Applied Physiology, Nutrition, and Metabolism

Ranking of iron, vitamin D and calcium intakes in relation to maternal characteristics of pregnant Canadian women

Journal: Manuscript ID Manuscript Type: Date Submitted by the Author: Complete List of Authors:

Applied Physiology, Nutrition, and Metabolism apnm-2015-0588.R1 Article 19-Feb-2016

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Morisset, Anne-Sophie; Centre de recherche du Centre hospitalier universitaire de Sherbrooke; Sainte Justine University Hospital Research Center Weiler, Hope; McGill University, Dubois, Lise; University of Ottawa, School of epidemiology Ashley-Martin, Jillian ; Dalhousie University, Perinatal Epidemiology Research Unit Shapiro, Gabriel; Sainte Justine University Hospital Research Center Dodds, Linda; Dalhousie University, Perinatal Epidemiology Research Unit Massarelli, Isabelle; Health Canada, Food Directorate Vigneault, Michel ; Health Canada, Food Directorate Arbuckle, Tye; Health Canada, Environmental Health Science and Research Bureau Fraser, William; Centre de recherche du Centre hospitalier universitaire de Sherbrooke; Sainte Justine University Hospital Research Center

Keyword:

pregnancy, nutrition, iron, vitamin D, calcium

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(i) Ranking of iron, vitamin D and calcium intakes in relation to

maternal characteristics of pregnant Canadian women (ii) Anne-Sophie Morisset, Hope A. Weiler, Lise Dubois, Jillian Ashley-Martin, Gabriel D. Shapiro, Linda Dodds, Isabelle Massarelli, Michel Vigneault, Tye E. Arbuckle, William D. Fraser

(iii) Address for correspondence:

William D. Fraser, MD Centre de recherche du CHUS (CRCHUS) 3001, 12e Avenue Nord, Sherbrooke, Qc, J1H 5N4

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Tel : 1-819-346-1110 poste 12875, Fax : 1-819-564-5445

[email protected]

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(iv) Anne-Sophie Morisset* et William D. Fraser : Centre de recherche du Centre hospitalier

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universitaire de Sherbrooke, Sherbrooke, Canada et Sainte Justine University Hospital Research Center, University of Montreal, Montreal, Canada. [email protected] et [email protected] Hope A. Weiler : School of Dietetics and Human Nutrition, McGill University, Montreal, Canada, [email protected] Lise Dubois: School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada, [email protected] Jillian Ashley-Marin and Linda Dodds: Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia, Canada, [email protected] and [email protected] Gabriel D. Shapiro : Sainte Justine University Hospital Research Center, University of Montreal, Montreal, Canada, [email protected] Isabelle Massarelli and Michel Vigneault : Food Directorate, Health Canada, Ottawa, Canada, [email protected] and [email protected] Tye E. Arbuckle:

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Environmental Health Science and Research Bureau, Health Canada, Ottawa, Canada, [email protected] * The first author is now assistant professor at Laval University, School of Nutrition. The study was conducted when she was the recipient of a postdoctoral fellowship from the FRSQ under the supervision of William D. Fraser and the co-supervision of Hope A. Weiler and Lise Dubois. William D. Fraser is supported by a CIHR Canada Research Chair

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ABSTRACT Introduction: Iron, vitamin D and calcium intakes in the prenatal period are important determinants of maternal and foetal health. Objective: To examine iron, vitamin D and calcium intake from diet and supplements in relation to maternal characteristics. Methods: Data were collected in a subsample of 1186 pregnant women from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort study including pregnant women recruited from 10 Canadian sites between 2008 and 2011. A FFQ was administered to obtain a ranking of iron, calcium and vitamin D intake (16-21 weeks of pregnancy). Intakes from supplements were obtained from a separate questionnaire (6-13 weeks of pregnancy). Women were divided into 2 groups according to the median total intake of each nutrient. Results: Supplement intake was an important contributor to total iron intake (median 74%: IQR 0-81%) and total vitamin D intake

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(median 60%: IQR 0-73%), while the opposite was observed for calcium (median 18%: IQR 0-

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27%). Being born outside of Canada was significantly associated with lower total intakes of iron, vitamin D and calcium (p≤0.01 for all). Consistent positive indicators of supplement use (iron,

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vitamin D and calcium) were maternal age over 30 years and holding a university degree. Conclusions: Among Canadian women, the probability of having lower iron, vitamin D and calcium intake is higher among those born outside Canada. Supplement intake is a major contributor to iron and vitamin D total intakes. Higher education level and age over 30 years were associated with supplement intake.

Key words: Pregnancy, nutrition, iron, vitamin D, calcium, food frequency questionnaire, supplements

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RÉSUMÉ Introduction : Les apports nutritionnels en fer, calcium et vitamine D durant la grossesse sont importants pour la santé de la mère et de l’enfant. Objectif : Examiner les apports nutritionnels en fer, vitamine D et calcium provenant de l’alimentation et des suppléments en association avec les caractéristiques maternelles. Méthodes : Un sous-échantillon de l’étude MIREC incluant 1186 femmes enceintes canadiennes recrutées sur 10 sites canadiens entre 2008 et 2011 a été examiné. Les apports nutritionnels provenant des aliments ont été estimés au deuxième trimestre avec un questionnaire de fréquence alimentaire (FFQ). Les apports nutritionnels provenant des suppléments ont été évalués par questionnaire à la fin du premier trimestre. Les femmes ont été divisées selon la médiane des apports totaux pour chacun des nutriments examinés. Résultats : Le supplément était un important contributeur de l’apport total en fer (médiane 74%: IIQ 0-81%)

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et en vitamine D (médiane 60%: IIQ 0-73%), contrairement au calcium (médiane 18%: IIQ 0-

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27%). Le fait d’être né à l’extérieur du Canada était associé significativement avec des apports plus faibles en fer, vitamine D et calcium (p≤0.01 pour tous). Le fait d’être âgé de plus de 30 ans

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et d’avoir complété des études universitaires ont été identifiés comme des déterminants d’une plus grande utilisation de suppléments (fer, vitamine D et calcium). Conclusions : Les femmes enceintes canadiennes qui sont nées à l’extérieur du pays sont plus à risque d’avoir des apports totaux plus faibles en fer, vitamine D et calcium.

Mots clés: Grossesse, nutrition, fer, vitamine D, calcium, questionnaire de fréquence alimentaire, suppléments

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INTRODUCTION Micronutrient status in pregnancy may affect maternal health, fetal wellbeing and birth outcomes, as well as the risk of chronic disease in the offspring (Barker et al. 1993; Blumfield et al. 2013). Consequently, insufficient micronutrient intake may have negative impacts on maternal and fetal health. Three micronutrients of particular importance for a healthy pregnancy are iron, vitamin D and calcium. Achieving Recommended Dietary Allowances (RDA) for these micronutrients in pregnancy can be challenging, especially for iron and vitamin D (Blumfield et al. 2013). Pregnancy is associated with an increased demand for iron to support the expansion of maternal blood volume and for fetal growth (Simpson et al. 2011). For this reason, dietary requirements are

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significantly increased during pregnancy compared to a non-pregnant state (18 mg to 27 mg/day) (Otten et al. 2006). Insufficient iron intakes have been associated with an increased risk of

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anemia, which in turn is associated with low birth weight and preterm birth (Scholl et al. 2000).

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Similarly, vitamin D has received particular attention in the last decade, as it is also important for maternal and fetal health, mostly for skeletal growth and development of the fetus (Simpson et al. 2011). Low vitamin D status, defined as serum 25(OH)D concentrations below 50 nmol/l, has also been associated with an increased risk of gestational diabetes mellitus (GDM), pre-eclampsia and low birth weight (Wei et al. 2013). Calcium intake during pregnancy is important for promoting bone health and possibly in reducing the risk of pre-eclampsia (Hofmeyr et al. 2010). As calcium absorption is augmented during pregnancy to support the increased demand (Olausson et al. 2012), there is less need to increase dietary intakes and it is easier to achieve the RDA (Blumfield et al. 2013). Dietary recommendations for vitamin D and calcium are similar to those for non-pregnant women (600 IU/day and 1000 mg/day, respectively) (Otten et al. 2006).

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Regarding supplement use, recommendations from the Institute of Medicine (IOM) suggest that all pregnant women at risk of nutritional deficiency should take a multivitamin/mineral supplement (Institute of Medicine 1992). Health Canada recommends 16-20 mg/day of iron from supplemental sources (Cockell et al. 2009). No specific recommendations concerning vitamin D and calcium intakes from supplements in pregnant women are suggested, as these dietary requirements should be met by food. To date, data focusing on nutrient intakes in large, national-scale samples of pregnant women are scarce. Furthermore, iron, calcium and vitamin D total intakes in Canadian women during pregnancy, including food and supplements intakes, have not been thoroughly investigated in relation to maternal characteristics. Therefore, our main objective was to examine total dietary intakes of iron, vitamin D and calcium during pregnancy in a population of Canadian women in

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relation to maternal age, pre-pregnancy body mass index (BMI), education level, household

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income and country of birth. An underlying objective was to validate the use of a food frequency questionnaire (FFQ) in a subsample of our study population.

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MATERIAL AND METHODS Subjects Details of the MIREC Study have been previously reported (Arbuckle et al. 2013). Briefly, 2001 women were recruited from 10 Canadian sites from 2008-2011 during their first trimester of pregnancy. Women were eligible for inclusion if they were < 14 weeks gestation at time of recruitment, ≥ 18 years of age, able to communicate in French or English, and planning to deliver in a participating hospital. Women with known foetal or chromosomal anomalies in the current pregnancy and women with serious medical complications were excluded from the study (Arbuckle et al. 2013). The population in the present analysis included 1186 mothers who had singleton live births and completed dietary surveys (FFQ and nutrient supplement questionnaire).

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Total iron, vitamin D and calcium dietary intakes

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Food frequency questionnaire

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At the second trimester visit, between 16 and 21 weeks of pregnancy, a one-month semiquantitative FFQ was administered to obtain a ranking of iron, calcium and vitamin D intake. The FFQ consisted of 46 food items listed in 6 subgroups (vegetables/ fruits/ meat, poultry, fish and alternatives/ milk products/ grain products/ other foods). For each food item, a frequency (days/weeks/months), a serving size (less than average (small)/ average / more than average (large)) and an example of an average serving size (ex: 250 ml or 1 cup) were presented. For each of the 46 questions in the FFQ, responses were converted to servings per day, with a 33% reduction factor for small servings and a 33% inflation factor for large servings. In order to assign a gram weight and amounts of nutrients to each item on the FFQ, foods were matched to corresponding foods in the 2010 Canadian Nutrient File. The serving size, gram weight and the amount of nutrient were calculated for each serving of the food item. In the case of questions consisting of food composites, the relative popularity of each food was estimated from the

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Canadian Community Health Survey Cycle 2.2 Nutrition (CCHS 2.2), a nationally representative Canadian survey on nutrition including pregnant and non-pregnant women) and the weighted average amount of nutrients per serving was calculated (Health Canada 2004). Based on the inherent assumptions of this FFQ, data was grouped according to above and below the median intakes. To evaluate the validity of the FFQ, a second FFQ was collected approximately two weeks after the first in a subsample of 115 MIREC subjects. On both occasions a 24-hour dietary recall was also administered in order to evaluate the validity and repeatability of the FFQ in pregnant women. The first FFQ and 24-hour recall were administered by trained research nurses at the second trimester visit. Repeat interviews were done over the phone. The 24-hour recalls were processed using the Nutrition Survey System (NSS) developed by the Food Directorate at Health

Nutrient supplement questionnaire

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Canada.

The nutrient supplement questionnaire was completed by participants around 16 weeks of pregnancy and consisted of a detailed list of supplements taken in the last 30 days (name and description of product/ drug identification number on bottle (Drug Identification Number (DIN) / Natural Product Number (NPN) / Homeopathic Medicine Number (DIN-HM)) /amount taken each time (# of pills, tabs, caps, teaspoon, etc.)/ frequency). Daily iron, calcium and vitamin D content were derived using Health Canada’s Drug Product database and/or the detailed ingredients list from the product monograph. Daily iron intake from supplements was compared to Health Canada recommendation (16 to 20 mg per day (Cockell et al. 2009)), and the proportion of women not taking any supplement was also calculated. In the absence of specific recommendations for supplemental intakes of vitamin D and calcium, only the proportion of women taking a daily supplement was calculated.

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Maternal and infant characteristics Data collected on maternal age, parity, education level, family income and country of birth were obtained from the baseline questionnaire administered at the first visit (between 6 and 13 weeks of pregnancy). Body weight was measured during study clinic visits throughout pregnancy and/or at delivery. Total gestational weight gain was calculated as the difference between maternal weight measured at delivery or at the last prenatal visit (≥37th week), and self-reported prepregnancy weight. Total gestational weight gain was compared to the 2009 IOM recommendations (Institute of Medicine 2009). Impaired glucose tolerance (IGT) and GDM were assessed by chart review based on the results of a 50 g glucose challenge test (GCT) and 75 or 100 g oral glucose tolerance test (OGTT), in accordance with guidelines from the Canadian Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada (Berger et

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al. 2002; CDA 2008). Subjects were assigned a diagnosis of IGT if one of the OGTT cut-off

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values was met or exceeded. If the result of the 1-hour 50-g GCT was ≥10.3 mmol/L, or if at least 2 of the cut-off values were met or exceeded on a 75-g or 100-g OGTT, a diagnosis of GDM was

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assigned. Infant birth weight was assessed from the hospital birth chart. Foetal growth was assessed using the sex-specific Canadian reference charts for birth weight for gestational age (Kramer et al. 2001). Infants were categorized as small-for-gestational-age (SGA) (where the birth weight was 90th percentile for gestational age) (Kramer et al. 2001). Statistical analysis Validation of the FFQ questionnaire Validity of the FFQ was assessed in a subset of the cohort as described above. The FFQ was administered to obtain a ranking of iron, calcium and vitamin D intakes. Correlations between

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recall and FFQ measurements (recall-FFQ pairs) were computed, first comparing the absolute amount of food in grams and absolute intakes of nutrients, then comparing the ranks of the amounts of food and the ranks of intakes of nutrients. For the gram amount and for each of the three nutrients studied, 4 correlation analyses were performed: the first recall intake against the first FFQ intake; the second recall intake against the second FFQ intake; the recall average intake (as a surrogate for usual intake) against the first FFQ intake; and; the recall average intake against the second FFQ intake. For each paired recall-FFQ measurement, Pearson product-moment correlation coefficients were estimated, which measures the degree of linear association between the FFQ and recall intakes. Spearman rank-order correlations were also computed to measure the degree to which the nutrient intakes from the 24-hour recall and from the FFQ were associated, but not necessarily linearly associated. A rank-order correlation of 100% means perfect positive

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correlation (i.e. when the FFQ intake ranks matched perfectly against those from the recalls). A correlation of 0% means the rank-orders were statistically independent. For each correlation

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estimate, a P-value was estimated to test the hypothesis of a non-zero correlation. These analyses

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were performed using SAS statistical software (version 9.2). Descriptive and multivariate logistic regression analyses Descriptive analyses for main characteristics of the subjects were performed. It was impossible to use continuous variables for nutrient intakes or a subdivision based on whether the RDA was achieved because the FFQ did not capture all nutrient sources and consequently total dietary nutrient intakes. Instead, women were divided into two groups of total nutrient intake (lower vs. higher) according to the median value of iron, vitamin D and calcium intake. Only 2 categories were used since the total diet varied mostly as a function of supplemental intakes; by categorizing women into two groups it best captured those taking lower supplemental amounts of iron, calcium or vitamin D compared to those taking higher supplemental amounts. For each nutrient, Student’s t tests were computed to ensure that both nutrient and supplement intakes were

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significantly lower in women with lower vs. higher total intakes. Typically supplemental intakes were low or high and thus tertiles were not necessary (e.g. 10 vs. 40 mg iron/supplement). Proportions of main food components contributing to each nutrient, women taking an iron supplement at least 16 mg/day (Health Canada guideline), and women not taking iron, vitamin D or calcium supplements were all determined. A Chi-square comparison was used to test differences in maternal characteristics between women with lower vs. higher total intake (for vitamin D, calcium and iron intake). Multivariate logistic regression analyses were performed to evaluate the odds of having lower nutrient intake in models including all clinically relevant maternal characteristics (maternal age, pre-pregnancy BMI, family income, education level and country of birth). Similar analyses were performed to determine indicators of iron, vitamin D and calcium supplement intakes. Interaction terms were not included in the models since this was not

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the purpose of these analyses. These analyses were performed using JMP statistical software version 10.0 (SAS Institute, Cary, NC, USA).

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RESULTS The main characteristics of the cohort are shown in Table 1. More than half of the women were over 30 years of age (73.0%). Most of them were in their first (44.9%) or second pregnancy (41.3%) at the time of the study. The majority of women had a university degree (63.5%) and were born in Canada (79.6%). One third of women entered pregnancy overweight (21.4%) or obese (14.0%) based on pre-pregnancy BMI, and 55.9% gained in excess of the current IOM gestational weight gain recommendations. Mean gestational age at delivery was 39.3±1.7 weeks and 82 mothers (3.2%) delivered prematurely. 4.6% of women gave birth to an SGA infant and 12.5% to an LGA infant. The prevalence of GDM was 4.2%, while IGT was observed in 4.4% of participants. Similar characteristics were found in the subsample of women included in the FFQ validation (data not shown).

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FFQ validation results

Table 2 shows comparisons between recall-FFQ pairs of responses in 115 subjects. The FFQ

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consistently underestimated total intakes of nutrients: by more than 50% for iron, by about 10% for vitamin D, and by about 30% for calcium. However, for all paired recall-FFQ intake totals, Pearson product-moment correlations were strictly positive: they ranged from 31% to 42% for iron, from 16% to 45% for vitamin D and, from 31% to 47% for calcium. All P-values for these correlations were below 0.01, with the exception of vitamin D (first recall vs. first FFQ). Finally, Spearman rank-order correlation estimates were consistently between 30% and 50%: they ranged from 42% to 50% for iron, from 30% to 47% for vitamin D and, 36% to 46% for calcium. All Pvalues for rank-order correlations were below 0.01. Regarding the repeatability of the FFQ, 50% of food-level responses were concordant (data not shown). For the remainder, the average discordance was small: two-tenths of a portion when one response was zero, and three-tenths when both responses were non-zero

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Micronutrients intakes Iron Figure 1A shows average iron intakes in women with higher vs. lower relative iron intakes (groups divided by median total iron intake). Iron intakes from diet as well as iron from supplements were both significantly higher in women with higher vs. lower total daily iron intakes (9.1±0.1 vs. 7.4±2.8 mg/d from diet, 50.1±1.3 vs. 17.5±0.5 mg/d from supplement, p