The impact of a biocellulose-based repair of fetal open spina bifida on the need to untether the cord: is it time to unify techniques for prenatal repair?

OBJECTIVE: To report the need for cord untethering after prenatal repair of open spina bifida using a unique biocellulose-based technique performed at a later gestational age. METHODS: An observational cohort study was conducted to determine the incidence of tethered cord syndrome. Between May 2013 and May 2022, we performed 172 procedures using the percutaneous fetoscopic approach in fetuses at 26-28 weeks of gestation. After placode dissection, a biocellulose patch was placed to cover the placode, a myofascial flap (when possible) was dissected, and the skin was closed. Owing to death or loss to follow-up, 23 cases were excluded. Cord tethering syndrome was defined as symptoms of medullary stretching, and the infants were evaluated and operated on by local neurosurgeons after an magnetic resonance imaging examination. Infants over 30-month had ambulation and neurodevelopment evaluations (PEDI scale). RESULTS: Among 172 cases operated at a median gestational age of 26.7 weeks and delivered at 33.2 weeks, 149 cases were available for postnatal follow-up, and cord untethering was needed in 4.4% of cases (6/136; excluding 13 cases younger than 12 months). Cerebrospinal fluid diversion and bladder catheterization were needed in 38% and 36% of cases, respectively. Of the 78 cases evaluated at 30 months, 49% were ambulating independently, and 94% had normal social function. CONCLUSION: The biocellulose-based technique was associated with a low rate of cord tethering, wich may be attributed to the lack of the duramater suture during prenatal repair, the formation of a neoduramater and/or later gestational age of surgery.

Longitudinal evolution of central nervous system anomalies in fetuses with open spina bifida fetoscopic repair and correlation with neurologic outcome.

BACKGROUND: Open spina bifida is associated with central nervous system anomalies such as abnormal corpus callosum and heterotopias. However, the impact of prenatal surgery over these structures remains unclear. OBJECTIVE: This study aimed to describe longitudinal changes of central nervous system anomalies before and after prenatal open spina bifida repair and to evaluate their relationship with postnatal neurologic outcomes. STUDY DESIGN: Retrospective cohort study of fetuses with open spina bifida who underwent percutaneous fetoscopic repair from January 2009 to August 2020. All women had presurgical and postsurgical fetal magnetic resonance imaging, at an average of 1 week before and 4 weeks after surgery, respectively. We evaluated defect characteristics in the presurgical magnetic resonance images; and fetal head biometry, clivus supraocciput angle, and the presence of structural central nervous system anomalies, such as abnormalities in corpus callosum, heterotopias, ventriculomegaly, and hindbrain herniation, in both presurgical and postsurgical magnetic resonance images. Neurologic assessment was performed using the Pediatric Evaluation of Disability Inventory scale in children who were 12 months or older, covering 3 different sections, namely self-care, mobility, and social and cognitive function. RESULTS: A total of 46 fetuses were evaluated. Presurgery and postsurgery magnetic resonance imaging were performed at a median gestational age of 25.3 and 30.6 weeks, with a median interval of 0.8 weeks before surgery, and 4.0 weeks after surgery. There was a 70% reduction in hindbrain herniation (100% vs 32.6%; P<.001), and a normalization of the clivus supraocciput angle after surgery (55.3 [48.8-61.0] vs 79.9 [75.2-85.4]; P<.001). No significant increase in abnormal corpus callosum (50.0% vs 58.7%; P=.157) or heterotopia (10.8% vs 13.0%; P=.706) was observed. Ventricular dilation was higher after surgery (15.6 [12.7-18.1] vs 18.8 [13.7-22.9] mm; P<.001), with a higher proportion of severe ventricular dilation after surgery (≥15mm) (52.2% vs 67.4%; P=.020). Thirty-four children underwent neurologic assessment, with 50% presenting a global optimal Pediatric Evaluation of Disability Inventory result and 100% presenting a normal social and cognitive function. Children with optimal global Pediatric Evaluation of Disability Inventory presented a lower rate of presurgical anomalies in corpus callosum and severe ventriculomegaly. When analyzed as independent variables to global Pediatric Evaluation of Disability Inventory scale, the presence of abnormal corpus callosum and severe ventriculomegaly showed an odds ratio of 27.7 (P=.025; 95% confidence interval, 1.53-500.71) for a suboptimal result. CONCLUSION: Prenatal open spina bifida repair did not change the proportion of abnormal corpus callosum nor heterotopias after surgery. The combination of presurgical abnormal corpus callosum and severe ventricular dilation (≥15 mm) is associated with an increased risk of suboptimal neurodevelopment.

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection†.

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses. Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed. Results: There were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus. Conclusion: In CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement.

Fetoscopic insufflation of heated-humidified carbon dioxide during simulated spina bifida repair is safe under controlled anesthesia in the fetal lamb.

OBJECTIVE: To assess the safety of Partial-Amniotic-Insufflation-of-heated-humidified-CO2 (hPACI) during fetoscopic spina bifida repair (fSB-repair). METHOD: A simulated fSB-repair through an exteriorized uterus under hPACI was performed in 100-day fetal lambs (term = 145 days) under a laboratory anesthesia protocol (n = 5; group 1) which is known to induce maternal-fetal acidosis and hypercapnia. Since these may not occur clinically, we applied a clinical anesthesia protocol (n = 5; group 2), keeping maternal parameters within physiological conditions, that is, controlled maternal arterial carbon dioxide (CO2) pressure (pCO2  = 30 mmHg), blood pressure (≥67 mmHg), and temperature (37.1-39.8°C). Our superiority study used fetal pH as the primary outcome. RESULTS: Compared to group 1, controlled anesthesia normalized fetal pH (7.23 ± 0.02 vs. 7.36 ± 0.02, p < 0.001), pCO2 (70.0 ± 9.1 vs. 43.0 ± 1.0 mmHg, p = 0.011) and bicarbonate (27.8 ± 1.1 vs. 24.0 ± 0.9 mmol/L, p = 0.071) at baseline. It kept them within clinically acceptable limits (pH ≥ 7.23, pCO2  ≤ 70 mmHg, bicarbonate ≤ 30 mm/L) for ≥120 min of hPACI as opposed to ≤30 min in group one. Fetal pO2 and lactate were comparable between groups and generally within normal range. Fetal brain histology demonstrated fewer apoptotic cells and higher neuronal density in the prefrontal cortex in group two. There was no difference in fetal membrane inflammation, which was mild. CONCLUSION: Fetoscopic insufflation of heated-humidified CO2 during simulated fSB-repair through an exteriorized uterus can be done safely under controlled anesthesia.

The Potential Applications of Augmented Reality in Fetoscopic Surgery for Antenatal Treatment of Myelomeningocele.

OBJECTIVE: To develop a preoperative planning method using augmented reality (AR) of a specific surgical procedure: fetoscopy for myelomeningocele repair. METHODS: Imaging data were acquired of a pregnant woman at 27 weeks of gestation whose fetus was diagnosed with myelomeningocele. The patient was identified as a candidate for fetoscopic repair of the spine defect, and an AR application for mobile device simulation was developed. The virtual customized model was created by analysis of the presurgical magnetic resonance imaging. A real-time AR interface was developed by using an application that enhanced the anatomical aspects of both mother and fetus. RESULTS: A virtual model for planning fetoscopy repair for myelomeningocele was developed. Preoperative and postoperative procedures were successfully carried out, emphasizing the beneficial role of the AR application. The use of the AR model allowed the multidisciplinary team to engage in discussion to determine the appropriate surgical approach. It also allowed a clearer explanation of the procedure to the parents enabling a better understanding of the parents regarding specifics characteristics of their baby's spine defect. CONCLUSIONS: This new preoperative platform using a virtual model represents an important tool to improve patient's comprehension, multidisciplinary discussion, and surgical planning. In addition, it can be used worldwide as a teaching tool in the fetal surgery field.

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.

Teaching and training the total percutaneous fetoscopic myelomeningocele repair.

Skin-over-biocellulose for Antenatal Fetoscopic Repair (SAFER) is a recently developed technique for fully percutaneous fetoscopic repair of myelomeningocele. The formation of a neo-dura mater triggered by the use of a biocellulose patch over the placode obviates the need of primary repair of fetal dura mater, and seems to further improve neurodevelopmental outcome. Insufflation of humidified carbon dioxide into the amniotic cavity requires proper training and a different equipment set from those used in the classic "under-water" fetoscopy. To shorten the learning curve of novice teams, we have developed a structured training course encompassing three critical steps: (1) visiting the proctor center, (2) selection of the first case, and (3) on-site training of the surgical team. Upon the site arrival, there will be: (1) theoretical lecture for all specialists involved in the fetal care, (2) simulation training, and (3) surgical proctoring. Proctor team can take over the surgery if the local team cannot complete. This training course has been successfully used in five different countries: Israel, Chile, Italy, USA and England and all local teams are already performing surgeries solo without any failures or maternal morbidity. Teaching new procedures in fetal medicine is challenging, because of the small number of candidate cases, and the direct relation of good outcomes and the number of cases operated. This proposed training modules may be adopted by other teams that want to embark on this type of novel minimally invasive treatment.

Ultrasound diagnosis of microcephaly: a comparison of three reference curves and postnatal diagnosis.

PURPOSE: To evaluate which reference curve (RC)-Snijders, Intergrowth 21st (IG21) and World Health Organization (WHO)-is more accurate for microcephaly diagnosis. METHODS: Retrospective cohort study with more than 30,000 exams in more than 11,000 women. Microcephaly was confirmed by a neonatologist at birth and positive predictive values (PPVs) and misdiagnosis were assessed. RESULTS: A total of 71 cases were confirmed as microcephaly at birth. IG21 and Snijders PPVs showed to be more significant over WHO's (p < 0.001), without difference between them (p = 0.39). All RC were superimposed and did not show significant difference. When evaluated in different fragments, three trends were observed (until 30 weeks, between 30 and 36 and after 36 weeks of gestational age), with the latter interval showing a significant difference between IG21 and WHO (p = 0.0079). Conversely, WHO exhibited only one misdiagnosis, a much lower rate than Snijders, who missed eight cases and IG21, nine. CONCLUSION: WHO's RC appears to misdiagnose fewer cases, which could be useful for a population screening, while IG21's RC presented a more significant PPV, being more useful for a more precise final diagnosis in reference centers.

Evaluation of Cases of Abdominal Wall Endometriosis at Universidade Estadual de Campinas in a period of 10 Years / Avaliação dos casos de endometriose de parede abdominal na Universidade Estadual de Campinas em um período de 10 anos

Abstract Purpose To determine the clinical and epidemiological characteristics of abdominal wall endometriosis (AWE), as well as the rate and recurrence factors for the disease. Methods A retrospective study of 52 women with AWE was performed at Universidade Estadual de Campinas from 2004 to 2014. Of the 231 surgeries performed for the diagnosis of endometriosis, 52 women were found to have abdominal wall endometriosis (AWE). The frequencies, means and standard deviations of the clinical characteristics of these women were calculated, as well as the recurrence rate of AWE. To determine the risk factors for disease recurrence, Fisher's exact test was used. Results The mean age of the patients was 30.71 ± 5.91 years. The main clinical manifestations were pain (98%) and sensation of a mass (36.5%).We observed that 94% of these women had undergone at least 1 cesarean section, and 73% had used medication for the postoperative control of endometriosis. The lesion was most commonly located in the cesarean section scar (65%). The recurrence rate of the disease was of 26.9%. All 14 women who had relapsed had surgical margins compromised in the previous surgery. There was no correlation between recurrent AWE and a previous cesarean section (p = 0.18), previous laparotomy (p = 0.11), previous laparoscopy (p = 0.12) and postoperative hormone therapy (p = 0.51). Conclusion Women with previous cesarean sections with local pain or lumps should be investigated for AWE. The recurrence of AWE is high, especially when the first surgery is not appropriate and leaves compromised surgical margins.

Resumo Objetivos Determinar as características clínicas e epidemiológicas da endometriose de parede, bem como sua taxa de recorrência e os fatores que levam a ela. Métodos Estudo retrospectivo, em que se avaliaram 52 mulheres com endometriose de parede na Universidade Estadual de Campinas no período de 2004 a 2014. Entre as 231 cirurgias para diagnosticar endometriose, foram encontradas 52 mulheres que apresentavam endometriose de parede. Foram calculadas as frequências, a média e o desvio padrão das características clínicas destas mulheres, bem como a taxa de recorrência da endometriose de parede. Para determinar os fatores de risco de recorrência, foi utilizado o teste exato de Fisher. Resultados A idade média das mulheres foi de 30.71 ± 5,91 anos. As principais manifestações clínicas foram dor (98%) e sensação do nódulo (36,5%). Foi observado que 94% dessas mulheres tinham pelo menos uma cesárea, e 73% destas fizeram uso de medicação para controle da endometriose no pós-operatório. A localizaçãomais frequente da lesão foi na cicatriz da cesárea (65%). A taxa de recorrência da doença foi de 26,9%. Todas as 14mulheres que tiveramrecidiva tinhammargens cirúrgicas comprometidas na cirurgia prévia. Não houve correlação entre a endometriose de parede recorrente e a cesariana prévia (p = 0,18), a laparotomia prévia (p = 0,11), a laparoscopia prévia (p = 0,12) e receber terapia hormonal no pós-operatório (p = 0,51). Conclusão Mulheres com antecedente de cesárea anterior com dor local ou nódulo devem ser investigadas com relação à endometriose de parede. A recorrência do endometrioma de parede é alta, principalmente quando a primeira cirurgia não é adequada, e deixa margens cirúrgicas comprometidas.

Evaluation of Cases of Abdominal Wall Endometriosis at Universidade Estadual de Campinas in a period of 10 Years.

Purpose To determine the clinical and epidemiological characteristics of abdominal wall endometriosis (AWE), as well as the rate and recurrence factors for the disease. Methods A retrospective study of 52 women with AWE was performed at Universidade Estadual de Campinas from 2004 to 2014. Of the 231 surgeries performed for the diagnosis of endometriosis, 52 women were found to have abdominal wall endometriosis (AWE). The frequencies, means and standard deviations of the clinical characteristics of these women were calculated, as well as the recurrence rate of AWE. To determine the risk factors for disease recurrence, Fisher's exact test was used. Results The mean age of the patients was 30.71 ± 5.91 years. The main clinical manifestations were pain (98%) and sensation of a mass (36.5%). We observed that 94% of these women had undergone at least 1 cesarean section, and 73% had used medication for the postoperative control of endometriosis. The lesion was most commonly located in the cesarean section scar (65%). The recurrence rate of the disease was of 26.9%. All 14 women who had relapsed had surgical margins compromised in the previous surgery. There was no correlation between recurrent AWE and a previous cesarean section (p = 0.18), previous laparotomy (p = 0.11), previous laparoscopy (p = 0.12) and postoperative hormone therapy (p = 0.51). Conclusion Women with previous cesarean sections with local pain or lumps should be investigated for AWE. The recurrence of AWE is high, especially when the first surgery is not appropriate and leaves compromised surgical margins.

Objetivos Determinar as características clínicas e epidemiológicas da endometriose de parede, bem como sua taxa de recorrência e os fatores que levam a ela. Métodos Estudo retrospectivo, em que se avaliaram 52 mulheres com endometriose de parede na Universidade Estadual de Campinas no período de 2004 a 2014. Entre as 231 cirurgias para diagnosticar endometriose, foram encontradas 52 mulheres que apresentavam endometriose de parede. Foram calculadas as frequências, a média e o desvio padrão das características clínicas destas mulheres, bem como a taxa de recorrência da endometriose de parede. Para determinar os fatores de risco de recorrência, foi utilizado o teste exato de Fisher. Resultados A idade média das mulheres foi de 30.71 ± 5,91 anos. As principais manifestações clínicas foram dor (98%) e sensação do nódulo (36,5%). Foi observado que 94% dessas mulheres tinham pelo menos uma cesárea, e 73% destas fizeram uso de medicação para controle da endometriose no pós-operatório. A localização mais frequente da lesão foi na cicatriz da cesárea (65%). A taxa de recorrência da doença foi de 26,9%. Todas as 14 mulheres que tiveram recidiva tinham margens cirúrgicas comprometidas na cirurgia prévia. Não houve correlação entre a endometriose de parede recorrente e a cesariana prévia (p = 0,18), a laparotomia prévia (p = 0,11), a laparoscopia prévia (p = 0,12) e receber terapia hormonal no pós-operatório (p = 0,51). Conclusão Mulheres com antecedente de cesárea anterior com dor local ou nódulo devem ser investigadas com relação à endometriose de parede. A recorrência do endometrioma de parede é alta, principalmente quando a primeira cirurgia não é adequada, e deixa margens cirúrgicas comprometidas.

[Beta thalassemia major and pregnancy during adolescence: report of two cases]. / Talassemia beta maior e gestação na adolescência: relato de dois casos.

Beta thalassemia major is a rare hereditary blood disease in which impaired synthesis of beta globin chains causes severe anemia. Medical treatment consists of chronic blood transfusions and iron chelation. We describe two cases of adolescents with beta thalassemia major with unplanned pregnancies and late onset of prenatal care. One had worsening of anemia with increased transfusional requirement, fetal growth restriction, and placental senescence. The other was also diagnosed with hypothyroidism and low maternal weight, and was admitted twice during pregnancy due to dengue shock syndrome and influenza H1N1-associated respiratory infection. She also developed fetal growth restriction and underwent vaginal delivery at term complicated by uterine hypotonia. Both patients required blood transfusions after birth and chose medroxyprogesterone as a contraceptive method afterwards. This report highlights the importance of medical advice on contraceptive methods for these women and the role of a specialized prenatal follow-up in association with a hematologist.

Talassemia beta maior e gestação na adolescência: relato de dois casos / Beta thalassemia major and pregnancy during adolescence: report of two cases

A talassemia beta maior é uma doença hematológica hereditária rara em que deficiência na síntese de cadeias globínicas beta causa anemia grave. O tratamento consiste de transfusão sanguínea e quelação de ferro. Descrevemos dois casos de adolescentes com talassemia beta maior, com gestação não planejada e início tardio de pré-natal. Uma delas apresentou piora da anemia, necessidade transfusional aumentada, restrição de crescimento fetal e senescência placentária. A outra apresentava também hipotireoidismo e baixo peso materno, e foi internada por duas ocasiões durante a gestação, por choque hemorrágico do dengue e por infecção respiratória associada a vírus influenza H1N1. Uma delas apresentou restrição de crescimento fetal e teve parto vaginal no termo complicado com hipotonia uterina. Ambas necessitaram de transfusão sanguínea no pós-parto e optaram por medroxiprogesterona como método contraceptivo subsequentemente. Esse relato ressalta a importância de orientação contraceptiva para essas mulheres e o papel do cuidado pré-natal especializado em conjunto com hematologista.

Beta thalassemia major is a rare hereditary blood disease in which impaired synthesis of beta globin chains causes severe anemia. Medical treatment consists of chronic blood transfusions and iron chelation. We describe two cases of adolescents with beta thalassemia major with unplanned pregnancies and late onset of prenatal care. One had worsening of anemia with increased transfusional requirement, fetal growth restriction, and placental senescence. The other was also diagnosed with hypothyroidism and low maternal weight, and was admitted twice during pregnancy due to dengue shock syndrome and influenza H1N1-associated respiratory infection. She also developed fetal growth restriction and underwent vaginal delivery at term complicated by uterine hypotonia. Both patients required blood transfusions after birth and chose medroxyprogesterone as a contraceptive method afterwards. This report highlights the importance of medical advice on contraceptive methods for these women and the role of a specialized prenatal follow-up in association with a hematologist.