In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.

Screening for Intimate Partner Violence in Trauma: Results of a Quality Improvement Project.

INTRODUCTION: Intimate partner violence (IPV) is common, especially among patients presenting with traumatic injury. We implemented an IPV screening program for patients admitted after trauma. We sought to determine whether specific demographic or clinical characteristics were associated with being screened or not screened for IPV and with IPV screen results. METHODS: Retrospective cohort study evaluating all patients admitted after trauma from July 2020-July 2022 in an Adult Level 1 Trauma Center. RESULTS: There were 4147 admissions following traumatic injury, of which 70% were men and 30% were women. The cohort was 46% White, 20% Asian, 15% Black, and 17% other races. Twenty-three percent were Hispanic or Latino/a. Seventy-seven percent were admitted for blunt injuries and 16% for penetrating injuries. Thirteen percent (n = 559) of the cohort was successfully screened for IPV. Screening rates did not differ by gender, race, or ethnicity. After adjustment for demographic and clinical factors, patients admitted to the intensive care unit were significantly less likely to be screened. Of the screened patients, 30% (165) screened positive. These patients were more commonly Hispanic or Latino/a, insured by Medicaid and presented with a penetrating injury. There were no differences in injury severity in patients who screened positive versus those who screened negative. CONCLUSIONS: There are significant barriers to universal screening for IPV, including injury acuity, in patients admitted following trauma. However, the 30% rate of positive screens for IPV in patients admitted following trauma highlights the urgent need to understand and address barriers to screening in trauma settings to enable universal screening.

Pandemic Recovery: Persistent Disparities in Access to Elective Surgical Procedures.

OBJECTIVE: To examine potential disparities in patient access to elective procedures during the recovery phase of the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: Elective surgeries during the pandemic were limited acutely. Access to surgical care was restored in a recovery phase but backlogs and societal shifts are hypothesized to impact surgical access. METHODS: Adults with electronic health record orders for procedures ("procedure requests"), from March 16 to August 25, 2019 and March 16 to August 25, 2020, were included. Logistic regression was performed for requested procedures that were not scheduled. Linear regression was performed for wait time from request to scheduled or completed procedure. RESULTS: The number of patients with procedure requests decreased 20.8%, from 26,789 in 2019 to 21,162 in 2020. Patients aged 36-50 and >65 years, those speaking non-English languages, those with Medicare or no insurance, and those living >100 miles away had disproportionately larger decreases. Requested procedures had significantly increased adjusted odds ratios (aORs) of not being scheduled for patients with primary languages other than English, Spanish, or Cantonese [aOR 1.60, 95% confidence interval (CI) 1.12-2.28]; unpartnered marital status (aOR 1.21, 95% CI 1.07-1.37); uninsured or self-pay (aOR 2.03, 95% CI 1.53-2.70). Significantly longer wait times were seen for patients aged 36-65 years; with Medi-Cal insurance; from ZIP codes with lower incomes; and from ZIP codes >100 miles away. CONCLUSIONS: Patient access to elective surgeries decreased during the pandemic recovery phase with disparities based on patient age, language, marital status, insurance, socioeconomic status, and distance from care. Steps to address modifiable disparities have been taken.

Robotic repair of perineal hernias: a video vignette and review of the literature.

BACKGROUND: Perineal hernias can be secondarily acquired following abdominoperineal resection of the rectum. While transabdominal minimally invasive techniques have traditionally used laparoscopy, there are few studies published on the robotic platform, which has been gaining popularity for other types of hernia repairs. We review the existing literature, share a video vignette, and provide practical tips for surgeons interested in adopting this approach. METHODS: A literature search in Pubmed was performed to include all articles in English describing robotic repair of perineal hernias with identification of variables of interest related to repair. A case presentation with an accompanying video vignette and lessons learned from the experience are provided. RESULTS: Seven case reports (four containing video) published between 2019 and 2022 were included. Most articles (n = 5) utilized the Da Vinci Si or Xi, and most patients (n = 5) had undergone abdominoperineal resection with neoadjuvant chemotherapy to treat rectal cancer. Patients were positioned in Trendelenburg with rightward tilt (n = 2), modified lithotomy (n = 1), or a combination of the two (n = 1). All articles (n = 7) reported closing the defect and using mesh. Three articles describe placing five ports (one camera, three robotic, one assistant). There were no significant intraoperative or postoperative complications reported, and no recurrence noted at 3-27 months follow-up. Based on our experience, as shown in the video vignette, we recommend lithotomy positioning, using porous polypropylene mesh anchored to the periosteum of the sacrum and peritoneum overlying the bladder and side wall, and placing a drain above the mesh. CONCLUSIONS: A robotic transabdominal approach to perineal hernia repair is a viable alternate to laparoscopy based on low complication rates and lack of recurrence. Prospective and longer duration data are needed to compare the techniques.

Survey of intrauterine red blood cell (RBC) transfusion practices in the United States.

BACKGROUND: A paucity of data exists about the current practice of fetal red blood cell (RBC) transfusion in the United States (US). This investigation describes intrauterine transfusion (IUT) RBC product selection and processing practices at different US institutions. METHODS: A transfusion medicine and maternal-fetal medicine (MFM) team designed a survey to interrogate and characterize RBCs utilized for IUT. This survey was distributed to seventy US institutions with fetal treatment centers (October 2020-April 2021) identified through the NAFTNet (North American Fetal Therapy Network). RESULTS: Thirty-seven institutions responded (response rate 53%, 37/70), but five were excluded for not performing IUTs. Most (84%; 27/32) performed 1-24 IUTs annually; two performed >50 IUTs/year. Group O, Rh(D) negative RBC units were always used by 66% (21/32), and 75% (24/32) provided hemoconcentrated RBCs by washing (17/24) or dry packing (6/24). Overall, 66% (21/32) targeted a hematocrit ≥75%. Fifty percent provided both leukocyte-reduced and CMV-negative RBC units. Irradiation of RBC units was performed within 6 h of issue at 63% (20/32) of sites. Most (81%, 26/32) used RBC units at <7 days of age after collection, 56% (18/32) always provided washed RBC units, while 19% (6/32) issued washed RBC only if fresh units are unavailable. Implicated maternal RBC alloantibodies were matched for 78% (25/32) of the time. The transfused volume was universally determined by the MFMs. DISCUSSION: Heterogeneity and lack of standardization exist in RBC product selection and special processing steps for IUTs in the US. Hence, the establishment of a consensus to standardize IUT protocols is needed.

Investigating attitudes toward prenatal diagnosis and fetal therapy for spinal muscular atrophy.

OBJECTIVE: In utero SMA treatment could improve survival and neurologic outcomes. We investigated the attitudes of patients and parents with SMA regarding prenatal diagnosis, fetal therapies, and clinical trials. METHODS: A multidisciplinary team designed a questionnaire that Cure SMA electronically distributed to parents and patients (>18 years old) affected by SMA. Multivariable ordinal logistic regression was used to analyze associations between respondent characteristics and attitudes. RESULTS: Of 114 respondents (60% of whom were patients), only 2 were prenatally diagnosed. However, 91% supported prenatal testing and 81% felt there had been a delay in their diagnosis. Overall, 55% would enroll in a phase I trial for fetal antisense oligonucleotide (ASO) while 79% would choose an established fetal ASO/small molecule therapy. Overall, 61% would enroll in fetal gene therapy trials and 87% would choose fetal gene therapies. Patients were less likely to enroll in a fetal gene therapy trial than parents enrolling a child (OR 0.31, p < 0.05). Older parental age and believing there had been excessive delay in diagnosis were associated with an interest in enrolling in a fetal ASO trial (OR 1.04, 7.38, respectively, p < 0.05). CONCLUSION: In utero therapies are promising for severe genetic diseases. Patients with SMA and their parents view prenatal testing and therapies positively, with gene therapy being favored.

Oral Feeding in Infants After Congenital Diaphragmatic Hernia Repair While on Non-invasive Positive Pressure Ventilation: The Impact of a Dysphagia Provider-Led Protocol.

Infants with congenital diaphragmatic hernia (CDH) who require non-invasive positive pressure ventilation or high flow nasal cannula are at risk for aspiration and delayed initiation of oral feeding. We developed a dysphagia provider-led protocol that involved early consultation with an occupational therapist or speech/language pathologist and modified barium swallow study (MBSS) to assess for readiness for oral feeding initiation/advancement on non-invasive positive pressure ventilation. The objective of this study was to retrospectively compare this intervention cohort to a historical control cohort to evaluate the protocol's impact on the time to initiate oral feeding. We describe the development and implementation of the protocol, the MBSS findings of the intervention cohort, and compared the control (n = 64) and intervention (n = 37) cohorts using Fischer's exact test and Mann-Whitney test. We found that both cohorts had similar prenatal and neonatal characteristics including age at extubation. Significantly more infants in the intervention cohort were on non-invasive positive pressure ventilation or high flow nasal cannula at the time of oral feeding initiation (84% vs. 28%, p < 0.0001). None of the control cohort infants underwent MBSS while on respiratory support. Of the intervention cohort, 15 infants underwent a MBSS while on non-invasive positive pressure ventilation; 6 had no evidence of laryngeal penetration and/or aspiration during swallowing. Infants in the control cohort initiated oral feeds significantly sooner after extubation (6 versus 11 days, p = 0.001) and attained full oral feeds earlier (20 days versus 28 days, p = 0.02) than the intervention group. There was no difference in the rate of gastrostomy tube placement (38%). Appropriate monitoring by a dysphagia provider and evaluation with clinical and radiological means are crucial to determine the safety of initiating oral feeding in term infants with CDH. Continued surveillance is needed to determine the long-term impact on oral feeding progression in this population.

Comparison of advanced techniques for local excision of rectal lesions: a case series.

BACKGROUND: Robotic transanal minimally invasive surgery (R-TAMIS) is an appealing alternative to transanal minimally invasive surgery (TAMIS) and transanal endoscopic microsurgery (TEM) for benign and early malignant rectal lesions that are not amenable to traditional open transanal excision. However, no studies to our knowledge have directly compared the three techniques. This study sought to compare peri-operative and pathologic outcomes of the three approaches. METHODS: The records of 29 consecutive patients who underwent TEM, TAMIS, or R-TAMIS at a single academic center between 2016 and 2020 were reviewed. Intra-operative details, pathological diagnosis and margins, and post-operative outcomes were recorded. The three groups were compared using chi-square and Kruskal-Wallis tests. RESULTS: Overall, 16/29 patients were women and the median age was 57 (interquartile range (IQR): 28-81). Thirteen patients underwent TEM, six had TAMIS, and 10 had R-TAMIS. BMI was lower in the R-TAMIS patients (24.7; IQR 23.8-28.7), than in TEM (29.3; IQR 19.9-30.2), and TAMIS (30.4; IQR 26.6-32.9) patients. High grade dysplasia and/or invasive cancer was more common in TAMIS (80%) and R-TAMIS (66.7%) patients than in TEM patients (41.7%). The three groups did not differ significantly in tumor type or distance from the anal verge. No R-TAMIS patients had a positive surgical margin compared to 23.1% in the TEM group and 16.7% in the TAMIS group. Length of stay (median 1 day for TEM and R-TAMIS patients, 0 days for TAMIS patients) and 30-day readmission rates (7.7% of TEM, 0% of TAMIS, 10% of R-TAMIS patients) also did not differ among the groups. Median operative time was 110 min for TEM, 105 min for TAMIS, and 76 min for R-TAMIS patients. CONCLUSIONS: R-TAMIS may have several advantages over other advanced techniques for transanal excisions. R-TAMIS tended to be faster and to more often result in negative surgical margins compared to the two other techniques.

A problem at any age: a case report of congenital malrotation with bowel ischemia in an 84-year-old.

BACKGROUND: Malrotation with bowel ischemia is classically thought of as a disease of infants. However, the true prevalence of malrotation in both the pediatric and adult population is unknown due to the unclear number of asymptomatic patients. CASE PRESENTATION: A previously healthy 84-year-old man with no prior abdominal surgeries presented with an acute abdomen and was found on CT to have small bowel located in the right hemiabdomen and an abnormal SMA-SMV relationship suggestive of intestinal malrotation, as well as pneumatosis intestinalis. He underwent an exploratory laparotomy, where he was found to have a paraduodenal space which did not contain any bowel but was the likely source of an internal hernia. His duodenojejunal flexure was located to the right of the spinal column, the cecum in the left lower quadrant, a thick congenital band at the proximal jejunum, and multiple Ladd's bands at the level of the duodenum. The bowel appeared viable and a Ladd's procedure was performed. The patient had an uneventful post-operative course. CONCLUSIONS: There is a lack of guidelines regarding screening for and management of asymptomatic malrotation in older children and adults. However, the traditional thinking is that asymptomatic malrotation diagnosed after two years of age poses minimal risk. This case illustrates the potential risk of an internal hernia in the setting of malrotation at any time during one's lifetime.

Racial/ethnic disparities among women receiving intrauterine transfusions for alloimmunization at a single fetal treatment center.

Disparities are prevalent in numerous areas of healthcare. We sought to investigate whether there were racial/ethnic disparities among pregnant women with the most severe form of alloimmunization who require intrauterine transfusions (IUT). We reviewed patients who underwent IUT for alloimmunization at a single fetal treatment center between 2015 and 2020. This "IUT cohort" was compared to an "Alloimmunization cohort": patients seen at our institution with a diagnosis of alloimmunization during pregnancy, who did not receive IUT. We collected maternal demographics including self-identified race/ethnicity and primary language, transfusion, and antibody characteristics. The cohorts were compared using unpaired t-tests, Mann-Whitney tests, and Fischer's exact tests, as appropriate. The IUT cohort included 43 patients and the alloimmunization cohort included 1049 patients. Compared to the alloimmunization cohort, there were significantly more patients of Latina descent in the IUT cohort (23.3% vs. 3.4%, p < .0001), and more non-English speakers (18.6% vs. 4.6%, p = .001). Twenty-one percent (9/43) of patients had immigrated to the United States, all of whom had pregnancies or miscarriages in their country of origin. A third of patients had new antibodies identified on serial screens during the current pregnancy. Significantly more women of Latina ethnicity and non-English speakers required IUTs compared to the cohort of women with alloimmunization. Insufficient access to care prior to arriving in the United States and among racial and ethnic minorities in the United States may contribute to these findings. Providers should be cognizant of potential, racial, and ethnic inequalities among women receiving intrauterine transfusions.

Designing an Intimate Partner Violence Screening Program for Surgical Residents in Trauma.

BACKGROUND: Intimate partner violence (IPV) commonly affects surgical patients, particularly trauma patients. However, baseline knowledge of IPV is poor among surgeons and screening is variable. We designed a project to educate surgical residents on IPV and standardize screening in all trauma patients. MATERIALS AND METHODS: Quality improvement frameworks and the Modified Provider Survey were used to examine residents' attitudes and behaviors regarding IPV at a level one trauma center. An educational curriculum was designed with a trainee-led, multidisciplinary team to address knowledge gaps, barriers, and relevant reporting laws, and provide framing language that normalized screening. RESULTS: Fifty-seven surgical residents (64% response rate) spanning post-graduate years 1-7 completed surveys. All respondents believed IPV was relevant to their patients, yet only 4% correctly identified the prevalence of IPV. Only 15% felt comfortable screening for IPV and 75% felt they had received inadequate training. The most common barriers to screening were insufficient knowledge of community resources and what to do if patients screened positive. Most residents grossly underestimated the incidence of IPV and 19% believe healthcare providers have a limited role in being able to help IPV victims. There were no significant differences in responses between male and female residents or among residents from different postgraduate levels. CONCLUSIONS: Surgical residents believe IPV is relevant, but few feel they have adequate training. Residents vastly underestimated the societal prevalence of IPV and the majority never screened patients for IPV. A residency-wide curriculum can address common misperceptions and perceived barriers.

Standardizing Discharge Opioid Prescriptions in Kidney Transplant Patients Decreases Opioid Usage.

BACKGROUND: Kidney transplant recipients are frequently prescribed excess opioids at discharge relative to their inpatient requirements. Recipients who fill prescriptions after transplant have an increased risk of death and graft loss. This study examined the impact of standardized prescriptions on discharge amount and number of outpatient refills. MATERIALS AND METHODS: A historical cohort (Group 1) was compared to a cohort without patient-controlled analgesia (Group 2) and a cohort in which providers prescribed no opioids to patients who required none on the day prior to discharge, and 10 pills to those who required opioids on the day prior (Group 3). Demographics, oral morphine equivalents (OMEs) prescribed on the day prior to and at discharge, and outpatient refills were collected. RESULTS: 270 recipients were included. There was a nonsignificant trend towards lower OMEs on the day prior to discharge in Groups 2 and 3. Nonopioid adjunct use increased (P < 0.001). Discharge OMEs significantly decreased (mean 87.2 in Group 1, 62.8 in Group 2, 26.6 in Group 3, P< 0.001). The number of patients discharged without opioids increased (23.8% of Group 1, 37.5% of Group 2, 60.6% of Group 3, P < 0.001). Group 3, Asian descent, and lower OMEs on the day prior were factors significantly associated with decreased discharge OMEs on multivariable linear regression. Twelve percent of Group 2 and 2% of Group 3 patients received an outpatient refill (P = 0.02). CONCLUSIONS: A protocol targeting discharge opioids significantly reduced the amount of opioids prescribed in kidney transplant recipients; most patients subsequently received no opioids at discharge.

Factors and Growth Trends Associated With the Need for Gastrostomy Tube in Neonates With Congenital Diaphragmatic Hernia.

OBJECTIVES: A third of infants with congenital diaphragmatic hernia (CDH) require a gastrostomy tube (GT) for nutritional support. We compared CDH infants who are GT-dependent to those able to meet their nutritional needs orally, to identify factors associated with requiring a GT and evaluate their long-term growth. METHODS: Patients with CDH repaired at a single institution between 2012 and 2020 were included. Charts were retrospectively reviewed for demographic, surgical, and post-operative details. Mann-Whitney test and Fischer exact test were performed to compare GT-dependent neonates (n = 38, experimental) with orally fed neonates (n = 63, control). Significance was set at <0.05. RESULTS: Thirty-eight percent received a GT (median 67 days, interquartile range [IQR] 50-88). GT-dependent neonates were significantly more likely to have a lower lung-to-head ratio (median 1.2, IQR 0.9-1.4, vs 1.6, IQR 1.3-2.0, IQR P < 0.0001), undergone patch or flap repair (79% vs 33%, P < 0.0001), and been hospitalized longer (median 47, IQR 24-75 vs 28 days, P < 0.0001). Fourteen of 38 had their GT removed (median 26 months, IQR 14-36). GT-dependent neonates initiated oral feeds (calculated as time since extubation) later (median 21, IQR 8-26, vs 8 days, IQR 4-13, P = 0.006). Height-for-age z scores remained stable after GT removal, while weight-for-age z scores dropped initially and began improving a year later. CONCLUSIONS: The need for a gastrostomy for nutritional support is associated with more severe CDH. Over a third of patients no longer needed a GT at a median of 26 months. Linear growth generally remains stable after removal. These results may help counsel parents regarding nutritional expectations.

Prenatal Gene Therapy.

Prenatal gene therapy could provide a cure for many monogenic diseases. Prenatal gene therapy has multiple potential advantages over postnatal therapy, including treating before the onset of disease, the ability to induce tolerance and cross the blood-brain barrier. In this chapter, we will describe in utero gene therapy and its rationale, clinical trials of postnatal gene therapy, preclinical studies of in utero gene therapy, and potential risks to the mother and fetus.

Barriers and facilitators to screening for intimate partner violence at a level 1 trauma center.

BACKGROUND: Intimate partner violence (IPV) is a significant public health problem that is associated with substantial health sequelae, including traumatic injury. Surgical professional societies recommend universal intimate partner violence screening in patients presenting after trauma, but this recommendation is not uniformly implemented. We designed and implemented a quality improvement project at our institution in July 2020 to enhance intimate partner violence screening. Although screening rates improved, they remained suboptimal. Therefore, we sought to examine barriers and facilitators to intimate partner violence screening from trauma clinicians' perspectives. STUDY DESIGN: We conducted a qualitative study using in-depth, semistructured interviews to understand the perspectives and experiences of trauma clinicians conducting intimate partner violence screening. A constructivist paradigm informed our study whereby our data collection approaches aimed to understand intimate partner violence screening from the perspectives of those tasked with implementing screening within real-world clinical settings. We used thematic analysis to analyze our data and generate themes related to barriers and facilitators to screening. RESULTS: We conducted interviews with 12 resident physicians and 2 advance practice providers. We identified 6 themes, 3 reflecting facilitator themes as (1) standardized education and workflow, (2) benefits of interdisciplinary teamwork, and (3) context of screening, and 3 reflecting barrier themes as (1) lack of time, (2) language misinterpretation, and (3) perceived inappropriateness of universal screening. CONCLUSION: Trauma clinicians described multiple facilitators and barriers to screening for intimate partner violence following traumatic injury, some of which were unique to the trauma setting. Projects seeking to achieve universal screening following traumatic injury may benefit from accounting for these factors when designing interventions.

Prenatal AAV9-GFP administration in fetal lambs results in transduction of female germ cells and maternal exposure to virus.

Prenatal somatic cell gene therapy (PSCGT) could potentially treat severe, early-onset genetic disorders such as spinal muscular atrophy (SMA) or muscular dystrophy. Given the approval of adeno-associated virus serotype 9 (AAV9) vectors in infants with SMA by the U.S. Food and Drug Administration, we tested the safety and biodistribution of AAV9-GFP (clinical-grade and dose) in fetal lambs to understand safety and efficacy after umbilical vein or intracranial injection on embryonic day 75 (E75) . Umbilical vein injection led to widespread biodistribution of vector genomes in all examined lamb tissues and in maternal uteruses at harvest (E96 or E140; term = E150). There was robust GFP expression in brain, spinal cord, dorsal root ganglia (DRGs), without DRG toxicity and excellent transduction of diaphragm and quadriceps muscles. However, we found evidence of systemic toxicity (fetal growth restriction) and maternal exposure to the viral vector (transient elevation of total bilirubin and a trend toward elevation in anti-AAV9 antibodies). There were no antibodies against GFP in ewes or lambs. Analysis of fetal gonads demonstrated GFP expression in female (but not male) germ cells, with low levels of integration-specific reads, without integration in select proto-oncogenes. These results suggest potential therapeutic benefit of AAV9 PSCGT for neuromuscular disorders, but warrant caution for exposure of female germ cells.

Robotic transanal excision of rectal lesions: expert perspective and literature review.

Transanal excision of benign lesions, moderately or well-differentiated rectal T1 adenocarcinomas is typically completed via transanal endoscopic microsurgery (TEM) or laparoscopic transanal minimally invasive surgery (TAMIS). Robotic platforms provide ergonomic comfort in an enclosed space, enhanced range of motion, and superior 3D visualization. This study sought to perform a literature review of robotic TAMIS (R-TAMIS) and provide expert commentary on the technique. A Pubmed literature search was performed. Study design, robot type, indication, techniques compared, surgical margins, conversion, complications, operative time, estimated blood loss, patient positioning, and defect closure were collected from included articles. Expert opinion on pre-operative planning, technical details, and possible pitfalls was provided, with an accompanying video. Twelve articles published between 2013 and 2022 were included. Five were case reports, three case series, two prospective cohort studies, one retrospective cohort study, and one Phase II trial. The Da Vinci Si (n = 3), Xi (n = 2), single port (n = 3) and flex robotic system (n = 2) were used. Five studies reported negative surgical margins, one reported positive margins, and six did not comment. Operating room time ranged from 45 to 552 min and EBL ranged from 0 to 100 mL. Patient positioning varied based on lesion location but included supine, prone, modified lithotomy, and prone jackknife positions. 11/12 studies reported defect closure, most commonly with V-Loc absorbable suture. We recommend pre-operative MRI abdomen/pelvis, digital rectal exam, and rigid proctoscopy; prone jackknife patient positioning to avoid collisions with robotic arms; and defect closure of full-thickness excisions with backhanded running V-Loc suture.

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Imaging modalities and management of prenatally diagnosed suprarenal masses: an updated literature review and the experience at a high volume Fetal Treatment Center.

BACKGROUND/PURPOSE: The differential diagnosis for prenatal suprarenal masses (SRMs) is broad and includes neuroblastoma, adrenal hemorrhage, and subdiaphragmatic extralobar pulmonary sequestration (SEPS). We sought to elucidate the appropriate postnatal management for fetuses found to have an SRM. METHODS: We conducted a retrospective review of patients prenatally diagnosed with SRM at our institution between 1998 and 2018. Prenatal characteristics, imaging, and neonatal outcomes were collected. We also performed a PubMed literature search and pooled analysis of all patients with a prenatally diagnosed SRM previously described in the literature. RESULTS: The literature review yielded 32 studies, of which 19 were single case reports. In our case series, 12 patients were included. Seven patients were delivered vaginally, one was terminated. Postnatal diagnoses included: SEPS (n = 5), adrenal hemorrhage (n = 3), polycystic kidney (n = 2), splenic cyst (n = 1), and unknown for one patient. All but two of the final diagnoses had been on the initial diagnostic differential. With the exception of the terminated fetus, all remain alive today. On pooled analysis, patients who underwent operative management were diagnosed later 32 versus 24 weeks and had a significant predominance of left-sided lesions (59.5 versus 39.2%). The published literature demonstrates a trend toward observation versus resection over the past 30 years. CONCLUSIONS: Patients prenatally diagnosed with an SRM have an excellent prognosis. Our series demonstrates a high incidence of SEPS, which were all resected, and adrenal hemorrhage, which were observed with repeat imaging. These patients can be followed with serial postnatal ultrasounds to determine the diagnosis prior to deciding the appropriate treatment.

In Utero Therapy for Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia is an anomaly that is often prenatally diagnosed and spans a wide spectrum of disease, with high morbidity and mortality associated with fetuses with severe defects. Congenital diaphragmatic hernia is thus an ideal target for fetal intervention. We review the literature on prenatal diagnosis, describe the history of fetal intervention for congenital diaphragmatic hernia, and discuss fetal endoscopic tracheal occlusion and the Tracheal Occlusion To Accelerate Lung growth trial results. Finally, we present preclinical studies for potential future directions.