Natural health products are popular among pregnant women in Australasia,1,2 yet potential risks of exposure to teratogenic herbs, vitamins and other substances raise concerns regarding the present lack of effective regulation of the complementary and alternative medicine (CAM) industry in New Zealand.Natural health (or CAM) products, including herb, mineral and vitamin supplements, are marketed for pregnancy on the basis of health promotion as well as to remedy pregnancy-associated ailments such as nausea and vomiting of pregnancy (NVP).Consumers may use them with the belief that they are ‘natural' and therefore safe; attracted by the autonomy of self-care; or wary of conventional medicines and their adverse effects.3However, not only is there little evidence of the efficacy or safety of CAMs promoted for pregnancy in New Zealand, but there are risks of toxicity from herbal ingredients and supplement overdosing, product contamination and adulteration, as well as interactions with conventional drugs.4CAMs are widely available from advertisements, pharmacies, health food stores, supermarkets, on the Internet and from medical practitioners.5 In New Zealand the CAM industry is substantial, with manufacturers' annual turnovers ranging from $100,000 to >$20M.6CAM use in pregnancy is specifically addressed by the New Zealand Ministry of Health (MOH) in the Food and Nutrition Guidelines for Healthy Pregnant and Breastfeeding Women which sets out evidence-based recommendations regarding the use of vitamins, minerals and herbs.7The guidance explicitly states that there is no requirement for a healthy pregnant woman to take multi-vitamin supplementation; and that a balanced diet is sufficient. It also states that ‘all herbs should generally be avoided'. It advocates discussion with the lead maternity carer regarding taking any supplements and herbs prior to their commencement. Unfortunately, research shows that CAM use is often not discussed with a primary care physician.8NVP is a common and distressing ailment of early pregnancy and the use of the herb ginger (Zingiber officinale) and vitamin B6 (pyridoxine) are popularly promoted. However, a recent Cochrane review of randomised controlled trials of therapies for mild-moderate NVP concluded that the evidence for a beneficial effect of ginger or pyridoxine supplementation was inconsistent and/or limited.9Matthews et al. found that while adverse effects had not been reported in trials using short courses of low dose ginger 1g daily or 30-75mg pyridoxine daily for NVP, this research was insufficient to prove safety.9 There are also concerns regarding potential toxicity of these substances: pyridoxine is neurotoxic at high doses10 and ginger is considered an emmenagogue (induces menstrual bleeding) in traditional medicine11 and its constituents have been shown to inhibit thromboxane synthetase activity12 and exhibit antiplatelet13 and cytotoxic properties14 although there is conflicting evidence.15,16NZ MOH guidelines recommend that pregnant woman choosing to use ginger for NVP do not exceed a daily dose of 1g and also advise an upper limit of 50mg pyridoxine daily.7The key issue that this study sought to investigate was the risks which a woman may face when seeking advice regarding NVP, and vitamin supplementation during pregnancy from pharmacies and health food stores (HFS) in Greater Wellington.Methods A search of The Yellow Pages telephone directory in February 2010 identified 26 Health Food Stores (HFS) in the Greater Wellington region. Of these, 5 were excluded: 3 were no longer in operation, 1 was a residential property, and 1 specialised in sports supplements. Twenty-one HFS and 21 geographically-matched pharmacies (on the basis of closest location to the HFS) were visited by the same researcher between the months of February to July 2010. With each visit, the researcher commenced a conversation with a retail assistant by saying she was 6-8 weeks pregnant, having problems with morning sickness, and enquiring about any herbal products which the retail assistant could recommend to help reduce nausea. The researcher would then ask what the retail assistant could recommend with regards to vitamin supplementation. Finally she asked which vitamins were important during pregnancy and if there were any to avoid. If questioned by the retail assistant, the researcher would reply, as appropriate, saying she was: 30 years old, married, excited about her first pregnancy, currently working in a clerical office job, and otherwise fit and healthy with no previous medical history. During each interaction, the researcher would take note of the products recommended and their prices, and upon leaving immediately complete a standardised data collection form to document the advice received. The ingredients of each recommended product were later confirmed by searching for the product on the Internet. The NZ MOH Food and Nutrition Guidelines of Healthy Pregnant and Breastfeeding Women (revised 2008) was the standard against which all advice was compared. For ingredients not noted therein, a database search using Medline was performed for evidence of safety during the first trimester of pregnancy. The following criteria were used to evaluate advice given: Products recommended for nausea in the first trimester of pregnancy Safe—Product contains ingredients which are not absolutely contraindicated in pregnancy or their daily dose does not exceed the upper limit recommended by NZ MOH guidelines, or, if the ingredient is unknown, there is no evidence that it may be unsafe by Medline search of the literature. Unsafe—Product contains ingredients which are absolutely contraindicated in pregnancy or the daily dose exceeds the upper limit recommended by NZ MOH guidelines, or, if the ingredient is unknown, there is evidence that it may be unsafe by Medline search of the literature. Advice regarding vitamin supplementation in early pregnancy - folic acid advice Correct—Dose advised corresponds with NZ MOH guidelines for supplementation with 800 mcg/day in low-risk pregnancy. Incorrect—Folic acid not recommended or dose advised was less than 800 mcg/day. Advice regarding vitamin supplementation in early pregnancy - Vitamin A overdose risk. Safe—Advice given did not pose risk of vitamin A overdose. This includes recommendation of a multivitamin product marketed for pregnancy which did not contain doses of vitamin A exceeding 3000mcg/day of retinol, even without demonstrating explicit vitamin A overdose awareness. Unsafe—Advised that there is no limit to vitamin dosing during pregnancy or recommended a product containing >3000 mcg/day of retinol or advised to take any generic multivitamin. Statistical analysis Paired contingency table analysis was used to examine the agreement between the matched pairs in advice between pharmacies and HFS. Statistical analysis was by an exact McNemar's test and a confidence interval for the difference in marginal proportions, representing the proportion of pharmacies that gave particular advice versus the proportion of matched HFS that gave advice.17 A statistically significant McNemar's test means the marginal proportions of the contingency table are different. In the analysis McNemar's test is based on an exact test whereas the confidence interval is based on asymptotic (large sample) assumptions. Where more than one product was recommended for nausea, the primary recommended products were compared in one analysis, and then the secondarily recommended products compared separately. The number of matched pharmacies/HFS was based on an earlier study comparing the advice from HFS assistants with that of pharmacy assistants given to an individual presenting with symptoms suggestive of moderate to severe asthma who should be referred to a medical practitioner18 Based on this, it was calculated that the study would need to have 19 store/pharmacy pairs to have 80% power to detect the difference. The study was approved by the Central Regional Ethics Committee. Results Data was collected from 21 HFS and 21 geographically-matched pharmacies in the Greater Wellington region. The investigator was advised by retail assistants in all the HFS, with 6/21 (28.6%) HFS advising further discussion with a naturopath (n=2) or GP (n=4). In 7/21 pharmacies, advice was indirectly (n=3) or directly (n=4) from the pharmacist. 9/21 (42.9%) of pharmacies referred the researcher to a GP (n=7) and/or midwife (n=2) during the interaction. Table 1 lists the products recommended for nausea and Table 2 summarises other recommendations made, including multivitamin supplementation. Table 1. Products recommended for nausea by Health Food Stores (HFS) and pharmacies (P), their retail price, ingredients and adherence with MOH guidelines Recommended products: Name, manufacturer (recommended by) Price range of products offered ($) Daily doses if maximum dose taken as directed on packet/ otherwise directed MOH recommendation (Y/N) Safe/Potentially unsafe (S/PU) Ginger+Vitamin B6: Morning Sickness Formula, Blackmores (8HFS, 10P) Ginger: Travel Calm Ginger, Blackmores (10P) Ginger syrup/ capsules, Lifestream (4HFS) Crystalised ginger (3HFS) Ginger drops, Botanicals (1HFS) Ginger from a general store e.g. Raw ginger/ ginger beer/ale (3HFS, 5P) Ginger tea, Planet Organic (2HFS) Raspberry leaf: Raspberry leaf, Blackmores (1P) Vitamin B6 supplements: From multivitamins (1HFS, 2P) Other vitamins: Morning Wellness Support, Clinicians (1P) Homeopathy: Morning medrelief, Naturopharm (11HFS) Nausyn, Weleda* (3HFS, 2P) Nausmed relief, Naturopharm (2HFS) Saccharum/Mel complex, Weleda (1HFS) Other: Acupressure wrist bands (11P) Frequent snacking (2HFS) 17.50-23.00 16.50-18.60 17.00-17.40 4.10-7.30 14.00 4.60-7.85 12.79 29.99 19.60-21.30 14.00-18.90 20.30-20.80 17.50 22.50-23.99 Ginger root 1.2g B6 75mg Ginger root 5.6g Ginger rhizome 1-3g Not directed ‘Ginger veg glyceride' 1g Not directed Not directed Rubus idaeus (Raspberry) leaf powder/equivalent 6g Varying levels in multivitamins - all <50mg Vit B6 75mg Vit C 75mg Vit K1 270mcg N/A N/A N/A N/A N/A N/A N N 1g=R (1HFS) >1g=N (3HFS) N Y N N N N N N N N N Y Y PU PU PU PU S PU PU PU S PU S S S S S S In brackets = Number of HPS and P recommendations for the product. *Also contains herb mixture called cardiodoron 250mg/15 drops = Digestion, equiv. fresh plant juice: Hyoscyamus niger, herb 1mg; onopordon acanthium, flower 25mg; Primula veris, flower 25mg. Nausyn is licensed by Medsafe as a Medicine. Advice given for nausea in the first trimester of pregnancy—5/21 (23.8%) of pharmacies and 1/21 (4.8%) of HFS made primary recommendations for nausea which were supported by the NZ MOH guidelines, with a non significant difference in marginal proportions of 19.1% (95%CI -2.3% to 40.4%), p=0.10. Both pharmacies (14/21, 66.7%) and HFS (7/21, 33.3%), made primary recommendations which were contrary to NZ MOH safety guidance. The difference in marginal proportions was 33.4% (95%CI 5.9% to 60.8%), p= 0.07. With regards to recommendations of second-line products which were contrary to MOH safety guidance, this occurred in 7/21 (33.3%) of pharmacies and 10/21 (47.6%) of HFS with a non significant difference in marginal proportions of -14.3% (95%CI -41.6% to 13.0%), p=0.51. The most common reason for a product being considered unsafe was that it provided >1g ginger ± >50 mg pyridoxine in the maximum daily dose as directed (Table 1). 7/21 (33.3%) of pharmacies and 0/21 (0%) of HFS advised GP consultation if nausea did not settle. Due to two zero cell counts in the paired contingency table, it was not possible to calculate McNemar's test or a confidence interval for the difference in paired proportions. Advice promoting a balanced diet with folic acid supplementation—1/21 (4.8%) of HFS and 0/21 (0%) of pharmacies correctly advised that a balanced diet, along with folic acid supplementation, was recommended during pregnancy in otherwise healthy young women. However, 0/21 of HFS and 18/21 (85.7%) of pharmacies primarily recommended Elevit by Bayer, a multivitamin product which is licensed by Medsafe. Due to zero cell counts in the paired contingency tables, it was not possible to calculate McNemar's test or a confidence interval for the difference in these paired proportions. Table 2. Summary of other products/ advice given. Numbers represent the total number of pharmacies (P) or Health Food Stores (HFS) giving recommendation (whether primary or secondary) Multivitamin supplements Other supplements

Natural health products are popular among pregnant women in Australasia,1,2 yet potential risks of exposure to teratogenic herbs, vitamins and other substances raise concerns regarding the present lack of effective regulation of the complementary and alternative medicine (CAM) industry in New Zealand.Natural health (or CAM) products, including herb, mineral and vitamin supplements, are marketed for pregnancy on the basis of health promotion as well as to remedy pregnancy-associated ailments such as nausea and vomiting of pregnancy (NVP).Consumers may use them with the belief that they are ‘natural' and therefore safe; attracted by the autonomy of self-care; or wary of conventional medicines and their adverse effects.3However, not only is there little evidence of the efficacy or safety of CAMs promoted for pregnancy in New Zealand, but there are risks of toxicity from herbal ingredients and supplement overdosing, product contamination and adulteration, as well as interactions with conventional drugs.4CAMs are widely available from advertisements, pharmacies, health food stores, supermarkets, on the Internet and from medical practitioners.5 In New Zealand the CAM industry is substantial, with manufacturers' annual turnovers ranging from $100,000 to >$20M.6CAM use in pregnancy is specifically addressed by the New Zealand Ministry of Health (MOH) in the Food and Nutrition Guidelines for Healthy Pregnant and Breastfeeding Women which sets out evidence-based recommendations regarding the use of vitamins, minerals and herbs.7The guidance explicitly states that there is no requirement for a healthy pregnant woman to take multi-vitamin supplementation; and that a balanced diet is sufficient. It also states that ‘all herbs should generally be avoided'. It advocates discussion with the lead maternity carer regarding taking any supplements and herbs prior to their commencement. Unfortunately, research shows that CAM use is often not discussed with a primary care physician.8NVP is a common and distressing ailment of early pregnancy and the use of the herb ginger (Zingiber officinale) and vitamin B6 (pyridoxine) are popularly promoted. However, a recent Cochrane review of randomised controlled trials of therapies for mild-moderate NVP concluded that the evidence for a beneficial effect of ginger or pyridoxine supplementation was inconsistent and/or limited.9Matthews et al. found that while adverse effects had not been reported in trials using short courses of low dose ginger 1g daily or 30-75mg pyridoxine daily for NVP, this research was insufficient to prove safety.9 There are also concerns regarding potential toxicity of these substances: pyridoxine is neurotoxic at high doses10 and ginger is considered an emmenagogue (induces menstrual bleeding) in traditional medicine11 and its constituents have been shown to inhibit thromboxane synthetase activity12 and exhibit antiplatelet13 and cytotoxic properties14 although there is conflicting evidence.15,16NZ MOH guidelines recommend that pregnant woman choosing to use ginger for NVP do not exceed a daily dose of 1g and also advise an upper limit of 50mg pyridoxine daily.7The key issue that this study sought to investigate was the risks which a woman may face when seeking advice regarding NVP, and vitamin supplementation during pregnancy from pharmacies and health food stores (HFS) in Greater Wellington.Methods A search of The Yellow Pages telephone directory in February 2010 identified 26 Health Food Stores (HFS) in the Greater Wellington region. Of these, 5 were excluded: 3 were no longer in operation, 1 was a residential property, and 1 specialised in sports supplements. Twenty-one HFS and 21 geographically-matched pharmacies (on the basis of closest location to the HFS) were visited by the same researcher between the months of February to July 2010. With each visit, the researcher commenced a conversation with a retail assistant by saying she was 6-8 weeks pregnant, having problems with morning sickness, and enquiring about any herbal products which the retail assistant could recommend to help reduce nausea. The researcher would then ask what the retail assistant could recommend with regards to vitamin supplementation. Finally she asked which vitamins were important during pregnancy and if there were any to avoid. If questioned by the retail assistant, the researcher would reply, as appropriate, saying she was: 30 years old, married, excited about her first pregnancy, currently working in a clerical office job, and otherwise fit and healthy with no previous medical history. During each interaction, the researcher would take note of the products recommended and their prices, and upon leaving immediately complete a standardised data collection form to document the advice received. The ingredients of each recommended product were later confirmed by searching for the product on the Internet. The NZ MOH Food and Nutrition Guidelines of Healthy Pregnant and Breastfeeding Women (revised 2008) was the standard against which all advice was compared. For ingredients not noted therein, a database search using Medline was performed for evidence of safety during the first trimester of pregnancy. The following criteria were used to evaluate advice given: Products recommended for nausea in the first trimester of pregnancy Safe—Product contains ingredients which are not absolutely contraindicated in pregnancy or their daily dose does not exceed the upper limit recommended by NZ MOH guidelines, or, if the ingredient is unknown, there is no evidence that it may be unsafe by Medline search of the literature. Unsafe—Product contains ingredients which are absolutely contraindicated in pregnancy or the daily dose exceeds the upper limit recommended by NZ MOH guidelines, or, if the ingredient is unknown, there is evidence that it may be unsafe by Medline search of the literature. Advice regarding vitamin supplementation in early pregnancy - folic acid advice Correct—Dose advised corresponds with NZ MOH guidelines for supplementation with 800 mcg/day in low-risk pregnancy. Incorrect—Folic acid not recommended or dose advised was less than 800 mcg/day. Advice regarding vitamin supplementation in early pregnancy - Vitamin A overdose risk. Safe—Advice given did not pose risk of vitamin A overdose. This includes recommendation of a multivitamin product marketed for pregnancy which did not contain doses of vitamin A exceeding 3000mcg/day of retinol, even without demonstrating explicit vitamin A overdose awareness. Unsafe—Advised that there is no limit to vitamin dosing during pregnancy or recommended a product containing >3000 mcg/day of retinol or advised to take any generic multivitamin. Statistical analysis Paired contingency table analysis was used to examine the agreement between the matched pairs in advice between pharmacies and HFS. Statistical analysis was by an exact McNemar's test and a confidence interval for the difference in marginal proportions, representing the proportion of pharmacies that gave particular advice versus the proportion of matched HFS that gave advice.17 A statistically significant McNemar's test means the marginal proportions of the contingency table are different. In the analysis McNemar's test is based on an exact test whereas the confidence interval is based on asymptotic (large sample) assumptions. Where more than one product was recommended for nausea, the primary recommended products were compared in one analysis, and then the secondarily recommended products compared separately. The number of matched pharmacies/HFS was based on an earlier study comparing the advice from HFS assistants with that of pharmacy assistants given to an individual presenting with symptoms suggestive of moderate to severe asthma who should be referred to a medical practitioner18 Based on this, it was calculated that the study would need to have 19 store/pharmacy pairs to have 80% power to detect the difference. The study was approved by the Central Regional Ethics Committee. Results Data was collected from 21 HFS and 21 geographically-matched pharmacies in the Greater Wellington region. The investigator was advised by retail assistants in all the HFS, with 6/21 (28.6%) HFS advising further discussion with a naturopath (n=2) or GP (n=4). In 7/21 pharmacies, advice was indirectly (n=3) or directly (n=4) from the pharmacist. 9/21 (42.9%) of pharmacies referred the researcher to a GP (n=7) and/or midwife (n=2) during the interaction. Table 1 lists the products recommended for nausea and Table 2 summarises other recommendations made, including multivitamin supplementation. Table 1. Products recommended for nausea by Health Food Stores (HFS) and pharmacies (P), their retail price, ingredients and adherence with MOH guidelines Recommended products: Name, manufacturer (recommended by) Price range of products offered ($) Daily doses if maximum dose taken as directed on packet/ otherwise directed MOH recommendation (Y/N) Safe/Potentially unsafe (S/PU) Ginger+Vitamin B6: Morning Sickness Formula, Blackmores (8HFS, 10P) Ginger: Travel Calm Ginger, Blackmores (10P) Ginger syrup/ capsules, Lifestream (4HFS) Crystalised ginger (3HFS) Ginger drops, Botanicals (1HFS) Ginger from a general store e.g. Raw ginger/ ginger beer/ale (3HFS, 5P) Ginger tea, Planet Organic (2HFS) Raspberry leaf: Raspberry leaf, Blackmores (1P) Vitamin B6 supplements: From multivitamins (1HFS, 2P) Other vitamins: Morning Wellness Support, Clinicians (1P) Homeopathy: Morning medrelief, Naturopharm (11HFS) Nausyn, Weleda* (3HFS, 2P) Nausmed relief, Naturopharm (2HFS) Saccharum/Mel complex, Weleda (1HFS) Other: Acupressure wrist bands (11P) Frequent snacking (2HFS) 17.50-23.00 16.50-18.60 17.00-17.40 4.10-7.30 14.00 4.60-7.85 12.79 29.99 19.60-21.30 14.00-18.90 20.30-20.80 17.50 22.50-23.99 Ginger root 1.2g B6 75mg Ginger root 5.6g Ginger rhizome 1-3g Not directed ‘Ginger veg glyceride' 1g Not directed Not directed Rubus idaeus (Raspberry) leaf powder/equivalent 6g Varying levels in multivitamins - all <50mg Vit B6 75mg Vit C 75mg Vit K1 270mcg N/A N/A N/A N/A N/A N/A N N 1g=R (1HFS) >1g=N (3HFS) N Y N N N N N N N N N Y Y PU PU PU PU S PU PU PU S PU S S S S S S In brackets = Number of HPS and P recommendations for the product. *Also contains herb mixture called cardiodoron 250mg/15 drops = Digestion, equiv. fresh plant juice: Hyoscyamus niger, herb 1mg; onopordon acanthium, flower 25mg; Primula veris, flower 25mg. Nausyn is licensed by Medsafe as a Medicine. Advice given for nausea in the first trimester of pregnancy—5/21 (23.8%) of pharmacies and 1/21 (4.8%) of HFS made primary recommendations for nausea which were supported by the NZ MOH guidelines, with a non significant difference in marginal proportions of 19.1% (95%CI -2.3% to 40.4%), p=0.10. Both pharmacies (14/21, 66.7%) and HFS (7/21, 33.3%), made primary recommendations which were contrary to NZ MOH safety guidance. The difference in marginal proportions was 33.4% (95%CI 5.9% to 60.8%), p= 0.07. With regards to recommendations of second-line products which were contrary to MOH safety guidance, this occurred in 7/21 (33.3%) of pharmacies and 10/21 (47.6%) of HFS with a non significant difference in marginal proportions of -14.3% (95%CI -41.6% to 13.0%), p=0.51. The most common reason for a product being considered unsafe was that it provided >1g ginger ± >50 mg pyridoxine in the maximum daily dose as directed (Table 1). 7/21 (33.3%) of pharmacies and 0/21 (0%) of HFS advised GP consultation if nausea did not settle. Due to two zero cell counts in the paired contingency table, it was not possible to calculate McNemar's test or a confidence interval for the difference in paired proportions. Advice promoting a balanced diet with folic acid supplementation—1/21 (4.8%) of HFS and 0/21 (0%) of pharmacies correctly advised that a balanced diet, along with folic acid supplementation, was recommended during pregnancy in otherwise healthy young women. However, 0/21 of HFS and 18/21 (85.7%) of pharmacies primarily recommended Elevit by Bayer, a multivitamin product which is licensed by Medsafe. Due to zero cell counts in the paired contingency tables, it was not possible to calculate McNemar's test or a confidence interval for the difference in these paired proportions. Table 2. Summary of other products/ advice given. Numbers represent the total number of pharmacies (P) or Health Food Stores (HFS) giving recommendation (whether primary or secondary) Multivitamin supplements Other supplements