Kelly Segal, PharmD Candidate, Nicole E. Cieri-Hutcherson, PharmD, BCPS, and Stacie Lampkin, PharmD, BCPPS, BCACP, AE-C
This guide reviews supplementation recommendations for pregnant women without concomitant disease states and without concurrent medications and can be used to aid the pharmacist in recommending and evaluating a prenatal vitamin for a patient.
The Pharmacist’s Role:
In order to advise patients seeking an over-the-counter (OTC) supplement, pharmacists should be aware of the dosing recommendations, risks, and benefits associated with vitamins and minerals during pregnancy. When determining the amount of a nutrient to recommend to a patient, the pharmacist must also consider any co-existing disease states and therapies used, including any other dietary supplements and prescriptions.
The American College of Obstetricians and Gynecologists (ACOG), the Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), and the United States Food and Drug Administration (FDA) have put forth recommendations on vitamin and mineral supplementation during pregnancy (Table 1). However, discrepancies in major organization recommendations make it difficult to determine the most appropriate multivitamin and are discussed in more detail below.
Table 1: Recommended Daily Intake of Select Vitamins and Minerals During Pregnancy
|Calcium||1,000 mg||N/A||1,300 mg||1,500 mg|
|Folic Acid/Folate||400 mcg||400 mcg||800 mcg||400 mcg|
|Iodine||200 mcg||220 mcg||N/A||N/A|
|Iron||27 mg||N/A||18 mg||30-60 mg|
|Vitamin A||10,000 IU||10,000 IU||8,000 IU||N/A|
|Vitamin B6||1.9 mg||N/A||2.5 mg||N/A|
|Vitamin B12||2.6 mcg||N/A||8 mcg||N/A|
|Vitamin C||85 mg||N/A||60 mg||N/A|
|Vitamin D||600 IU||N/A||400 IU||N/A|
|Vitamin E||N/A||N/A||30 IU||N/A|
American College of Obstetricians and Gynecologists (ACOG); Centers for Disease Control and Prevention (CDC); Docosahexaenoic Acid (DHA); Food and Drug Administration (FDA); World Health Organization (WHO) N/A = No recommendation available
Omega-3 Fatty Acids and Docosahexaenoic Acid (DHA)
Increased intake of omega-3 fatty acids has been associated with decreased maternal depression, reduced risk of preterm birth, a decline in pediatric allergy rates, improved developmental and neurocognitive outcomes in infants, as well as higher visual acuity.8,9 It is recommended that pregnant women consume 650 mg of omega-3 fatty acids, 300 mg of which should be DHA. This may be obtained through fish oil supplementation or proper diet.10 Most seafood, including fish, contain these essential omega-3 fatty acids.11 The primary source for infant DHA intake is dependent on maternal intake.8
To obtain necessary amounts of DHA, pregnant women can consume approximately 1 to 2 servings of seafood per week.11 Sufficient consumption of seafood would reduce the need for a supplement high in DHA. Two servings of seafood are enough to aid in fetal development and limit the potential to be negatively affected by mercury or toxins in seafood.11
DHA has been shown to aid in growth and development of fetal central nervous system as it is a structural fat in the brain and eyes.10 A deficiency in omega-3 fatty acids during pregnancy has been associated with visual deficits in the fetus.11 Higher levels of omega-3 supplementation during pregnancy, ranging from 528-2700 grams per day, have been shown to increase cord blood omega-3 fatty acid incorporation when compared to approximately 100 mg per day.8
Pregnant women in the United States tend to lack sufficient omega-3 fatty acids, often due to fear of mercury or contaminants.11 In addition, socioeconomic status affects quantity and quality of omega-3 fatty acids obtained by pregnant women.8 During pregnancy, levels of inflammatory markers are increased, which aids in maintaining a healthy pregnancy by protecting from invading organisms.12 Increased adipose mass is associated with activation of inflammatory pathways.
Excessively high levels of inflammation, such as in overweight pregnant women, are associated with low birth weight, preterm delivery, gestational diabetes, and pre-eclampsia.12 High levels of inflammation during pregnancy may also increase risk of metabolic diseases for the fetus such as obesity, type 2 diabetes, dyslipidemia, and hypertension later in life. Adequate omega-3 supplementation may reduce inflammation in obese or overweight pregnant women, as well as decrease expression of inflammatory genes in adipose tissue or placenta.12 Omega-3 supplementation also reduces plasma triglyceride levels, a cardiovascular risk factor.12
It is important to consume omega-3 fatty acids with DHA during the third trimester of pregnancy as this is when the most neural and retinal development occurs.9,10 In addition, the third trimester is when maternal DHA stores are mobilized and placental transfer of DHA is preferential to other fatty acids and will determine levels of DHA incorporated into the infant brain.8
Pyridoxine (Vitamin B6) and Cobalamin (Vitamin B12)
Vitamin B6 helps form red blood cells and helps the mother’s body appropriately utilize protein, fat, and carbohydrates to benefit the fetus.2 Vitamin B6 also aids with reducing nausea and vomiting during pregnancy.13 When compared to a placebo group, the severity of nausea was lower in women who took vitamin B6 or ginger with 46% of placebo recipients developing heartburn, stomachache, and nausea during treatment, compared to only 16% of women taking vitamin B6.13 Vitamin B12 is also needed to form red blood cells and maintain the nervous system.2 Low levels of B12 during pregnancy have been shown to contribute to anemia and may cause infertility.14 Recommendations for Vitamin B6 and B12 should be considered regardless of trimester.
Folic acid is essential in preventing birth defects, such as neural tube defects, involving the brain and spine.2 Folic acid supports the growth and proper development of the fetus and placenta.2 It is recommended that folic acid be taken beginning at least 1 month before pregnancy, as well as during pregnancy.2 A daily consumption of 400 mcg of folic acid before and during pregnancy reduces the chance of having neural tube defects.15 In a study of 2104 pregnant women given a folic acid supplement, no neural tube defects were seen, whereas 6 neural tube defects were seen among 2052 pregnancies given trace element supplement.16 A folic acid supplement is highly recommended for women planning pregnancy to minimize the chance of neural tube defects.16
Pregnancy increases iron requirements as it aids in production of increased blood volume and red blood cells for transfer of oxygen to the fetus.2 If iron levels are low during pregnancy, there is an increased risk of preterm delivery or low birth weight.2,17 In a study of 60 women who took an iron supplement during pregnancy, the mean birth weight that was 30.81 grams greater than those women who did not take an iron supplement.17 In addition, taking an iron supplement reduced the risk of anemia for the mother by 70%.17 A specific trimester has not been discussed as to when iron should be taken.
According to the WHO, pregnant women may require a greater supplementation of iodine as it is essential for brain development of the fetus.7 A lack of iodine during pregnancy may lead to brain damage in the child as the concentration of thyroxine (T4) decreases and the child may experience neurologic abnormalities.18 The diminished T4 levels may also cause hypothyroidism and possibly goiter for the mother and fetus.18 Suggestions for iodine should be considered regardless of trimester and may be taken throughout the whole pregnancy.
Calcium and Vitamin D
Calcium is essential during pregnancy as it aids in building strong bones and teeth for the fetus.2,19 Calcium deficiency is rare, but is related to hypertensive disorder during pregnancy. Supplementation of calcium may help reduce hypertensive disorder during pregnancy and risk of pre-eclampsia.19 In addition, decreased intake of calcium can result in a vitamin D deficiency.20
Vitamin D is necessary to build the baby’s teeth and bones by promoting the absorption of calcium.2 It also aids in development of healthy eyesight and skin, and may help decrease the risk of preeclampsia and preterm birth.2,20 Preterm births have been seen to be lowest for women who conceived during the summer and fall, when vitamin D intake is highest.20 Vitamin D deficiency may not only lead to preeclampsia, but other complications in the child, such as asthma.21 African American women have a higher risk of preeclampsia and complications, and should consider vitamin D supplementation during pregnancy.20 Vitamin D and calcium supplementation should be considered throughout the whole pregnancy.
Preeclampsia consists of 2 stages. The first stage involves reduced perfusion of the maternal blood vessels to the placenta, while the second stage is the cascade of events afterwards.20 Vitamin D helps genes associated with normal implantation and angiogenesis function properly to avoid the stages of preeclampsia.20
Women in the United Kingdom provided with a multivitamin containing 900 IU of vitamin D per day reduced the chance of preeclampsia by 32%.20 A similar trend was found in Norway, where pregnant women who were given 15-20 mcg of vitamin D in their first half of pregnancy decreased their risk of preeclampsia by 25%.20 In addition, the highest incidences of preeclampsia have been reported in the winter, when sun exposure and vitamin D intake is lowest.20 Most individuals' main source of vitamin D comes from the sun, so pregnant women living in areas where sunlight exposure is limited should be taking a vitamin D supplement.20
Like calcium, Vitamin A helps promote bone growth for the baby.2 In addition, vitamin A aids in forming healthy skin and eyesight.2 An upper limit for Vitamin A consumption exists at no more than 10,000 units per day due to some reports of teratogenicity above that level. Pregnant women lacking vitamin A have shown negative impact on fetal pancreas development.22 There is no specific trimester in which Vitamin A should be taken, however special attention should be paid to maintaining limits below the recommended limit.
A 25-year-old pregnant female in her first trimester with no significant medical history, no known allergies and no current prescription or OTC medications comes to the pharmacy counter asking for a prenatal vitamin recommendation. Her obstetrician advised her to start a multivitamin and that she could obtain 1 from the pharmacy. She brings a bottle to the counter with the following label:
Directions: Take one capsule by mouth once daily
|Folic Acid/Folate||800 mcg|
|Vitamin A||4000 IU|
|Vitamin B6||2.5 mg|
|Vitamin B12||4 mcg|
|Vitamin C||100 mg|
|Vitamin D||400 IU|
|Vitamin E||11 IU|
- Calcium is low when compared to the FDA and ACOG recommendations. It contains only 150 mg of calcium, whereas the recommended dosage is approximately 1,000 mg (ACOG) – 1,500 mg (WHO). Low calcium is common in a variety of prenatal supplements, thus, additional calcium supplementation is necessary to meet the recommended dose if this product is used.
- The prenatal multivitamin contains 800 mcg of folic acid which is equivalent to the FDA's suggestion. ACOG, CDC, and WHO indicate that 400 mcg of Folic Acid should be consumed during pregnancy.
- Regarding the iodine dosage, CDC and ACOG recommend between 200 and 220 mcg of iodine per day for women during pregnancy. The iodine dose of 150 mcg in the example supplement does not fall in the range of recommended iodine intake. It may be beneficial to obtain additional iodine through diet.
- In addition, a prenatal with higher dosage of Vitamin A may be of benefit as the example supplement only contains 4,000 IU while WHO recommends 8,000 IU. CDC and ACOG recommend to not exceed 10,000 IU of Vitamin A per day.
- The vitamin B6 concentration of the multivitamin meets the FDA recommendation of 2.5 mg but exceeds ACOG recommendation of 1.9 mg. The vitamin B12 concentration of 4 mcg lies between ACOG's suggestion of 2.6 mcg and FDA's 8 mcg.
- The vitamin C quantity of 100 mg exceeds ACOG's recommendation of 85 mg and FDA's 60 mg.
- 400 IU of Vitamin D is contained in this supplement which is equivalent to the FDA's recommendation.
- Even though benefits have been exhibited from DHA supplementation in pregnancy none of the organizations indicate a specific dosage to consume. This multivitamin contains 200 mg of DHA while other articles have recommended 300 mg DHA.8
Overall, the prenatal multivitamin contains all the vitamin and mineral supplementation as recommended by ACOG, CDC, FDA, and WHO. However, it does not meet the recommended dosage for calcium, folic acid, iodine and vitamin A. It may still be a viable option if the patient is aware of the role of vitamin and minerals during pregnancy and may consider additional supplementation (through diet or additional products). The patient may also find an alternative prenatal vitamin that contains an appropriate amount of all vitamins and minerals, which may include a prescribed multivitamin as opposed to an over-the-counter product.
The recommendations in this guide focus on women who are pregnant without concomitant disease states or medications. However, the pharmacist should keep in mind that additional vitamins and minerals may be beneficial in certain populations, disease states, or concomitant medications. Each vitamin and mineral has its own purpose and benefit for the mother and fetus.
The pharmacist can help provide the patient with recommendations regarding supplements while being aware that the perfect prenatal multivitamin may not exist. Thus, the pharmacist should inform the patient of the positive effects and potential risk associated with vitamin and mineral supplementation.
- Mcalpine J, Scott R, Scuffham P, Perkins A, Vanderlelie J. The association between third trimester multivitamin/mineral supplementation and gestational length in uncomplicated pregnancies. Women Birth. 2016;29(1),41-46.
- Nutrition during pregnancy. American College of Obstetricians and Gynecologists. Accessed here: https://www.acog.org/-/media/Womens-Health/nutrition-in-pregnancy.pdf. May 18, 2018.
- Folic Acid. Center for Disease Control and Prevention. Accessed here: https://www.cdc.gov/ncbddd/folicacid/index.html. May 18, 2018.
- CDC. Trace Elements: Iodine. National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population. Center for Disease Control and Prevention. Accessed here: https://www.cdc.gov/nutritionreport/pdf/Nutrition_Book_complete508_final.pdf. May 18, 2018.
- Dietary Supplement Labeling Guide: Appendix C. Food and Drug Administration. Accessed here: https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/DietarySupplements/ucm070620.htm. May 18. 2018.
- WHO recommendation on calcium supplementation during pregnancy. World Health Organization. Accessed here: https://extranet.who.int/rhl/topics/preconception-pregnancy-childbirth-and-postpartum-care/antenatal-care/who-recommendation-calcium-supplementation-during-pregnancy. May 18, 2018.
- WHO. Guideline: Daily iron and folic acid supplementation in pregnant women. Geneva, World Health Organization. 2012. Accessed here: http://apps.who.int/iris/bitstream/handle/10665/77770/9789241501996_eng.pdf?sequence=1. May 18, 2018.
- Nordgren TM, Lyden E, Anderson-Berry A, Hanson C. Omega-3 fatty acid intake of pregnant women and women of childbearing age in the United States: potential for deficiency? Nutrients. 2017;9(3):197.
- Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation. Am J Clin Nutr. 2009;89(2):678S–684S.
- Greenberg JA, Bell SJ, Ausdal, WV. Omega-3 fatty acid supplementation during pregnancy. Rev Obstet Gynecol. 2008;1(4):162–169.
- Coletta JM, Bell SJ, Roman AS. Omega-3 Fatty Acids and Pregnancy. Rev Obstet Gynecol. 2010;3(4):163-171.
- Kordoni ME, Panagiotakos D. Can dietary omega-3 fatty acid supplementation reduce inflammation in obese pregnant women?.Hell J Atheroscler. 2017;8:121-128.
- Firouzbakht M, Nikpour M, Jamali B, Omidvar S. Comparison of ginger with vitamin B6 in relieving nausea and vomiting during pregnancy. Ayu. 2014;35:289-293.
- Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008;29:101-107.
- Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001;285(23):2981-2986.
- Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. NEJM. 1992;327(26):1832-1835.
- Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;7:CD004736.
- Harding KB, Peña-Rosas JP, Webster AC, et al. Iodine supplementation for women during the preconception, pregnancy and postpartum period. Cochrane Database Syst Rev. 2017;3:CD011761.
- NHS. Vitamins, supplements, and nutrition in pregnancy. National Health Service. 2017 Jun 01.
- Bodnar LM, Simhan HN. Vitamin D may be a link to black-white disparities in adverse birth outcomes. Obstet Gynecol Surv. 2010;65(4):273-284.
- Hollis BW, Wagner CL. Vitamin D supplementation during pregnancy: improvements in birth outcomes and complications through direct genomic alteration. Mol Cell Endocrinol. 2017;453:113-130.
- Chien CY, Lee HS, Cho CH, et al. Maternal vitamin A deficiency during pregnancy affects vascularized islet development. J Nutr Biochem. 2016;36:51-59.