUMI) for quantifying placental vessel density (VD) in pregnancies diagnosed with FGR. METHODS: This pilot case-control study enrolled subjects in the third trimester with a diagnosis of FGR (n = 40) and gestational age-matched controls with normal fetal growth (n = 20) at a 2:1 ratio, respectively. The Verasonics Vantage ultrasound system was used to perform HUMI on each participant at one timepoint. Scanning involved randomized singular value decomposition-based clutter filtering to identify the villous tree, followed by step-by-step scanning to acquire 3-dimensional-like data. Mean VD was calculated from three ultrasound measurements per subject. Additional clinical and pathology data were also collected and compared. RESULTS: Sixteen participants were utilized to establish the scanning protocol and 2 met exclusion criteria at delivery. Thus, VD was successfully measured on 42 pregnancies scanned at 35 weeks 5 days on average. In FGR (n = 24), placental VD was significantly reduced compared to controls (P < .01). VD measures were as good at predicting FGR as systolic/diastolic (S/D) ratios (area under the curve 0.86 versus 0.80). In a smaller cohort, VD in placentas with a diagnosis of inflammatory villitis (n = 10) by histology showed an increase in VD compared to those without inflammation (P = .01). Low VD was correlated with increased S/D ratios (P = .03). CONCLUSIONS: HUMI is useful for identifying altered placental vascularization in utero for FGR. VD may be a valuable indicator for placental health and could lead to improved risk stratification methods considering underlying biology.

Ultrasound Guidance to Replicate Transuterine BioGlue Injection in the Fetal Hydrocephalus Sheep Model.

INTRODUCTION: Congenital hydrocephalus often results in irreversible and severe damage to the brain despite postnatal interventions. The potential for prenatal intervention to mitigate these deleterious effects underscores the importance of a suitable animal model. We aimed assess the results of an ultrasound-guided transuterine approach to replicate the BioGlue injection fetal hydrocephalus model. METHODS: Pregnant ewes were anesthetized at 95 days of gestation and BioGlue was injected into the fetal cisterna magna under ultrasound guidance through the uterus. Ventriculomegaly was assessed by MRI and histology. RESULTS: Nine pregnant ewes were included in the study, and their fetuses were divided into the BioGlue intervention group (n = 9 fetuses) or the control group (n = 7 fetuses) who were not injected. Although hydrocephalus was noted in 5 of 9 fetuses in the intervention group, the ability to induce hydrocephalus went from 0% to 100% in the last 3 fetuses following technical modifications. None of the controls developed hydrocephalus. Fetal brains with hydrocephalus demonstrated increased IBA1+ compared to control animals. CONCLUSIONS: While technical challenges were noted, the ultrasound-guided transuterine approach to replicate the BioGlue fetal hydrocephalus model in sheep showed consistent and reproducible results. This model offers the advantage of directly visualizing the location of the needle tip and injection of the BioGlue. This technique offers an alternative for testing novel approaches for prenatal congenital hydrocephalus treatment.

Fetal surgery is not associated with increased inflammatory placental pathology.

OBJECTIVE: Fetal surgery has improved neonatal outcomes; however, it is unknown if the intervention contributes to the developmental of inflammatory pathologies in the placenta. Here, an association between fetal surgery and placental pathology was examined. METHOD: This case-control study compared pregnancies with fetal surgery (n = 22), pregnancies with an indication for fetal surgery but without an intervention being done (n = 13), and gestational-age and fetus-number matched controls (n = 36). Data on maternal, infant, and placental outcomes were abstracted. Additionally, immunohistochemistry identified expression of lymphoid and myeloid cells in the placenta on a subset of cases. Comparisons were performed using Kruskal-Wallis or Pearson's chi-squared tests. RESULTS: Maternal characteristics were comparable between groups. Most fetal interventions were for diaphragmatic hernia, spina bifida, or twin-to-twin transfusion syndrome. Fetuses who were operated on before birth were more likely to be born preterm (p = 0.02). There was no increase in the rate of observed placental pathologies or immune cell infiltration in fetal surgery cases compared to controls. CONCLUSION: The data suggest that fetal surgery is not associated with increased inflammatory or morphologic pathology in the placenta. This observation supports the growing field of fetal surgery.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Ethical considerations of maternal-fetal surgery.

The practice of maternal-fetal surgery (MFS) has expanded from lethal fetal conditions to conditions which are significantly disabling but not a lethal fetal abnormality. The inclusion of myelomeningocele within the scope of MFS in the 1990s sparked a renewed debate over the ethics of MFS. While demonstrating increasing efficacy and range of application, MFS continues to be ethically fraught due to the inherent tension between maternal and fetal interests. Ethical issues central to MFS include the patienthood of the fetus; the balance of risks and benefits between the woman and fetus; informed consent for experimental procedures; and determination of conditions that meet ethical qualifications for MFS intervention. These concerns are likely to persist and evolve as perinatal medicine continues to advance. Here we summarize the current state of MFS ethics, highlighting the major positions in the literature thus far as well as examine future directions. It is essential robust discussions of these important issues continue both to ensure ethical medical practice and to provide support to clinicians, pregnant women, and their families.

Innovative Fetal Therapy for a Giant Congenital Pulmonary Airway Malformation with Hydrops.

INTRODUCTION: Congenital pulmonary airway malformations (CPAMs) complicated by hydrops portend significant morbidity and mortality, with fetal survival estimates less than 10%. CASE PRESENTATION: We report successful use of ultrasound-guided radiofrequency ablation at 21-week gestation in a hydropic fetus with CPAM, with subsequent resolution of hydrops. Thirty-two-week MRI noted persistent mediastinal shift, and US at 36 weeks and 5 days noted polyhydramnios. Maternal gestational hypertension prompted delivery at 37 weeks, with a cesarean section performed after a failed trial of labor. The infant required CPAP at 100% and weaned to 21%. Tachypnea persisted, and chest CT on day of life 2 demonstrated multiple large cysts in the right lower lobe with anterior pneumothorax. On day of life 3, she successfully underwent a thoracoscopic right lower lobectomy. Adhesions to the chest wall and rib abnormalities were noted. She was extubated to CPAP at the conclusion of the procedure. She was able to wean to 21% on POD2 and transitioned to oral feeds. Her chest tube was removed with resultant ex vacuo pneumothorax noted. She remained asymptomatic and was discharged home on room air POD11. Pathology confirmed a type 1 CPAM. CONCLUSION: In utero radiofrequency ablation may be an adjunct to the management of large CPAM.

Estimated fetal weight and severe neonatal outcomes in preterm prelabor rupture of membranes.

Objectives Our aim was to study the association of clinical variables obtainable before delivery for severe neonatal outcomes (SNO) and develop a clinical tool to calculate the prediction probability of SNO in preterm prelabor rupture of membranes (PPROM). Methods This was a prospective study from October 2015 to May 2018. We included singleton pregnancies with PPROM and an estimated fetal weight (EFW) two weeks before delivery. We excluded those with fetal anomalies or fetal death. We examined the association between SNO and variables obtainable before delivery such as gestational age (GA) at PPROM, EFW, gender, race, body mass index, chorioamnioitis. SNO was defined as having at least one of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or neonatal death. The most parsimonious logistic regression models was constructed using the best subset selection model approach, and receiver operator curves were utilized to evaluate the prognostic accuracy of these clinical variables for SNO. Results We included 106 pregnancies, 42 had SNO (39.6%). The EFW (area under the receiver operating characteristic curve [AUC]=0.88) and GA at PPROM (AUC=0.83) were significant predictors of SNO. The addition of any of the other variables did not improve the predictive probability of EFW for the prediction of SNO. Conclusions The EFW had the strongest association with SNO in in our study among variables obtainable before delivery. Other variables had no significant effect on the prediction probability of the EFW. Our findings should be validated in larger studies.

Placental Location and the Development of Hypertensive Disorders of Pregnancy.

OBJECTIVES: Abnormal placentation is an important factor in the pathogenesis of preeclampsia. As a result of diminished blood flow, the incidence of preeclampsia might be higher in patients with laterally located placentas compared to patients with centrally located placentas. The objective of this study was to evaluate the relationship between placental location and the development of hypertensive disorders of pregnancy. METHODS: Patients with singleton pregnancies who were seen in our ultrasound unit and delivered at our institution from October 2014 to April 2015 were included. The incidence of hypertensive disorders was compared in those with a lateral placental location and those with centrally located placentas (placental locations other than lateral). Baseline characteristics and pregnancy outcomes were compared between groups. The χ2 test, Fisher exact test, Mann-Whitney U test, and t test were used when appropriate. P < .05 was considered significant. RESULTS: We included 464 patients; 411 (88.57%) had centrally located placentas, and 53 (11.42%) had laterally located placentas. The incidence of hypertensive disorders of pregnancy was similar between groups (21% versus 19%; P = .71). Gestational age at delivery (P = .73), and small for gestational age (P = .96) were also similar between our study groups. CONCLUSIONS: In our study, there was no difference in the rate of hypertensive disorders of pregnancy between patients with central and laterally located placentas.

Doppler evaluation of the fetal pulmonary artery pressure.

Background The Doppler effect has allowed the characterization of several vessels in maternal-fetal circulation that have been used for practical purposes. Our review of the literature showed a paucity of information about fetal pulmonary artery pressure (FMPAP) and its behavior in regard to gestational age (GA). The objectives of the study were to evaluate a formula to calculate the main FMPAP and its correlation with GA. Methods A total of 337 fetuses without obvious pathology were studied prospectively using Doppler evaluation of the FMPAP. Using the fetal main pulmonary artery Doppler acceleration time (FMPAT), we obtained the FMPAP using the following formula: FMPAP=90 - (0.62×FMPAT). Regression analyses, Pearson's bivariate correlation and paired sample t-test were used when appropriate. Results FMPAT increases while FMPAP decreases with GA. Pearson's correlation coefficient for FMPAP and GA was -0.544 (P-value<0.001) and for FMPAT and GA was 0.556 (P-value<0.001). FMPAP and FMPAT were highly correlated (R=-0.972; P<0.001). Conclusion Pulmonary artery pressure in the fetus decreases with GA.

Middle cerebral artery peak systolic velocity in perinatal cytomegalovirus infection.

A middle cerebral artery peak systolic velocity value (MCA-PSV) persistently greater than 1.5 times the median of the normal population is utilized to detect moderate and severe anemia in fetuses at risk. Cytomegalovirus (CMV) is the most common perinatal infection and can cause fetal anemia. We present four cases with CMV perinatal infection. Although their MCA-PSV values were the highest recorded in normal as well as in anemic fetuses, only two of them developed moderate or severe anemia. These findings suggest that high MCA-PSV values in cases with perinatal CMV infection may have a different pathophysiologic mechanism than anemia.

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia--diagnosis and management.

OBJECTIVE: We sought to provide evidence-based guidelines for the diagnosis and management of fetal anemia. METHODS: A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the Cochrane Library. The search was restricted to English-language articles published from 1966 through May 2014. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was used for defining the strength of recommendations and rating the quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. RESULTS AND RECOMMENDATIONS: We recommend the following: (1) middle cerebral artery peak systolic velocity (MCA-PSV) measured by ultrasound Doppler interrogation be used as the primary technique to detect fetal anemia; (2) amniotic fluid delta OD450 not be used to diagnosis fetal anemia; (3) MCA-PSV assessment be reserved for those patients who are at risk of having an anemic fetus (proper technique for MCA-PSV evaluation includes assessment of the middle cerebral artery close to its origin, ideally at a zero degree angle without angle correction); (4) if a fetus is deemed at significant risk for severe fetal anemia (MCA greater than 1.5 multiples of the median or hydropic), fetal blood sampling be performed with preparation for an intrauterine transfusion, unless the pregnancy is at a gestational age when the risks associated with delivery are considered to be less than those associated with the procedure; (5) if a fetus is deemed at significant risk for severe fetal anemia, the patient be referred to a center with expertise in invasive fetal therapy; (6) MCA-PSV be considered to determine the timing of a second transfusion in fetuses with anemia, and, alternatively, a predicted decline in fetal hemoglobin may be used for timing the second procedure; and (7) pregnancies with a fetus at significant risk for fetal anemia be delivered at 37-38 weeks of gestation unless indications develop prior to this time.

Predicting fetal lung maturity using the fetal pulmonary artery Doppler wave acceleration/ejection time ratio.

OBJECTIVE: To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid. METHODS: We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant. RESULTS: Forty-three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58-96%) for predicting immature surfactant/albumin ratio results. CONCLUSION: The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values.

A novel translational model of percutaneous fetoscopic endoluminal tracheal occlusion - baboons (Papio spp.).

INTRODUCTION: Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications. MATERIAL AND METHODS: Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed. RESULTS: The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group. DISCUSSION: This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied.

The impact of fetal surgical procedures on perinatal anxiety and depression.

BACKGROUND: Perinatal mental illness presents a significant health burden to both patients and families. Many factors are hypothesized to increase the incidence of perinatal depression and anxiety in the fetal surgical population, including uncertain fetal prognosis and inherent risks of surgery and preterm delivery. OBJECTIVE: This study aimed to determine the incidence and disease course of postpartum depression and anxiety in the fetal surgery population. STUDY DESIGN: A retrospective medical record review study was conducted of fetal surgery patients delivering between November 2016 and November 2021 at an academic level IV perinatal healthcare center. Demographics and surgical, obstetrical, and psychiatric diagnoses were abstracted. Standard descriptive analyses were performed. RESULTS: Eligible patients were identified (N=119). Fetal surgery was performed at a mean gestational age of 22.8 weeks (standard deviation, 4.11). Laser ablation of placental anastomoses (n=51) and in utero myelomeningocele repair (n=22) were the most common procedures. Of 119 patients, 34 (28.6%) were diagnosed with preexisting depression or anxiety, with 19 (55.9%) and 17 (50.0%) on baseline medication for depression or anxiety, respectively, before surgery. Of 85 patients, 23 (27.1%) without a history of anxiety or depression had new identification of one or both after delivery. Of note, 2 patients experienced suicidal ideation after delivery. Of the 119 patients, 8 (6.7%) and 12 (10.1%) initiated a new psychiatric medication during or after pregnancy, respectively, and 19 (16.0%) received a therapy referral. Among patients with baseline anxiety or depression, 20 of 34 patients (58.8%) experienced an exacerbation after delivery, 9 of 34 patients (26.5%) were referred for therapy, 9 of 34 patients (26.5%) were changing dose or medication for anxiety, and 11 of 34 patients (32.4%) were changing dose or medication for depression. Of the 119 patients, 24 (20.2%) experienced new or worsening depression or anxiety after the standard 6-week postpartum visit. CONCLUSION: Among patients undergoing fetal surgery, a high incidence of postpartum depression and anxiety was identified, with most patients with prepregnancy anxiety or depression experiencing exacerbation after delivery. The timeframe to clinical presentation with depression or anxiety symptoms may be delayed beyond the traditional 6-week postpartum period and into the first postpartum year. This observation could be attributed to de novo postpartum exacerbation or a lack of standardized treatment approaches earlier in the disease course or antepartum period. Understanding effective longitudinal supportive interventions is an essential next step.

A Systematic Review and Meta-Analysis of Physiologic Variables in Sheep Fetuses.

The fetal sheep model has been widely used in fetal therapy research. However, there is a significant degree of variability among published normal values. Our study aimed to evaluate the literature available on normal values for hemodynamics, blood gases, and acid-base status in the sheep fetus and to determine the best possible estimation of such physiologic values. We conducted a systematic review with a comprehensive search of several databases. We included 189 articles in the database and over 2,800 sheep fetuses. Analysis revealed a mean umbilical blood flow of 202 mL/kg/min (95% CI: 182 to 223); mean arterial pCO2 of 49.8 mm Hg (95% CI: 49.2 to 50.3); mean arterial pO2 of 22.3 mm Hg (95% CI: 21.9 to 22.7); mean arterial pH of 7.35 (95% CI: 7.3487 to 7.3562); and mean arterial oxygen saturation of 59.8 (95% CI; 58 to 61.7). Our findings were punctuated by a high heterogeneity, for which we conducted several subanalyses. The results showed high heterogeneity and small study effect in the literature available and provided our best assessment of relevant variables on normal hemodynamics, blood gases, and acid-base status in the fetus after using strategies to mitigate the risk of bias present in the literature.

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Impact of asymptomatic and mild COVID-19 infection on fetal growth during pregnancy.

BACKGROUND: During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR). STUDY DESIGN: This is a single institution, retrospective cohort study of patients ages 16-55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. RESULTS: Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). CONCLUSION: Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.

Report of an Experiment With a Fetal Ex-Utero Support System in Piglets.

Extreme prematurity remains one of the leading causes of neonatal death. An ex-utero treatment strategy that allows the fetus to develop beyond this period until capable of tolerating the transition to post-natal physiology would significantly impact the quality of care offered for this pre-viable patient population. In this study, we report our experience with an ex-utero support system for fetal pigs with the goal of support and survival for eight hours. Our experiment included two pigs at a gestational age equivalent to a 32-week human fetus. Following ultrasound assessment and delivery via hysterotomy, the fetuses were transferred to a 40 L glass aquarium filled with warmed lactated Ringer's solution and connected to an arteriovenous (AV) circuit that included a centrifugal pump and a pediatric oxygenator. Fetus 1 was successfully cannulated and survived for seven hours (expected maximum duration of eight hours). Fetus 2 died shortly after hysterotomy, secondary to failure at the cannulation stage. Our results suggest that ex-utero support of the premature fetal pig is feasible, contributing to a scarce body of evidence. However, further studies are needed before effectively translating an artificial placenta system into the clinical arena.