Open surgery for in utero repair of spina bifida: Microneurosurgery versus standard technique - A systematic review.

BACKGROUND/OBJECTIVES: Prenatal myelomeningocele (MMC) repair has been shown to improve neurological outcomes. It has been suggested that decreases in the hysterotomy diameter during surgery can improve perinatal outcomes without altering neurologic outcomes. The objective of this study is to describe and compare the main maternal and fetal outcomes of fetuses undergoing open surgery for MMC repair, through the different modifications (standard-classical, mini-hysterotomy, and microneurosurgery). DATA SOURCE: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Ovid, SciELO, LILACS, PROSPERO. RESULTS: From a total of 112 studies, seven case series were selected including 399 fetuses with open fetal surgery, five studies using the classical technique (n = 181), one with mini-hysterotomy (n = 176), and one with the microneurosurgery technique (n = 42). The mini-hysterotomy and microneurosurgery techniques presented a lower risk of preterm delivery (21.4% and 30%, respectively) compared to the classic technique (47.3%), premature rupture of membranes (78%, 62%, and 72.5 %, respectively), oligohydramnios (0% and 72.5%, respectively), dehiscence of hysterotomy, maintaining the same frequency of Chiari reversion (78%, 62%, and 72.5%, respectively), postnatal correction requirement (0%, 4.8%, and 5.8%, respectively), and lower frequency of requirement for a ventriculoperitoneal shunt placement (13.0%, 7.5%, and 29.1%, respectively). CONCLUSION: The least invasive techniques (minihysterotomy-microneurosurgery) are possible and reproduceable, as they are associated with better maternal and perinatal outcomes.

Fetal open spinal dysraphism repair through a mini-hysterotomy: Influence of gestational age at surgery on children's ability to walk.

OBJECTIVE: To analyze the impact of gestational age (GA) at the time of fetal open spinal dysraphism (OSD) repair through a mini-hysterotomy on the ability of children to walk. METHODS: Children who underwent in utero repair of OSD and had formal neurological assessment after 2.5 years of age were compared regarding their ability to walk in relation to pre-surgical predictors. RESULTS: Sixty-nine children fulfilled the inclusion criteria. Among them, 63.7% (44/69) were able to walk with or without orthesis. Fetal OSD correction performed earlier in gestation (from 19.7 to 26.9 weeks) was associated with a higher probability of walking with or without orthesis (p = 0.033). The median GA at delivery was 35.3 weeks. Multivariate binary logistic regression showed that the upper anatomical level of the OSD ( L5) (p < 0.004; OR: 10.31 [95% CI: 2.07-51.28]) and GA at the time of fetal surgery (p = 0.026; OR = 0.68 [95% CI: 0.48-0.95]) were independent predictors of the postnatal ability to walk with or without orthesis. CONCLUSION: Fetuses with OSD who were operated on earlier in pregnancy (range: 19.7-26.9 weeks), were more likely to walk with or without orthesis.

Serial neurosonography in fetuses with congenital heart defects shows mild delays in cortical development.

INTRODUCTION: Neurodevelopmental delay is more common in children born with congenital heart defects (CHD), even with optimal perinatal and peri-operative care. It is hypothesized that fetuses with CHD are prone to neurological impairment in utero due to their cardiac defect, possibly leading to delayed cortical development. METHODS: Cerebral cortical maturation was assessed with advanced neurosonographic examinations every 4 weeks in fetuses with CHD and compared to control fetuses. Five different primary fissures and four areas were scored (ranging 0-5) by blinded examiners using a cortical maturation scheme. RESULTS: Cortical staging was assessed in 574 ultrasound examinations in 85 CHD fetuses and 61 controls. Small differences in grading were seen in Sylvian and cingulate fissures. (Sylvian fissure: -0.12 grade, 95% CI (-0.23; -0.01) p = 0.05, cingulate fissure: -0.24 grade, 95% CI (-0.38; -0.10) p = <0.001. Other cortical areas showed normal maturation as compared to control fetuses. CONCLUSION: Small differences were seen in three of the nine analyzed cortical areas in CHD fetuses, in contrast to previous reports on progressive third-trimester delay. The clinical implications of the small differences however, remain unknown.

COVID-19 infection during pregnancy: fetus as a patient deserves more attention.

The novel coronavirus disease 2019 (COVID-19) pandemic is causing concern also for the management and outcome of COVID-19-positive pregnant women and their offspring, as reported cases are rare. Current evidence suggests the association of COVID-19 infection in pregnancy with both severe maternal morbidity requiring intensive care and perinatal complications (preterm birth with consequent neonatal morbidity and even perinatal death). Most of the reported cases focused specifically on the maternal outcomes and possible vertical transmission, but less attention has been paid to fetus as a patient in such pregnancies. The use of antenatal steroids and fetal neuroprotection with magnesium sulfate is clearly underreported. Several recently issued guidelines suggest lowering the upper gestational age for antenatal steroid administration and also advocate extreme caution or even restraining from the use of magnesium sulfate. Also, the rate of cesarean deliveries among COVID-19 women is unacceptably high. Here we provide arguments for NOT changing the existing guidelines and caution against cesarean delivery that was the prevalent delivery mode in the reported cases and case series.

Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida.

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

Prenatal therapy for fetal cardiac disorders.

Fetal cardiac abnormalities are some of the commonest congenital disorders seen in prenatal life. They can be anatomical or functional and can develop de novo or as a consequence of either maternal or fetal disease. Untreated, morbidity and mortality rates are high for hypoplastic left heart disorders and for some fetal tachy and bradyarrhythmias. Optimum management strategies are often not clear because of the lack of knowledge about the precise natural history of some of these conditions. Prenatal therapy ranges from invasive fetal cardiac intervention to maternal administration of drugs for transplacental transfer to the fetus. This comprehensive review covers many fetal cardiac disorders and various prenatal therapeutic options that are available.

Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline.

Objective: To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. Conclusions: The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.

Fetal Treatment 2017: The Evolution of Fetal Therapy Centers - A Joint Opinion from the International Fetal Medicine and Surgical Society (IFMSS) and the North American Fetal Therapy Network (NAFTNet).

More than 3 decades ago, a small group of physicians and other practitioners active in what they called "fetal treatment" authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful reassessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with a brief discussion of the necessary minimum expertise and systems base for the provision of different types of interventions for both the mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, and subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety.

[Preliminary results from the French study on prenatal repair for fetal myelomeningoceles (the PRIUM study)]. / Résultats préliminaires de l'étude PRIUM : programme de réparation in utero des myéloméningocèles.

OBJECTIVES: To present the preliminary results of the PRIUM study, a French pilot study of prenatal repair for myelomeningoceles (MMC). MATERIAL AND METHODS: The fetal surgery for MMC is offered in cases of patients that did not opt for termination of pregnancy. RESULTS: Thirty-six patients were referred in an 18-month period. Eight patients were not eligible for prenatal repair. Another type of dysraphism was made in 6 cases (one spina-lipoma, 5 cases of limited dorsal myeloschisis). Twenty-two patients were eligible to fetal surgery. A prenatal repair was performed in three cases (14%). Four patients opted for a conventional postnatal treatment. Fifteen patients opted for termination of the pregnancy. CONCLUSION: The establishment of a prenatal repair of MMC protocol in France was justified. The experience of the first 18months of this study however suggests that only a limited number of couples will choose this procedure after specialized counseling in a reference center.

The North American Fetal Therapy Network Consensus Statement: Management of Complicated Monochorionic Gestations.

The North American Fetal Therapy Network is a consortium of 30 medical institutions in the United States and Canada with established expertise in fetal therapy and other forms of multidisciplinary care for complex fetal disorders. This publication is the third in a series of articles written by NAFTNet about monochorionic pregnancies. In this article, we provide the general obstetric practitioner with information regarding management options available for complications of monochorionic gestations. This information may be useful for a better understanding of the pathophysiology of the various conditions, for better patient counseling, for timely referral to a regional treatment center, and for ongoing comanagement after treatment.

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.

Prospects for fetal surgery.

Until about forty years ago, the womb shielded the fetus from observation and therapy. The rapid changes in the diagnosis and treatment of human fetal anatomical abnormalities are due to improved fetal imaging studies as well as fetal sampling techniques (e.g. amniocentesis, chorionic villus sampling), and a better understanding of fetal pathophysiology derived from laboratory animals. Fetal therapy is the logical culmination of progress in fetal diagnosis. In other words, the fetus is now a patient. The fetal surgical treatment of the most severe form of spina bifida - myelomeningocele (MMC) - will be used as a paradigm to illustrate progress in and future prospects for fetal surgery. This review will focus on the rationale for in utero repair in the context of pathologic observations and animal models of MMC, outcomes from human fetal MMC repair including the recently completed Management of Myelomeningocele Study (MOMS trial), and future research directions.

Efectividad del doble test bioquímico como prueba de cribado de síndrome de Down en el segundo trimestre / Effectiveness of the double test in screening for Down syndrome in the second trimester of pregnancy

Para determinar la población de riesgo de síndrome de Down a la que debe recomendarse realizar una te ́cnica invasiva para obtener un cariotipo fetal existen varias pruebas de cribado. En nuestro centro se realiza con el cribado del primer trimestre (edad materna + - translucencia nucal +b-HCG + PAPP-A). Cuando éste no es posible, se realiza el doble test (AFP+b- HCG) como cribado de segundo trimestre. Los resultados del doble test en nuestro centro son insatisfactorios ya que tenemos una tasa de detección del 0%, con una tasa de falsos positivos del 7,7%. Por ello consideramos que es necesaria la utilización de otros criterios alternativos para la selección de las mujeres de riesgo de síndrome de Down en el segundo trimestre (AU)

Several screening tests are available to identify the population at risk of Down syndrome. This population should then be recommended to undergo an invasive technique to obtain a fetal karyotype. In our hospital, screening is done by the combined test (maternal age + nuchal translucency + b subunit of human chorionic gonadotropin [b-HCG] + pregnancy- associated plasma-A [PAPP-A]) during the first trimester of pregnancy. When this test is not feasible, we request the double test (alpha-fetoprotein [AFP] + b-HCG) as a second trimester screening test. The results of the double test in our hospital were unsatisfactory because the detection rate was 0% with a false positive rate of 7.7%. Therefore, we believe alternative criteria should be used to select women at risk of having a child with Down syndrome in the second trimester (AU)