Efficacy of weekly vitamin D supplementation in pregnancy: maternal and neonatal outcomes in a Greek cohort

Efficacy of weekly vitamin D supplementation in pregnancy: maternal and neonatal outcomes in a Greek cohort | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 10 December 2025 V1 Latest version Share on Efficacy of weekly vitamin D supplementation in pregnancy: maternal and neonatal outcomes in a Greek cohort Authors : Tsiara E , Chandakas S , Charos D 0000-0002-5855-6437 [email protected] , and Vivilaki V Authors Info & Affiliations https://doi.org/10.22541/au.176540412.21751427/v1 229 views 143 downloads Contents Abstract 1. Introduction 2. Material & Methods Pretest of the protocol Subjects not participatingin the study Handling of missing Data Relation of newborn’s Vitamin D across gender(0 : girls , 1:boys) Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Vitamin D deficiency during pregnancy remains a common phenomenon, with potential consequences for the mother and the newborn. Objective: The aim of the study was to investigate the efficacy of different dosages of vitamin D supplementation in pregnant women in Greece and their effect on maternal and neonatal vitamin D levels. Methods: In a randomized, single-blind study of 192 pregnant women, three different doses of vitamin D3 (8400, 12800, 16800 IU/week) were administered from the 12th week of gestation until delivery. 25(OH)D levels were recorded in the 3rd month of gestation, at delivery and on the 3rd day of life of the newborns. Results: The majority of pregnant women were vitamin D deficient in the first trimester (91%), while at the end of pregnancy the percentage was 80%. In contrast, only 15% of newborns had low levels. The administration of 16800 IU/week from the 3rd month was associated with the complete absence of newborns with deficiency (<15 ng/ml). Conclusion: Supplemental vitamin D during pregnancy is safe and effective for the prevention of deficiency in mothers and newborns. Doses ≥16800 IU/week seem to offer the best protection. Manuscript Title: Efficacy of weekly vitamin D supplementation in pregnancy: maternal and neonatal outcomes in a Greek cohort Tsiara Eleni 1 , Chandakas Stefanos 2 , Charos Dimitrios 3 , Vivilaki Victoria 3 1. Midwife, Mitera Hospital, Athens, Greece, [email protected] 2. Obstetrician – Gynecologist, Mitera Hospital, Athens, Greece, [email protected] 3. Department of Midwifery, University of West Attica, Athens, Greece, [email protected] Corresponding Author: Charos Dimitrios, PhD, 171 Alexandras Ave., “AgiosSavvas” Oncology Hospital, Athens E-mail address: [email protected] https://orcid.org/0000-0002-5855-6437 Funding Statement Not applicable Conflict of Interest Disclosure : The authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the Scientific Council of the Mitera Maternity Hospital (Approval Number: 93/27.07.2021) Patient Consent Statement: Informed consent was obtained from all subjects involved in the study. Data Availability Statement: The data are not publicly available due to confidentiality restrictions. Acknowledgements Not applicable Authors’ contributions All authors contributed to the design, data analysis and wrote the manuscript text. All authors approved the final manuscript. Abstract Background: Vitamin D deficiency during pregnancy remains a common phenomenon, with potential consequences for the mother and the newborn. Objective: The aim of the study was to investigate the efficacy of different dosages of vitamin D supplementation in pregnant women in Greece and their effect on maternal and neonatal vitamin D levels. Methods: In a randomized, single-blind study of 192 pregnant women, three different doses of vitamin D3 (8400, 12800, 16800 IU/week) were administered from the 12th week of gestation until delivery. 25(OH)D levels were recorded in the 3rd month of gestation, at delivery and on the 3rd day of life of the newborns. Results: The majority of pregnant women were vitamin D deficient in the first trimester (91%), while at the end of pregnancy the percentage was 80%. In contrast, only 15% of newborns had low levels. The administration of 16800 IU/week from the 3rd month was associated with the complete absence of newborns with deficiency (<15 ng/ml). Conclusion: Supplemental vitamin D during pregnancy is safe and effective for the prevention of deficiency in mothers and newborns. Doses ≥16800 IU/week seem to offer the best protection. Keywords: pregnancy, vitamin D supplementation, deficiency, neonatal outcome 1. Introduction The implication of vitamin D in multiple biological routes such as immunomodulation, cellular proliferation and differentiation led to extensive research regarding the determination of the optimal serum levels and the clinical consequences of low or high blood concentrations. Serum vitamin D levels are mainly expressed by 25(OH)D that determines the deficient, insufficient or sufficient vitamin D status. Based on the fact that vitamin D is found naturally only in limited food resources, such as egg yolk, salmon, and liver, maternal 25(OH)D levels depend mostly on the amount of sunlight exposure and on vitamin D supplementation. 1 During the last years, a special attention has been paid to gestational hypovitaminosis D in relation to pregnancy outcomes. Vitamin D has an increasingly recognized repertoire of nonclassical actions, such as promoting insulin action and secretion, immune modulation and lung development. 2,3 It therefore has the potential to influence many factors in the developing fetus. Maternal vitamin D during pregnancy is of vital importance as 25(OH)D readily passes through the hemochorial placenta and determines fetal and neonatal vitamin D status. There is little information on vitamin D intake in pregnancy and lactation and few studies on clinical outcomes. Some have suggested that the requirement for vitamin D in these women may be up to 6000 iu/day and the ideal vitamin D regimen to prevent and treat vitamin D insufficiency in utero is unknown. 4,5 Pre-eclampsia and neonatal hypocalcemia are the most prevalent complications of maternal hypocalcemia and are clearly linked to substantial morbidity. A statistical association of glucose intolerance and hypovitaminosis D has been established. Maternal vitamin D is crucial for fetal bone development. Fetal lung development and neonatal immune conditions such as asthma may relate in part to maternal vitamin D levels. 6,7 In conclusion, hypovitaminosis D may be associated with hypertension, pre-eclampsia and increased caesarean section rates. There are no multicenter randomized control trials showing that vitamin D supplementation alters these putative risks. 8 There are a few published studies on hypovitaminosis D in pregnant women and their newborns in Greece, but so far there is no unanimously accepted therapeutic protocol for this serious condition which carries a significant risk for fetal and newborn morbidity. 9-11 The aim of this study is to determine the necessary vitamin D supplementation in a cohort of Greek pregnant women. The main goals of my research are: a) to record the demographic data and the general history of pregnant women who are involved in the study, b) to determine the efficacy and safety of different therapeutic protocols for vitamin D supplementation during pregnancy and c) to establish any comorbidity in the mother or fetus that is related to vitamin D insufficiency or deficiency. 2. Material & Methods Background The central task of the research is to examine some of the effects of Vitamin D supplementation during pregnancy.Can medication on mother with Vitamin D supplement have positive effect on newborn’s Vitamin D?Are there any external factors that affect Vitamin D in infants?In order to answer the above questions, a protocol with Vitamin D supplementation was introduced. Hospital where the protocol was tested In order to examine the effect of different dose of Vitamin D on newborn, we observe the behavior of pregnant women served in a major Maternity & Gynecological Hospital (https://www.mitera.gr/en/maieytiki-gynaikologiki-kliniki/) for a duration of 28 months (January 2019 till April 2021). Once a pregnant woman’srecord is filed on the secretary’s office, a random number from a digital clock classify them, totally random, into one out of three groups. The group member A, B or C is logged on the register of the survey. This way our sample of pregnant women were blindly categorized into three distinct groups, almost of identical size. MiteraHospitalhas a robust GDPR protocol.All participant, but one, consent to participate in the administration of the medicinal product (https://www.mitera.gr/en/personal-data-protection-policy/). The administration of Vitamin D is on the standard treatment during pregnancy and covered by the confidentiality agreement each pregnant had signed before admitted in the hospital. No personal or sensible data were entered into the survey register. Factors considered to record on the survey The following measures were considered as exploratory factors for the observed value of infantile Vitamin D. Mother Profile • Mother’s blood group;in case Vitamin D is absorbed differently depending on mothers’ blood group • Number of previous labors. • Mother’s age Labor Conditions • Week of labor • Effect of Anticoagulant Treatment • Effect of thyroid disease • Twins Newborn’s Profile Gender Infant’s weight; more as an important exogenous variable, since it is interesting to examine a causative relation between Vitamin D and newborn’s weight. Pretest of the protocol Relevant data from UK show that there is evidence for applying a similar protocol in Greece, without any negative effects.From the early 2010’s occasionally usage of Vitamin D on mothers with deficient values, less than 15 ng/ml, in MITERA hospitaldemonstrated encouraging measurements on children with no side effects. This event encouraged us to formalize and systemically apply the treatment in this current survey. Experimental Design All pregnant women of one Consultant’s clinic in a main maternity hospital in Athens were included in the study. The clinic is well established in Athens for several years and it includeswomenof different age from many parts of the country. Because of its reputation, women expect to have high quality of service provision and therefore the administration of a vitamin-D is regarded as good clinical practice and was widely accepted and welcomed. Greek populationhashigh exposure to sunannually. However, several studies indicate that a significant percentage of the population has vitamin-D insufficiency of deficiency. 9-11 A single blind randomized design was used in order to define three groups Table 1.Study design Untitled Document Generated on Wed Dec 10 18:06:19 2025 by LaTeXML Table 2. Medical treatment of subject belonging on each of the three groups Mother Vitamin D Mother Vitamin D Newborn Vitamin D Group A Random numbers 0.19 Not measured Standard treatment, i.e. 8400 iu weekly Measured Measured Group B Random numbers 20.39 Measured 12800 iu weekly Measured Measured Group C Random numbers 40.59 Measured 16800 iu weekly Measured Measured Comments Script for group A: “You will take vitamin D that is proven to be good for the baby” Script for group B: “You will take vitamin D that is proven to be good for the baby” Script for group C: “You will take vitamin D that is proven to be good for the baby” Pregnant Vitamin on 3 rd month is not measured on GROUP A as this was the standard operational procedure in hospital Pregnant Vitamin on 3 rd month is prescribed on GROUP B and C in order mother to have the planned quantity. Absorption is defined as “Mother’s Vitamin D level in 9 th month” minus “Mother’s Vitamin D level in 3 rd month of pregnancy” Sample Size determination In order to determine the sample size, alpha and beta parameters will be used according to the established statistical analysis. Alpha = 0.05 : The probability of a type-I error – finding a difference when a difference does not exist. Most medical literature uses an alpha cut-off of 5% (0.05) – indicating a 5% chance that a significant difference is actually due to chance and is not a true difference. Beta = 0.20 : The probability of a type-II error – not detecting a difference when one actually exists, indicating a 20% chance that a significant difference is missed. Beta is directly related to study power, Power = 1 – β = 80% From the pilot measurements, the standard deviation of vitamin D in children is around 10.From a discussion with the medical team, it was considered to be very interesting if the medication group could have 5 more units of vitamin D than the control group.Adding these numbers, an initial sample of 60 women is estimated to be adequate in each group (Z value (alpha parameter)= 1,95, Z value (beta parameter) =0,84). This is considered a sample size where we could detect a statistical difference of 5 units or more between groups. 12 The sample Pregnant women were split randomly (in a blind way, according to a random number determined by the second of a clock at the time of the file in the secretary’s office into three different groups) Table 3. The sample of the study 1 20 Group A 5/1/2019 12/1/2019 2 51 Group B 8/1/2019 21/1/2019 3 48 Group C 12/1/2019 14/1/2019 … … … 40 … 45 Group B 12/10/2020 DENIED * … … … 192 15 Group A 20/3/2021 23/3/2021 193 98 Group C 20/3/2021 23/3/2021 * Case 40 was the only one excluded as she refused participating in the study Figure 1. Flowchart of the sampling Subjects not participatingin the study Since there was only one woman who did not participate in the study, it was feasible to proceedto a second phase. The data (Vitamin-D levels and baby’s weight) were communicated verbally topregnantwomenandwere in the anticipated range of group A (control group). Thus, the excluded case was not involved in the validity of the findings. Response rate was almost 100%, as a result of the script convincing. The role of Vitamins in human health is widely accepted in Greece with culture in farming sector and traditional Mediterranean diet. Vitamin D is a nutrition supplement without significant side effects. The sampling distribution of group is as follows: Group A= 65, Group B= 60, Group= C=67. In group C, two women carried twins; there were 69 newborns in this group, adding to a total of 194 newborns. Measurement and bias procedures Blind categorization of women in three groups eliminates the effect of any subconscious factor.Validity deals with the levels of Vitamin D measured. Since this is done in a qualified lab, it is taken as granted. Two different staff members recorded each woman’sdata collected in the survey. In case of discrepancy between the two measurements a third measurement was repeated in order validity to be assured. The distribution of Vitamin D either for newborn or for mother is almost normal,letting us to conclude that the measure of central tendency is a valid, consistent proxy of the underlying real population measure. If the distribution was not normal, as observed, but uniform, we would then have a random, unreliable, measurement process. Clinical sensitivity was tested internally with the scientific staff of the clinic in order to examine the extent. Most important issues were measured.The process is clearly understood by mothers and by the technical staff. Handling of missing Data In very few cases, 4 in total, there were missing measurements of newborn’s Vitamin D levels, since for operational reasons, it was impossible to get a valid observed value. Most women were willing to participate as medication with Vitamin D is a standard medical procedure.All statistical procedures used have the option to take into account of the missing values. Demographic Data The following table (4) demonstrates the distribution of the sample used in the survey Table 4. Demographic characteristics Mother’s Age (years) 33,7 4,9 Newborn’s weight (grammars) 3005,9 336,7 0 No 181 1 Yes 11 Total 192 Number of Labors N 1st 119 2nd 61 3rd 11 4th 1 Total 192 Blood type N Α(-) 8 Α(+) 66 ΑΒ(+) 7 Β(-) 1 Β(+) 23 Ο(-) 14 Ο(+) 73 Total 192 Extra Medication N 0 no medicine 149 1 Medicines included in the factors examined 43 Total 192 Gender of newborn N Girl 89 Boy 105 Total 194 Main research issues and statistical hypotheses Do Mothers and Infants have high or low values of Vitamin D? Hypothesis 1: There are many mothers and children with lowlevel of Vitamin D Statistical method used to test the hypothesis: Frequency tables of percentage of vitamin D on mother and infant What is the degree of Relation of mother and infant Vitamin D level? Hypothesis 2: There is relation of mother’s and child’s Vitamin D level Statistical method used to test the hypothesis: Correlation analysis Is there a significant improvement on vitamin D levels of group C and B over group A? Hypothesis 3a: Infants in Group B have more vitamin D than these in group A Hypothesis 3b: Infants in Group C have more vitamin D than these in group A Hypothesis 3C: Infants in Group C have more vitamin D than these in group B Statistical method used to test the hypothesis: T-test of difference of mean will reveal if the extra amount of vitamin D is worth being administered In accordance with every observational study, cross tabulation of grouping variable with other factors will determine if there are any interesting differences. Are there any factors considered in the study that can affect Vitamin-D levels? Effect of Anticoagulant Treatment / Effect of thyroid disease / Insulin A multiple regression analysis on infantile vitamin D will determine the most important factors that simultaneously affect positively or negatively the infant. 3. RESULTS - Statistical Analysis Issue 1. Increase of Vitamin D level In total, the increase of Vitamin D levels from the initial measurement till the moment of birth is highly significant (sig. .000) The increase of the measured value of Vitamin D on women at the time of labor is almost double in group C (M=36.4) than in group B (M=57.3) The variability of the increase is relatively high since the personal characteristics of each pregnant woman has a prominent role. This fact does not allow us to conclude that the increase of Vitamin D in group C is higher than of B {ANOVA F value = 2.210, Sig. = 0.140 (>0.05)} Issue 2. Infantile Weight and Vitamin D level between groups Birth weight (M): Group A = 2970.38, Group = 3046.33, Group =3004.13, Total= 3005.88. Mean value of birth weight is the same across all groups (F stat = .793 p.value Sig.= .454). (Bonferroni method) Group C differs from both A and B, while B and A are quite undistinguishable Issue3. Relation of mother’s and infant’s Vitamin D level The correlation of mother and infant Vitamin D level at the same moment is high and statistically significant(Correlation=0,755, p=0,000). Since the two human beings are related to the same environment, one can detect that there is one-way relation; an increase on mother’svitamin D levelwill lead to a significant increase on newborn’svitamin D level. Figure 2: The correlation of mother and infant Vitamin D level Issue4. Effect of Anticoagulation Treatment Absorption rate [(Final – Initial ) / Initial] is greater in group C than in group B when anticoagulantsareused.Additionally, newborn’s vitamin D level is slightly higher when anticoagulantsareadministered in pregnancy (Absorption= F-value (3.337) and p=0.069) and (Newborn vitamin D = F-value (2.039) and p=0.0155). Thus,anticoagulation treatment seems to affect mother’s absorption mechanism leading tosignificantlyhigherVitamin D levels in newborns. Issue5. Effect of thyroid disease There was no control group/mechanism for the effect of thyroid disease during the course of the pregnancy.The majority of samples requiring treatment for thyroid disease were observed on group C;as a consequence, it is inappropriate to make any statistical comparison. Only from observational point of view, F statistics value and significance p-value were recorded. Issue6. Levels of Vitamin D at the moment of labor There is an effect of grouping variable on the vitamin levels at the time of birth (Mother: F-value= 18.902, p 0.000) and (New born: F-value= 24.874, p 0.000) Issue7. Mother’s Vitamin D level<30ng/ml on first visit 91% of all groups had vitamin D level <30ng/ml on first visit and no group difference Issue8.Mother’s Vitamin D<20ng/ml on the first visit More than 50% of mothers had Vitamin D level <20ng/ml on their first visit Group B and C differ, but not significantly on the initial value Issue9. Newborn’sVitamin<15ng/ml Similarly, 6% ofNewborn’s level had<15ng/ml, on group C none Issue10. Newborn’s Vitamin D<20ng/ml Similarly, 14% ofNewborn’s level had20ng/ml Similarly, 85% ofNewborn’s level had >20ng/ml, on group C all Issue12. Mother’sVitamin D <30ng/ml in labor Similarly, 85% ofMother’s level had <30ng/ml, on group C less (60%) Issue13. Mother’s Vitamin D <20ng/ml in labor Similarly, 35% of Mother’s level had 30ng/ml in labor Similarly, 20% of Mother’s level had >30ng/ml, on group C 2/5 (40%) Overall, due to the inherent correlation of mother’s and newborn’ vitamin D levels, all the aforementioned mentioned statistical results are summarized in the following table. Issue15. More significant predictors of infant’sVit-D level A stepwise multiple regression analysis was run in order to find which factor plays the most prominent role in newborn’s Vitamin D level. The following table 3.27 displays the Regression coefficient in predicting newborn’s Vitamin D level. The goodness of fit test (R-Square) is high (0.566). There is high correlation between newborn’s vitamin D level and exploratory variables likethemother’sgestationalage and the number of labors that she had lifelong(two related measures). • Women giving birth to infants at higher gestational age, result in infants with higher levels of vitamin D. • The first labor newbornsshowed higher levels vitamin D. • All other factors have arelatively smaller effect and significance. Isue 16. Premature delivery and treatment with Vit-D supplements Due to random sampling frame, on group B, only one premature birth was recorded. This fact it is making impossible to draw any meaningful conclusions. Additionally, in group C there is a very small number of prematurechildbirths. T-value (Equal variances not assumed) = 0,15 and Sig. (2-tailed) = 0,89.Thus, there is no higher level of Vitamin Din premature newbornsin comparison with normal births STATISTICAL ANALYSIS OF THE EFFECT OF VARIOUS FACTORS ON NEWBORN’S VITAMIN D LEVEL Relation of newborn’s Vitamin D across gender(0 : girls, 1:boys) There is no evidence that boys and girls behave differently within the three treatment groups. Neither gender nor gender by group interaction are significant (sig.677). Relation of newborn’s Vitamin D level and type of labor There is no evidence that C-section operation affects newborn’s Vitamin D level on all three treatment groups. Neither gender nor gender by group interaction are significant (sig.751). There is a hint of interaction effect, since group C with caesarean operation has observed less Vitamin D levels than anticipated. Relation of newborn’s Vit-D levels with thyroid disease Whenevermothers suffer from thyroid disease, newborns in groups B and C havelower levels of vitamin D. Relation of Vitamin D treatment andanticoagulationtreatment There is no significant relation despite the fact thatanticoagulation therapy is related with higher level of Vitamin D in newborns (sig .155). In case of administrating anticoagulants on control group there is a tendency for higher levels of Vitamin D in infants compared to vitamin D levels of infants belongingto group B. Relation of newborn’s Vitamin D level with Insulin dependent mother Only three mothersrequired administration of insulin, and they were all assigned on group C.Therefore, any statistical analysis is invalid. Relation of newborn’s Vitamin D level with premature labor There is no significant effect of vitamin D administration on premature labor (sig .253). In groups A& C with a minimum sample size, the hypothesis that premature labor (“premature”) has different levels of vitamin D in newborns compared to normal population is rejected. Relation of newborn’s Vitamin D level with first labor Although there is not a significant effect of the first labor on newborn’s Vitamin D level, all groups seem to have slightly lowerlevel of newborn’s vitamin D in the case of an experienced mother with more than one labor as compared to pregnant women on their first labor (sig .274).An explanation of this, may be the confounding effect of age; inevitably the first labor is at smaller age with a younger body. Relation of Vitamin D supplementation with newborn’s vitamin D levels The administration of vitamin D supplementation has an interesting, almost significant, effect on group Asubjects. The mean value on newborns’ Vitamin D level is much higher in group C compared to group A. Future work can be done to quantifytheideal medical treatment during pregnancy. Relation of newborn’svitamin D level with infant’s weight In all three groups there is no linear correlationbetweennewborn’sVitamin D levels and its weight. Relation of newborn’s Vitamin D level with initial mother’s Vitamin D level before treatment Clearly, the observed Vitamin D of the infant is unrelated with his/her initial mother’s measurement. Relation of newborn’s Vitamin D level with its mother’s Vitamin D level at the same time The tie in the measurements of Vitamin D levels for the mother and the newborn at the time of labor shows a correlation of almost 0.8;thisissimilar to as the two bodies were the same. The regression lines that link mother’s vitamin D level to her newbornare almost identical in the three groups, with the difference of the constant term indicating the starting level. Figure 3:Relation of newborn’s Vitamin D level with its mother’s Vitamin D level Clearly, the relation is almost identical in all groups, and the administration dose of vit-D supplementation has a parallel effect, which is greater and more efficient in group C. Vit-D supplementation dosage and Vit-D levels on mother & child at the moment of birth and their difference On group C, there is a propotional higher increase in mother and newborn’s vitamin D levels Figure 4: The mean of the groups Relation of newborn’s Vitamin Dlevel with mother’s absorption ability The rate that mother absorbs Vitamin D is the key component to newborn’s vitamin D since it is highly correlated (Correlation = 0.591 &p-value a mother absorbs more vitamin D then her child will have proportionally high level of vitamin D. Relation of newborn’s Vitamin Dlevel with increase of mother’s Vitamin D level from 3 rd month of gestationtilldelivery In accordance with the previous findings, the higher the percentage of increase of Vitamin D levels in mother’s measurements on 9 th month versus the 3 rd month of pregnancy, the higher the vitamin D levels on a newborn. If a pregnant womanhas Vitamin D insufficiency/deficiency, and following Vitamin D supplementation during pregnancy increased her Vitamin D levels, then the child will benefit from this medication. Table 5. The table that follows summarizes the main statistical findings → There are many newborns with low level /Less than benchmark 15ng/ml A lot of newborn / mother have vit-D deficiency There are many mothers with low levels /Less than benchmark 20ng/ml and few scarcity Vitamin D of Mother first visit under 30ng/ml All (91%), no group differences Vitamin D of mother on the first visit under 20ng/ml >half (58%) of cases no group differences Vitamin D of newborn under 15ng/ml 1/20 (6%), on group C none Vitamin D of newborn under 20ng/ml 1/7 (14%) on group C none Vitamin D of newborn over 20ng/ml 6/7 (85%), on group C all Vitamin D of mother on labor under 30ng/ml 4/5 (80%) on group C less (3/5 60%) Vitamin D of mother on labor under 20ng/ml 1/3 (35%) on group C 1/5 (17%) Vitamin D of mother on labor over 30ng/ml 1/5 (20%) on group C 2/5 (40%) → Increase of Vitamin D On group C more than on group B Group B differ from group A No difference Group C differ from group A Yes, statistically different Group C differ from group B Yes, statistically different → Relation of mother and newbornVitamin D measurement Strong Positive, significant Increase in the dose of medication in mother will increase child Vitamin D Yes, Very significant More significant predictors of newborn Vitamin D Amount of Vitamin on mother and absorbed quantity, Age of mother → Relation of newborn’sVitamin D across gender Not significant Relation of newborn’s Vitamin D and caesarean operation Not significant Group C with caesarean operation seem to have lower Vitamin D values than anticipated Relation of Vitamin D with thyroid disease Not significant When there is thyroid disease, medication group B and C have lower values of vitamin D Relation of Vitamin D treatment with Anticoagulation Treatment Not significant In case of Anticoagulant Treatment on control group there is a tendency for more Vitamin D, as if infants’ mother belongs to group B Relation of Vitamin D with Insulin Rare Relation of Vitamin D treatment with premature labor : Not significant Not effect of Vitamin D dose on premature labor Same value of Vitamin D on normal infants and on early childbirth infants Relation of Vitamin D treatment with first labor Not significant First labor has slightly bigger values of Vitamin D Possible age confounding effect Relation of Vitamin D treatment with pharmacy treatment Slightly significant (on 90% confidence) On group A medical treatment has more Vitamin D than pregnant without Relation of newborn’s Vitamin D with infantile weight Unrelated Observed newborn’s Vitamin D level and initial mother’s measurement Unrelated Relation of newborn’s Vitamin D with its mother Vitamin D at the same time Strongly related The tie on the measurements of Vitamin D on mother and newborn at the moment of labor is as the two bodies were the same. There is a propotional increase in mother’s and newborn’s vitamin D level relative to the treatment dose P<0.000 Relation of newborn’s Vitamin Dwith absorption from mother Strongly related P<0.000 Relation of newborn’s Vitamin Dwith increase of mother’s Vitamin D from 3 rd month to labour Strongly related If a mother requires Vitamin D supplementation, and during pregnancy increased her vit-D levels, then the newborn will benefit from this medication P<0.000 • Group C seems to differ significantly from the other two groups of the study demonstrating higher effect on the measured Vitamin D levels in newborns. • In many categories of statistical analysis, Group B seems to have similar results with Group A. • Vitamin D absorption is an important factor and is clearly related to women’s clinical features. • First labor from younger women seem to requirehigher dose of Vitamin D supplementation. • Premature birth is not associated with higher values of vitamin D. 4. Discussion Since a strong relationship between 25(OH)D concentrations in mother-newborn pair has been established, inadequate maternal 25(OH)D levels during gestation would have a significant impact on fetal and neonatal vitamin D status. It has been proven that deficient vitamin D status during pregnancy will result in a deficient fetus, whilevitamin D stores will be diminished approximately at the 8thweek of life. Gestational vitamin D insufficiency has now been linked to a range of disorders, such as osteoporotic bone disease, altered brain development and adult mental health, autoimmune disease, asthma and food allergies. In some cases, profound maternal vitamin D deficiency presents as neonatal rickets. Furthermore, recent findings suggested that the increased prevalence of vitamin D deficiency/insufficiency during pregnancy would have consequences for the fetus and offspring bone health in later life. 13-19 Currently, a level of at least 30 ng/ml 25(OH)D is considered as sufficient, values between 29 and 20 ng/ml as insufficiency and levels less than 20 ng/ml as deficiency in adults. In newborns a value below 20 ng/ml is considered as insufficiency while levels below 15 ng/ml as deficiency. 20 The aim of this study is to measurevitaminD3levels(OH-VitD3) in pregnant women and their infants and also to determine external factors that can affect vitamin D absorption. The primary question that has to be answered is whether vitamin D supplementation therapy during pregnancy has any effect on newborns’vitamin D levels.The vitamin Dsupplementationwhich was administered was different in each group and covered by the confidentiality agreement that every pregnant woman signed before entering the hospital. No personal or sensible data were incorporated on the register. During this study we had to determine the efficacy and safety of different treatment protocols for vitamin D supplementation in pregnancy and to ascertain any comorbidity in the mother or fetus that is linked to vitamin D insufficiency or deficiency.Data from UK showed that there is evidence for applying a similar protocol in Greecewithout any negative effects. 8 Our findings are consistent with randomized controlled studies from big tertiary referral units in the Western world. 20-22 The main findings of our study are the following: 1. Newborns absorb Vitamin D from their mother(P<0.000). 2,3 2. If a mother on the 3 rd gestational month has vitamin D value less than 30ng/ml, medication with 12800 iu weekly shall have proportional effect on infant’svitamin D measurement. 3. Vitamin D supplementation with a dose of 16800 iu weekly from the 3 rd month of pregnancy seems to have a significant effect on fetal vitamin D levels, resulting probably to no infant with vitamin D deficiency (less than 15ng/ml). 4. Midwives and doctors can monitor and adjust the medication, since there is not a constant absorption rate in all mothers, considered other medication mother is in need for. Subject variability of mothers is important for vitamin D absorption. 5. In our survey there in no indication of adverse effect of Vitamin D on newborn’s weight or premature labor. 5,6,17 6. Group C seems to be distinguished from the other two groups of the study, with higher effect on the measured Vitamin D level of newborns. In many statistical categories, Group B seems to be indifferent from Group A. 7. Premature labor / birth is not associated with highermaternallevels of vitamin D. 17 In conclusion, vitamin D supplementation during pregnancy is safe and provides an efficient therapeutic modality to prevent neonatal vitamin D deficiency/insufficiency. There is still necessity for further randomized controlled studies in order to determine a universally accepted treatment protocol for vitamin D supplementation in gravidity. REFERENCES 1. De-Regil LM, Palacios C, AnsaryA et al. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev 2012;2:CD008873. 2. Hollis BW. Vitamin D requirement during pregnancy and lactation. J Bone Miner Res 2007;22Suppl 2:V39–44. 3. Yu CK, Sykes L, Sethi M, Teoh TG, Robinson S. Vitamin D deficiency and supplementation during pregnancy. ClinEndocrinol (Oxf) 2009;70:685–90. 4. Salle, BL, Delvin EE, Lapillonne A, Bishop NJ, Glorieux FH. Perinatal metabolism of vitamin D. Am. J. Clin. Nutr, 2000 ; 71 :1317S-24S. 5. ViethStreym S, Kristine Moller U, Rejnmark L et al. Maternal and infant vitamin D status during the first 9 months of infant life-a cohort study. Eur J ClinNutr 2013 ; 67 :1022. 6. Mahon P, Harvey N, Crozier S et al. Low maternal vitamin D status and fetal bone development: cohort study. J Bone Miner Res 2010;25:14–9. 7. Morley R, Carlin JB, Pasco JA, Wark JD. Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J ClinEndocrinolMetab 2006;91:906–12. 8. RCOG. Vitamin D in Pregnancy. Scientific Impact Paper June 2014;43:1-11. 9. Sideri V, Antonakos G, Fretzayas a et al. Hypovitaminosis D in healthy pregnant women and their newborns in Greece. EndocrMetab Immune Disord Drug Targets 2019;19:159-65. 10. Anatoliotaki M, Tsilimigaki A, Tsekoura T et al. Congenital rickets due to maternal vitamin D deficiency in a sunny island of Greece. ActaPaediatr 2003 ; 92 : 389- 91. 11. Nicolaidou P, Hatzistamatiou Z, Papadopoulou A et al. Low vitamin D status in mother-newborn pairs in Greece. Calcif Tissue Int 2006;78:337-42. 12. Karlsson J, Engebretsen L, Dainty K. ISAKOS scientific committee Considerations on sample size and power calculations in randomized clinical trials. Arthroscopy2003;19:997–9. 13. Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM. Associationbetween maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes:systematic review and meta-analysis of observational studies. BMJ 2013;346:f1169. 14. Gulseth HL, Gjelstad IM, Tierney ACet al. Serum vitamin D concentration does not predict insulin action or secretion in European subjects with the metabolic syndrome. Diabetes Care 2010;33:923–5. 15. Clifton-Bligh RJ, McElduff P, McElduff A. Maternal vitamin D deficiency, ethnicity and gestational diabetes. Diabet Med 2008;25:678–84. 16. Makgoba M, Nelson SM, Savvidou M, Messow CM, Nicolaides K, Sattar N. First-trimester circulating 25-hydroxyvitamin D levels and development of gestational diabetes mellitus. Diabetes Care 2011;34:1091–3. 17. Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF. Association between vitamin D deficiency and primary cesarean section. J ClinEndocrinolMetab 2009;94:940–5. 18. Kovacs CS. Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcome from human and animal studies. Am J ClinNutr 2008;88:520S–528S. 19. Wei SQ, Qi HP, Luo ZC, Fraser WD. Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2013;26:889–99. 20. Kiely M, Hemmingway A, O’Callaghan KM. Vitamin D in pregnancy: Current perspectives and future directions. TherAdvMusculoskelet Dis 2017 ; 9 :145-54. 21. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 2011;26:2341–57. 22. Steer PJ. Is vitamin D supplementation in pregnancy advisable? Lancet 2013;381:2143–5. Information & Authors Information Version history V1 Version 1 10 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords antenatal care diagnostic studies endocrinology general obstetrics termination of pregnancy: medical Authors Affiliations Tsiara E Maieftirio Mitera View all articles by this author Chandakas S Maieftirio Mitera View all articles by this author Charos D 0000-0002-5855-6437 [email protected] Panepistemio Dytikes Attikes View all articles by this author Vivilaki V Panepistemio Dytikes Attikes View all articles by this author Metrics & Citations Metrics Article Usage 229 views 143 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Tsiara E, Chandakas S, Charos D, et al. Efficacy of weekly vitamin D supplementation in pregnancy: maternal and neonatal outcomes in a Greek cohort. Authorea . 10 December 2025. 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