Professional Documents
Culture Documents
Abstract
Pregnancy is a dynamic state that requires increased nutrient intakes in order to support the growing fetus, placenta and maternal
tissues, and hence a successful pregnancy outcome. Although maternal micronutrient deficiencies during pregnancy are often associ-
ated with pregnancy complications, as well as adverse fetal growth and development, evidence to support routine vitamin and min-
eral supplementation is relatively scarce. This review summarises existing evidence and special considerations regarding folic acid,
vitamin B12, vitamin D, calcium, zinc, iron, selenium and iodine supplementation on pregnancy outcomes. Current practice recom-
mendations are for routine supplementation of folic acid and iodine, but recommendations regarding other vitamins and minerals
are based on an individualised approach in pregnancy, with supplementation restricted to women with insufficient dietary intakes
or established deficiencies. This review aims to support pharmacists in evaluating the appropriateness of various individual and
multicomponent vitamin and mineral supplements and providing balanced and up-to-date information to women who are either
planning pregnancy or are already pregnant.
© 2018 The Society of Hospital Pharmacists of Australia Journal of Pharmacy Practice and Research (2018) 48, 186–192
doi: 10.1002/jppr.1438
Micronutrient supplementation in pregnancy 187
© 2018 The Society of Hospital Pharmacists of Australia Journal of Pharmacy Practice and Research (2018) 48, 186–192
188 R. L. Wilson et al.
Table 2 Key micronutrient content of four leading pregnancy multivitamins available in Australia
Dose (tablets/day) 1 2 1 1
Micronutrient content
Folic acid (micrograms) 800 250 500 500
Vitamin B12 (micrograms) 2.6 1.3 0 2.6
Vitamin D3 (colecalciferol; micrograms) 5 12.5 5 15
Calcium (mg) 125 50 20 20
Iron (mg) 60 5 5 5
Iodine (micrograms) 220 75 250 250
Zinc (mg) 11 5.5 12 11
Selenium (micrograms) 50 32.5 16.25 65
vitamin D supplementation in pregnancy, there is evi- and 15 470 women, predominantly from countries
dence to support a reduction in the risk of offspring where calcium intake is predicted to be lower. Indeed,
wheeze by age 3 years (RR 0.81; 95% CI 0.67–0.98).22 the greatest effect was seen in trials undertaken among
Furthermore, low maternal serum vitamin D concentra- women with low-calcium diets (eight trials, 10 678
tions are correlated with low neonatal levels. This is women; RR 0.36; 95% CI 0.20–0.65). Furthermore, high-
important because vitamin D deficiency in the neonate dose calcium supplementation compared with placebo
and the infant has been associated with impaired skele- significantly reduces the risk of preterm birth (11 trials,
tal development and an increased incidence of hypocal- 15 275 women; RR 0.76; 95% CI 0.60–0.97), but does not
caemic seizures.23 Although routine screening and appear to affect the risk of delivering a small-for-gesta-
supplementation with vitamin D is not currently recom- tional age infant (four trials, 13 615 women; RR 1.05;
mended, women should be assessed for vitamin D defi- 95% CI 0.86–1.29).35
ciency based on established risk factors (Table 3) and
offered treatment as appropriate.
IRON
Journal of Pharmacy Practice and Research (2018) 48, 186–192 © 2018 The Society of Hospital Pharmacists of Australia
Micronutrient supplementation in pregnancy 189
Table 3 Summary of current recommendations regarding vitamin and mineral supplementation in pregnancy (adapted from The Royal
Australian and New Zealand College of Obstetricians and Gynaecologists24)
Folic acid All women should take at least 0.4 mg A higher daily dose of 5 mg should be recommended for women
daily for a minimum of 1 month at increased risk of NTD:
before conception and for the • Pre-existing diabetes mellitus
first 12 weeks of pregnancy • Family history of NTD or women with a child with NTD
• Women taking folate antagonists
(e.g. carbamazepine, valproic acid)
• Increased BMI (>30 kg/m2)
• Malabsorption syndrome (e.g. inflammatory bowel disease)
Iodine All women who are pregnant, breast-feeding, Mandatory in areas of regional deficiency
or considering pregnancy should
take 150 micrograms/day
Vitamin B12 Routine supplementation not recommended Consider supplementation in pregnancy and lactation for women
who are vegetarian or vegan
Vitamin D Routine screening and supplementation of Offer vitamin D screening to women with limited exposure to
vitamin D is not currently recommended sunlight (e.g. because they are predominantly indoors or
usually protected from the sun when outdoors), or those who
have dark skin or a prepregnancy BMI >30 kg/m2
Calcium Routine supplementation not recommended Supplementation (≥1000 mg/day) is recommended for women
who avoid dairy in their usual diet and do not consume
alternative high-calcium foods (e.g. calcium-enriched soya milk)
Iron Routine supplementation is not recommended. Risk factors for iron deficiency include:
All women should have their haemoglobin • Previous anaemia or iron deficiency
assessed at the first antenatal visit and • Multiparity (para >2)
again around 28 weeks gestation • Consecutive pregnancy <1 year following delivery
BMI = body mass index; N/A = not applicable; NTD = neural tube defects.
benefits of routine iron supplementation in a developed 28 weeks gestation. Women who are identified as anae-
setting are unclear. Of interest is that studies have mic should be appropriately investigated and treated
demonstrated that intermittent (i.e. two or three times a with iron supplements if iron deficiency is the identified
week on non-consecutive days) supplementation regi- cause. Specific risk factors for iron deficiency are out-
mens produced similar maternal and infant outcomes as lined in Table 3 and can be used to guide screening
daily supplementation, but with a reduction in associ- practices. Specific guidelines for the management of
ated side effects and a lower risk of high levels of hae- anaemia in pregnancy have been published elsewhere.41
moglobin in mid- and late pregnancy.38 Therefore,
intermittent regimens have been proposed as a feasible
alternative to daily iron supplementation. Despite uncer- IODINE
tain evidence surrounding routine iron supplementation,
all women should have their haemoglobin and ferritin Iodine is an essential component of thyroid hormones,
assessed at the first antenatal visit and again around which are necessary for brain development in utero.42
© 2018 The Society of Hospital Pharmacists of Australia Journal of Pharmacy Practice and Research (2018) 48, 186–192
190 R. L. Wilson et al.
Journal of Pharmacy Practice and Research (2018) 48, 186–192 © 2018 The Society of Hospital Pharmacists of Australia
Micronutrient supplementation in pregnancy 191
2 Black RE. Micronutrients in pregnancy. Br J Nutr 2001; 85(Suppl severity of childhood asthma in Costa Rica. Am J Respir Crit Care
2): S193–7. Med 2009; 179: 765–71.
3 Roberts CT. IFPA Award in Placentology Lecture: complicated 21 Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil
interactions between genes and the environment in placentation, during pregnancy associated with lower risk of Type I diabetes in
pregnancy outcome and long term health. Placenta 2010; 31 the offspring. Diabetologia 2000; 43: 1093–8.
(Suppl): S47–53. 22 Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E.
4 Woodside JV, McCall D, McGartland C, Young IS. Micronutrients: Vitamin D supplementation during pregnancy: state of the
dietary intake v. supplement use. Proc Nutr Soc 2005; 64: 543–53. evidence from a systematic review of randomised trials. BMJ 2017;
5 Insitute of Medicine. Dietary reference intakes for vitamin A, vitamin 359: j5237.
K, arsenic, boron, chromium, copper, iodine, iron, manganese, 23 Markestad T. Effect of season and vitamin D supplementation on
molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: plasma concentrations of 25-hydroxyvitamin D in Norwegian
The National Academies Press; 2001. infants. Acta Paediatr 1983; 72: 817–21.
6 National Health and Medical Research Council. Nutrient reference 24 The Royal Australian and New Zealand College of Obstetricians
values for Australia and New Zealand. Canberra: National Health and Gynaecologists. Vitamin and mineral supplementation and
and Medical Research Council; 2005. pregnancy. 2014. Available from https://www.ranzcog.edu.au/
7 Wagner C. Biochemical role of folate in cellular metabolism. Clin RANZCOG_SITE/media/RANZCOG-MEDIA/Women's%20Health/
Res Reg Affairs 2001; 18: 161–80. Statement%20and%20guidelines/Clinical-Obstetrics/Vitamin-and-
8 Wilson R, Davies G, Desilets V, Reid G, Summers A, Wyatt P, mineral-supplementation-in-pregnancy-(C-Obs-25)-Review-Nov-
et al. The use of folic acid for the prevention of neural tube defects 2014,-Amended-May-2015.pdf?ext=.pdf. Accessed 27 February
and other congenital anomalies. J Obstet Gynaecol Can 2003; 25: 2018.
959–73. 25 Trotter M, Hixon BB. Sequential changes in weight, density, and
9 Tamura T, Picciano MF. Folate and human reproduction. Am J percentage ash weight of human skeletons from an early fetal
Clin Nutr 2006; 83: 993–1016. period through old age. Anat Rec 1974; 179: 1–18.
10 De-Regil LM, Pena-Rosas JP, Fernandez-Gaxiola AC, Rayco-Solon 26 Koo WW, Walters JC, Esterlitz J, Levine RJ, Bush AJ, Sibai B.
P. Effects and safety of periconceptional oral folate Maternal calcium supplementation and fetal bone mineralization.
supplementation for preventing birth defects. Cochrane Database Obstet Gynecol 1999; 94: 577–82.
Syst Rev 2015; 12: CD007950. 27 Tolaymat A, Sanchez-Ramos L, Yergey AL, Vieira NE, Abrams
11 Lassi ZS, Salam RA, Haider BA, Bhutta ZA. Folic acid SA, Edelstein P. Pathophysiology of hypocalciuria in preeclampsia:
supplementation during pregnancy for maternal health and measurement of intestinal calcium absorption. Obstet Gynecol 1994;
pregnancy outcomes. Cochrane Database Syst Rev 2013; 3: 83: 239–43.
CD006896. 28 Taufield PA, Ales KL, Resnick LM, Druzin ML, Gertner JM,
12 Shin JS, Choi MY, Longtine MS, Nelson DM. Vitamin D effects on Laragh JH. Hypocalciuria in preeclampsia. N Engl J Med 1987; 316:
pregnancy and the placenta. Placenta 2010; 31: 1027–34. 715–18.
13 Rosanoff A, Dai Q, Shapses SA. Essential nutrient interactions: 29 Frenkel Y, Barkai G, Mashiach S, Dolev E, Zimlichman R, Weiss
does low or suboptimal magnesium status interact with vitamin D M. Hypocalciuria of preeclampsia is independent of parathyroid
and/or calcium status? Adv Nutr 2016; 7: 25–43. hormone level. Obstet Gynecol 1991; 77: 689–91.
14 Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, 30 Kazerooni T, Hamze-Nejadi S. Calcium to creatinine ratio in a
Roberts JM. Maternal vitamin D deficiency increases the risk of spot sample of urine for early prediction of pre-eclampsia. Int J
preeclampsia. J Clin Endocrinol Metab 2007; 92: 3517–22. Gynaecol Obstet 2003; 80: 279–83.
15 Baker AM, Haeri S, Camargo CA Jr, Espinola JA, Stuebe AM. A 31 Belizan JM, Villar J, Repke J. The relationship between calcium
nested case-control study of midgestation vitamin D deficiency intake and pregnancy-induced hypertension: up-to-date evidence.
and risk of severe preeclampsia. J Clin Endocrinol Metab 2010; 95: Am J Obstet Gynecol 1988; 158: 898–902.
5105–9. 32 Repke JT, Villar J. Pregnancy-induced hypertension and low birth
16 Perez-Ferre N, Torrejon MJ, Fuentes M, Fernandez MD, Ramos A, weight: the role of calcium. Am J Clin Nutr 1991; 54(Suppl): 237S–41S.
Bordiu E, et al. Association of low serum 25-hydroxyvitamin D 33 Villar J, Repke J, Belizan JM, Pareja G. Calcium supplementation
levels in pregnancy with glucose homeostasis and obstetric and reduces blood pressure during pregnancy: results of a randomized
newborn outcomes. Endocr Pract 2012; 18: 676–84. controlled clinical trial. Obstet Gynecol 1987; 70: 317–22.
17 Bodnar LM, Simhan HN. Vitamin D may be a link to Black-White 34 Belizan JM, Villar J. The relationship between calcium intake and
disparities in adverse birth outcomes. Obstet Gynecol Surv 2010; 65: edema-, proteinuria-, and hypertension-getosis: an hypothesis. Am
273–84. J Clin Nutr 1980; 33: 2202–10.
18 Leffelaar ER, Vrijkotte TG, van Eijsden M. Maternal early 35 Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR.
pregnancy vitamin D status in relation to fetal and neonatal Calcium supplementation during pregnancy for preventing
growth: results of the multi-ethnic Amsterdam Born Children and hypertensive disorders and related problems. Cochrane Database
their Development cohort. Br J Nutr 2010; 104: 108–17. Syst Rev 2014; 3: CD001059.
19 Marjamaki L, Niinisto S, Kenward MG, Uusitalo L, Uusitalo U, 36 Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman
Ovaskainen ML, et al. Maternal intake of vitamin D during SR, Branca F, et al. Global, regional, and national trends in
pregnancy and risk of advanced beta cell autoimmunity and type haemoglobin concentration and prevalence of total and severe
1 diabetes in offspring. Diabetologia 2010; 53: 1599–607. anaemia in children and pregnant and non-pregnant women for
20 Brehm JM, Celedon JC, Soto-Quiros ME, Avila L, Hunninghake 1995–2011: a systematic analysis of population-representative data.
GM, Forno E, et al. Serum vitamin D levels and markers of Lancet Glob Health 2013; 1: e16–25.
© 2018 The Society of Hospital Pharmacists of Australia Journal of Pharmacy Practice and Research (2018) 48, 186–192
192 R. L. Wilson et al.
37 Moll R, Davis B. Iron, vitamin B 12 and folate. Medicine 2017; 45: 53 Perkins AV, Vanderlelie JJ. Multiple micronutrient
198–203. supplementation and birth outcomes: the potential importance of
38 Pe~na-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T. Daily selenium. Placenta 2016; 48: S61–5.
oral iron supplementation during pregnancy. Hoboken, NJ: The 54 Tara F, Maamouri G, Rayman MP, Ghayour-Mobarhan M,
Cochrane Library; 2015. Sahebkar A, Yazarlu O, et al. Selenium supplementation and the
39 Pe~na-Rosas JP, De-Regil LM, Dowswell T, Viteri FE. Daily oral iron incidence of preeclampsia in pregnant Iranian women: a
supplementation during pregnancy. Hoboken, NJ: The Cochrane randomized, double-blind, placebo-controlled pilot trial. Taiwan J
Library; 2012. Obstet Gynecol 2010; 49: 181–7.
40 Scholl TO. Iron status during pregnancy: Setting the stage for 55 Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath
mother and infant. Am J Clin Nutr 2005; 81: 1218S–22S. SC, et al. Effect of selenium on markers of risk of pre-eclampsia in
41 Achebe MM, Gafter-Gvili A. How I treat anemia in pregnancy: UK pregnant women: a randomised, controlled pilot trial. Br J
iron, cobalamin, and folate. Blood 2017; 129: 940–9. Nutr 2014; 112: 99–111.
42 Hetzel BS, Potter BJ, Dulberg EM. The iodine deficiency disorders: 56 Han L, Zhou SM. Selenium supplement in the prevention of
nature, pathogenesis and epidemiology. World Rev Nutr Diet 1990; pregnancy induced hypertension. Chin Med J (Engl) 1994; 107: 870–1.
62: 59–119. 57 Rumbold A, Duley L, Crowther CA, Haslam RR. Antioxidants for
43 WHO. Iodine deficiency in Europe and its control: current status, preventing pre-eclampsia. Hoboken, NJ: The Cochrane Library; 2008.
progress and recent trends. In: Andersson M, Benoist B, Darnton- 58 Balogun OO, da Silva Lopes K, Ota E, Takemoto Y, Rumbold A,
Hill I, Delange F, editors. Iodine deficiency in Europe: a continuing Takegata M, et al. Vitamin supplementation for preventing miscarriage.
public health problem. Geneva: WHO Press; 2007. p. 20–32. Hoboken, NJ: The Cochrane Library; 2016.
44 Harding KB, Pe~ na-Rosas JP, Webster AC, Yap CM, Payne BA, Ota 59 Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin
E, et al. Iodine supplementation for women during the preconception, C supplementation in pregnancy. Hoboken, NJ: The Cochrane
pregnancy and postpartum period. Hoboken, NJ: The Cochrane Library; 2015.
Library; 2017. 60 Xu H, Perez-Cuevas R, Xiong X, Reyes H, Roy C, Julien P, et al.
45 Prasad AS. Essential and toxic element: trace elements in human health An international trial of antioxidants in the prevention of
and disease. Amsterdam, Netherlands: Elsevier; 2013. preeclampsia (INTAPP). Am J Obstet Gynecol 2010; 202:
46 Maret W. Molecular aspects of human cellular zinc homeostasis: 239.e1–e10.
redox control of zinc potentials and zinc signals. Biometals 2009; 61 Mastroiacovo PA, Mazzone T, Addis A, Elephant E, Carlier P, Vial
22: 149–57. T, et al. High vitamin A intake in early pregnancy and major
47 Caulfield LE, Black RE. Zinc deficiency. In: Ezzati M, Lopez malformations: a multicenter prospective controlled study.
AD, Rodgers A, Murray CJL editors. Comparative quantification of Teratology 1999; 59: 7–11.
health risks: global and regional burden of disease attributable to 62 Duerbeck NB, Dowling DD. Vitamin A: too much of a good
selected major risk factors. Geneva: World Health Organization; thing? Obstet Gynecol Surv 2012; 67: 122–8.
2004. p. 257–79.
48 Wilson RL, Bianco-Miotto T, Leemaqz SY, Grzeskowiak LE,
Dekker GA, Roberts CT. Early pregnancy maternal trace mineral This activity has been
status and the association with adverse pregnancy outcome in a accredited for 0.5 hours
cohort of Australian women. J Trace Elem Med Biol 2018; 46: of Group 1 CPD activ-
103–9. ity (or 0.5 CPD credits)
49 Ota E, Mori R, Middleton P, Tobe-Gai R, Mahomed K, Miyazaki suitable for inclusion in
an individual pharma-
C, et al. Zinc supplementation for improving pregnancy and infant
cist’s CPD plan, which
outcome. Cochrane Database Syst Rev 2015; 7: CD000230. can be converted to
50 Mistry HD, Broughton Pipkin F, Redman CW, Poston L. Selenium 0.5 hours of Group 2
in reproductive health. Am J Obstet Gynecol 2012; 206: 21–30. CPD (or 1 CPD credit)
51 Rayman MP, Bode P, Redman CW. Low selenium status is upon successful com-
associated with the occurrence of the pregnancy disease pletion of the relevant
assessment activity. No:
preeclampsia in women from the United Kingdom. Am J Obstet
S2018/17.
Gynecol 2003; 189: 1343–9.
52 Nawrot TS, Staessen JA, Roels HA, Den Hond E, Thijs L, Fagard
RH, et al. Blood pressure and blood selenium: a cross-sectional
and longitudinal population study. Eur Heart J 2007; 28: 628–33.
Journal of Pharmacy Practice and Research (2018) 48, 186–192 © 2018 The Society of Hospital Pharmacists of Australia