Use of folic acid and delivery outcome: a prospective registry study

doi:10.1016/S0890-6238(02)00041-2

Reproductive Toxicology

Volume 16, Issue 4, July–August 2002, Pages 327-332

https://doi.org/10.1016/S0890-6238(02)00041-2 Get rights and content

Abstract

Periconceptional use of folic acid is thought to reduce the risk for both neural tube defects and other congenital malformations. Most published data were obtained retrospectively. We used the Swedish Medical Birth Registry to study congenital malformations in infants born of women who reported the use of folic acid in early pregnancy (of which 70% probably used it also preconceptionally) and compared them with population rates. We divided the material according to two major confounders: subfertility problems and use of antiepileptic drugs. We found no protective effect of folic acid tablet use on the rate of congenital malformations but data on neural tube defects were scarce. Our results support the scepticism recently expressed in the literature on the beneficial effect of folic acid in preventing congenital malformations, especially of a non-neural tube defect type.

Introduction

During recent decades, a large number of studies have been published on the periconceptional use of folic acid and the occurrence of congenital malformations, notably neural tube defects (NTD). The studies have been performed using different methodology. Some studies were based on retrospective interviews of mothers of malformed infants and controls [1], [2], other on studies of enzymes relevant for folic acid metabolism [3], or measurements of folic acid or related substances in maternal or fetal compartments [4]), and one was a randomized study [5].

Intervention studies using folic acid supplementation or food fortification have not given clear-cut results [6]. The best known intervention study, which described a protective effect on the neural tube rate, is that from China [7]. The authors described a reduction of neural tube defect rate of 70% in north China (with a high NTD rate) and 40% in south China (with a low NTD rate) after supplementation with folic acid tablets.

Some studies have found a protective effect of folic acid on the rate of other congenital malformations than neural tube defects, e.g. facial clefts [8], [9], congenital heart defects [10], limb reductions and urogenital malformations [11], and anal atresia [12]. Also in the randomized study [5], a reduction in the rate of non-NTD malformations was seen. A recent review [13] discusses critically and in great detail the postulated preventive effect of folic acid supplementation on the occurrence of neural tube defects, notably spina bifida.

The present study describes findings from a prospective recording of drug use in early pregnancy in Sweden and the presence of congenital malformations in the offspring.

Section snippets

Material and methods

The study is based on data from the nationwide Swedish Medical Birth Registry [14]. This register contains data from the antenatal care clinics, from the delivery units, and the pediatric examination of the newborn infants. The register is based on copies of the original medical documents, used throughout Sweden. About 1–2% of the infants born in Sweden are missing in the register.

Since July 1994, data on drug use during pregnancy have been included in the register. This information is based on

Presence of congenital malformations after folic acid use

We identified 5331 infants whose mothers had reported the use of folic acid in early pregnancy. Among them, 221 had a diagnosis of a congenital malformation (4.1%) in the Medical Birth Registry and a further nine were identified only in the Registry of Congenital Malformations. During the same years, 584,010 infants were registered in the Medical Birth Registry, 20,590 with a congenital malformation diagnosis (3.5%). The crude OR for having a congenital malformation after maternal use of folic

Discussion

The present study found no effect of folic acid supplementation on the rate of congenital malformation in women who did not use anticonvulsants or reported a period of involuntary childlessness. This result is opposite to what is usually stated in the literature even though some doubts on the beneficial effects of folic acid have recently been expressed.

In contrast to the majority of the published studies, we used prospectively collected data, obtained by interviews in early pregnancy. Recall

Acknowledgements

The study was supported by grants to B.K. from Åke Wibergs Stiftelse and Knut and Alice Wallenberg’s Foundation.

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Vitamins, minerals and trace elements
2015, Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment: Third Edition
A varied and balanced composition of the daily diet is the preferred basis for supplying vitamins and minerals. However, diet and multivitamin use are unlikely to consistently prevent deficiencies, thus supplementation with additional specific nutrients is often needed. While folic acid may be the only vitamin identified to date that is supplemented even before conception, in many countries, multi vitamins/mineral tablets are used prior to, and during pregnancy, in order to provide coverage for any deficiencies in the diet. These recommendations may be especially important for the vegan and vegetarian who may not receive sufficient vitamins in their diets as well as appropriate amounts of iron. Questions have arisen with regard to additional supplementation of Vitamins A and D where an absence in the diet or lack of exposure to sunshine before and during pregnancy may occur. This chapter discusses the use of dietary supplements for preventing postnatal depression, the possible risks of preterm delivery and dietary nutrient intake, and it touches briefly on pregnant women following gastric bypass surgery.
The gene transfection efficiency of a folate-PEI600-cyclodextrin nanopolymer
2009, Biomaterials
Citation Excerpt :
Therefore, CyD are suitable to be used as biocompatible and solubility-enhancing moieties for the synthesis of biodegradable polymers. In addition to modifying and optimizing the polymeric gene carrier backbones, different target-specific ligands, including various signal transduction proteins, transfer proteins [22,23], and small molecules like folic acid [24,25] have also been explored to promote target-specific gene delivery in vitro and in vivo. Folate, in particular, has been found to be an optimal ligand for targeting tumor cells due to its low immunogenicity, low toxicity, and high affinity to the folate receptor, which is over-expressed in certain cancer cells [26].
The success of gene therapy relies on a safe and effective gene delivery system. In this communication, we describe the use of folate grafted PEI₆₀₀–CyD (H₁) as an effective polyplex-forming plasmid delivery agent with low toxicity. The structures of the polymer and polyplex were characterized, and the in vitro transfection efficiency, cytotoxicity, and in vivo transfection of H₁ were examined. We found that folate molecules were successfully grafted to PEI₆₀₀–CyD. At N/P ratios between 5 and 30, the resulting H₁/DNA polyplexes had diameters less than 120 nm and zeta potentials less than 10 mV. In various tumor cell lines examined (U138, U87, B16, and Lovo), the in vitro transfection efficiency of H₁ was more than 50%, which could be improved by the presence of fetal bovine serum or albumin. The cytotoxicity of H₁ was significantly less than high molecular weight PEI-25 kDa. Importantly, in vivo optical imaging showed that the efficiency of H₁-mediated transfection (50 μg luciferase plasmid (pLuc), N/P ratio = 20/1) was comparable to that of adenovirus-mediated luciferase transduction (1 × 10⁹ pfu) in melanoma-bearing mice, and it did not induce any toxicity in the tumor tissue. These results clearly show that H₁ is a safe and effective polyplex-forming agent for both in vitro and in vivo transfection of plasmid DNA and its application warrants further investigation.
Maternal obesity and neonatal congenital cardiovascular defects
2008, International Journal of Gynecology and Obstetrics
Citation Excerpt :
To observe the pure effect of obesity we excluded all women with prepregnancy or gestational diabetes. The theories of associations between isolated CHDs and maternal obesity or improper nutrition (as a periconceptional deficiency in vitamins) with are not well supported [11–18]. In this study, we found no significant differences among groups between periconceptional multivitamin intake and isolated CHDs in the newborn.
To determine whether isolated congenital heart defects (CHDs) were associated with maternal obesity.
In a retrospective study we compared the incidence and severity of isolated CHDs in the offspring of 428 women divided into 3 groups, one of women of normal weight (n = 141), one of obese women (n = 228), and one of morbidly obese women (n = 59) according to their body mass index.
There were 143 mild (66.8%), 44 moderate (20.6%), and 27 complex (12.6%) forms of CHDs in the offspring and septal defects were the most common (61.7%). No significant differences were found among the 3 groups of women regarding the type or severity of CHDs in their respective offspring, or the corrective cardiac surgery required.
No association was found between maternal weight and isolated CHDs in the offspring.
Vitamins, Minerals and Trace Elements
2007, Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment: Second Edition
Vitamins, minerals and trace elements
2007, Drugs During Pregnancy and Lactation
Use of folic acid supplementation and risk for dizygotic twinning
2004, Early Human Development
An increase in dizygotic twinning rate after folic acid supplementation has previously been described, but in a recent study from China, no such effect was seen.
To further investigate the association between use of folic acid supplement and dizygotic twinning.
Using the Swedish Medical Birth Registry, the rate of dizygotic twinning among infants of women who reported the use of folic acid was studied, taking a number of confounders into consideration. Comparisons were made with all women recorded in the register.
Unlike-sexed twin pairs were used as representatives of dizygotic twinning.
A number of confounders for the association between folic acid use and twinning were identified and taken into consideration. Women who were immigrants (who used less folic acid and had slightly lower twinning rates than women born in Sweden) and women who reported subfertility problems or treatment for subfertility (who had a high use of folic acid and a high twinning rate) were excluded, and adjustment was then made for year of birth, maternal age, parity, and smoking in early pregnancy. Folic acid use and twinning risk increased with maternal age and decreased with parity. Smokers used less folic acid than nonsmokers. Concomitant use of other drugs was no important confounder except for those used at subfertility. The odds ratio (OR) for dizygotic twinning after folic acid supplementation was then 1.71 (95%CI=1.21–2.42) and for the years 2000–2001 even 2.09 (95%CI=1.39–3.12).
There is an increase in twinning rate after folic acid supplementation in a Western population which should be taken into consideration when folic acid supplementation or food fortification is recommended.

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View full text

Use of folic acid and delivery outcome: a prospective registry study

Abstract

Introduction

Section snippets

Material and methods

Presence of congenital malformations after folic acid use

Discussion

Acknowledgements

Reprod. Toxicol.

Lancet

Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects

Epidemiology

Periconceptional nutrient intake and risk for neural tube defect-affected pregnancies

Epidemiology

5,10-Methylentetrahydrofolate reductase gene variants and congenital anomalies: a huge review

Am. J. Epidemiol.

Amniotic fluid homocystein levels, 5,10-methylentetrahydrofolate reductase genotypes, and neural tube closure sites

Am. J. Med. Genet.

Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation

N. Engl. J. Med.

Prevention of neural-tube defects with folic acid in China

N. Engl. J. Med.

Maternal multivitamin use and orofacial clefts in offspring

Teratology