Spina bifida

Spina bifida is a birth defect in which the vertebral column is open, often with spinal cord involvement. The most clinically significant subtype is myelomeningocele (open spina bifida), which is a condition characterized by failure of the lumbosacral spinal neural tube to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with the level of the lesion. Occurring in approximately 1 per 1,000 births worldwide, myelomeningocele is one of the most common congenital malformations, but its cause is largely unknown. The genetic component is estimated at 60-70%, but few causative genes have been identified to date, despite much information from mouse models. Non-genetic maternal risk factors include reduced folate intake, anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by periconceptional supplementation with folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is achieved by ultrasonography, enabling women to seek termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II brain malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of myelomeningocele has been associated with improved early neurological outcome compared with postnatal operation. Myelomeningocele affects quality of life during childhood, adolescence and adulthood, posing a challenge for individuals, families and society as a whole. For an illustrated summary of this Primer, visit: http://go.nature.com/fK9XNa

Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model

Objective: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model. Methods: In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D re-constructions, and a 3D-CT cephalometric analysis were performed. Results: The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used. Conclusions: None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed. Copyright (c) 2006 S. Karger AG, Basel

Can host reaction animal models be used to predict and modulate skin regeneration?

The study of host reactions in the biomedical and tissue engineering (TE) fields is a key issue but somehow set aside where TE constructs are concerned. Every day new biomaterials and TE constructs are being developed and presented to the scientific community. The combination of cells and biomolecules with scaffolding materials, as TE constructs, make the isolation and the understanding of the effect of each one those elements over the overall host reaction difficult. Eventually, all variables influence the host reaction and the performance of the constructs. For this reason, current assessment of the in vivo performance of TE constructs follows individual approaches, using specific animal models to independently provide insights regarding the contribution of the biomaterials/scaffolds towards the host reaction, and of all the constructs regarding their functionality. Skin wound healing progress into tissue regeneration or repair is highly dependent on the specificities of the inflammatory stage, as demonstrated by comparison between fetal and adult mechanisms. Thus, it would be expected that insights acquired from host tissue reaction evaluation to biomaterials/scaffolds would be explored to predict healing progression and improve the functionality of skin TE constructs. The rational of this review is to make a comprehensive analysis of to what extent the knowledge obtained from the evaluation of in vivo host reactions to implantable biomaterials/scaffolds has been used in the design of skin TE strategies, by promoting tissue regeneration rather than repair.T.C.S. acknowledges Grant No. RL3-TECT-NORTE-01-0124-FEDER-000020, co-financed by the North Portugal Regional Operational Programme (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund

Prenatal treatment of type I congenital cystic adenomatoid malformation by intrauterine fetal thoracentesis

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38193/1/1870170912_ftp.pd

Prenatal diagnosis of congenital diaphragmatic hernia not amenable to prenatal or neonatal repair: Brachmann-de Lange syndrome

Brachmann-de Lange syndrome (BDLS) is a variable multiple congenital anomaly syndrome that occasionally includes congenital diaphragmatic hernia (CDH). CDH per se is commonly diagnosed antenatally and has been corrected with increasing success in utero and by neonatal repair with extracorporeal membrane oxygenation (ECMO). In utero repair requires normal karyotype as well as the absence of other lethal anomalies. Postnatal repair in combination with ECMO has resulted in improved neonatal outcome and has been recommended in all cases not having in utero repair. We describe a fetus diagnosed with a diaphragmatic hernia at 18 weeks of gestation in a woman whose only other pregnancy has been a 16 week abortus diagnosed with Fryns syndrome (FS). FS is a lethal, variable congenital anomaly syndrome that includes CDH, which is thought to contribute to the lethality of the syndrome. In utero repair was considered, but rejected because of the position of the liver and suspected FS. The Patients elected to carry the pregnancy to term. Postnatal repair with ECMO was considered; however, the infant died at several hours of age because of severe pulmonary hypoplasia, being considered ineligible for ECMO. The diagnosis of BDLS was made at autopsy and suggests that the first case may, in fact, have been BDLS. In spite of recent success in the repair of CDH both in et ex utero, CDH in association with BDLS is likely lethal, and women with fetuses diagnosed antenatally with CDH and BDLS should be counseled as such. © 1993 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38260/1/1320470717_ftp.pd

The prenatal ultrasonographic detection of myelomeningocele in patients referred to Children's Hospital Medical Center: a cross sectional study

BACKGROUND: To find out about the prenatal diagnosis rate of myelomeningocele (MMC) by ultrasound scan in patients referred to the Children's Hospital Medical Center in Tehran, Iran from July 2004 to July 2005. METHODS: We included 140 children born with MMC and who were referred for management, surgery and treatment of complications associated with it. The ultrasound reports were examined. Data on sex, age, location of MMC, time of prenatal ultrasound and the trimester in which the diagnosis was made along with the results of the diagnosis (MMC, hydrocephalus, or both), were collected. RESULTS: Among the studied patients, 136 (97.1%) cases had prenatal ultrasound, amongst those, 58 (42.6%) sonographic evaluations were diagnostic for hydrocephalus and/or MMC. The prenatal ultrasound was positive for MMC in 16 (11.8%), hydrocephalus in 25 (18.4%) and both MMC and hydrocephalus in 17 (12.5%) cases. Among all cases with prenatal diagnosis of MMC, 3.4% were detected in the first, 31% in the second and 65.5% in the third trimester. Thoracic/thoracolumbar lesions were found prenatally in 40% of cases, which is significantly higher than the detection rate of other locations including cervical/cervicothoracic and lumbar/lumbosacral/sacral regions diagnosed only in 0% and 21% of cases respectively. CONCLUSION: There is a large difference between the detection rate of our population (24.3%) compared to others (68%). Pregnant women should have an ultrasound at 20–22 week for detection of congenital anomalies including MMC

Monochorionic triamniotic triplet pregnancy with a co-triplet fetus discordant for congenital cystic adenomatoid malformation of the lung

BACKGROUND: Spontaneous monochorionic triamniotic pregnancy is rare and is at increased risk for pregnancy complications. The presence of an anomalous fetus further complicates the management. CASE PRESENTATION: We present a case of monochorionic triamniotic triplet pregnancy diagnosed at 15 weeks of gestation with one fetus having developed a multicystic lung lesion, suggestive of congenital cystic adenomatoid malformation (CCAM). At 24 weeks, the largest cyst measured 10 mm in diameter. We managed the pregnancy conservatively and delivered three live male fetuses with birth weights 1560 g, 1580 g and 1590 g at 35 weeks of gestation. Two newborns were admitted to the neonatal intensive care unit with respiratory distress, the third one died due to sepsis 7 days postpartum. One of the newborns was discharged healthy at 24 days postpartum. The newborn with CCAM developed a pneumothorax on the right side, recovered after treatment, and was discharged after one month. Computerized tomography (CT) of the infant at 3 months demonstrated two cystic lesions in the middle lobe of the right lung measuring 25 mm and 15 mm. A repeat CT of the infant at 6 months showed a 30 mm solitary cystic mass. CONCLUSION: Monochorionic triamniotic triplet pregnancy with a co-triplet fetus discordant for CCAM, present rarely and can be managed conservatively. These findings may help in decision making and counselling of parents

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

OBJECTIVES: The Management Of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida (SB). Recently developed alternative techniques may reduce maternal risks yet should do without compromising on fetal neuroprotective effects. We aimed to assess the learning curve of different fetal SB closure techniques. METHODS: We searched Medline, Web of Science, Embase, Scopus and Cochrane databases and the grey literature to identify relevant articles without language restriction from January 1980 until October 2018. We systematically reviewed and selected studies reporting all consecutive procedures and with a postnatal follow-up ≥12 months. They also had to report outcome variables necessary to measure the learning curve defined by fetal safety and efficacy. Two independent authors retrieved the data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effect model when heterogeneous. To measure the learning curve, we used two complementary methods. With the group splitting method, competency was defined when the procedure provided comparable results to the MOMS trial for 12 outcome variables representative for (1) the immediate surgical outcome, (2) short-term neonatal neuroprotection and (3) long-term neuroprotection at ≥12 months. Then, when the patients' raw data were available, we performed cumulative sum (CUSUM) analysis based on a composite binary outcome defining a successful surgery. It combined four clinically relevant variables for safety (fetal death within 7 days) and for efficacy (neuroprotection at birth). RESULTS: We included 17/6024 (0.3%) studies with low and moderate risks of bias. Fetal SB closure was performed via standard-hysterotomy (n=11), mini-hysterotomy (n=1) or fetoscopy [exteriorized-uterus single-layer (n=1), percutaneous single-layer (n=3) or percutaneous two-layer closure (n=1)]. Only outcomes for the standard-hysterotomy could be meta-analyzed. Overall, outcomes significantly improved 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 uterus-exteriorized single-layer fetoscopy, competency was not respectively reached by cases 81 and 28 available for analysis. CONCLUSIONS: The number of cases operated correlates with the outcome of SB fetal closure and ranges from 35 cases for standard-hysterotomy to ≥56-57 cases for minimally invasive modifications. Our observations provide important information for institutions eager to establish a new fetal center, develop a new technique or train their team, and inform referring clinicians, potential patients and third-parties