Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model.

OBJECTIVES: A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero leakage of cerebrospinal fluid (CSF) and exposure of the fetal spinal cord to amniotic fluid. We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair in a validated SBA fetal lamb model. METHODS: A well-powered superiority study was conducted in the validated SBA fetal lamb model (n = 7 per group). The outcomes of lambs which underwent watertight or non-watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term = 145 days). At ∼75 days, fetal lambs underwent standardized induction of lumbar SBA. At ∼100 days, they were assigned to an either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1-2 days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint-movement score, locomotor grade and Motor Evoked Potential (MEP); four-score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint-movement score ≥ 9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three-score skin-repair-quality scale based on visual assessment of the quality of the skin repair (suture inter-run distance ≤ 3 mm, absence of tear and absence of ischemia), with high quality defined by a score ≥ 2/3 and low quality by a score < 2/3, and assessed its relationship with improved outcome. RESULTS: Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4/4 in 5/7 vs 0/7 lambs) as evidenced by: a significant 100% (vs 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% vs 100%); better hindlimb motor function, with higher joint-movement score, locomotor grade and MEP area under the curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non-watertight SBA repair did not achieve the same level of neuroprotection (score of 4/4 in 1/7 lambs) compared with unrepaired lambs, with: a non-significant 86% (vs 14%) reversal of hindbrain herniation; high CSF leakage (43% vs 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (≥ 2/3) intraoperative skin-repair-quality score were associated with improved outcome, but the watertightness test and skin-repair-quality scale could not be used interchangeably due to result discrepancies. CONCLUSIONS: Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal-cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin-repair-quality score (≥ 2/3) correlates with neuroprotection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Comparison of ultrasound and magnetic resonance imaging parameters in predicting survival in isolated left-sided congenital diaphragmatic hernia.

OBJECTIVE: To compare test characteristics of ultrasound- and magnetic resonance imaging (MRI)-derived parameters in predicting newborn survival in cases of isolated left-sided congenital diaphragmatic hernia (CDH). METHODS: This was a retrospective study involving 85 fetuses with an isolated left CDH. All had detailed prenatal evaluation, prenatal care, delivery and postnatal care at a single institution. Ultrasound images were reviewed to allow calculation of the lung-to-head ratio (LHR) and the observed/expected LHR (O/E-LHR), and MRI images were reviewed to determine the observed/expected total lung volume (O/E-TLV) and the percent herniated liver (%HL). Univariable logistic regression was used to evaluate each parameter for its ability to predict survival. Receiver-operating characteristics (ROC) curves were constructed and test characteristics were determined for each parameter as a predictor of survival. RESULTS: The overall survival for all fetuses included was 65%. Pseudo-R(2) values for all parameters were similar and were statistically significant as predictors of survival, with %HL having the highest pseudo-R(2) , of 0.28. ROC curve analysis showed ultrasound-determined parameters (LHR and O/E-LHR) to have a similar area under the curve (AUC), of 0.70, whilst MRI parameters (O/E-TLV and %HL) had AUC values of 0.82 and 0.84, respectively. At ROC-curve-determined cut-off values, MRI parameters had better test characteristics than did ultrasound parameters. At a standardized 5% false-positive rate, %HL performed best, with a sensitivity of 0.54 and a specificity of 0.95. At clinically employed cut-off values, sensitivity was similar for all parameters but MRI parameters provided the best combination of sensitivity and specificity, as evidenced by better likelihood ratios. CONCLUSIONS: A variety of measures have been proposed as antenatal predictors of survival in CDH. Ultrasound parameters function at a similar level, whereas MRI-determined parameters appear to offer better predictive value.

Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life.

OBJECTIVE: The objective of this study was to longitudinally evaluate the neurodevelopmental (ND) outcome in congenital diaphragmatic hernia (CDH) survivors during the first 3 years of life. STUDY DESIGN: The study cohort consists of 47 CDH survivors that were enrolled in our prospective, follow-up program between July 2004 and September 2010, and underwent serial ND evaluations during the first 3 years of life. ND outcomes were evaluated using the Bayley Scales of Infant Development (BSID)-II or BSID-III. Persistent ND impairment was defined as a score that remained 79 for the cognitive, language and psychomotor domains at the most recent follow-up visit compared with the first assessment. RESULT: The median age at first and last evaluation was 8 (range, 5 to 15) and 29 (range, 23 to 36) months, respectively. During the follow-up, ND scores improved to average in 17%, remained average in 60%, remained delayed in 10%, improved from severely delayed to mildly delayed in 2% and deteriorated from average to delayed in 15%. Motor scores improved to average in 26%, remained average in 55%, remained delayed in 8% and improved from severely delayed to mildly delayed in 11%. Intrathoracic liver position (P=0.004), preterm delivery (P=0.03), supplemental O2 requirement at day of life 30 (P=0.007), age at discharge (P=0.03), periventricular leukomalacia (PVL; P=0.004) and initial neuromuscular hypotonicity (P=0.01) were associated with persistent motor delays. No relationship was found between patient's characteristics and the risk of persistent cognitive and language delays. CONCLUSION: (1) The majority of children with CDH are functioning in the average range by early preschool age, (2) most children who had early delays showed improvement in their ND outcome, (3) children showing delays in all the three domains were the least likely to show improvement and (4) CDH severity appears to be predictive of persistent psychomotor delays.

Radiofrequency ablation vs bipolar umbilical cord coagulation in the management of complicated monochorionic pregnancies.

OBJECTIVE: The application of radiofrequency ablation (RFA) termination procedures to complicated cases involving monochorionic twins offers the potential of a less invasive option when compared to endoscopic techniques. The purpose of this study was to compare outcomes between these two techniques. METHODS: A retrospective review was undertaken of all cases of complicated monochorionic twin gestations treated at the Children's Hospital of Philadelphia from July 1996 to December 2010. Cases were identified from the fetal treatment database and data extracted in a uniform fashion from the patients' charts. RESULTS: A total of 149 cases were identified with procedures performed on 146. Indications for selective termination of one fetus were twin reversed arterial perfusion sequence in 53, severe twin-to-twin transfusion syndrome in 43, discordance for fetal anomalies in 26 and selective intrauterine growth restriction in 24. Eighty-eight cases were managed with bipolar cord coagulation (BCC) and 58 with RFA. The procedures in all cases were technically successful in achieving selective termination. The mean gestational age at the time of the procedure was 20.9 ± 2.7 weeks in the BCC group vs 20.2 ± 2.2 weeks in the RFA group (P = 0.1). The median gestational age at delivery was 34.7 (interquartile range (IQR), 29.2-38.6) weeks for the BCC group vs 33.0 (IQR, 23.4-38.9) weeks in the RFA group (P = 0.073). Mean birth weight did not differ between the two groups. The procedure-to-delivery time was 87.1 ± 42.1 days for the BCC group vs 73.8 ± 47.2 days for the RFA group (P = 0.1). Overall survival was 85.2% in the BCC group vs 70.7% in the RFA group (P = 0.014). This was attributed primarily to a survival rate of 10.5% in the RFA group compared with 31.6% in the BCC group for cases where delivery occurred before 28 weeks' gestation (P = 0.01). Premature rupture of the membranes occurred in 27.3% in the BCC group vs 13.7% in the RFA group (P = 0.05). Preterm labor was more common in the BCC group than in the RFA group (22.4 vs 7%, respectively; P = 0.009). CONCLUSION: Despite the smaller caliber of the instrument, RFA is not associated with a decrease in the overall complication rate for selective termination procedures. The technique used for selective termination should still be determined by technical considerations but patients should be informed of the survival rate associated with each technique.

The relationship of seizure activity and chronic epilepsy in early infancy and short-term neurodevelopmental outcome following fetal myelomeningocele closure.

We explored the relationship between seizure activity (SA) and/or chronic epilepsy (CE) and short-term neurodevelopmental outcomes following fetal myelomeningocele (fMMC) surgery. Retrospective databases and a parental questionnaire focusing on common complications of hindbrain herniation associated with MMC were used to determine the incidence of seizures following fMMC surgery. The Bayley Scales of Infant Development II was used to evaluate the neurocognitive outcomes. The available 3-year outcome data were used for analysis. 54 children underwent fMMC closure at our institution between 1998 and 2003. 48 (89%) families participated. The shunt rate was 50% (n=24). Seizures developed in 8/48 (17%) children, 2 (8%) non-shunted and 6 (25%) shunted (P=0.07). Of those six, 3 developed CE. Neurodevelopmental scores in the average range were found in both non-shunted and 3 shunted fMMC children. The remaining 3 shunted toddlers had CE and significant neurodevelopmental delays. Of those, 2 had severe intracranial hemorrhage and one developed frequent apneic spells in combination with epilepsy. The incidence of seizures in fMMC children was similar to previously reported data of postnatally repaired MMC patients. SA alone without CE was not associated with a worse neurocognitive outcome. The occurrence of severe acquired intracranial injury and CE, however, appeared to be correlated with adverse neurocognitive outcome following fMMC surgery.

Reversal of hindbrain herniation after maternal-fetal surgery for myelomeningocele subsequently impacts on brain stem function.

The aim of our study was to delineate whether the reversal of hindbrain herniation (HH) following fetal myelomeningocele (fMMC) closure subsequently reduces the incidence and severity of HH-associated brainstem dysfunction (BSD). Prior to the NIH-sponsored Management of Myelomeningocele Study (MOMS) trial, 54 children underwent fMMC closure at our institution. Forty-eight (89%) families participated in a structured survey focusing on HH-associated BSD (e.g., apnea, neurogenic dysphagia [ND], gastro-esophageal reflux disease [GERD], neuro-ophthalmologic disturbances [NOD]). Median age at follow-up was 72 months (range: 46-98). Fifty-percent required shunting. HH-related symptoms were completely absent in 15 (63%) non-shunted and 10 (42%) shunted children (P=0.15). No HH-related death occurred and none developed severe persistent cyanotic apnea. ND was reported in 2 (8%) non-shunted and 9 (38%) shunted infants (P=0.03). Mild GERD (medically managed) developed in 2 (8%) without and 6 (25%) with shunt placement (P=0.24). NOD was found in 6 (25%) and 13 (54%) of non-shunted and shunted children, respectively (P=0.07). The majority of fMMC children developed no or only mild BSD at follow-up. Our data support the hypothesis that neurodevelopmental deficits associated with MMC are at least partially acquired and that reversal of HH following fMMC surgery may help to reduce the incidence and severity of BSD.

Retinoic acid induced myelomeningocele in fetal rats: characterization by histopathological analysis and magnetic resonance imaging.

The prevention of human neural tube defects by folic acid administration and the potential for fetal surgical intervention for myelomeningocele (MMC) have renewed interest in the molecular pathways and pathophysiology of spina bifida. Animal models for assessment of the early developmental biology and pathophysiology of this lesion are needed. The goal of this study was to develop and characterize a non-surgical rat model of MMC. Time-dated Sprague-Dawley rats were gavage fed different doses of retinoic acid (RA) dissolved in olive oil at E10 (maternal n = 55, fetal n = 505). Control animals received olive oil alone (maternal n = 20, fetal n = 265) or were untreated (maternal n = 5, fetal n = 63). Fetuses were analyzed by detailed histopathology and MRI. Overall, isolated MMC occurred in 60.7% (307/505) of RA-exposed fetuses and no controls. Histopathology confirmed the entire spectrum of severity observed in human MMC, ranging from exposure of the cord with intact neural elements to complete cord destruction. MRI of the brain of MMC fetuses confirmed structural changes similar to humans with Arnold-Chiari malformation, including downward displacement of the cerebellum to just above the foramen magnum and compression of the developing medulla into a small posterior fossa. In conclusion, the RA-induced rat model of MMC is developmentally and anatomically analogous to human MMC. This relatively efficient and cost-effective model of MMC should facilitate investigation of the developmental biology and pathophysiology of MMC, and may be useful for the evaluation of further strategies for prenatal treatment.

Fetal head biometry following in-utero repair of myelomeningocele.

OBJECTIVE: To evaluate the impact of prenatal myelomeningocele repair on fetal head biometry. METHODS: Fifty fetuses underwent open fetal myelomeningocele repair at our institution between January 1998 and July 2002. All had serial head circumference (HC) and lateral ventricular diameter (VD) measurements taken preoperatively and weekly for 8 weeks after repair. Cortical index (CI) was defined as HC/VD. Measurements were compared with gestational age-matched values from nomograms. One-sample t-test, ANOVA and repeated measures analysis were used to assess HC, VD and CI after fetal repair. RESULTS: Preoperatively, the HC in fetuses with myelomeningocele was smaller than control values (186.4 vs. 198.8 mm, P = 0.0004). Eight weeks' postoperatively this difference had resolved (293 vs. 301.6 mm, P = 0.76). The mean increase in CI after repair was 20% (P = 0.02) compared with the predicted 51% in normal cases. The average increase in VD was 3.9 mm (38.8%, P < 0.001). CONCLUSIONS: Mid-gestational repair of myelomeningocele alters fetal head growth. Increased CI suggests HC changes are not due to ventriculomegaly alone.

Intensive training of patients with hypertension is effective in modifying lifestyle risk factors.

The burden of insufficiently treated arterial hypertension is still underestimated. In addition to pharmacological therapy, patient training is a valuable therapeutic option. During 1998-1999, the Institute for Preventive Medicine conducted an intensive training programme in cooperation with regional practitioners. The goal of this programme was to educate patients about their disease and motivate them to comply with the therapy. To evaluate the effectivity of this programme, 126 patients with arterial hypertension were trained. They received eight training sessions of 90 min each. In 90 patients blood pressure measurements before and 6 months after training were available. In addition, data concerning health status and lifestyle risk factors were analysed with standardised questionnaires. There was a marked reduction in blood pressure after 6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by 0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline of blood pressure was also greater in obese patients, but did not reach statistical significance. The activity score for physical exercise increased overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about hypertension increased as well (P<0.01). Of all the quality life measurements, the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the patients' self-estimation. In conclusion, training of hypertensive patients has a profound effect on blood pressure control. It motivates patients to change lifestyle risk factors, namely to lose weight, and increases the patients' physical activity level, thereby decreasing the patients' blood pressure. Thus, intensive training programmes are effective and should be used on a widespread basis.

Myomectomy during the first trimester associated with fetal limb anomalies and hydrocephalus in a twin pregnancy.

OBJECTIVES: To present the complications of a twin pregnancy after first trimester myomectomy and to discuss the possible etiologic relationship. CASE REPORT: A 44-year-old primigravida with a dichorionic-diamniotic twin pregnancy underwent myomectomy in another hospital at 12 weeks' gestational age. At 28 weeks the patient was referred to our unit because of ventriculomegaly and limb anomalies in the second twin. The patient underwent a Caesarean section at 37 weeks of gestation delivering twin A, a healthy female weighing 3235 g and twin B, a female weighing 2810 g with hydrocephalus and limb anomalies (clubfeet and hypoplasia of the nails and terminal phalanges). The placenta from twin A was normal, but in the placenta of twin B haemorrhage, thrombosis and infarction were noted. CONCLUSIONS: Despite several reports of myomectomy in pregnancy without any problems for mother and fetus, the authors believe that myomectomy - especially in the first trimester - may be associated with the type of problems observed in the present case. The pathophysiological relationship between placental trauma and haemodynamic alterations as a possible cause of the malformations in twin B is discussed.

[Fetal surgery for severe congenital abnormalities]. / Fetale Chirurgie für schwere kongenitale Fehlbildungen.

BACKGROUND: Over the past two decades the diagnosis of life threatening congenital malformations has evolved rapidly. Sophisticated and powerful new imaging and sampling techniques have stripped the veil of mystery from the once secretive fetus. Early detection and close follow-up of the fetus with congenital malformations have allowed us to define their natural history, determine the clinical features that affect clinical outcome, and plan management approaches to improve prognosis. Fetal surgical intervention is the logical culmination of the progress in fetal diagnosis. The purpose of this article is to describe the current techniques and recent advances in prenatal diagnosis and fetal intervention of severe congenital malformation. MATERIAL AND METHODS: A complete review of the literature and our own experience concerning fetal surgery was performed. RESULTS: Although most prenatally diagnosed malformations are best managed by appropriate medical and surgical therapy after maternal transport and planned delivery at a tertiary care center, an expanding number of simple anatomical abnormalities with predictable, lethal consequences have been successfully corrected before birth. A malformation amenable to prenatal surgical intervention must fulfill a number of conditions. It must be severe enough to warrant the risks associated with in utero treatment and must be reliably detectable before birth. Additionally, the pathophysiology must be reversible by fetal surgery, significantly improving the prognosis over post-natal treatment. Many technical intricacies of open fetal surgery have been solved, but pre-term labor and premature rupture of membranes remain a omnipresent risks to both the mother and the fetus. To reduce maternal morbidity and the risk of prematurity we developed minimally invasive techniques to treat the fetus prenatally. Current indications of fetal surgery include the treatment of congenital diaphragmatic hernia, cystic adenomatoid malformation of the lung, sacrococcygeal teratoma, obstructive uropathy, twin-to-twin-transfusion-syndrome and myelomeningocele. Minimally invasive surgical techniques (FETENDO) have significantly lessened the incidence of preterm labor and promise to extend the indications for fetal surgical intervention. CONCLUSIONS: Fetal surgical therapy for severe congenital malformations may improve the outcome of selected patients. The development of FETENDO will in all probability reduce the importance of open fetal surgery in the future.

Large placental chorioangioma as a cause of sudden intrauterine fetal death. A case report.

A giant placental chorioangioma was diagnosed in a fetus at 22 weeks of gestation by prenatal ultrasound screening and color Doppler imaging. Although no signs of fetal hydrops and cardiac decompensation were observed, the situation of the fetus deteriorated rapidly and in utero fetal death occurred at 26 weeks, attributed to bleeding from ruptured sinusoids within the tumor. Prenatal diagnosis of chorioangioma and treatment modalities are discussed.

Incidence of contralateral patent processus vaginalis in children with inguinal hernia.

PURPOSE: The aim of this study was to investigate the incidence of contralateral patent processus vaginalis (PPV) in children with inguinal hernia using direct laparoscopic inspection. METHODS: This study evaluates the incidence and size of contralateral PPVs in 143 children (96 boys, 47 girls) with clinically unilateral indirect inguinal hernia who underwent laparoscopic hernia repair. During repair, the contralateral internal inguinal ring was evaluated for PPV. RESULTS: Boys with hernias on the right side had wide-open contralateral PPVs in 26% of cases compared with 11% in girls. Boys with hernias on the left side had wide-open contralateral PPVs in 30% of cases compared with 38% in girls. In all 4 groups, there were small contralateral openings in 15% to 20% of cases. CONCLUSION: Contralateral PPV seems to occur less commonly than previously assumed.

Effect of preeclampsia on umbilical cord blood hematopoietic progenitor-stem cells.

OBJECTIVE: The aim of the present study was to determine the influence of preeclampsia on cord blood hematopoietic progenitor-stem cells obtained at delivery because cord blood is increasingly used clinically for stem cell retrieval as an alternative to bone marrow. STUDY DESIGN: Umbilical cord blood was collected from patients fulfilling the criteria for preeclampsia and from gestational age- and birth weight-matched control subjects at delivery (patient/control subjects ratio, 1:2). Cord blood volume and nucleated cell content were measured, and the number of hematopoietic progenitor-stem cells was determined by means of fluorescence-activated cell sorting with the CD34(+) epitope and by means of colony assays with different hematopoietic growth factors. In addition, the expression of adhesion molecules by CD34(+) progenitor-stem cells was examined. RESULTS: In pregnancies affected by preeclampsia, volume and nucleated cell and total CD34(+) cell contents in the collected cord blood were significantly smaller compared with those of control subjects. Furthermore, there was a trend toward a smaller relative number of CD34(+) cells and colony-forming units per nucleated cell in cord blood samples from preeclamptic patients. No difference in the expression of the cell-adhesion molecules leukocyte function-associated antigen 1, very late activation antigen 4, and L-selectin by CD34(+) cells could be found. CONCLUSION: This study shows that preeclampsia affects umbilical cord blood volume and nucleated cell and progenitor-stem cell numbers obtained at birth.

Two case reports of rare fetal tumors: an indication for surface rendering?

Fetal tumors are rare and can be difficult to diagnose in utero. This report describes one case of an extrarenal rhabdoid tumor and one case of a giant congenital melanocytic nevus. Both presented with moderate polyhydramnios and were prenatally detected at 31 weeks of gestation with two-dimensional ultrasound. The application of the surface mode of three-dimensional ultrasound improved the visualization of these tumors especially for the parents and the multidisciplinary team. Three-dimensional sonography proved to be a valuable addition to the prenatal armamentarium for the evaluation of these fetal tumors although it is not mandatory for their assessment and clinical management.

Ciliated epithelium in a midgut enteric duplication: a case report.

We report the case of a 7-year-old male child with a cystic tumour attached to the caecum close to the ileocaecal valve. The histological examination showed that the cyst had a ciliated epithelial lining, containing serous and mucous glands, with surrounding smooth muscle, inner circular and outer longitudinal layers. The cyst was interpreted as an intestinal duplication lined with respiratory epithelium. This structure and its location, originating from the midgut, is not in accordance with the typical conception of the embryogenesis. The clinical picture and treatment are described and compared to other findings in the literature.

Tetrachlorodecaoxide does not jeopardize anastomotic healing: an experimental study in animals.

Tetrachlorodecaoxide (TCDO) is a negatively-charged complex of chlorine and oxygen commonly used for the treatment of infected external wounds. However, it displays antiadhesive properties when applied intra-abdominally. In rats, small-bowel and a large-bowel anastomoses were performed and one-half of the animals received TCDO. It was found that TCDO did not alter the bursting pressures of small and large-bowel anastomoses at 1, 3 and 9 days postoperatively.

Congenital diaphragmatic hernia associated with a gastroesophageal duplication cyst: a case report.

Severe left congenital diaphragmatic hernia was diagnosed in a baby prenatally, and she underwent hernia repair on the sixth postnatal day of life. She was found to have a huge symptomatic gastroesophageal duplication cyst on day 24 of life. A thoracoabdominal dissection allowed successful cyst excision. J Pediatr Surg 36:626-628.