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PubMed2000

Periconceptional intake of vitamin supplements and risk of multiple congenital anomalies.

Numerous studies have reported reduced risks for a variety of single congenital anomaly phenotypes associated with maternal periconceptional use of vitamin supplements containing folic acid. Here we investigated whether periconceptional use of vitamin supplements containing folic acid by women altered their risk for delivering infants with multiple congenital anomalies (MCAs). Data were derived from a case-control study representing deliveries (fetal deaths and infants) from 2 California counties between January 1993 and July 1996. MCAs were defined as 2 or more congenital anomalies affecting more than one organ system or a major anomaly in combination with 2 minor anomalies. Controls were randomly selected from nonmalformed live-born infants. Telephone interviews were conducted with 112 (73.7% of eligible) case and 195 (78.0% of eligible) control mothers. Compared to women who did not use multivitamin supplements containing folic acid in the period 3 months before through 3 months after conception, women who used in this time period were observed to have an elevated risk to deliver fetuses or infants with MCAs, odds ratio = 2.6 (95% confidence interval 1.1-6.2). This elevated risk was not substantially altered (adjusted odds ratio = 2.9 [0.8-10.3]) by adjusting for maternal race/ethnicity, education, gravidity, body mass index, alcohol consumption, and cigarette smoking. No particular organ system seemed to be uniquely represented among the MCA fetuses and infants whose mothers used vitamin supplements. The observed elevated risk associated with maternal vitamin use is considered to be preliminary and needs to be replicated in other populations.

Abnormalities, Multiple↗
PubMed2000

Maternal iodine supplements in areas of deficiency.

BACKGROUND: Iodine deficiency is the leading preventable cause of intellectual impairment in the world. Although iodine supplementation is generally considered to be safe, there is a possibility of high doses of iodine suppressing maternal thyroid function. OBJECTIVES: The objective of this review was to assess the effects of iodine supplementation before or during pregnancy in areas of iodine deficiency. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: All acceptably controlled trials of maternal iodine supplementation during pregnancy with clinical outcomes. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by two reviewers. MAIN RESULTS: Three trials involving 1551 women were included. In two trials, iodine supplementation was associated with a statistically significant reduction in deaths during infancy and early childhood (relative risk 0.71, 95% confidence interval 0. 56 to 0.90). Iodine supplementation was associated with decreased prevalence of endemic cretinism at the age of four years (relative risk 0.27, 95% confidence interval 0.12 to 0.60) and better psychomotor development scores between four to 25 months of age. REVIEWER'S CONCLUSIONS: Iodine supplementation in a population with high levels of endemic cretinism results in an important reduction in the incidence of the condition with no apparent adverse effects.

Child, Preschool↗
PubMed2002

Pre-conception and antenatal screening for the fragile site on the X-chromosome.

BACKGROUND: Fragile X is the most common cause of mental retardation after Down syndrome. It is the commonest inherited cause of mental retardation, and results from a dynamic mutation in a gene on the long arm of the X chromosome. Various strategies are used for prenatal screening. OBJECTIVES: To determine whether pre-conceptual or antenatal screening for Fragile X carrier status in apparently low risk women confers any additional benefit over the existing practice of offering testing to women thought to be at increased risk. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2001), the Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1980 to 2001), and reference lists of articles. SELECTION CRITERIA: Randomised clinical trials comparing women being tested regardless of family history (intervention group) with women tested only when there is a family history of either fragile X and/or other undiagnosed mental illness/impairment (control group). DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and extracted data. MAIN RESULTS: No trials were included. REVIEWER'S CONCLUSIONS: No information is available from randomised trials to indicate whether routine pre-conceptual or antenatal screening for fragile X carrier status confers any benefit over testing women thought to be at increased risk.

Female↗
PubMed2003

Do multivitamin or folic acid supplements reduce the risk for congenital heart defects? Evidence and gaps.

Congenital heart defects are among the most common congenital anomalies and are the leading cause of infant death due to congenital anomalies. Except for a few known measures, effective primary prevention is not yet feasible for most heart anomalies. Recent reports have associated the use of multivitamin supplements around the time of conception and during early pregnancy with a reduced risk for heart defects in the offspring. We review and discuss the evidence and suggest a framework for further investigation in this area.

Case-Control Studies↗
PubMed2005

Reported multivitamin consumption and the occurrence of multiple congenital anomalies.

The purpose of this case-control study was to determine whether multivitamin use is associated with the occurrence of multiple congenital anomalies (MCA). MCA case-infants were infants with two or more major birth defects affecting at least two different organ systems, with no recognized chromosome abnormality or single gene disorder. Control-infants were a random sample of live births with no major birth defects from the same population (metropolitan Atlanta) and time period (1993-1997) as the case-infants. Exposure to multivitamins, cereals, and supplements was ascertained from a maternal telephone interview and classified based on folic acid content. We compared women who used multivitamins three or more times per week with women who were not exposed to vitamins/cereals/supplements during the periconceptional period (3 months before pregnancy through the first trimester), adjusting for maternal age, education, race/ethnicity, first degree family history of a major birth defect, pre-pregnancy maternal body mass index, gravidity, and first trimester alcohol use and cigarette smoking. Periconceptional multivitamin use was associated with MCA among all infants (adjusted odds ratio [aOR]=2.4, 95% confidence interval [CI] 0.9-6.7), and especially when analysis was limited to those with no family history of major defects (aOR=4.0, 95% CI 1.3-12.8). MCA-infants with urinary obstructive defects were more common among multivitamin-exposed infants than among unexposed infants, but this defect did not occur within a consistent pattern of defects. While these findings provide some support for one previous study, the interpretation remains unclear given the proven protective effect of multivitamins containing folic acid on isolated neural tube defects and possibly other types of defects.

Abnormalities, Drug-Induced↗
PubMed2005

Folate-related genes and omphalocele.

Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate-related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin II (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C-->T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P=0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C-->T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required.

Adult↗
PubMed2003

Diarrhea: a new risk factor for neural tube defects?

BACKGROUND: Neural tube defects (NTDs) affect approximately 4000 US pregnancies annually. Folic acid supplementation taken before conception protects against the occurrence of NTDs. Adequate levels of vitamin B12 also appear to play a significant role. Gastrointestinal disturbances, such as those caused by diarrhea, might negatively affect the availability of these vitamins, thereby increasing the risk of these birth defects. METHODS: To determine whether periconceptional diarrhea increases the risk of NTD-affected pregnancies, a population-based case-control study was conducted in the 14 Texas-Mexico border counties. Information on diarrhea and other risk factors was ascertained by in-person interview. Study subjects were Mexican-American women who resided and delivered in any border county during 1995-2000. Case women, identified through active surveillance, had liveborn or stillborn infants or fetuses diagnosed with anencephalus, spina bifida, or encephalocele. Control women were randomly selected from women delivering normal live births in study area health facilities. RESULTS: One or more episodes of periconceptional diarrhea were associated with increased risk of NTD-affected pregnancies compared to no episodes of diarrhea (OR = 3.7, 95% CI = 1.8-7.6). This association was independent of fever, obesity, maternal age, maternal birthplace, income, prior unproductive pregnancy, and dietary plus multivitamin folate intake, known risk factors for NTDs. CONCLUSIONS: Confirmation of this new risk factor might have public health implications due to the feasibility of modifying exposure.

Adult↗
PubMed2004

Periconceptional multivitamin intake during early pregnancy, genetic variation of acetyl-N-transferase 1 (NAT1), and risk for orofacial clefts.

BACKGROUND: Periconceptional supplementation of multivitamins that include folic acid have been shown to prevent several birth defects, including neural tube defects and orofacial clefts. We investigated whether polymorphic variants of fetal acetyl-N-transferase 1 (NAT1), an enzyme involved in the catabolism of folates, differentially interacted with maternal multivitamin use during early pregnancy to alter the risk of delivering an infant with an orofacial cleft malformation. METHODS: Using a large population-based case-control study, we genotyped 421 California infants born with an isolated cleft and 299 controls for two NAT1 polymorphisms. RESULTS: Compared to the homozygous wild-type genotypes, odds ratios for isolated cleft lip with/without cleft palate were slightly increased among infants who were homozygous for the variant alleles of NAT1 1088 and 1095. For isolated cleft palate, no similar associations with these two NAT1 variants were observed. For NAT1 1088 genotypes, we did not observe any differential risks for clefts related to maternal multivitamin intake. For NAT1 1095 genotypes, however, we found a two-fold higher risk for isolated cleft lip with/without cleft palate among infants who were homozygous for the variant allele and whose mothers did not take multivitamins during early pregnancy. CONCLUSIONS: We found evidence suggestive of an interaction between the NAT1 1095 polymorphism and lack of maternal multivitamin use that increased risks of isolated cleft lip with/without cleft palate.

Adult↗
PubMed2005

The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida.

BACKGROUND: The risk of having a child with a neural tube defect (NTD) can be reduced by maternal, periconceptional supplementation with folic acid, but the underlying folate-dependent protective mechanism remains unclear. N-acetyltransferase 1 is involved in acetylation of aromatic and heterocyclic amines and the catabolism of folates. Hence, functional polymorphisms in NAT1, the gene encoding N-acetyltransferase 1, are plausible risk factors for NTDs. Such variants could exert an influence on the risk of NTDs via their role in acetylation or folate catabolism and could act through the maternal or the embryonic genotype. METHODS: NAT1 C1095A genotypes and information on maternal, periconceptional multivitamin use and smoking were obtained as part of a family-based study of spina bifida. Associations between spina bifida and the embryonic and maternal NAT1 C1095A genotypes, and potential NAT1 C1095A genotype-exposure interactions were evaluated using log-linear modeling. RESULTS: The analyses provided no evidence that the embryonic or maternal NAT1 C1095 genotypes influence the risk of spina bifida independently, or through interactions with maternal use of multivitamins. There was evidence that the embryonic, and possibly the maternal, NAT1 C1095A genotype influence the risk of spina bifida via interactions with maternal smoking status. CONCLUSIONS: The genotype for the NAT1 C1095A polymorphism does not appear to be an independent risk factor for spina bifida. However, the results of these analyses provide preliminary evidence that this polymorphism may be associated with the risk of spina bifida in the offspring of women who smoke during early pregnancy.

Arylamine N-Acetyltransferase↗
PubMed2006

Prevalence of periconceptional folic acid use and perceived barriers to the postgestation continuance of supplemental folic acid: survey results from a Teratogen Information Service.

BACKGROUND: Fewer than 40% of U.S. women are taking folic acid supplements periconceptionally at a time when the risk of neural tube defects (NTDs) can be reduced by supplementation. A better understanding of the vitamin-taking habits of childbearing-age women and effective methods for improving periconceptional supplement use are needed. METHODS: A telephone survey conducted through the California Teratogen Information Service (TIS) between August 2003 and January 2004 assessed the prevalence and characteristics of pregnant callers who did not use folic acid supplements in the periconceptional period, and explored attitudes toward advice to continue vitamin use following pregnancy in order to be protected in a future pregnancy. RESULTS: A total of 327 pregnant women who called the TIS for information agreed to participate in the survey. More than half (53.2%) were not taking folic acid-containing supplements in the periconceptional period. Predictors of lack of use included a higher prepregnancy body mass index, younger maternal age, non-white race/ethnicity, lower education level, and unplanned pregnancy. One-quarter of the women said they would be willing to continue taking vitamins after the pregnancy if advised to do so by a physician. The remainder identified obstacles to following that advice--notably, not planning to become pregnant again and the belief that enough folate is derived from diet alone. CONCLUSIONS: More than half of the callers to the TIS were not compliant with recommendations regarding periconceptional folic acid supplementation. This represents an opportunity for TIS specialists and physicians to intervene in a current pregnancy to encourage maintenance of supplement use in the subsequent interpregnancy interval.

Adult↗
PubMed2005

Periconceptional vitamin useand leukemia risk in children with Down syndrome: a Children's Oncology Group study.

BACKGROUND: Periconceptional vitamin supplementation reduces the risk of neural tube defects, and possibly may reduce the risk of certain childhood malignancies, including acute lymphoblastic leukemia (ALL). Because children with Down syndrome (DS) experience a 20-fold higher risk of leukemia than the general population, the authors evaluated whether periconceptional vitamin supplementation reduced the risk of leukemia in children with DS. METHODS: From 1997 to 2002, 158 children ages birth-18 years with DS and acute leukemia (n = 61 children with acute myeloid leukemia [AML] and n = 97 children with ALL) were enrolled through the Children's Oncology Group in North America. Children with DS alone (n = 173) were identified through the cases' pediatric clinics and frequency matched to cases on age. Mothers of cases and controls completed a telephone interview that included questions regarding vitamin supplement use in the periconceptional period and after knowledge of pregnancy. RESULTS: A decreased risk of leukemia was observed with vitamin supplementation in the periconceptional period (odds ratio [OR] = 0.63; 95% confidence interval [95% CI], 0.39-1.00). When stratified by leukemia type, the reduced risk was observed for ALL (OR = 0.51; 95% CI, 0.30-0.89), but not for AML (OR = 0.92; 95% CI, 0.48-1.76). Compared with vitamin use in the periconceptional period, use only after knowledge of pregnancy was associated with an increased risk of leukemia (OR = 1.61; 95% CI, 1.00-2.58). This was observed for both ALL and AML. CONCLUSIONS: These data added to a growing body of evidence that suggests that periconceptional vitamin use may be protective in the development of certain childhood cancers.

Adolescent↗
PubMed2005

Prenatal diagnosis of spinal muscular atrophy: Indian scenario.

OBJECTIVES: To study the psychosocial issues associated with prenatal diagnosis of SMA in India and the use of SMN1 copy number analysis for carrier detection prior to offering prenatal diagnosis. METHODS: Homozygous deletion of SMN1 gene was done by PCR-RFLP. Copy number analysis of SMN1 gene was performed by quantitative PCR. RESULTS: We report our experience of eight cases of prenatal diagnosis for SMA and the use of carrier detection prior to offering prenatal diagnosis. Quantitative PCR results show that SMN1 copy number analysis is useful to identify couples at risk. CONCLUSION: Case analyses depict unique psychosocial issues associated with prenatal diagnosis of SMA from India.

Chorionic Villi Sampling↗
PubMed2002

Three years after the dutch folic acid campaign: growing socioeconomic differences.

BACKGROUND: We investigated periconceptional awareness and the use of folic acid tablets 3 years after the 1995 campaign in the northern Netherlands. We studied whether the socioeconomic differences we found in 1996 with respect to awareness and use of folic acid remained in 1998. METHODS: The present study took place in 1998. Pregnant women were asked to complete a questionnaire. RESULTS: A total of 452 women completed the questionnaire in 1998. Sixty percent of the women with a lower level of education and 85% of the women with a higher level of education had heard of folic acid before pregnancy. Newspapers and magazines were the most often cited sources of information. Fifty percent of the women with a lower educational level used folic acid, while this figure was 80% for the group with higher education. CONCLUSION: Awareness and use of folic acid increased after the 1995 campaign. However, socioeconomic differences with respect to awareness of folic acid remained and even increased with respect to knowledge of the advised period. Use of folic acid is also associated with level of education more strongly than in 1996. Therefore, fortification of staple foods is an attractive option.

Awareness↗
PubMed1994

Does patient semen quality alter during an in vitro fertilization (IVF) program in a manner that is clinically significant when specific counseling is in operation?

PURPOSE: It has been shown that the stress of infertility may impair semen quality. Whether counseling can attenuate this affect is unproven. This study examines, in an IVF program setting, where specific counseling is in operation, whether semen collected on the day of oocyte recovery is significantly different from that obtained during the prior clinical suitability assessment of the couple. RESULTS: In the 125 consecutive couples examined, there were no significant overall differences in semen volume or sperm density. There was a significant increase in sperm motility on the day of oocyte retrieval (P < 0.001). Twenty-three patients (18.4%) showed an increase in quality, and 21 (16.8%) a decrease, on the day of oocyte recovery. The environment of production appeared to exert no influence. Fertilization failure occurred in seven couples, three (14%) of whom presented for the first time with decreased semen parameters on the day of IVF. This compares with 1 of 23 (4%) fertilization failure in those whose parameters increased. CONCLUSION: The semen quality of the vast majority of the patients studied in this highly counseled program does not appear to be significantly affected by the superstress of participation in the day of oocyte recovery.

Adult↗
PubMed2003

Prevention of neural tube defects: effect of an intervention aimed at implementing the official recommendations.

OBJECTIVES: The periconceptional intake of 0.4 mg folic acid is recommended in many countries to prevent neural tube defects. This paper describes the poor implementation of corresponding guidelines in Germany, the effectiveness of an intervention-based on providing adequate information and the problems associated with the implementation. METHODS: Two cross sectional studies investigated knowledge, attitude, and behaviour of randomly sampled gynaecologists (n = 24/27), pharmacists (n = 21/21), and women in childbed (n = 131/118) before and after the information campaign. RESULTS: Before the intervention, 3.8% of the women implemented folic-acid-prophylaxis compared with 9.3% afterwards (p = n.s.). The awareness of the prophylaxis before pregnancy correlated with socio-economic status and rose from 28% (before) to 42% after intervention (p < 0.05). Before the intervention, 38% of the gynaecologists and 38% of the pharmacists recommended the prophylaxis compared with 74% (p < 0.05) and 43% (p = n.s.) afterwards. CONCLUSIONS: The effect of the intervention was small. To improve the situation, fortification of specially selected and labelled food should be considered. An accompanying nationwide information campaign should focus on women with lower socio-economic status.

Female↗
PubMed1999

Drug use in first pregnancy and lactation: a population-based survey among Danish women. The EUROMAP group.

OBJECTIVE: To examine the drug prescription pattern in Danish women from 12 weeks prior to conception until 12 weeks post-partum. METHOD: A drug utilization study based on The North Jutland Prescription Database. The Danish pharmacies use a computerized accounting system for all subsidized drugs and this was linked to the Danish Medical Birth Registry concerning prescription patterns for all women who had given birth in the county of North Jutland from 1991 to 1996. RESULTS: The analysis included 16,001 primiparous women, who had redeemed 34,834 prescriptions prior to, during and after pregnancy. During pregnancy 44.2% of the women received prescriptions for at least one drug. Users received 2.6 prescriptions on average during pregnancy: 5% of the users redeemed 24.2% of all prescriptions. The proportion of women who redeemed prescriptions for more than three different drugs was 2.7%. The majority of prescriptions were for antibiotics (28.7%), gynaecological drugs (13.3%) and anti-asthma drugs (7.6%). The post-partum prescription proportion was 34.0% and the majority of the prescriptions during this period were for penicillins (20.1%), ophthalmologicals (15.5%) and corticosteroids for dermatological use (5.7%). CONCLUSION: A high proportion of the women received drugs during pregnancy. The pattern of drug use within the Anatomical Therapeutical Chemical (ATC) groups changed, i.e. the amount of broad spectrum antibiotics decreased and the proportion of prescriptions for local use increased. A small proportion of women redeemed prescriptions for more than three different drugs during pregnancy.

Adult↗