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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 3  |  Issue : 3  |  Page : 67-72

Vitamin D levels and antenatal complications in pregnant Nigerian Igbo women


1 Department of Obstetrics and Gynaecology, Nnamdi Azikiwe Teaching Hospital (NAUTH), Nnewi; Centre for Health and Allied Legal and Demographical Development Research and Training, Nnamdi Azikiwe University (NAU), Awka, Nigeria
2 Department of Chemical Pathology, NAU, Nnewi, Nigeria
3 Department of Community Medicine, NAUTH, Nnewi, Nigeria
4 Department of Obstetrics and Gynaecology, Nnamdi Azikiwe Teaching Hospital (NAUTH), Nnewi, Nigeria
5 Department of Obstetrics and Gynaecology, Nnamdi Azikiwe Teaching Hospital (NAUTH); Department of Human Biochemistry, NAU, Nnewi, Nigeria
6 Centre for Health and Allied Legal and Demographical Development Research and Training, Nnamdi Azikiwe University (NAU), Awka; Department of Human Biochemistry, NAU, Nnewi, Nigeria

Date of Submission19-May-2021
Date of Decision15-Jun-2021
Date of Acceptance06-Jul-2021
Date of Web Publication03-Nov-2022

Correspondence Address:
Joseph Ifeanyi Brian-D Adinma
Department of Obstetrics and Gynecology, Nnamdi Azikiwe University and Teaching Hospital, Nnewi; Centre for Health and Allied Legal and Demographical Development Research and Training, Nnamdi Azikiwe University, Awka
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jascp.jascp_12_21

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  Abstract 


Background: Serum levels of Vitamin D have been linked to some complications in pregnancy such as diabetes mellitus and premature rupture of membranes (PROM). While some studies suggest inverse relationship between serum Vitamin D levels and poor pregnancy outcomes, others report a J-shaped (curvilinear) or U-shaped relationship. Objective: The objective of the study is to determine the relationship between serum Vitamin D and some selected pregnancy complications among pregnant Nigerian Igbo women. Subjects and Methods: A prospective, cross-sectional study conducted on 256 consecutive consenting antenatal women in Anambra state, Southeastern Nigeria. Maternal blood obtained was assayed for 25 hydroxyvitamin D3 using high-pressure liquid chromatography. A pro forma was used to elicit information with respect to the biosocial characteristics of the subjects. Data obtained were analyzed using SPSS version 23, and the relationship between Vitamin D levels and antenatal complications was determined using Chi-square at P < 0.05 at 95% confidence interval being considered statistically significant. Results: The overall results showed that no participant had hypovitaminosis D. It also showed that there is maximum safe limit for serum Vitamin D beyond which the prevalence of hypertensive disorders/preeclampsia, preterm labor, and PROM rises. However, higher serum Vitamin D appears to be protective against clinical and laboratory-diagnosed malaria and malaria parasitemia. The study showed an inverse relationship between the degree of malaria parasitemia and serum Vitamin D levels. Conclusion: Despite the importance of Vitamin D in both skeletal and extra-skeletal health, there appears to be a safe upper limit. Therefore, Vitamin D supplementation should be reserved for proven cases of hypovitaminosis in pregnancy, especially in our locality where there is abundance of sunshine and low prevalence of hypovitaminosis D.

Keywords: Antenatal complication, Igbo, Nigeria, pregnant, Vitamin D, women


How to cite this article:
Brian-D Adinma JI, Ahaneku JE, Adinma ED, Ugboaja JO, Oguaka VN, Adinma-Obiajulu ND, Edet MM. Vitamin D levels and antenatal complications in pregnant Nigerian Igbo women. J Appl Sci Clin Pract 2022;3:67-72

How to cite this URL:
Brian-D Adinma JI, Ahaneku JE, Adinma ED, Ugboaja JO, Oguaka VN, Adinma-Obiajulu ND, Edet MM. Vitamin D levels and antenatal complications in pregnant Nigerian Igbo women. J Appl Sci Clin Pract [serial online] 2022 [cited 2022 Dec 6];3:67-72. Available from: http://www.jascp.org/text.asp?2022/3/3/67/360442




  Introduction Top


Pregnancy is associated with maternal physiologic change as well as intense fetal growth and development. Adequate intake of macronutrients and micronutrients during pregnancy ensures that these processes are facilitated; however, undernutrition and overnutrition may result in adverse pregnancy outcomes.[1] Vitamin D – a fat-soluble micronutrient, naturally occurs in few foods with exception of fatty fish livers, so dermal synthesis is the major natural source of the vitamin.[2]

Both dietary and dermally synthesized Vitamin D are biologically inactive and require enzymatic conversion to active metabolites. It undergoes conversions in the liver to 25-hydroxyvitamin D (25[OH]D) which is the major circulating form of Vitamin D and then in the kidney to 1,25[OH]D, the active form of Vitamin D.

Severe Vitamin D deficiencies which cause rickets in children and osteomalacia in both children and adults are now rare (except in those with malabsorption syndrome or with low exposure to sunlight), but subclinical Vitamin D deficiency, as measured by low serum 25(OH)D, is very common. This degree of Vitamin D deficiency may contribute to the development of osteoporosis and an increased risk of fractures and falls in older adults.[2]

In addition to calcium-related effects, Vitamin D has an increasingly recognized nonclassical (noncalcium) action, such as promoting insulin action and secretion, immune modulation, and lung development. Therefore, it has the potential to influence many factors in the developing fetus.[3] Adequate Vitamin D levels are necessary during pregnancy because of increasing demand for calcium by the fetus.[4],[5] Low maternal circulating 25(OH)D levels in pregnancy have been associated with risks of recurrent pregnancy losses, preeclampsia, gestational diabetes, maternal infections, preterm birth, small-for-gestational-age (SGA) infants, and poor offspring health.[4],[6],[7]

A recent systematic review and meta-analysis shows that Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length but was not associated with other maternal and neonatal outcomes such as preeclampsia, gestational diabetes mellitus, SGA, low birth weight, preterm birth, and cesarean section.[8]

Vitamin D is thought to influence feto–maternal and placental function in several ways, including immune modulation during the establishment of maternal immune response to the placenta as well as regulation of target genes associated with proper implantation of the placenta.[9],[10],[11] Vitamin D plays an important role in the production of antimicrobial peptides such as cathelicidin (requires 25(OH)D as a substrate) involved in preventing infection during pregnancy or early childhood.[12],[13]

Vitamin D is involved with the production of sex steroids and regulation of syncytiotrophoblastic expression of human chorionic gonadotropin[14],[15] and has influence on musculoskeletal growth.[16] Availability of energy to the fetus has also been shown to be under the influence of Vitamin D by way of insulin and glucose metabolism in animal and in vitro studies.[9],[17],[18]

The optimal level of Vitamin D for an optimal skeletal and extra-skeletal health has remained a great controversy; even more controversial is the optimal level in pregnancy. Trials on Vitamin D supplementation, and the Institute of Medicine (IOM) systematic review favor maintaining the serum 25(OH)D concentration between 20 and 40 ng/ml (50–100 nmol/l), whereas other experts favor maintaining 25(OH)D levels between 30 and 50 ng/ml (75–125 nmol/l)[19] while Vitamin D insufficiency is regarded as serum Vitamin D levels of 21–29 ng/ml and Vitamin D deficiency is serum Vitamin D levels of <20 ng/ml.

The IOM, however, noted that there was some concern at serum 25(OH)D concentrations above 50 ng/ml (125 nmol/l). These concerns were based upon the increase in fracture in patients treated with high-dose Vitamin D and conflicting studies describing a potential increased risk for some cancers (e.g., pancreatic, prostate) and mortality with levels above 30–48 ng/ml (75–120 nmol/l).[19]

In the current study, the optimal serum levels of Vitamin D level will be regarded as 30–50 ng/ml (75–125 nmol/l), while serum levels <30 ng/ml (75 nmol/l) and >50 ng/ml will be regarded as low and high levels, respectively.

In the present study, the correlation between maternal Vitamin D status and antenatal complications, viz., hypertensive disorders/preeclampsia, diabetes in pregnancy, premature rupture of membranes (PROM), preterm labor, malaria parasitemia, as well as eventual mode of delivery was sought.

Subjects and Methods

This is a prospective, cross-sectional study, conducted on 256 consecutive consenting parturient women in two locations in Anambra state of Southeastern Nigeria – Nnamdi Azikiwe University Teaching Hospital Nnewi and Holy Rosary Maternity Hospital Waterside Onitsha, to determine the Vitamin D status of the pregnant women and its relationship antenatal complications, such as hypertensive disorders/preeclampsia, diabetes in pregnancy, PROM, preterm labor, and malaria parasitemia.

Ethical approval was obtained from the ethical committees of the study institutions, and participatory consent was elicited and obtained from the parturient women following painstaking explanation and counseling on the nature of the study.

Relevant meetings were held between the study investigators and the head of department of obstetrics and gynecology of the study institutions together with the resident doctors; the nurses and chemical pathologists involved in the study to facilitate a clear understanding and correct conduct of the exercise.

Blood samples were taken from the women during the antenatal period. Serum obtained from each maternal blood sample was labeled and stored at −800°C and ultimately assayed for 25 hydroxyvitamin D2 and D3 using high-pressure liquid chromatography.[20]

A pro forma was completed for each subject and elicited information with respect to the biosocial characteristics of the patient – age, parity, gestational age, occupation, social class, complexion, and place of residence. The social class of the women was derived from Olusanya classification using of the educational level of the woman and her husband's occupation.[21]

Data obtained from the pro forma and study blood sample were coded and keyed into the computer for analysis. Data analysis was performed using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, NY, USA). The variables in the pro forma were cross-tabulated with the mean Vitamin D levels of the subjects. Comparison of variables was performed using Student's t-test and ANOVA where necessary. Correlation between Vitamin D levels, mode of delivery, antenatal complications, and malaria parasitemia was determined using Chi-square. P < 0.05 at 95% confidence interval was considered statistically significant.


  Results Top


[Table 1] shows the biosocial characteristics of the participants. Out of the 256 antenatal women recruited and analyzed in the study, 93 (36.3%) were aged between 25 and 29 years, while 89 (34.8%) were aged between 30 and 34 years. Seventy-three (28.5%) participants were nulliparous (28.5%), while 8 (3.1%) were grand multiparous. [Table 1] also shows the gestational age at recruitment as well as the social class of the participants.
Table 1: Biosocial characteristics of the participants (n=256)

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The mean serum Vitamin D level in the population under study was 45.43 ± 11.48 ng/ml. Displayed in [Table 2] are the categories of serum Vitamin D levels of the participants which are categorized into three, viz., low serum Vitamin D level (<30 ng/ml), optimal serum Vitamin D level (30–50 ng/ml), and high serum Vitamin D level (>50 ng/ml). Twenty participants (7.81%) had serum Vitamin D levels of <30 ng/ml, while 152 participants (59.38%) had serum Vitamin D level of between 30 ng/ml and 50 ng/ml and 84 participants (32.81%) had serum Vitamin D level of above 50 ng/ml.
Table 2: Categories of serum Vitamin D levels of the participants

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[Table 3] shows the distribution of the participants by the mean levels of Vitamin D and the presence or otherwise of antenatal complications. Seventy-two (28.1%) participants were noted to have at least one antenatal complication, while 184 (71.9%) did not have any antenatal complication. The mean serum Vitamin D level of participants with at least one antenatal complication was 53.28 ng/ml, while the mean serum Vitamin D level for participants without any antenatal complication was 42.67 ng/ml. None of the recruited participants was noted to have diabetes in in pregnancy. Five participants (2%) had hypertension in pregnancy/preeclampsia with a mean serum Vitamin D of 66.19 ng/ml, while 251 (98%) did not have hypertension with a mean serum Vitamin D of 44.42 ng/ml. Eight participants (3.1%) had PROM with a mean serum Vitamin D of 55.19 ng/ml, while 148 (96.9%) did not have PROM with a mean serum Vitamin D of 44.78 ng/ml [Table 3].
Table 3: Distribution by antenatal complications for Vitamin D status of the pregnant women (n=256)

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Preterm labor was observed in 13 participants (5.1%) with a mean serum Vitamin D level of 56.23 ng/ml, while 243 participants (94.9%) did not have preterm labor with a mean serum Vitamin D level of 44.55 ng/ml. One hundred and forty-four participants (56.3%) did not have malaria in pregnancy with a mean serum Vitamin D level of 50.99 ng/ml, while 117 participants (43.8%) had malaria in pregnancy with a mean serum Vitamin D level of 43.99 ng/ml. The degree of parasitemia is inversely proportional to the mean serum Vitamin D level. Those with mild degree of parasitemia (+) had the highest mean serum Vitamin D level of 50.62 ng/ml as noted in 16 participants, followed by those with moderate parasitemia (++) with a mean serum Vitamin D level of 40.80 ng/ml noted in 104 participants. Those with severe parasitemia (+++) as noted in 24 participants had the lowest mean serum Vitamin D level of 38.48 ng/ml [Table 3].

In [Table 4], the antenatal complications found in the various categories of serum Vitamin D levels of the participants are recorded. Among the category of participants with low Vitamin D levels (<30 ng/ml), four (20%) were noted to have at least one complication while 16 (80%) had no complication. As for those with optimal serum Vitamin D (30–50 ng/ml), only 18 (11.84%) had at least one antenatal complication while 134 (88.16%) did not have any complication. Incidentally, 50 (59.52%) of those with high serum Vitamin D levels (>50 ng/ml) had at least one antenatal complication, while 34 (40.48%) did not have any complication [Table 4].
Table 4: Antenatal complications in the various categories of Vitamin D levels

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Preterm labor was noted in 13 (15.48%) out of the 84 participants with high serum Vitamin D level, while none of the participants with optimal or low serum Vitamin D level had preterm labor.

In the same vein, PROM was not recorded among the participants with optimal or low serum Vitamin D level, but 8 (9.62%) of those with high serum Vitamin D level developed PROM.

As for preeclampsia, none of the participants with low or optimal Vitamin D was noted to develop the condition; however, 5 (5.95%) of the participants with high level of Vitamin D had preeclampsia.

Clinically diagnosed malaria in pregnancy was observed in 4 (20.0%), 52 (34.21%), and 56 (66.6%) of participants with low, optimal, and high serum Vitamin D levels, respectively. When the degree of malaria parasitemia was assessed, 4 (12.5%), 52 (37.12%), and 56 (66.0%) of the participants with low, optimal, and high serum Vitamin D levels, respectively, had nil malaria parasitemia, while 28 (87.5%), 88 (62.86%), and 20 (33.33%) of those with low, optimal, and high Vitamin D levels, respectively, had at least (+) of malaria parasitemia [Table 4].


  Discussion Top


Adequate serum Vitamin D levels have been linked to good maternal and perinatal outcomes. Poor Vitamin D status in the perinatal period may have short-term (e.g., preeclampsia) or long-term consequences (in the offspring) on bone, immune system (autoimmune diseases, allergy), and general health. The precise threshold for optimal Vitamin D status during pregnancy, lactation, or in the neonate is not well defined.[22] In the population under study, the mean serum Vitamin D level was 45.43 ± 11.48 ng/ml. This is lower than the mean serum Vitamin D level of 51.98 ng/ml found among pregnant women in a study in Lagos, western part of Nigeria,[23] but higher than found among pregnant women in another study done in the northern part of Nigeria where it was 21.23 ng/ml among the Purdah-practicing and 36.06 ng/ml among the non-Purdah–practicing population.[24] The disparities noted in these regions will be as a result of different levels of exposure to sunlight as well as level of intake of the precursors. The Purdah-practicing women in the Northern Nigeria are minimally exposed to sunlight unlike the population under study where exposure to sunlight is common.

More than half (59.38%) of the participants had optimal serum Vitamin D level (30–50 ng/ml) with a mean of 39.85 ± 5.21 ng/ml, while 7.81% and 32.81% had low and high levels, respectively. In this study, low Vitamin D level is regarded as serum Vitamin D levels <30 ng/ml. This range is inclusive of what is regarded as Vitamin D insufficiency (21–29 ng/ml) and Vitamin D deficiency (≤20 ng/ml) by other authors.[23],[24] In this study, no participant had hypovitaminosis D (Vitamin D deficiency). This is close to the findings of an earlier study in the same environment among pregnant women with hypovitaminosis prevalence of 2.5%[25] but in contrast with the findings in a similar study done in Western Nigeria where the prevalence among the pregnant population was 29%.[23] In another study conducted among poor Nomadic Fulani women of Northen Nigeria, a high Vitamin D prevalence rate of 83% was reported. This is in spite of the exposure of the women to abundant sunshine.[26] This buttresses the import of nutrition in the prevention of hypovitaminosis D.

This study re-echoes the question on what level of serum Vitamin D that is “safe.” As shown in [Table 3], the mean serum Vitamin D of the participant who developed complications in pregnancy was 53.28 ng/ml which is within the level regarded as high in this study, while the mean serum level for those without complications was 42.66 ng/ml which is well within the level regarded as optimal in this study. The IOM has noted some concern at serum Vitamin D concentrations above 50 ng/ml (125 nmol/l). These include increase in fracture in patients treated with high-dose Vitamin D and conflicting studies describing a potential increased risk for some cancers (e.g., pancreatic, prostate) and mortality with levels above 30–48 ng/ml (75–120 nmol/l).[19]

In terms of the various complications assessed for, no participant was noted to have gestational diabetes mellitus.

While five participants developed preeclampsia with a mean serum Vitamin D of 66.18 ng/ml, while those who did not had a mean serum Vitamin D level of 44.42 ng/ml. This disparity was statistically significant at P < 0.05.

In the same vein, the mean serum Vitamin D level of the participants who had PROM and preterm labor was 55.19 ng/ml and 56.22 ng/ml, respectively, while their counterparts without these complications had a mean serum Vitamin D level of 44.78 ng/ml and 44.55 ng/ml, respectively. These disparities are statistically significant at P < 0.05. Also noteworthy is the fact that the mean Vitamin D levels among those with PROM and preterm labor were well within the range regarded as high serum Vitamin D in this study, while the serum Vitamin D level for those without these complications was within the optimal serum Vitamin D levels.

Pérez López et al. in a recent systematic review and meta analysis showed that even though Vitamin D supplementation during pregnancy was associated with increased serum Vitamin D level as well as increased birth weight and length, it was however not associated with other maternal and neonatal outcomes such as preeclampsia, gestational diabetes mellitus, SGA, low birth weight, preterm birth, and cesarean section.[8]

There have been studies to suggest that there is not a linear correlation between Vitamin D supplementation (and hence increased serum Vitamin D level) and maternal and neonatal outcomes. More so, various obstetric endpoints are thought to have varying cutoffs.[6] Studies have suggested that hypervitaminosis D may have negative effects on some obstetric variables.[27],[28]

In fact, the IOM Committee having assessed the emerging evidence has suggested that there is a curvilinear (J-shaped) or U-shaped curve for several outcomes related to Vitamin D, including cardiovascular disease, vascular calcification, falls, frailty, pancreatic cancer, and all-cause mortality, with the lowest risk at moderate levels and increased risk at both low and high levels of Vitamin D. Several risks have been identified for some outcomes at serum Vitamin D levels above 50 ng/ml (125 nmol/l).[29] Such U-shaped relationship could not be established in this study since none of the participants had hypovitaminosis D (serum Vitamin D ≤20 ng/ml).

However, our study suggests that there is a safe upper margin for serum Vitamin D level in pregnancy and this may be about 50 ng/ml in consistent with the IOM recommendation.

As for those who were clinically diagnosed to have malaria in pregnancy, their mean serum Vitamin D level was 50.98 ng/ml while those without malaria had a mean serum Vitamin D level of 43.99 ng/ml. The degree of malaria parasitemia was found to be inversely proportional to the mean serum Vitamin D level. These differences were statistically significant at P < 0.05.


  Conclusion Top


While high serum Vitamin D levels appear to be protective against malaria, this study shows there are likely concerns for increased prevalence of preeclampsia, preterm labor, and PROM at levels 50 ng/ml. Therefore, routine supplementation of Vitamin D in pregnancy should be reserved for proven cases of serum Vitamin D insufficiency or deficiency. This is especially so in our environment where there is abundance of sunshine and low prevalence of hypovitaminosis D.

Financial support and sponsorship

The research work was supported by the Tertiary Education Trust Fund (TETFUND) of Nigeria with the grant number: TETF/ESS.D/6.11/NOM.RP/BAS&BNAS (BATCH 4 RP).

Conflicts of interest

There are no conflicts of interest-ssses



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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