Recurrence Of Neural Tube Defects Research Articles

A study on the magnitude of neural tube defects among newborns delivered at a tertiary care hospital

Background: In a developing fetus during the stages of embryogenesis, various congenital malformations tend to occur, among which neural tube defects (NTDs) are one of the more serious conditions. They result due to the failure of the closure of the neural tube along its length, which may lead to cranial or spinal defects. This may present with the wastage of the pregnancy as a stillbirth or, in cases of live birth, with serious complications and associated disabilities such as varying degrees of paralysis, neurogenic bladder, and incontinence of urine and stools and hydrocephalus. Numerous risk factors have been linked with the occurrence of NTDs such as genetic susceptibility, low socioeconomic status, exposure to teratogens such as methotrexate, trimethoprim, aminopterin, and valproate and other antiepileptic drugs during pregnancy, deficiency of vitamins like folate and B12 in females and the risk of recurrence of NTDs in future pregnancies to a female with a past pregnancy having NTD. Aims and Objectives: The present study aims to determine the prevalence and types of NTDs among newborns and to study associated anomalies among them with NTDs. Materials and Methods: General Hospital Palanpur, a tertiary care hospital connected with Banas Medical College and Research Institute, Palanpur, was the site of the study. In the current study, the total number of births was recorded during a 3-year period from 2019 to 2021, and total NTDs data were gathered and analyzed to determine the prevalence of NTDs at the hospital, as well as the various types and related abnormalities. Results: The total number of deliveries in the span of 2019–2021 was 3437 of which 21 cases of NTDs were noted. Out of 21, twelve were male and nine were female, which makes it 57.14% male preponderance compared to females. Moreover, the prevalence of NTDs comes out to be 6.1/1000 births in the span of 3 years. Furthermore, this study suggested that among the NTDs, 61.90% were meningomyelocele which makes it more prevalent than encephalocele and spina bifida. It is also seen that NTDs were more common in multigravida females with gravida <3 and gravida ≥3 (28.57% and 47.61%, respectively) and in multipara females with parity <3 and ≥3 (80.95% and 19.04%, respectively). Conclusion: The prevalence of NTDs is not uncommon in our sector, which needs to be addressed by periconceptional folic acid supplementation for all women of childbearing age.

Role of Folate and Folic Acid During Pregnancy

Abstract: Pregnancy represents a period of fast tissue growth of maternal and foetal tissues that's related to enhanced energy and nutrient needs. Maternal nutrition throughout gestation period, has being essential for best offspring development, reducing long unwellness burden and for general health throughout life. Maternal Folate throughout pregnancy might have numerous roles in offspring health, as well as neurodevelopment and psychological feature performance in childhood. Folate is crucial for C1 metabolism, a network of pathways concerned in many biological processes as well as nucleotide synthesis, deoxyribonucleic acid repair and methylation reactions. The periconceptional use of pteroylglutamic acid (Folic Acid ) containing supplements reduces the primary incidence, as well as recurrence of neural tube defects. Folic Acid (FA) are artificial form of a necessary vitamin generically considered Folates or B9. It is concerned in one-carbon metabolism, and it's been connected to lowering neural tube Defect (NTD). National programs to mandate fortification of food with Folic Acid have reduced the prevalence of NTDs worldwide . The indisputable protecting role of Folic Acid in the hindrance of NTD, in addition to the low compliance of women to Folic Acid recommendations, has aroused the choice of mandatory Folic Acid fortification, a policy currently in place in over eighty countries worldwide. Mandatory food fortification needs food makers to feature Folic Acid to certain foods (e.g. starch or grain products), whereas voluntary fortification permits Folic Acid to be added to foods at the discretion of manufacturers. Food fortification with Folic Acid because the intervention is likely to achieve increasing Folic Acid intake among populations throughout the world. The objective of this article is to discuss the Role of Folic Acid and Folate during pregnancy and to review the role of Folate and Folic Acid , metabolism , absorption and Folic Acid effects on maternal on the basis of recent findings that are important for implementation of fortified food to design future studies. Keywords: Neurodevelopment, Methylation Reactions, Pteroylglutamic Acid, Bioavailability, Monoglutamates.

Folate fortification-should the UK adopt it?

British Journal of Community NursingVol. 24, No. Sup7 NutritionFolate fortification—should the UK adopt it?Pauline van Roijen, Rucha KurtkotiPauline van RoijenEditor, Nursing and Residential CareSearch for more papers by this author, Rucha KurtkotiEditor, British Journal of Community NursingSearch for more papers by this authorPauline van Roijen; Rucha KurtkotiPublished Online:2 Jul 2019https://doi.org/10.12968/bjcn.2019.24.Sup7.S5AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References British Dietetic Association. Food fact sheet. Folic acid. 2018. https://tinyurl.com/y8omfsrn (accessed 16 June 2019) Google ScholarDepartment of Health and Social Care. Fortifying flour with folic acid: government to consult. 2018. https://tinyurl.com/y258v9tl (accessed 16 June 2019) Google ScholarDolin CD, Deierlein AL, Evans MI. Folic acid supplementation to prevent recurrent neural tube defects: 4 milligrams is too much. Fetal Diagn Ther. 2018; 44:161–165. https://doi.org/10.1159/000491786 Crossref, Medline, Google ScholarHoughton LA, Gray AR, Rose MC et al.. Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects. Am J Clin Nutr. 2011; 94(1):136–141. https://doi.org/10.3945/ajcn.110.004549 Crossref, Medline, Google ScholarMorris J, Rankin J, Draper E et al.. Prevention of neural tube defects in the UK: a missed opportunity. Arch Dis Childhood. 2016; 101:604–607. https://doi.org/10.1136/archdischild-2015-309226 Crossref, Medline, Google ScholarWhite S. Water fluoridation—what it is and how it helps dental health. 2016. https://tinyurl.com/h9jb84p (accessed 16 June 2019) Google Scholar FiguresReferencesRelatedDetails 1 July 2019Volume 24Issue Sup7ISSN (print): 1462-4753ISSN (online): 2052-2215 Metrics History Published online 2 July 2019 Published in print 1 July 2019 Information© MA Healthcare LimitedPDF download

Periconceptional folic acid supplementation: Knowledge, attitudes and counselling practice of Serbian pharmacists and pharmacy technicians

Background/Aim. The protective effect of periconceptional folic acid supplementation in reducing the risk of neural tube defects (NTDs) and other adverse pregnancy outcomes has been scientifically confirmed. The present study aimed to assess knowledge, attitudes, and practice (KAP) of community pharmacists and pharmacy technicians with regards to counselling women of reproductive age on adequate folate intake. Methods. The cross-sectional study was conducted among the nationwide stratified sample of pharmacists and pharmacy technicians, practicing in both private and state-owned community pharmacies in Serbia. The detailed literature review, expert consultation and pre-testing were employed in the questionnaire development. The descriptive and inferential statistical analyses were performed using the SPSS software ver. 22. Results. Among 730 survey participants, 96.6% correctly identified types of deformities that could be prevented by folic acid and 77.0% recognized recommended dosage for women capable of becoming pregnant. However, fewer were able to recognize the optimal timing for folic acid supplementation (61.1%) and the proper dose for the NTD recurrence prevention (42.9 %). While 43.2% of pharmacy technicians thought that it was not their responsibility to provide a counselling concerning the measures for the prevention of congenital anomalies, only 4.7% of licensed pharmacists and none of the interns were of that opinion (?2 = 198.287; df = 4; p < 0.001). The majority of respondents (54.7%) reported provision of informative consultation concerning folic acid once a week, or few times a month, while only 10 stated to do so on a daily basis. In addition, based on self-report, only 36.7% of participants communicates information and advice regarding adequate folate status at their own initiative, while the rest addresses this topic only on the patients request, i.e., reactively. Conclusion. Although participants acknowledged the importance of their role in preconception health promotion, our findings revealed certain knowledge gaps as well as dominantly reactive counselling practice. Tailored educational interventions and professional support are needed to improve the engagement of community pharmacy personnel in this area of public health.

Acid folic and pregnancy: A mandatory supplementation

Neural tube defects (NTD) occur in 0.5 to 2 per 1000 pregnancies with various handicaps for the affected child. It is now well established that folic acid deficiency (absolute or relative) is a predisposing factor to this type of malformation. Several randomized controlled trials showed that high-dose folic acid (4mg) is an essential factor for prevention of neural tube defects recurrence and significantly prevents the first occurrence of neural tube defects with a lower dose (0.4mg). Other etiologies can favor the occurrence of NTD such as MTHFR polymorphism, some antiepileptic therapies, obesity and pregestational mellitus diabetes. Necessity of a preconception folic acid supplementation or at least folate nutritional status evaluation should be known for all of us including patients and public.

What are the benefits of folate consumption during pregnancy?

EVIDENCE-BASED ANSWER Maternal folic acid supplementation taken from before conception through the first trimester reduces primary and recurrent neural tube defects (NTDs) by more than 65%. Folic acid supplementation during pregnancy decreases maternal megaloblastic anemia at the time of delivery by about 80%. Folic acid supplementation does not reduce rates of cleft palate, cleft lip, congenital heart defects, miscarriage, preterm delivery, or stillbirth, or affect mean birthweight (SOR: A, meta-analyses of RCTs).

Should the dose of folic acid be adjusted for Mexican population? The pilot prevention program implemented in Nuevo Leon, Mexico.

In 1980 Smithells et al. reported that the intake of folic acid (FA) prevents the recurrence of neural tube defects (NTDs)[1]. After this and several other studies were conducted, the intake of 400 micrograms of folic acid per day, at least three months before and three months during pregnancy for prevention of NTD, was proposed [2,3,4]. Other strategies were also developed to increase folate blood levels in woman of childbearing age such as promoting the consumption of folate rich foods and food fortification (flour and most recently rice) [5]. Nevertheless, results have not been as expected due to poor consumption of folic acid supplements [6]. As a result, in the year 2000, a novel strategy was developed in order to increase folate blood levels in Mexican women. The results of the strategy are presented, as well as, a discussion about how to personalize a program for different populations.

The recurrence risk of neural tube defects (NTDs) in a population with high prevalence of NTDs in northern China.

BackgroundAlthough a number of studies have reported the recurrence risk of NTDs in developed countries, there is little data on the rate of recurrence of NTDs in northern China, a region of high prevalence of NTDs.MethodsBased on the population-based birth defects surveillance system of five counties, we identified women who had an NTD affected pregnancy from 2004-2015 and a retrospective survey was conducted. The rate of recurrence of NTDs was calculated by the number of recurrent NTDs divided by the first NTDs. Maternal age, body mass index (BMI), gestational weeks, education, and occupation were collected. Information on folic acid (FA) supplements, time and dosage were also recorded.ResultsAmong 851 women who had a previous NTD-affected pregnancy, there were 578 subsequent pregnancies, with 10 recurrent NTDs, a 1.7% recurrence rate. The recurrence rate was 1.5% and 2.6% for those taking FA supplements and without FA supplementation respectively. Women with recurrent NTDs had higher BMI before pregnancy compared to those who had a second pregnancy without NTDs. Among the recurrent NTDs, the majority were spina bifida.ConclusionsThe recurrence rate of NTDs was approximately five times higher than the overall prevalence in the same region of northern China. Risk of recurrence appeared lower among women who took FA supplements. These findings are consistent with the reduction in NTD frequency in the population since introduction of the nationwide FA supplement program. Data on recurrence rates in northern China will inform power calculations for future intervention studies.

Neural tube defects: Risk factors and preventive measures.

For the last 25years, it has been proven that the occurrence or recurrence of neural tube defects can be prevented with the administration of folic acid before and early pregnancy. At present, over 80 countries in the world, except Japan, have mandated the fortification of wheat flour and/or rice with folic acid, which has resulted in a significant reduction in the prevalence of neural tube defects. In 2000, the Japanese government recommended folic acid 400μg daily for young women of childbearing age and women who are planning to conceive. In 2002, the government started to present information about the importance of folic acid in the development of fetuses in the Mother-Child Health Booklet annually. Despite these endeavors, the prevalence of neural tube defects has remained unchanged. We discuss the risk factors of neural tube defects and propose preventive measures to decrease the number of neonates with neural tube defects. We believe that the government should implement the fortification of staple food with folic acid very soon, which will eventually decrease not only the neonatal mortality and morbidity, but also the economic burden on our health care system.

Inositol, neural tube closure and the prevention of neural tube defects.

Susceptibility to neural tube defects (NTDs), such as anencephaly and spina bifida is influenced by genetic and environmental factors including maternal nutrition. Maternal periconceptional supplementation with folic acid significantly reduces the risk of an NTD‐affected pregnancy, but does not prevent all NTDs, and “folic acid non‐responsive” NTDs continue to occur. Similarly, among mouse models of NTDs, some are responsive to folic acid but others are not.Among nutritional factors, inositol deficiency causes cranial NTDs in mice while supplemental inositol prevents spinal and cranial NTDs in the curly tail (Grhl3 hypomorph) mouse, rodent models of hyperglycemia or induced diabetes, and in a folate‐deficiency induced NTD model. NTDs also occur in mice lacking expression of certain inositol kinases. Inositol‐containing phospholipids (phosphoinositides) and soluble inositol phosphates mediate a range of functions, including intracellular signaling, interaction with cytoskeletal proteins, and regulation of membrane identity in trafficking and cell division. Myo‐inositol has been trialed in humans for a range of conditions and appears safe for use in human pregnancy. In pilot studies in Italy and the United Kingdom, women took inositol together with folic acid preconceptionally, after one or more previous NTD‐affected pregnancies. In nonrandomized cohorts and a randomized double‐blind study in the United Kingdom, no recurrent NTDs were observed among 52 pregnancies reported to date.Larger‐scale fully powered trials are needed to determine whether supplementation with inositol and folic acid would more effectively prevent NTDs than folic acid alone. Birth Defects Research 109:68–80, 2017. © 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.

Using state and provincial surveillance programs to reduce risk of recurrence of neural tube defects in the United States and Canada: A missed opportunity?

Once a woman has had a fetus or infant affected with a neural tube defect (NTD), the risk of recurrence is approximately 3%. This risk can be significantly reduced by folic acid supplement consumption during the periconceptional period; however, this requires women at risk to be adequately informed about the appropriate dosage and timing of supplement intake before planning another pregnancy. As birth defects surveillance programs are tasked with identifying and documenting NTD-affected pregnancies and births, they are in a unique position to support recurrence prevention activities. In 2015, we surveyed state and provincial birth defects surveillance programs to assess their NTD recurrence prevention activities. The online survey was sent to programs in 52 United States (U.S.) jurisdictions and all 13 provinces and territories in Canada. Findings were compared with a similar survey conducted in 2005 among U.S. programs. In 2015, of the 44 U.S. and Canadian surveillance programs that responded, only 9 programs (7 U.S. and 2 Canadian) reported currently having activities specifically directed toward preventing NTD recurrence. Compared with a 2005 survey of U.S. programs, the number of U.S. programs working on NTD recurrence prevention decreased by almost 50% (from 13 to 7 programs). The number of birth defects surveillance programs with NTD recurrence prevention activities has decreased over the past decade due to a range of barriers, most notably a lack of resources. However, while some recurrence prevention activities require part-time staff, other activities could be accomplished using minimal resources. Birth Defects Research (Part A) 106:875-880, 2016.© 2016 Wiley Periodicals, Inc.

In memoriam: Dr. Andrew Czeizel.

In memoriam: Dr. Andrew Czeizel.

Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

Effects and safety of periconceptional oral folate supplementation for preventing birth defects.

It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies. We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach. Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term. Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.

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.

Preconception care: nutritional risks and interventions.

IntroductionThere is increasingly a double burden of under-nutrition and obesity in women of reproductive age. Preconception underweight or overweight, short stature and micronutrient deficiencies all contribute to excess maternal and fetal complications during pregnancy.MethodsA systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on maternal, newborn and child health (MNCH) outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture.ResultsMaternal pre-pregnancy weight is a significant factor in the preconception period with underweight contributing to a 32% higher risk of preterm birth, and obesity more than doubling the risk for preeclampsia, gestational diabetes. Overweight women are more likely to undergo a Cesarean delivery, and their newborns have higher chances of being born with a neural tube or congenital heart defect. Among nutrition-specific interventions, preconception folic acid supplementation has the strongest evidence of effect, preventing 69% of recurrent neural tube defects. Multiple micronutrient supplementation shows promise to reduce the rates of congenital anomalies and risk of preeclampsia. Although over 40% of women worldwide are anemic in the preconception period, only one study has shown a risk for low birth weight.ConclusionAll women, but especially those who become pregnant in adolescence or have closely-spaced pregnancies (inter-pregnancy interval less than six months), require nutritional assessment and appropriate intervention in the preconception period with an emphasis on optimizing maternal body mass index and micronutrient reserves. Increasing coverage of nutrition-specific and nutrition-sensitive strategies (such as food fortification; integration of nutrition initiatives with other maternal and child health interventions; and community based platforms) is necessary among adolescent girls and women of reproductive age. The effectiveness of interventions will need to be simultaneously monitored, and form the basis for the development of improved delivery strategies and new nutritional interventions.

Differentiation of early first‐trimester cranial neural tube defects

Neural tube defects (NTDs) are one of the most commonly reported birth defects and are the result of failure of primary neurulation, the folding and fusion of the neural plate1. We report on three early first-trimester cases with different types of cranial neural tube defects (NTD) not previously reported in ultrasound studies. Previously, it was believed that the process of neural tube closure occurred in a ‘zipper-like’ fashion, starting at one point and proceeding in both cranial and caudal directions. However, neural tube closure is a more complex process. More recently, Nakatsu et al. described three different closure initiation sites of the human neural tube after studying miscarried embryos2. Following from this closure model six different types of cranial NTDs were distinguished, based on location of the closure defect (Figure S1)2. Survival rates significantly decreased if the rhombencephalon, or fourth ventricle, was involved in the defect (Types III, IV and V) with two-thirds of cases failing to survive beyond 7 weeks' gestational age. Embryos with total dysraphism (Type VI) failed to survive at an even earlier stage. However, 70% of the embryos with a rostral defect (Types I and II) did survive beyond 7 weeks. In Case 1 (crown–rump length (CRL), 23 mm) and Case 2 (CRL, 13 mm) a cranial defect was seen from the mesencephalon to the rhombencephalon, suggestive of Type IV (Figure 1 and Figure S2). In Case 3 (CRL, 14 mm) the neural tube did not close at the parietal region of the head and most likely represents a Type II cranial NTD (Figure 2). We concluded that some of the different types of cranial NTDs can be diagnosed in vivo using high-frequency two- and three-dimensional transvaginal ultrasound during the early first trimester of pregnancy. Increasing awareness of the existence of different types of cranial NTDs is important in beginning to unravel the etiology of the development of NTDs. If good documentation exists the different types of cranial NTDs might be linked to different genetic pathways or environmental factors3. However, since the moment of demise in the majority of cases appears to be before 10 weeks' gestation, detection remains a challenge. The existence of different types of cranial NTDs is a rather recent insight and the implications for counseling are not yet well understood. Understanding the cause of these malformations might contribute to determination of increased risks in couples and development of new prevention strategies. The in vivo detection of cranial NTDs raises the question whether these women are at increased risk for recurrence of NTD. If so, in a subsequent pregnancy, an increased dosage of supplemental folic acid is indicated and additional ultrasound examinations are recommended. In conclusion, different types of cranial NTDs can be diagnosed using transvaginal ultrasound examination in early pregnancy. Detection of these NTDs is of particular importance in beginning to understand etiology, in developing prevention strategies, in counseling patients and in initiating new research projects. This research was financially supported by Erasmus Trustfonds, Erasmus MC Vriendenfonds, Meindert de Hoop Foundation and Fonds NutsOhra. L. Baken*†, N. Exalto†, B. Benoit‡, P. J. van der Spek§, E. A. P. Steegers† and I. A. L. Groenenberg† †Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands; ‡Department of Obstetrics and Gynecology, Princess Grace Hospital, Monaco; §Department of Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands *Correspondence. (e-mail: l.baken@erasmusmc.nl) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Indian perspective on clinical aspects, usage, and guidelines of folic Acid.

Folic acid (pteroylmonoglutamic acid) is the stable, fully oxidized form of folate which is used in food fortification and supplements. Keen interest has been generated in folic acid due to its suggested role in prevention of various disorders. Strong evidence from clinical trials indicates preventive effect of folic acid on both occurrence and recurrence of neural tube defects. It also plays a significant role in mitigating the risk of cardiovascular disorders through homocysteine regulation. In addition, the beneficial effect of folic acid in various types of cancers, neurological disorders, conditions affecting pregnancy, and other clinical conditions has been reported in literature. Various guidelines reinforce the need for women to obtain adequate amount of folic acid either through food fortification or supplements. In India, national guidelines on the proper dose of folic acid to pregnant women are not available. Given its significant beneficial effects on health, awareness should be spread among communities on the usage and benefits of folic acid.

Meckel Gruber syndrome - a single gene cause of recurrent neural tube defects

Meckel Gruber syndrome (MGS), an autosomal recessive disorder characterised by posterior encephalocoele, multicystic kidneys and post-axial polydactyly should be recognised by obstetricians and paediatricians to counsel parents regarding the 25% recurrence risk. We report a consanguineous family with MGS affecting three infants.

BJOG Editor's Choice

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