Dr Treasure McGuire
BPharm, BSc (Pharmacology), PG
Dip Clinical and Hosp Pharm, PhD
Dr Brett MacFarlane
BPharm Hons PhD FACP MPS
Learning objectives
After completing this activity pharmacists should be able to:
- describe the key consequences of nutrition and nutrient levels on pregnancy outcomes
- describe the evidence base for recommendation of nutrient supplementation in pregnancy
- describe the changes in nutrient intake necessary to provide a healthy pregnancy and baby.
2010 Competency standards: 1.3, 4.26.1, 6.2, 6.3, 7.3
2016 Competency standards: 1.3, 3.2
Accreditation number: A1806ITK1
Expiry date: 1 June 2020
This activity has been accredited for 1.5 hours of Group 1 CPD (or 1.5 CPD credits) suitable for inclusion in an individual pharmacist’s CPD plan which can be converted to 1.5 hours of Group 2 CPD (or 3.0 CPD credits) upon successful completion of relevant assessment activities.
Introduction
In Australia in 2015:1
• 304,268 women gave birth
• the average age of women giving birth (30.3 years) continued to rise, (up from 29.7 years in 2005)
• 8.7% of infants were pre-term and 0.4% post-term
• 9 perinatal deaths occurred for every 1,000 births.
However, 1 in 6 couples had difficulty achieving a pregnancy.2
Nutrition is increasingly being recognised as playing a key role in health outcomes, particularly when pregnant or breastfeeding..
The dietary state of play in Australia
The 2013 Australian Dietary Guidelines are underpinned by extensive reviews of best available research evidence, as well as significant dietary modelling to ensure that nutrient and energy requirements are met for each age and gender group.
For healthy women, dietary modelling shows it is possible to meet nutritional requirements by following the recommended intakes from the five food groups: eating plenty (and a variety) of vegetables and fruit, including some nuts and seeds, wholegrain cereal foods, reduced-fat dairy foods and lean meats, fish (particularly those rich in omega-3 fats) or poultry, as well as small amounts of poly- or monounsaturated fats and oils.
There is also strong evidence that it is better for health and reducing risk of chronic diseases to meet nutrient needs from whole foods rather than supplements.3, 4
However, it is increasingly evident that poor nutrition and obesity are becoming common in women of reproductive age, in low- and high-income countries; and that typical diets fall short of recommendations, particularly in adolescents.5
Examples where nutrient supplementation may be required:4
• Strict vegetarians who consume no animal foods may need supplements of vitamin B12, omega-3 fats, iron and zinc. As these nutrients are less available from plant sources, intake needs to be much higher than for non-vegetarians.
• Vitamin D supplements may also be needed by those with little exposure to sunlight, e.g. the elderly, veiled women and people of darker skin types.
• Peri-conceptional folic acid supplements are required for women planning a pregnancy, and during the first 3 months of pregnancy, plus eating foods naturally rich in folate.
• Pregnant and breastfeeding women have increased iodine requirements.
Advice from an appropriate health professional should always be sought before commencing supplementation.
The 2013 Australian Dietary Guidelines recommend adults eat the following per day, depending on their age and gender:3
• at least six serves of grain foods
• 5–6 serves of vegetables
• 2 serves of fruit
• 2.5 serves of dairy products
• approximately three serves of lean meat and alternatives.
Table 1: Results from the National Health Measures Survey (2011–12)
The Australian Bureau of Statistics (ABS), National Nutrition and Physical Activity Survey (NNPAS 2011–12), released May 2016, found fewer than 4% of Australians are eating enough vegetables and legumes each day, and most are failing to meet the minimum number of serves recommended for the five major food groups.6
The NNPAS presented national level information on usual intake of selected nutrients and compared them with Nutrient Reference Values (NRVs).7 Usual nutrient intakes are an estimate of what people ‘usually’ eat, versus what they reported eating on the particular days they were surveyed.
Mandatory fortification of bread-making flour with folic acid was introduced in Australia in 2009 to reduce the incidence of neural tube defects (NTDs) in the Australian population by increasing the folic acid intake of women of child-bearing age. Fortification of food with folic acid remains voluntary in New Zealand.
Mandatory fortification of bread with iodised salt in Australia and New Zealand was introduced in 2009.9
Despite these strategies, the NNPAS reported that:6
• approximately 1 in 12 (9%) females (aged 19 and over) did not meet their folate requirements (dietary folate equivalents) based on their intakes from foods
• 8% of females did not meet their iodine requirements.
Also:6
• approximately 16% of females had inadequate thiamin intake
• 73% of females aged two years and over did not meet their calcium requirements
• 23% of females did not meet their iron requirements
• approximately 95% or more of all females had an adequate intake of protein, vitamin C, vitamin B12, phosphorus and selenium.
Another ABS study, the National Health Measures Survey (NHMS 2011–12), involved collection of a range of blood and urine samples, from over 11,000 participants across Australia. Samples were analysed for various chronic disease and nutrient biomarkers, including tests for folate, iodine, vitamin B12, and ferritin (a measure of iron stores in the body). It was also a key data source for measuring the effectiveness of mandatory fortification of food in increasing folate and iodine levels within the population. Results on nutrient levels in women of child-bearing age were generally encouraging, with the main concerns being for iodine and vitamin D deficiency.
Results of the NHMS are summarised in Table 1.10
.Nutrient intake recommendations in pregnant women
Health professional guidelines recommend that women of child-bearing age (16 to 44 years) maintain higher levels of selected nutrients to best prepare for pregnancy.15, 16, 17
While an increasing cohort of couples use nutrient supplementation when planning to conceive, or are having difficulty conceiving, there are still women falling pregnant who have not taken a supplement.
Table 2 describes the consensus on the need for routine supplementation in pregnancy with key micronutrients, their nutrient reference values and recommended supplemental dose in pregnant women.
Table 2: Essential micronutrients, their Nutrient Reference Values (NRVs) and Australian recommended supplemental doses for pregnancy
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists’ (RANZCOG) statement on Vitamin and Mineral Supplementation in Pregnancy states that most proprietary pregnancy and lactation multivitamin preparations are adequate for the majority of pregnancies. The most common exceptions will be vegetarians/vegans needing additional iron and women requiring a high dose (5 mg) of folic acid or pharmacological doses of vitamin D.18
.Folic acid
The neural tube (the precursor to the embryo’s central nervous system, comprising the brain and spinal cord) normally closes completely by the end of the fourth week after conception.19
In 2007, Oakley reported that approximately 220,000 neonates are born with neural tube defects (NTDs), including spina bifida, every year, mainly in developing countries and primarily because of malnutrition. The author noted that this could be corrected via mandated food fortification with folic acid.20
Clinical studies and animal experiments over 50 years have identified various nutritional, environmental and genetic risk factors for NTDs, including:19,20, 21, 22
1) Maternal diet and nutritional status
• Folic acid deficiency – In 1991, the UK Medical Research Council (MRC) vitamin study research group conducted a pivotal large-scale randomised control trial (RCT) of folic acid supplementation (4 mg per day), in a total of 1,031 women who had previous pregnancies affected with NTDs. The recurrence rate of NTDs was 1.0% (5/514) in the folic acid supplemented group, versus 3.5% (18/517) among control mothers. The relative risk in the former group was 0.28, indicating a 72% preventive effect of folic acid on NTDs.22
However, folic acid is not a panacea to prevent NTD occurrence in all cases. About 30% of NTD recurrence is not folic acid preventable, which suggests that a proportion of NTDs are resistant to folic acid.19,21
• Vitamin B12 deficiency is also a risk factor for NTDs.20,21
2) Genetic factors19,21
• NTDs aggregate in some families, with a 2–5% risk of NTD recurrence in subsequent pregnancies.
• NTDs occur more often in near relatives of an NTD-affected baby than in the population as a whole, but the prevalence is less than the 25%, or 50% prevalence predicted from simple dominant or recessive gene inheritance.
• NTDs occur more frequently in multiple than single births.
3) Environmental factors21
• Diseases such as epilepsy, diabetes, haemolytic anaemia
• High maternal BMI
• Drug abuse
• Maternal medication use
• High body temperature during first trimester
4) Anti-epileptic drugs (AEDs)21
Anti-epileptic drugs (AEDs) alter folate metabolism in the embryo, decrease plasma folate concentrations and are the most potent drugs that lead to the development of NTDs. AEDs appear to cause impairment of folate absorption, competitive interaction between folate co-enzymes and drugs, and an increased demand for folate as a co-enzyme for anti-epileptic hydroxylation.
Analysis of 983 offspring delivered by mothers who had been treated for epilepsy indicated that 90.0% were exposed to AEDs in utero. Malformations occurred in 9.0% of exposed, versus 3.1% in the non-exposed group. The prevalence of malformations increased with the number of AEDs administered (7.8% for one AED, 9.6% for two, 11.5% for three, 13.5% for four and 15.4% for five).
Data from Australian and international birth registries consistently show that, of the AEDs, sodium valproate is associated with the highest risk of malformations, particularly for spina bifida.
Reported rates of malformations in babies born to mothers taking valproate range from 6.2% in the UK to 13.3% in Australia (it should be noted that there are methodological differences between these studies, which is likely to account for at least some of the variability reported).24
Rates of malformations associated with exposure to carbamazepine and lamotrigine are variable but tend to be lower than for valproate. Studies investigating rates of malformations associated with exposure to the newer AEDs (gabapentin, topiramate, levetiracetam, oxcarbazine and zonisamide) are small, therefore making risk assessment difficult.26 However, analysis tends to suggest that lamotrigine and levetiracetam have low risk of teratogenesis, while there may be a dose-related teratogenic effect of topiramate when taken in early pregnancy.24
Malformations associated with valproate exposure also seem to be dose dependent, with doses above 800–1,000 mg valproate having a significantly greater risk compared to lower doses. These higher doses of valproate are also associated with greater risk of effects on postnatal cognitive development, such as lower IQ.26, 27
The Therapeutic Guidelines recommend that women taking valproate, who are planning to become pregnant, should not take doses higher than 600 mg daily, though this will depend on the requirements of the individual patient.28
5) Other drugs that affect folate metabolism/prevent its absorption:21
• Sulfonamides – sulfamethoxazole, sulfadoxine-pyrimethamine, sulfasalazine
• Trimethoprim
• Rifampicin
• Methotrexate
• Azathioprine
• Aspirin
• Antacids
6) Vitamin A
Evidence indicates that the prevalence of dose-related NTDs in babies born to mothers consuming over 15,000 IU of preformed vitamin A per day, from food and supplements, was 3.0%; while that among babies born to mothers consuming <5,000 IU was only 1.3%.29
.Folic acid supplementation
Folic acid supplementation can prevent first- and second-time occurrence of NTDs, such as spina bifida, by repleting intracellular folate stores.30
Over 50 countries have mandated the fortification of wheat flour with folic acid, meaning that over two-thirds of the world’s population have access to folic acid fortified flour.9
Introduction of mandatory folic acid addition to bread-making wheat flour in Australia occurred in 2009 and there has subsequently been a significant reduction in the prevalence of folate deficiency, including in women of child-bearing age.31
There has also been a reduction in the prevalence of NTDs by 14.4%, to approximately five per 10,000 births, in the years after mandatory folic acid fortification (2009–11), compared to the years before (2008–09).32
The prevalence of NTDs in Aboriginal populations has reduced by 68% since mandatory folic acid fortification was introduced.33 However, the prevalence of NTDs is still almost double in Aboriginal and Torres Strait Islander (ATSI) infants compared to that in the non-Indigenous population.34
Therefore, there is an urgent need to improve diet and access to folate-rich foods or increase the levels of supplementation in ATSI populations.
Guidelines for folic acid supplementation in pregnancy
The Australian Government Department of Health and Aging (DoHA) recommends regular folate supplementation (minimum of 500 microg daily) for all sexually active women. Supplementation should begin one month (but ideally twelve weeks) prior to conception, to replete intracellular folate stores, and continue for the first 12 weeks of pregnancy.17
RANZCOG recommends that folic acid should be taken for a minimum of one month before conception and for the first 12 weeks of pregnancy. The recommended dose of folic acid is at least 400 microg daily, to aid the prevention of NTDs.
Where there is a known increased risk of NTD (e.g. patients taking AEDs, pre-pregnancy diabetes mellitus, previous child or family history of NTD or maternal BMI >30), or a risk of folate malabsorption, a high dose (5 mg) folic acid supplement is recommended.
While it is well established that pre-pregnancy and early pregnancy dietary supplementation with folic acid is effective in reducing the incidence of NTDs, a dose that is both effective and safe for women at risk of NTD is still to be determined and is the subject of ongoing research.18
The Therapeutic Guidelines also recommend a high dose of 5 mg of folic acid for women taking AEDs. Supplementation should commence three months before and continue for three months after conception.
The eTG reiterates the view of RANZCOG regarding the need for more studies to clarify the optimal dose of folic acid, particularly in women taking AEDs.28
.Iodine
It is estimated that over 1.8 billion people worldwide do not take sufficient iodine in their diet, putting them at risk of iodine deficiency.36
Iodine is an essential nutrient needed in small amounts to make thyroid hormones, which are responsible for regulating growth, development and metabolism.
Very little iodine is required to meet the body’s needs, with an RDI ranging from 150 microg per day in non-pregnant women, increasing to 220 microg in pregnancy and to 270 microg in breastfeeding.16
However, it can be challenging to meet these needs given that naturally occurring iodine is low in most foods and beverages, except iodised salt, seafood, fortified bread and some dairy. So, the World Health Organisation (WHO) recommends that iodine is added to salt (iodised) to increase intake and potentially prevent problems caused by iodine deficiency.35
Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, foetal and infant needs.
The foetal brain is vulnerable to damage from reduced circulating maternal thyroxine levels, so pregnant (and breastfeeding) women are at greater risk of iodine deficiency and delivering children with preventable neurodevelopmental disorders.16
Consequences of low iodine levels may include:36, 37
• maternal hypothyroidism or goitre
• gestational hypertension
• increased risk of premature labour
• pregnancy loss
• developmental delays ranging from mild intellectual impairment to cretinism.
Evidence for iodine supplementation in pregnancy
The provision of iodine supplements may help to meet the increased iodine needs during pregnancy and the postpartum period, and prevent or correct iodine deficiency and its consequences.
A 2017 Cochrane review concluded there were insufficient data for any meaningful conclusions on the benefits and harms of routine iodine supplementation in healthy women before, during, or after pregnancy. They found evidence of benefit (reduced likelihood of postpartum hyperthyroidism) and harm (increased likelihood of digestive intolerance) in settings with mild to moderate iodine deficiency.
They also found effects, mostly positive, on some indicators of iodine intake and iodine or thyroid status. They stressed that the review findings must be interpreted with caution due to the small number of trials and small number of included women, and also due to the low (or very low) quality of the evidence.36
Guidelines for iodine supplementation in pregnancy
Medical bodies in several countries, including Australia, have concluded that the potential benefits of iodine supplementation in pregnancy and breastfeeding (and in some countries in women before pregnancy) outweigh the potential harms.
The WHO recommends 250 microg of iodine daily in pregnancy and lactation to meet the increased demands. However, this recommendation is primarily for developing countries with no iodine food fortification programs.35
DoHA indicates pregnant women have an RDI of 220 microg of iodine and women who are breastfeeding an RDI of 270 microg daily (from all sources, including diet and supplements).
Women obtain some iodine from iodised salt, fortified bread, some dairy and seafood; however, as iodine requirements increase during pregnancy, a supplemental dose of iodine of 150 microg daily is recommended.17,18,38
The Australian population is only mildly iodine deficient, but women of child-bearing age are more likely to be iodine deficient (according to the WHO description of iodine deficiency in pregnancy and breastfeeding) than the general Australian population.11
RANZCOG states that taking an iodine supplement, at the recommended dose of 150 microg daily, will not lead to an excessive iodine intake.12
As only small amounts of iodine can be stored and any excess is excreted there are no added benefits of taking supplements containing more than 150 microg of iodine.12 Women with pre-existing thyroid conditions should seek advice from their medical practitioner before taking a supplement.12
Iron
In Australia in 2011–12, around 760,000 people aged 18 years and over (4.5%) were at risk of anaemia, with women more likely to be at risk than men (6.4% compared with 2.5% respectively).39
The prevalence of iron deficiency anaemia (IDA) during pregnancy is generally low (<20%) in developed countries, but higher in developing countries (35–75%), and in ATSI women (25–40%).39,40
IDA in pregnancy causes adverse outcomes for the mother and the child, including increased risk of:41
• maternal mortality
• premature birth
• low birth weight
• neurodevelopmental impairment in infants.
In pregnancy, iron demands increase by 20–30% due to:42
• an expanded red blood cell volume (increased total iron need is approximately 500 mg)
• demands of developing foetus and placenta (increased total iron need is approximately 300 mg)
• blood loss around the time of delivery.
This equates to an extra 800 mg of iron across the duration of the pregnancy, i.e. 5–6 mg per day, versus 1 mg per day when not pregnant.
However, iron requirements are not uniform throughout the three trimesters of pregnancy:42,43
• 1st trimester – requirements (estimated at 0.8 mg daily) are lower than before pregnancy as menstruation ceases
• 2nd and 3rd trimesters – as pregnancy advances, maternal red blood cell mass increases and placental and foetal growth accelerates, causing a rise in physiologic iron requirements.
The amount of total iron available from a mixed diet, including meat (haem iron), is approximately 18%, versus total iron available from a vegetarian diet (non-haem iron) of approximately 10%.44
However, most iron in the Australian diet comes from cereals and plant foods, with less than 20% coming from meat products. So, vegetarians who eat a varied and well-balanced diet, rich in wholegrains, legumes, nuts, seeds, dried fruits, iron-fortified cereals and green, leafy vegetables are not at greater risk of iron deficiency anaemia than non-vegetarians.44
Iron absorption is:44
• up-regulated by iron deficiency
• down-regulated in inflammation and iron repletion
• enhanced by acids (vitamin C), red meat, sugars e.g. fructose
• inhibited by:
o polyphenols (in tea, coffee and red wine)
o phytic acid (in wholegrains, rice, legumes)
o oxalic acid (in spinach and beetroot)
o bivalent minerals – calcium, zinc, manganese
o antacids and proton pump inhibitors.
From the second trimester, iron requirements increase substantially, to support foeto-placental development and maternal adaptation to pregnancy; hence the increased RDI.
To meet these requirements:
• dietary iron absorption increases (from 7% at 12 weeks, to 36% at 24 weeks, and 59% at 36 weeks)44,45
• the mobilisation of iron from body stores increases.
Evidence for iron supplementation in pregnancy
There is insufficient evidence to determine if women with mild anaemia (who are otherwise healthy), will benefit from anaemia treatment, with adverse effects of treatment potentially outweighing the benefits.1
There is a potential dose response relationship between the dose of iron and reported adverse events (morning sickness and constipation).46 An excessively high iron intake may also expose women to oxidative stress, lipid peroxidation, impaired glucose metabolism and gestational hypertension.4647
A 2016 Cochrane review of 44 trials in 43,274 women compared daily oral iron supplementation with various control groups (folic acid only, placebo, no intervention, other vitamin/mineral supplements without iron or folic acid). Most evidence was derived from studies comparing iron with no iron supplementation. In most trials, women took supplements before 20 weeks gestation and continued until delivery, with a usual elemental iron dose of 60 mg daily (range 30–240 mg) and folic acid 400 microg daily.48
Use of iron or iron/folic acid supplements was associated with a reduced risk of anaemia and iron deficiency during pregnancy. There was some indication that maternal iron supplements during pregnancy could improve outcomes for babies (birthweight and preterm birth) but evidence was not of high quality. Implementation of iron supplementation recommendations may produce heterogeneous results depending on the populations’ background risk for low birthweight and anaemia, as well as the level of adherence to the intervention.48
The Lancet recently reported that many women of reproductive age in the UK do not meet even the lower reference intake amounts for iron, with 96% of women of reproductive age having an intake of iron and folate below daily recommendations for pregnancy.5
Guidelines for iron supplementation in pregnancy
The WHO recommends:49
• daily oral iron and folic acid supplementation with 30–60 mg of elemental iron and 400 microg of folic acid for pregnant women to prevent maternal anaemia, puerperal sepsis, low birth weight and preterm birth
• a higher dose of elemental iron in pregnant women with diagnosed anaemia or in settings where anaemia in pregnant women is a severe public health problem.
In contrast, in the Australian setting, DoHA and the Australian National Research and Medical Research Council (NHMRC) supplementation recommendations include:
• Do not routinely offer iron supplementation to women during pregnancy; and for women to continue with a diet rich in iron.17,50
• Increasing intake of iron-rich foods reduces the risk of iron deficiency.50
• Iron supplementation is only recommended when a deficiency is identified as it does not benefit the health of the woman or baby. Not only does unnecessary iron supplementation offer no benefit, it may be harmful.17
• For women with identified iron-deficiency anaemia, low-dose supplementation is as effective as high dose, with fewer side effects.50
• For women with low dietary iron intake, intermittent supplementation is as effective as daily supplementation in preventing iron-deficiency anaemia, with fewer side effects.50
• Where iron supplementation is required to prevent maternal anaemia, a daily elemental iron dose of 27–45 mg is recommended.16 Iron requirements increase from the second trimester onward.42,43 Iron supplementation may cause or worsen adverse effects such as morning sickness and constipation.50
These statements are supported by the following evidence.
Recent studies provide high-level evidence on lower doses of iron supplementation. Iron supplements that are low dose (e.g. 20 mg),50 or taken less often than daily, appear to be effective in managing anaemia in pregnancy with fewer gastrointestinal side effects, compared with high-dose (e.g. 80 mg) or daily supplements.50,51,52
The iron demands of pregnancy and lactation are particularly pronounced due to the expanded red cell volume, blood loss around the time of delivery and the demands of the developing foetus and placenta. Iron supplementation will generally be recommended for women at particular risk of iron deficiency. This includes some vegetarians and women with a multiple pregnancy.18
All women should have their haemoglobin level checked at the first antenatal visit and again at approximately 28 weeks’ gestation, and any anaemia investigated and treated. Routine iron supplementation is not recommended in every pregnancy.18
Women with diagnosed IDA will need additional supplementation, with a specific iron supplement, containing at least 60 mg of iron daily.18
Vitamin D
Vitamin D comprises two main molecular species that share vitamin activity:
• cholecalciferol (vitamin D3, derived from cholesterol and synthesised by animal organisms)
• ergocalciferol (vitamin D2, derived from ergosterol, found in vegetables).
In early pregnancy, vitamin D (mainly D3, the predominant form in maternal blood) is involved in regulation of cytokine metabolism and modulation of the immune system, contributing to embryo implantation and regulating hormone secretion.53
Vitamin D deficiency is surprisingly common in pregnancy, even in countries with sunny climates, and appears to be associated with an increased risk of developing pre-eclampsia and gestational diabetes mellitus.53
Vitamin D is transferred from mother to foetus via the placenta. Low maternal serum levels of vitamin D in pregnancy are associated with low neonatal serum levels.53, 54
Vitamin D deficiency in the neonate and the infant is associated with impaired skeletal development and an increased incidence of hypocalcaemic seizures.54, From the mother’s perspective, vitamin D deficiency is known to be an important risk factor for the development of osteoporosis in later life.18
DoHA indicates that there is limited evidence supporting screening of all women for vitamin D deficiency in pregnancy as it is not possible to reliably identify women who are vitamin D deficient.
Estimates of vitamin D deficiency in Australia vary but are higher than previously thought. Therefore, screening of at-risk women is recommended.17
Most of our vitamin D comes from the action of ultraviolet light on skin. Therefore, women at risk of vitamin D deficiency include those:18
• of darker skin type – produce less vitamin D for a given sunlight exposure
• with limited sun exposure – spend time predominantly indoors
• protected from sun outdoors, e.g. veiled women, those using sunscreen on a regular basis
• with a pre-pregnancy BMI >30.
A 2016 Cochrane review included 15 RCTs involving 2,833 women. Nine trials compared the effects of vitamin D alone, with no supplementation or a placebo, and 6 trials of vitamin D plus calcium with no supplementation. Daily vitamin D doses ranged between 200 IU to 2,000 IU (5–50 microg).56
Results showed vitamin D supplements during pregnancy:56
• improve vitamin D levels, as measured by 25-hydroxyvitamin D concentrations, at term
• may reduce the risk of delivering a baby prematurely (<37 weeks gestation)
• result in a lower risk of pre-eclampsia
• reduce the risk of low birthweight babies (<2,500 g)
• increase the risk of preterm birth when vitamin D and calcium are combined.
The review found that data on adverse effects due to vitamin D supplementation for the mother were not well reported.
The clinical significance of the increase in women’s vitamin D levels is unclear and results should be interpreted with caution as only a few small trials of low quality assessed these outcomes.
The investigators concluded that with the available evidence, it is unclear whether vitamin D supplementation should be given as part of routine antenatal care to improve maternal and infant outcomes.56
Guidelines for vitamin D supplementation in pregnancy
DoHA recommends that women at risk of vitamin D deficiency should be screened to determine if they may benefit from vitamin D supplementation.50
RANZCOG suggests supplementation for all pregnant women where vitamin D deficiency is suspected and blood levels taken (consensus-based recommendation).18
The RANZCOG consensus-based recommendation indicates the following doses of vitamin D:
Pregnant women with vitamin D level above 50 nmol/L
• commence 400 IU (10 microg) vitamin D daily as part of a pregnancy multivitamin.
Pregnant women with vitamin D level below 50 nmol/L
• 30–49 nmol/L, commence 1,000 IU (25 microg) daily
• <30 nmol/L should commence 2,000 IU (50 microg) daily.
Repeat the vitamin D level at 28 weeks’ gestation.
Calcium
Calcium is the most abundant mineral in the human body, with 99% located in the skeleton and in teeth. Calcium is essential for foetal development, and maternal requirements increase during pregnancy (approximately 50 mg daily at 20 weeks and up to 330 mg daily at delivery) and lactation.55
Adequate calcium intake during pregnancy promotes higher birth weight, reduced risk of preterm delivery and better blood pressure control.53
It has been proposed that low-dose supplementation with calcium during pregnancy reduces the risk of developing both gestational hypertension and pre-eclampsia; however, excessively high levels correlate with increased risk of developing HELLP (Haemolysis, Elevated Liver enzymes and Low Platelets) syndrome.53
Guidelines for calcium supplementation in pregnancy
Recommendations for calcium intake differ internationally, with WHO recommending 1,500–2,000 mg daily from the 20th week of gestation, especially for women at risk of gestational hypertension. If this intake cannot be met through diet, a calcium supplement rather than a multivitamin dose form would be required.53
In contrast, NHMRC recommends an RDI of calcium for women of 1,000 mg daily (1,300 mg for 14–18-year-olds). The RDI does not change in pregnant or breastfeeding women.16
RANZCOG also recommends 1,300 mg daily for 14–18-year-olds, and 1,000 mg daily for 19–50-year-olds. They recommend a supplement of at least 1,000 mg for women who are unlikely to achieve the RDI for calcium through diet.18
Omega-3 fatty acids
There is a growing evidence base for dietary fish, rich in omega-3 polyunsaturated fatty acids (n-3PUFA) to be consumed in pregnancy, as humans cannot synthesise these essential nutrients. n-3PUFA status, particularly docosahexaenoic acid (DHA), contributes to the structural component of the foetal brain and retina, with uptake maximal during the second half of gestation; however, the benefits of supplementation are not known.
Guidelines for DHA supplementation in pregnancy
Consensus guidelines recommend women should aim to consume 200 mg DHA daily during pregnancy;57 however, RANZCOG identifies that, for many women, this is not feasible without supplementation.18
Other nutrients
The DoHA Antenatal Care Clinical Practice Guidelines indicate that supplementation with other vitamins including A, C and E do not benefit pregnant women and may be associated with dose-related adverse outcomes. This is particularly the case for vitamin A which has been associated with congenital malformation.17
Summary
Dietary intake of some essential nutrients is inadequate in the Australian population and this may have implications in pregnancy.
Other maternal risks, including disease states, high body mass index, medication use and environmental factors can further impact nutrient levels and pregnancy outcomes.
The prevalence of neural tube defects, including spina bifida, is decreasing in Australia. This may be related to mandatory fortification of certain foods with folic acid. The prevalence of NTDs in Aboriginal and Torres Strait Islander children is higher than in non-Aboriginal children.
Australian guidelines recommend that:
• Sexually active women should take regular folic acid supplements.
• All women planning pregnancy should supplement with at least 400 microg of folic acid daily, commencing four weeks (but ideally 12 weeks) before conception and continuing throughout the first 12 weeks of pregnancy.
• Women at high risk of folate deficiency should take 5 mg of folic acid daily.
• Women planning a pregnancy, pregnant women and those breastfeeding should supplement with iodine 150 microg daily to achieve the RDI for iodine of 220 microg daily in pregnancy and 270 microg daily in lactation.
• Routine supplementation with iron during pregnancy is not recommended in the first trimester. Pregnant women and women planning pregnancy should be encouraged to maintain a healthy diet rich in iron. The presence of iron deficiency and iron deficiency anaemia should be assessed by a doctor before supplementation is commenced. Lower doses of iron are as effective at treating iron deficiency as higher doses, with fewer side effects.
• RANZCOG recommends that pregnant women at risk of low vitamin D should be screened for deficiency. Women with vitamin D blood levels indicating deficiency should take the following doses: <30 nmol/L – 2,000 IU; 30–49 nmol/L – 1,000 IU. Pregnant women with a vitamin D level above 50 nmol/L should take 400 IU as part of a pregnancy multivitamin.
• Regular dietary intake of calcium is recommended during pregnancy; if this is not feasible, supplementation may be necessary.
• Foods rich in omega-3 fatty acids should be consumed during pregnancy; however, if this is not feasible, supplementation may be necessary.
References available on request.
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1. The National Nutrition and Physical Activity Survey found that 95% or more of Australian females had adequate intake of which of the following nutrients?
a) Calcium
b) Folate
c) Iodine
d) Iron
e) Vitamin B12
2. Blood level data from the National Health Measures Survey (2011–12) indicated deficiency of which two nutrients is of most concern in the Australian population?
a) Folate and iodine
b) Folate and vitamin B12
c) Iodine and vitamin B12
d) Iodine and vitamin D
e) Vitamin D and vitamin B12
3. Which two nutrients are recommended for routine supplementation in women during the peri-conception and antenatal periods?
a) Calcium and vitamin D
b) Folate and calcium
c) Folate and iodine
d) Folate and vitamin B12
e) Vitamin D and iodine
4. Which antiepileptic drug is associated with the highest risk of spina bifida?
a) Carbamazepine
b) Levetiracetam
c) Oxcarbazine
d) Sodium valproate
e) Topiramate
5. Which one of the following statements about folic acid supplementation in pregnancy is correct?
a) All women planning pregnancy are recommended to supplement with at least 400 microg of folic acid daily.
b) Women with high risk of folate deficiency should supplement with 5 mg of folic acid daily.
c) Although rates of neural tube defects in Aboriginal and Torres Strait Islander (ATSI) children are decreasing, they are still almost double that of non-ATSI children.
d) Folic acid supplementation should commence four weeks (ideally 12 weeks) before conception and continue for the first 12 weeks of pregnancy.
e) All of the above statements are correct.
6. Which of the following are risk factors for neural tube defects (NTDs)?
a) Previous child with NTD or family history of NTD
b) High maternal Body Mass Index
c) Maternal diabetes mellitus
d) Exposure of the foetus to drugs that affect folate metabolism e.g. antiepileptic drugs
e) All of the above are risks for NTDs.
7. Which one of the following statements about iodine supplementation in pregnancy is correct?
a) All women in Australia planning pregnancy and those who are pregnant or breastfeeding should take a supplemental dose of iodine of 150 microg daily.
b) The recommended daily intake (RDI) of iodine for pregnant women in Australia (from all sources: diet and supplements) is 150 microg daily.
c) Australian sugar is iodised.
d) Iodine requirements significantly increase during pregnancy to produce growth hormone.
e) All of the above statements are correct.
8. At what stage of pregnancy are iron requirements increased?
a) Pre-conception
b) First trimester
c) Second and third trimesters
d) Increased iron requirements are the same throughout the entire pregnancy.
e) Iron requirements do not increase during pregnancy.
9. Which one of the following statements about iron supplementation in pregnancy is correct?
a) There is sufficient evidence to support the benefits of anaemia treatment in women with mild anaemia who are otherwise healthy.
b) A 2016 Cochrane review found that use of iron or iron/folic acid supplements was associated with a reduced risk of anaemia and iron deficiency during pregnancy.
c) Routine iron supplementation for all pregnant women is recommended by the National Health and Medical Research Council.
d) Low dose iron has been shown to be inferior to higher doses for managing anaemia in pregnancy.
e) All of the above statements are correct.
10. According to RANZCOG, what dose of vitamin D3 would be recommended for a pregnant woman with a vitamin D blood level of 60 nmol/L?
a) 100 IU
b) 200 IU
c) 400 IU
d) 1,000 IU
e) 2,000 IU