Open Access, Peer-reviewed
pISSN 2508-4887
eISSN 2508-4895
    Perinatology. 2017 Mar;28(1):4-10. English.
    Published online Mar 31, 2017.
    https://doi.org/10.14734/PN.2017.28.1.4
    Copyright © 2017 The Korean Society of Perinatology
    Original Article

    Maternal Anemia and Vitamin D deficiency: associations with neonatal hemoglobin levels and the vitamin D status

    Sook-Hyun Park, MD, PhD
      • Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea.
    • Correspondence to: Sook-Hyun Park, MD, PhD. Department of Pediatrics, Kyungpook National University School of Medicine, 130 Dongdeokro, Jung-gu, Daegu 41944, Korea. Tel: +82-53-200-5704, Fax: +82-53-425-6683, Email: park_sh@knu.ac.kr
    Received October 19, 2016; Revised December 30, 2016; Accepted January 01, 2017.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Objective

    To evaluate maternal anemia and vitamin D deficiency and their associations with the neonatal hemoglobin (Hb) levels and the vitamin D status.

    Methods

    This retrospective study enrolled a total of 120 newborns delivered at Kyungpook National University Children's Hospital between June 2015 and June 2016. Maternal anemia was defined as an Hb level<11 g/dL and vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25-OHD) concentration<20 ng/mL.

    Results

    The mean neonatal and maternal serum 25-OHD concentrations were 20.1±12.5 ng/mL, and 16.9±7.3 ng/mL, respectively. Sixty-eight (56.7%) of the infants and 85 (70.8%) of the mothers were vitamin D deficient. The mean maternal hemoglobin levels were 11.7±1.6 g/dL, and 38 (31.7%) of the mothers had anemia. Thirty-four (89.5%) of mothers with anemia were vitamin D deficient. After adjusting for the confounding factors, maternal vitamin D deficiency increased the risk of maternal anemia by 4.061 times (95% confidence interval [CI], 1.238–13.320; P=0.021), and neonatal vitamin D deficiency by 8.283 times (95% CI, 2.861-23.980; P<0.001) compared with maternal vitamin D non-deficiency group. One-year older maternal age decreased the risk of neonatal vitamin D deficiency (odds ratio, 0.913; 95% CI, 0.841–0.991; P=0.029).

    Conclusion

    Maternal vitamin D deficiency increased the risk of maternal anemia and neonatal vitamin D deficiency regardless of maternal ferritin concentrations under non-inflammatory condition. A younger maternal age may be a risk factor for neonatal vitamin D deficiency associated with maternal anemia, and maternal vitamin D deficiency.

    Keywords
    Anemia; Vitamin D deficiency; 25-hydroxyvitamin D

    Introduction

    Low vitamin D status has been reported in Korean newborns and pregnant women.1, 2 The results from previous studies indicated that the vitamin D levels in Korean preterm infants were lower than those in infants in Northern European countries.3, 4 Vitamin D deficiency remains a common micronutrient disorder despite of encouragement to vitamin D supplements. Vitamin D plays an important role in calcium and bone metabolism, and potential associations between vitamin D and immune modulators, erythropoiesis, and iron homeostasis have been reported.5, 6

    The vitamin D levels are associated with the hemoglobin (Hb) levels and anemia in adult patients with diabetes, chronic kidney disease, and heart failure.7, 8, 9, 10 During inflammation, the Hb levels and the erythropoietin concentrations are positively correlated with the serum 25-hydroxyvitamin D (25-OHD) concentrations.6 The reasons underlying the association between vitamin D and anemia are emerging, and vitamin D may be involved in iron homeostasis. Vitamin D helps to maintain low serum hepcidin concentrations.11, 12 Hepcidin is a peptide hormone that regulates normal iron status, and its levels increase during iron overloads and inflammation to prevent iron absorption.12 Recent data have suggested that lower vitamin D levels may increase the risk of anemia independent of obesity, inflammation, kidney dysfunction, folate levels, and the iron status.6, 13, 14 The maternal 25-OHD concentrations at delivery may be positively correlated with the maternal Hb levels and erythropoietin concentrations during pregnancy.15

    The high incidence of vitamin D deficiency at birth in Korean newborns suggested low vitamin D status in Korean pregnant women.2, 3, 4 Therefore, it needs to evaluate the association between low vitamin D status and anemia in pregnant women, and also association between maternal vitamin D status and neonatal Hb levels.

    This study aimed to evaluate the neonatal Hb levels and vitamin D status associated with maternal anemia and vitamin D deficiency at delivery.

    Methods

    1. Subjects

    This retrospective study enrolled a total of 120 newborns delivered at Kyungpook National University Children's Hospital between June 2015 and June 2016. Cases were included if the maternal blood samples were obtained within 1 week of delivery and the neonatal blood samples were obtained from the cord blood or on the day the baby was born. Infants were excluded if they had culture-proven infections, congenital major anomalies, or chromosomal abnormalities, and mothers were excluded if they had a fever accompanied by a temperature of >38℃, C-reactive protein levels>0.5 mg/dL, and leukocytosis, which was defined as a white blood cell count>15,000 µ/L, before delivery and pathology-proven amnionitis, or if they had chronic kidney disease or autoimmune disorders.

    2. Methods

    The maternal and neonatal demographic and clinical characteristics were collected by reviewing the medical records. The maternal clinical data included the maternal age, the delivery mode, and the presence of gestational diabetes and preeclampsia. The neonatal clinical data included the admission date, sex, gestational age, birth weight, height, and the head circumference.

    The maternal and neonatal Hb levels, serum ferritin concentrations, which were used as a marker of the iron status, and serum 25-OHD concentrations were measured. The serum concentrations of calcium, phosphorous, alkaline phosphatase (ALP), and iron were additionally measured in the newborns. The Hb levels, serum ferritin concentrations, and the 25-OHD concentrations were assessed using a flow cytometer and an automated blood cell counter, electrochemilumincescence immunoassay using an automated method (Elecsys ferritin, Cobas®, Roche, Switzerland), and a radioimmunoassay (DIAsource 25OH-Vit.D3-Ria-CT kit, DIAsource ImmunoAssays S.A., Louvain-la-Neuve, Belgium), respectively.

    Maternal anemia was defined as an Hb level<11 g/dL16 and vitamin D deficiency was defined as a serum 25-OHD concentration<20 ng/mL.5 Iron deficiency was identified when the serum ferritin concentrations were <12 ng/mL.17 Maternal anemia group and non-anemia group were categorized based on Hb level<11 g/dL. Vitamin D deficiency group and vitamin D non-deficiency group were divided by serum 25-OHD concentration<20 ng/mL.

    3. Statistical analysis

    The statistical analyses were performed using IBM SPSS software, version 22.0 (IBM Corporation, Armonk, NY, USA). Student's t-test was used to compare the continuous variables that included the laboratory and clinical data, and the chi-square test or Fisher's exact test were used to compare the categorical data. Partial correlation models were used to determine associations between the Hb levels and the serum 25-OHD concentrations after adjusting for the confounding factors. A multiple regression analysis was performed to identify the independent factors associated with the neonatal Hb levels and the 25-OHD concentrations. Logistic regression analysis was used to determine the risks of maternal anemia and neonatal vitamin D deficiency in relation to maternal vitamin D deficiency. Statistical significance was defined as a P-value<0.05.

    Results

    1. Characteristics of subjects

    The clinical characteristics and laboratory findings of 120 infants are presented in Table 1. The mean gestational age was 33.6±3.1 weeks, and the mean birth weight was 2,105±32 g. The mean neonatal Hb levels were 15.6±1.8 g/dL, and the mean neonatal 25-OHD concentrations were 20.1±12.5 ng/mL. Sixty-eight (56.7%) of the infants had vitamin D deficiency, and the 25-OHD concentrations were below 10 ng/mL in 25 infants (20.8%).

    Table 1
    Baseline Characteristics of the Participants

    The mean maternal Hb levels were 11.7±1.6 g/dL, and the mean maternal 25-OHD concentrations were 16.9±7.3 ng/mL. The incidence of maternal anemia and vitamin D deficiency were 38 (31.7%), and 85 (70.8%), respectively (Table 2). Seventeen of the mothers (14.2%) revealed iron deficiency.

    Table 2
    Comparison of Clinical and Laboratory Characteristics Associations with Maternal Anemia and Vitamin D Deficiency

    2. Comparison of neonatal and maternal characteristics associated with maternal anemia and vitamin D deficiency

    Maternal age was younger, and maternal and neonatal 25-OHD concentrations were significantly lower in maternal anemia group compared with maternal non-anemia group (Table 2). Majority of mothers with anemia (89.5%) were involved in vitamin D deficiency. Neonatal Hb levels, maternal and neonatal serum ferritin concentrations were not different between maternal anemia group and non-anemia group. Gestational age, birth weight, height, head circumference, delivery mode, and the incidence of maternal complications such as diabetes, preeclampsia were not significantly different in maternal anemia group compared to maternal non-anemia group.

    Female infants, lower neonatal 25-OHD concentrations, younger maternal age, and lower maternal Hb levels were associated with maternal vitamin D deficiency (Table 2). Mean neonatal Hb levels was lower in maternal vitamin D deficiency group (15.3±1.7 ng/dL) compared to maternal vitamin D non-deficiency group (16.1±2.0 ng/dL), which was not statistically significant (P=0.072). The neonatal serum calcium, phosphorous, and ALP levels, maternal and neonatal ferritin concentrations did not differ between the maternal vitamin D deficiency group and vitamin D non-deficiency group. Gestational age, birth weight, height, head circumference, delivery mode, and maternal complications also were not different between the maternal vitamin D deficiency group and vitamin D non-deficiency group.

    3. Correlations among the Hb levels, serum ferritin concentrations, and serum 25-OHD concentrations

    The neonatal Hb levels were positively correlated with gestational age (r=0.283, P=0.002), birth weight (r=0.234, P=0.011), and maternal 25-OHD concentrations (r=0.194, P=0.035) but not with maternal Hb levels, neonatal 25-OHD concentrations, neonatal and maternal ferritin concentrations after adjusting for season. The neonatal 25-OHD concentrations were significantly correlated with maternal 25-OHD concentrations (r=0.707, P<0.001), maternal Hb levels (r=471, P<0.001), and maternal age (r=0.257, P=0.005), but not with neonatal and maternal ferritin concentrations after adjusting for season.

    The maternal Hb levels were positively correlated with maternal age (r=0.336, P<0.001), maternal ferritin concentrations (r=0.218, P=0.017), and maternal 25-OHD concentrations (r=0426, P<0.001). The maternal 25-OHD concentrations were also positively correlated with maternal age after adjusting season (r=0.233, P<0.010).

    A multiple regression analysis was performed to identify the independent factors associated with neonatal Hb levels and 25-OHD concentrations (Table 3). The neonatal Hb levels were not significantly correlated with maternal Hb levels, maternal and neonatal 25-OHD concentrations. The neonatal Hb levels were inversely correlated neonatal ferritin concentrations (β=-0.006, P=0.001). The neonatal 25-OHD concentrations were positively correlated with maternal Hb levels (β=2.154, P<0.001), and maternal 25-OHD concentrations (β=1.058, P<0.001).

    Table 3
    Multiple Regression Analysis of the Factors Associated with Neonatal Hemoglobin Levels and 25-Hydroxyvitamin D Concentrations

    4. Maternal vitamin D deficiency associations with maternal anemia and neonatal vitamin D deficiency

    It was analyzed the impact of maternal vitamin D deficiency associations with maternal anemia and neonatal vitamin D deficiency after adjusting for the potential confounding factors. An increase in the maternal age by 1 year reduced the risk of neonatal vitamin D deficiency (odds ratio [OR], 0.913; 95% confidence interval [CI], 0.841-0.991; P=0.029), maternal anemia (OR, 0.875; 95% CI, 0.800-0.956; P=0.003), and maternal vitamin D deficiency (OR, 0.862; 95% CI, 0.781-0.953; P=0.004) after adjusting season.

    Maternal vitamin D deficiency increased the risk of maternal anemia by 4.061 times (95% CI 1.238-13.320, P=0.021) compared with maternal vitamin D non-deficiency group after adjusting for season, maternal age, and maternal serum ferritin concentrations. The risk of neonatal vitamin deficiency increased by 8.283 times (95% CI 2.861-23.980, P<0.001) in maternal vitamin D deficiency group compared to maternal vitamin D non-deficiency group after adjusting season, gestational age, birth weight, maternal age.

    Discussion

    In present study, maternal 25-OHD concentrations were positively correlated with neonatal 25-OHD concentrations and maternal Hb levels, but not with neonatal Hb levels. Maternal Hb levels were correlated with neonatal and maternal 25-OHD concentrations and maternal ferritin concentrations, but not with neonatal Hb levels. Almost 90% of mothers with anemia were vitamin D deficient. Maternal vitamin D deficiency increased the risk of neonatal vitamin D deficiency and maternal anemia independent from maternal age, season, and ferritin concentrations.

    Thomas et al. reported that pregnant women with vitamin D deficiencies at delivery had a 4-8-times greater risk of anemia than those who did not have vitamin D deficiencies,15 and that the maternal 25-OHD concentrations were positively correlated with the maternal Hb concentrations and the serum iron concentrations, but not with the serum ferritin concentrations.15 Serum iron concentrations have also been shown to positively correlate with the 25-OHD concentrations, and this was accentuated in association with inflammation-induced anemia.18 Vitamin D is involved in inflammation-induced anemia by downregulating proinflammatory cytokines, and it also affects iron metabolism by suppressing the release of hepcidin and stimulating ferroportin expression in monocytes.19, 20 In present study, it was excluded mothers who had chronic kidney disease, autoimmune diseases, and evidence of infections. The findings from the present study showed that the maternal 25-OHD concentrations were significantly positively correlated with the maternal Hb levels in the absence of inflammation. Vitamin D deficiency increased the risk of anemia, and this was independent of the serum ferritin concentrations as a marker of iron status. This finding supports the evidence for the role that vitamin D plays in erythropoiesis in which it increases burst-forming uniterythroid proliferation.21

    The prevalence of vitamin D deficiency differs according to race, latitude, season, age, maternal diseases, including diabetes and hypertension, and socioeconomic status.18 In present study, there were no differences between the maternal vitamin D deficiency group and vitamin D non-deficiency group in relation to the incidence of maternal diabetes and preeclampsia. The vitamin D status among Korean people is lower compared with other races,22, 23 and the findings from one of our previous studies showed that, as far as we were able to determine, the serum 25-OHD concentrations in Korean preterm infants were the lowest of any race.3 In an adult group, a younger age can also be a risk factor.18 Maternal vitamin D deficiency was prevalent among the younger pregnant women. Although the mechanism underlying the impact of age on the metabolism of vitamin D remains unknown, age had an impact on the maternal vitamin D status after adjusting for the potential confounding factors in the present study.

    In present study, maternal inflammatory conditions were excluded, but the maternal 25-OHD concentrations were significantly correlated with the maternal Hb levels. The risk of maternal anemia was four-times greater in the maternal vitamin D deficiency group compared with vitamin D non-deficiency group. Since infants with anemia were not included, the association between maternal vitamin D deficiency and neonatal anemia could not be evaluated. Furthermore, the neonatal Hb levels did not correlate with the maternal Hb levels and neonatal 25-OHD concentrations in the present study. The maternal 25-OHD concentrations during pregnancy were directly correlated with the neonatal vitamin D status, and this agrees with the findings from previous studies.24, 25, 26 It has not defined how vitamin D involves in fetal erythropoiesis and the association between Hb levels and the duration of maternal vitamin D deficiency on fetal period. Maternal 25-OHD concentrations were measured once near delivery in present study, so, there is a limitation to identify the role of vitamin D as an independent factor associated with fetal erythropoiesis.

    The data describing the maternal and neonatal characteristics were collected from the medical records in the present study, and they did not contain information about maternal factors, including vitamin D supplementation during pregnancy, sun-exposure activities, and obesity, which may have influenced the vitamin D status. Therefore, generalizing the association between the maternal age and the vitamin D status represents a study limitation. The only maternal iron status marker included in this study was the serum ferritin concentration and the maternal vitamin D status was only measured near delivery. The effects of other iron status markers and the longitudinal vitamin D status during pregnancy on the neonatal Hb levels and the 25-OHD concentrations remain to be determined. Maternal complications and the neonatal characteristics, including the birth weight, height, and the head circumference, and the serum calcium, phosphorous, and ALP levels, did not differ significantly in infants with maternal anemia and vitamin D deficiency compared to those without maternal anemia and vitamin D deficiency in the present study. Further studies involving large numbers of subjects are necessary to identify the role that the maternal vitamin D status during pregnancy plays in relation to the maternal Hb levels, fetal erythropoiesis, and neonatal long-term complications, and to define an adequate maternal vitamin D status during pregnancy to prevent maternal anemia and neonatal vitamin D deficiency.

    In conclusion, maternal vitamin D deficiency increased the risk of neonatal vitamin D deficiency and maternal anemia regardless of maternal ferritin concentrations under non-inflammatory condition. A younger maternal age may be a risk factor for maternal anemia, maternal vitamin D deficiency, and neonatal vitamin D deficiency.

    Notes

    Conflict of interest:No potential conflict of interest relevant to this article was reported.

    References

      1. Choi R, Kim S, Yoo H, Cho YY, Kim SW, Chung JH, et al. High prevalence of vitamin D deficiency in pregnant Korean women: the first trimester and the winter season as risk factors for vitamin D deficiency. Nutrients 2015;7:3427–3448.
      1. Shin YH, Yu J, Kim KW, Ahn K, Hong SA, Lee E, et al. Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA). Korean J Pediatr 2013;56:439–445.
      1. Park SH, Lee GM, Moon JE, Kim HM. Severe vitamin D deficiency in preterm infants: maternal and neonatal clinical features. Korean J Pediatr 2015;58:427–433.
      1. Lee JE, Lee WK, Jeon KW, Sin JB. Vitamin D status in early preterm infants. Neonatal Med 2016;23:143–150.
      1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–281.
      1. Smith EM, Tangpricha V. Vitamin D and anemia: insights into an emerging association. Curr Opin Endocrinol Diabetes Obes 2015;22:432–438.
      1. Meguro S, Tomita M, Katsuki T, Kato K, Oh H, Ainai A, et al. Plasma 25-hydroxyvitamin d is independently associated with hemoglobin concentration in male subjects with type 2 diabetes mellitus. Int J Endocrinol 2011;2011:362981.
      1. Zittermann A, Jungvogel A, Prokop S, Kuhn J, Dreier J, Fuchs U, et al. Vitamin D deficiency is an independent predictor of anemia in end-stage heart failure. Clin Res Cardiol 2011;100:781–788.
      1. Patel NM, Gutierrez OM, Andress DL, Coyne DW, Levin A, Wolf M. Vitamin D deficiency and anemia in early chronic kidney disease. Kidney Int 2010;77:715–720.
      1. Perlstein TS, Pande R, Berliner N, Vanasse GJ. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: association with anemia of inflammation. Blood 2011;117:2800–2806.
      1. Lee JA, Hwang JS, Hwang IT, Kim DH, Seo JH, Lim JS. Low vitamin D levels are associated with both iron deficiency and anemia in children and adolescents. Pediatr Hematol Oncol 2015;32:99–108.
      1. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090–2093.
      1. Shin JY, Shim JY. Low vitamin D levels increase anemia risk in Korean women. Clin Chim Acta 2013;421:177–180.
      1. Atkinson MA, Melamed ML, Kumar J, Roy CN, Miller ER 3rd, Furth SL, et al. Vitamin D, race, and risk for anemia in children. J Pediatr 2014;164:153–158.
      1. Thomas CE, Guillet R, Queenan RA, Cooper EM, Kent TR, Pressman EK, et al. Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy. Am J Clin Nutr 2015;102:1088–1095.
      1. Nutritional anaemias. Report of WHO scientific group. World Health Organ Tech Rep Ser 1968;405:5–37.
      1. Demaeyer EM. Preventing and controlling iron deficiency anaemia through primary health care: A guide for health administrators and programme managers. Geneva: World Health Oganization; 1989
        Available from:URL://http://www.who.int/nutrition/publications/micronutrients/anaemia_iron_deficiency/9241542497/en/.
      1. Smith EM, Alvarez JA, Martin GS, Zughaier SM, Ziegler TR, Tangpricha V. Vitamin D deficiency is associated with anaemia among African Americans in s US cohort. Br J Nutr 2015;113:1732–1740.
      1. Zughaier SM, Alvarez JA, Sloan JH, Konrad RJ, Tangpricha V. The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes. J Clin Transl Endocrinol 2014;1:19–25.
      1. Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, et al. Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol 2014;25:564–572.
      1. Aucella F, Scalzulli RP, Gatta G, Vigilante M, Carella AM, Stallone C. Calcitriol increases burst-forming unit-erythroid proliferation in chronic renal failure. A synergic effect with r-HuEpo. Nephron Clin Pract 2003;95:c121–c127.
      1. Jang H, Koo FK, Ke L, Clemson L, Cant R, Fraser DR, et al. Culture and sun exposure in immigrants East Asian women living in Australia. Women Health 2013;53:504–518.
      1. Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, et al. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med 2006;260:245–254.
      1. Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr 2007;137:447–452.
      1. Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF. Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr (Phila) 2007;46:42–44.
      1. Vio Sterym S, Kristine Moller U, Rejnmark L, Heickedorff L, Mosekilde L, Vestergaard P. Maternal and infant vitamin D status during the first 9 months of infant life-a cohort study. Eur J Clin Nutr 2013;67:1022–1028.
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    MeSH Terms
    Anemia*
    Ferritins
    Gyeongsangbuk-do
    Humans
    Infant
    Infant, Newborn
    Maternal Age
    Mothers
    Retrospective Studies
    Risk Factors
    Vitamin D Deficiency*
    Vitamin D*
    Vitamins*
    Metrics
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