Jane H. Dean

DECLINE IN PREVALENCE OF NEURAL TUBE DEFECTS IN A HIGH-RISK REGION OF THE UNITED STATES

Objectives. To conduct surveillance for neural tube defects (NTDs) in a high-risk region of the United States and to prevent occurrence and recurrence of NTDs through the periconceptional use of folic acid supplements. Design. Active and passive methods were used for surveillance of NTD-affected pregnancies and births during a 6-year period (October 1992–September 1998). Individual genetic counseling was used to prevent NTD recurrences and a public awareness campaign was used to reduce NTD occurrences. Setting. State of South Carolina. Patients. All cases of spina bifida, anencephaly, and encephalocele identified among 278 122 live births and fetal deaths to South Carolina residents during 1992–1998 were included. Main Outcome Measure. Changes in occurrence and recurrence rates during a 6-year period. Results. Over the 6 years of surveillance, the prevalence rates for NTDs decreased from 1.89 to .95 cases per 1000 live births and fetal deaths. The prevalence decrease is explained primarily by a decrease in cases of spina bifida. Isolated NTDs accounted for 297/360 (82%) NTDs and 63/360 (18%) had at least 1 other structural anomaly. Females predominated among isolated NTDs but the sex distribution was equal among NTD cases with other anomalies. Prevalence rates for whites (1.48 cases per 1000 live births and fetal deaths) were higher than rates for blacks (.87 cases per 1000 live births and fetal deaths). There were no NTD recurrences in 113 subsequent pregnancies to mothers of infants with isolated NTDs who took periconceptional folic acid. The rate of periconceptional folic acid use among women of childbearing years increased from 8% to 35% during the 6-year project period. Conclusion. The prevalence of NTDs in a high-risk region has declined coincident with the increased periconceptional use of folic acid supplements among women of childbearing age.neural tube defects, high-risk region, birth defects, folic acid, spina bifida, anencephaly, encephalocele.

Economic Evaluation of a Neural Tube Defect Recurrence-Prevention Program

BACKGROUND Women with a pregnancy affected by a neural tube defect (NTD) are encouraged to take folic acid prior to a subsequent pregnancy, but it is unknown whether organized attempts to identify and counsel such women to prevent recurrent NTDs are cost effective. METHODS Data from the South Carolina recurrence-prevention program for October 2001-September 2002 were analyzed between October 2002 and December 2003 to calculate costs. Cost-effectiveness modeling of the program during 1992-2006 was conducted during 2007. Results were calculated for three scenarios based on recurrence risk, supplement use, and the effectiveness of folic acid in preventing recurrences. For each scenario, quality-adjusted life years (QALYs) were calculated separately using prevented NTD-affected live births; prevented NTD-affected births (including fetal deaths); and all prevented NTD-affected pregnancies. RESULTS The prevention program cost approximately

Long Term Maintenance of Neural Tube Defects Prevention in a High Prevalence State

155,000 per year in 2003 dollars to protect 35 pregnancies and prevent approximately one NTD. The direct costs associated with an NTD depend on type and outcome, but are approximately

Periconceptional multivitamin folic acid use, dietary folate, total folate and risk of neural tube defects in South Carolina

560,000 in 2003 dollars for a live birth with spina bifida. The base-case cost-effectiveness ratio was

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

39,600 per QALY gained from avoided NTD-affected live births and stillbirths, and

Surveillance for Anencephaly and Spina Bifida and the Impact of Prenatal Diagnosis—United States, 1985–1994

14,700 per QALY gained from the avoidance of all NTD-affected pregnancies. The baseline NTD recurrence risk and the use of folic acid supplements by women who are at high risk for an NTD-affected pregnancy were influential parameters. CONCLUSIONS The South Carolina NTD recurrence-prevention program appears comparable in cost effectiveness to other preventive services. Other states might consider including NTD recurrence prevention in birth defect-prevention programs.

Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant neural tube defects

OBJECTIVE To assess the efficacy of folic acid (FA) supplementation and fortification in preventing neural tube defects (NTDs) in a high prevalence region of the United States. STUDY DESIGN Active and passive surveillance methods were used to identify all fetuses/infants affected with an NTD in South Carolina. Prevalence rates were compared with FA intake to determine the effects of increased intake on NTD occurrence and recurrence. RESULTS From 1992 to 2009, 916 NTD cases occurred in South Carolina, with isolated defects comprising 79% of cases. The NTD rate decreased 58% during this period. There was one NTD-affected pregnancy in 418 subsequent pregnancies (0.2%) in mothers with earlier NTD-affected pregnancies who consumed periconceptional FA supplements, and there were 4 NTDs in 66 pregnancies (6.1%) in which the mother did not take FA supplements. FA supplementation increased from 8% to 35% from 1992 to 2007, and knowledge of the protective benefits of FA increased from 8% to 65% in women of childbearing age. CONCLUSIONS Increased periconceptional intake of FA appeared to reduce NTDs in a high-prevalence region. The rate of spina bifida and anencephaly in South Carolina is now essentially the same (0.69 cases per 1000 live births and fetal deaths) as the 1998 to 2005 US rate (0.69).

Periconceptional multivitamin folic acid use, dietary folate, total folate, and risk of neural tube defects in South Carolina

Abstract PURPOSE: To investigate whether dietary folate or multivitamin folic acid taken 3 months before conception and during the first 3 months of pregnancy reduces the risk of isolated occurrent neural tube defect (NTD)-affected pregnancies. METHODS: This population-based case control study conducted between 1992 and 1997 included 179 women with NTD-affected pregnancies and 288 randomly selected controls. Women completed a food frequency questionnaire and were interviewed about lifestyle behaviors, pregnancy histories and use of multivitamins. RESULTS: Use of 0.4 mg or more of multivitamin folic acid at least 3 times per week during the periconceptional period showed no statistically significant reduction in NTD risk [adjusted odds ratio (AOR) = 0.55, 95% confidence interval (CI) = 025, 1.22]. After adjusting for covariates, protective effects for NTDs were observed at the highest quartiles of dietary folate and total folate (daily dietary folate plus daily multivitamin folic acid); the respective odds ratios were 0.40 (95% CI = 0.19, 0.84) and 0.35 (95% CI = 0.17, 0.72). CONCLUSIONS: This study illustrates some of the difficulties in determining effects of folic acid and dietary folate in a population where the consumption of foods rich in folate and the use of multivitamins are increasing and the rate of NTDs is declining. Studies are needed to monitor future changes in folate levels and their effect on health.

Surveillance for anencephaly and spina bifida and the impact of prenatal diagnosis--United States, 1985-1994.

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.

Fragile X syndrome: growth, development, and intellectual function.

PROBLEM/CONDITION The reported prevalence of anencephaly and spina bifida in the United States has steadily declined since the late 1960s. During this time, the ability to diagnose these defects prenatally has progressed rapidly. Many U.S. birth defects surveillance systems ascertain defects only among live-born infants or among infants and fetuses beyond a certain gestational age, thus excluding defects among pregnancies prenatally diagnosed as being affected by a neural tube defect (NTD) and electively terminated before the gestational age limit. The impact of prenatal diagnosis and subsequent pregnancy termination on the reported prevalence of anencephaly and spina bifida in the United States has not been well established. However, assessment of this impact is crucial to the use of surveillance data to monitor trends in the occurrence of NTDs and the effectiveness of interventions for these defects (e.g., increased consumption of folic acid). REPORTING PERIOD This report presents data from birth defects surveillance systems in six states over different time periods: Arkansas, 1985-1989; California, 1989-1991; Georgia, 1990-1991; Hawaii, 1988-1994; Iowa, 1985-1990; and South Carolina, 1992-1993. DESCRIPTION OF SYSTEMS Population-based data about a) live-born and stillborn infants with anencephaly and spina bifida and b) pregnancies electively terminated after prenatal diagnosis of these defects were analyzed from the Arkansas Reproductive Health Monitoring System; the California Birth Defects Monitoring Program; CDCs Metropolitan Atlanta Congenital Defects Program; the Iowa Birth Defects Registry, the University of Iowa, and the Iowa Department of Public Health; and the Greenwood Genetic Center in South Carolina. Data also were analyzed from the Hawaii Birth Defects Monitoring Program, which includes data for some women who were not residents of the state. The systems differed in the size and racial/ethnic composition of the populations studied, the surveillance methods used, the completeness of ascertainment, and the availability and utilization of prenatal testing and pregnancy termination. RESULTS AND INTERPRETATION Among all pregnancies ascertained in which the infant or fetus had anencephaly or spina bifida, the percentages that were electively terminated ranged from 9% in Arkansas to 42% in Atlanta and Hawaii, with a corresponding increase in the adjusted prevalence of these defects compared with the prevalence at birth. In each system, pregnancies associated with anencephaly were terminated more frequently than were those associated with spina bifida. These data indicate that the impact of prenatal diagnosis and subsequent pregnancy termination on the prevalence at birth of anencephaly and spina bifida differs among geographic areas and populations. Comprehensive surveillance for these defects requires inclusion of pregnancies that are prenatally diagnosed and then terminated. ACTIONS TAKEN CDC will use these data to promote the inclusion of prenatally diagnosed and terminated pregnancies in estimates of the prevalence of anencephaly and spina bifida generated by birth defects surveillance programs in the United States. Including such pregnancies is crucial to the ability of these programs to monitor trends accurately and to establish the effectiveness of interventions, including the use of folic acid, for these defects.