<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.1 400-500 mcg daily for all women in preconception at least 4 wks before conception. 5mg folic acid is recommended for high-risk women, e.g. Hx NTD, diabetes mellitus and body mass index (BMI &gt;30 kg/m2)2,3</li><li> Iodine: vital for the production of maternal thyroid hormone, foetal brain, and central nervous system (CNS) development. 150 mcg daily is recommended2,3</li><li>Vitamin D: seems to have a preconception role in immunomodulatory and tissue remodeling responses.4 Assess levels and recommend dose accordingly2,3</li><li>Other important preconception nutrients: include omega-3 fatty acids, vitamin C, vitamin E, B vitamins, calcium, iron, zinc, selenium and CoQ10</li></ul><h2>Description</h2><ul><li>Preconception care (PCC) includes counselling and the provision of biomedical, behavioural and social health interventions to optimise the health of women and their partners prior to pregnancy and improve health-related outcomes for themselves and their children2</li><li>Each year it is estimated that 10% of Australian women become pregnant, yet only 50% of Australian women plan their pregnancies2</li><li>There is growing evidence to support that optimising health in the preconception period is crucial to improving both short and long term outcomes for mother and babies2</li><li>Poor maternal health and diet in the early stages of pregnancy can lead to impaired fetal and infant growth, poor birth outcomes and long-term effects of cardiovascular and metabolic health2</li><li>The developmental origins of health and disease is the concept whereby the intrauterine environment is understood to have a profound impact on one’s entire lifetime health. For example, if the mother is obese at the time of conception then her child is more likely to be overweight and develop a cardiovascular and metabolic disease2</li><li>GPs report that there is a lack of women presenting in the preconception stage, they are more likely to present for acute conditions or difficulty in conceiving.2 Therefore, pharmacists as a primary caregiver play a vital role in recognising women at the preconception stage and referring them to visit their GP</li></ul>

<h2>Management guidelines</h2><ul><li>Recommend a visit to GP for preconception counselling including substance and medication use, screening for sexually transmissible infections and other infectious diseases, and weight assessment</li><li>Assess for special needs for example: overweight, obese, those with diabetes mellitus, vegetarians and vegans and history of anaemia</li><li>Recommend a preconception multivitamin that includes 500 mcg/day of folic acid, 150 mcg/day of iodine and vitamin D</li></ul>

Management

<h2>Primary recommendations</h2><h2>FOLIC ACID</h2>Mechanism of action<ul><li>Prevents the first and second-time occurrence of NTD such as spina bifida and anencephaly1</li><li>Folate has antioxidant properties and is important for oocyte quality and maturation, implantation, placentation, foetal growth in addition to organ development5</li></ul>Research<ul><li>Cochrane review of five trials, involving 7391 pregnancies (2033 with a history of pregnancy affected by NTD and 5358 with no history of NTD) shows the protective effect of daily folic acid supplementation in doses ranging from 0.36 mg (360 mcg) to 4 mg (4000 mcg) a day, with and without other vitamins and minerals, before conception and up to 12 weeks of pregnancy for preventing the reoccurrence of these defects1</li><li>The Cochrane author’s concluded that folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects1</li><li>A review of research shows that a higher intake of folic acid from food and supplements during pregnancy reduces the primary incidence of NTD by 41% to 69%6</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 gestation1</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 gestation1</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 actionNot fully understood:<ul><li> Production of maternal thyroid hormone, fetal brain and CNS development2</li></ul>Research<ul><li>Iodine deficiency acts as a chronic nutritional deficiency aggravated by pregnancy and maternal hypothyroxinemia that can imprint cells or central nervous system of the offspring and exert effects postnatally.9 The authors concluded iodine also plays a pivotal role that substantially contributes to postnatal development and plasticity or neural tissues9 </li><li>Dosage</li><li><ul><li>150 mcg daily while pregnant and breastfeeding2</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)8</li><li>UL for women adults 19+ yr and pregnancy 19-50 yr 1100 mcg/day10</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 monitor7</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 monitor7</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 monitor7</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>VITAMIN D</h2>Mechanism of action<ul><li>Preconception - immunomodulatory and tissue remodeling responses4</li><li>Reduces the risk of small-for-gestational-age babies and impaired fetal skeletal development2</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><li>New data linking Vitamin D status with pregnancy loss and live birth. The authors report increased rates of pregnancy and live birth in women with sufficient serum concentrations of 25-hyroxyvitamin D. These observations were dependent on concentrations of 25-hydroxyvitamin D preconception but not at 8 weeks gestation. This study suggested a new perspective on vitamin D and pregnancy by suggesting a target concentration for 25-hydroxyvitamin D of 75 nmol/L or more, consistent with the Endocrine Society recommendations4</li></ul>Dosage<ul><li>1000 IU/day (women with vitamin D 30-49 nmol/L)2</li><li>2000 IU/day (women with vitamin D &lt; 30 nmol/L)2</li><li>Emerging research shows that the benefits of 75nmol/L or more 25-hydroxyvitamin D for pregnant women might reflect preconception requirements for vitamin D, involving immunomodulatory and tissue remodeling responses that are distinct from the effects of vitamin D later in pregnancy. Further research is still needed4</li></ul>Adverse effects<ul><li>Well tolerated when taken in appropriate doses11</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 effect. No significant adverse effect expected. Assess nutrient status and supplement if indicated7</li><li>Atorvastatin: may decrease the blood level of drugs via induction of CYP3A4. Interaction is possible. Use with caution under the supervision of a healthcare professional and monitor7</li><li>Budesonide (oral): nutrient effect on the drug, may increase drug efficacy. No significant adverse effect expected in humans. Assess nutrient status and supplement if indicated7</li><li>Cimetidine: inhibits an enzyme involved in the conversion of vitamin D to its active form in the liver and affect vitamin D metabolism in men. Assess nutrient status and supplement if indicated7</li><li>Heparin and low-molecular-weight heparin: decrease the metabolism of vitamin D to its active form. Assess nutrient status and supplement if indicated7</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 hours7</li><li>Sirolimus: may increase the metabolism of sirolimus. Interaction theoretical. Avoid concomitant use7</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 a HCP and monitor7</li></ul></li></ul><h2>OTHER IMPORTANT PRECONCEPTION NUTRIENTS</h2><ul><li>Omega-3 fatty acids: promotes healthy circulation12 and therefore important nutrient for foetalplacental blood flow. Fatty acids are important for the reproductive processes including steroidogenesis, associations between monounsaturated fatty acids and polyunsaturated fatty acids and fecundability have been shown among normal BMI women.20 High trans fatty acid intake and low omega-3 fatty acid intake have been associated with reduced fecundity21</li><li>Vitamin C: antioxidant and important for steroidogenesis, supportive of progesterone and lowers follicle stimulating hormone.13 Vitamin C utilisation is higher around the time of ovulation and may help hormonal stimulation of normal ovulation. The developing follicle also requires adequate vitamin C to mature14</li><li>Vitamin E: antioxidant and important for steroidogenesis. Lower concentrations of vitamin E (and vitamin C) were observed among women with recurrent spontaneous abortions linked to a luteal phase defect than among women with better reproductive outcomes13</li><li>B vitamins: play an essential role in energy production and support normal conception. B12 is important for infant neurological sequelae2</li><li>Calcium: prevention of pre-eclampsia. Assess women with inadequate dietary intake (&lt;1000 mg daily)2</li><li>Iron: prevention of pregnancy-related iron deficiency.2 Women with iron deficiency identified by blood test: oral supplementation with at least 60 mg of elemental iron daily2</li><li>Zinc: antioxidant and plays a role in ovulation and the menstrual cycle in addition to sexual development5</li><li>Selenium: antioxidant trace nutrient, which may be important for the newly fertilised oocyte and may play a protective role towards the early embryo15,16</li><li>CoQ10: antioxidant and important for reproduction, body levels of CoQ10 are known to decrease with age therefore important nutrient for the older prospective mother17,18</li></ul><h2>RESTRICTION</h2><ul><li>Vitamin A: Limit vitamin A supplements to 3000 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 conception2</li></ul> 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>Avoid smoking, alcohol and illicit drug consumption: inform women and their partners that there is no ‘safe’ level of alcohol consumption for a developing foetus, therefore, abstinence in the preconception period and during pregnancy is advised. Tobacco affects foetal growth and evidence exists that for women who stop smoking during pregnancy their children have better cognitive ability. Referring to Quitline or therapy groups where necessary2,3</li><li>Limit caffeine: to 300 mg or less per day (equivalent 2 to 3 standard cups of coffee a day). Be mindful of other forms of caffeine in black tea, energy drinks and gym supplements2</li><li>Advise on a healthy diet:2 include good food sources of iron, calcium, B vitamin, and iodine. </li><li>Vegans and vegetarians: are likely to have increased deficiencies in amino acids, zinc, calcium, iron and vitamins D and B12.2 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 week2</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 listeriosis</li><li>Weight reduction in those who are overweight (Body Mass Index 25-29.9 kg/m2) or obese (BMI &gt;30 kg m2): a study has shown that a 10% decrease in pre-pregnancy BMI could decrease stillbirth risk by 10%.19 Therefore overweight and obese women and men should be set realistic goals of losing 5-10% of their body weight before conception2</li><li>Preconception control of blood glucose levels for women with type 1 and type 2 diabetes: shown to decrease the incidence of congenital malformations, miscarriage, birth weight abnormalities, and preterm birth2</li><li>Exercise: 150 minutes of exercise per week or 30 minutes on most days2</li><li>Encourage regular brushing of teeth and dental flossing: dental health check2</li><li>Environmental exposures: assess the work, home, and recreational environments, with attention to specific environmental toxins such as lead, heavy metals and solvents (e.g. paint strippers)3</li><li>Avoid cat litter, garden soil, raw/undercooked meat, and unpasteurised milk products, wash fruit and vegetables: to reduce exposure to Toxoplasmosis3</li><li>Frequent hand-washing: can reduce the risk of cytomegalovirus and parvovirus. For those working in child care, to reduce risk by wearing gloves when changing nappies3</li><li>Inter-pregnancy interval: perinatal outcomes are worse with inter-pregnancy intervals less than 18 months or more than 59 months, affecting preterm birth, low birth weight and small-size-for-gestational age3</li></ul>

Diet & lifestyle

<h2>References</h2> 1. De-Regil L et al. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database of Systematic Review 2015, Issue 12
 2. Dorney E et al. Preconception care. Australian Journal of General Practice. Vol 47, No. 7, July 2018
 3. 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 2019
 4. Hewison M. The earlier the better: preconception vitamin D and protection against pregnancy loss. Lancet, Diabetes &amp; Endocrinology. June 2018. https:// www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30178-5/fulltext. Accessed 05/03/2019
 5. Ebisch I et al. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Human Reproduction Update, Vol. 13. N0.2 pp 163-174, 2007
 6. Natural medicines. Folic acid monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional. aspx?productid=1017 Accessed 4th March 2019
 7. Blackmores Institute. Complementary Medicine Interaction Guide. 10th edition. Accessed 7th March 2019
 8. Natural medicines. Iodine monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional. aspx?productid=35 Accessed 4th March 2019
 9. Velasco I et al. Iodine as Essential Nutrient during the First 1000 Days of Life. Nutrients 2010 Mar, 10(3):290
 10. National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand. https://www.nrv.gov.au/nutrients/iodine Accessed 4th March 2019
 11. Natural medicines. Vitamin D monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional. aspx?productid=929 Accessed 4th March 2019
 12. Covington M. Omega-3 Fatty Acids. American Family Physician. 2004 Jul 1;70(1):133-140
 13. Mumford S et al. Serum Antioxidants are associated with serum reproductive hormones and ovulation among healthy women. The Journal of Nutrition. Nutritional Epidemiology. Pub online Nov 18, 2015
 14. Luck M et.al. Ascorbic Acid and Fertility. Biology of Reproduction 1995 52, 262-266
 15. Zachara B et al. Blood selenium and glutathione peroxidases in miscarriage. British Journal of Obstetrics and Gynaecology. March 2001 Vol 108; 244- 247
 16. Beckett G et al. Selenium and endocrine systems. J Endocrinol 2005 Mar 184(3):455 -465
 17. Noia G et al. The antioxidants (coenzyme Q10) in materno-fetal physiopathology). Minerva Ginecol. 1999 Oct; 51 (10) :385-91
 18. Crane F. Biochemical functions of coenzyme Q10. J Am Coll Nutr. Vol 20 (6) 2001: 591-598
 19. Schummers L et al. Risk of adverse pregnancy outcomes by pre-pregnancy body mass index: a population-based study to inform pre-pregnancy weight loss counseling. Obstet Gynecol. 2015 Jan; 125(1):133-43
 20. Mumford S et al. Preconception Plasma Phospholipid Fatty Acids and Fecundability. J Clin Endocrinol Metab 2018 Dec 1; 103(12):4501-4510
 21. Wise L et al. Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies. Am J Epidemiol. 2018 Jan 1; 187(1):60-74

Preconception

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