<h2>Description</h2>Pregnancy is a critical period when maternal nutrition and lifestyle choices are major influences on mother and child health.1 Inadequate levels of key nutrients during crucial periods of foetal development may predispose the infant to chronic conditions in later life. Improving the wellbeing of mothers, infants, and children is vitally important to the health of the next generation.1 <h2>Practice points</h2><ul><li>Folic acid: prevents the first and second-time occurrence of neural tube defects (NTD) such as spina bifida and anencephaly.22 400-500 mcg daily at least 4 wks before conception and for the first 12 weeks of pregnancy. 5 mg folic acid is recommended for high-risk women, e.g. Hx NTD, diabetes mellitus and body mass index (BMI &gt;30kg/m2)23</li><li>Iodine: vital for the production of maternal thyroid hormone, foetal brain and central nervous system (CNS) development.23 150 mcg daily is recommended1</li><li>Vitamin D: supports bone and muscle health, low maternal levels in pregnancy are associated with low neonate levels, which are associated with impaired skeletal development and increased incidence of hypocalcaemic seizures in the neonate.6 Assess 25-(OH)D levels and recommend dose accordingly</li><li>Omega 3: important for neurodevelopmental outcome and reduction of preterm labour. If the dietary intake of omega-3 is low, consider supplementation. A Cochrane review found the optimum dose to prevent pre-term births was a daily supplement of between 500 and 1000 mg of an omega-3 (containing at least 500 mg of DHA) starting at 12 weeks of pregnancy29</li><li>An assessment of individual needs: dictates the recommendation of iron, calcium and vitamin B12 in pregnancy</li></ul>

<h2>Management principles</h2><ul><li>Manage in conjunction with a qualified specialist practitioner2</li><li>Identify individuals with special needs: overweight, obese, those with diabetes mellitus, vegetarians, vegan and history of anaemia</li><li>Aim is to move towards optimal health with minimally invasive interventions2</li><li>Encourage simple lifestyle strategies to optimise wellbeing: adequate rest, stress management, exercise, adequate sleep, fresh air, adequate sun exposure3</li><li>Advise cessation of smoking and recreational drug use; avoid alcohol consumption; avoid potential teratogens such as certain medications and X-rays4</li><li>Maintain optimal gestational weight4</li></ul>

Management

<h2>Primary recommendations</h2><h2>FOLIC ACID</h2>Mechanism of action<ul><li>Necessary for the production and maintenance of new cells, which is especially important during periods of rapid cell division and growth14</li></ul>Research<ul><li>Adequate periconceptional folate has the capacity to prevent 70% of all cases of neural tube defects15</li><li>The neural tube has normally closed completely by the end of the 4th week after fertilisation14, therefore, it is recommended to supplement prior to conception</li></ul>Dosage<ul><li>All women preconception: 400-500 mcg daily for at least 4 weeks prior to pregnancy and for the first 12 weeks of gestation22,23</li><li>High risk (previous NTD, anticonvulsant medication, gestational diabetes mellitus, malabsorption and a BMI &gt;30 kg/m2): 5 mg daily for at least 4 weeks prior to pregnancy and for the first 12 weeks of gestation22,23</li></ul>Adverse effects<ul><li>Generally, well tolerated in doses less than 1 mg per day</li><li>A dose of 5 mg per day can cause abdominal cramps, diarrhea, and rash6</li></ul>Key interactions<ul><li>Phenytoin: may decrease drug effect. The interaction is likely. Use only under the supervision of healthcare professional (HCP) and monitor phenytoin blood concentration7 </li><li>Co-trimoxazole, sulphazalazine, phenytoin, phenobarbital, primidone, and methotrexate: may decrease blood levels of the nutrient. Interaction is possible. Assess and monitor nutrient status and supplement if indicated7 </li><li>Fluorouracil and capecitabine: folic acid may increase the toxicity of fluorouracil and capecitabine. Interaction is possible. Avoid concomitant use7 </li><li>Methotrexate: interaction is possible. Follow the Australian Medicines Handbook’s recommendations for concurrent use of folic acid and methotrexate7</li></ul><h2>IODINE</h2>Mechanism of action<ul><li> Production of maternal thyroid hormone, fetal brain and CNS development23</li><li> During pregnancy the thyroid gland produces 50% more thyroid hormone than usual; therefore, iodine intake must be increased accordingly. A deficiency during critical periods of brain development may impair the development of the growing brain10,11</li></ul>Research<ul><li>Research shows that Australian women are typically not receiving the National Health Medical Research Council’s (NHMRC) recommendations for iodine intake24 </li><li>Dosage</li><li><ul><li>Supplement with 150 mcg/day1</li><li>The NHMRC recommends supplementation for all Australian pregnant and breastfeeding women and any women considering pregnancy11</li><li>World Health Organization (WHO) recommend a daily dose of an iodine supplement 250 mcg/day for pregnant women27</li></ul></li><li>Adverse effects</li><li><ul><li>Orally well tolerated when taken in amounts that do not exceed the Tolerable Upper Intake Level (UL)25</li><li>UL for women adults 19+ yr and pregnancy 19-50 yr 1100 mcg/day26</li></ul></li><li>Key interactions</li><li><ul><li>Amiodarone: may increase blood levels of iodine. The interaction is possible. Use with caution under the supervision of an HCP and monitor21</li><li>Antithyroid drugs: may increase drug effects. Iodine may precipitate hypothyroidism. The interaction is theoretical. Use with caution under the supervision of an HCP and monitor21</li><li>Lithium: iodine at high doses may increase the hypothyroid activity of lithium carbonate. The interaction is possible. Use with caution under the supervision of an HCP and monitor21</li><li>Thyroid hormone: iodine at very high doses may precipitate or exacerbate hyper or hypothyroidism. Use with caution under the supervision of an HCP and monitor21</li></ul></li><li><h2>VITAMIN D</h2></li><li> Mechanism of action <ul><li>Maintains calcium and phosphorous metabolism assisting bone and muscle health13 </li><li>Low maternal levels in pregnancy are associated with low neonatal levels which in turn, are associated with impaired skeletal development and an increased incidence of hypocalcaemic seizures in the neonate6 </li><li>Deficiency is known to be an important risk factor or the development of osteoporosis in later life for the mother6</li></ul> Research <ul><li>Vitamin D deficiency has been linked to adverse events in pregnancy such as pre-eclampsia, preterm birth, small-for-gestational-age birth and gestational diabetes4 </li></ul> Dosage <ul><li>Blood tests for vitamin D measure 25-(OH)D nmol/L</li><li>Pregnant women with below 50 nmol/L <ul><li>Levels 30–49 nmol/L, commence 1000 IU (25 mcg)/day6</li><li>Levels &lt;30 nmol/L should commence 2000 IU (50 mcg)/day6</li><li>Check 25-(OH)D level at 28 weeks gestation6</li></ul> </li><li>Pregnant women above 50 nmol/L12 <ul><li>These women should take 400 IU (10mcg)/day as part of a pregnancy multivitamin6</li><li>Supplement to achieve 25(OH)D ≥50 nmol/L6</li></ul> </li><li>Adverse effects</li><li><ul><li>Well tolerated when taken in appropriate doses28</li></ul></li><li>Key interactions</li><li><ul><li>Anticonvulsants and antiretrovirals: vitamin D3 improves bone mineral density and decreases the risk of bone-related side effects. No significant adverse effect expected. Assess nutrient status and supplement if indicated21</li><li>Atorvastatin: vitamin D3 may decrease the blood level of this drug via induction of CYP3A4. Interaction is possible. Use with caution under the supervision of an HCP and monitor21</li><li>Budesonide (oral): vitamin D3 may increase drug efficacy. No significant adverse effect expected in humans. Assess nutrient status and supplement if indicated21</li><li>Cimetidine: inhibits an enzyme involved in the conversion of vitamin D to its active form in the liver and affects vitamin D metabolism in men. Assess nutrient status and supplement if indicated21</li><li>Heparin and low-molecular-weight heparin (LMWH): decrease the metabolism of vitamin D to its active form. Assess nutrient status and supplement if indicated21</li><li>Orlistat: vitamin D absorption may be decreased. Assess nutrient status and supplement if indicated. The interaction may be minimised by separating the dose of medication and vitamin D by at least 2 hours21</li><li>Sirolimus: vitamin D3 may increase the metabolism of sirolimus. Interaction theoretical. Avoid concomitant use21</li><li>Thiazide diuretics: vitamin D3 may increase the risk of hypercalcaemia if taken with calcium supplements and/or thiazide diuretics. Use with caution under the supervision of an HCP and monitor21</li></ul></li><li><h2>OMEGA-3 FATTY ACIDS</h2></li><li> Mechanism of action <ul><li>Neurodevelopmental outcome6</li><li>Reduction of pre-term labour6</li><li>Increased foetal growth. A possible mechanism for this is that omega-3 increases the ratio of prostacyclin to thromboxane, thereby reducing blood viscosity and facilitating increased placental blood flow, which benefits foetal growth30</li></ul> Research <ul><li>A Cochrane review of 70 randomised controlled trials in over 19,000 women, comparing omega-3 fatty acids as supplements or as food, stand-alone interventions or with a co-intervention found that increasing omega-3 fatty acids intake during pregnancy reduced the risk of preterm birth (&lt;37 weeks) by 11% - from 134 to 119 per 1000 births [risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97] and reduced the risk of early preterm birth (&lt;34 weeks) by 42% - from 46 to 27 per 1000 births (RR 0.58, 95% CI 0,44 to 0.77)29</li><li>Supplementing pregnant women with omega-3 fatty acids during the third trimester may increase birth weight and gestational age, potentially leading to better outcomes for the infant30 </li></ul> Dosage <ul><li>Women whose dietary intake is low, should consider supplementation6 </li><li>A Cochrane review found the optimum dose to reduce preterm births was a daily supplement containing between 500 and 1000 mg of long-chain omega-3 fats (containing at least 500 mg of DHA) starting at 12 weeks of pregnancy29</li></ul> Adverse effects <ul><li>Women may experience fishy burps as a result of taking fish oil supplements. Advise that fish oil supplements are best taken with food and odourless fish oil capsules are available</li></ul> Key interactions <ul><li>Antihypertensive drugs: may have an additive hypotensive effect depending on fish oil dose. BP should be monitored when the patient is on high-dose fish oil21</li><li>Anticoagulant and antiplatelet agents: high doses of fish oil (&gt;3 g/day omega-3 fatty acids) may increase the risk of bleeding with these drugs. There is conflicting data: multiple clinical trials have found no increase in the risk of bleeding with antiplatelet or anticoagulant drugs, however, there are some studies that suggest an interaction, particularly at higher doses. Use with caution under the supervision of an HCP and monitor21</li><li>Chemotherapeutic agents: may decrease drug effect. Avoid concomitant use21</li></ul> </li></ul> </li></ul> For more information on key interactions visit: <a href="~/link.aspx?_id=4471DACF65C148EA8FD82B23FD6712D4&_z=z">https://www.blackmoresinstitute.org/interactions</a>

Primary

<h2>Secondary recommendations</h2><h2>IRON</h2>Mechanism of action<ul><li>Increased iron demands in pregnancy due to expanded red cell volume, blood loss at delivery, demands of the developing foetus and placenta6</li><li>Low levels may increase the risk for premature birth, low birth weight and adverse effects on cognitive and physical development8</li></ul>Research<ul><li>For pregnancy-related iron deficiency, taking iron at an average dose of 20-225 mg of elemental iron per day, increases maternal haemoglobin by up to 1 gram/dL when compared with placebo, and reduces the risk of maternal anaemia by 62% to 73%32</li></ul>Dosage<ul><li>Supplementation is recommended for those with established deficiency and those at risk of deficiency (including vegetarians, women with a multiples)6</li><li>Haemoglobin levels should be checked at the first antenatal visit and again at approximately 28 weeks’ gestation6</li><li>Pregnancy-related iron deficiency – elemental iron 20-225 mg/day has been used32</li></ul>Adverse effects<ul><li>Orally, iron can cause gastrointestinal irritation, abdominal pain, constipation or diarrhoea, nausea, and vomiting</li><li>At doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron in adults with normal iron stores, gastrointestinal adverse effects are uncommon32</li><li>Certain forms of iron such as iron glycinate are gentler on the digestive system with lower constipation and low nausea effects, and the iron is more bioavailable</li><li>Key interactions</li><li>For each of these drugs avoid concomitant use. If iron is indicated, an interaction may be reduced by taking 4-6 hours before or 2 hours after drug:21</li><li><ul><li>Captopril: may decrease blood levels of the drug. Interaction is possible, the severity of outcome moderate21</li><li>Penicillamine: may decrease drug absorption. An interaction is likely and severity of outcome moderate-high21</li><li>Mycophenolate: may decrease drug absorption. Interaction is possible and severity of outcome high21</li><li>Tetracycline and quinolone: may decrease drug absorption. An interaction is likely and severity of outcome moderate-high21</li><li>Thyroid hormone: may decrease drug absorption. An interaction is likely and severity of outcome moderate21</li></ul></li></ul><h2>VITAMIN B12</h2>For vegetarians and vegans, supplementation is recommended.6 Vegan mothers will need supplementation throughout pregnancy and during lactation in sufficient amounts to ensure adequate amounts for themselves and the child.19Mechanism of action<ul><li>Untreated maternal deficiency of B12 may cause neurological sequelae in exclusively breastfed infants6</li><li>Thrombophilic tendency may be minimised by ensuring adequacy of B12 along with folate, Vitamin B2 and B66</li></ul>Research<ul><li>A systematic review found a B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49).37 Further randomised controlled trials are needed37</li></ul>Dosage<ul><li>Pregnancy RDI is 2.6 μg/day19</li></ul>Adverse effects<ul><li>Oral supplementation appears to be well tolerated18</li></ul>Key interactionsFor each of these drugs avoid concomitant use. If iron is indicated, an interaction may be reduced by taking 4-6 hours before or 2 hours after drug:21<ul><li>Chloramphenicol: major interaction rating, do not take this combination33</li></ul><h2>CALCIUM</h2>For pregnant women who are avoiding dairy (e.g. lactose intolerant) and who are not consuming alternative high calcium foods or who are falling under the calcium RDI of 1300 mg (14-18 years) and 1000 mg (19-50 years).6Mechanism of action<ul><li>Antihypertensive effect: inadequate dietary calcium can play a role in the development of hypertension34</li><li>Bone mineral density effect: calcium appears to play a role in the development of hypertension34</li></ul>Research<ul><li>A Cochrane systematic review reported a benefit of calcium supplementation, with at least 1000 mg/day during pregnancy, in reducing the incidence of hypertensive disorders and preterm labour. The effect on pre-eclampsia was greater for women with low baseline calcium intake6</li></ul>Dosage<ul><li>Supplementation of ≥1000 mg/day may reduce the incidence of hypertensive disorders (including pre eclampsia) and preterm labour, especially in those with low dietary intake, and is recommended for those who avoid dairy or other high -calcium foods6</li></ul>Adverse effects<ul><li>Oral calcium is well-tolerated. More common adverse effects are gastrointestinal in nature and include belching, flatulence, constipation, diarrhoea, and stomach upset34</li></ul>Key interactions<ul><li>Beta-blockers (atenolol, sotolol): calcium may decrease absorption of the drug. Possible interaction and moderate severity of outcome. The interaction may be minimised by separating the dose of medication and calcium by at least 2 hours21</li><li>Bisphosphonates, tetracycline or quinolone antibiotics, thyroid hormones: calcium may decrease the absorption of the drug. Interaction is possible and moderate severity of outcome. The interaction may be minimised by separating the dose of medication and calcium by at least 2 hours</li><li>Calcium channel blockers (verapamil): calcium may decrease the hypotensive effect of the drug. Interaction is possible and the severity of outcome is moderate. Use with caution under the supervision of an HCP and monitor</li><li>Thiazide diuretics: may increase the risk of hypercalcaemia with these drugs. Interaction is possible and the severity of outcome moderate. Use with caution under the supervision of an HCP and monitor</li></ul><h2>RESTRICTION</h2>Vitamin ALimit vitamin A supplements to 3000 mcg (10 000 IU) per day. Vitamin A over this level can lead to an increased risk of miscarriage and CNS malformations. Dietary sources do not pose a risk at normal levels. All synthetic derivatives of retinol should be ceased at least one month prior to conception.23 For more information on key interactions visit: <a href="~/link.aspx?_id=4471DACF65C148EA8FD82B23FD6712D4&_z=z">https://www.blackmoresinstitute.org/interactions</a>

Secondary

<h2>Diet and lifestyle recommendations</h2><ul><li>Eat a healthy and balanced diet: include vegetables and fruit, whole grains, protein (lean meats, fish, eggs, tofu, nuts and seeds, legumes/beans), dairy and/or alternatives. Recommend women who are underweight or overweight to see their GP or a dietician6,35</li><li>Drink plenty of water: pregnant women have increased water requirements6,35</li><li>Enjoy daily exercise: low to moderate-intensity physical activity during pregnancy is associated with a range of health benefits and is not associated with adverse outcomes35</li><li>Quit smoking: if the woman smokes, emphasise the benefits of quitting as early as possible in the pregnancy and discuss any concerns she or her family may have about stopping smoking. Recommend smoking cessation and cognitive behavioural therapy35</li><li>Stop drinking alcohol: maternal alcohol consumption may adversely affect the developing foetus35</li><li>Limit caffeine: The Australian Dept. of Health and Ageing suggests limiting intake during pregnancy to 2-3 cups of coffee or 6 cups of tea a day (i.e. &lt;300 mg caffeine). Also, limit caffeinated beverages such as coke and energy drinks35</li><li>Avoid long distance travel: it is associated with an increased risk of venous thrombosis and pulmonary embolism35</li><li>Visit your dentist: for an oral health check35</li><li>A good night’s sleep of up to 8 hours a night: is essential in pregnancy, and post-partum, to help reduce fatigue, depression mood disturbances and exhaustion35</li><li>Vegans and vegetarians: are likely to have increased deficiencies in amino acids, zinc, calcium, iron and vitamins D and B12.36 Refer to a GP to assess</li><li>Avoid fish containing high levels of mercury (shark, billfish, tuna, swordfish): eat two to three serves of other types of fish per week36</li><li>Avoid pate, soft cheeses (e.g. feta, brie, blue vein), prepackaged salads, deli meats, and chilled/smoked seafood: wash all fruit and vegetables before eating, to reduce exposure to listeriosis36</li><li>Avoid cat litter, garden soil, raw/undercooked meat, and unpasteurised milk products, wash fruit and vegetables: to reduce exposure to Toxoplasmosis36</li></ul>

Diet & lifestyle

<h2>References</h2>1. Position of the Academy of Nutrition and Dietetics: Nutrition and Lifestyle for a Healthy Pregnancy Outcome. J Acad Nutr Diet. 2014;114:1099-1103. 2. Sarris J, Wardle J. Clinical naturopathy 2e. Elsevier 2014 3. Kotsirilis V, Vitetta L, Sali A. A guide to evidence-based integrative and complementary medicine. Elsevier 2011 4. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2013. College Statement - Routine Antenatal Assessment in the Absence of Pregnancy Complications 5. NHMRC 2016. Healthy Eating During Your Pregnancy. N55b 6. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2014. College Statement - Vitamin and Mineral Supplementation and Pregnancy.7. WHO. Guideline: Daily iron and folic acid supplementation in pregnant women. Geneva, World Health Organization, 2012. 8. Peña-Rosas JP, Viteri FE. Effects and safety of preventive oral iron or iron+folic acid supplementation for women during pregnancy (Review) Cochrane Database of Systematic Reviews 2009, Issue 4. 9. Melamed N et al. Iron supplementation in pregnancy – does he preparation matter? Arch Gynecol Obstet 2007;276:601-04 10. NHMRC 2009. Literature Review: Iodine Supplementation During Pregnancy and Lactation 11. NHMRC 2010. Public Statement: Iodine supplementation for pregnant and breastfeeding women. 12. Paxton GA et al. Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement. MJA 2013;198(3) 13. Nowson CA et al. Vitamin D and health in adults in Australia and New Zealand: a position statement. MJA 2012;19;6(11) 14. Macaldowie A &amp; Hilder L 2011. Neural tube defects in Australia: prevalence before mandatory folic acid fortifi cation. Cat. no. PER 53. Canberra: AIHW. 15. National Institute of Clinical Studies. Evidence-Practice Gaps Report Vol 2 2005. Encouraging periconceptual use of folic acid supplements. 16. Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, 10-14 November, 2008, WHO, Geneva. 17. Hofmeyr GJ et al. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews 2014, Issue 6. Art. No.: CD001059. DOI:10.1002/14651858.CD001059.pub4. 18. Braun L, Cohen M. Herbs and Natural Supplements – an evidence-based guide. 4th ed. Elsevier 2015 19. NHMRC. Nutrient Reference Values for Australia and New Zealand. National Health and Medical Research Council 200520. Natural medicines. Folic acid monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1017 Accessed 4th March 201921. Blackmores Institute. Complementary Medicines Interaction Guide. https://www.blackmoresinstitute.org/interactions Accessed 2nd April 201922. De-Regil L et al. Effects of safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database of Systematic Review 2015, Issue 1223. Dorney E et al. Preconception care. Australian Journal of General Practice. Vol 47, No. 7, July 201824. Hine T et al. Iodine-containing supplement use by pregnant women attending antenatal clinics in Western Australia. Aust N Z J Obstet Gynaecol. 201825. Natural medicines. Iodine monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=35 Accessed 4th March 201926. National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand. https://www.nrv.gov.au/nutrients/iodine Accessed 4th March 201927. World Health Organization. Iodine supplementation in pregnant and lactating women. Guidance summary. https://www.who.int/elena/titles/guidance_summaries/iodine_pregnancy/en/ Accessed 3rd April 201928. Natural medicines. Vitamin D monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=929 Accessed 4th March 201929. Middleton P et al. Omega-3 fatty acid addition during pregnancy. Cochrane Database of Systematic Reviews 2018, Issue 11. DOI:10.1002/14651858. CD00340230. Vinding R et al. Fish oil supplementation in Pregnancy Increases Gestational Age, Size for Gestational Age, and Birth Weight in Infants: A Randomized Controlled Trial. J. Nutr 9 November 2018. https://doi.org/10.1093/jn/nxy20431. South Australian Health &amp; Medical Research Institute (SAHMRI) Taking omega-3s to give your baby a great start in life. https://www.sahmriresearch.org/our-research/themes/healthy-mothers-babies-children/research-list/omega3 Accessed 3rd April 201932. Natural medicines. Iron monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=912 Accessed 3rd April 201933. Natural medicines. B12 monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=926 Accessed 3rd April 201934. Natural medicines. Calcium monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional. aspx?productid=781 Accessed 3rd April 201935. Australian Government Department of Health. Clinical practice guidelines. Pregnancy care. 2018 edition36. Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 9th edn. Melbourne. RACGP, 2016. Available at https://www.racgp.org.au/clinical-resources/clinical-guidelines/key-racgp-guidelines/view-all-racgp-guidelines/red-book/preventive-activities-prior-topregnancy. Accessed 4th March 201937. Rogne T et al. Associations of maternal vitamin B12 concentration in pregnancy with the risks of preterm birth and low birth weight: A systematic review and meta-analysis of individual participant data. Am J Epidemiol 2017 Feb 1; 185(3):212-223

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