Multivitamin Use and the Risk of Preterm Birth

Anjel Vahratian1 , Anna Maria Siega-Riz1,2,3, David A. Savitz3,4 and John M. Thorp, Jr.3,5

1 Department of Maternal and Child Health, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
2 Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
3 Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
4 Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
5 Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Received for publication October 8, 2002; accepted for publication November 20, 2003.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Previous research suggests that multivitamin use before and during pregnancy can diminish diet-related deficiencies of certain micronutrients and potentially prevent preterm birth. To assess this association, the authors performed an analysis by using data from the Pregnancy, Infection, and Nutrition Study (n = 2,010). Women were recruited at 24–29 weeks of pregnancy from four prenatal care clinics in North Carolina from August 1995 to June 2000. For women who took multivitamins prior to pregnancy, compared with nonusers, the adjusted risk ratio was 0.50 (95% confidence interval: 0.20, 1.25) for delivering preterm (<37 weeks). In contrast, prenatal and periconceptional use, compared with nonuse, were not related to preterm birth, with adjusted risk ratios of 1.1. Preconceptional multivitamin use was inversely associated with both early (<35 weeks; adjusted odds ratio = 0.59, 95% confidence interval: 0.12, 2.76) and late (35–36 weeks; adjusted odds ratio = 0.40, 95% confidence interval: 0.12, 1.40) preterm birth; findings were based on only two and three exposed cases, respectively. These results suggest that, compared with nonusers, women who take multivitamin supplements prior to conception may have a reduced risk of preterm birth, but further studies are needed with a larger sample of preconceptional users.

delivery, obstetric; infant, premature; pregnancy; vitamins

Abbreviations: Abbreviations: CI, confidence interval; PIN, Pregnancy, Infection, and Nutrition.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The effect of suboptimal maternal nutritional status on birth outcomes and pregnancy complications has been found in human observational and animal experimental studies and, to a lesser degree, through randomized clinical trials (15). The timing of the exposure is always of interest in these studies because of the critical time windows for the development of the placenta and fetus. The majority of past studies have examined nutritional factors only during pregnancy, with some studies providing multivitamin supplements to women once pregnancy has been determined or even later when prenatal care begins to improve the nutritional levels of certain micronutrients (i.e., iron, folate, and zinc) during pregnancy. Depending on the specific nutrient and its role in placental and fetal development, waiting until pregnancy is diagnosed may be too late to have a beneficial impact on the course of the pregnancy and its outcome. In addition, since 50 percent of pregnancies in the United States are unintended (6), many women would miss out if only planned pregnancies were exposed to supplement use. Thus, public health professionals encourage women of reproductive age, regardless of their intentions regarding pregnancy, to use a daily multivitamin prior to conception as a preventive measure.

Although the relation with neural tube defects and folic acid is established, it is unclear whether preconceptional and prenatal multivitamin use affects other birth outcomes. Previous research suggests that multivitamin use before and during pregnancy can diminish diet-related deficiencies of certain micronutrients (e.g., folate and iron) and potentially prevent preterm birth (7). Specifically, supplementation studies with folic acid suggest an association between higher folate levels and longer gestation (8, 9). It is hypothesized that folate supplementation promotes a cell-rich placenta, which is beneficial for fetal growth in the last trimester of pregnancy (9, 10). A recent randomized controlled trial of iron supplementation showed that the prevalence of preterm birth was lower with universal supplementation of 30 mg of iron compared with placebo among women with sufficient iron stores at the start of pregnancy (Siega-Riz et al., University of North Carolina at Chapel Hill, unpublished manuscript), and one other study showed a beneficial effect on reducing the incidence of preterm low-birth-weight infants (11).

To our knowledge, only three studies to date have examined the relation between the timing of multivitamin supplement use and the risk of preterm birth (7, 12, 13). However, the findings from these studies are inconsistent. A randomized controlled trial found a higher, but not significantly different rate of preterm birth among periconceptional multivitamin users compared with those who took a trace element (13). In comparison, a retrospective analysis reported an inverse association between periconceptional use and preterm birth, compared with nonuse, with an adjusted odds ratio of 0.72 (95 percent confidence interval (CI): 0.40, 1.30) (12). A third, prospective analysis reported an inverse association between prenatal use, compared with nonuse, and both preterm and very preterm (<33 completed weeks of gestation) birth, with adjusted odds ratios on the order of 0.55–0.66 for preterm and 0.21–0.44 for very preterm birth, depending on whether gestational age was based on date of the last menstrual period or an obstetric estimate (7).

In each analysis, the authors defined the exposure and outcome of interest as a dichotomous variable. Generally, multivitamin use was defined as either periconceptional or prenatal use versus nonuse (12, 13), with the periconceptional period ranging from 1 month prior to conception through 2–3 months of pregnancy. With regard to preterm birth, we know of only one study that looked at early versus late preterm birth as well (7). Thus, our study sought to fill in the gaps related to the exposure time window and preterm birth subtypes by exploring the relation between multivitamin use and the risk of preterm birth using data from the Pregnancy, Infection, and Nutrition (PIN) Study.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Study design and sample
The PIN Study is a prospective cohort study designed to examine determinants of preterm birth. Women were recruited at 24–29 weeks of pregnancy from four prenatal care clinics in central North Carolina: the University of North Carolina Resident and Private Physician Obstetric Clinics and the Wake County Department of Human Services and Wake Area Education Prenatal Care Clinics. Women less than 16 years of age, non-English-language speakers, or women undergoing a multiple-gestation pregnancy were excluded from participating.

Blood, urine, and genital tract specimens were collected from participants at the time of recruitment; in addition, a food frequency questionnaire assessed preconceptional supplement use and dietary intake in the second trimester. A telephone interview was conducted shortly afterwards to collect information on sociodemographic characteristics, the current pregnancy, reproductive and medical histories, and health behaviors. Delivery logs were examined to determine birth outcome information on all participants. The PIN Study was approved by the institutional review boards of the University of North Carolina School of Medicine and Wake Medical Center.

Women were recruited for this study from August 1995 to June 2000. During this time, 5,194 women were identified as eligible for participation, and 3,163 (61 percent) were recruited successfully. Slightly more White women than Black women were recruited into the PIN Study in comparison to the women who refused to participate. More notable differences were found when the different study sites were compared; the health department clinics had a greater proportion of refusals and more women who could not be contacted than the teaching hospital did. The study had somewhat greater success in recruiting highly educated (>16 years of education) and older (age >35 years) women. The risk of preterm birth was similar among the successfully recruited women compared with those who refused (14). Of those women recruited successfully, 2,586 completed both the food frequency questionnaire and the telephone interview. Excluded from this analysis were 180 women who reported incomplete information on multivitamin intake and 396 women who did not report complete information on potential confounders. Thus, this analysis was limited to women for whom information from these sources was complete (n = 2,010). Compared with the original study population, this sample included a higher proportion of White, more highly educated, and married women.

Birth outcome
The outcome of interest for this analysis was preterm birth, defined as a delivery prior to 37 completed weeks of gestation. Gestational age was determined on the basis of a self-reported estimate of the date of the last menstrual period or an estimate derived from an ultrasound examination when the date of the last menstrual period was unknown. When the two estimates were within 14 days of each other, the estimated date of the last menstrual period was used. However, if the estimates differed by more than 14 days, the ultrasound estimate was used. One of three obstetricians examined the charts for all preterm deliveries to determine whether the delivery was spontaneous or medically indicated. For additional insight, preterm deliveries were subdivided into spontaneous and medically indicated preterm as well as early (<35 completed weeks of gestation) and late (35–36 completed weeks of gestation) preterm. A medically indicated preterm delivery was defined as induction of labor or cesarean section without labor before 37 weeks of gestation based on the health of the mother or fetus.

Exposure of interest and selected covariates
Multivitamin use was the exposure of interest for this analysis. This variable was constructed based on responses from both the screening/telephone interview (at the time of the screener at 24–29 weeks or telephone interview, which was at 27–29 weeks) and the food frequency questionnaire, and it consisted of four levels of the exposure time window: preconceptional use only, prenatal use only, periconceptional (preconceptional and prenatal) use, and nonuse. Together, these categories represented all possible combinations of multivitamin intake prior to and during pregnancy. The food frequency questionnaire ascertained preconceptional use, while the main telephone interview or screener established prenatal use. For this analysis, preconceptional use referred to intake anytime before pregnancy, while prenatal use referred to intake anytime during pregnancy up until the time of interview or recruitment. Women who responded that they did not take multivitamins before or during pregnancy were identified as nonusers. Information regarding potential confounders was obtained from the medical record, the telephone interview, the diet questionnaire, and specimen collection at the time of recruitment.

Statistical analysis
Descriptive analyses were conducted to assess the distributions of the various covariates across each of the four levels of multivitamin use. Student’s t tests or chi-square tests were used to assess statistical significance (p < 0.05). The proportion of preterm births in this sample was 11.5 percent. Thus, log-linear regression models were used to compute crude and adjusted risk ratios and 95 percent confidence intervals for the effect of multivitamin use on the risk of preterm birth, because an odds ratio would overestimate the risk ratio when the outcome is common (>10 percent). To isolate spontaneous preterm births, we repeated this analysis after excluding medically indicated preterm births.

We did not include interaction terms in the full model because previously published studies did not suggest the presence of effect modification by maternal race and stratified analyses did not reveal any effect modification. Potential confounders were included in the full model if they were risk factors for preterm birth and were associated with multivitamin use in the source population, based on a p value of ≤0.20. These covariates included maternal race, parity, marital status, maternal health during pregnancy, vomiting during pregnancy, estimated energy intake, and estimated vitamin A, vitamin C, calcium, iron, folate, and zinc intake per 1,000 kcal. However, only those covariates that changed the beta coefficient of the multivitamin variable by more than 10 percent were retained in the final model. These covariates included maternal race, parity, marital status, maternal health status during pregnancy, vomiting during pregnancy, estimated energy intake, and estimated iron and folate intake per 1,000 kcal. Logistic regression models examined the effect of multivitamin use on early and late preterm birth, and crude and adjusted odds ratios and 95 percent confidence intervals were computed because the proportions of early (4.7 percent) and late (7.4 percent) preterm births in this sample were less than 10 percent. All analyses were performed by using the Statistical Analysis System (SAS), version 8.1 (SAS Institute, Inc., Cary, North Carolina).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Periconceptional (30 percent) and prenatal (54 percent) users comprised the majority of the study population. Of the four multivitamin groups, preconceptional users had the lowest rate of preterm birth (5.4 percent). In comparison, the preterm birth rate was between 11 and 13 percent for periconceptional, prenatal, and nonusers. Sociodemographic, medical, and behavioral information on participants is presented in table 1 according to their multivitamin use. Women who reported multivitamin use both before and during pregnancy were, on average, older, married, more educated, and more financially secure than the rest of the population. Preconceptional users reported the highest frequency of nausea (86.0 percent) or vomiting (46.2 percent) among all four groups, suggesting that this was a possible explanation for their not taking supplements during pregnancy. Means and standard deviations of selected estimated dietary intakes of certain nutrients (per 1,000 kcal) are presented in table 2 according to multivitamin use. Periconceptional users consistently recorded higher levels of each nutrient (per 1,000 kcal) compared with the other groups.


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TABLE 1. Selected characteristics, according to multivitamin use, of women in the Pregnancy, Infection, and Nutrition Study, 1995–2000
 

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TABLE 2. Means (standard deviations) of selected estimated dietary intake factors, according to multivitamin use, for women in the Pregnancy, Infection, and Nutrition Study, 1995–2000
 
Unadjusted risk ratios showed an inverse association between preconceptional or periconceptional multivitamin use, compared with nonuse, and preterm birth (table 3). After adjustment for maternal race, marital status, parity, self-reported maternal health status during pregnancy, vomiting during pregnancy, estimated energy intake, and estimated daily iron intake and folate intake per 1,000 kcal, the risk of preterm birth for preconceptional users remained lower than that for the other groups (adjusted risk ratio = 0.50, 95 percent CI: 0.20, 1.25). In comparison, the risk of preterm birth for periconceptional and prenatal users increased slightly after adjustment to 1.10 and 1.14, respectively, suggesting little to no association.


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TABLE 3. Effect of multivitamin use on preterm delivery for women in the Pregnancy, Infection, and Nutrition Study, 1995–2000
 
When preterm birth was subdivided into early versus late preterm birth, preconceptional use was associated with a very imprecise suggestion of a reduction in the risk of both early and late preterm birth, with adjusted odds ratios of 0.59 (95 percent CI: 0.12, 2.76; n = 2 cases) for early preterm birth and 0.40 (95 percent CI: 0.12, 1.40; n = 3 cases) for late preterm birth. Prenatal and periconceptional use were each weakly associated with early preterm birth, with adjusted odds ratios of 1.56 (95 percent CI: 0.72, 3.35) and 1.41 (95 percent CI: 0.71, 2.79), respectively, whereas no association was found with late preterm birth. When the analysis was repeated after excluding medically indicated preterm births to isolate spontaneous preterm births, similar findings were reported for most groups, although an inverse association was no longer present between preconceptional use and early preterm birth (adjusted odds ratio = 1.01, 95 percent CI: 0.19, 5.23; n = 2 cases). The inverse association between preconceptional use and late preterm birth was stronger after we excluded medically indicated preterm births (adjusted odds ratio = 0.24, 95 percent CI: 0.03, 1.91; n = 1 case). However, the confidence intervals widened in subgroup analyses, a reflection of the imprecision in the estimates due to the small number of cases.


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
This analysis demonstrates that, compared with nonusers, women who use multivitamin supplements prior to conception may have a reduced risk of preterm birth. Previous studies have found an association between multivitamin use and preterm birth, but only for periconceptional or prenatal users, not preconceptional users. Shaw et al. (12) explored whether a risk reduction in preterm delivery could be associated with maternal periconceptional multivitamin use. In a letter to the editor, the authors described a retrospective analysis of a cohort of livebirths in California from 1987 to 1989 originally used as controls in a case-control study of orofacial clefts. They reported an adjusted odds ratio of 0.72 (95 percent CI: 0.40, 1.30) for women who used vitamins, compared with nonusers, anytime from 1 month prior to conception until 3 months postconception. However, a limitation of this study was that the authors adjusted for maternal race and cigarette smoking only, and information on multivitamin use was collected retrospectively. Factors related to maternal health status during pregnancy or dietary intake were not assessed.

Scholl et al. (7) conducted a prospective cohort study of low-income, urban women in New Jersey who participated in the Camden Study from 1985 to 1995. The sample was restricted to women with singleton pregnancies who entered prenatal care during their first and second trimesters of pregnancy. The authors reported an odds ratio of 0.66 (95 percent CI: 0.47, 0.93) for women who used vitamins during the first and second trimester of pregnancy, compared with nonusers, and after adjusting for multiple confounders similar to those in our study. However, the focus of their study was prenatal use; preconceptional use was assessed as a potential confounder only. Moreover, the authors studied a very low income population of young women (mean age of 18 years).

In our study, preconceptional users had higher rates of nausea and vomiting compared with prenatal, periconceptional, and nonusers. They also had the lowest rate of preterm births. It is possible that the nausea and vomiting prevented women from continuing their supplement use during pregnancy; vomiting has been associated with a lack of multivitamin supplementation early in pregnancy (15). Moreover, previous research indicates that women who experience nausea and vomiting early in pregnancy are less likely to deliver preterm (1618). Huxley suggests that "a reduced nutrient intake in early pregnancy lowers maternal levels of the anabolic hormones, insulin, and IGF-1 [insulin-like growth factor-1]. This helps to ensure that nutrient delivery to the placenta is sufficient to ensure adequate placental growth" (19, pp. 780–781). The etiology of nausea and vomiting is not well understood, but it is thought that the hormonal response to the pregnancy state may cause the nausea and vomiting and as such serve as an indication that the body is accepting the pregnancy state.

In our analysis, vomiting during pregnancy was retained as a confounder in modeling the association between multivitamin use and preterm birth. In contrast, nausea during pregnancy did not meet the criteria for confounding. The PIN Study assessed vomiting during pregnancy based on responses to the following two questions: "Have you vomited five or more days in a row during this pregnancy because of nausea?" and "Have you vomited during this pregnancy because of nausea?". Thus, this covariate measured the frequency of vomiting specific to nausea during pregnancy rather than from a condition irrespective of the current pregnancy. In multivariate analyses, adjustment for this covariate had a minimal effect on the risk ratios for preterm birth for any exposure group and only slightly increased the odds of early preterm birth for periconceptional (from 1.50 to 1.56) and prenatal (from 1.39 to 1.41) users. The reduction in the risk of preterm birth for preconceptional users remained after adjustment and merits further study.

Strengths of this analysis include a comprehensive definition of multivitamin use that assessed preconceptional, prenatal, and periconceptional intake as separate categories. In addition, multiple sociodemographic, behavioral, dietary, and medical factors were considered as potential confounders. However, the small number of women categorized as preconceptional users, compared with the other exposure levels, was a limitation of this observational study, as reflected in the wide confidence intervals.

The findings of our study must be interpreted with recognition of its other limitations. Generalizability may be limited to low- and moderate-income women receiving prenatal care. Since the recruitment period for this study occurred at 24–29 weeks of pregnancy, women who entered prenatal care in the third trimester or not at all were excluded from this analysis. This approach could have introduced selection bias because women at higher risk of adverse birth outcomes were excluded from the sample; this loss may have been differential by vitamin use.

Dietary data were assessed by using a semiquantitative food frequency questionnaire and are subject to the errors inherent in this mode of data collection. Information on supplement use was collected separately for each time period. However, within those time periods, we know that compliance with taking the supplements is less than ideal; thus, our assumption of a constant level during the time period is imperfect. Information on dietary intake and supplement use during the third trimester was lacking.

Lastly, because of the observational nature of our data, we cannot entirely exclude the possibility that important confounders were omitted from the analysis or that adjustment for confounders was incomplete. Moreover, we acknowledge that the patterns observed in our data may have been the result of random error, given the small numbers in some cells and the lack of statistical significance, and may have added some uncertainty to our findings.

Women who use multivitamin supplements prior to conception, compared with nonusers, may have a reduced risk of preterm birth. However, this protective effect may be limited to late preterm deliveries, although the precision of these estimates diminished in subgroup analyses. It is thought that the determinants between early and late preterm birth differ. Romero et al. (20) reported that at least 40 percent of all preterm deliveries occur among mothers who have an intrauterine infection. Moreover, among early preterm deliveries, there is a greater frequency of intrauterine infection (21). Whereas early preterm birth is more than likely pathologic, late preterm birth without growth restriction may be related to medical complications during pregnancy, error associated with the measurement of gestational age, or other unknown factors. It is difficult to interpret our results for preconceptional multivitamin use and late preterm birth because only five of 93 preconceptional users delivered preterm; of those five women, three delivered a late preterm infant. While this modest sample is a limitation of our analysis of subsets of preterm birth, this association merits further study with a larger sample of preconceptional users. Finally, we recognize that preconceptional use may be a proxy for overall healthiness; previous research suggests that supplement use is generally higher among those who perceive their health as excellent or very good (22). In this analysis, women who used multivitamins prior to conception, compared with nonusers, were more likely to report their health status as excellent or good and had higher levels of most nutrients (per 1,000 kcal).


    ACKNOWLEDGMENTS
 
This study was supported by grant HD28684 from the National Institute of Child Health and Human Development, National Institutes of Health; cooperative agreements S455/16-17 through the Association of Schools of Public Health/Centers for Disease Control and Prevention and U64/CCU412273 through the Centers for Disease Control and Prevention; grant 6-FY99-401 from the March of Dimes Birth Defects Foundation; and funds from the Wake Area Health Education Center in Raleigh, North Carolina.

The authors appreciate the cooperation and support of all study staff members and prenatal care providers.


    NOTES
 
Correspondence to Anjel Vahratian, Department of Obstetrics and Gynecology, University of Michigan at Ann Arbor, L4000 Women’s Hospital, 1500 East Medical Center Drive, Ann Arbor, MI 48108-0276 (e-mail: amv{at}med.umich.edu). Back


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Institute of Medicine. Nutrition during pregnancy and lactation: an implementation guide. Committee on Nutritional Status During Pregnancy and Lactation, Food and Nutrition Board, Subcommittee for Clinical Application Guide. Washington, DC: National Academy Press, 1992.
  2. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000;71:1295S–303S.[Abstract/Free Full Text]
  3. Keen CL, Clegg MS, Hanna LA, et al. The plausibility of micronutrient deficiencies being a significant contributing factor to the occurrence of pregnancy complications. J Nutr 2003;133:1597S–605S.[Abstract/Free Full Text]
  4. Villar J, Merialdi M, Gulmezoglu AM, et al. Nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and preterm delivery: an overview of randomized controlled trials. J Nutr 2003;133:1606S–25S.[Abstract/Free Full Text]
  5. Merialdi M, Carroli G, Villar J, et al. Nutritional interventions during pregnancy for the prevention or treatment of impaired fetal growth: an overview of randomized controlled trials. J Nutr 2003;133:1626S–31S.[Abstract/Free Full Text]
  6. Abma JC, Chandra A, Mosher WD, et al. Fertility, family planning, and women’s health: new data from the 1995 National Survey of Family Growth. Vital Health Stat 23 1997;May:1–114.
  7. Scholl TO, Hediger ML, Bendich A, et al. Use of multivitamin/mineral prenatal supplements: influence on the outcome of pregnancy. Am J Epidemiol 1997;146:134–41.[Abstract]
  8. Zittoun J, Blot I, Hill C, et al. Iron supplements versus placebo during pregnancy: its effects on iron and folate status on mothers and newborns. Ann Nutr Metab 1983;27:320–7.[ISI][Medline]
  9. Rolschau J, Kristoffersen K, Ulrich M, et al. The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark: Part I. Eur J Obstet Gynecol Reprod Biol 1999;87:105–10.[CrossRef][ISI][Medline]
  10. Rolschau J. A prospective study of the placental weight and content of protein, RNA and DNA. Acta Obstet Gynecol Scand 1978;72(suppl):28–43.
  11. Cogswell ME, Parvanta I, Ickes L, et al. Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr 2003;78:773–81.[Abstract/Free Full Text]
  12. Shaw G, Liberman R, Todoroff K, et al. Low birth weight, preterm delivery, and periconceptional vitamin use. J Pediatr 1997;130:1013–14.
  13. Czeizel AE, Dudas I, Metneki J. Pregnancy outcomes in a randomized control trial of periconceptional multivitamin supplementation. Arch Gynecol Obstet 1994;255:131–9.[CrossRef][ISI][Medline]
  14. Savitz DA, Dole N, Williams J, et al. Determinants of participation in an epidemiological study of preterm delivery. Paediatr Perinat Epidemiol 1999;13:114–25.[CrossRef][ISI][Medline]
  15. Emelianova S, Mazzotta P, Einarson A, et al. Prevalence and severity of nausea and vomiting of pregnancy and effect of vitamin supplementation. Clin Invest Med 1999;22:106–10.[ISI][Medline]
  16. Furneaux EC, Langley-Evans AJ, Langley-Evans SC. Nausea and vomiting of pregnancy: endocrine basis and contribution to pregnancy outcome. Obstet Gynecol Surv 2001;56:775–82.[CrossRef][ISI][Medline]
  17. Tierson FD, Olsen CL, Hook EB. Nausea and vomiting of pregnancy and association with pregnancy outcome. Am J Obstet Gynecol 1986;155:1017–22.[ISI][Medline]
  18. Petridou E, Salvanos H, Skalkidou A, et al. Are there common triggers of preterm deliveries? Br J Obstet Gynecol 2001;108:598–604.[CrossRef][ISI]
  19. Huxley RR. Nausea and vomiting in early pregnancy: its role in placental development. Obstet Gynecol 2000;95:779–82.[Abstract/Free Full Text]
  20. Romero R, Espinoza J, Chaiworapongsa T, et al. Infection and prematurity and the role of preventive strategies. Semin Neonatol 2002;7:259–74.[CrossRef][Medline]
  21. Watts DH, Krohn MA, Hillier SL, et al. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992;79:351–7.[Abstract]
  22. Bender MM, Levy AS, Schucker RE, et al. Trends in prevalence and magnitude of vitamin and mineral supplement usage and correlation with health status. J Am Diet Assoc 1992;92:1096–101.[ISI][Medline]




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