Clinical presentation and outcomes of neonates born with neural tube defects- an experience from a level III B NICU in Western India.

PURPOSE: Neural tube defects (NTDs) are one of the most common congenital anomalies and a cause of chronic disability. The study was done to study outcomes of neural tube defects admitted at a tertiary level neonatal intensive care unit (NICU) from 2018 to 2022, a period of 4 years that also coincided with the COVID pandemic. The secondary outcome was to study the clinical presentation, associated anomalies and epidemiological features. METHODS: It was a retrospective observational study; data of infants was obtained from medical records and analysis was done. RESULTS: Thirty-four neonates were enrolled, of which there were 16 (47%) males and 18 (53%) females. History of pre-pregnancy maternal folate intake was present in 4 (11.7%) cases. 33 (97%) babies were diagnosed with meningomyelocele (MMC) and one each had anencephaly, iniencephaly and encephalocele, of which one had frontal and two had occipital encephalocele. The median age of surgery was 16 days of life with primary repair being the most common procedure followed by MMC repair with VP shunt. Twenty babies (58.8%) were discharged successfully, while 9 (26.5%) expired and 5 (14.7%) were discharged against medical advice; which can be attributed to the financial problems of the patients in a developing country. The overall deaths in our series were four (26.5%) which is slightly higher than other studies which may be due to the fact that this study was conducted during the COVID era with lesser rates of folate supplementation, reduced access to prenatal diagnosis coupled with poor follow-up and compliance of patients post-surgical repair. CONCLUSION: This study emphasizes the importance of periconceptional folic acid supplementation, prenatal diagnosis, early surgery and meticulous follow-up as being pivotal to improving outcomes in children with NTDs.

Multi-Institutional Review From the Pediatric Colorectal and Pelvic Learning Consortium of Minor Spinal Cord Dysraphism in the Setting of Anorectal Malformations: Diagnosis, Treatment, and Outcomes.

BACKGROUND/RATIONALE: Anorectal malformations (ARM) are associated with congenital anomalies of the spine, but the impact of a minor spinal cord dysraphism (mSCD) on fecal continence in the setting of ARM remains unclear. MATERIALS/METHODS: A retrospective review was performed utilizing data from the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) registry. The patient cohort was reviewed for ARM type, mSCD screening/incidence/neurosurgical intervention and age-based BMP utilization. RESULTS: 987 patients with ARM were categorized into mild (38%), moderate (32%) or complex (19%). 694 (70%) had normal spinal (NS) status. 271 (27.5%) patients had mSCD. MRI alone (49%) was the most common screening test for mSCD. US screening had a positive predictive value of 86.3% and a negative predictive value of 67.1%. Surgical intervention rates for mSCD ranged between 13% and 77% at a median age of 0.6-5.2 years. 726 (73.6%) patients were prescribed BMP (74.4% NS, 77.5% mSCD). Laxatives were most utilized BMP in all groups <5yo. ≥5yo, enema utilization increased with ARM complexity independent of spine status (with or without neurosurgical intervention). Neurosurgical intervention did not affect BMP utilization at any age or with any ARM when mSCD was identified. CONCLUSIONS: MSCD influence on bowel function in the setting ARM remains unclear. No significant impact of mSCD was noted on ARM patient bowel management program utilization. Variability exists within PCPLC site with screening and intervention for mSCD in patients with ARM. Future studies with standardized care may be needed to elucidate the true impact of mSCD on long term patient outcomes in ARM patients. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: III.

Trends in termination of pregnancy for neural tube defects in England and Wales from 2007 to 2017: Observational prospective study.

BACKGROUND/OBJECTIVE: Neural tube defects (NTDs) affect approximately 300,000 pregnancies worldwide each year. Many of these pregnancies are lost to miscarriage or termination of pregnancy. Here, we have analysed the trends of termination of pregnancy for NTDs from the national data for England and Wales. METHODS: Data for all terminations for residents in England and Wales for the period of 2007-2017 were obtained through Health and Social Act 4 (HSA4) submitted to the Department of Health. Using the ICD-10 codes, terminations for NTDs were selected for analysis. The statistical test Chi-squared was performed using SPSS-v25, where appropriate. RESULTS: In the 11-year period, there were 28,866 terminations under Ground E; of which 4425 (15.33%) had a diagnosis of NTD. The number of NTD cases increased over the time period from 308 in 2007 to 517 in 2017 (67.9%). Significant results were also seen when analysing the relationship between ethnicity, gestation and terminations where an NTD was diagnosed. CONCLUSION: With the availability of routine prenatal ultrasound, the termination for NTDs is on the rise in England and Wales, in spite of the health advice of periconceptional folic acid. This study demonstrates the need for implementation of further programmes to increase public health awareness of folic supplementation and government initiation of fortification to reduce NTDs.

Neonatal ten-year retrospective study on neural tube defects in a second level University Hospital.

BACKGROUND: Aim of this retrospective study was to describe clinical characteristics, diagnostic work-up, management and follow-up of newborns with neural tube defects (NTDs), admitted to the Mother and Child Department of the University Hospital of Palermo, in a ten years period. METHODS: The medical records of 7 newborns (5 males and 2 females) admitted, over a 10-year period from January 2010 to March 2020, to our Department on the first day of life were reviewed. Analyzed data were related to familiar and/or maternal risk factors (consanguinity, maternal preexisting and/or gestational diseases, exposure to teratogen/infectious agents, lack of preconception folic acid supplement), demographic (ethnicity/origin, residence) and clinical features (eventual use of assisted reproduction techniques, prenatal diagnosis, gestational age, fetal presentation, type of delivery, birth weight, preoperative imaging, antibiotics and analgesics use, description of the surgery intervention, length of hospital stay, comorbidities, complications), and follow-up. RESULTS: In our sample we observed a wide spectrum of NTDs: 3 newborns had open NTDs, namely myelomeningocele (2 lumbosacral, one of which associated with extradural lipoma, and 1 sacral), and 4 closed ones, including 2 with meningocele (occipital), 1 filar lipoma associated with dermal sinus, and 1 terminal myelocystocele. Our patients were discharged between 8 and 22 days of life. The neurodevelopmental follow-up showed a favorable outcome for 4 of the 7 patients, and the appearance over time of neurological impairment (motor and/or autonomic) in the newborns with open NTDs. CONCLUSIONS: This study describes familiar and/or maternal risk factors and demographic and clinical features of a single-center series of newborns with NTDs. It may provide a further outline of the actual phenotypic spectrum of these malformations, and new insights into epidemiological aspects and comprehensive management of the patients, including diagnostic work-up and follow-up evaluations.

A Case Report of a 4-Year-Old Boy with Intradural Spinal Cord Abscess Successfully Treated with Adjuvant Hyperbaric Oxygen Therapy.

Intradural spinal cord abscesses are rare infections in early childhood and usually result from pre-existing congenital anomalies of the spinal column. The formation of abscess may be the result of hematogenous spread. It is treated by surgical and parenteral antibiotic treatment, but some special cases may require additional treatments. This article presents a 4-year-old male patient who was previously operated on for spina bifida (meningocele and tethered cord syndrome) at another hospital. Upon complaints of not being able to walk after one month, he was operated on with the diagnosis of spinal intradural abscess and referred to our clinic to continue his treatment. The patient underwent an emergency operation when his new spinal magnetic resonance imaging (MRI) at our hospital showed progression of intradural abscess. Due to no regression of neurological deficits in the follow-up and the risk of another operation, antimicrobial treatment as well as hyperbaric oxygen therapy (HBOT) was planned. At the end of 20 HBOT treatment sessions, the patient started to walk with support and the antibiotic treatment was completed in six weeks. In cases where surgical and antimicrobial treatments have failed, HBOT should be considered as an additional treatment method in children with spinal abscess.

A unique methylation pattern co-segregates with neural tube defect statuses in Han Chinese pedigrees.

Neural tube defects (NTDs) are a complex trait associated with gene-environment interactions. Folic acid deficiency and planar cell polarity gene mutations account for some NTD cases; however, the etiology of NTDs is still little understood. In this study, in three Han Chinese NTD pedigrees (two with multiple affected children), with no information on folic acid deficiency or supplement, we examined genome-wide methylation profiles of each individual in these families. We further compared methylation status among cases and normal individuals within the pedigrees. A unique methylation pattern co-segregated with affected status: NTD cases had more hypermethylated than hypomethylated CpG islands; genes with different methylations clustered in pathways associated with epithelial-to-mesenchymal transition (ZEB2, SMAD6, and CDH23), folic acid/homocysteine metabolism (MTHFD1L), transcription/nuclear factors (HDAC4, HOXB7, SOX18), cell migration/motility/adhesion, insulin and cell growth, and neuron/axon development. Although the genetics of NTD are likely complex, epigenetic changes may concentrate in certain key pathways.

Spinal cord malformations.

Malformations of the spinal cord are one of the most frequent malformations. They should be clearly divided into two completely different families of malformations: open dysraphisms and occult dysraphisms. Open dysraphism mostly consists in myelomeningocele (MMC). Its incidence is 1/1000 live births with a wide variation. Folic acid supplementation has been shown to reduce its risk. In most cases, the diagnosis is done prenatally by serum screening and ultrasound and may lead to termination of pregnancy. In case of decision to continue pregnancy, surgical treatment must be achieved during the first days of life, and in 50 to 90% of cases, a ventricular shunt must be installed. The follow-up of these children must be continued throughout life looking for late complications (Chiari II and syringomyelia, vertebral problems, neuropathic bladder, tethered cord). Occult dysraphisms are a heterogeneous group of malformations. Lipomas (filum and conus) are the most frequent and their treatment remains controversial. Diastematomyelia, neurenteric cysts, dermal sinus, and more complex forms (Currarino syndrome) belong to this group. Most of them can and must be diagnosed prenatally or at birth by careful examination of the lower back for the cutaneous stigmata of the disease to decrease the risk of neurological, urological, or orthopedic permanent handicap.

Neural tube defects: review of experimental evidence on stem cell therapy and newer treatment options.

The failure of closure of the neural tube during development leads to malformations called neural tube defects (NTDs). The most common neural malformations in humans include anencephaly, encephalocele, exencephaly, craniorachischisis spina bifida with or without myelomeningocele, lipomyeloschisis, lipomyelomeningocele, meningocele and myelocystocele. Current preventive strategies are mainly based on pharmacologic/folic acid supplementation. However, stem cell-based and other combination approaches may emerge as potential treatment options for NTDs. This review provides an account of experimental evidence on stem cell therapy and newer treatment options for NTDs which have become available in recent years.

Evaluation of anorectal function in patients with tethered cord syndrome: saline enema test and fecoflowmetry.

OBJECT: Disturbance in anorectal function is a major factor restricting the activities of daily living in patients with spinal cord disorders. To detect changes in anorectal motilities due to a tethered spinal cord, anorectal functions were evaluated using a saline enema test and fecoflowmetry before and after patients underwent untethering surgery. METHODS: The bowel functions in five patients with a tethered cord syndrome (TCS) were evaluated by performing a saline enema test and fecoflowmetry. The contractile activity of the rectum, the volume of infused saline tolerated in the rectum, anal canal pressure, and the ability to evacuate rectal content were examined. The characteristic findings in anorectal motility studies conducted in patients with TCS were a hyperactive rectum, diminished rectal saline-retention ability, and diminished maximal flow in saline evacuation. A hyperactive rectum was considered to be a major contributing factor to fecal incontinence. In one asymptomatic patient diminished anal squeezing pressure was exhibited and was incontinent to liquid preoperatively, but recovered after surgery. Two patients who underwent surgery for myeloschisis as infants complained of progressive fecal incontinence when they became adolescents. In one patient fecal incontinence improved but in another patient no improvement was observed after untethering surgery. CONCLUSIONS: Fecodynamic studies allow the detection of neurogenic disturbances of the anorectum in symptomatic and also in asymptomatic patients with TCS. More attention should be paid to the anorectal functions of patients with TCS.