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.

Levels of folate receptor autoantibodies in maternal and cord blood and risk of neural tube defects in a Chinese population.

BACKGROUND: After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. METHODS: From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71-6.80) and 5.53-fold increased odds (95% CI, 1.90-16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35-2.75) and 3.49 (95% CI, 1.45-8.39), respectively. A dose-response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. CONCLUSION: Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose-response manner. Birth Defects Research (Part A) 106:685-695, 2016. © 2016 Wiley Periodicals, Inc.

Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study.

Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception.

PATTERNS OF NEURAL TUBE DEFECTS AT TWO TEACHING HOSPITALS IN ADDIS ABABA, ETHIOPIA A THREE YEARS RETROSPECTIVE STUDY.

BACKGROUND: Neural tube defects (NTDs), one of the most common congenital malformations, are potentially preventable cause of perinatal morbidity and mortality. OBJECTIVES: To give baseline description of NTDs and their outcome at two teaching hospitals in Addis Ababa, Ethiopia. MATERIALS AND METHODS: A retrospective cross sectional descriptive study conducted from September 2009 to August 2012. RESULTS: During the study period out of 28,961 deliveries 177 cases of NTDs were identified, giving an overall NTD prevalence of 6.1/1000. Only 12% (21/177) were diagnosed before 28 weeks of gestation. The mean gestational age at diagnosis of NTDs was 33.8 weeks (±5.5). Majority, 93.2% (165/177), had antenatal care (ANC) follow-up. Most, 72% (127/177), were diagnosed by ultrasound before delivery while 28% (50/177) were identified at the time of delivery or expulsion. Majority, 85.3% (151/177), never received folic acid supplementation. Only less than 1% (2/177) of the mothers started taking folic acid supplementation pre-conceptionally. Only a third, 33.3% (59/177), of the fetuses were born alive while only 13.6% (24/177) were discharged alive. Myelomeningocele, identified in 51.4% (91/177), was the commonest NTD in this study. CONCLUSION AND RECOMMENDATIONS: The proportion of NTDs in this study is among the highest globally reported rates. The practice of periconceptional folic acid supplementation is negligible. And although most had ANC follow-up the vast majority of NTDs were diagnosed late in the third trimester. It is, therefore, highly recommended to consider implementing national preventive strategies to reduce the prevalence of NTDs in Ethiopia.

When folic acid fails: Insights from 20 years of neural tube defect surveillance in South Carolina.

Neural tube defects (NTDs) are the most common of the severe malformations of the brain and spinal cord. Increased maternal intake of folic acid (FA) during the periconceptional period is known to reduce NTD risk. Data from 1046 NTD cases in South Carolina were gathered over 20 years of surveillance. It was possible to determine maternal periconceptional FA use in 615 NTD-affected pregnancies. In 163 occurrent (26.9%) and two recurrent (22%) NTD cases, the mothers reported periconceptional FA use. These women were older and more likely to be white. Maternal periconceptional FA usage was reported in 40.4% of cases of spina bifida with other anomalies but in only 25.2% of isolated spina bifida cases (P = 0.02). This enrichment for associated anomalies was not noted among cases of anencephaly or of encephalocele. Among the 563 subsequent pregnancies to mothers with previous NTD-affected pregnancies, those taking FA had a 0.4% NTD recurrence rate, but the recurrence without FA was 8.5%. NTDs with other associated findings were less likely to be prevented by FA, suggesting there is a background NTD rate that cannot be further reduced by FA. Nonetheless, the majority (73.9%) of NTDs in pregnancies in which the mothers reported periconceptional FA use were isolated NTDs of usual types. Cases in which FA failed in prevention of NTDs provide potential areas for further study into the causation of NTDs. The measures and techniques implemented in South Carolina can serve as an effective and successful model for prevention of NTD occurrence and recurrence.

Is low iron status a risk factor for neural tube defects?

BACKGROUND: Folic acid supplements can protect against neural tube defects (NTDs). Low folate and low vitamin B12 status may be maternal risk factors for having an NTD affected pregnancy. However, not all NTDs are preventable by having an adequate folate/ B12 status and other potentially modifiable factors may be involved. Folate and vitamin B12 status have important links to iron metabolism. Animal studies support an association between poor iron status and NTDs, but human data are scarce. We examined the relevance of low iron status in a nested NTD case-control study of women within a pregnant population-based cohort. METHODS: Pregnant women were recruited between 1986 and 1990, when vitamin or iron supplementation in early pregnancy was rare. Blood samples, taken at an average of 14 weeks gestation, were used to measure ferritin and hemoglobin in 64 women during an NTD affected pregnancy and 207 women with unaffected pregnancies. RESULTS: No significant differences in maternal ferritin or hemoglobin concentrations were observed between NTD affected and nonaffected pregnancies (case median ferritin 16.9 µg/L and hemoglobin 12.4 g/dl versus 15.4 µg/L and 12.3g/dl in controls). As reported previously, red cell folate and vitamin B12 concentrations were significantly lower in cases. Furthermore, there was no significant association of iron status with type of NTD lesion (anencephaly or spina bifida). CONCLUSION: We conclude that low maternal iron status during early pregnancy is not an independent risk factor for NTDs. Adding iron to folic acid for periconceptional use may improve iron status but is not likely to prevent NTDs.

Respuesta de la pupila fetal en las anomalías del sistema nervioso / Pupil response in fetuses with nervous system anomalies

Objetivo: Estudiamos el estado pupilar basal y la respuesta de la pupila fetal al Doppler color (DC) en casos con malformaciones del sistema nervioso antes de las 23 semanas.Material y métodos: Las pupilas de 12 fetos con alguna malformación del sistema nervioso fueron estudiadas mediante ultrasonidos entre las semanas 16 y 23 de gestación. Las áreas de las pupilas e iris en situación basal y posterior al estímulo DC fueron comparadas con los datos de normalidad previamente publicados.Resultados: La gran mayoría de los fetos tenían alguno de los parámetros analizados anormales, sobre todo en el tipo de respuesta al DC y la cuantificación de ésta. Habitualmente las malformaciones del sistema nervioso presentan una respuesta inversa a la esperada y/o responden de forma exagerada.Conclusión: Estos resultados permiten utilizar este tipo de test en el estudio fetal de alta resolución que realizamos antes de las 22 semanas. Este reflejo fetal puede indicarnos el estado sináptico de una de las vías nerviosas fetales y el tono refléxico fetal. (AU)

The acoustic stimulation test in the anencephalus: preliminary results.

It is not yet clear whether the acoustic stimulus influences the fetus by auditory or vibrational pathways. The anencephalic fetus is an interesting model for the study of the pathway for receipt of acoustic stimulation because of the near absence of cerebral hemispheres. After the traditional nonstress test (NST), the response to acoustic stimulation was assessed in eight fetal heart rate (FHR) recordings of six anencephalic fetuses of gestational age between 18 and 39 weeks. Although four preterm fetuses demonstrated nonreactive results in the NST, two term fetuses revealed reactive NSTs. However, none of these six anencephalic fetuses responded to acoustic stimulation. These data suggest that the cerebral cortex is the origin or transmission route of the FHR response to acoustic stimulation. We hypothesize that the normal fetus might receive externally applied sounds via auditory pathways rather than vibratory pathways, at least in term pregnancy.

Prenatal diagnosis of neural-tube defects with a monoclonal antibody specific for acetylcholinesterase.

An immunoassay for acetylcholinesterase (AChE), based on a monoclonal antibody (AE-2), gave the following results when applied to a panel of amniotic fluids: (a) among 651 samples with normal outcome and normal alphafetoprotein (AFP) values there were 2 (0.31%) false positives; (b) of 9 samples with normal outcome and raised AFP values 1 had a raised AChE titre; (c) all 48 samples from anencephaly cases had raised AChE values; (d) among 49 samples from open spina bifida cases (2 of which had normal AFP values), 48 had raised AChE titres. It is suggested that a monoclonal-antibody-based immunoassay may displace polyacrylamide gel electrophoretic analysis of AChE as a complementary test to AFP in prenatal diagnosis of neural-tube defects, since it is a quantitative test largely independent of operator skill and experience.