Auswahl der wissenschaftlichen Literatur zum Thema „Prenatal Surgery“

Although modem neonatal surgery is a very young subject, it started only after the second world war, the progress is remarkable. The well intergrated interdisciplinary team among pediatric surgeons, pediatricians, neonatologits, anaesthetists, and other relevant specialists made this progress possible. Neonatal surgrey has been influenced by the advances in prenatal diagnosis. Neonatal surgical emergencies are related to perinatal conditions such as better antenatal care, including ultrasonogram examination, encourage the high risk pregnant women to deliver at pediatric/perinatal centers where obstetricians, pediatricians or neonatologist, pediatric surgeon, anesthetist are working as a team. Prenatal diagnosis has been one of the most challenging aspects in perinatology, and may directly related to the task of the pediatric surgeons to salvage certain type of malformations. Some experience of perinatal surgery is also discussed.

OBJECTIVEHospital readmission is an important quality metric that has not been evaluated in prenatal versus postnatal myelomeningocele (MMC) repair. This study compares hospital readmission outcomes between these two groups as well as their etiologies.METHODSThe medical records of patients who had undergone MMC repair in the period from 2011 to 2017 at a single academic medical center were retrospectively reviewed. Collected clinical data included surgery and defect details, neonatal intensive care unit (NICU) stay, and any readmissions or surgical procedures up to 1 year after surgery. Patient and defect characteristics, readmission outcomes at 30 and 60 days and 1 year after discharge from the NICU, and cerebrospinal fluid (CSF) diversion surgery rates were analyzed with the two-tailed t-test and/or k-sample test on the equality of medians.RESULTSA total of 24 prenatal and 34 postnatal MMC repairs were completed during the study period. Prenatally repaired patients were born more prematurely (p < 0.001) and with lower birth weights (p < 0.001), although the NICU stay was similar between the two groups (p = 0.59). Fewer prenatally repaired patients were readmitted at 30 days (p = 0.005), 90 days (p = 0.004), and 1 year (p = 0.007) than the postnatal repair group. Hydrocephalus was the most common readmission etiology, and 29% of prenatal repair patients required CSF diversion at 1 year versus 81% of the postnatal repair group (p < 0.01). Prenatal patients who required CSF diversion had a higher body weight (p = 0.02) and an older age (p = 0.01) at the time of CSF diversion surgery than the postnatal group.CONCLUSIONSPatients with prenatal MMC repair had fewer hospital readmissions at 30 days, 60 days, and 1 year than the postnatal repair group, despite similar NICU lengths of stay. The prenatal repair group had lower requirements for CSF diversion at 1 year and was older with greater body weights at the time of CSF diversion surgery, compared to those of the postnatal repair group. Future study of hospital quality metrics such as readmissions should be performed to better understand outcomes of these two procedures.

OBJECTIVEThe Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for myelomeningocele (MMC). The present study sought to determine how MOMS influenced the clinical recommendations of pediatric neurosurgeons, how surgeons’ risk tolerance affected their views, how their views compare to those of their colleagues in other specialties, and how their management of hydrocephalus compares to the guidelines used in the MOMS trial.METHODSA cross-sectional survey was sent to all 154 pediatric neurosurgeons in the American Society of Pediatric Neurosurgeons. The effect of surgeons’ risk tolerance on opinions and counseling of prenatal closure was determined by using ordered logistic regression.RESULTSCompared to postnatal closure, 71% of responding pediatric neurosurgeons viewed prenatal closure as either “very favorable” or “somewhat favorable,” and 51% reported being more likely to recommend prenatal surgery in light of MOMS. Compared to pediatric surgeons, neonatologists, and maternal-fetal medicine specialists, pediatric neurosurgeons viewed prenatal MMC repair less favorably (p < 0.001). Responders who believed the surgical risks were high were less likely to view prenatal surgery favorably and were also less likely to recommend prenatal surgery (p < 0.001). The management of hydrocephalus was variable, with 60% of responders using endoscopic third ventriculostomy in addition to ventriculoperitoneal shunts.CONCLUSIONSThe majority of pediatric neurosurgeons have a favorable view of prenatal surgery for MMC following MOMS, although less so than in other specialties. The reported acceptability of surgical risks was strongly predictive of prenatal counseling. Variation in the management of hydrocephalus may impact outcomes following prenatal closure.

El mielomeningocele (MMC) és una malformació congènita caracteritzada per l'extrusió de la medul·la com a conseqüència d'una falta de fusió d'arcs vertebrals que dóna lloc a una lesió neurològica. El pronòstic motor dels nadons afectes de MMC s’estableix després del naixement amb la determinació del nivell neurològic mitjançant l’exploració dels moviments de les extremitats inferiors. Proposem que, d’una manera similar a l’exploració postnatal, l’avaluació ecogràfica sistemàtica dels moviments de les extremitats inferiors en fetus amb MMC podria ser realitzada per explorar el nivell neurològic prenatal i proporcionar informació sobre el pronòstic de la futura capacitat de deambulació, abans del naixement. Objectius: Establir la correlació entre el nivell neurològic prenatal i el postnatal en casos sotmesos a la reparació intraúter del MMC, analitzar la reproductibilitat de la interpretació de la tècnica per l’avaluació ecogràfica del nivell neurològic prenatal, correlacionar el nivell neurològic prenatal amb el nivell anatòmic de la lesió, analitzar l’evolució del nivell neurològic en els casos que no es van operar prenatalment i descriure els casos de MMC valorats a l’Hospital Universitari Vall d’Hebron. Mètodes: Estudi prospectiu observacional que inclou fetus afectes de MMC operats prenatalment. Els patrons de moviments de les extremitats inferiors dels fetus afectes van ser avaluats sistemàticament per ecografia per un expert en medicina materno-fetal i un especialista en rehabilitació. D'acord amb la funció nerviosa coneguda associada a cada grup muscular, es va establir el nivell neurològic prenatal. Totes les exploracions ecogràfiques van ser gravades i, posteriorment, van ser analitzades per dos observadors amb nivells d’expertesa diferents, els quals van interpretar cada exploració gravada per assignar el nivell neurològic, en dues ocasions diferents i cegats pels resultats de l’altre. La concordança entre el nivell neurològic assignat amb la tècnica d’ecografia prenatal i el nivell neurològic assignat després del naixement amb l’exploració neurològica clàssica va ser avaluada mitjançant l’índex de Kappa ponderat (wk). El mateix índex va ser utilitzat per establir la concordança entre el nivell neurològic i el nivell anatòmic i per analitzar la reproductibilitat intra- i interobservador. Resultats: Es van valorar 93 fetus amb MMC. Després de l'assessorament, els pares decidien si desitjaven cirurgia prenatal (26 casos), interrupció de l’embaràs (48 casos) o cirurgia postnatal (2 casos). Cinc pacients no complien els criteris d'inclusió per a la cirurgia prenatal i tres van ser exclosos després del naixement. En els 18 fetus que es van sotmetre cirurgia i que es van analitzar, la concordança entre els nivells neurològics prenatals i postnatals assignats va ser del 91,7% per a l'extremitat dreta (wκ = 0,80) i 88,9% per l'esquerra (wκ = 0,73). La concordança entre el nivell anatòmic i el nivell neurològic va ser del 62,0% (wκ = 0,024). Vint-i.vuit exploracions van ser registrades i avaluades per l’estudi de reproductibilitat. L'acord entre els observadors i l’expert en medicina materno-fetal es va mantenir constant per a l'observador amb major grau d’experiència (wκ = 0,82) i va augmentar (wκ = 0,66 - wκ = 0,72), per l'altre observador. La variabilitat inter- i intraobservador per l’observador més experimentat va ser wκ = 0,72 i wκ = 0,94, respectivament. Conclusions: La correlació entre l’assignació prenatal i postnatal dels nivells neurològics obtinguda en aquest estudi mostra que l'avaluació del nivell neurològic és factible abans del naixement. La concordança per l’avaluació prenatal dels nivells neurològics va ser excel·lent per als observadors amb diferents graus d'experiència. Aquesta tècnica d'avaluació ecogràfica dels moviments de les extremitats inferiors té el potencial de proporcionar informació precisa i individualitzada sobre el pronòstic de deambulació en fetus amb MMC operats prenatalment.
Myelomeningocele (MMC) is a congenital malformation characterized by the extrusion of the spinal cord as a result of a lack of fusion of vertebral arches leading to a neurological lesion. Motor prognosis of neonates affected by MMC is usually established after birth by the examination of lower limb movements to determine the neurological level of lesion. We propose that, in a similar manner, a systematic ultrasound evaluation of lower-limb movements in fetuses with MMC should be performed to explore the prenatal neurological level of lesion and provide the prognosis for future ambulation before birth. Objectives: To establish the correlation between the prenatal and postnatal neurological level in fetuses with MMC repaired in utero, to assess the reliability of the interpretation of the technique for the ultrasound evaluation of the prenatal neurological level, to correlate the prenatal neurological level with the anatomical level of lesion, to assess the evolution of the neurological level in cases not operated prenatally and to describe the MMC cases evaluated in Hospital Universitari Vall d’Hebron. Methods: prospective observational study including fetuses with MMC operated on prenatally. The patterns of movements in the affected fetuses’ lower limbs were evaluated systematically by ultrasound examination by a maternal-fetal medicine expert and a specialist in rehabilitation. According to the known nerve function associated with each muscle group, the segmental level of neurological lesion was established before birth. All ultrasound scans were recorded and, afterwards, were analyzed by two observers, with different levels of experience, who interpreted each recorded scan to assign the neurological level, two different times and blinded to each other’s results. The agreement for the neurological levels assigned, between the prenatal ultrasound technique and the classical neurological clinical examination after birth, was tested using the weighed kappa (wκ) index. The same index was used to establish the agreement between neurological level and anatomical level and to test the inter-observer and intra-observer reproducibility. Results: Ninety-three fetuses with MMC were evaluated. After counseling, the parents opted for prenatal surgery (26 cases), termination of pregnancy (48 cases) or postnatal repair (2 cases). Five patients did not fulfil the inclusion criteria for prenatal surgery and three were excluded after birth. In the 18 fetuses that underwent surgery and were analyzed, the agreement between prenatal and postnatal neurological levels assigned was 91.7% for the right limb (wκ=0.80) and 88.9% for the left limb (wκ = 0.73). The agreement between neurological level and anatomical level was 62.0% (wκ=0.024). Twenty-eight scans were recorded and evaluated to assess the reproducibility. The agreement between the observers and the expert in maternal-fetal medicine remained constant for the observer with greater experience (wκ=0.82) and increased (wκ=0.66 - wκ=0.72) for the other one. Inter-observer and intra-observer variability for the most experienced observer were wκ=0.72 and wκ=0.94, respectively. Conclusions: The agreement found between prenatal and postnatal assignment of neurological level of lesion in this study shows that the evaluation of neurological level is feasible before birth. The agreement for the prenatal evaluation of the neurological level was excellent for observers with different degrees of expertise. This technique of ultrasound evaluation of lower-limb movements has the potential to provide accurate individualized information about the ambulation prognosis of fetuses with MMC operated on prenatally.

Following the publishing of the Management of Myelomeningocele Study, the advantages of in utero repair for fetal myelomeningoceles became points of interest for fetal surgeons. There are many variables that must align in order to have success in this type of repair. When a patient is eligible for this prenatal procedure it is preferable to perform it rather than do the repair postnatally as neurological outcomes for the infant tend to be much better following earlier intervention. It is very important to have a clear preoperative plan before beginning any fetal surgery. In doing so, one limits unforeseen events that may arise. With this in mind, we chose to analyze factors that affect the rates of patch placement (in lieu of a primary skin closure) during the prenatal repair and rates of shunt placement after the infant is born. A retrospective study was conducted on patients who underwent in utero repair for a myelomeningocele or myeloschisis defect at the Colorado Fetal Care Center. Multivariate analyses were performed to identify which preoperative, intraoperative, and postoperative factors were statistically significant (p ≤ 0.05) in predicting patch and shunt placement. Neuroimaging was found to be a key tool in predicting patch and shunt placement. Additionally, gestational age during prenatal intervention was found to be predictive of patch placement while the preoperative degree of cerebellar descent relative to the foramen magnum as well as 2-week hindbrain herniation classification were found to be predictive of shunt placement. These crucial findings will give physicians a framework to use when creating their preoperative plans and in doing so will allow for higher chances of success with this complex procedure.

Intrauterine and perinatal factors have been linked to risk of testicular cancer and breast cancer in the offspring. In particular, many studies have provided evidence that supports the hypothesis of an intrauterine component in the origin of breast cancer. Human studies to examine the underlying biological mechanisms, however, have been limited. In Chapter 1, we review the likely role of stem cells in hormone-mediated carcinogenic process, particularly as intermediate steps between in utero exposure to hormones and breast cancer. We summarize also studies related to the assumptions of the hypothesis concerning in utero exposure. In Chapter 2 and 3, we report a reproducibility study for hormone assay and a population-based study that measured stem cell potential to explore mechanisms mediating the relation between in utero exposure to pregnancy hormones and cancer risk in the offspring. In these studies, we utilized umbilical cord blood collected two collection sites. Cord blood donors were 99 women, 18 years or older, who delivered a singleton birth. We assayed plasma concentrations of estradiol, unconjugated estriol, testosterone, progesterone, prolactin, sex-hormone binding globulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3). We observed in a reproducibility study that assays of these plasma hormones and binding proteins are reliable. For stem cell potential, we measured concentrations of CD34+, CD34 +CD38− cells, CD34+c-kit +. We applied linear regression analysis and controlled for maternal and neonatal characteristics. Data from two sample collection sites were analyzed separately and collectively. Based on the pooled data further taking into account cord sample collection sites, we found that CD34+ increases with increasing E3 (23% per SD increase, p = 0.02) and IGF-1 (25% per SD increase, p = 0.04). A similar increase was observed for IGFBP-3 (p = 0.05). E3, T, SHBG, and progesterone were weakly associated with CD34+CD38 −. These findings indicate that levels of growth factors and steroid hormones are associated with stem cell potential in human umbilical cord blood and point to a potential mechanism that may mediate the relation between in utero exposure to hormones and cancer risk in the offspring.

abstract: This thesis reviews the initial cases of fetal surgery to correct myelomeningocele, a severe form of spina bifida, and discusses the human and social dimensions of the procedure. Myelomeningocele is a fetal anomaly that forms from improper closure of the spinal cord and the tissues that surround it. Physicians perform fetal surgery on a developing fetus, while it is in the womb, to mitigate its impacts. Fetal surgery to correct this condition was first performed experimentally in the mid-1990and as of 2020, it is commonly performed. The initial cases illuminated important human and social dimensions of the technique, including physical risks, psychological dimensions, physician bias, and religious convictions, which affect decision-making concerning this fetal surgery. Enduring questions remain in 2020. The driving question for this thesis is: given those human and social dimensions that surround fetal surgery to correct myelomeningocele, whether and when is the surgery justified? This thesis shows that more research is needed to answer or clarify this question.
Dissertation/Thesis
Masters Thesis Biology 2020

abstract: Clinically meaningful emotional and behavioral problems are thought to be present beginning in infancy, and may be reliably assessed in children as young as 12 months old. However, few studies have investigated early correlates of emotional and behavioral problems assessed in infancy. The current study investigates the direct and interactive contributions of early infant and caregiver characteristics thought to play an important role in the ontogeny of behavior problems. Specifically, the study examines: (1) the links between temperamental reactivity across the first year of life and behavior problems at 18 months, (2) whether children high in temperamental reactivity are differentially susceptible to variations in maternal sensitivity, (3) the extent to which child temperamental risk or susceptibility may further be explained by mothers’ experiences of stressful life events (SLEs) during and before pregnancy. Data were collected from 322 Mexican American families during prenatal, 6-, 12-, 18-, and 24-week home interviews, as well as during 12- and 18-month lab interviews. Mother reports of SLEs were obtained between 23-40 weeks gestation; temperamental negativity and surgency at 6 weeks and 12 months; and internalizing and externalizing behaviors at 18 months. Maternal sensitivity during structured mother-infant interaction tasks at the 6-, 12-, 18-, and 24-week visits was assessed by objective observer ratings. Study findings indicated that maternal SLEs before birth were associated with more infant negativity across the first year of life, and that negativity in turn was associated with more internalizing problems at 18 months. Ecological stressors thought to be associated with sociodemographic risk factors such as low-income and ethnic minority status may begin to exert cascades of influence on children’s developmental outcomes even before birth.
Dissertation/Thesis
Doctoral Dissertation Psychology 2016

Advances in prenatal imaging and the introduction of screening policies enable identification of high-risk pregnancies which can be followed up more meticulously. First-trimester evaluation is also used for assessment of risk for fetal anomalies. Further investigation may reveal a fetal anomaly. When the prognosis is poor, and treatment cannot wait until birth, fetal intervention may be warranted. This can be medical or surgical, some as simple as a needle-guided fetal blood transfusion. Over the last two decades, fetal surgery has become more popular, boosted by instrument development for minimal access fetal surgery and by successful clinical trials. More recently, open fetal surgery has become more popular again, following a successful trial on in utero repair of neural tube defects. Though not a lethal condition, prenatal surgery improves outcome as demonstrated in a randomized controlled trial. In the latter half of pregnancy, surgical intervention on the fetus requires adequate fetal anaesthesia.