Neonatal Risks of Vitamin D and Iodin Supplementations during Pregnancy

Background: The consumption of dietary supplements (DS) has increased by almost 10% last decade. This trend may be true also for pregnant women; however, it was reported that pregnant women do not sufficient and correct knowledge on nutritional needs during pregnancy. Thus, we here attempted to determine the French situation of how French pregnant women take DS and its social-clinical significance using questionnaires, with special reference to vitamin D (VD) overtaking. Materials and Methods: A prospective mul-ti-centric study was performed in three maternities in Paris. One hundred-fifty questionnaires were administered to pregnant women by midwife. Results: Thirty-four patients were interviewed at the maternity ward of the Deaco-nesses, 61 at the Pitié-Salpêtrière and 55 at Armand Trousseau. During pregnancy, DS started mainly during the first trimester. Frequently, doctors in-itially prescribe them and women tended to continue to take them thereafter. Possible VD overdosage was observed. Conclusion: We here characterized French pregnant women in terms of DS during pregnancy and also, to our knowledge, for the first time emphasized the risk of vitamin D overdose during pregnancy in France. However, since the cumulative dose throughout the pregnancy was not determined here, definite conclusion of whether women re-ally take overdose of this supplement may not be made. Women of higher so-cio-professional society tended to consume more DS during pregnancy, and, thus, further monitoring may be needed especially to this fraction of


Introduction
In less than a decade, the consumption of food supplements has increased by almost 10% [1] [2]. Dietary supplements of pregnancy have been implicated in cases of hypercalcemia and neonatal hypothyroidism [3]. In pregnant women, as well as in the general population, energy intakes are recommended as: 55% of carbohydrates, 30% -35% of lipids and 10% -15% of proteins [4] [5]. Folic acid needs to be supplemented in the pre-conception period and until the end of the first trimester and in vitamin D at the 6th [5] [6]. No supplementation is needed for other vitamins [4] [7]. Knowledge needs to be emphasized in pregnant women about nutritional needs during pregnancy [8]. Taking medication during pregnancy can affect the fetus so pregnant women need to ask a health professional (midwife, doctor, pharmacist) before taking any pills or drugs [9] [10].  [11]. Nutrient deficiencies are rare in the general population except for vitamin D, where nearly 50% of the general populations are in deficit [12] [13].
The midwives, doctors and pharmacists should be aware of the risk of neonatal hypercalcemia after vitamin D supplementation during pregnancy [14]- [19].
National College of Gynecologists-Obstetricians (CNGOF) in 1997 and the National Agency for Sanitary Safety, Food, Environment, Work (ANSES) have recommended to monitor the DS in their real conditions of use and identifies adverse effects [20] [21]. They study the consumption of DS since 1998 and during the period 2006-2007 that shown 20% of adults have consumed (DS), twice in women (26.5%) than in men (12.6%). Consumers generally have a high level of education. At the national level, there is higher consumption in the South and East 22% against 18% in the North and West. The motivation for the purchase is mainly due to the prescription or advice from a health professional (58%), the place of purchase is mainly in pharmacy (54%) and rarely on the internet (1%). The main expectations of consumers are: "fight against fatigue" (33%), "solve a health problem" (21%), "stay healthy/fight against diseases" (17%). Among women, 6% of consumers say they consume it to meet the needs related to pregnancy. Finally, "balancing one's current diet" and "supplementing insufficient dietary intake" only account for 3% and 2% of motivations. The study shows that DS intake is influenced by the seasons, more important in winter than during the summer [1].
In June 2017, the INCA 3 study is published. It was conducted over the 2014-2015 period. Compared to the previous study, there is an increase in DS consumption (from 20% to 29%). The main place of purchase is still the pharmacy (45%) but the purchase by internet has grown strongly from 1% to 11%. Women, people with a high level of education and seasonality are consistent characteristics in DS consumption. We know that the main consumers are 18 to 44 years old [2].
The selling price of the DS is not regulated. His purchase therefore represents C. Lecoq, R. Serreau Open Journal of Obstetrics and Gynecology a certain budget. This is why the studies found on the subject are on populations from favored countries. A study conducted in the United States, Germany, Sweden and Finland shows that pregnancy DS consumption is associated in all countries with primiparity; on the other hand, women under 25 years old are less likely to be users. Some factors such as high level of education are found in the United States and Sweden but not in Finland and Germany. Tobacco use is associated with lower turnover in the Nordic countries, the United States and Germany, but this factor is not significant. In Finland, alcohol consumption during pregnancy and pathological first-trimester markers are related to an increase in DS consumption. This can be explained by a probable representation of the DS which differs according to the countries. In Finland, where consumption is increased in the event of a "pejorative" event for pregnancy (pathological serum markers, tobacco consumption) the DS would be represented as a remedy that could combat these derogatory events. In Sweden and Germany, overweight people (body mass index (BMI) > 25 kg/m 2 ) tend to use less DS. Finally, in the United States, where ethnicity studies are permitted, there is no link with pregnancy DS consumption [22].
A study conducted in Saudi Arabia shows that the use of pregnancy DS was very high (71.5%). Factors such as education level, household income, having 1 or 2 children are associated with DS consumption. BMI, professional activities do not affect consumption. 81.6% of respondents believe that supplementation is important and that neonatal outcomes are better and the study shows that there is no association. Consumers take a majority of DS following the advice of their doctor (65.7%) [23].
We have seen that many pregnancy DS consumption factors and DS more generally are common as the socioeconomic level. Some parameters were found to be consumption factors in some countries but not in others (tobacco). Now states that vitamin B9 intake should not be continued beyond the first trimester of pregnancy, which is in line with the recommendations in force. Regarding the vitamin D intake, the intake of 400 IU/day (10 μg/day) is in agreement with the Open Journal of Obstetrics and Gynecology recommendations. Iodine contributions must be found in the foods rich in iodine (milk and dairy products, crustaceans, eggs, enriched salt…) and that only the patients at high risk (geographical area deficiency, smoking…) are likely to have drug supplementation throughout the pregnancy. For iron, the AFSSA recalls that women must be supplemented in cases of iron deficiency anemia and systematic supplementation is not justified, and that the ideal to prevent anemia is to have a varied diet and balanced. Finally, the AFSSA says that these DS are not adapted to the nutritional needs of all pregnant women without distinction and adds that the information leaflets should draw attention to the risks of simulation induced by the DS and other enriched foods and the consumption of several products was discouraged [25].
In May 2017, ANSES described 84 cases reports about DS adverse reactions during pregnancy [3]. Eighteen were imputable. The adverse effects are mainly hypercalcemia and neonatal hypothyroidism. 2 cases were strongly imputable, eleven cases of possible accountability, and five cases of questionable accountability. ANSES confirmed that 5 cases of neonatal hypercalcemia and 2 cases of neonatal hypothyroidism where DS would be involved. In reported cases, DS were not the only source of vitamin D or iodine. ANSES informed pregnant women to be advised by a health professional on the use of DS during pregnancy.

Material & Method
The study focused on the population of patients giving birth in the 12th and 13th districts of Paris. Indeed, there are maternities of different types, public and private of collective interest.
The expected number of patients surveyed is at least 134 in total, to have significant results.
The distribution of the workforce varies according to the type of maternity.
That is 23% of patients interviewed in type 1, 40% in type 2 and 37% in type 3, as observed in the 2016 national perinatal survey [26]. All patients were asked about their living conditions and the course of their pregnancy, including the recommended supplements. Patients who consumed DS had additional questions about their use of these products, their use during this pregnancy.
The inclusion criteria were French language comprehension, she had to have given birth for at least 24 hours. The criteria for non-inclusion were that the patient was in the service of the diaper suites but had not given birth (patient being tripped); patients who cannot communicate orally in French (foreign patients who do not speak French, hearing-impaired patients who cannot communicate otherwise than by sign language).

Results
The study was conducted from November 16, 2018 to January 23, 2019. The total number of patients that could be included in the study was 150. The questionnaire was distributed in 3 maternity homes in the East of Paris: The Deaconesses (type 1), La Pitié-Salpêtrière (type 2), and Armand Trousseau (type 3).
Thirty-four patients were interviewed at the maternity ward of the Deaconesses, 61 at the Pitié-Salpêtrière and 55 at Armand Trousseau.
Pregnancy supplements were found to start mainly during the first trimester (p < 0.000001). Following a medical prescription (p = 0.0001) and the prescriber was usually a gynecologist-obstetrician (p = 0.000008) with a prescription (p < 0.0000001). Other prescribers were general practitioners, midwives and nutritionists.

Discussion
This is, to our knowledge, the first report on the risk of vitamin D overdose during pregnancy in France Regarding the risk of vitamin D overdose; this is the first study to address this risk.
As a first step, we will see if the surveyed population corresponds to the model Open Journal of Obstetrics and Gynecology of patients having a pregnancy in France, then we will see if the profile of the consumers of dietary supplements of pregnancy is different from that of the consumers of the general population. Finally, we will see if our study finds the same characteristics in consumers than in the National Perinatal Survey 2016 [26].
The proportion of patients of French origin is lower in this population than at national level (48% vs. 81.4%) and the same is true for French nationality (79.3% vs. 85.9%) ( Table 1) For the socio-professional categories, there is a very large share of senior managers and intellectual professions (32.7% vs. 13.3%). This is explained by the fact that Paris is an economic engine of France and that many large companies are headquartered in Paris or La Défense, the business district. Given the location of the study, as well as the specificity of the Paris region, it seems difficult to expand the results obtained at a national level ( Table 2).  Higher socio-professional category consumed more DS than general population. Prescription was the main motivation for taking DS [24].
This study showed that follow-up by a gynecologist-obstetrician was associated with an increase in DS intake, contrary to pregnancies followed by midwives in maternity where patients do not consume dietary supplements. It should be noted that in the literature no study has been done on the practice of prescriptions by midwives and in particular on the prescription of vitamins during pregnancy.
The literature is not unanimous on certain criteria that may influence the consumption of DS such as smoking, marital status. No smoking status before pregnancy and PACS were associated with an increase in DS intake.
In this study, a very small proportion (2/59) of patients were aware of a potential risk of overdose. Although the patients are not very aware of this risk, we will specifically study the case of folic acid (vitamin B9), vitamin D and iodine.  (Table 3). Finally, from a metabolic point of view, vitamin B9 is a water-soluble vitamin and in the case of high consumption, it is eliminated mainly in faeces and in a smaller quantity in the urine [19]. Thus the amounts of folic acid absorbed and circulating are quite low.
The recommended vitamin D intake during pregnancy was the single dose of a 100,000 IU ampoule at the beginning of the 7th month. Or daily intake of 400 IU from the beginning of pregnancy or 1000 IU/day at the beginning of the third quarter, but these types of patterns are more restrictive [20]. In non-consuming patients, almost three-quarters (70/91) of them had the recommended vitamin D supplementation.
As previously stated, overdosed patient with vitamin D was defined with pregnancy supplements for the duration of her pregnancy and having received a vitamin D ampoule dosed at 100,000 IU at the beginning of the 7th month or at another time of pregnancy. In this study, this proportion represents more than 3/4 of the patients. Thus, it was important to be vigilant to a possible over con-  This study was able to show that the profile of women who consume pregnancy supplements was similar to the general population of these consumers.
The proportion of these people is around 40% in the study population. DS consumption was made mainly during the first trimester and part of this population continues throughout the pregnancy. These food supplements was overwhelmingly prescribed by gynecologists-obstetricians and purchased in pharmacies.
A relatively small number of patients were aware of the risk of overdose [28].
Recommendations need to be updated with new vegan and vegeterian habits during pregnancy.

Conclusion
This is, to our knowledge, the first report on the risk of vitamin D overdose during pregnancy in France. However, since the cumulative dose throughout the pregnancy was not determined here, definite conclusion of whether women really take overdose of this supplement may not be made. Women of higher socio-professional society tended to consume more DS during pregnancy, and thus further monitoring may be needed especially to this fraction of women.