Micronutrient status of pregnant women with fetal congenital malformations

封面


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅存取

详细

BACKGROUND: Congenital malformations of the central nervous system have extremely severe consequences, which makes it important to study their development and diagnosis during embryogenesis. Therefore, particularly relevant are studies in the field of prevention of fetal сongenital malformations.

AIM: The aim of this study was to assess the micronutrient status (vitamin D, serum and erythrocyte folic acid, vitamin B12) and homocysteine levels in women with induced abortion in the second trimester of pregnancy based on fetal indications (fetal сongenital malformations).

MATERIALS AND METHODS: This prospective cohort study enrolled 53 women with induced abortion for medical reasons from the fetus in the second trimester of gestation. All pregnant women were divided into two groups. Group 1 included 28 individuals without an established chromosomal abnormality in the fetus: with fetal сongenital malformations and no neural tube defects (n = 16) or with fetal сongenital malformations and neural tube defects (n = 12). Group 2 consisted of 25 pregnant women with established chromosomal abnormalities in the fetus.

RESULTS: In pregnant women with fetal сongenital malformations and neural tube defects, blood serum vitamin B12 level correlated with erythrocyte folic acid level and was lower compared with women with fetal сongenital malformations and no neural tube defects (p < 0.05). No significant differences were found for other parameters. In pregnant women with fetal сongenital malformations, homocysteine level did not differ from that in women with normal fetal development at this stage of pregnancy. Meanwhile, folic acid and vitamin B12 levels in women with fetal сongenital malformations were lower compared with pregnant women without this pathology (p < 0.001).

CONCLUSIONS: The features of micronutrient status found in patients with fetal сongenital malformations, in particular with neural tube defects, and the relationships between its individual parameters indicate complex etiologies of these pathologies. The data obtained indicate the expediency of assessing one-carbon metabolic parameters in the mother not only during pregnancy, but also at the stage of preconception preparation, as well as the need for additional research related to adequate control of vitamin intake and assessment of methionine cycle gene polymorphism.

作者简介

Yulia Milyutina

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: milyutina1010@mail.ru
ORCID iD: 0000-0003-1951-8312
SPIN 代码: 6449-5635

Cand. Sci. (Biol.)

俄罗斯联邦, Saint Petersburg

Margarita Shengelia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: bakleicheva@gmail.com
ORCID iD: 0000-0002-0103-8583

MD

俄罗斯联邦, Saint Petersburg

Olesya Bespalova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN 代码: 4732-8089

MD, Dr. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Olga Pachuliya

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: for.olga.kosyakova@gmail.com
ORCID iD: 0000-0003-4116-0222
SPIN 代码: 1204-3160

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Aleksandra Blazhenko

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: alexandrablazhenko@gmail.com
ORCID iD: 0000-0002-8079-0991
SPIN 代码: 8762-3604

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Kirill Denisov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: denisov4work@gmail.com
俄罗斯联邦, Saint-Petersburg

Anastasia Sazonova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: nastenka.sazonova.97@mail.ru
俄罗斯联邦, Saint-Petersburg

Andrey Korenevsky

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

编辑信件的主要联系方式.
Email: a.korenevsky@yandex.ru
ORCID iD: 0000-0002-0365-8532
SPIN 代码: 7942-6016

Dr. Sci. (Biol.)

俄罗斯联邦, Saint-Petersburg

参考

  1. Finnell RH, Caiaffa CD, Kim SE, et al. Gene environment interactions in the etiology of neural tube defects. Front Genet. 2021;12. doi: 10.3389/fgene.2021.659612
  2. Martino F, Magenta A, Pannarale G, et al. Epigenetics and cardiovascular risk in childhood. J Cardiovasc Med (Hagerstown). 2016;17(8):539–546. doi: 10.2459/JCM.0000000000000334
  3. Morris JK, Springett AL, Greenlees R, et al. Trends in congenital anomalies in Europe from 1980 to 2012. PLoS One. 2018;13(4). doi: 10.1371/journal.pone.0194986
  4. Detrait ER, George TM, Etchevers HC, et al. Human neural tube defects: developmental biology, epidemiology, and genetics. Neurotoxicol Teratol. 2005;27(3):515–524. doi: 10.1016/j.ntt.2004.12.007
  5. Greene ND, Copp AJ. Neural tube defects. Annu Rev Neurosci. 2014;37:221–242. doi: 10.1146/annurev-neuro-062012-170354
  6. Practice Bulletin No. 187: Neural tube defects. Obstet Gynecol. 2017;130(6):e279–e290. doi: 10.1097/AOG.0000000000002412
  7. Avagliano L, Massa V, George TM, et al. Overview on neural tube defects: from development to physical characteristics. Birth Defects Res. 2019;111(19):1455–1467. doi: 10.1002/bdr2.1380
  8. Peake JN, Knowles RL, Shawe J, et al. Maternal ethnicity and the prevalence of British pregnancies affected by neural tube defects. Birth Defects Res. 2021;113(12):968–980. doi: 10.1002/bdr2.1893
  9. Geneti SA, Dimsu GG, Sori DA, et al. Prevalence and patterns of birth defects among newborns in southwestern Ethiopia: a retrospective study. Pan Afr Med J. 2021;40:248. doi: 10.11604/pamj.2021.40.248.25286
  10. Tsiklauri R, Jijeishvili L, Kherkheulidze M, et al. Neural tube defects and micronutrients deficiency prevalence in Georgia. Georgian Med News. 2020;(298):61–66.
  11. Li H, Zhang J, Chen S, et al. Genetic contribution of retinoid-related genes to neural tube defects. Hum Mutat. 2018;39(4):550–562. doi: 10.1002/humu.23397
  12. Golden JA, Chernoff GF. Multiple sites of anterior neural tube closure in humans: evidence from anterior neural tube defects (anencephaly). Pediatrics. 1995;95(4):506–510.
  13. Copp AJ, Greene ND. Neural tube defects--disorders of neurulation and related embryonic processes. Wiley Interdiscip Rev Dev Biol. 2013;2(2):213–227. doi: 10.1002/wdev.71
  14. Copp AJ, Adzick NS, Chitty LS, et al. Spina bifida. Nat Rev Dis Primers. 2015;1. doi: 10.1038/nrdp.2015.7
  15. Janik K, Manire MA, Smith GM, Krynska B. Spinal cord injury in myelomeningocele: prospects for therapy. Front Cell Neurosci. 2020;14:201. doi: 10.3389/fncel.2020.00201
  16. Greene ND, Copp AJ. Development of the vertebrate central nervous system: formation of the neural tube. Prenat Diagn. 2009;29(4):303–311. doi: 10.1002/pd.2206
  17. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Folic acid supplementation for the prevention of neural tube defects: US preventive services task force recommendation statement. JAMA. 2017;317(2):183–189. doi: 10.1001/jama.2016.19438
  18. Czeizel AE, Dudás I, Vereczkey A, et al. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients. 2013;5(11):4760–4775. doi: 10.3390/nu5114760
  19. Chon J, Field MS, Stover PJ. Deoxyuracil in DNA and disease: genomic signal or managed situation?. DNA Repair. 2019;77:36–44. doi: 10.1016/j.dnarep.2019.02.014
  20. Crider KS, Yang TP, Berry RJ, et al. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr. 2012;3(1):21–38. doi: 10.3945/an.111.000992
  21. Lv X, Zhou D, Ge B, et al. Association of folate metabolites and mitochondrial function in peripheral blood cells in Alzheimer’s disease: a matched case-control study. J Alzheimers Dis. 2019;70(4):1133–1142. doi: 10.3233/JAD-190477
  22. van Gool JD, Hirche H, Lax H, et al. Folic acid and primary prevention of neural tube defects: a review. Reprod Toxicol. 2018;80:73–84. doi: 10.1016/j.reprotox.2018.05.004
  23. Levine SZ, Kodesh A, Viktorin A, et al. Association of maternal use of folic acid and multivitamin supplements in the periods before and during pregnancy with the risk of autism spectrum disorder in offspring. JAMA Psychiatry. 2018;75(2):176–184. doi: 10.1001/jamapsychiatry.2017.4050
  24. Raghavan R, Riley AW, Volk H, et al. Maternal multivitamin intake, plasma folate and vitamin B12 levels and autism spectrum disorder risk in offspring. Paediatr Perinat Epidemiol. 2018;32(1):100–111. doi: 10.1111/ppe.12414
  25. Yajnik CS, Deshpande SS, Jackson AA, et al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia. 2008;51(1):29–38. doi: 10.1007/s00125-007-0793-y
  26. McGowan EC, Hong X, Selhub J, et al. Association between folate metabolites and the development of food allergy in children. J Allergy Clin Immunol Pract. 2020;8(1):132–140.e5. doi: 10.1016/j.jaip.2019.06.017
  27. Cordero AM, Crider KS, Rogers LM, et al. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. Morb Mortal Wkly Rep. 2015;64(15):421–423.
  28. Hao L, Yang QH, Li Z, et al. Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial. Am J Clin Nutr. 2008;88(2):448–457. doi: 10.1093/ajcn/88.2.448
  29. Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural tube defects. Arch Dis Child. 1976;51(12):944–950. doi: 10.1136/adc.51.12.944
  30. Daly LE, Kirke PN, Molloy A, et al. Folate levels and neural tube defects. Implications for prevention. JAMA. 1995;274(21):1698–1702. doi: 10.1001/jama.1995.03530210052030
  31. Crider KS, Devine O, Hao L, et al. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014;349. doi: 10.1136/bmj.g4554
  32. Cortellino S, Wang C, Wang B, et al. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol. 2009;325(1):225–237. doi: 10.1016/j.ydbio.2008.10.020
  33. Juriloff DM, Harris MJ. Insights into the etiology of mammalian neural tube closure defects from developmental, genetic and evolutionary studies. J Dev Biol. 2018;6(3):22. doi: 10.3390/jdb6030022
  34. Lee S, Gleeson JG. Closing in on mechanisms of open neural tube defects. Trends Neurosci. 2020;43(7):519–532. doi: 10.1016/j.tins.2020.04.009
  35. Molloy AM, Pangilinan F, Brody LC. Genetic risk factors for folate-responsive neural tube defects. Annu Rev Nutr. 2017;37:269–291. doi: 10.1146/annurev-nutr-071714-034235
  36. Burren KA, Savery D, Massa V, et al. Gene-environment interactions in the causation of neural tube defects: folate deficiency increases susceptibility conferred by loss of Pax3 function. Hum Mol Genet. 2008;17(23):3675–3685. doi: 10.1093/hmg/ddn262
  37. Buyukkurt S, Binokay F, Seydaoglu G, et al. Prenatal determination of the upper lesion level of spina bifida with three-dimensional ultrasound. Fetal Diagn Ther. 2013;33(1):36–40. doi: 10.1159/000341568
  38. Steele JW, Kim SE, Finnell RH. One-carbon metabolism and folate transporter genes: Do they factor prominently in the genetic etiology of neural tube defects? Biochimie. 2020;173:27–32. doi: 10.1016/j.biochi.2020.02.005
  39. Osterhues A, Ali NS, Michels KB. The role of folic acid fortification in neural tube defects: a review. Crit Rev Food Sci Nutr. 2013;53(11):1180–1190. doi: 10.1080/10408398.2011.575966
  40. Heseker HB, Mason JB, Selhub J, et al. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid. Br J Nutr. 2009;102(2):173–180. doi: 10.1017/S0007114508149200
  41. Stothard KJ, Tennant PW, Bell R, et al. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA. 2009;301(6):636–650. doi: 10.1001/jama.2009.113
  42. Korkmaz L, Baştuğ O, Kurtoğlu S. Maternal obesity and its short- and long-term maternal and infantile effects. J Clin Res Pediatr Endocrinol. 2016;8(2):114–124. doi: 10.4274/jcrpe.2127
  43. Werler MM, Ahrens KA, Bosco JL, et al. Use of antiepileptic medications in pregnancy in relation to risks of birth defects. Ann Epidemiol. 2011;21(11):842–850. doi: 10.1016/j.annepidem.2011.08.002
  44. Becerra JE, Khoury MJ, Cordero JF, et al. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics. 1990;85(1):1–9.
  45. Kakebeen AD. Niswander L. Micronutrient imbalance and common phenotypes in neural tube defects. Genesis. 2021;59(11). doi: 10.1002/dvg.23455
  46. De Wals P, Tairou F, Van Allen MI, et al. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med. 2007;357(2):135–142. doi: 10.1056/NEJMoa067103
  47. Tang K-F, Li Y-L, Wang H-Y. Quantitative assessment of maternal biomarkers related to one-carbon metabolism and neural tube defects. Sci Rep. 2015;5. doi: 10.1038/srep08510
  48. Yang M, Li W, Wan Z, Du Y. Elevated homocysteine levels in mothers with neural tube defects: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2017;30(17):2051–2057. doi: 10.1080/14767058.2016.1236248
  49. Saraswathy KN, Kaur L, Talwar S, et al. Methylenetetrahydrofolate reductase gene-specific methylation and recurrent miscarriages: a case-control study from North India. J Hum Reprod Sci. 2018;11(2):142–147. doi: 10.4103/jhrs.JHRS_145_17
  50. Kirke PN, Molloy AM, Daly LE, et al. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med. 1993;86(11):703–708.
  51. Groenen PM, van Rooij IA, Peer PG, et al. Marginal maternal vitamin B12 status increases the risk of offspring with spina bifida. Am J Obstet Gynecol. 2004;191(1):11–17. doi: 10.1016/j.ajog.2003.12.032
  52. Sirinoglu HA, Pakay K, Aksoy M, et al. Comparison of serum folate, 25-OH vitamin D, and calcium levels between pregnants with and without fetal anomaly of neural tube origin. J Matern Fetal Neonatal Med. 2018;31(11):1490–1493. doi: 10.1080/14767058.2017.1319924
  53. Daglar K, Tokmak A, Kirbas A, et al. Maternal serum vitamin D levels in pregnancies complicated by neural tube defects. J Matern Fetal Neonatal Med. 2016;29(2):298–302. doi: 10.3109/14767058.2014.999037
  54. Larqué E, Morales E, Leis R, et al. Maternal and foetal health implications of vitamin D status during pregnancy. Ann Nutr Metab. 2018;72(3):179–192. doi: 10.1159/000487370
  55. Hamza M, Halayem S, Mrad R, et al. Implication de l’épigénétique dans les troubles du spectre autistique: revue de la littérature. Encephale. 2017;43(4):374–381. (In Fr.) doi: 10.1016/j.encep.2016.07.007
  56. Tous M, Villalobos M, Iglesias L, et al. Vitamin D status during pregnancy and offspring outcomes: a systematic review and meta-analysis of observational studies. Eur J Clin Nutr. 2020;74(1):36–53. doi: 10.1038/s41430-018-0373-x
  57. Eyles D, Brown J, Mackay-Sim A, et al. Vitamin D3 and brain development. Neuroscience. 2003;118(3):641–653. doi: 10.1016/s0306-4522(03)00040-x
  58. Sánchez-Hernández D, Anderson GH, Poon AN, et al. Maternal fat-soluble vitamins, brain development, and regulation of feeding behavior: an overview of research. Nutr Res. 2016;36(10):1045–1054. doi: 10.1016/j.nutres.2016.09.009
  59. Greene ND, Copp AJ. Inositol prevents folate-resistant neural tube defects in the mouse. Nat Med. 1997;3(1):60–66. doi: 10.1038/nm0197-60
  60. Cavalli P, Cavallari U, Unfer V, et al. Caffeine intake and risk of neural tube defects. Birth Defects Res A Clin Mol Teratol. 2011;91(1):67–68. doi: 10.1002/bdra.20739
  61. Ferrazzi E, Tiso G, Di Martino D. Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2020;253:312–319. doi: 10.1016/j.ejogrb.2020.06.012
  62. Kerkeshko GO, Arutjunyan AV, Arzhanova ON, et al. Folate therapy optimization in complicated pregnancy. Journal of Obstetrics and Women’s Diseases. 2013;62(6):25–36. (In Russ.) doi: 10.17816/JOWD62625-36
  63. Li Z, Ren A, Zhang L, et al. Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China. Birth Defects Res A Clin Mol Teratol. 2006;76(4):237–240. doi: 10.1002/bdra.20248

补充文件

附件文件
动作
1. JATS XML
2. Fig. 1. Nutrient status parameters and homocysteine levels in groups of pregnant women with fetal congenital malformations with or without a chromosomal abnormality: a, serum folic acid; b, erythrocyte folic acid; c, serum homocysteine; d, serum vitamin B12; e, serum vitamin D. CA, chromosomal abnormalities

下载 (316KB)
3. Fig. 2. Correlations between nutrient status parameters in groups of pregnant women with fetal congenital malformations: a, correlation relationships (red lines indicate significant associations); b, correlation relationships between folic acid and vitamin B12 levels in the group of women without neural tube defects; c, correlation relationships between folic acid and vitamin B12 levels in the group of women with neural tube defects. FAser, serum folic acid; FAer, erythrocyte folic acid; HC, serum homocysteine; B12, serum vitamin B12; D, serum vitamin D; NTD, neural tube defect; rs, Spearman’s rank correlation value; * p < 0.05

下载 (266KB)
4. Fig. 3. Nutrient status parameters and homocysteine levels in groups of pregnant women with fetal congenital malformations with or without neural tube defects: a, serum folic acid; b, erythrocyte folic acid; c, serum homocysteine; d, serum vitamin B12; e, serum vitamin D. NTD, neural tube defect; * p < 0,05

下载 (312KB)
5. Fig. 4. Nutrient status parameters and homocysteine levels in groups of pregnant women with fetal congenital malformations or with normal fetal development: a, serum homocysteine (n = 434 with normal development, n = 53 with congenital malformations); b, serum folic acid (n = 71 with normal development, n = 53 with congenital malformations; c, serum vitamin B12 (n = 71 with normal development, n = 53 with congenital malformations). MFCM, multiple fetal congenital malformations; * p < 0.001

下载 (171KB)

版权所有 © Eсо-Vector, 2023

Creative Commons License
此作品已接受知识共享署名-非商业性使用-禁止演绎 4.0国际许可协议的许可。

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».