Congenital Central Nervous System Defects Research Articles

Development of a Core outcome set for fetal Myelomeningocele (COSMiC): study protocol

BackgroundOpen spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity, yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies.MethodsThe COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists/paediatricians and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies.DiscussionDevelopment and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long-term childhood outcomes.Trial registrationInternational Prospective Register of Systematic Reviews (PROSPERO) CRD42018104880. Registered on December 5, 2018. Core Outcome Measures in Effectiveness Trials (COMET): 1187

The association between severe fetal congenital heart defects and placental vascular malperfusion lesions.

Studies have shown an association between infant with congenital heart defects (CHD) and the risk of preeclampsia. We aimed to characterize placental histopathology from pregnancies who underwent termination of pregnancy (TOP) because of severe CHD. This was a case control study. The medical files of all TOPs due to fetal congenital malformations were reviewed. Cases with CHD included hypoplastic left heart, transposition of great arteries, AV canal, tetralogy of Fallot, double outlet RV, and coractation of aorta. The controls included TOPs due to congenital central nervous system defects (CNS group) that were matched in a 1:1 ratio, by gestational age and maternal age. Placental lesions were classified to maternal and fetal vascular malperfusion (MVM and FVM) and inflammatory lesions. Higher rates of any MVM or FVM lesion were observed in placentas from the CHD group (n = 32) as compared with the CNS group (n = 32), 40.6% versus 12.5% respectively, p = .02. As compared with the CNS group, the CHD group had more abnormal coiling of umbilical cord (p = .01). Placental vascular malperfusion lesions are more common in pregnancies complicated with CHD as compared with CNS malformations. These findings support the hypothesis of similar etiopathogenetic factors, contributing to the development of preeclampsia and CHD.

Comparison of prenatal and postnatal MRI findings in the evaluation of intrauterine CNS anomalies requiring postnatal neurosurgical treatment

To assess the diagnostic capability of fetal magnetic resonance imaging (MRI) in children suspected antenatally to harbor central nervous system (CNS) defects that require immediate postnatal neurosurgical treatment. Between 2003 and 2005, 13 fetal MRI scans were performed in mothers suspected to have fetuses with congenital CNS defects that would require surgery soon after birth. Comparisons between antenatal and postnatal scans were made with emphasis on diagnostic accuracy of antenatal examinations. All mothers were scanned using heavily T2-weighted fat-saturated sequences, allowing rapid acquisitions to avoid movement artefacts. Imaging quality was satisfactory in all patients. Diagnoses made antenatally were: myelomeningocele in seven, meningocele in one, diastematomyelia in one, occipital meningocele in one, and isolated hydrocephalus in three children. Of the seven children with antenatal diagnosis of myelomeningocele, one proved to have spinal lipoma postnatally. The patient who antenatally was diagnosed with meningocele proved to have spinal lipoma postnatally. These two were early antenatal MR scans. Antenatal diagnosis of hydrocephalus was made in five of the six confirmed myelomeningocele patients, which was verified postnatally. Antenatal diagnosis of Chiari II malformation was made in all six confirmed myelomeningocele patients. The antenatal diagnoses of occipital meningo-encephalocele and isolated hydrocephalus were verified postnatally. Antenatal diagnosis of diastematomyelia was not verified postnatally. Fetal MRI scanning is an effective, noninvasive method of assessing in-utero CNS abnormalities. The diagnostic accuracy has improved to allow prediction of clinical outcome and counseling for possible treatment, but is not perfect yet to allow counseling for termination of pregnancy.

Spina bifida--a vanishing nightmare?

Detailed analysis is presented on the dramatic decline in spina bifida births and other congenital central nervous system defects in the past 12 years, in both Sheffield and the rest of Great Britain. In Sheffield, there was an average of 20 spina bifida births per year up to 1972, but since then there has been a progressive fall to only one in 1984. This decrease may be partly attributable to antenatal diagnosis and terminations of affected pregnancies, but there is no known explanation for the rest of the fall, which has also been experienced throughout Great Britain. The virtual elimination of spina bifida is now possible, as long as the existing methods of prevention and antenatal diagnostic facilities are used even more fully. Relaxation of our effort and a reverse in the 'natural' trend could bring the incidence of spina bifida back to where it was 15 years ago.

Congenital defects and occupational factors. A comparison of different methodological approaches.

In a previous study of children with congenital CNS (central nervous system) defects (N = 120), it was shown that exposure had occurred more often among the study mothers than among their referents. In the present study this population, extended with a one-year material of parents of children with oral clefts (N = 102) and their referents, was analyzed in a conventional way concerning occupational factors. This procedure was carried out in order to determine whether information on occupational factors only would provide enough hints to confirm known information concerning exposure, which had been acquired with the more-detailed but laborious interview method. No significant differences were observed in a comparison between the study groups and their referents when work of the mothers outside the home during pregnancy was considered. According to the social class grouping, classes 3 and 4 appeared more often among parents of children with congenital CNS defects than among their referents. With respect to industrial classification, manufacturing and different community services occurred more often among mothers of children with congenital CNS defects and oral clefts than among their referents. Some clustering could be observed with regard to the occupations of the parents in the two study groups as compared to their referents. When the material was methodologically processed in the conventional way described, no obvious conclusions could be drawn about exposure.