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mineral supplements and gestational length in uncomplicated pregnancies
Women and Birth 29 (2016) 41–46
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ORIGINAL RESEARCH – QUANTITATIVE
The association between third trimester multivitamin/mineral supplements and gestational length in uncomplicated pregnancies J.M. McAlpine a,b, R. Scott c, P.A. Scuffham c, A.V. Perkins a, J.J. Vanderlelie a,* a
School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold Coast Campus, Southport, QLD, Australia Department of Women’s and Newborn Health, Gold Coast University Hospital, Southport, QLD, Australia c School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Southport, QLD, Australia b
A R T I C L E I N F O
Article history: Received 13 April 2015 Received in revised form 27 July 2015 Accepted 28 July 2015 Keywords: Pregnancy Postdates Third trimester Multivitamins Micronutrients
A B S T R A C T
Background: Widespread use of maternal micronutrient supplements have been correlated to gestational length and outcome in women predisposed to pre-eclampsia and preterm birth. However, research is yet to be conducted examining the influence of micronutrient supplements on outcomes at term in uncomplicated pregnancies. Aim: To analyse the relationship between third trimester micronutrient supplementation and gestation length at birth, demographics and maternal birthing outcomes in well women at term in a South East Queensland representative population. Methods: This research retrospectively analysed existing data pertaining to 427 uncomplicated, pregnancies birthing at the Gold Coast and Logan Hospitals using information gathered through the Environments for Healthy Living Study and Queensland perinatal data collection. Data were analysed using SPSS v20 by Chi square, ANOVA and regression analysis. Findings: Women in the third trimester taking individual zinc, folic acid or iron supplements in combination with a multivitamin were twice as likely to birth beyond 41 completed weeks (AOR 2.054, 95% CI 1.310–7.383, p = 0.038) then those who did not take any supplement when controlled for established confounders. Non supplement users were found to experience a lower rate of post dates labour and requirements for induction (AOR 0.483, 95% CI 0.278–0.840, p = 0.01). Conclusion: Length of gestation demonstrates significant associations with micronutrient supplementation practices. Well women consuming third trimester individual micronutrient supplements in addition to multivitamins experienced a longer gestation at term compared to women taking no micronutrients, increasing their risk for postdates induction of labour. Crown Copyright ß 2015 Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd) on behalf of Australian College of Midwives. All rights reserved.
1. Introduction Post-dates gestation and prolonged pregnancy pose an increased risk to both mother and baby, routinely managed through induction of labour in the post-dates period.1 While the mechanisms responsible for parturition have yet to be fully elucidated, maternal nutritive status has been identified as contributing to its onset and progression,2 with suboptimal nutrition largely associated with poor perinatal outcomes.3
* Corresponding author at: School of Medical Science, Griffith University Gold Coast Campus, Parklands Drive, Southport, QLD 9726, Australia. Tel.: +61 07 5552 8746. E-mail address: j.vanderlelie@griffith.edu.au (J.J. Vanderlelie).
The importance of adequate maternal micronutrition in facilitating healthy foetal development and supporting the increased demands of pregnancy on maternal physiology has prompted increasing proportions of women to choose a multivitamin preparation during pregnancy.2,3 Multivitamin and mineral supplementation has been found to reduce pregnancy complications, such as pre-eclampsia and preterm birth, when utilised in the first trimester.2,4 However, there is a lack of similar research regarding the physiology of term and post-dates gestation and effect of third trimester micronutrient supplements on the length of gestation at term and beyond. This research retrospectively examined the relationship between micronutrient supplementation in the third trimester, length of gestation and birthing outcomes in an Australian cohort from South East Queensland, providing a valuable foundation for
http://dx.doi.org/10.1016/j.wombi.2015.07.185 1871-5192/Crown Copyright ß 2015 Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd) on behalf of Australian College of Midwives. All rights reserved.
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ongoing research to improve antenatal nutrition counselling and birthing outcomes in well women at term (Fig. 1). 2. Literature review Human parturition is defined as normal if its onset, coordination and progress occur within a set of defined parameters.5 Any birth occurring between 40 and 42 weeks is deemed post-dates, with pregnancy continuing beyond 42 weeks considered prolonged.6 Risk to both mother and baby commonly associated with such gestations is routinely managed through induction of labour in the post-dates period.1 The labour initiation process is physiologically dependent on uterine change from a quiescent to a contractile state. Hormonal, mechanical and inflammatory influences are known to contribute to this change, as is maternal nutritive state.7,8 Deficiencies in several key micronutrients have been linked with inflammatory processes associated with preterm labour and pre-eclampsia.9 While the effects of malnutrition on pregnancy outcome has been well documented in the developing world, suboptimal nutrition remains a significant public health issue in the developed world, with up to 3 billion people considered malnourished as a result of undernourishment, and micronutrient deficiencies in the presence and absence of adequate macronutrition.10 A large systematic review recently reported that the Australian population is subject to a number of micronutrient deficiencies, with intakes of thiamine, vitamin A, folate, vitamin D, calcium, iron, magnesium and zinc below the estimated average requirement in Australian women.11 Supplementation of micronutrients such as folate, B group vitamins, selenium, vitamin C, vitamin E, zinc and bcarotene have demonstrated improvements in immune function and a reduction in inflammation and placental oxidative stress, and maybe important in improving perinatal outcomes in both high risk pregnancies, especially those in the developing world.9 Despite this work, population level research is limited regarding the effects of micronutrient supplementation on maternal outcomes at term. While maternal and infant nutrition in the developed world demonstrates vastly superior outcomes with regard to perinatal morbidity and mortality, most fail to meet
World Health Organisation recommendations regarding intervention at term.12 This is reflected in the Australian perinatal data statistics, with the national labour induction rate remaining at 25% over the last decade, of which 25% were undertaken for management of prolonged pregnancy.13 This equates to 3530 postdates inductions in 2012 in Queensland alone.13 Considering that primary health care providers are a major source of information regarding healthy eating during pregnancy,14 it is interesting to note that women report the information they receive to be both inconsistent and contradictory.15 Given that appropriate nutrition education and support has the capacity to improve maternal birth outcomes,16 it is essential that primary carers have an understanding of the potential implications of suboptimal nutrition counselling and micronutrient intake during the third trimester of pregnancy. 3. Participants and methods The Environments for Healthy Living (EFHL) is a prospective longitudinal study conducted by Griffith University across the Logan, Beaudesert, Gold Coast Health Districts in South East Queensland (QLD) and Tweed Heads in northern New South Wales (NSW), Australia.17 EFHL is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12610000931077) with detailed methodologies previously published.17 The EFHL study was approved by the Griffith University Human Ethics Committee (MED/16/06/HREC, MED/23/11/HREC). Additional ethical approval was obtained from each recruiting hospital (Logan HREC/06QPAH/ 96, Gold Coast Hospital HREC/06/GCH/52). All women included in this cohort gave written consent for the release of their perinatal data from hospital collections. The target population for this research was pregnant women in the South East Queensland region. From November 2006 – October 2011, a total 2619 live births were recorded from mothers recruited to the EFHL study in the QLD sites; this equated to 23.4% of total births in the target population hospitals during the recruitment periods. Data were collected from the maternal baseline survey and hospital perinatal data records for the Logan and Gold Coast
100 90 80
% Onset of Labour
70 60 No supplements
50
Folic acid + MV Iron + MV
40
Zinc + MV
30 20 10 0 37
38
39
40
41
42
Weeks Gestation
Fig. 1. Effect of micronutrient supplementation on gestational length of well women at term in completed weeks.
J.M. McAlpine et al. / Women and Birth 29 (2016) 41–46
hospitals in QLD. Beaudesert and Tweed Heads health district data were excluded due to inconsistent reporting of data relating to supplement use at these sites (n = 1031). The original dataset encompassed the experiences of 2697 women. Women were excluded if they underwent induction of labour for other medical reasons (such as reduced foetal movements) or for no documented reason (n = 972), were diagnosed with gestational diabetes (n = 204), experienced preterm birth (n = 103), elected a caesarean section (n = 81), were diagnosed with hypertensive disorders or pre-eclampsia (n = 38), twin pregnancies (n = 29), experienced an emergency caesarean section without labour (n = 18), or elected induction for social reasons (n = 13). Data pertaining to third trimester supplement use was obtained from the maternal baseline survey with regard to calcium, iron, folic acid and zinc in addition to commercial multivitamin preparations and miscellaneous supplements. Any woman reporting the use of a specific multivitamin preparation in the ‘other supplements’ category was also included in the analysis. Data was excluded from analysis if multivitamin/mineral supplements were taken in combination with supplements such as raspberry leaf and omega-3 and 6 to exclude the effects of these supplements on maternal birth outcomes at term. The final dataset comprised of 427 well women birthing at the Gold Coast and Logan Hospitals at term. This was analysed retrospectively, examining the relationship between gestational length and demographics, supplements and birthing outcomes using SPSS v20. All categorical data were suitable for analysis using the Chi Square test, highlighting preliminary relationships for further analysis. Significance was accepted at p 0.05 level for all measures and results presented as frequency (percentage), Pearson Chi Square value (x2) and degrees of freedom (df). Logistic regression analysis allowed further exploration of these relationships and examined the contribution of each independent variable while controlling for covariates, the relationship between covariates in relation to the dependent variable, and confounders. Normality checks were performed on the continuous variable gestation at birth (in days) and were found to demonstrate normal distribution. Gestation was initially analysed using one way ANOVA (F-value, eta squared and p-value) to determine significant associations. Linear regression was used to assess the relationship between gestation (days) and micronutrient supplementation practices identified as significant with regard to gestational length. Supplementation groups included no supplementation, multivitamin only, and multivitamin in combination with each of iron, zinc, folate and calcium. Covariates for analysis included maternal age at delivery (continuous), smoking status during pregnancy (yes, no), indigenous status (i.e. Aboriginal/Torres Strait islander descent) (yes, no), socioeconomic status (income quintile), parity (nulliparous, multiparous) and gestational diabetes (yes, no) due to the association between these factors and possible confounding by health promoting behaviours that are likely associated with multivitamin use. Potential confounders were retained in the model if they altered multivitamin exposure by >10%. Each model contained indigenous status and parity as confounders with regard to length of gestation, and each model controlled for known demographic correlations with the supplement in question. Significance remained at p 0.05 level for all measures. Data were stratified by confounders established during demographic and supplement use analysis. 4. Results Third trimester multivitamin/mineral supplementation was reported by 23% of women in the cohort. Multivitamin/mineral
43
users were more likely to be >25 years of age, with a prepregnancy BMI between 25 and 29.9 and of non-indigenous descent. The relationships between length of gestation at birth, and demographic characteristics are presented in Table 1. Significant associations were identified between length of gestation, parity (p = 0.019), and indigenous status (p = 0.031). No significant relationships were determined between micronutrient practices and demographic characteristics such as socioeconomic status, BMI, maternal education or smoking status. For supplement use, significant direct associations were found between length of gestation and the use of folic acid plus a multivitamin (p = 0.007), iron plus a multivitamin (p = 0.004) and zinc plus a multivitamin (p = 0.019). Interestingly a significant inverse association was determined between length of gestation and the unsupplemented pregnancies (p = 0.008).
Table 1 Demographic profile and mean length of gestation (n = 427). Variable
Sex of baby Male Female Maternal age group <20 20–30 >30 Hospital birthed Gold Coast Logan Maternal education level
>5% missing data. Statistically significant.
Dataset total n (% group)
Gestation Mean (days)
F-, p-Value
206 (48.4) 220 (51.6)
282.02 282.62
1.105, 0.354
39 (9.1) 239 (56.0) 149 (34.9)
282.10 282.59 281.85
0.644, 0.526
169 (39.6) 258 (60.4)
282.59 282.10
0.632, 0.427
4 93 137 129
274.75 282.26 282.42 282.28
1.444, 0.218
(0.9) (21.8) (32.2) (30.3)
63 (14.8) 80 78 71 69 59
282.48
(22.4) (21.8) (19.9) (19.3) (16.5)
283.04 282.33 281.80 282.72 282.22
0.441, 0.779
31 (8.0) 195 (50.5) 160 (41.5)
280.90 281.79 282.88
1.988, 0.138
409 (95.8) 18 (4.2)
282.16 285.44
4.672, 0.031**
310 (72.8) 116 (27.2)
282.17 282.65
0.482, 0.448
60 (20.3) 236 (79.7)
283.50 281.42
5.594, 0.019**
228 (53.4) 199 (46.6)
278.43 286.66
352.639, <0.001**
331 (77.9) 55 (12.9) 39 (9.2)
281.80 284.45 282.36
6.118, 0.002**
99 (23.2) 328 (76.8)
283.82 281.92
7.113, 0.008*
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Preliminary results indicate that primiparous women experienced a mean gestation 2.08 days longer than multiparous women (283.50 vs 281.42). Women declaring Aboriginal or Torres Strait Islander descent also demonstrated increased length of gestation, with a mean length approximately 3.28 days longer than their nonindigenous counterparts (285.44 vs 282.16) in this cohort. Additionally, women taking an individual micronutrient in addition to multivitamin supplements experienced a mean gestation of up to 4.15 days longer (Ca + Multi 285.35; Folate + Multi 285.48; Fe + Multi 286.05; Zn + Multi 286.07) than those women not using any supplements (281.92) at all in the third trimester. Both sets of variables were retained as confounders in the linear regression analysis. The regression model encompassing all predictors with regard to no supplements accounted for 5.2% (R2 = 0.052) of the variance in gestation. Subsequently, the absence of supplement use demonstrated a significant linear relationship with length of gestation. Of the confounding variables only parity demonstrated a statistically significant relationship (p = 0.015) with length of gestation. Indigenous status made no unique contribution in this model (Table 2). The negative regression coefficients (B = 0.146 95% CI: 3.639, 0.475) suggest that even when taking into account significant confounders, women who did not take micronutrient supplements during the third trimester were significantly more likely to deliver closer to term. The models examining the relationship between gestation and individual supplements including folic acid (p = 0.003; R2 = 0.047), iron (p = 0.001; R2 = 0.052), and zinc (p = 0.005; R2 = 0.043) utilised in combination with multivitamins were significant. Parity and indigenous status were identified as significant confounders for all supplementation combinations and were included in subsequent regression analyses. The regression coefficients of these analyses suggested that when taking into account significant confounders (Parity, indigenous status), the use of individual micronutrients in combination with multivitamins in the third trimester was significantly associated with increased length of gestation, despite the opposing effect of parity (Table 2). However, with regard to the use of no supplements at all, the negative regression coefficient suggests those women not taking any supplements experienced a gestation closer to 40 weeks independent of the unique contributions of both parity and indigenous status (Table 2). Chi squared and logistic regression analysis of the categorical maternal birthing outcomes onset of labour (induced vs spontaneous) and gestation code (>37–40 completed weeks, 40, 41, and
Table 2 Linear regression analysis – mean gestation and micronutrients (n = 427). Predictor variable
Standardised regression coefficient (95% CI)
No supplements** Parity Indigenous status Calcium + Multivitamin** Parity Indigenous status Maternal education level Folic acid + Multivitamin** Parity Indigenous status Iron + Multivitamin** Parity Indigenous status Zinc + Multivitamin** Parity Indigenous status
0.146 0.140 0.109 0.096 0.140 0.116 0.003 0.130 0.140 0.118 0.148 0.140 0.118 0.114 0.144 0.116
* **
(3.639, 0.475) (3.759, 0.410) (0.096, 7.021) (0.559, 6.638) (3.802, 0.394) (0.045, 7.324) (0.688, 0.720) (0.467, 6.616) (3.764, 0.408) (0.156, 7.297) (0.968, 7.100) (3.761, 0.413) (0.192, 7.313) (0.047, 7.920) (3.833, 0.467) (0.097, 7.249)
Statistically significant. Mahalanobis distance > critical value, Cook’s distance < 1.
p-Value 0.011* 0.015* 0.056 0.098 0.016* 0.047* 0.965 0.024* 0.015* 0.041* 0.010* 0.015* 0.039* 0.047* 0.012* 0.044*
42 completed weeks) also demonstrate relationships of statistical significance. Chi squared analysis determined that women not consuming supplements birthed between 37 and 40 completed weeks in approximately 19% (range: 18.9–19.3%) of cases compared to none of the women (0%) taking combined supplements within the same time frame. With regard to gestation advancing beyond 40 completed weeks, the analysis revealed that women taking a supplement combination birthed after 41 completed weeks in up to 77.3% of cases (range: 73.3–77.3%), compared to approximately 52% (range: 52.1–52.7%) of those women not taking the supplement combination. Logistic regression confirmed these relationships with the supplemented group more than twice as likely to birth beyond 41 completed weeks (AOR 2.054, 95% CI 1.310–7.383, p = 0.038). Analysis of the relationship between onset of labour and supplement use also demonstrated a similar trend with those women taking micronutrient and multivitamin combinations experiencing a post-dates induction rate of up to 72.7% (p = 0.021). In comparison, women who did not use any supplements were less than half as likely to be induced in the post-dates period (AOR 0.483, 95% CI 0.278–0.840, p = 0.010) with only 43% of cases requiring induction (p = 0.009) (Table 3). Due to high rates of induction the influence of micronutrients on onset of labour loses significance as gestation advances when the analyses controlled for gestation at birth (AOR2 0.557, 95% CI 0.221–1.408, p = 0.216) (Table 3). 5. Discussion Research regarding third trimester micronutrient supplementation and term birthing outcomes in well women is scarce. To date, the majority of literature deservedly focuses on preterm birth and pre-eclampsia.18 Preterm birth is a major determinant of perinatal morbidity and mortality in the developed world and has been heavily investigated with significant advances in knowledge regarding the mechanisms and management of such pathologies.3,18–21 Deficiencies in several key micronutrients have been linked with the inflammatory processes involved with preterm labour and pre-eclampsia, hence their efficacy in extending gestation in those women identified as exhibiting risk of these presentations.2 However, a lack of similar research regarding the physiology of term and post-dates gestation has limited our understanding regarding the effect of such micronutrient supplements on length of gestation at term and beyond. The Environments for Healthy Living Birth Cohort is a longitudinal birth cohort collecting data from mothers and their babies from South East Queensland and may be considered representative of the broader population in this region with rates of obesity,22,23 and supplement use24 consistent with that of the local and Australian populations. There are however notable differences between this cohort and the general South East Queensland population in relation to a reduce incidence of preeclampsia22 and lower rates of other health determinants such as substance abuse, smoking, diabetes and essential hypertension when compared to that of the general Australian population.25 For this reason the rates of confounding were in this study were relatively low and it has been hypothesised previously4 that recruitment to a study called ‘Environments for Health Living’ may have skewed participation to those women whose health status was generally good. In the context of this study analysing the effect of multivitamin supplementation in well women at term, this shift towards a healthier cohort may be considered positive. In this South East Queensland population micronutrient supplementation demonstrated significant associations with length of gestation and onset of labour. Those women not taking supplements experienced markedly shorter gestations than those
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Table 3 Association between onset of labour and supplement use. Third trimester supplement use
n (%)
No supplements Spontaneous onset 187 (57.0) Induction of labour 141 (43.0) Folic acid + multivitamin Spontaneous onset 7 (30.4) Induction of labour 16 (69.6) Iron + multivitamin Spontaneous onset 6 (27.3) Induction of labour 16 (72.7) y
Unadjusted odds ratio (p-value)
95% Confidence interval
Adjusted odds ratio 1 (p-value)y
95% Confidence interval
Adjusted odds ratio 2 (p-value)z
95% Confidence interval
1 0.498* (p = 0.012)
Referent 0.290–0.857
1 0.483* (p = 0.010)
Referent 0.278–0.840
1 0.557 (p = 0.216)
Referent 0.221–1.408
1 3.018* (p = 0.049)
Referent 1.005–9.064
1 3.143* (p = 0.044)
Referent 1.030–9.589
1 2.077 (p = 0.422)
Referent 0.348–12.381
1 4.212* (p = 0.016)
Referent 1.308–13.558
1 4.425* (p = 0.014)
Referent 1.355–14.451
1 2.428 (p = 0.337)
Referent 0.397–14.849
Adjusted confounder parity (onset), *statistically significant (p < 0.05). z Adjusted confounders parity and gestation at birth, *statistically significant.
using a multivitamin and micronutrient combination (281.92 days vs 285.35–286.07 days). In relation to the onset of labour we identified similar significant associations when women combined a multivitamin preparation with an individual micronutrient (folic acid, iron and zinc) supplement (Table 3). However when controlling for length of gestation at birth the association between onset and supplement use lost significance. This is indeed may be indicative of policy requirement for induction rather than medical need and the secondary nature of this analysis precluded us from making any further assessments of medical need in those inducted. As such the results of this analysis need to be considered in light of its limitations. While the data collected in this cohort has strengths such as EFHL sample size and data stability17 and reliability of hospital perinatal data,26,27 there also have notable limitations. These included heavy reliance on self-administration of the questionnaire and the self-reported nature of information. Generalised recruitment after 24 weeks of gestation resulted in a heterogeneity in both the cohort and the perspective of responses. Additionally, retrospective reporting of maternal birthing outcomes and associations were problematic, with significant difficulties encountered with missing data in critical variables such as BMI, parity, gestational length in days and supplement use. We were also unable to specifically study the content of each multivitamin/ mineral supplement used in the EFHL cohort and specific data on the duration of use within a particular trimester was not recorded which may have biased our results. Finally, although we adjusted significant confounding factors in our analysis unmeasured residual confounding may have also been a factor in this analysis. The third trimester of pregnancy is a known inflammatory state,9 homeostatically controlled in normal pregnancy. Up-regulation of inflammatory molecules play an essential role in the development of the systemic inflammatory responses required for cervical, myometrial and decidua changes and the spontaneous onset of labour.28,29 Considering previously established findings regarding inflammatory processes and spontaneous preterm labour, it is clear that inflammation plays a critical role in labour initiation regardless of gestation.28 Folate, iron and zinc have each demonstrated relationships with inflammatory molecules and processes.8,30–32 Supplementation of each of these micronutrients has also proven effective in reducing the rate of spontaneous preterm birth in supplemented cohorts.21,33 This supports previous findings regarding the anti-inflammatory properties of these micronutrients at a homeostatic and therapeutic level, and suggest that they act in this capacity against the inflammatory processes of preterm labour. This being the case it is plausible to hypothesise that these micronutrients in excess in well women at term continue to act in this manner, thereby suppressing the natural and necessary inflammatory processes responsible for spontaneous labour and contributing to increased gestational length in our cohort.
These findings have implications for nutrition counselling for women in the antenatal period, particularly with regard to supplement utilisation would suggest that the need for supplementation by healthy women be carefully considered and monitored on an individual basis. Further research is necessary to confirm these findings in similar cohorts. 6. Conclusion Length of gestation demonstrates significant associations with micronutrient supplementation practices. Well women consuming third trimester individual micronutrient supplements in addition to multivitamins experienced a longer gestation at term compared to women taking no micronutrients, increasing their risk for postdates gestation and induction of labour. This may be due to the excessive use of micronutrient supplements and the suppression of the inflammatory processes necessary for spontaneous labour. Sources of funding Core funding to support EFHL is provided by Griffith University. Conflict of interest statement The authors wish to declare that there are no conflicts of interest relevant to this work. Acknowledgements The research reported in this publication is part of the Griffith Study of Population Health: Environments for Healthy Living (EFHL) (Australian and New Zealand Clinical Trials Registry: ACTRN12610000931077). Core funding to support EFHL is provided by Griffith University. The EFHL project was conceived by Professor Rod McClure, Dr Cate Cameron, Professor Judy Searle and Professor Ronan Lyons. We gratefully acknowledge all EFHL project and research staff, in addition to participating hospital administrative staff and hospital antenatal and birth suite midwives for their valuable contributions to the study. References 1. Vayssie`re C, Haumonte J-B, Chantry A, Coatleven F, Debord MP, Gomez C, et al. Prolonged and post-term pregnancies: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol 2013;169(1):10–6. 2. Catov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA. Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr 2011;94(3):906–12. 3. Kawai K, Spiegelman D, Shankar AH, Fawzi WW. Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries:
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J.M. McAlpine et al. / Women and Birth 29 (2016) 41–46 meta-analysis and meta-regression. Bull World Health Organ 2011;89(6). 402–11B. Vanderlelie J, Scott R, Shibl R, Lewkowicz J, Perkins A, Scuffham P. First trimester multivitamin use is associated with reduced risk of preeclampsia among overweight and obese women.. Griffith University; 2013. National Institute for Health Clinical Excellence. Intrapartum care: management and delivery of care to women in labour (guideline 55). 2007. Mittendorf R, Williams MA, Berkey CS, Cotter PF. The length of uncomplicated human gestation. Obstet Gynecol 1990;75(6):929–32. Sfakianaki AK. Prenatal vitamins: a review of the literature on benefits and risks of various nutrient supplements. Formulary 2013;48(2):77–82. Dhobale M, Chavan P, Kulkarni A, Mehendale S, Pisal H, Joshi S. Reduced folate, increased vitamin B12 and homocysteine concentrations in women delivering preterm. Ann Nutr Metab 2012;61(1):7–14. Walker JJ. Inflammation preeclampsia. Pregnancy Hypertens 2011;1(1): 43–7. International Food Policy Research Institute. Global nutrition report 2014: actions and accountability to accelerate the world’s progress on nutrition. Washington, DC. 2014. Blumfield ML, Hure AJ, Macdonald-Wicks L, Smith R, Collins CE. A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries. Nutr Rev 2013;71(2):118–32. Organisation WH. Recommendations for induction of labour. Geneva. 2011. Hilder L, Zhichao Z, Parker M, Jahan S, Chambers GM. Australia’s mothers and babies 2012. Canberra: AIHW; 2014. de Jersey SJ, Nicholson JM, Callaway LK, Daniels LA. An observational study of nutrition and physical activity behaviours, knowledge, and advice in pregnancy. BMC Pregnancy Childbirth 2013;13:115. Wennberg AL, Lundqvist A, Ho¨gberg U, Sandstro¨m H, Hamberg K. Women’s experiences of dietary advice and dietary changes during pregnancy. Midwifery 2013;29(9):1027–34. Girard AW, Olude O. Nutrition education and counselling provided during pregnancy: effects on maternal, neonatal and child health outcomes. Paediatr Perinat Epidemiol 2012;26:191–204. Cameron C, Scuffham P, Spinks A, Scott R, Sipe N, Ng SK, et al. Environments for Healthy Living (EFHL) Griffith birth cohort study: background and methods. Matern Child Health J 2012;16(9):1896–905. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 2010;88(1):31–8. Bloomfield FH. How is maternal nutrition related to preterm birth? Annu Rev Nutr 2011;31:235–61.
20. Hauth JC, Clifton RG, Roberts JM, Spong CY, Myatt L, Leveno KJ, et al. Vitamin C and E supplementation to prevent spontaneous preterm birth: a randomized controlled trial. Obstet Gynecol 2010;116(3):653–8. 21. Papadopoulou E, Stratakis N, Roumeliotaki T, Sarri K, Merlo DF, Kogevinas M, et al. The effect of high doses of folic acid and iron supplementation in early-tomid pregnancy on prematurity and fetal growth retardation: the mother–child cohort study in Crete, Greece (Rhea study). Eur J Nutr 2013;52(1):327–36. 22. Callaway LK, Prins JB, Chang AM, McIntyre HD. The prevalence and impact of overweight and obesity in an Australian obstetric population. Med J Aust 2006;184:56–9. 23. Daly RM, Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Sikaris KA, et al. Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clin Endocrinol (Oxf) 2012;77:26–35. 24. Frawley J, Adams J, Sibbritt D, Steel A, Broom A, Gallois C. Prevalence and determinants of complementary and alternative medicine use during pregnancy: results from a nationally representative sample of australian pregnant women. Aust N Z J Obstet Gynaecol 2013;53:347–52. 25. Australian Bureau of Statistics. In: Statistics ABO, editor. Year book Australia. Canberra: ABS; 2012. 26. Quantin C, Benzenine E, Ferdynus C, Sediki M, Auverlot B, Abrahamowicz M, et al. Advantages and limitations of using national administrative data on obstetric blood transfusions to estimate the frequency of obstetric hemorrhages. J Public Health 2013;35(1):147–56. 27. Lain SJ, Hadfield RM, Raynes-Greenow CH, Ford JB, Mealing NM, Algert CS, et al. Quality of data in perinatal population health databases: a systematic review. Med Care 2012;50(4):e7–20. 28. Stephen G, Lui S, Hamilton S, Stevens A, Jones R. PLD.24 gene expression profiling of human decidua during term labour: inflammation as a key driver of labour. Arch Dis Child Fetal Neonatal Ed 2014;99(Suppl. 1):A113. 29. Unal ER, Cierny JT, Roedner C, Newman R, Goetzl L. Maternal inflammation in spontaneous term labor. Am J Obstet Gynecol 2011;204(3):223.e1–e. 30. Kim MW, Hong SC, Choi JS, Han JY, Oh MJ, Kim HJ, et al. Homocysteine, folate and pregnancy outcomes. J Obstet Gynaecol 2012;32(6):520. 31. Sahni S. Dinitrosyl iron complexes and their role in patho-physiological conditions. ProQuest, UMI Dissertations Publishing; 2011. 32. Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr 1998;68(2 Suppl):499S. 33. Mori R, Ota E, Middleton P, Tobe-Gai R, Mahomed K, Bhutta ZA. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev 2012:7.
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Women and Birth journal homepage: www.elsevier.com/locate/wombi
ORIGINAL RESEARCH – QUANTITATIVE
The association between third trimester multivitamin/mineral supplements and gestational length in uncomplicated pregnancies J.M. McAlpine a,b, R. Scott c, P.A. Scuffham c, A.V. Perkins a, J.J. Vanderlelie a,* a
School of Medical Science, Menzies Health Institute Queensland, Griffith University Gold Coast Campus, Southport, QLD, Australia Department of Women’s and Newborn Health, Gold Coast University Hospital, Southport, QLD, Australia c School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Southport, QLD, Australia b
A R T I C L E I N F O
Article history: Received 13 April 2015 Received in revised form 27 July 2015 Accepted 28 July 2015 Keywords: Pregnancy Postdates Third trimester Multivitamins Micronutrients
A B S T R A C T
Background: Widespread use of maternal micronutrient supplements have been correlated to gestational length and outcome in women predisposed to pre-eclampsia and preterm birth. However, research is yet to be conducted examining the influence of micronutrient supplements on outcomes at term in uncomplicated pregnancies. Aim: To analyse the relationship between third trimester micronutrient supplementation and gestation length at birth, demographics and maternal birthing outcomes in well women at term in a South East Queensland representative population. Methods: This research retrospectively analysed existing data pertaining to 427 uncomplicated, pregnancies birthing at the Gold Coast and Logan Hospitals using information gathered through the Environments for Healthy Living Study and Queensland perinatal data collection. Data were analysed using SPSS v20 by Chi square, ANOVA and regression analysis. Findings: Women in the third trimester taking individual zinc, folic acid or iron supplements in combination with a multivitamin were twice as likely to birth beyond 41 completed weeks (AOR 2.054, 95% CI 1.310–7.383, p = 0.038) then those who did not take any supplement when controlled for established confounders. Non supplement users were found to experience a lower rate of post dates labour and requirements for induction (AOR 0.483, 95% CI 0.278–0.840, p = 0.01). Conclusion: Length of gestation demonstrates significant associations with micronutrient supplementation practices. Well women consuming third trimester individual micronutrient supplements in addition to multivitamins experienced a longer gestation at term compared to women taking no micronutrients, increasing their risk for postdates induction of labour. Crown Copyright ß 2015 Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd) on behalf of Australian College of Midwives. All rights reserved.
1. Introduction Post-dates gestation and prolonged pregnancy pose an increased risk to both mother and baby, routinely managed through induction of labour in the post-dates period.1 While the mechanisms responsible for parturition have yet to be fully elucidated, maternal nutritive status has been identified as contributing to its onset and progression,2 with suboptimal nutrition largely associated with poor perinatal outcomes.3
* Corresponding author at: School of Medical Science, Griffith University Gold Coast Campus, Parklands Drive, Southport, QLD 9726, Australia. Tel.: +61 07 5552 8746. E-mail address: j.vanderlelie@griffith.edu.au (J.J. Vanderlelie).
The importance of adequate maternal micronutrition in facilitating healthy foetal development and supporting the increased demands of pregnancy on maternal physiology has prompted increasing proportions of women to choose a multivitamin preparation during pregnancy.2,3 Multivitamin and mineral supplementation has been found to reduce pregnancy complications, such as pre-eclampsia and preterm birth, when utilised in the first trimester.2,4 However, there is a lack of similar research regarding the physiology of term and post-dates gestation and effect of third trimester micronutrient supplements on the length of gestation at term and beyond. This research retrospectively examined the relationship between micronutrient supplementation in the third trimester, length of gestation and birthing outcomes in an Australian cohort from South East Queensland, providing a valuable foundation for
http://dx.doi.org/10.1016/j.wombi.2015.07.185 1871-5192/Crown Copyright ß 2015 Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd) on behalf of Australian College of Midwives. All rights reserved.
J.M. McAlpine et al. / Women and Birth 29 (2016) 41–46
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ongoing research to improve antenatal nutrition counselling and birthing outcomes in well women at term (Fig. 1). 2. Literature review Human parturition is defined as normal if its onset, coordination and progress occur within a set of defined parameters.5 Any birth occurring between 40 and 42 weeks is deemed post-dates, with pregnancy continuing beyond 42 weeks considered prolonged.6 Risk to both mother and baby commonly associated with such gestations is routinely managed through induction of labour in the post-dates period.1 The labour initiation process is physiologically dependent on uterine change from a quiescent to a contractile state. Hormonal, mechanical and inflammatory influences are known to contribute to this change, as is maternal nutritive state.7,8 Deficiencies in several key micronutrients have been linked with inflammatory processes associated with preterm labour and pre-eclampsia.9 While the effects of malnutrition on pregnancy outcome has been well documented in the developing world, suboptimal nutrition remains a significant public health issue in the developed world, with up to 3 billion people considered malnourished as a result of undernourishment, and micronutrient deficiencies in the presence and absence of adequate macronutrition.10 A large systematic review recently reported that the Australian population is subject to a number of micronutrient deficiencies, with intakes of thiamine, vitamin A, folate, vitamin D, calcium, iron, magnesium and zinc below the estimated average requirement in Australian women.11 Supplementation of micronutrients such as folate, B group vitamins, selenium, vitamin C, vitamin E, zinc and bcarotene have demonstrated improvements in immune function and a reduction in inflammation and placental oxidative stress, and maybe important in improving perinatal outcomes in both high risk pregnancies, especially those in the developing world.9 Despite this work, population level research is limited regarding the effects of micronutrient supplementation on maternal outcomes at term. While maternal and infant nutrition in the developed world demonstrates vastly superior outcomes with regard to perinatal morbidity and mortality, most fail to meet
World Health Organisation recommendations regarding intervention at term.12 This is reflected in the Australian perinatal data statistics, with the national labour induction rate remaining at 25% over the last decade, of which 25% were undertaken for management of prolonged pregnancy.13 This equates to 3530 postdates inductions in 2012 in Queensland alone.13 Considering that primary health care providers are a major source of information regarding healthy eating during pregnancy,14 it is interesting to note that women report the information they receive to be both inconsistent and contradictory.15 Given that appropriate nutrition education and support has the capacity to improve maternal birth outcomes,16 it is essential that primary carers have an understanding of the potential implications of suboptimal nutrition counselling and micronutrient intake during the third trimester of pregnancy. 3. Participants and methods The Environments for Healthy Living (EFHL) is a prospective longitudinal study conducted by Griffith University across the Logan, Beaudesert, Gold Coast Health Districts in South East Queensland (QLD) and Tweed Heads in northern New South Wales (NSW), Australia.17 EFHL is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12610000931077) with detailed methodologies previously published.17 The EFHL study was approved by the Griffith University Human Ethics Committee (MED/16/06/HREC, MED/23/11/HREC). Additional ethical approval was obtained from each recruiting hospital (Logan HREC/06QPAH/ 96, Gold Coast Hospital HREC/06/GCH/52). All women included in this cohort gave written consent for the release of their perinatal data from hospital collections. The target population for this research was pregnant women in the South East Queensland region. From November 2006 – October 2011, a total 2619 live births were recorded from mothers recruited to the EFHL study in the QLD sites; this equated to 23.4% of total births in the target population hospitals during the recruitment periods. Data were collected from the maternal baseline survey and hospital perinatal data records for the Logan and Gold Coast
100 90 80
% Onset of Labour
70 60 No supplements
50
Folic acid + MV Iron + MV
40
Zinc + MV
30 20 10 0 37
38
39
40
41
42
Weeks Gestation
Fig. 1. Effect of micronutrient supplementation on gestational length of well women at term in completed weeks.
J.M. McAlpine et al. / Women and Birth 29 (2016) 41–46
hospitals in QLD. Beaudesert and Tweed Heads health district data were excluded due to inconsistent reporting of data relating to supplement use at these sites (n = 1031). The original dataset encompassed the experiences of 2697 women. Women were excluded if they underwent induction of labour for other medical reasons (such as reduced foetal movements) or for no documented reason (n = 972), were diagnosed with gestational diabetes (n = 204), experienced preterm birth (n = 103), elected a caesarean section (n = 81), were diagnosed with hypertensive disorders or pre-eclampsia (n = 38), twin pregnancies (n = 29), experienced an emergency caesarean section without labour (n = 18), or elected induction for social reasons (n = 13). Data pertaining to third trimester supplement use was obtained from the maternal baseline survey with regard to calcium, iron, folic acid and zinc in addition to commercial multivitamin preparations and miscellaneous supplements. Any woman reporting the use of a specific multivitamin preparation in the ‘other supplements’ category was also included in the analysis. Data was excluded from analysis if multivitamin/mineral supplements were taken in combination with supplements such as raspberry leaf and omega-3 and 6 to exclude the effects of these supplements on maternal birth outcomes at term. The final dataset comprised of 427 well women birthing at the Gold Coast and Logan Hospitals at term. This was analysed retrospectively, examining the relationship between gestational length and demographics, supplements and birthing outcomes using SPSS v20. All categorical data were suitable for analysis using the Chi Square test, highlighting preliminary relationships for further analysis. Significance was accepted at p 0.05 level for all measures and results presented as frequency (percentage), Pearson Chi Square value (x2) and degrees of freedom (df). Logistic regression analysis allowed further exploration of these relationships and examined the contribution of each independent variable while controlling for covariates, the relationship between covariates in relation to the dependent variable, and confounders. Normality checks were performed on the continuous variable gestation at birth (in days) and were found to demonstrate normal distribution. Gestation was initially analysed using one way ANOVA (F-value, eta squared and p-value) to determine significant associations. Linear regression was used to assess the relationship between gestation (days) and micronutrient supplementation practices identified as significant with regard to gestational length. Supplementation groups included no supplementation, multivitamin only, and multivitamin in combination with each of iron, zinc, folate and calcium. Covariates for analysis included maternal age at delivery (continuous), smoking status during pregnancy (yes, no), indigenous status (i.e. Aboriginal/Torres Strait islander descent) (yes, no), socioeconomic status (income quintile), parity (nulliparous, multiparous) and gestational diabetes (yes, no) due to the association between these factors and possible confounding by health promoting behaviours that are likely associated with multivitamin use. Potential confounders were retained in the model if they altered multivitamin exposure by >10%. Each model contained indigenous status and parity as confounders with regard to length of gestation, and each model controlled for known demographic correlations with the supplement in question. Significance remained at p 0.05 level for all measures. Data were stratified by confounders established during demographic and supplement use analysis. 4. Results Third trimester multivitamin/mineral supplementation was reported by 23% of women in the cohort. Multivitamin/mineral
43
users were more likely to be >25 years of age, with a prepregnancy BMI between 25 and 29.9 and of non-indigenous descent. The relationships between length of gestation at birth, and demographic characteristics are presented in Table 1. Significant associations were identified between length of gestation, parity (p = 0.019), and indigenous status (p = 0.031). No significant relationships were determined between micronutrient practices and demographic characteristics such as socioeconomic status, BMI, maternal education or smoking status. For supplement use, significant direct associations were found between length of gestation and the use of folic acid plus a multivitamin (p = 0.007), iron plus a multivitamin (p = 0.004) and zinc plus a multivitamin (p = 0.019). Interestingly a significant inverse association was determined between length of gestation and the unsupplemented pregnancies (p = 0.008).
Table 1 Demographic profile and mean length of gestation (n = 427). Variable
Sex of baby Male Female Maternal age group <20 20–30 >30 Hospital birthed Gold Coast Logan Maternal education level
>5% missing data. Statistically significant.
Dataset total n (% group)
Gestation Mean (days)
F-, p-Value
206 (48.4) 220 (51.6)
282.02 282.62
1.105, 0.354
39 (9.1) 239 (56.0) 149 (34.9)
282.10 282.59 281.85
0.644, 0.526
169 (39.6) 258 (60.4)
282.59 282.10
0.632, 0.427
4 93 137 129
274.75 282.26 282.42 282.28
1.444, 0.218
(0.9) (21.8) (32.2) (30.3)
63 (14.8) 80 78 71 69 59
282.48
(22.4) (21.8) (19.9) (19.3) (16.5)
283.04 282.33 281.80 282.72 282.22
0.441, 0.779
31 (8.0) 195 (50.5) 160 (41.5)
280.90 281.79 282.88
1.988, 0.138
409 (95.8) 18 (4.2)
282.16 285.44
4.672, 0.031**
310 (72.8) 116 (27.2)
282.17 282.65
0.482, 0.448
60 (20.3) 236 (79.7)
283.50 281.42
5.594, 0.019**
228 (53.4) 199 (46.6)
278.43 286.66
352.639, <0.001**
331 (77.9) 55 (12.9) 39 (9.2)
281.80 284.45 282.36
6.118, 0.002**
99 (23.2) 328 (76.8)
283.82 281.92
7.113, 0.008*
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Preliminary results indicate that primiparous women experienced a mean gestation 2.08 days longer than multiparous women (283.50 vs 281.42). Women declaring Aboriginal or Torres Strait Islander descent also demonstrated increased length of gestation, with a mean length approximately 3.28 days longer than their nonindigenous counterparts (285.44 vs 282.16) in this cohort. Additionally, women taking an individual micronutrient in addition to multivitamin supplements experienced a mean gestation of up to 4.15 days longer (Ca + Multi 285.35; Folate + Multi 285.48; Fe + Multi 286.05; Zn + Multi 286.07) than those women not using any supplements (281.92) at all in the third trimester. Both sets of variables were retained as confounders in the linear regression analysis. The regression model encompassing all predictors with regard to no supplements accounted for 5.2% (R2 = 0.052) of the variance in gestation. Subsequently, the absence of supplement use demonstrated a significant linear relationship with length of gestation. Of the confounding variables only parity demonstrated a statistically significant relationship (p = 0.015) with length of gestation. Indigenous status made no unique contribution in this model (Table 2). The negative regression coefficients (B = 0.146 95% CI: 3.639, 0.475) suggest that even when taking into account significant confounders, women who did not take micronutrient supplements during the third trimester were significantly more likely to deliver closer to term. The models examining the relationship between gestation and individual supplements including folic acid (p = 0.003; R2 = 0.047), iron (p = 0.001; R2 = 0.052), and zinc (p = 0.005; R2 = 0.043) utilised in combination with multivitamins were significant. Parity and indigenous status were identified as significant confounders for all supplementation combinations and were included in subsequent regression analyses. The regression coefficients of these analyses suggested that when taking into account significant confounders (Parity, indigenous status), the use of individual micronutrients in combination with multivitamins in the third trimester was significantly associated with increased length of gestation, despite the opposing effect of parity (Table 2). However, with regard to the use of no supplements at all, the negative regression coefficient suggests those women not taking any supplements experienced a gestation closer to 40 weeks independent of the unique contributions of both parity and indigenous status (Table 2). Chi squared and logistic regression analysis of the categorical maternal birthing outcomes onset of labour (induced vs spontaneous) and gestation code (>37–40 completed weeks, 40, 41, and
Table 2 Linear regression analysis – mean gestation and micronutrients (n = 427). Predictor variable
Standardised regression coefficient (95% CI)
No supplements** Parity Indigenous status Calcium + Multivitamin** Parity Indigenous status Maternal education level Folic acid + Multivitamin** Parity Indigenous status Iron + Multivitamin** Parity Indigenous status Zinc + Multivitamin** Parity Indigenous status
0.146 0.140 0.109 0.096 0.140 0.116 0.003 0.130 0.140 0.118 0.148 0.140 0.118 0.114 0.144 0.116
* **
(3.639, 0.475) (3.759, 0.410) (0.096, 7.021) (0.559, 6.638) (3.802, 0.394) (0.045, 7.324) (0.688, 0.720) (0.467, 6.616) (3.764, 0.408) (0.156, 7.297) (0.968, 7.100) (3.761, 0.413) (0.192, 7.313) (0.047, 7.920) (3.833, 0.467) (0.097, 7.249)
Statistically significant. Mahalanobis distance > critical value, Cook’s distance < 1.
p-Value 0.011* 0.015* 0.056 0.098 0.016* 0.047* 0.965 0.024* 0.015* 0.041* 0.010* 0.015* 0.039* 0.047* 0.012* 0.044*
42 completed weeks) also demonstrate relationships of statistical significance. Chi squared analysis determined that women not consuming supplements birthed between 37 and 40 completed weeks in approximately 19% (range: 18.9–19.3%) of cases compared to none of the women (0%) taking combined supplements within the same time frame. With regard to gestation advancing beyond 40 completed weeks, the analysis revealed that women taking a supplement combination birthed after 41 completed weeks in up to 77.3% of cases (range: 73.3–77.3%), compared to approximately 52% (range: 52.1–52.7%) of those women not taking the supplement combination. Logistic regression confirmed these relationships with the supplemented group more than twice as likely to birth beyond 41 completed weeks (AOR 2.054, 95% CI 1.310–7.383, p = 0.038). Analysis of the relationship between onset of labour and supplement use also demonstrated a similar trend with those women taking micronutrient and multivitamin combinations experiencing a post-dates induction rate of up to 72.7% (p = 0.021). In comparison, women who did not use any supplements were less than half as likely to be induced in the post-dates period (AOR 0.483, 95% CI 0.278–0.840, p = 0.010) with only 43% of cases requiring induction (p = 0.009) (Table 3). Due to high rates of induction the influence of micronutrients on onset of labour loses significance as gestation advances when the analyses controlled for gestation at birth (AOR2 0.557, 95% CI 0.221–1.408, p = 0.216) (Table 3). 5. Discussion Research regarding third trimester micronutrient supplementation and term birthing outcomes in well women is scarce. To date, the majority of literature deservedly focuses on preterm birth and pre-eclampsia.18 Preterm birth is a major determinant of perinatal morbidity and mortality in the developed world and has been heavily investigated with significant advances in knowledge regarding the mechanisms and management of such pathologies.3,18–21 Deficiencies in several key micronutrients have been linked with the inflammatory processes involved with preterm labour and pre-eclampsia, hence their efficacy in extending gestation in those women identified as exhibiting risk of these presentations.2 However, a lack of similar research regarding the physiology of term and post-dates gestation has limited our understanding regarding the effect of such micronutrient supplements on length of gestation at term and beyond. The Environments for Healthy Living Birth Cohort is a longitudinal birth cohort collecting data from mothers and their babies from South East Queensland and may be considered representative of the broader population in this region with rates of obesity,22,23 and supplement use24 consistent with that of the local and Australian populations. There are however notable differences between this cohort and the general South East Queensland population in relation to a reduce incidence of preeclampsia22 and lower rates of other health determinants such as substance abuse, smoking, diabetes and essential hypertension when compared to that of the general Australian population.25 For this reason the rates of confounding were in this study were relatively low and it has been hypothesised previously4 that recruitment to a study called ‘Environments for Health Living’ may have skewed participation to those women whose health status was generally good. In the context of this study analysing the effect of multivitamin supplementation in well women at term, this shift towards a healthier cohort may be considered positive. In this South East Queensland population micronutrient supplementation demonstrated significant associations with length of gestation and onset of labour. Those women not taking supplements experienced markedly shorter gestations than those
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Table 3 Association between onset of labour and supplement use. Third trimester supplement use
n (%)
No supplements Spontaneous onset 187 (57.0) Induction of labour 141 (43.0) Folic acid + multivitamin Spontaneous onset 7 (30.4) Induction of labour 16 (69.6) Iron + multivitamin Spontaneous onset 6 (27.3) Induction of labour 16 (72.7) y
Unadjusted odds ratio (p-value)
95% Confidence interval
Adjusted odds ratio 1 (p-value)y
95% Confidence interval
Adjusted odds ratio 2 (p-value)z
95% Confidence interval
1 0.498* (p = 0.012)
Referent 0.290–0.857
1 0.483* (p = 0.010)
Referent 0.278–0.840
1 0.557 (p = 0.216)
Referent 0.221–1.408
1 3.018* (p = 0.049)
Referent 1.005–9.064
1 3.143* (p = 0.044)
Referent 1.030–9.589
1 2.077 (p = 0.422)
Referent 0.348–12.381
1 4.212* (p = 0.016)
Referent 1.308–13.558
1 4.425* (p = 0.014)
Referent 1.355–14.451
1 2.428 (p = 0.337)
Referent 0.397–14.849
Adjusted confounder parity (onset), *statistically significant (p < 0.05). z Adjusted confounders parity and gestation at birth, *statistically significant.
using a multivitamin and micronutrient combination (281.92 days vs 285.35–286.07 days). In relation to the onset of labour we identified similar significant associations when women combined a multivitamin preparation with an individual micronutrient (folic acid, iron and zinc) supplement (Table 3). However when controlling for length of gestation at birth the association between onset and supplement use lost significance. This is indeed may be indicative of policy requirement for induction rather than medical need and the secondary nature of this analysis precluded us from making any further assessments of medical need in those inducted. As such the results of this analysis need to be considered in light of its limitations. While the data collected in this cohort has strengths such as EFHL sample size and data stability17 and reliability of hospital perinatal data,26,27 there also have notable limitations. These included heavy reliance on self-administration of the questionnaire and the self-reported nature of information. Generalised recruitment after 24 weeks of gestation resulted in a heterogeneity in both the cohort and the perspective of responses. Additionally, retrospective reporting of maternal birthing outcomes and associations were problematic, with significant difficulties encountered with missing data in critical variables such as BMI, parity, gestational length in days and supplement use. We were also unable to specifically study the content of each multivitamin/ mineral supplement used in the EFHL cohort and specific data on the duration of use within a particular trimester was not recorded which may have biased our results. Finally, although we adjusted significant confounding factors in our analysis unmeasured residual confounding may have also been a factor in this analysis. The third trimester of pregnancy is a known inflammatory state,9 homeostatically controlled in normal pregnancy. Up-regulation of inflammatory molecules play an essential role in the development of the systemic inflammatory responses required for cervical, myometrial and decidua changes and the spontaneous onset of labour.28,29 Considering previously established findings regarding inflammatory processes and spontaneous preterm labour, it is clear that inflammation plays a critical role in labour initiation regardless of gestation.28 Folate, iron and zinc have each demonstrated relationships with inflammatory molecules and processes.8,30–32 Supplementation of each of these micronutrients has also proven effective in reducing the rate of spontaneous preterm birth in supplemented cohorts.21,33 This supports previous findings regarding the anti-inflammatory properties of these micronutrients at a homeostatic and therapeutic level, and suggest that they act in this capacity against the inflammatory processes of preterm labour. This being the case it is plausible to hypothesise that these micronutrients in excess in well women at term continue to act in this manner, thereby suppressing the natural and necessary inflammatory processes responsible for spontaneous labour and contributing to increased gestational length in our cohort.
These findings have implications for nutrition counselling for women in the antenatal period, particularly with regard to supplement utilisation would suggest that the need for supplementation by healthy women be carefully considered and monitored on an individual basis. Further research is necessary to confirm these findings in similar cohorts. 6. Conclusion Length of gestation demonstrates significant associations with micronutrient supplementation practices. Well women consuming third trimester individual micronutrient supplements in addition to multivitamins experienced a longer gestation at term compared to women taking no micronutrients, increasing their risk for postdates gestation and induction of labour. This may be due to the excessive use of micronutrient supplements and the suppression of the inflammatory processes necessary for spontaneous labour. Sources of funding Core funding to support EFHL is provided by Griffith University. Conflict of interest statement The authors wish to declare that there are no conflicts of interest relevant to this work. Acknowledgements The research reported in this publication is part of the Griffith Study of Population Health: Environments for Healthy Living (EFHL) (Australian and New Zealand Clinical Trials Registry: ACTRN12610000931077). Core funding to support EFHL is provided by Griffith University. The EFHL project was conceived by Professor Rod McClure, Dr Cate Cameron, Professor Judy Searle and Professor Ronan Lyons. We gratefully acknowledge all EFHL project and research staff, in addition to participating hospital administrative staff and hospital antenatal and birth suite midwives for their valuable contributions to the study. References 1. Vayssie`re C, Haumonte J-B, Chantry A, Coatleven F, Debord MP, Gomez C, et al. Prolonged and post-term pregnancies: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol 2013;169(1):10–6. 2. Catov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA. Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr 2011;94(3):906–12. 3. Kawai K, Spiegelman D, Shankar AH, Fawzi WW. Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries:
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