Rate Of Neural Tube Defects Research Articles

Neural tube defects in the Republic of Ireland in 2009-11

Neural tube defects (NTDs) are associated with deficient maternal folic acid peri-conceptionally. In Ireland, there is no mandatory folic acid food fortification, partly due to declining NTD rates in recent years. The aim of this study was to ascertain the incident rate of NTD during the period 2009-11 and describe epidemiologically NTD in Ireland. Cases were ascertained through multiple sources, including three regional congenital anomaly registers, all maternity hospitals nationally and paediatric hospitals providing care for children with spina bifida in the Republic of Ireland during the period 2009-11. From 225 998 total births, 236 NTDs were identified, giving an incidence of 1.04/1 000 births, increasing from 0.92/1 000 in 2009 to 1.17/1 000 in 2011. Of all cases, 45% (n = 106) had anencephaly, 49% (n = 115) had spina bifida and 6% (n = 15) had an encephalocoele; 78% (n = 184) were liveborn or stillborn and 22% (n = 52) were terminations abroad. Peri-conceptional folic acid supplement intake was 13.7% among the 52.5% (n = 124) of cases whose folic acid supplement intake was known. The incidence of NTDs in the Republic of Ireland appears to be increasing. Renewed public health interventions, including mandatory folic acid food fortification, must be considered to reduce the incidence of NTD.

Influence of free folic acid supplement for women of childbearing age in Xinhui, Jiangmen on neural tube defects and medication compliance

Objective To study the perinatal death and neural tube defects after the implementation of free folic acid for women of childbearing age in Xinhui,Jiangmen.Methods Free folic acid was given to the women of childbearing age in Xinhui,Jiangmen from April 2011 to April 2013.Perinatal deaths and neural tube defects were statistically analyzed and compared before and after the project.Folic acid use by the women in different years were statistically analyze and compared.Results After the women took folic acid,perinatal mortality dropped from 0.65％ to 0.54％,the rate of neural tube defects dropped from 0.18％ to 0.04％,with statistical differences (P ＜ 0.05); the usage rate of folic acid rose from 23.5％ in 2009 to 73.5％ in 2013,the rate of medication compliance of folic acid rose from 12.7％ in 2009 to 63.8％ 2013,with statistical differences(P ＜ 0.05).Conclusions After the implementation of free folic acid for women of childbearing age,the perinatal mortality and the incidence of neural tube defects obviously decrease and the usage rates of folic acid and medication compliance rise year by year. Key words: Women of childbearing age; Folic acid; Neural tube defects; Drug usage rate

Impacto de la fortificación de la harina de trigo con ácido fólico en los defectos del tubo neural, en Lima, Perú

En los últimos años, estudios observacionales en algunos países de América Latina y el mundo demostraron una asociación favorable entre la fortificación de la harina con ácido fólico y la reducción de casos con defectos del tubo neural (DTN). Objetivos: Determinar la tasa de incidencia global (TIG) de DTN y su reducción en el periodo posfortificación (2006-2010) de la harina de trigo con ácido fólico. Diseño: Observacional, descriptivo y retrospectivo. Lugar: Instituto Nacional Materno Perinatal INMP, Lima, Perú. Participantes: Recién nacidos entre los años 2006-2010. Intervenciones: Se revisó 88 236 historias clínicas de recién nacidos. Se obtuvo promedios, desviación estándar, frecuencias absolutas y relativas; la tendencia de las incidencias fue medida con Prais Winsten. Se calculó el IC 95% para la TIG con la prueba de Poissón. Principales medidas de resultados: Tasa de Incidencia global de DTN. Resultados: Hubo 77 historias de RN con DTN, que representaron una TIG de 8,73 por 10 000 (IC 95%: 6,9 a 10,9), siendo la incidencia más alta 15,6 x 10 000 (IC 95%: 10,2 a 22,9) el año 2006 y la más baja 7,6 por 10 000 (IC95%: 4,1 a 13,0) el año 2010. Las incidencias de los tipos DTN fueron: espina bífida 6,7 por 10 000 (IC 95%: 5,1 a 8,6), anencefalia 1,9 por 10 000 (IC 95%: 1,1 a 3,1) y encefalocele 1 por 10 000 (IC 95%: 0,1 a 0,6). Conclusiones: La incidencia de los DTN en el INMP disminuyó a 8,7 por 10 000 RN en el periodo posfortificación (2006-2010) de la harina de trigo con ácido fólico, evidenciando impacto positivo de la intervención.

Health needs assessment for congenital anomalies in middle-income countries: Examining the case for neural tube defects in Brazil.

Recent economic improvement in Brazil has been reflected in better maternal-child health indicators, with decreases in infant and perinatal mortality. However, under-five mortality due to congenital disorders remained unchanged, and congenital disorders have become the second leading cause of infant mortality. In the present study, we used the PHG Foundation Health Needs Assessment (HNA) Toolkit with the objective of first assessing the burden of disease caused by neural tube defects (NTDs) in Brazil and the impact of interventions already put in place to address the burden, and second to evaluate and prioritize further interventions and policies required for its prevention and treatment. The results from these two components of the HNA process are described in this paper. The published literature was reviewed to identify studies of NTDs (prevalence; morbidity; prenatal, perinatal, and postnatal mortality; treatment or prevention). Data on indicators of maternal and child health were obtained directly from the Brazilian Ministry of Health, through the online Live Births Information System (SINASC) and from the Mortality Information System (SIM). Descriptive analyses included reports of the rates of NTD in liveborns, fetal, and infant deaths. Differences between folic acid flour pre-fortification (2001-2004) and post-fortification (2006-2010) periods were expressed as prevalence rate ratios. Around 20% of fetal deaths were related to congenital disorders with approximately 5% of those being NTDs. For infant mortality, congenital disorders were notified in approximately 15% of cases, with NTDs present in 10% of the malformed children. Although statistically significant, the prevalence rate ratio (PRR) for spina bifida in live births was only 0.937 (95% confidence interval (CI) 0.884-0.994), a decrease of 6.3% when comparing the pre and post-fortification periods. The impact of fortification seemed to be more visible in fetal deaths due to anencephaly (PRR = 0.727, 95% CI 0.681-0.777) and for spina bifida (PRR = 0.700, 95% CI 0.507-0.967) with associated decreases of 27.3 and 30%. The lower impact of folic acid fortification in Brazil, compared to other Latin-American countries, can be due to differences in dietary habits, concentration of folic acid in flour, as well as characteristic population ethnic composition. The HNA led to the identification of the needs to be addressed in Brazil, including the improvement of reporting congenital disorders within the nationwide birth certification system, and revision of the policy of flour folic acid fortification.

Trehalose prevents neural tube defects by correcting maternal diabetes-suppressed autophagy and neurogenesis

Preexisting maternal diabetes increases the risk of neural tube defects (NTDs). The mechanism underlying maternal diabetes-induced NTDs is not totally defined, and its prevention remains a challenge. Autophagy, an intracellular process to degrade dysfunction protein and damaged cellular organelles, regulates cell proliferation, differentiation, and apoptosis. Because autophagy impairment causes NTDs reminiscent of those observed in diabetic pregnancies, we hypothesize that maternal diabetes-induced autophagy impairment causes NTD formation by disrupting cellular homeostasis, leading to endoplasmic reticulum (ER) stress and apoptosis, and that restoration of autophagy by trehalose, a natural disaccharide, prevents diabetes-induced NTDs. Embryos from nondiabetic and type 1 diabetic mice fed with or without 2 or 5% trehalose water were used to assess markers of autophagy, ER stress, and neurogenesis, numbers of autophagosomes, gene expression that regulates autophagy, NTD rates, indices of mitochondrial dysfunction, and neuroepithelial cell apoptosis. Maternal diabetes suppressed autophagy by significantly reducing LC3-II expression, autophagosome numbers, and GFP-LC3 punctate foci in neuroepithelial cells and by altering autophagy-related gene expression. Maternal diabetes delayed neurogenesis by blocking Sox1 neural progenitor differentiation. Trehalose treatment reversed autophagy impairment and prevented NTDs in diabetic pregnancies. Trehalose resolved homeostatic imbalance by correcting mitochondrial defects, dysfunctional proteins, ER stress, apoptosis, and delayed neurogenesis in the neural tubes exposed to hyperglycemia. Our study demonstrates for the first time that maternal diabetes suppresses autophagy in neuroepithelial cells of the developing neural tube, leading to NTD formation, and provides evidence for the potential efficacy of trehalose as an intervention against hyperglycemia-induced NTDs.

Resultados del Programa de Prevención de Defectos de Tubo Neural en Chile mediante la fortificación de la harina con ácido fólico: Período 2001-2010

Congenital malformations (CMF) have an important role in infant mortality. Neural tube defects (NTD) have great relevance from both social and public health points of view. The ECLAMC (Collaborative Latin American Study of Congenital Malformations) maintains in Chile an epidemiological surveillance of CMF prevalence rate at birth since 1969. To assess the effect of wheat flour folic acid fortification on the prevalence of NTD. Only Anencephaly, Spina bifida and Cephalocele were considered as NTD. All children born in the maternities incorporated to ECLAMC between 1969 and 1999 were considered as belonging to the pre folic acid fortification period and those who were born from 2001 to 2010 were considered as belonging to the post fortification period. The NTD prevalence rate at birth in the pre fortification period was 17.03/10,000. In the second period, there were 291,996 births and among them, 280 newborns were affected by a form of NTD (9.59 in 10,000 births). This represents a 44% decrease (p < 0.01). Anencephaly rate fell from 7.16/10,000 to 3.67/10,000, representing a 49% lower rate (p < 0.01). Spina bifida rate decreased from 8.61/10,000 to 4.49/10,000, representing a 48% lower rate (p < 0.01). Cephalocele had a 20% non-significant reduction. Wheat flour fortification with folic acid reduced by 44% the prevalence rate of NTD at birth. This means that NTDs were prevented in 185 Chilean newborns each year.

Food Fortification and Decline in the Prevalence of Neural Tube Defects: Does Public Intervention Reduce the Socioeconomic Gap in Prevalence?

Objective: A significant decline in the prevalence of neural tube defects (NTD) through food fortification has been reported. Questions remain, however, about the effectiveness of this intervention in reducing the gap in prevalence across socioeconomic status (SES). Study Design: Using health number and through record linkage, children born in Ontario hospitals between 1994 and 2009 were followed for the diagnosis of congenital anomalies. SES quintiles were assigned to each child using census information at the time of birth. Adjusted rates and multivariate models were used to compare trends among children born in different SES groups. Results: Children born in low SES areas had significantly higher rates of NTDs (RR = 1.25, CI: 1.14–1.37). Prevalence of NTDs among children born in low and high SES areas declined since food fortification began in 1999 although has started rising again since 2006. While the crude decline was greater in low SES areas, after adjustment for maternal age, the slope of decline and SES gap in prevalence rates remained unchanged overtime. Conclusions: While food fortification is successful in reducing the prevalence of NTDs, it was not associated with removing the gap between high and low SES groups.

Using spatial multilevel regression analysis to assess soil type contextual effects on neural tube defects

The rate of neural tube defects (NTDs) in Shanxi Province is the highest world widely. Both human and environmental factors can induce NTDs, but various studies ignored contextual effects. This research examines whether there are significant soil type contextual effects on the rate of NTDs. A spatial two-level regression model is used to quantify the magnitude of contextual effects. Spatial autocorrelated errors structure is used to control autocorrelation of residuals. The results suggest that the spatial multilevel model fit the data better than non-spatial multilevel models. Our findings indicate that there are significant soil type contextual effects on the rate of NTDs, even after taking into account of fertilizer and net income. More attentions should be focused on how characteristics of each soil type may affect the rates of NTDs in further studies, which is a relevant issue for understanding etiology of NTDs.

Folate-related gene variants in Irish families affected by neural tube defects

Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19 bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (“risk genotypes”) and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p = 0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms.

Birth prevalence of neural tube defects: a population-based study in South-Eastern Hungary

Primary prevention by periconceptional folic acid supplementation can significantly reduce the risk of neural tube defects. EUROCAT, the European network of population-based registries for the epidemiologic surveillance of congenital anomalies, lacks sufficient data on the birth prevalence of neural tube defects in Hungary before and after the promotion of primary prevention by folic acid. Our aims were to compare the birth prevalence of neural tube defects (myelomeningocele, anencephaly and encephalocele) over two 12-year periods in South-Eastern Hungary. Further aims were to compare our data to those ones in other areas in Europe. Data were collected from the databases of the Department of Hungarian Congenital Abnormality Registry. The total and live birth prevalence rate of neural tube defects were calculated and compared over 1980-1991 and 1994-2005. In addition, the trends in the total birth prevalence, the number of live births and terminations for and stillbirths with neural tube defects were analysed throughout the period of 1994-2005. A significant decline was found in the total and live birth prevalence of myelomeningocele, anencephaly and encephalocele over 1994-2005 compared to the period of 1980-1991. The total birth prevalence of neural tube defects, however, showed a trend of increase after 1994, with declining number of live births and increasing number of terminations for neural tube defects. Public health measures are warranted in order to replace termination of pregnancy with primary prevention in South-Eastern Hungary.

619 An Outbreak of Neural Tube Defects in Iraq: a Case Report

AimThe aim of this study was to report an outbreak of Neural Tube Defects (NTDs) in Iraq, and to highlight the possible responsibilities of international and local authorities for an...

Reduction in Embryonic Malformations and Alleviation of Endoplasmic Reticulum Stress by Nitric Oxide Synthase Inhibition in Diabetic Embryopathy

Maternal diabetes-induced neural tube defects (NTDs) are associated with increased programmed cell death (apoptosis) in the neuroepithelium, which is related to intracellular nitrosative stress. To alleviate nitrosative stress, diabetic pregnant mice were fed via gavage an inhibitor of nitric oxide (NO) synthase (NOS) 2, L-N6-(1-iminoethyl)-lysine (L-NIL; 80 mg/kg), once a day from embryonic (E) day 7.5 to 9.5 during early stages of neurulation. The treatment significantly reduced NTD rate in the embryos, compared with that in vehicle (normal saline)-treated diabetic group. In addition to alleviation of nitrosative stress, endoplasmic reticulum (ER) stress was also ameliorated, assessed by quantification of associated factors. Apoptosis was reduced, indicated by caspase 8 activation. These results show that nitrosative stress is important in diabetes-induced NTDs via exacerbating ER stress, leading to increased apoptosis. Oral treatment with NOS-2 inhibitor alleviates nitrosative and ER stress, decreases apoptosis, and reduces NTDs in the embryos, providing information for further interventional studies to reduce diabetes-associated birth defects.

Wheat flour fortification with folic acid: Changes in neural tube defects rates in Chile

In January 2000, Chilean Ministry of Health mandated the addition of folic acid (FA) to wheat flour in order to reduce the risk of neural tube defects (NTDs). This policy resulted in significant increases in serum and red cell folate in women of fertile age 1 year after fortification. To evaluate the effect of wheat flour fortification on the prevalence of NTDs in Chile we designed a prospective hospital-based surveillance program to monitor the frequency of NTDs in all births (live and stillbirths) with birth weight≥500 g at the nine public maternity hospitals of Santiago, Chile from 1999 to 2009. During the pre-fortification period (1999-2000) the NTD rate was 17.1/10,000 births in a total of 120,566 newborns. During the post-fortification period (2001-2009) the NTD rate decreased to 8.6/10,000 births in a total of 489,915 newborns, which translates into a rate reduction of 50% (RR: 0.5; 95% CI: 0.42-0.59) for all NTDs. The rate reduction by type of NTD studied was: 50% in anencephaly (RR: 0.5; 95% CI: 0.38-0.67), 42% in cephalocele (RR: 0.58; 95% CI: 0.37-0.89), and 52% in spina bifida (RR: 0.48; 95% CI: 0.38-0.6). Rates showed significant reduction both in stillbirths and live births: 510.3 to 183.6/10,000 (RR=0.36; 95% CI: 0.25-0.53) and 13.3 to 7.5/10,000 (RR=0.56; 95% CI: 0.47-0.68), respectively. In Chile, fortification of wheat flour with FA has proven to be an effective strategy for the primary prevention of NTDs.

Preconception Women’s Health and Pediatrics: An Opportunity to Address Infant Mortality and Family Health

THE U.S. INFANT mortality rate remains unacceptably high, with large disparities found by race. Increasingly, research has demonstrated that interventions must go beyond ensuring access to care and prenatal focus to address the preconception health of women. Critical fetal development occurs in the earliest weeks after conception, often before a woman is aware of her pregnancy. The Maternal Child Health Bureau’s life course initiatives and the Centers for Disease Control’s preconception health initiatives are placing infant mortality and child health in a life course context, that is, uniting the reproductive health and pediatric longitudinal perspectives. In the recent report “Clinical Preventive Services forWomen”, the Institute ofMedicine recommended annual well-women visits incorporating preconception care, and Healthy People 2020 includes a section of objectives on preconception health and behaviors. With growing scientific recognition that early antecedents of child and adult health start prenatally and even preconceptionally, women’s health is key. Pediatric clinicians have been leaders in the efforts to reduce infant mortality and in family-centered care, but how can pediatrics further contribute? A golden opportunity exists to serve as preconception care (PCC) clinicians for preconceptional adolescents and interconceptional mothers seen in practice.

The essential role of protein kinase Cδ in diabetes-induced neural tube defects

Background: Maternal diabetes causes neural tube defects (NTDs) in the embryos via activating protein kinase Cs (PKCs), which regulate programmed cell death (apoptosis). The aims of this study are to investigate the role of proapoptotic PKCδ in NTD formation and the underlying mechanisms. Methods: PKCδ heterozygous (pkcδ+/−) female mice were diabetic (DM) induced by intravenous injection of streptozotocin. Occurrence of NTDs was evaluated at embryonic day 11.5 and compared between wild type (WT) and PKCδ homozygous (pkcδ−/−) embryos. Changes in oxidative and endoplasmic reticulum (ER) stress-associated factors and stress-response c-Jun N-terminal kinases (JNKs) were assessed using Western blot assay. Results: Compared to DM/WT, the DM/PKCδ−/− embryos had significantly lower NTD rate and lower levels of oxidative and ER stress factors and JNK activation. These values were similar to those in the non-diabetic control group. Conclusion: PKCδ plays a critical role in diabetes-induced NTDs, potentially through increasing oxidative and ER stress and JNK-associated stress-response pathways.

Presence of Carbamazepine in Drinking Water Does Not Appear to Cause Neural Tube Defects in Mice

In May of 2006, our lab suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. Exposure to a teratogenic agent in tap water was identified as the cause. Pharmaceuticals have emerged as ubiquitous contaminants of drinking water. One such NTD inducing drug, carbamazepine (CBZ), was analyzed. CBZ was detected in several ground, surface, and tap waters, ranging in concentrations from 0.28 ng/L to 9.5 ng/L. To test whether CBZ was responsible for NTDs, we exposed mice to CBZ in 2 water types. In well water, CBZ concentrations were at 15 and 1500 ng/L. In double distilled water, CBZ concentrations were at 6 and 1500 ng/L. Both studies found no significant differences in NTD rates among the dose groups. As no dose effect was observed, we concluded that CBZ was not directly responsible for the malformations; however it is possible a mixture of contaminants, including CBZ, may be involved.Grant Funding Source : NIH‐NIHSR21E5016886‐01

First-Trimester Screening for Neural Tube Defects Using Alpha-Fetoprotein

Objective: To assess the potential value of maternal serum alpha-fetoprotein (AFP) at 11–13 weeks’ gestation in early screening for fetal neural tube defects (NTDs). Methods: Maternal serum AFP at 11–13 weeks’ gestation was measured in 32 cases of fetal NTDs, including 18 cases of acrania and 14 cases of spina bifida, and 1,500 unaffected controls. The measured serum AFP was converted into multiple of the expected median (MoM) after adjustment for gestational age and maternal characteristics and Mann-Whitney test was used to determine the significance of difference in the mean MoM of serum AFP in the NTD group to that in the controls. Results: The mean AFP MoM in the NTD group (1.76, 95% CI 1.39–2.23) was significantly higher than in the controls (p < 0.0001). The mean AFP MoM was not significantly different between the cases of acrania and cases of spina bifida (1.78 vs. 1.75; p = 0.722). The detection rates of NTD in screening by serum AFP were 50.0% (95% CI 31.9–68.1) and 37.5% (95% CI 21.1–56.3) at fixed false-positive rates of 10 and 5%, respectively. Conclusion: Measurement ofmaternal serum AFP at 11–13 weeks’ gestation may be useful in screening for fetal NTDs.

Evolution of prenatal detection of neural tube defects in the pregnant population of the city of Barcelona from 1992 to 2006

To assess the prenatal ultrasound detection rates (DR) of neural tube defects (NTDs) and its evolution over the 1992 to 2006 period in the pregnant population of the city of Barcelona. Data on the population-based register of birth defects were used to assess the evolution of the prenatal DR for isolated NTD, including anencephaly, spina bifida and encephalocele by trimester of gestation. In the register, 127 isolated NTD cases, including 71 anencephalic fetuses, 49 spina bifidas and 7 encephaloceles were noted. Overall, prenatal ultrasound DR for isolated NTD was 94%. All fetuses with anencephaly or encephalocele were prenatally detected (100% DR), whereas DR for spina bifida was 84%, with no apparent variation over the observation period. An important increase in first trimester DRs was observed for anencephaly, rising from 16% in the first years of the study (1992-1996) to 71% in the last years (2002-2006). A high DR (94%) for isolated NTD was observed in the city of Barcelona. The single significant change across the study period was an increase in the first trimester DR for anencephaly (from 16% to 71%).

Do assisted conception twins have an increased risk for anencephaly?

The incidence rates of anterior neural tube defects, anencephaly and encephalocele appear increased among twins compared with singletons. The current study aimed to evaluate whether the etiology of this phenomenon is related to twinning, assisted reproductive technology (ART), or both. The study cohort consisted of parturient women who were referred to our ultrasonography unit between January 1998 and December 2009 due to suspicion of severe fetal abnormality. The study cohort was divided into two subgroups based on mode of conception: spontaneous and ART (including IVF and ICSI). The subgroups were further subdivided into singleton and multiple pregnancies. We also compared pregnancies diagnosed with anencephaly in the study group to all live births in the Department of Obstetrics and Gynecology. Anencephaly was diagnosed in 43 fetuses out of 1154 (3.7%) pregnancies diagnosed with severe fetal anomaly. Anencephaly was diagnosed in 9 out of 78 twin pregnancies (11.5%); of these, 8 of 45 (17.8%) were ART conceived and 1 of 33 (3%) spontaneously conceived. A significant correlation was found between twinning and anencephaly, with an odds ratio (OR) of 3.4 [confidence interval (CI) = 1.3-8.9, P= 0.011], while no significant correlation was found between ART and anencephaly. A significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 6.6, CI = 2.8-15.3, P< 0.01). Analyzing the distribution of pregnancies diagnosed with anencephaly in the study group compared with the total number of live births in the department revealed a significant correlation between twinning and anencephaly, with an OR of 11.4 (CI = 4.9-26.5, P< 0.01), with no significant correlation between ART and anencephaly. Among all live births, a significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 24.6, CI = 11.4-53.2, P< 0.01). Our data suggest that twin pregnancies conceived by ART constitute a high-risk group for anencephaly, due to a possible synergistic effect of twinning and ART.

Efficacy of Flour Fortification with Folic Acid in Women of Childbearing Age in Iran

Background: Flour fortification with folic acid is one of the main strategies for improving folate status in women of childbearing age. No interventional trial on the efficacy of folic acid fortification has been conducted so far in Iran. Objectives: To study the effects of flour fortification with folic acid on any reduction in neural tube defects (NTDs) and folate status of women of childbearing age. Methods: In a longitudinal hospital-based study, 13,361 postpartum women were studied after admission for childbirth before and after fortification. In addition, two cross-sectional surveys were conducted before (2006) and after flour fortification (2008). The cluster sampling method was used and 580 women, 15–49 years old, were studied as a representative sample of Golestan province in the north of Iran. Fasting blood samples were collected to measure serum vitamin B₁₂, folate and plasma homocysteine. Sociodemographic data, health characteristics and dietary intake were determined. Results: The mean daily intakes of folate from natural food before and after flour fortification were 198.3 and 200.8 µg/day, respectively. The total folate intake increased significantly from 198.3 to 413.7 µg/day after fortification (p < 0.001). Folate intake increased by an average of 226 µg/day from fortified bread. The mean serum folate level increased from 13.6 to 18.1 nmol/l; folate deficiency decreased from 14.3 to 2.3% (p < 0.001). The incidence rate of NTDs declined by 31% (p < 0.01) in the post-fortification period (2.19 per 1,000 births; December 2007 to December 2008) compared to the pre-fortification period (3.16 per 1,000 births; September 2006 to July 2007). Conclusions: Implementation of mandatory flour fortification with folic acid can lead to a significant increase in serum folate and a significant decrease in NTDs.