Neurocognitive Effects of Fetal Exposure to Anesthesia.

Surgery during pregnancy occurs when maternal or fetal needs outweigh the status quo, yet much uncertainty remains regarding the effects of anesthesia and surgery on fetal neurodevelopment. This article will review common maternal and fetal indications for invasive procedures, along with contemporary research on fetal neurodevelopment following anesthesia and surgery, focusing on future areas of investigation.

Enhanced Recovery after Surgery: Benefits for the Fetal Surgery Patient.

BACKGROUND: The fetoscopic approach to the prenatal closure of a neural tube defect (NTD) may offer similar advantages to the newborn compared to prenatal open closure of a NTD, with a reduction in maternal risks. Enhanced recovery after surgery (ERAS) protocols have been applied to different surgical procedures with documented advantages. We modified the perioperative care of patients undergoing in utero repair of myelomeningocele with the goal of enhancing the recovery. A retrospective study comparing traditional management to the ERAS protocol was conducted. AIMS: Primary aim was to evaluate the length of stay (LOS). Secondary outcomes included pain scores, time to oral intake, opioid-induced side effects, and respiratory complications. METHODS: Thirty patients who underwent a mid-gestation fetoscopic closure of a NTD were included. Data analyzed include demographics, comorbidities, LOS, anatomical location of the NTD, magnesium sulfate doses and duration of administration, oxygen requirements, duration of the postoperative epidural infusion, duration of surgery and anesthesia, incidence of postoperative nausea and vomiting, respiratory complications, time to oral intake, pain scores, and sedation scores. Differences between the treatment groups were compared using the independent sample t-test or Mann-Whitney Ʋ test. RESULTS: Of the 30 patients, 10 patients were managed according to the ERAS protocol and 20 patients according to the traditional management (1:2 ratio). The mean gestational age at the time of intervention for the traditional and ERAS groups was 24.9 ± 0.5 weeks and 24.8 ± 0.5 weeks, respectively. Compared to the traditional group, the LOS was reduced in the ERAS group to 112.5 ± 12.6 h (4.7 ± 0.5 days) from 179.7 ± 87.9 h (7.5 ± 3.7 days) (p = 0.012). The time to oral intake was also shorter 502.6 ± 473.4 min versus 1015.6 ± 698.2 min; p = 0.049. Oxygen requirements were prolonged in the traditional group (1843.7 ± 1262.6 min vs. 1051.7 ± 1078.1 min p = 0.052). The total duration of magnesium sulfate was longer for patients in the traditional group (2125.6 ± 727.1 min vs. 1429.5 ± 553.8 min; p = 0.006). No statistically significant difference in pain scores was observed between the groups. CONCLUSIONS: Establishing an ERAS protocol for fetoscopic in utero repair of NTDs approach is feasible with the advantages of decreased postoperative LOS, reduced oxygen requirements, lower duration of magnesium sulfate infusion, and facilitation of earlier oral intake without compromising the pain scores.

Anesthesia-Related Factors Associated with Preterm Labor and Delivery after Open Fetal Surgery.

BACKGROUND: Fetal surgery, such as for meningomyelocele repair, has a clear clinical fetal benefit. In patients who undergo in utero repair of meningomyelocele, for example, there is reduced long-term disease morbidity. However, despite the beneficial effects of early intervention, women who undergo fetal interventions have an increased risk of preterm labor and delivery. Several surgery-related factors have been described but no specific anesthesia-related factors. OBJECTIVE: The aim of this study was to determine if any aspects of the perioperative anesthetic management influenced maternal complications following in utero surgery. METHODS: This was a retrospective chart review of the anesthetic management of mothers and fetuses who presented for open and fetoscopic myelomeningocele repair, between 2011 and 2015, at Texas Children's Fetal Center®. RESULTS: Forty-six women underwent open or fetoscopic repair of neural tube defects at our institution. We found the maternal heart rate in the postoperative period to be associated with a higher likelihood of preterm labor, but not delivery. The odds of having preterm delivery was higher for nulliparous patients and those with lower intraoperative diastolic pressure. CONCLUSIONS: Our findings confirm what has been previously reported regarding the association of nulliparity with preterm delivery. Additionally, this study highlights the importance of maintaining stable perioperative hemodynamics during the intraoperative and postoperative phases of care for patients undergoing in utero surgery.

Anesthesia for Maternal-Fetal Interventions: A Consensus Statement From the American Society of Anesthesiologists Committees on Obstetric and Pediatric Anesthesiology and the North American Fetal Therapy Network.

Maternal-fetal surgery is a rapidly evolving specialty, and significant progress has been made over the last 3 decades. A wide range of maternal-fetal interventions are being performed at different stages of pregnancy across multiple fetal therapy centers worldwide, and the anesthetic technique has evolved over the years. The American Society of Anesthesiologists (ASA) recognizes the important role of the anesthesiologist in the multidisciplinary approach to these maternal-fetal interventions and convened a collaborative workgroup with representatives from the ASA Committees of Obstetric and Pediatric Anesthesia and the Board of Directors of the North American Fetal Therapy Network. This consensus statement describes the comprehensive preoperative evaluation, intraoperative anesthetic management, and postoperative care for the different types of maternal-fetal interventions.

Airway management for neonates requiring ex utero intrapartum treatment (EXIT).

In utero congenital malformations in the fetus can occasionally lead to an obstructed airway at birth accompanied by hypoxic injury or peripartum demise, without intervention. Ex utero intrapartum treatment (EXIT) may help reduce morbidity and mortality associated with challenging airways by providing extra time on uteroplacental circulation to secure the airway. Meticulous preparation and planning are crucial for this procedure. Many different types of congenital malformations can result in a difficult airway, but there is no correlation between specific malformations and a required type of airway intervention. Based on our experience and literature review, an airway process flow diagram has been created to help assist teams in decision-making for airway intervention in a neonate during the EXIT procedure. The management of the airway in this scenario involves additional unique considerations that accompany handling a partially delivered newborn in the uterine environment. Extensive preparation and team rehearsal are essential to the success of this procedure.

Evaluation and Disposition of Fetal Myelomeningocele Repair Candidates: A Large Referral Center Experience.

BACKGROUND: Fetal myelomeningocele (fMMC) repair yields superior outcomes to postnatal repair and is increasingly offered at select fetal centers. OBJECTIVES: To report the fMMC referral process from initial referral to evaluation and surgical intervention in a large fetal referral center. METHODS: We conducted a retrospective cohort study of patients referred to Texas Children's Fetal Center for fMMC between September 2013 and January 2018, reviewing the process from referral to final disposition. The stepwise evaluation included a phone interview followed by multidisciplinary consultation at our fetal center. We modified the Management of Myelomeningocele Study inclusion and exclusion criteria to allow a maternal body mass index of 35-40 on an individual basis. RESULTS: A total of 204 referrals were contacted for a phone interview; 175 (86%) pursued outpatient evaluation, and 80 (46%) of them qualified for repair. Among the eligible patients, 37 (46%) underwent fetoscopic repair, 20 (25%) underwent open repair, and 17 (21%) declined prenatal surgery. Of the 89 noneligible patients (53%) excluded upon outpatient evaluation, 64 (72%) were excluded for fetal and 17 (19%) for maternal reasons. No hindbrain herniation (16%) and maternal BMI and/or hypertension (5%) were the most common reasons for fetal and maternal exclusion, respectively. A total of 31% of our referral population underwent fetal surgery. CONCLUSIONS: A small percentage of fMMC referrals ultimately undergo prenatal surgery. Stepwise evaluation and multidisciplinary teams are key to the success of large referral programs.

Cervical lymphatic malformations: Prenatal characteristics and ex utero intrapartum treatment.

BACKGROUND: The ex utero intrapartum treatment (EXIT) is utilized to transition fetuses with prenatally diagnosed airway obstruction to postnatal life. We describe the unique clinical course, diagnosis, treatment, and outcomes of patients with cervical lymphatic malformation (CLM) managed with EXIT. METHODS: Review of fetuses with diagnosed CLM was delivered by EXIT (2001-2018) in a tertiary referral fetal center. Outcomes included survival, tracheostomy at discharge, neonatal course after delivery, and pulmonary hypoplasia. Data are reported as median [range] and rate (%). RESULTS: Out of 45 patients delivered by EXIT, 10 were delivered for CLM: seven had polyhydramnios, one had nonimmune hydrops, five delivered preterm, and three were emergency EXITs. The EXIT time and estimated blood loss were 125 minutes (95, 158) and 900 mL (500, 1500), respectively. Airway was secured in all. There was one neonatal death (day 8) with prematurity, sepsis, and pulmonary hypoplasia. Three out of nine were discharged with a tracheostomy. CONCLUSION: In CLM, close monitoring for structural neck involvement and development of polyhydramnios are important and may be an indication for EXIT as the optimal delivery mode. An experienced multidisciplinary team is a key factor for an effective approach to the obstructed airway in CLM.

Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction.

BACKGROUND: Patients with a prenatal diagnosis of lower urinary tract obstruction (LUTO) may undergo prenatal interventions, such as vesicoamniotic shunt (VAS) placement, as a temporary solution for relieving urinary tract obstruction. A recent FDA communication has raised awareness of the potential neurocognitive adverse effects of anesthesia in children. We hypothesized as to whether a prenatal LUTO staging system was predictive of the number of anesthesia events for prenatally diagnosed LUTO patients. METHODS: We retrospectively reviewed the prenatal and postnatal clinical records for patients with prenatally diagnosed LUTO from 2012 to 2015. Patients were stratified by prenatal VAS status and by LUTO disease severity according to Ruano et al. (Ultrasound Obstet Gynecol. 2016). RESULTS: 31 patients were identified with a prenatal LUTO diagnosis, and postnatal records were available for 21 patients (seven patients in each stage). When combining prenatal and postnatal anesthesia, there was a significant difference in the number of anesthesia encounters by stage (1.6, 3.7, and 6.7 for Stage I, II, and III respectively, p = .034). Upon univariate analysis, higher gestational age (GA) at birth was associated with a decreased number of anesthesia events in the first year (p = .031). CONCLUSIONS: The majority of infants with prenatally diagnosed LUTO will undergo postnatal procedures with general anesthesia exposure in the first year of life. Patients with higher prenatal LUTO severity experienced a higher number of both prenatal and postnatal anesthesia encounters. In addition, higher GA at birth was associated with fewer anesthesia encounters in the first year. LEVEL OF EVIDENCE: This is a prognostic study with Level IV evidence.

Fetal Surgery Decreases Anesthesia-Induced Neuroapoptosis in the Mid-Gestational Fetal Ovine Brain.

BACKGROUND: Studies demonstrating an association between anesthesia and brain cell death (neuroapoptosis) in young animals were performed without accompanying surgery. This study tests the hypothesis that fetal surgery decreases anesthesia-induced neuroapoptosis. MATERIALS AND METHODS: Seventy-day-pregnant ewes received 2% isoflurane for 1 h (low dose [LD]) or 4% for 3 h (high dose [HD]) with or without fetal surgery (S). Unexposed fetuses served as controls (C). Fetal brains were processed for neuroapoptosis using anti-caspase-3 antibodies. Data were analyzed using ANOVA. RESULTS: Twenty-eight fetal sheep were evaluated. Dentate gyrus neuroapoptosis was lower in the HD+S group (13.1 ± 3.76 × 105/mm3) than in the HD (19.1 ± 1.40 × 105/mm3, p = 0.012) and C groups (18.3 ± 3.55 × 105/mm3, p = 0.035). In the pyramidal layer of the hippocampus, neuroapoptosis was lower in the HD+S group (8.11 ± 4.88 × 105/mm3) than in the HD (14.8 ± 2.82 × 105/mm3, p = 0.006) and C groups (14.1 ± 4.54 × 105/mm3, p = 0.019). The LD+S group showed a trend towards a significant decrease in neuroapoptosis in the pyramidal layer (LD+S 7.51 ± 1.48 vs. LD 13.5 ± 1.87 vs. C 14.1 ± 4.54 × 105/mm3, p = 0.07) but not in the dentate gyrus. Fetal surgery did not affect neuroapoptosis in the frontal cortex or endplate. CONCLUSIONS: Fetal surgery decreases isoflurane-induced neuroapoptosis in the dentate gyrus and the pyramidal layer of mid-gestational fetal sheep. Long-term effects of these observations on memory and learning deserve further exploration.

Food and Drug Administration warning on anesthesia and brain development: implications for obstetric and fetal surgery.

There has been growing concern about the detrimental effects of certain anesthetic agents on the developing brain. Preclinical studies in small animal models as well as nonhuman primates suggested loss or death of brain cells and consequent impaired neurocognitive function following anesthetic exposure in neonates and late gestation fetuses. Human studies in this area are limited and currently inconclusive. On Dec. 14, 2016, the US Food and Drug Administration issued a warning regarding impaired brain development in children following exposure to certain anesthetic agents used for general anesthesia, namely the inhalational anesthetics isoflurane, sevoflurane, and desflurane, and the intravenous agents propofol and midazolam, in the third trimester of pregnancy. Furthermore, this warning recommends that health care professionals should balance the benefits of appropriate anesthesia in young children and pregnant women against potential risks, especially for procedures that may last >3 hours or if multiple procedures are required in children <3 years old. The objective of this article is to highlight how the Food and Drug Administration warning may impact the anesthetic and surgical management of the obstetric patient. Neuraxial anesthesia (epidural or spinal anesthesia) is more commonly administered for cesarean delivery than general anesthesia. The short duration of fetal exposure to general anesthesia during cesarean delivery has not been associated with learning disabilities. However, the fetus can also be exposed to both intravenous and inhalation anesthetics during nonobstetric or fetal surgery in the second and third trimester; this exposure is typically longer than that for cesarean delivery. Very few studies address the effect of anesthetic exposure on the fetus in the second trimester when most nonobstetric and fetal surgical procedures are performed. It is also unclear how the plasticity of the fetal brain at this stage of development will modulate the consequences of anesthetic exposure. Strategies that may circumvent possible untoward long-term neurologic effects of anesthesia in the baby include: (1) use of nonimplicated (nongamma-aminobutyric acid agonist) agents for sedation such as opioids (remifentanil, fentanyl) or the alpha-2 agonist, dexmedetomidine, when appropriate; (2) minimizing the duration of exposure to inhalational anesthetics for fetal, obstetric, and nonobstetric procedures in the pregnant patient, as much as possible within safe limits; and (3) commencing surgery promptly and limiting the interval between induction of anesthesia and surgery start time will help decrease patient exposure to inhalational agents. While the Food and Drug Administration warning was based on duration and repetitive nature of exposure rather than concentration of inhalational agents, intravenous tocolytics can be considered for intraoperative use, to provide uterine relaxation for fetal surgery, in lieu of high concentrations of inhalational anesthetic agents. Practitioners should consider the type of anesthesia that will be administered and the potential risks when scheduling patients for nonobstetric and fetal surgery.

Prenatal management of fetal intrapericardial teratoma: a systematic review.

OBJECTIVES: The purpose of this systematic review is to provide a comprehensive overview on the clinical course, perinatal outcome, and effectiveness of prenatal management options for pericardial teratoma. METHODS: A comprehensive search including Ovid MEDLINE, Ovid EMBASE, and Scopus was conducted from inception to September 2016. All studies that reported the prenatal course of pericardial teratoma in singleton or twin gestations were considered eligible. Standardized forms were used for data abstraction by two independent reviewers. RESULTS: Out of 217 screened abstracts, 59 studies reporting 67 fetuses with pericardial teratoma were included. Twenty-three singleton fetuses and 3 fetuses in twin gestations underwent prenatal treatment, and 20 (76.9%) of them were hydropic at the time of intervention. Of those, 15/20 (75%) had a favorable outcome. In the non-intervention group (n = 41), 26 (63.4%) developed hydrops, and out of those, 8 (30.8%) had a favorable outcome. CONCLUSION: Prenatal fluid drainage and other prenatal techniques have been utilized in the treatment of intrapericardial teratoma. While most fetuses tolerated pericardiocentesis, the neonatal benefit of this procedure is still uncertain, and outcomes of other interventions had variable success. Prenatal intervention for pericardial teratoma may be an option in specialized units but, given the maternal and fetal risks, needs careful consideration. © 2017 John Wiley & Sons, Ltd.

Fetoscopic Open Neural Tube Defect Repair: Development and Refinement of a Two-Port, Carbon Dioxide Insufflation Technique.

OBJECTIVE: To describe development of a two-port fetoscopic technique for spina bifida repair in the exteriorized, carbon dioxide-filled uterus and report early results of two cohorts of patients: the first 15 treated with an iterative technique and the latter 13 with a standardized technique. METHODS: This was a retrospective cohort study (2014-2016). All patients met Management of Myelomeningocele Study selection criteria. The intraoperative approach was iterative in the first 15 patients and was then standardized. Obstetric, maternal, fetal, and early neonatal outcomes were compared. Standard parametric and nonparametric tests were used as appropriate. RESULTS: Data for 28 patients (22 endoscopic only, four hybrid, two abandoned) are reported, but only those with a complete fetoscopic repair were analyzed (iterative technique [n=10] compared with standardized technique [n=12]). Maternal demographics and gestational age (median [range]) at fetal surgery (25.4 [22.9-25.9] compared with 24.8 [24-25.6] weeks) were similar, but delivery occurred at 35.9 (26-39) weeks of gestation with the iterative technique compared with 39 (35.9-40) weeks of gestation with the standardized technique (P<.01). Duration of surgery (267 [107-434] compared with 246 [206-333] minutes), complication rates, preterm prelabor rupture of membranes rates (4/12 [33%] compared with 1/10 [10%]), and vaginal delivery rates (5/12 [42%] compared with 6/10 [60%]) were not statistically different in the iterative and standardized techniques, respectively. In 6 of 12 (50%) compared with 1 of 10 (10%), respectively (P=.07), there was leakage of cerebrospinal fluid from the repair site at birth. Management of Myelomeningocele Study criteria for hydrocephalus-death at discharge were met in 9 of 12 (75%) and 3 of 10 (30%), respectively, and 7 of 12 (58%) compared with 2 of 10 (20%) have been treated for hydrocephalus to date. These latter differences were not statistically significant. CONCLUSION: Fetoscopic open neural tube defect repair does not appear to increase maternal-fetal complications as compared with repair by hysterotomy, allows for vaginal delivery, and may reduce long-term maternal risks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02230072.

Feasibility and Outcomes of Fetoscopic Tracheal Occlusion for Severe Left Diaphragmatic Hernia.

OBJECTIVE: To evaluate feasibility and initial outcomes of fetoscopic tracheal occlusion for severe diaphragmatic hernia compared with a historical cohort who had not received fetal tracheal occlusion. METHODS: Outcomes in a prospective observational cohort who underwent fetoscopic tracheal occlusion for severe fetal left diaphragmatic hernia without associated anomalies were compared with our historical nontreated cohort of matched fetuses of similar severity. Fetuses were classified using the same ultrasonography and magnetic resonance imaging methodology-prospectively in the fetoscopic tracheal occlusion group and retrospectively in the historical nontreated cohort. Obstetric and postnatal outcomes were evaluated and compared. RESULTS: Between January 2004 and June 2015, 218 fetuses with diaphragmatic hernia were evaluated. Twenty (9%) fetuses had severe left diaphragmatic hernia (lung-head ratio 1.0 or less and liver herniation), of which 9 of 20 were managed without tracheal occlusion. Eleven were offered the procedure and in 10, it was successful. Mean (±standard deviation) gestational age was 27.9±1.1 weeks at attempted balloon placement, 34.1±1.1 weeks at removal, and 35.3±2.2 weeks at delivery. One patient required an ex utero intrapartum treatment procedure at delivery to remove the balloon. There were no maternal complications or fetal deaths. All neonates underwent postnatal repair with a patch. The 6-month, 1-year, and 2-year survival rates were significantly higher in our treated cohort than in our nontreated historical cohort (80% compared with 11%, risk difference 69%, 95% confidence interval [CI] 38-100%, P=.01; 70% compared with 11%, risk difference 59%, 95% CI 24-94%, P=.02; and 67% compared with 11%, risk difference 56%, 95% CI 19-93%, P=.04, respectively) with reduced need for extracorporeal membrane oxygenation (30% compared with 70%, risk difference 40%, 95% CI 10-79%, P=.05). CONCLUSION: Fetoscopic tracheal occlusion is feasible and is associated with improved postnatal outcomes in severe left diaphragmatic hernia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00881660.

Factors associated with fetal shunt dislodgement in lower urinary tract obstruction.

OBJECTIVE: To identify factors associated with fetal shunt dislodgement in lower urinary tract obstruction (LUTO). METHODS: We conducted a retrospective study of 42 consecutive fetuses with a diagnosis of LUTO in a tertiary fetal center between April 2013 and November 2015. Possible factors associated with prenatal shunt dislodgment were evaluated in fetuses who underwent shunt placement, including gestational age at diagnosis, gestational age at procedure, presence of 'keyhole sign', initial fetal bladder volume and wall thickness, prenatal ultrasonographic renal characteristics, amniotic fluid volume, presence of ascites prior to shunting, and type of fetal shunt. RESULTS: Nineteen (46.3%) fetuses underwent shunt placement at a median gestational age of 19 (range: 16.3-31.1) weeks. Shunt dislodgement occurred in 10 (52.6%) patients. A total of 35 procedures were performed; among which 16 (45.7%) were repeat procedures. The only prenatal factor associated with shunt dislodgement was the type of the shunt; Kaplan-Meier analysis indicated that the Rocket was associated with increased likelihood of remaining orthotopic (p = 0.04). CONCLUSION: Fetal shunt dislodgement occurs in approximately half of the patients and appears to be associated with the type of the shunt. Future research is necessary to develop better shunt systems and to investigate different fetal therapeutic approaches. © 2016 John Wiley & Sons, Ltd.

A comparison of the Truview PCD and the GlideScope Cobalt AVL video-laryngoscopes to the Miller blade for successfully intubating manikins simulating normal and difficult pediatric airways.

BACKGROUND: Video-laryngoscopes provide better glottic visualization, but tracheal intubation times are longer, compared to conventional direct laryngoscopy in adult patients with normal airways. The objective of this randomized crossover study was to compare times to successful tracheal intubation with video-laryngoscope and direct laryngoscopy in manikins simulating infants with normal and abnormal airways. METHODS: Thirty experienced pediatric anesthesia practitioners performed tracheal intubation in three distinct manikins simulating infants with (i) a normal airway (ii), an anterior larynx, and (iii) the Pierre Robin sequence anatomy. These were performed using a standard Miller #1 blade, the GlideScope Cobalt AVL, and the Truview PCD video-laryngoscope, first in a normal neck and then an unstable cervical spine scenario (18 intubations/subject). The specific assigned order of devices and manikins for each participant was based on a three by three Latin square design to minimize carryover effects between the model and the device. Predefined times to intubation were analyzed by Cox regression model and Kaplan-Meier survival curves. RESULTS: Intubation times were shorter and success rates were higher with the Miller blade compared to either the GlideScope or the Truview videoscope in all three manikins in both scenarios, but did not differ between the GlideScope and the Truview devices. Improved intubation times and success rates in the unstable cervical spine scenario compared to the normal neck were attributed to learning effects with sequential intubation. CONCLUSION: Higher success rates and shorter intubation times with the Miller blade compared to either video-laryngoscope may reflect greater experience with direct laryngoscopy, need for more video-laryngoscopy training, or result from the manikin design. Individual practitioners may differ in their preference of device for intubating a child with anticipated difficult airway based on their previous experiences, self-assessment of their skills, and evaluation of the child's airway anatomy.

Defining and predicting 'intrauterine fetal renal failure' in congenital lower urinary tract obstruction.

BACKGROUND: The aim of this study was to identify predictors of 'intrauterine fetal renal failure' in fetuses with severe congenital lower urinary tract obstruction (LUTO). METHODS: We undertook a retrospective study of 31 consecutive fetuses with a diagnosis of LUTO in a tertiary Fetal Center between April 2013 and April 2015. Predictors of 'intrauterine fetal renal failure' were evaluated in those infants with severe LUTO who had either a primary composite outcome measure of neonatal death in the first 24 h of life due to severe pulmonary hypoplasia or a need for renal replacement therapy within 7 days of life. The following variables were analyzed: fetal bladder re-expansion 48 h after vesicocentesis, fetal renal ultrasound characteristics, fetal urinary indices, and amniotic fluid volume. RESULTS: Of the 31 fetuses included in the study, eight met the criteria for 'intrauterine fetal renal failure'. All of the latter had composite poor postnatal outcomes based on death within 24 h of life (n = 6) or need for dialysis within 1 week of life (n = 2). The percentage of fetal bladder refilling after vesicocentesis at time of initial evaluation was the only predictor of 'intrauterine fetal renal failure' (cut-off <27 %, area under the time-concentration curve 0.86, 95 % confidence interval 0.68-0.99; p = 0.009). CONCLUSION: We propose the concept of 'intrauterine fetal renal failure' in fetuses with the most severe forms of LUTO. Fetal bladder refilling can be used to reliably predict 'intrauterine fetal renal failure', which is associated with severe pulmonary hypoplasia or the need for dialysis within a few days of life.

Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain.

BACKGROUND: Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. OBJECTIVE: The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. STUDY DESIGN: Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. RESULTS: A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2% isoflurane exposure compared to controls (1.57 ± 0.22 × 10(6)/mm(3) vs 1.01 ± 0.44 × 10(6)/mm(3), P = .02). Fetuses at 70 days gestation with repeated exposure demonstrated decreased frontal cortex neurons at day 130 when compared to age-matched controls (2.42 ± 0.3 × 10(5)/mm(3) vs 7.32 ± 0.4 × 10(5)/mm(3), P = .02). No significant difference in neuroapoptosis was observed between the repeated exposure group and controls in the hippocampus, cerebellum, or basal ganglia. CONCLUSION: Repeated isoflurane exposure in midgestation sheep resulted in increased frontal cortex neuroapoptosis. This persisted into late gestation as decreased neuronal cell density. While animal studies should be extrapolated to human beings with caution, our findings suggest that the number of anesthetic/sedative exposures should be considered when contemplating the risks and benefits of fetal intervention as certain fetal therapies may need to be repeated.

Prenatal Identification of Pierre Robin Sequence: A Review of the Literature and Look towards the Future.

Fetal ultrasonography is an important tool used to prenatally diagnose many craniofacial conditions. Pierre Robin sequence (PRS) is a rare congenital deformation characterized by micrognathia, glossoptosis, and airway obstruction. PRS can present as a perinatal emergency when the retropositioned tongue obstructs the airway leading to respiratory compromise. More predictable and reliable diagnostic studies could help the treating medical team as well as families prepare for these early airway emergencies. The medical literature was reviewed for different techniques used to prenatally diagnose PRS radiologically. We have reviewed these techniques and suggested a possible diagnostic pathway to consistently identify patients with PRS prenatally.