AAP News（2008年）
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2008年 年間提供AAPニュース
＜AAP news 2007-023=20071116＞
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＜AAP news 2007-021=20070909＞
＜AAP news 2007-020=20070708＞
＜AAP news 2007-019=20070627＞
＜AAP news 2007-018=20070602＞
＜AAP news 2007-017=20070522＞
＜AAP news 2007-016=20070511＞
＜AAP news 2007-016=20070511＞
＜AAP_NEWS_2008_004_20080215＞
Key Words: Folate, folic acid, pregnancy, complications, fetal growth, malformations, lactation, male reproduction
Key research findings relative to the question of whether maternal use of folic acid before and during pregnancy reduces the chance that offspring will be born with a congenital heart defect or an orofacial cleft are reviewed in this paper. Observational studies in general support an association between maternal use of multivitamins containing folic acid and a reduction in the occurrence of congenital heart defects and orofacial clefts. Results from one randomized controlled trial (RCT) provide the strongest evidence that multivitamins prevent congenital heart defects, but this RCT did not provide evidence that multivitamins prevent orofacial clefts. In addition, most observational and interventional studies are not designed to detect an independent effect from folic acid. Early studies suggested that periconceptional multivitamin use was associated with an increased occurrence of both miscarriages and multiple births, which has resulted in a great deal of controversy about the safety of folic acid use during pregnancy. We also review reports that were designed to answer these questions with more definitive data. When more substantial evidence about the effect of periconceptional folic acid on the occurrence of congenital heart defects and orofacial clefts is reported, we will have additional support for promoting folic acid intervention programs. All women capable of becoming pregnant should continue to consume 400 μg/d of folic acid in addition to a healthy diet as advised.
Key words: apoptosis/folic acid/homocysteine/placenta/trophoblast
＜AAP_NEWS_2008_003_20080214＞
＜AAP_NEWS_2008_002_20080128＞
＜AAP_NEWS_2008_001_20080101＞
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葉酸の気になる報告⑥としてランセットに葉酸摂取がIVFにおける双胎の発生に関与していると言う報告を掲載しています。
この背景には、米国などは食品に葉酸含有強化を義務化している背景に加え、神経管障害予防のサプリメント摂取が葉酸摂取の増大傾向にあるのかもしれないと言う事です。この傾向はカナダにおける先天性障害を半減させた事もありますが、同様の影響もある様で、英国にもその影響が及ぶ事の警鐘と考えられている様です。
今後の胚移植数が年齢にもよりますが、原則１個と言う事になりましたが、葉酸の高濃度摂取がＭＤツインの発生に関わるかもしれない報告です。
① Homocysteine and Folate Levels as Risk Factors for Recurrent Early Pregnancy Loss
Obstetrics & Gynecology 2000;95:519-524
Objective: To estimate the relative risk of recurrent early pregnancy loss for different total plasma homocysteine and serum folate concentrations.
Methods: In a case-control study, we measured homocysteine (fasting and afterload), folate (serum and red cells), pyridoxal 5'-phosphate, and cobalamin concentrations in 123 women who had at least two consecutive spontaneous early pregnancy losses each and compared concentrations with those of 104 healthy controls.
Results: Women with recurrent early pregnancy losses had significantly lower serum folate concentrations than controls, whereas the other measurements were similar to those of controls. Elevated homocysteine, fasting greater than 18.3 μmol/L and afterload greater than 61.5 μmol/L, was a risk factor for recurrent early pregnancy loss, with odds ratios (ORs) and 95% confidence intervals (95% CIs) of 3.6 (1.2, 12.7) and 2.7 (0.9, 8.8) in the group with recurrent miscarriages: 6.4 (1.9, 24.3) and 4.3 (1.2, 17.3) in primary aborters, and 4.2 (1.3, 15.4) and 3.4 (1.0, 12.8) in those with three or more miscarriages. The ORs (95% CIs) in the same study populations for serum folate concentrations less than 8.4 nmol/L were 2.1 (0.9, 4.8), 2.7 (1.0, 7.8), and 3.2 (1.3, 8.1), respectively. A significant dose-response relationship between serum folate concentrations and risk of recurrent early pregnancy loss suggested a protective effect by high serum folate concentrations.
Conclusion: Elevated homocysteine and reduced serum folate concentrations were risk factors for recurrent spontaneous early pregnancy losses. Folic acid supplementation might be beneficial in women with histories of early pregnancy loss.
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② Folate and human reproduction
Am. J. Clinical Nutrition, May 1, 2006; 83(5): 993 - 1016.
The influence of folate nutritional status on various pregnancy outcomes has long been recognized. Studies conducted in the 1950s and 1960s led to the recognition of prenatal folic acid supplementation as a means to prevent pregnancy-induced megaloblastic anemia. In the 1990s, the utility of periconceptional folic acid supplementation and folic acid food fortification emerged when they were proven to prevent the occurrence of neural tube defects. These distinctively different uses of folic acid may well be ranked among the most significant public health measures for the prevention of pregnancy-related disorders. Folate is now viewed not only as a nutrient needed to prevent megaloblastic anemia in pregnancy but also as a vitamin essential for reproductive health. This review focuses on the relation between various outcomes of human reproduction (ie, pregnancy, lactation, and male reproduction) and folate nutrition and metabolism, homocysteine metabolism, and polymorphisms of genes that encode folate-related enzymes or proteins, and we identify issues for future research.
http://www.ajcn.org/cgi/reprint/83/5/993
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③ Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage
American Journal of Clinical Nutrition, Vol. 81, No. 5, 1213S-1217S, May 2005
ABSTRACT
Key Words: Folic acid, heart defects, orofacial clefts, miscarriages, multiple births
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④ Effect of folic acid on homocysteine-induced trophoblast apoptosis
Mol. Hum. Reprod., September 1, 2004; 10(9): 665 - 669
In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 μmol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.
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⑤ Plasma Folate Levels and Risk of Spontaneous Abortion
JAMA, October 16, 2002; 288(15): 1867 - 1873.
JAMA. 2002;288:1867-1873.
Context Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies.
Objective To study the association between plasma folate levels and the risk of spontaneous abortion.
Design, Setting, and Population Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks.
Main Outcome Measure Risk of spontaneous abortion vs maternal plasma folate level.
Results Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (2.19 ng/mL [4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and 6.17 ng/mL [14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33).
Conclusion Low plasma folate levels were associated with an increased risk of early spontaneous abortion.
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⑥ High folate intake plus IVF may increase twin births By Stephen Daniells
05-May-2006-- Women undergoing IVF fertility treatment have a higher chance of twins if their folate intake is above the recommended dose, says new research.
"Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining livebirth rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age," said lead researcher Paul Haggarty from the University of Aberdeen, UK. In-vitro fertilization (IVF) is a popular treatment for infertility and 20 per cent of treatment cycles result in pregnancy and livebirth. Most IVF practitioners increase the chance of pregnancy by implanting multiple embryos. Indeed, in the UK double embryo implantation is the norm.
The new prospective cohort study, published in the latest issue of The Lancet (vol.367, pp. 1513-1519), reports that women undergoing IVF and with excessive folate intake during pregnancy have increased births of twins. This is an issue to be considered, say the researchers, with the expected introduction of folic acid flour fortification in the UK.
In the UK expectant mothers are currently prescribed and recommended to take folate supplements to reduce the risk of neural tube defects. However, studies suggest that a lack of compliance is undermining these recommendations, and calls are growing for the introduction of fortification of flour with folic acid. In 1998 the US introduced fortification measures; a move that has seen the number of birth defects fall by 25 per cent. Similar strategies in Canada have seen the instance of birth defects cut in half.
The Aberdeen researchers enrolled 602 women undergoing IVF treatment. Dietary and supplemental intake of folate and vitamin B12 was calculated from self-administered food frequency questionnaires, with 528 women completing the questionnaire. Blood samples were also taken to measure plasma folate and vitamin B12 levels, and red blood cell folate levels.
The researchers found that the average folate intake from food was 311 micrograms, while the vitamin B12 intake was 6.5 micrograms. For women who took supplements, 73 per cent took the recommended daily amount (400 micrograms per day), while nine per cent took less that the RDA.
"High folate status (high intake and concentration of plasma and red cell folate) before pregnancy increases the chance of twins, but not the likelihood of a successful pregnancy after IVF," said Haggarty.
For a 100 microgram per day change in plasma-derived folate intake, the researchers calculated that the chance of twins increased by 22 per cent.
Increased vitamin B12 intake was also associated with an increased chance of twins, but the researchers said that this was possibly a secondary effect due to "significant covariance between plasma folate and vitamin B12."
The results, says Haggarty, have practical implications in light on the expected introduction of fortification of flour with folic acid.
"If the level of fortification achieved in the USA (increased intake of about 200 micrograms per day) were repeated in the UK, we calculate that the odds ration for IVF twin birth would be 1.48, or 1.62 based on the plasma folate-derived estimate of intake," said the researchers.
The lower of these estimates would translate into a increase of 600 twin births associated with IVF.
The USA is reported to have seen a 12 per cent increase in twin births for fertility treated mothers since the introduction of mandatory folic acid fortification in 1998.
"The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt," said Haggarty. "But the associated risks of multiple births after IVF need to be addressed."
Since bread is a staple in most diets, flour has been seen as the ideal vehicle to improve iron intake for a population. Studies have shown that folic acid is more easily absorbed from fortified foods (85 per cent) and supplements (100 per cent) than the folate found naturally in foods (50 percent).
The US fortification program has not been a total success story however, with a commentary published in the journal Pediatrics (Sept. 2005, Vol. 116, pp.753-755) claiming fortification levels need to be increased.
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「生殖環境とｐ５３とカルニチン」
ｐ５３遺伝子の失活は癌の約半数に関わるとされますし、その発現機構はアポトーシスの誘導とリン酸化に関わる事が示唆されています。
Nature. 2007 Nov 29;450(7170):721-4
① p53 regulates maternal reproduction through LIF
Wenwei Hu1,3 , Zhaohui Feng 1,3 , Angelika K. Teresky1 & Arnold J. Levine1,2
1. Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08903, USA
2. The Simons Center for Systems Biology, The Institute for Advanced Study, Princeton, New Jersey 08540, USA
3. These authors contributed equally to this work.
Correspondence to: Arnold J. Levine1,2 Correspondence and requests for materials should be addressed to A.J.L. (Email: alevine@ias.edu).
Extensive studies have shown that p53 is important in tumour prevention1. However, little is known about its normal physiological function. Here we show that p53 is important in reproduction, in a gender-specific manner. Significant decreases in embryonic implantation, pregnancy rate and litter size were observed in matings with p53 -/- female mice but not with p53 -/- male mice. The gene encoding leukaemia inhibitory factor (LIF), a cytokine critical for implantation2, was identified as a p53-regulated gene that functions as the downstream mediator of this effect. p53 can regulate both basal and inducible transcription of LIF. Loss of p53 decreased both the level and function of LIF in uteri. Lower LIF levels were observed in the uteri of p53 -/- mice than in those of p53 +/+ mice, particularly at day 4 of pregnancy, when transiently induced high levels of LIF were crucial for embryonic implantation. This observation probably accounts for the impaired implantation of embryos in p53 -/- female mice. Administration of LIF to pregnant p53 -/- mice restored maternal reproduction by improving implantation. These results demonstrate a function for p53 in maternal reproduction through the regulation of LIF. Evidence is accumulating that p53 may have a similar function in humans.
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Free Radic Biol Med. 2007 Dec 15;43(12):1656-69. Epub 2007 Sep 14.
② Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: Role of carnitine and lipoic acid.
Tamilselvan J, Jayaraman G, Sivarajan K, Panneerselvam C.
Department of Medical Biochemistry, Dr. AL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Mitochondrial dysfunction has been implicated in the regulation of myofiber loss during aging, possibly by apoptotic pathways. However, the mitochondrial-mediated pathway of apoptosis by cytochrome c in skeletal muscle remains ambiguous. To understand this, we have studied the upstream and downstream events of cytochrome c release, and assessed the efficacy of carnitine and lipoic acid cosupplementation. The results show that elevated levels of cytosolic cytochrome c activate apoptosis in aged rats, and was confirmed further by in vitro caspase-3 assay. Interestingly, the exogenous addition of cytochrome c results in a much higher increase of caspase-3 activity in aged treated rats than age-matched control rats, strongly suggesting that cytochrome c is a limiting factor for caspase-3 activation in the cytosol. Carnitine and lipoic acid supplement decreased apoptosis in aged rats by maintaining mitochondrial membrane integrity and thereby preventing further loss of cytochrome c in vivo. Furthermore, the upregulation of p53 observed in aged rats is attributed to the loss of outer mitochondrial membrane integrity and subsequent release of cytochrome c through BH3-only proteins. In conclusion, the p53-dependent activation of the mitochondrial-cytochrome c pathway of apoptosis in the present study suggests the existence of cross talk between mitochondria and nucleus. However, the exact molecular mechanism remains to be explored. Oral supplements of carnitine and lipoic acid play an antiapoptotic role in aged rat skeletal muscle by protecting mitochondrial membrane integrity.
PMID: 18037131 [PubMed - in process]
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In Vivo. 2000 May-Jun;14(3):401-5.
③ The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice.
Yoshida G, Horiuchi M, Kobayashi K, Jalil MD, Iijima M, Hagihara S, Nagao N, Saheki T.
Department of Biochemistry, Faculty of Medicine, Kagoshima University, Japan.
Cardiotrophin-1 (CT-1) is a novel cytokine which is involved in the growth and survival of cardiac cells. We examined whether CT-1 plays a role in the development of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice. The CT-1 mRNA level was quantitatively measured by the competitive RT-PCR method. In contrast to other models including spontaneously hypertensive rats, CT-1 mRNA in the ventricles of JVS mice was comparable to the control at 5 days and was less than half the control value at 2 and 8 weeks when the ventricles of the JVS mice were highly hypertrophied. There were no significant differences in CT-1 mRNA levels in the lung, liver, kidney, small intestine and skeletal muscle between the JVS and control mice at 2 weeks. We did not find any difference between JVS and control mice at 2 weeks in the mRNA level of ventricular leukemia inhibitory factor (LIF) which binds to the same receptor as CT-1. Furthermore, almost no phosphorylated STAT3 (signal transducer and activator of transcription 3), downstream of the LIF receptor and the gp130 signaling subunit, was observed in the ventricles of JVS and control mice. These data show that the CT-1 signaling pathway does not play a significant role in the development of cardiac hypertrophy in JVS mice. Furthermore, we could not detect any differences in insulin-like growth factor I and II mRNA levels. All these data suggest distinct differences in the mechanisms of cardiac hypertrophy between JVS mice and other model animals.
PMID: 10904873 [PubMed - indexed for MEDLINE]
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卵巣機能とDHEA投与における臨床検討
http://humrep.oxfordjournals.org/cgi/reprint/21/11/2845
１．cox hazard modelとの比較⇒ミトコンドリア機能（cox；ミトコンドリアのアポトーシスの引き金）
２．micronized DHEA
J Assist Reprod Genet. 2007 Dec;24(12):629-34. Epub 2007 Dec 11.
Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function.
OBJECTIVE: We assessed the role of DHEA supplementation on pregnancy rates in women with diminished ovarian function.
DESIGN: This is a case control study of 190 women with diminished ovarian function. The study group includes 89 patients who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4 months prior to entry into in vitro fertilization (IVF). The control group is composed of 101 couples who received infertility treatment, but did not use DHEA. The primary outcome was clinical pregnancy after the patient's initial visit. We developed a Cox proportional hazards model to compare the proportional hazards of pregnancy among women using DHEA with the controls group.
RESULTS: Cumulative clinical pregnancy rates were significantly higher in the study group (25 pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in study group (HR 3.8; 95% CI 1.2-11.8; p < 0.05).
CONCLUSIONS: DHEA treatment resulted in significantly higher cumulative pregnancy rates. These data support a beneficial effect of DHEA supplementation among women with diminished ovarian function.
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①ＩＵＧＲと２型糖尿病の関連性の示唆
IUGRの背景にL-カルニチン（ＣＰＴ－Ⅰ）の存在が推察されるという実験動物（ラット）での報告です。妊婦の糖尿病が増加傾向であることは、日本糖尿病・妊婦学会でも発表されています。背景のミトコンドリア機能低下が推察されるところですが、IUGRにもミトコンドリア機能の影響が示唆された報告です。
① Changes in the Expression of Hypothalamic Lipid Sensing Genes in Rat Model of Intrauterine Growth Retardation (IUGR).
Puglianiello A, Germani D, Antignani S, Tomba GS, Cianfarani S.
Pediatr Res. 2007 Apr;61(4):433-7.
Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. The mechanisms underlying this phenomenon are unknown. Recent data suggest that some of the molecular defects underlying type 2 diabetes reside in the CNS. The enzyme carnitine palmitoyltransferase-1 (CPT1) regulates long-chain fatty acid (LCFA) entry into mitochondria, where LCFA undergo beta-oxidation. Hypothalamic inhibition of CPT1 decreases food intake and suppresses endogenous glucose production. Our aim was to investigate the effects of uterine artery ligation, a procedure that mimics uteroplacental insufficiency, on the CNS expression of CPT1 and other key enzymes of LCFA metabolism. Bilateral uterine artery ligation was performed on d 19 of gestation in the pregnant rat; sham-operated pregnant rats served as controls. Hypothalamus, cerebellum, hippocampus, and cortex were dissected and analyzed at birth by real-time PCR. Nonesterified fatty acid (NEFA) serum levels were significantly higher in IUGR pups (p < 0.0001). In IUGR rats, the hypothalamic expression of CPT1 isoform C (p = 0.005) and acetyl-CoA .arboxylase (ACC) isoforms alpha (p < 0.05) and beta (p = 0.005) were significantly decreased. The data presented here support the hypothesis that an abnormal intrauterine milieu can induce changes in hypothalamic lipid sensing. ABBREVIATIONS::
PMID: 17515867 [PubMed - in process]
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②ホモシステインは、流産以外にも妊娠合併症のリスクファクターの１つとの報告
② Homocysteine is lower in the third trimester of pregnancy in women with enhanced folate status from ontinued folic acid supplementation.
Holmes VA, Wallace JM, Alexander HD, Gilmore WS, Bradbury I, Ward M, Scott JM, McFaul P, McNulty H. Northern Ireland Centre for Food and Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, UK.
Clin Chem. 2005 Mar;51(3):629-34. Epub 2004 Dec 22.
BACKGROUND: In many countries, current recommendations are that women take a daily 400-mug folic acid supplement from before conception until the end of the 12th week of gestation for the prevention of neural tube defects. Low folate status is associated with an increased concentration of plasma total homocysteine (tHcy), a risk factor associated with pregnancy complications such as preeclampsia. METHODS: In a longitudinal study, we determined tHcy and corresponding folate status in 101 pregnant women at 12, 20, and 35 weeks of gestation, in 35 nonpregnant controls sampled concurrently, and in a subgroup (n = 21 pregnant women and 19 nonpregnant controls) at 3 days postpartum. RESULTS: Plasma tHcy was significantly lower throughout pregnancy compared with nonpregnant controls, with values lowest in the second trimester before increasing toward nonpregnant values in the third trimester. Importantly, mean tHcy concentrations were lower in pregnant women taking folic acid supplements than in those not, an effect that reached significance in the third trimester (5.45 vs 7.40 micromol/L; P <0.05). During the third trimester, tHcy concentrations were significantly higher in pregnant women with a history of miscarriage than in women with no previous history (8.15 vs 6.38 micromol/L; P <0.01). CONCLUSIONS: This is the first longitudinal study to show that homocysteine concentrations increase in late pregnancy toward nonpregnant values; an increase that can be limited by enhancing folate status through continued folic acid supplementation. These results indicate a potential role for continued folic acid supplementation in reducing pregnancy complications associated with hyperhomocysteinemia.
PMID: 15615817 [PubMed - indexed for MEDLINE]
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③血漿葉酸レベルと自然流産の相関性の報告
③ Plasma folate levels and risk of spontaneous abortion.
George L, Mills JL, Johansson AL, Nordmark A, Olander B, Granath F, Cnattingius S.
Department of Medical Epidemiology, Huddinge University Hospital, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
JAMA. 2002 Oct 16;288(15):1867-73.
CONTEXT: Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies.
OBJECTIVE: To study the association between plasma folate levels and the risk of spontaneous abortion.
DESIGN, SETTING, AND POPULATION: Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks.
MAIN OUTCOME MEASURE: Risk of spontaneous abortion vs maternal plasma folate level.
RESULTS: Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33).
CONCLUSION: Low plasma folate levels were associated with an increased risk of early spontaneous abortion.
PMID: 12377085 [PubMed - indexed for MEDLINE]
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