Presented by Nikki Warren, BHSc, N.D., M.H., M.NHAA., Chairperson of ARONAH

Supplementing with the right nutrients according to each trimester

Overview

• Why there is a need for a separate prenatal supplement for trimester one

• Ways to reduce morning sickness

• The benefits of supplementation for mum and baby

• Brief discussion on methylation

• Haemodilution

• Pre-eclampsia

• Gestational diabetes

Birth defects & infant deaths

• Between 1997-2010, the three leading causes of infant death have remained unchanged – perinatal conditions, birth defects and symptoms, signs & abnormal findings (two thirds of these were due to SIDS).

• Birth defects accounted for 26% of all infant deaths of which there are 5 in every 1000.

• Around 6.2% of babies are of low birthweight. Babies born to younger and older mothers (aged less than 20 or 40 and over) were more likely to be of low birthweight – 8.6% and 7.6% respectively. Health risks associated with low birthweight include significant disabilities, type 2 diabetes, hypertension, metabolic and cardiovascular diseases and even obesity in later life.

Ref: Australian Institute of Health and Welfare 2012. A picture of Australia’s children 2012. Cat. no. PHE 167. Canberra: AIHW

Preterm birth

• In 2011, 8.3% of babies were born preterm, a slight increase since 2004 when it was 8.2%.

• Worldwide, preterm birth complicates approximately 5-10% of all births and is the major cause of perinatal mortality and long-term physical and neurological morbidity both in Western and developing countries.

• Complications include acute respiratory, gastrointestinal, immunologic, central nervous system, hearing and vision problems, as well as longer-term motor, cognitive, visual, hearing, behavioural, social-emotional health and growth problems.

Reference: Li Z, Zeki R, Hilder L & Sullivan EA 2013. Australia’s

mothers and babies 2011. Perinatal statistics series no. 28.Cat. no.

PER 59.Canberra: AIHW National Perinatal Epidemiology and

Statistics Unit

Preventative prenatal care

Outcomes we wish to avoid in pregnancy include:

• Miscarriage

• Hyperemesis gravidarum

• Preterm birth

• Low birth weight

• Pre-eclampsia

• Gestational diabetes

• Birth defects

• In addition we aim to maximise a child’s potential:

- Intellectually

- Emotionally

- Physically

Safety of CAM treatments during pregnancy

• Even though herbal medicine and nutritional supplementation are considered safer than pharmaceuticals, we need to be wary of safety.

• The body undergoes enormous stress during pregnancy and this affects the way the body metabolises food, medications and herbs. Motility of the digestive tract declines and this can lead to an increase in the absorption of nutrients and herbs.

• However, correctly chosen CAM treatments which are deemed to be safe to use during pregnancy can greatly benefit the mother which in turn benefits the baby. If there is an absence of evidence then use risk versus benefit.

• Remember - absence of evidence does not mean it is not safe or effective.

Morning sicknessUp to 85% of women suffer from morning sickness which varies from mild nausea to severe nausea and vomiting several times a day (otherwise known as hyperemesis gravidarum). It usually starts around 6 weeks gestation and resolves by week 14-16 of pregnancy.

Morning sickness is debilitating, affects a woman’s ability to work and as a result creates a significant public health issue that has a psychological, emotional and social impact on women and their families and an economic impact on society.

Women need to be educated on what aggravates morning sickness and they need a solution that is not pharmaceutical. Currently women who see their doctor for morning sickness will often be prescribed Zofran (ondansetron) which may be harmful to the foetus.

Morning sickness – PUQE scoreIn the last 12 hours, how many hours have you felt nauseated or sick to your stomach?

> 6 hrs (5 pts.)

4-6 hrs (4 pts)

2-3 hrs (3 pts)

≤ 1 hr (2 pts)

Not at all (1 pt)

In the last 12 hours, how many times have you vomited?

7 or more (5 pts)

5-6 (4 pts)

3-4 (3 pts)

1-2 (2 pts)

None (1 pt)

In the last 12 hours, how many times have you had retching or dry heaves without bringing anything up?

7 or more (5 pts)

5-6 (4 pts)

3-4 (3 pts)

1-2 (2 pts)

None (1 pt)

Total score is sum of replies to each of the three questions.

Nausea Score:

Mild NVP = 6

Moderate NVP = 7-12 – monitor closely

Severe NVP = 13 – refer to doctor or midwife

Morning sickness

Factors that are avoidable:

• Iron and Zinc supplements can cause nausea and vomiting. This is well documented in the literature, especially in the case of iron during early pregnancy (Gill, 2009).

• Hcg stimulates the thyroid. Avoid high doses of iodine (Luetic, 2010, BALLABIO, 1991).

• High doses of vitamins B1, B2 and B3 can cause nausea in some women.

• Hyperemesis gravidarum has been associated with helicobacter pylori in this systematic review and meta-analysis (Sandven, 2009) (Namkin et al., 2016). This needs to be diagnosed and treated prior to conception.

• Possible role of high dose choline supplementation aggravating morning sickness. One of the reasons ginger works as an anti-emetic is that it is anticholinergic.

References:

BALLABIO, M., POSHYACHINDA, M. & EKINS, R.P. 1991. Pregnancy-induced changes in thyroid function: Role of Human chorionic gonadotropin as putative regulator of maternal thyroid Journal of Clinical Endocrinology & Metabolism, 73, 824-831.

GILL, S. K., MALTEPE, C. & KOREN, G. 2009. The effectiveness of discontinuing iron-containing prenatal multivitamins on reducing the severity of nausea and vomiting of pregnancy. Journal of obstetrics and gynaecology, 29, 13-16.

LUETIC, A. T. M., B. 2010. Is hyperthyroidism underestimated in pregnancy and misdiagnosed as hyperemesis gravidarum? Medical Hypotheses, 75,383-386.

NAMKIN, K., ZARDAST, M. & BASIRINEJAD, F. 2016. Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran. Iran J Pediatr, 26, e3768.

SANDVEN, I. 2009. Helicobacter pylori infection and hyperemesis gravidarum: a systematic review and meta-analysis of case–control studies. Acta obstetricia et gynecologica Scandinavica, 88, 1190 -1200

Morning sickness

There are a few factors that can help ease

nausea and vomiting during pregnancy:

• 75mg of vitamin B6 has been shown in several studies published in peer-reviewed journal articles to reduce the frequency and severity of nausea and vomiting in pregnancy and is equivalent to ginger in efficacy*. In most studies, capsules were taken 2-3 times daily.

• Stabilising blood sugar helps, therefore the nutrients chromium, biotin and alpha lipoic acid in particular may help ease morning sickness. Other nutrients play a role in carbohydrate metabolism including nicotinamide, pantothenic acid, riboflavin-5-phosphate, thiamine hydrochloride, pyridoxal-5-phosphate, hydroxocobalamin, magnesium, manganese and zinc.

• Ginger is a traditional remedy for morning sickness and has been shown repeatedly in studies published in peer-reviewed studies to be effective. However the longest study was only 3 weeks, therefore safety hasn’t been established for the entire first trimester although it should be noted that in the 3 week study, effectiveness increased over time. Most women will start taking ginger around 6 weeks and keep taking for at least 6-8 weeks. I find advising them to drink ginger tea and chew on crystallised ginger as needed is helpful.

ReferencesBABAEI, A. H. F., M. H. 2014. A randomized comparison of vitamin B6 and dimenhydrinate in the treatment of nausea and vomiting in early pregnancy. Iranian Journal of Nursing and Midwifery Research 19, 199.

ENSIYEH, J. S., M-A. C. 2009. Comparing ginger and vitamin B6 for the treatment of nausea and vomiting in pregnancy: a randomised controlled trial. Midwifery, 25, 649-653.

HAJI SEID JAVADI, E., SALEHI, F. & MASHRABI, O. 2013. Comparing the effectiveness of vitamin b6 and ginger in treatment of pregnancy-induced nausea and vomiting. Obstetrics & Gynecology International, 2013.

SAHAKIAN, V., ROUSE, D., SIPES, S., ROSE, N. & NIEBYL, J. 1992. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: A randomized, double-blind placebo-controlled study. International Journal of Gynecology and Obstetrics, 38, 151.

SMITH, C., CROWTHER, C., WILLSON, K., HOTHAM, N. & MCMILLIAN, V. 2004. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstetrics & Gynecology, 103, 639-645.

VUTYAVANICH, T., WONGTRA-NGAN, S. & RUANGSRI, R-A. 1995. Pyridoxine for nausea and vomiting of pregnancy: A randomized, double-blind, placebo-controlled trial. American Journal of Obstetrics and Gynecology, 173, 881-884.

Morning sickness – dietary guidelines

• Eat frequently – at least every 2 hours

• Crystallised ginger when feeling nauseous

• Ginger tea – grate 1 tsp ginger and steep in hot water

• Carry some Quick Eze in handbag – neutralising the stomach acids can help reduce nausea

• Snack on almonds and other nuts to stabilise blood sugar

• Snack on apples, raisins, nuts and cheese – high in chromium

• Eat protein last thing at night – yoghurt or nuts

• Dry crackers or ginger biscuits on rising may help

• If TSH is less than 1 tell her to drink lemon balm tea

• Address constipation – x2 kiwifruit at night usually helps

• Drink chamomile and peppermint tea – x1 bag of each in a cup

Trimester 1 - Prevention of miscarriage

About 10% of known pregnancies end in miscarriage.

Most early miscarriages occur because of chromosomal abnormalities due to errors introduced during meiotic disjunction in the oocyte or sperm.

A recent study showed that low total antioxidant status is associated with miscarriage (Omeljanuik et al, 2015).

Zinc and selenium deficiencies can cause chromosome changes due to the fact they are an essential component of genetic material therefore a deficiency in zinc and/or selenium is associated with an increased risk of miscarriage.

Alpha lipoic acid is an excellent antioxidant that recycles vitamins C, E and CoQ10 and a study has recently shown that 100mg of alpha lipoic acid with 100mg of magnesium taken daily from week 14 reduced the risk of preterm labour (Parente et al. 2014).

References

OMELJANIUK, W. J., SOCHA, K., BORAWSKA, M. H., CHARKIEWICZ, A. E., LAUDANSKI, T., KULIKOWSKI, M. & KOBYLEC, E. 2015. Antioxidant status in women who have had a miscarriage. AdvMed Sci, 60, 329-34.

PARENTE, E., COLANNINO, G. & FERRARA, P. 2014. Efficacy of Magnesium and Alpha Lipoic Acid Supplementation in Reducing Premature Uterine Contractions. Open Journal of Obstetrics and Gynecology, 04, 578-583.

Prevention of miscarriage – methylation

issues

Hyperhomocysteinaemia is the most common thrombophilia and this thrombophilic tendency is minimised by an adequacy of folate, vitamins B2, B6 and B12. The activated forms of these B vitamins overcome any MTHFR single-nucleotide polymorphisms (SNPs).

Interestingly, white Caucasians have a higher incidence of the MTHFR C677T SNP with 4-25% homozygous and 40-50% heterozygous compared to black people who only have 2% homozygous and 20% heterozygous.

All B vitamins need to be at adequate levels during gestation for the child to reach its full genetic growth potential. If the mother becomes depleted of nutrients at any stage later in the pregnancy this can lead to a growth restricted baby or a small for gestational age baby and this is linked to a number of diseases later in life.

If genes are not switched on or off at the right time during embryogenesis then things will go wrong – cell replication won’t happen as it should.

Higher levels of serum B12 led to a higher live birth rate by 26%.

Ref: Gaskins et al. 2015, American Journal of Clinical Nutrition

What’s wrong with folic acid?Folic acid needs to be converted to dihydrofolate (DHF) and then tetrahydrofolate (THF) – dihydrofolate reductase is the enzyme that metabolises DHF into THF.

If a woman is heterozygous for C677T then she has a 40% reduction in the ability to metabolise folic acid into its active form.

If she is homozygous she has a 70% reduction.

This means that folic acid is the wrong type of folate for her – she needs 5-MTHF if she is homozygous or if she is heterozygous for both C677T and A1298C.

Folate should always be combined with adequate B12 - 5-MTHF in combination with B12 (and B6 and B2) is required to convert homocysteine into methionine which is then converted into SAMe (essential for healthy neurotransmitter function). Also B12 is just as important as folate for preventing neural tube defects (Ray et al., 2007).

A recent meta-analysis confirms a significantly increased ASD risk in children with C677T polymorphism and that periconceptional folate supplementation reduces the risk (Pu et al., 2013)

References

PU, D., SHEN, Y. & WU, J. 2013. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res, 6, 384-92.

RAY, J.G. et al. 2007. Vitamin B12 and the risk of neural tube defects in a folic-acid fortified population. Epidemiology. 18(3):362-366.

B12 metabolism

Methylcobalamin and adenosylcobalamin are both active forms of B12 that have different biochemical roles.

Methylcobalamin is primarily involved in the formation of blood, homocysteine metabolism and development of the brain during childhood.

Adenosylcobalamin is primarily involved in carbohydrate, fat and amino-acid metabolism and a deficiency interferes with the formation of myelin.

Therefore, supplementation must either be a combination of both active forms OR hydroxocobalamin which easily converts to either form and it has been shown that the oral route is just as effective as intramuscular (Thakkar and Billa, 2015)

Reference:

THAKKAR, K. & BILLA, G. 2015. Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. Eur J Clin Nutr, 69, 1-2.

B12 supplementation

• Hydroxocobalamin (hydroxygroup attached to cobalamin) is better retained by the body than cyanocobalamin (cyanide attached to cobalamin) and does not contain a methyl group like methylcobalamin (Charles, 1984)

• B12 is just as important as folate in preventing neural tube defects and it is recommended that serum B12 levels should be higher than 221pmol/L prior to pregnancy to reduce the risk (Ray, 2003, Ray et al., 2008, Molloy et al., 2009)

References:

CHARLES, A., HALL, J.A., BEGLEY, & GREEN-COLLIGA, P.D. 1984. The availability of therapeutic hydroxocobalamin to cells. Blood,63, 335-341.

MOLLOY, A. M., KIRKE, P. N., TROENDLE, J. F., BURKE, H., SUTTON, M., BRODY, L. C., SCOTT, J. M. & MILLS, J. L. 2009. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics, 123, 917-23.

RAY, J. G. 2003. Vitamin B12 insufficiency and the risk of fetal neural tube defects. Qjm, 96,289-295.

RAY, J. G., GOODMAN, J., O'MAHONEY, P. R., MAMDANI, M. M. & JIANG, D. 2008. High rate of maternal vitamin B12 deficiency nearly a decade after Canadian folic acid flour fortification. QJM, 101, 475-7.

Nutritional requirements in trimesters 2 & 3

• Haemodilution is the increase in blood volume due to an increase in total volume of plasma and a decrease in the proportion of red blood cells relative to plasma.

• From 6 to 10 weeks there is an increase in plasma volume that rises sharply through the 2nd trimester, peaks at 24-26 weeks and plateaus at 32 weeks.

• It results in low haemoglobin levels (and also slightly affects ferritin) and low serum/plasma levels of other nutrients.

• Nutritional requirements in the 2nd and 3rd trimesters increase due to increased demands from the baby, especially iodine, iron, zinc, calcium and magnesium.

Reference:

• Faupel-Badger, J. (2007). Plasma volume expansion in pregnancy: implications for biomarkers in population studies. Hypothesis/commentary.

Fat soluble vitamins

RANZCOG recommends that there is little evidence to support routine supplementation of the fat soluble vitamins A, betacarotene, E and K during pregnancy.

However they are supportive of vitamin D supplementation and if the woman has proven cholestasis then vitamin K supplementation is required because of reduced vitamin K absorption. Vitamin K has poor placental transfer which is why babies are given vitamin K at birth.

Vitamin E is easily obtained from the diet – RDI is 7mg.

References:

RANZCOG, Vitamin and Mineral Supplementation and Pregnancy, 2014.

Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium and carotenoids (2000)

Concerns about vitamin AThe RDI of vitamin A in pregnancy is 800mcg daily. Personally I think the safest way to obtain vitamin A is through the diet. This means advising women to drink full cream milk and full fat yoghurt, eat meat, eat butter over margarine and even cook with butter, seafood, eat eggs regularly (eggs are a powerhouse of nutrients including iodine so they are fantastic in pregnancy). We all need a certain amount of saturated fat in our diets, it is trans-fats that are harmful.

Cod liver oil can vary from 270mcg to 1500mcg per teaspoon (best to avoid in case of overdose)

1 cup full cream milk = 92mcg

1 cup full fat yoghurt = 83mcg

Chicken breast = 36mcg

85gms mackerel = 42mcg

28 grams cheddar cheese = 90mcg

2 eggs = 186mcg

1 T butter = 130mcg

½ cup ice cream (as a special treat!) = 162.9mcg

If you have a pregnant woman who is vegetarian and doesn’t eat dairy products then you should advise her to take a vitamin A supplement – no more than 800mcg or 1500iu of retinyl palmitate. Be wary of cod liver oil – many women read on the internet that this is a good thing to take during pregnancy (Weston A. Price).

We commonly see betacarotene in prenatal supplements, however there are a lot of people who can’t convert beta-carotene into vitamin A – approximately 25% of white people* and one estimate is 45% of the population as a whole. Betacarotene is unstable in supplements and easily obtained through the diet. Also be aware that beta-carotene supplementation has been shown to inhibit the absorption of lutein by more than 50%*.

*Reference – The Textbook of Natural Medicine, Pizzorno & Murray.

Iron SupplementationIron deficiency anaemia affects 22% of women in the Western world compared with 52% in non-industrialised countries and the risk increases with each subsequent pregnancy.

It is important to get iron supplementation right during pregnancy and blood tests for ferritin should be done at the end of each trimester to assess the requirement for supplementation. The RDI of iron in pregnancy is 27mg daily.

We know that iron-deficiency anaemia is associated with an increased risk of maternal mortality (especially if she has a postpartum haemorrhage), infection, premature delivery, low birthweight and may adversely affect the baby’s brain development and neurocognition (Lozoff, 2006). However we know that excess iron intake has also been associated with adverse outcomes including low birthweight and premature delivery (Casanueva, 2003).

High dose iron supplementation may cause constipation and may reduce the absorption of other minerals such as zinc, copper, chromium, molybdenum, manganese and magnesium (Hambidge et al., 1987) (O’Brien, 2000) and vice versa, zinc and manganese supplementation may impair iron absorption so we need to get the balance right!

We know that iron supplements cause nausea and vomiting in the first trimester, so what do we do if the woman is iron deficient? Several studies have shown intermittent iron supplementation to be just as effective as daily iron supplementation. The referenced study showed no difference between weekly, three times a week or daily supplementation in terms of serum iron and haemoglobin levels (Bouzari, 2011)

References:

BOUZARI, Z., BASIRAT, Z., ZEINAL ZADEH, M., CHERATI, S. Y., ARDEBIL, M. D., MOHAMMADNETAJ, M. & BARAT, S. 2011. Daily versus intermittent iron supplementation in pregnant women. BMC Research Notes, 4, 444-449.

CASANUEVA, E. V., F.E. 2003. Iron and Oxidative Stress in Pregnancy. Journal of Nutrition, 133, 1700S-8S.

HAMBIDGE, K. M., KREBS, N. F., SIBLEY, L. & ENGLISH, J. 1987. Acute effects of iron therapy on zinc status during pregnancy. Obstetrics and gynecology, 70, 593-596.

LOZOFF, B. G., M. K. 2006. Iron deficiency and brain development. Seminars in Pediatric Neurology, 13, 158-165.

O’BRIEN, K. O., ZAVALETA, N., CAULFIELD, L.E., WEN, J. ABRAMS, S.A. 2000. Prenatal Iron Supplements Impair Zinc Absorption in Pregnant Peruvian Women. The Journal of Nutrition, 130, 2251-2255

Iron Assessment

“Normal” is 20-250ug/L, however in NZ in recent years they have changed the lower normal range to 30ug/L. I find in practice that women feel better with a ferritin over 50ug/L (pregnant or not).

Preferably we need to boost ferritin prior to conception – 80ug/L or higher is ideal. Check c-reactive protein as well though because ferritin can be falsely raised with inflammation.

Test ferritin at the end of each trimester:

13 weeks

26-28 weeks

36 weeks

6 weeks post-partum

• If ferritin is more than 80 ug/L (mcg/L) at 13 weeks then continue with Prenatal Trimester One which is iron-free.

• If ferritin is 40-80 ug/L advise her to take Prenatal Trimester 2 & 3.

• If ferritin is 30-40 ug/L then supplement with 40-50mg iron bisglycinate daily.

• If ferritin is less than 30 ug/L at 13 weeks then the woman needs additional iron and should be closely monitored (ferritin tests every 2 months from that point on). I would recommend 100mg of iron bisglycinate daily.

Biotin supplementation

• Biotin deficiency is teratogenic and suboptimal biotin status occurs in 50% of pregnant women (Perry et al, 2014).

• Biotin is an effective blood sugar stabiliser which is helpful not only for controlling the symptoms of morning sickness but also prevention of gestational diabetes.

• The maximum dose of biotin per day (including pregnant and breastfeeding women) is 500mcg according to Health Canada.

• Biotin supplementation is essential for those with pyroluria.

Ref: Perry et al. (2014). Journal of Nutrition.

Zinc supplementation

• Zinc is essential in pregnancy, however oral zinc

supplementation can cause nausea (whether pregnant or not).

• The RDI of zinc in pregnancy is 11mg daily.

• Zinc citrate is gentle on the stomach and taking only 5.5mg in

one dose should not cause nausea if the supplement is taken

after food.

• For a woman that requires a high dose of zinc (e.g. high

copper levels), try a transdermal zinc cream which can be

ordered from a compounding pharmacist.

Zinc supplementation

Zinc sufficiency is important during pregnancy. Zinc deficiency greatly affects the women’s labour as sufficient zinc is vital for an on-time, quick labour, less tearing and helps prevent postnatal depression. It has also been found that zinc deficient babies cry excessively and are difficult to console (Lazebnik et al).

Zinc is required for more than 300 enzyme reactions including serotonin and GABA synthesis and in fact has the second highest concentration of all transition metals in the brain.

There is a TGA warning that has to go on to all supplements containing more than 25mg of zinc that it can be harmful if taken in large doses or over a long period of time. That is because zinc antagonises copper, however you need 60mg of zinc daily before it starts affecting copper levels and treatment of high copper levels using zinc is usually 100mg daily.

Oral zinc supplementation during the first trimester can cause nausea. Zinc supplementation in the absence of food at any time, pregnant or not can have an emetic effect. A transdermal zinc cream bypasses the digestive system and therefore reduces the likelihood of causing nausea.

References:

Rafeeinia et al. (2014). The Open Biochemistry Journal. Serum copper, zinc and lipid peroxidation in pregnant women with preeclampsia in Gorgan.

Lazebnik et al. (1988), American Journal of Obstetrics & Gynecology. Zinc status, pregnancy complications and labor abnormalities.

Trace Elements in Human and Animal Nutrition, 5th ed, vol 2, p. 84., Walter Mertz

Copper supplementationCopper levels naturally rise during pregnancy due to rising oestrogen levels which increase hepatic caeruloplasmin synthesis therefore increasing serum copper levels and this is well documented in the literature (Crayton & Walsh, 2007).

Through clinical experience I have discovered that women usually have high levels of copper in the blood and low zinc prior to pregnancy. Adding more copper during pregnancy increases the risk of high copper levels and subsequent postnatal depression (Crayton and Walsh, 2007)

In pregnancy, excess copper levels (i.e. higher than 45 umol/L (micromole) – normal reference range pre-pregnancy is 11-22 umol/L) can be associated with intrauterine growth restriction, preeclampsia and neurological disease.

There is also an interesting case study of a link between copper excess in pregnancy and autism in the baby (Walker et al, 2011).

References:

CRAYTON, J. W. & WALSH, W. J. 2007. Elevated serum copper levels in women with a history of post-partum depression. J Trace Elem Med Biol, 21,17-21.

WALKER, L. R., RATTIGAN, M. & CANTERINO, J. 2011. A case of isolated elevated copper levels during pregnancy. Journal of Pregnancy, 2011.

Vitamin D deficiencyDark skinned and veiled women are particularly at risk (Grover & Morley, 2001).

People these days have a sun phobia (melanoma risk) so virtually everyone is at risk of a deficiency but particularly the following:

• Women with a high number of pregnancies and prolonged breastfeeding.

• Women with low cholesterol prior to conception.

• Women with GI inflammatory disorders

• Vegans and vegetarians.

Food sources include mackerel, herring, tinned salmon and sardines, egg yolk, butter, full cream milk.

Reference:

Grover, SR & Morley, R (2001). Vitamin D deficiency in veiled or dark-skinned pregnant women. Med J Aust; 175(5):251-252.

Vitamin D Assessment

The “normal” range is 50-250mmol/L, however in reality we should be aiming for the following:

• <50 Deficiency (needs 4000iu daily then re-test in one month)

• 50-80 Insufficiency (needs 2000iu daily then re-test in 3 months)

• 80-250 Sufficient – Test at the end of each trimester

• >250 Excess

Be careful of vitamin D overdose in pregnancy – “Hypercalcemia during pregnancy due to excessive vitamin D intake can lead to several adverse effects in the foetus including suppression of parathyroid hormone, hypocalcemia, tetany, seizures, aortic valve stenosis, retinopathy, and mental and/or physical retardation in the infant”

Ref: Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf.

IodineIodine deficiency is widespread in Australia and NZ due to deficient

soils and an iodine deficient diet.

Unfortunately pregnant women have an increased renal clearance of

iodine. Maternal deficiency can lead to goitre, cretinism, congenital

anomalies, miscarriage, stillbirth, an infant with a lowered IQ,

learning difficulties, motor skill problems and hearing difficulties

(Hamaoui, 2003).

“Of all the essential micronutrients, iodine is unusual in that there is

only modest somatic storage, most occurring in the thyroid.

Maintaining a euthyroid condition therefore requires continual access

to dietary iodine, a challenge that grows during pregnancy” (Forbes,

2014).

However even with daily iodine supplementation during pregnancy,

T4 levels still drop in the second trimester without an increase in TSH

suggesting it is a normal physiological function (Brucker-Davis et al.,

2013)

Soy milk and raw cruciferous vegetables are goitrogenic.

Good food sources include fish, shellfish, miso soup, eggs and iodised

salt (71mcg in ¼ tsp iodised salt, 100mcg in ¼ tsp of Nirvana Organics

Himalayan crystal salt).

References:

BRUCKER-DAVIS, F., PANAIA-FERRARI, P., GAL, J.,

FENICHEL, P. & HIERONIMUS, S. 2013. Iodine

Supplementation throughout Pregnancy Does

Not Prevent the Drop in FT4 in the Second and

Third Trimesters in Women with Normal Initial

Thyroid Function. European Thyroid J, 2, 187-94.

FORBES, S. 2014. Pregnancy sickness and parent-

offspring conflict over thyroid function. J Theor

Biol, 355, 61-7.

HAMAOUI, E. (2003). Nutritional assessment and

support during pregnancy. Gastroenterology Clin

N Am: (32);59-121.

IodineWe do need to careful about not overdoing it when it comes to iodine supplementation in the first trimester.

Hcg, the pregnancy hormone naturally stimulates the thyroid in the first trimester and so we see a drop in TSH. A hyperthyroid state in the first trimester is associated with increased nausea or vomiting (NVP) or hyperemesis gravidarum and in fact it has been suggested that a woman who doesn’t suffer NVP could be hypothyroid (Forbes, 2014)

Also, excess iodine of more than 200mcg per day in the first half of pregnancy has been associated with an increased risk of a TSH higher than 3 and subclinical or even overt hypothyroidism later in pregnancy (Rebagliato et al., 2010)

Iodine supplementation should be limited to 150mcg in the first trimester to err on the side of caution with the balance coming from her diet. The RDI of iodine in pregnancy is 220mcg daily.

References:

FORBES, S. 2014. Pregnancy sickness and parent-offspring conflict over thyroid function. J Theor Biol, 355, 61-7.

REBAGLIATO, M., MURCIA, M., ESPADA, M., ALVAREZ-PEDREROL, M., BOLUMAR, F., VIOQUE, J., BASTERRECHEA, M., BLARDUNI, E., RAMON, R., GUXENS, M., FORADADA, C. M., BALLESTER, F., IBARLUZEA, J. & SUNYER, J. 2010. Iodine intake and maternal thyroid function during pregnancy. Epidemiology, 21,62-9.

Iodine Assessment

Urinary iodine tests are not appropriate to diagnose iodine deficiency. Urine iodide reflects only recent iodine intake.

Iodine deficiency is best assessed using TSH, T4 and T3 although low T3 can be an indication of zinc and/or selenium deficiency.

Reference:

Zimmermann MB. Methods to assess iron and iodine status. Br J Nutr. 2008;99(Suppl3):S2–9.

Rasmussen LB, Ovesen L, Christiansen E. Day-to-day and within-day variation in urinary iodine excretion. Eur J Clin Nutr. 1999;53:401–7.

Choline

• Choline is essential for brain development of the baby and the RDI is 450mg daily.

• Eggs have a high choline content with 147mg per egg.

• 100gms of cooked veal contains 123mg.

• 1 cup of milk contains 35mg.

• Choline is mostly found in animal products so vegans are most at risk of deficiency.

• Choline deficiency during pregnancy may have lifelong effects on the child’s brain function, in particular memory and attention.

Ref: Zeisel, S.H. Nutritional importance of choline for brain development. Journal of the American College of Nutrition, 2004. 23(sup6), pp. 621S-626S.

Pre-eclampsia: symptoms

Pre-eclampsia occurs in 2-8% of pregnancies, takes place in the

late second or third trimester and symptoms include:

• Hypertension

• Oedema particularly of the lower extremities

• Protein in the urine

• Sudden weight gain

• Headaches

• Changes in vision

Pre-eclampsia: risk factors

Strong risk factors:

• Previous pre-eclampsia or hypertension in pregnancy

• Autoimmune disorders, including systemic lupus erythematosus or anti phospholipid syndrome

• Chronic kidney disease

• Hypertension

• Diabetes (type 1 or type 2)

Moderate risk factors:

• First pregnancy

• Age 40 years or more

• Pregnancy interval greater than 10 years

• BMI of more than 35

• PCOS

• Family history of pre-eclampsia

• Multiple pregnancy

• Women who have donated a kidney were twice as likely to have pre-eclampsia than matched women who had not donated a kidney

• Women with MTHFR polymorphisms are at greater risk due to greater risk of folate deficiency and its effect on homocysteine metabolism. Supplementation with folate throughout pregnancy has been associated with lower homocysteine levels and a reduced risk of preeclampsia.

• A 2015 meta-analysis showed an increased risk of pre-eclampsia associated with MTHFR C677T genotype especially for Asians and Caucasians. Hyperhomocysteinaemia leads to a 3-8 fold increased risk of pre-eclampsia and homocysteine is lowered with adequatelevels of vitamins B6, B12 and folate.

References:

• Mol, B.W.J., et al., Pre-eclampsia. The Lancet, 2016. 387(10022): p. 999-1011.

• Hechtman, L. Clinical Naturopathic Medicine, 2012

• Wu, X., et al., Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis. J Assist Reprod Genet, 2015. 32(5): p. 797-805.

Pre-eclampsia: complications

Complications associated with pre-eclampsia include:

• Intrauterine growth restriction and premature birth which increases the risk of bronchopulmonary dysplasia and cerebral palsy.

• Reduced perfusion of the organs due to vasoconstriction, increased coagulation resulting in microthrombi, reversible hypercholesterolaemia, increased oxidative stress, increased inflammation and hyperhomocysteinaemia.

• There may be serious complications for the mother including liver rupture, stroke, pulmonary oedema, kidney failure, stroke and eclampsia and is the second highest direct cause of maternal death.

• Pre-eclampsia predisposes a woman to postnatal depression and cardiovascular issues later in life.

References:

• Mol, B.W.J., et al., Pre-eclampsia. The Lancet, 2016. 387(10022): p. 999-1011.

• Hechtman, L. Clinical Naturopathic Medicine, 2012.

Pre-eclampsia: Cu and Zn

• This condition is associated with increased levels of lipid peroxidation in the blood and placenta and elevated ROS in the placenta, during delivery and the period following birth.

• An increased copper concentration has been found in many studies and this may be due to the fact that copper produces the highly reactive hydroxyl radical which can begin the lipid peroxidation process and may cause endothelial cell damage.

• The Cu/Zn ratio has been found to be significantly higher in women with pre-eclampsia than healthy pregnant women.

• Serum caeruloplasmin and uric acid levels have the best diagnostic accuracy for oxidative stress in women with pre-eclampsia.

References:

• Rafeeinia, A., Serum copper, zinc and lipid peroxidation in pregnant women with preeclampsia in gorgan. Open Biochemistry Journal 2014. 8: p. 83-88.

• Nikolic, A., et al., Ceruloplasmin and antioxidative enzymes in pre-eclampsia. J Matern Fetal Neonatal

Pre-eclampsia: prevention• Supplementing with magnesium may help due to the fact it is a vasodilator and is able to reduce blood pressure. A study found a

significant decrease in serum magnesium in women with pre-eclampsia compared to normal healthy pregnant women and the treatment used for the prevention and treatment of eclampsia is magnesium sulfate (Jafrin et al).

• Another RCT found that 300mg of magnesium citrate given from week 25 of pregnancy significantly prevented an increase in diastolic BP during the last weeks of pregnancy compared to placebo (Bullarbo et al).

• Magnesium glycinate is not excreted from the kidneys as quickly as magnesium citrate (Klotter, J)

• A recent meta-analysis showed that serum zinc is lower in women with pre-eclampsia than healthy pregnant women and moderate zincsupplementation was recommended to reduce the incidence of pre-eclampsia (Ma et al)

• A recent systematic review showed there is some evidence that vitamin D supplementation could reduce the risk of pre-eclampsia as well as increase length and head circumference at birth (De-Regil et al)

• The WHO recommends high dose calcium supplementation for women with low dietary calcium intake. 1.5-2 grams daily. If supplementing with a good quality calcium such as calcium citrate, 1000-1200mg should be sufficient (von Dadelszen & Magee; Mol et al) A Cochrane review reported a benefit of calcium 1000mg daily in reducing preterm labour and hypertensive disorders.

• Supplementing with a multivitamin in the preconception period has been shown to reduce the risk of pre-eclampsia especially in lean women (Bodnar et al)

References:

• Jafrin, W., et al., An evaluation of serum magnesium status in pre-eclampsia compared to the normal pregnancy. Mymensingh Med J, 2014. 23(4): p. 649-53.

• Bullarbo, M., et al., Magnesium supplementation to prevent high blood pressure in pregnancy: a randomised placebo control trial. Arch Gynecol Obstet, 2013. 288(6): p. 1269-74.

• Klotter, J., Magnesium deficiency and cardiovascular disease. Townsend Letter, 2014. 370(2): p. 27.

• Ma, Y., X. Shen, and D. Zhang, The Relationship between Serum Zinc Level and Preeclampsia: A Meta-Analysis. Nutrients, 2015. 7(9): p. 7806-20.

• De-Regil LM, P.C., Lombardo LK & Peña-Rosas JP., Vitamin D supplementation for women during pregnancy. Sao Paulo Medical Journal, 2016. 134(3): p. 274-275.

• von Dadelszen, P. and L.A. Magee, Pre-eclampsia: an update. Curr Hypertens Rep, 2014. 16(8): p. 454.

• Mol, B.W.J., et al., Pre-eclampsia. The Lancet, 2016. 387(10022): p. 999-1011.

• Bodnar, L.M., et al., Periconceptional multivitamin use reduces the risk of preeclampsia. Am J Epidemiol, 2006. 164(5): p. 470-7.

Gestational diabetes: symptoms

• Gestational diabetes occurs in 1-14% of pregnancies, usually

takes place in the late second or third trimester and symptoms

include:

• Unusual thirst

• Excessive urination

Although it is often asymptomatic.

Gestational diabetes: risk factors

Non-modifiable risk factors:

• Family history of type 2 diabetes

• GDM in a previous pregnancy

• Age >35

• Particular ethnic groups

Modifiable risk factors:

• High BMI prior to pregnancy

• Excessive maternal weight gain during pregnancy

• Low levels of exercise

Gestational diabetes: complications

Maternal effects:

• Poor birth outcomes due to macrosomia – increased risk of perineal trauma and caesarean delivery

• Placental abruption

• Increased risk of pre-eclampsia

Foetal effects:

• Macrosomia (birthweight >4.5kg)

• Neonatal hypoglycaemia

• Respiratory distress syndrome

• Bone fractures

• Nerve palsies

• Greater incidence of preterm birth

• Child is more likely to be obese at risk for developing type 2 diabetes

Gestational diabetes: prevention

• Regular exercise – 30 minutes daily.

• Increase fibre, good fats and protein in the diet to help satisfy hunger and stabilise blood sugar.

• Cinnamon and fenugreek are blood sugar stabilisers and the amounts used in food are considered to be safe during pregnancy.

• Gymnema has not been studied for gestational diabetes but there is no evidence of harmful foetal effects. Studies have shown benefit in the treatment of type 2 diabetes.

• Magnesium may be beneficial due to the fact it is a co-factor in many enzymes involved in glucose metabolism. Studies have found lower levels of magnesium in women with GDM than healthy pregnant women.

• Zinc generates an insulin-like effect and studies have found that women with GDM have lower serum levels of zinc than healthy pregnant women.

• Lower selenium levels are found in women with GDM and as well as improving insulin sensitivity, selenium is an antioxidant. The RDI during pregnancy is 65mcg

• 100mg daily of vitamin B6 resulted in significant improvement of glucose tolerance in women with GDM.

• Vitamin D deficiency may be a risk factor for developing GDM.

Reference: Clinical Naturopathic Medicine, 2012, Leah Hechtman.

Gestational diabetes: preventionA study in 1999 compared a group of women taking 4mcg chromium picolinate per kg per day (e.g. women weighed 70kg she would be taking 280mcg), a group of women taking 8mcg chromium picolinate per kg per day to placebo.

Result – after 8 weeks the 4mcg group had significantly lower HbA1c compared to baseline and both supplemented groups had significantly lower fasting glucose and insulin levels compared to baseline.

Biotin in high doses has been found to substantially lower fasting glucose in type II diabetics without side effects and a review article has suggested that chromium and biotin in combination may be effective in the prevention and treatment of gestational diabetes. Health Canada states that 500mcg of biotin is the safe upper limit for women during pregnancy and breastfeeding.

Antioxidants may have a beneficial effect. Alpha lipoic acid is an excellent antioxidant as well as being involved in glucose metabolism and an interesting study on rats showed that supplementation with ALA resulted in a significant reduction in congenital abnormalities and intrauterine growth restriction compared to diabetic rats who were not treated. The authors stated that the study highlighted the possible role of antioxidants in the normal processes of embryo survival, growth and development.

References

Jovanovic, L., Gutierrez, M., Peterson, C.M. & Jovanovic, L., Chromium supplementation for women with gestational diabetes mellitus. The Journal of Trace Elements in Experimental Medicine, 1999. 12(2): p. 91 -97

Mccarty, M.F., High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes. Medical hypotheses, 1999. 52(5): p. 401 -406.

Al Ghafli, M.H.M., Padmanabhan, R. , Kataya, H.H. & Berg, B., Effects of α-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat foetuses.Molecular and Cellular Biochemistry, 2004. 261(1): p. 123 -135

Case study

• 33 year old woman, had a miscarriage 9 weeks prior to coming to see me. After hearing the heartbeat on ultrasound at 7 weeks she miscarried one week later. No morning sickness with this pregnancy. Had not had period since.

• Diet and lifestyle was excellent and had recently quit stressful job.

• Heterozygous A1298C

• Prolactin - 33.5ug/L (normal range <25)

• Homocysteine - 5.5 umol/L

• Ferritin – 193 ug/L

• CRP – 0.4 mg/L

• TSH – 1.5 mU/L

• Red cell zinc – 167 umol/L

• Copper – 11.4 umol/L

• Vitamin D – 55 nmol/L

• Weight – 51.8kg, BMI 19.54

• BP – 92/66

Case study continued

Treatment plan:

• Vitex 1000mg daily

• Custom vitamin/mineral formula with 75mg of vitamin B6 and 1000iu vitamin D and no iron

• Transdermal zinc cream – 50mg daily

• Probiotic – x1 daily

• Prenatal DHA – x2 daily

Returned to see me one month later and announced she was pregnant. Continued treatment plan and advised to stop taking Vitex at 8 weeks.

Follow up at 14 weeks gestation:

Ferritin – 167

Plasma zinc – 10

Copper – 18

Had felt slightly queasy but took this as a reassuring sign that everything was well with the pregnancy.

• Changed custom formula – no iron and 50mg of zinc added to formula.

Follow up at 28 weeks gestation:

Ferritin – 32

Red cell zinc – 211 (180-260)

Copper - 30

TSH – 1.5

Vitamin D – 55

• Zinc reduced to 25mg and iron bisglycinate included 25mg

Case study continued

• Gave birth to a healthy 7lb 5oz baby girl at 40 + 4. Birth went

smoothly and only gas was used during transition.

• Follow up at 3 months post-partum:

• Ferritin – 104

• Vitamin D – 84

• TSH – 1.4

• Copper – 14

• Plasma zinc – 12

Excipients commonly used

Excipients:• Microcrystalline cellulose – emulsifier, safe.

• Calcium hydrogen phosphate – flowing agent, mineral, safe and beneficial.

• Silica – flowing agent, mineral, safe and beneficial.

• Vegetable capsule (Vcap).

Excipients commonly used in tablets:• Magnesium stearate – used as a flowing agent, may affect release time of active ingredients.

• Povidone – disintegrant and tablet binder.

• Croscarmellose sodium – disintegrant, can cause issues for people with gluten intolerance.

• Crospovidone – disintegrant.

• Hypromellose – binder and component of tablet coatings.

• Macrogol 400 – binder and component of tablet coatings, commonly used as a laxative.

• Iron oxide or titanium dioxide – tablet coatings, colourings.

• Carnauba wax – tablet coating and binder.

Questions

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