Resolution of the Council of Experts "An Individualized Approach to Micronutrient Supplementation during Pregnancy"

On September 29, the XIII Regional Forum «Mother and Child» and the Plenary Board of the Russian Society of Obstetricians and Gynecologists set up Experts Council dedicated to an individualized approach to micronutrient supplementation during pregnancy. There was a presentation of the Protocol of a prospective internationalmulticenterobservationalstudyforassessing the incidence of pregnancy complications and outcomes in women using various vitamin supplementations during preconception period and pregnancy (the UNONA study). The participants of the meeting were leading experts in the field of obstetrics, gynecology, nutrition, genetics, pharmacology and clinical research from Russia, Kazakhstan and Uzbekistan.

The meeting was devoted to the discussion of demographic problems of modern society, the possibilities of preventing complicated pregnancy using evidence-based medicine and providing nutritional supplementation to pregnant women. The meeting also presented the Protocol on the new observational study UNONA, which will provide the new data on the clinical effects of vitamin and mineral complex in real clinical practice for pregnant women in Russia and in the countries of Commonwealth of Independent States (CIS).

The participants of the meeting noted that the current demographic situation in Russia is of serious concern. The present situation is characterized by a decrease in the birth rate; moreover, a complicated course of pregnancy and unfavorable pregnancy outcomes, as well as the prevalence of congenital malformations, which have a negative impact on the child’s health in the long term pose a threat [1, 2].

In the prevention of pregnancy complications, along with the treatment of somatic pathology, maintaining a healthy lifestyle and providing all necessary macronutrients and micronutrients at a sufficient level are of great importance [3]. Micronutrients are essential food substances (vitamins, minerals) and vitamin-like compounds that cannot be synthesized in the body, therefore their intake from food is absolutely necessary for maintaining vital functions. Unfortunately, despite the relative increase in economic indicators over the past two decades and the growing interest in a healthy lifestyle, the micronutrient deficiency level remains very high. According to the Federal Research Center of Nutrition and Biotechnology, the proportion of pregnant and nursing women in Russia who have polyhypovitaminosis (deficiency of three or more vitamins at once) ranges from 20 to 40%, and according to some data, up to 70–80% [3, 4]. At the same time, according to internal estimates of the company Bayer, the number of women receiving complete preconception care, which also includes the use of folic acid or multivitamins, does not exceed 10% [5].

Micronutrient deficiency results in a negative impact on the course of pregnancy, fetal development, immune status, and also cause a lack of vitamins in breast milk [3]. Folic acid deficiency is a leading exogenous factor in the formation of neural tube defects [6]. Multiple studies and meta-analyses have established a correlation between insufficient levels of vitamin D in the blood and preeclampsia, the development of diabetes in pregnant women and low birth weight [7].

Along with this, a positive effect of correction of hypovitaminosis with vitamin and mineral complex for both mother and child has been proved [8].

In this regard, the appearance of new clinical guidelines «Normal pregnancy» in 2019 were of special significance. The guidelines regulate the use of vitamin and mineral complex during pregnancy. The Council of Experts noted the necessity to add some more information to the clinical guidelines «Normal pregnancy» due to the recent published data in this area.

Thus, the participants of the meeting emphasized the need for an individual approach to micronutrient supplementation during pregnancy, based on the identification of risk factors for hypovitaminosis. The low-risk group includes women without previous risks for birth defects and without somatic diseases; patients with normal research indicators (hemoglobin level of 120 g/L, body mass index (BMI) in the range of 18.5–30 kg/m2), living in favorable conditions and having a varied diet are also in this group. The criterion for being classified as a high-risk group is the presence of at least one of the following factors: age 35 years and older, hemoglobin level less than 120 g/L, BMI ≥ 30 kg/ m2 or less than 18.5 kg/m2, complicated obstetric and gynecological history, concomitant diseases, improper lifestyle, nutritional disorders or administration of medications that impair the metabolism of vitamins and minerals [9].

Women at high risk for hypovitaminosis need its correction using special vitamin and mineral complexes for pregnant women who have indications for the treatment of hypovitaminosis. Taking into account the increased needs during pregnancy, women at low risk for hypovitaminosis are recommended to use vitamin and mineral supplements containing 50–100% of the daily vitamin requirement. This approach will reduce not only the risk of fetal malformations, but also pregnancy complications [9].

The administration of vitamin and mineral supplements to women in highly developed countries has shown a number of positive effects (prevention of many congenital abnormalities, including intrauterine growth retardation), so the use of vitamin and mineral complex should be recommended even in a group of women at low risk for hypovitaminosis [10].

The Council of Experts concluded that there is a need to increase the number of recommendations for the use of folic acid both during pregnancy and in the preconception period. It is recommended to start taking folic acid supplements 1-3 months before conception and for at least the first 12 weeks of pregnancy at a dose of 400–800 mcg per day. This particular mode of administering folic acid is supported by many international guidelines, as it has shown a decrease in the risk of neural tube defects and other malformations [11–13].

It is necessary to clarify the administered dosage of vitamin A. Its deficiency is associated with a number of malformations, the risk of respiratory distress syndrome and disorders of the immune system [14]. Vitamin A deficiency is not so common, so the routine administration of vitamin A as a mono-preparation is not recommended, but it can be included in specially developed vitamin and mineral complex for pregnant women. Dosages of vitamin A are 700– 1000 mcg of retinol equivalents (RE) and correspond to the normal daily requirements during pregnancy [15, 16].

There is a growing need for evidence-based clinical data obtained in real clinical practice and for the relevant population. Unfortunately, there is not enough data on the best regimens of the vitamin and mineral support during pregnancy for the population of Russia and the CIS countries. More evidence is required for the benefits of vitamin and mineral supplements compared to folic acid mono-preparations. It is also necessary to obtain more information about the effects of vitamin and mineral complexes when they are taken in the preconception period and their possible impact not only on the risk of malformations, but also on pregnancy complications.

Therefore, Bayer initiated an international prospective study to assess the incidence of pregnancy complications and outcomes in women who take various vitamin supplementations during preconception period and during pregnancy (UNONA). The Council of Experts reviewed and approved the concept of the Protocol of the UNONA study, which will be further submitted to the regulatory bodies and published in the registry ClinicalTrials.gov. The research is planned to be conducted in 2021–2024, and its results are expected to be published in the future.

The study is planned to include 1,500 women in Russia, Belarus, Kazakhstan, and Uzbekistan. The women are going to be divided into groups for the analysis of the effects of the «Elevit» vitamin and mineral complex in comparison with folic acid, depending on the risk for vitamin deficiency and the time of beginning the use of vitamin and mineral supplements, namely preconception period or the first trimester of pregnancy. The results of the study are expected to provide additional data for recommendations on individualization of micronutrient supplementation, depending on the current needs of the patient.

The Council of Experts was held with the support of JSC BAYER (Russia).

Council of Experts

Gennady T. Sukhikh, Academician of the RAS, Dr. Med. Sci., Professor, Honored Scientist of Russia, Director of the FSBI “National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov», Ministry of Healthcare of the Russian Federation; Head of the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Postgraduate Education, Federal State Autonomous Educational Institution of Higher Education "First Moscow State Medical University named after I.M. Sechenov", Ministry of Healthcare of the Russian Federation

Vladimir N. Serov, Academician of the RAS, Dr. Med. Sci., Professor, Honored Scientist of the Russian Federation, President of the RSOG, Chief Researcher of the Organizational and Methodological Department of the Scientific and Organizational Support Service of the FSBI “National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov», Ministry of Healthcare of the Russian Federation

Natalia V. Aganezova, Dr. Med. Sci., Professor of the Department of Obstetrics and Gynecology, North-Western State Medical University named after I.I. Mechnikov

Natalia V. Artymuk, Dr. Med. Sci., Professor, Chief External Obstetrician-Gynecologist of the Ministry of Health of Russia in the Siberian Federal District, Head of the Department of Obstetrics and Gynecology, Kemerovo State Medical University, President of the Kemerovo Regional Public Organization "Association of Obstetricians and Gynecologists"

Igor I. Baranov, Dr. Med. Sci., Professor, Head of the Organizational and Methodological Department of the FSBI “National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov», Ministry of Healthcare of the Russian Federation

Nadezhda V. Bashmakova, Dr. Med. Sci., Professor, Chief External Specialist Obstetrician-Gynecologist of the Ministry of Health of Russia in the Ural Federal District, Chief Researcher of the Ural Research Institute of Maternity and Infancy

Elena A. Gorodnova, PhD, MPH, Head of the Clinical Research Center of the Department for Organization of Scientific Activities of the FSBI “National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov», Ministry of Healthcare of the Russian Federation

Olga A. Gromova, Dr. Med. Sci., Professor, Leading Researcher, Scientific Director of the Institute of Pharmacoinformatics, Federal Research Center "Informatics and Management" RAS

Svetlana O. Dubrovina, Dr. Med. Sci., Professor, Chief Researcher of the Obstetric and Gynecological Department, Rostov State Medical University of the Ministry of Health of the Russian Federation, Professor of the Department of Obstetrics and Gynecology No. 1

Dilorom P. Kamilova, PhD, Chief IVF Specialist of the Mother and Child Group (Moscow)

Diprabo T. Kajumova, PhD, Associate Professor of the Department of Obstetrics and Gynecology of the Tashkent Medical Academy, Scientific Director of the Department of Gynecology of the TMA

Igor Yu. Kogan, Corresponding member RAS, Dr. Med. Sci., Professor, Director of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Chief External Reproductive Health Specialist, St. Petersburg Health Committee

Vera M. Kodentsova, Dr. Biol. Sci., Professor, Chief Researcher of the Laboratory of Vitamins and Minerals of the Federal Research Center for Nutrition, Biotechnology and Food Safety

Alexander G. Konoplyannikov, Dr. Med. Sci., Professor of the Department of Obstetrics and Gynecology of the Pediatric Faculty of the Russian National Research Medical University named after N.I. Pirogov, Ministry of Health of the Russian Federation

Irina V. Kuznetsova, Dr. Med. Sci., Professor, Head of the direction "Gynecological Endocrinology", Scientific Director, Higher medical school MMC Moscow academic IVF clinic (Moscow)

Irina V. Nefedova, Physician, Head of Healthcare Professionals, Bayer Consumer Health

Anton S. Olenev, PhD, Associate Professor, Chief Freelance Specialist in Obstetrics and Gynecology of the Moscow Department of Health, Head of Perinatal Center of the City Clinical Hospital No. 24 (Moscow)

Stanislav V. Pavlovich, PhD, Associate Professor, Scientific Secretary, Head of Training Unit, Professor of the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, Sechenov University

Natalia M. Podzolkova, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, RMANPO

Viktor E. Radzinsky, Honored Scientist of the Russian Federation, Corresponding Member of RAS, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology with a course of Perinatology at the Medical Institute of the Peoples' Friendship University of Russia, President of the Interdisciplinary Association of Reproductive Medicine Specialists (MARS), Co-Chairman of the All-Russian Information and Educational Initiative "Neonatology and Pediatrics: Development of Clinical Practices"

Gulnara S. Svyatova, Dr. Med. Sci., Professor, Head of the Republican Medical and Genetic Consultation of the Republican State Enterprise on the REM "Scientific Center for Obstetrics, Gynecology and Perinatology", Ministry of Health of the Republic of Kazakhstan, President of the Republican Association of Medical Geneticists

Olga F. Serova, Chief External Specialist of the Ministry of Health of the Moscow Region for obstetrics and gynecology, Chief Physician of the Moscow Regional Perinatal Center, Moscow Region, Balashikha

Margarita Yu. Skvortsova, PhD, Head of the Academic Department, Associate Professor of the Department of Obstetrics and Gynecology, RMANPO

Kirill A. Sokolov, obstetrician-gynecologist, Head of Medical and Clinical Department Russia, Ukraine and CIS countries, Consumer Health Division, Bayer Consumer Health

Nana K. Tetruashvili, Dr. Med. Sci., Head of the Department of Prevention and Therapy of Miscarriage of the FSBI “National Medical Research Center of Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov», Ministry of Healthcare of the Russian Federation

Talshun M. Ukubasova, Doctor of Medicine, Professor, National Research Center for Motherhood and Childhood, Nursultan, Kazakhstan

Marina B. Khamoshina, Dr. Med. Sci., Professor of the Department of Obstetrics and Gynecology with a course of Perinatology at the Medical Institute of the Peoples' Friendship University of Russia

Maria I. Yarmolinskaya, Professor of the Russian Academy of Sciences, Dr. Med. Sci., Professor, Head of the Department of Endocrinology of Reproduction, Federal State Budgetary Scientific Institution "Research Institute of Obstetrics, Gynecology and Reproduction named after D.O. Ott”; Professor of the Department of Obstetrics and Gynecology, I.I. Mechnikov North-Western State Medical University; Head of the Center for Innovative Methods of Diagnosis and Treatment of Endometriosis; Deputy Chief Obstetrician-Gynecologist of the Health Committee of St. Petersburg, President of the Society of Obstetricians gynecologists of St. Petersburg and North-West region, Russia