Journal of Obstetrics and Gynaecology
, January 2009; 29(1): 13–16OBSTETRICS
The effectiveness of discontinuing iron-containing prenatal
multivitamins on reducing the severity of nausea and vomiting
of pregnancy
S. K. GILL
1,2, C. MALTEPE1 & G. KOREN1,21
The Motherisk Program, The Hospital for Sick Children and 2Department of Pharmacology, University of Toronto, Toronto,Ontario
Summary
Nausea and vomiting of pregnancy (NVP) is experienced by the majority of pregnant women, and can negatively affect a women’s quality of life. It has been suggested in observational studies that iron-containing prenatal multivitamins may increase the severity of NVP. The objective of this study was to determine whether decreasing iron exposure can mitigate NVP symptoms. Data were collected from a prospective cohort at the Motherisk Program in Toronto. Women (n¼97) seeking advice on managing severe NVP were advised to discontinue prenatal multivitamin administration and switch to folic acid, an adult multivitamin or a children’s chewable multivitamin. Two-thirds (63 out of 97) (p50.001) of those women qualitatively reported an improvement in NVP symptoms after discontinuation of iron-containing prenatal multivitamins. These findings were verified quantitatively using both the pregnancy-unique quantification of emesis and nausea (PUQE) (p50.001) and well-being (p50.001) scoring systems. This is the first interventional study showing that discontinuation of iron results in improvement of NVP symptoms. Our data suggest that avoiding iron-containing prenatal multivitamins in the first trimester is effective in improving NVP symptoms in the majority of pregnant women suffering from morning sickness.
Keywords
Nausea and vomiting of pregnancy (NVP), iron, prenatal multivitamin supplementation
Introduction
Nausea and vomiting of pregnancy (NVP) is experienced by 80% of pregnant women (Nguyen and Einarson 2006). Symptoms commonly occur between the 4th and 9th weeks of pregnancy until the 12th–16th weeks of pregnancy; however, for 20% of pregnant women, symptoms persist throughout pregnancy of which 1–3% experience the most severe form,
hyperemesis gravidarum (Miller 2002). NVP can drastically impact a woman’s quality of life and her ability to function, especially when improperly managed (Attard et al. 2002). Causative factors that may trigger or worsen NVP need to be identified to help manage this condition appropriately. Certain factors have been shown to aggravate NVP including certain medical conditions such as acid reflux (Koch 2002), migraines (Eliakim et al. 2000) and thyroid disorders (Eliakim et al. 2000; Hod et al. 1994), maternal age at conception (Louik et al. 2006), gravidity (Louik et al. 2006) and the use of iron containing prenatal multivitamin supplementation (Koren and Pairaudeau 2006). Multivitamin supplementation in pregnancy has been shown to be important for the health and well-being of both mother and child (Kontic-Vucinic et al. 2006). It has been very well established that nutritional requirements for pregnant women are often not met through diet alone; therefore, to ensure that sufficient metabolic demands are being met, and that adverse health outcomes are prevented, neonatal multivitamin supplementation is strongly recommend by health authorities (Kontic-Vucinic et al. 2006). Recent studies have shown that folate-containing prenatal multivitamin supplementation may decrease the risk for congenital anomalies (Goh et al. 2006), in addition to prevention of neural tube defects, as well as decreasing the risks for certain paediatric cancers (Goh et al. 2007). Despite the strong evidence to support the use of folate in the periconceptional period, a large proportion of women do not use, or discontinue multivitamins in pregnancy (Koren and Pairaudeau 2006). Discontinuation of multivitamin supplementation is usually associated with factors such as tablet size, and pre-existing gastrointestinal conditions and/or symptoms which can worsen NVP (Nguyen et al. 2008). An important factor in NVP associated with multivitamin supplementation during pregnancy is the iron content (Hyder et al. 2002). Iron is an important mineral in pregnancy especially since most women do not consume sufficient amounts through their diet to replenish iron stores. To avoid iron-deficiency anaemia in pregnancy, the recommended daily dose is 27 mg (Health Canada 2005), and iron content in prenatal multivitamins ranges from 27–60 mg. Iron, however, is associated with adverse effects including heartburn, constipation, diarrhoea, nausea and vomiting (Melamed et al. 2007). These symptoms can either directly or indirectly aggravate NVP symptoms alreadyexperienced by pregnant women leading to discontinuation of prenatal multivitamin supplementation. The primary objective of this study was to quantify the effectiveness of discontinuation of iron containing prenatal multivitamins on the severity of NVP.Methods
The Motherisk Program, located at the Hospital for Sick Children in Toronto, has a specialised helpline for the management of NVP, which, we believe is the only such service worldwide. Women from Canada and the USA who are experiencing NVP can call a toll-free information service to receive pharmacological and nonpharmacological advice on the management of NVP. This evidence-based counselling is standardised so that every woman is offered similar strategies to help manage her NVP. The intervention evaluated in the present study is routine in our service; women suffering from NVP are advised to discontinue their iron-containing prenatal vitamins substituting it with a preparation not containing iron. All data collected by the NVP Helpline from January 2005 to April 2007 were evaluated. Inclusion criteria consisted of women who had previously been using a prenatal multivitamin at the time of initial counselling, who were advised to discontinue the iron-containing prenatal multivitamin and switch to folic acid, an adult multivitamin or a children’s chewable multivitamin. Women who did not meet these requirements or those who were not stabilised on their medication to manage NVP, if they were taking any, were excluded from analysis. A standard follow-up interview was conducted, where a detailed quantification of symptoms was obtained: (1) a self-report of how the woman perceived her symptoms at follow-up (better, same, or worse); (2) validated quantitative scores were obtained including: (a) the Pregnancyunique quantification of emesis and nausea (PUQE) score (Koren et al. 2002) was measured at baseline and after the intervention (Table I) and (b) The Well-being score (Koren et al. 2005) ranging from 1–10 was recorded based on how the woman felt overall compared with how she felt before pregnancy. We also recorded the time of the NVP symptoms that appeared, other medical conditions, gravidity, maternal age at conception, gestational age at the initial interview and gestational age at follow-up. Mean PUQE and well-being scores were calculated at the initial interview and after the intervention. The unpaired
t-test was used to compare the mean scores between the initial and final scores within groups, and Kruskal–Wallis test with post-hoc Dunn’s tests was used to compare the mean PUQE and well-being scores among the groups. w2 and Fisher’s Exact test were used to calculate differences in categorical values.Results
Out of 97 patients meeting our inclusion criteria, 63 women reported improvement in NVP after discontinuation of the iron-containing prenatal vitamins. Overall, compared with women who reported feeling either the same or worse, there was a favourable effect in 65% of the women (
p50.001). There were no significant differences in both the initial PUQE scores (p¼0.18) (Figure 1) or the initial Well-being scores (p¼0.24) (Figure 2) among the three groups (better, same, worse). After the intervention, the women who reported improvement had a significantly lower PUQE score: better vs same (p50.001), better vs worse (p50.001) and same vs worse (p50.05) (Figure 1). Similarly, there were significant differences in the final Well-being score between better vs same (p50.001) and better vs worse (p50.001) (Figure 2). There were no significant differences in the maternal age, gestational age, gravidity, and the onset of NVP between the responders and the rest (Table II). There were significant differences in the prevalence of medical conditions among the groups, with women reporting improvement, or staying the same having more medical conditions compared to women who felt worse (p¼0.04 and p¼0.005, respectively). There were no significant differences in the prevalence of medical conditions among women who reported feeling better and women who reported feeling the same (p¼0.08).Discussion
Our data document the effectiveness of withholding iron in improving the severity of NVP, and hence, highlights the role of iron in aggravating this condition. The majority of women reported feeling better within several days of discontinuing their iron-containing prenatal multivitamins indicating that it was the removal of the iron and not the natural resolution of NVP symptoms. In addition to subjective reports, the women who reported feeling better had lower PUQE scores and higher Well-being scores. Certain potential confounding factors were considered in our analysis. It has been shown that as maternal age or the number of pregnancies increases (Louik et al. 2006), women are more likely to experience NVP. We did not detect differences in maternal age or gravidity among those who improved and those who did not. Furthermore, the gestational ages did not differ at the time of the initial interview and at the time of follow-up between the three groups. Similarly, the gestational age at time of initial NVP symptoms did not differ among the three groups as well. These results indicate no differences among the three groups in factors that are associated with increased risk and severity of NVP. It appears, though, that women with preexisting medical conditions were more likely to benefit from the removal of iron. Previous studies have alluded to the adverse effects of prenatal multivitamin supplementation is due to iron content as well. In a recent study involving 164 women post-partum, almost half reported at least one adverse effect from iron supplements including constipation (27.4%) and nausea (10.8%) (Melamed et al. 2007). Other studies have also indicated that compliance is negatively affected by the adverse effects of iron especially in women who are experiencing NVP and gastrointestinal conditions (Koren and Pairaudeau 2006; Hyder et al. 2002). In one randomised, crossover, open labelled study in 135 pregnant women, the compliance and tolerability between PregVit
1, a prenatal vitamin taken twice a day with iron (35 mg) in one pill and calcium in the other pill, and Materna1 (60 mg iron) were determined (Ahn et al. 2006). Compliance with the use of PregVit1 and Materna1 were similar; however, women who were using PregVit1 experienced a 30% reduction in constipation rate as compared with Materna1 (Ahn et al. 2006). Furthermore, compliance of Materna1 was negatively associated with the severity of NVP; whereas, no such correlation was found for PregVit1 (Ahn et al. 2006). While the adverse effects of iron on NVP have been inferred in previous studies, this is the first interventional study demonstrating that removal of iron from prenatal multivitamins results in symptom improvement. In the present study, the amount of iron in the prenatal multivitamins varied between 27 and 60 mg. Our sample size was insufficient to study the dose characteristics of the adverse effects of iron; however, this study provides a strong rationale to conduct a randomised controlled trial to determine the effects of iron-containing prenatal multivitamins on the severity of NVP. Most cases of NVP subside by the end of the first trimester of pregnancy. During the first trimester there are no increased requirements for iron, and hence, decreasing or avoiding iron supplementation in women suffering from NVP should not lead to iron deficiency. If NVP persists in the second and third trimesters, iron should be supplemented either orally or, if NVP is still severe, parenterally. This practise of not supplementing routinely with iron in the first trimester is already successfully conducted in the UK.Acknowledgements
The Motherisk NVP helpline is supported by an unrestricted grant from Duchesnay, Inc., Canada. GK is holder of the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation (Hospital for Sick Children) and the Ivey Chair in Molecular Toxicology (Department of Medicine, University of Western Ontario). The authors alone are responsible for the content and writing of the paper.
Table I. Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system. The PUQE scale is a validated scoring
system to quantify the severity of NVP based on quantification of the 3 physical symptoms of NVP (nausea, vomiting and retching) (Koren
et al. 2002).
How many hours in past 12 hrs had you
felt nauseated/sick to stomach?
None (1) 1 hr or less (2) 2–3 hrs (3) 4–6 hrs (4) 46 hrs (5)
How many times in the past 12 hrs
did you vomit?
7 times (5) 5–6 times (4) 3–4 times (3) 1–2 times (2) None (1)How many times in the past 12 hrs
did you experience gagging or retching
or dry heaves?
None (1) 1–2 times (2) 3–4 times (3) 5–6 times (4) 7 times (5)
PUQE score: _______.
Discontinuing iron-containing prenatal multivitamins reduced NVP severity
Figure 1. PUQE scores before and after intervention by women’s qualitative response (‘better’, ‘same’, ‘worse’).
Figure 2. Well-being scores of women prior to and after discontinuation of prenatal vitamin supplementation by women’s qualitative response.
Table II. Confounding factors examined among the three groups
of response.
Confounding
factors
Values
among groups
Maternal age at conception (years) Better: 31.5+5.0
Same: 32.7+4.1
Worse: 34.1+4.8
Gravidity Better: 2.0+1.2
Same: 2.4+1.3
Worse: 2.0+1.1
Gestational age at initial interview (weeks) Better: 9.8+3.9
Same: 9.5+3.5
Worse: 9.1+1.9
Gestational age at follow-up (weeks) Better: 12.5+3.9
Same: 11.4+3.7
Worse: 11.3+2.7
Gestational age at onset of NVP (weeks) Better: 5.7+3.4
Same: 5.8+1.0
Worse: 6.2+1.9
Prevalence of Medical Conditions
(number of women)
Better: 32*
Same: 19#
Worse: 0
*p¼0.04 compared to worse; #p¼0.005 compared to worse
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