Aromatherapy for First Trimester Nausea,Vomiting,and Subjective Well-Being: A Blinded,Randomized,Placebo Controlled Clinical Trial of Three Essential Oils

Abstract

Background:

Pregnant patients often seek natural remedies when they experience pregnancy-induced nausea and vomiting (PINV). Scant evidence exists to quantify the beneficial effects of essential oil inhalation as a remedy for PINV, yet is identified as a common integrative and complementary medicine treatment, particularly during the first trimester. The purpose of this trial was to evaluate the effects of aromatic essential oils on nausea, vomiting, and quality of life during the first 13 weeks of pregnancy.

Methods:

This was a 4-arm randomized, blinded, placebo controlled clinical trial to evaluate the potential of grapefruit, ginger, and peppermint essential oils on nausea, vomiting, and overall quality of life. Citrus paradisi is cold pressed from the citrus rind, Zingiber officinale is extracted from the root of the herb, and Mentha x piperita is extracted from the leaves of the plant. The essential oils were diluted in avocado oil for skin application. The placebo consisted of avocado oil. Participants were recruited through the research practice's database and completed the intervention in their own homes to mimic real world scenarios. Seventy-four pregnant women within their first trimester were randomized into four groups, including the placebo group.

Results:

Outcomes were measured using the Quantification of Emesis 24-hour scale (PUQE-24), a validated measurement of nausea, vomiting, and quality of life during pregnancy. All groups improved on all measures progressively during the trial. When placebo and intervention groups were compared, there was no significant difference between groups on sleep and nausea outcomes. Ginger essential oil was found to reduce retching and the use of aromatherapy in general improved well-being.

Introduction

Background

During the 13-week first trimester of pregnancy, up to 75% of pregnant individuals experience pregnancy-induced nausea and vomiting (PINV) for an average of 34.6 days.¹ For many expectant people, these symptoms are intermittent, but 80% of patients with PINV report feeling these symptoms persistently throughout the day.² This has the potential to reduce overall quality of life, and many individuals have found that PINV negatively affects their performance at work, at home, and in relationships.^3
–5

There is no known cause of PINV, though rapidly rising hormone levels are believed to play a contributing role.⁶ A myriad of interventions are utilized to address this widespread health concern. These range from pharmacological treatments to diet and lifestyle changes to alternative medicine approaches such as acupressure, vitamins, and herbal extracts such as essential oils.⁷ An extensive body of literature has been devoted to reviewing the efficacy of these interventions, which vary in efficacy.^8,9

With a wide range of choices from which to choose, pregnant patients frequently indicate a preference for natural solutions during pregnancy; this is often attributed to a perception that natural remedies are safer than pharmaceuticals.^4,10 Natural options, such as aromatherapy with essential oils, are often self-prescribed, though many midwives report recommending supplements and botanical medicines.^11
–13

However, despite this widespread usage little is known about the safety and efficacy of botanical interventions, such as aromatherapy, for routine pregnancy concerns such as PINV. This lack of quality scientific evidence produces a wide range of inconsistent recommendations among nurses, midwives, and obstetricians for pregnant patients, in part due to inconsistencies in education on the risks and benefits of botanical interventions such as aromatherapy during pregnancy.¹⁴

Aromatherapy refers to the use of essential oils, which are volatile compounds extracted from aromatic plants. These volatile oils provide effects through inhalation of the aromas, through topical applications to the skin, and in specific cases, through ingestion. Inhalation can be achieved by using a diffuser, but dosing is more precise when a personal inhaler is used or the oils are applied to the skin near the face. Inhalation of essential oils has been shown to reduce feelings of anxiety, to increase stamina, and to improve well-being, throughout the lifespan.^15,16 Among pregnant people, scant evidence exists to quantify the beneficial effects of essential oil inhalation, particularly during the first trimester.

As-needed inhalation of lemon essential oil during the first trimester has been found to have a small reduction effect on overall nausea and vomiting scores.¹⁷ Peppermint essential oil has also been studied for nausea and vomiting of pregnancy, but with mixed results. Some studies find that it has a small, but statistically significant beneficial effect on PINV, while others find that its effects are consistent with those of a placebo.^18
–20 Blending peppermint essential oil with lavender does not change the size of the effect.²¹

Despite the scarcity of scientific evidence, aromatherapy is frequently cited as one of the most common integrative and complementary medicine interventions during pregnancy, as reported by both pregnant patients and their healthcare providers.^22,23 This is particularly concerning given that rates of integrative and complementary medicine usage during pregnancy is close to that of non-pregnant individuals.²⁴

Objectives

The purpose of this study was to examine the effects of three different essential oils on first trimester (13 weeks) PINV and subjective well-being, as compared to a placebo. This study is reported using the CONSORT checklist for reporting clinical trials with the Herbal Medicinal Interventions extension.^25,26

Methods

Trial Design

This four-arm study was a balanced randomized (1:1:1:1), single blinded, placebo-controlled parallel-group clinical trial conducted in the United States among otherwise healthy pregnant patients in their first trimester.

Participants

Participants were eligible for inclusion if they met the following criteria: first trimester of pregnancy (<13 weeks at the end of the trial), aged 18–45, and lived in the United States. Participants with a high risk pregnancy, a diagnosis of hyperemesis gravidarum, or who were under medical care for PINV were excluded to avoid the influence of other treatments on the outcomes of interest. Participants with tobacco use in the home were also excluded due to the potential for tobacco to interfere with the odor-based intervention.

Patients were recruited via e-mail sent to individuals in the research center's database as well as through online advertisements. The study was conducted in accordance with the Declaration of Helsinki and adhered to Good Clinical Practice guidelines. Ethical approval for the study protocol and the informed consent documents was obtained by a central IRB prior to the recruitment of the first participant. The trial was also registered at ClinicalTrials.gov, NCT03513536. All participants were informed of the risks and benefits of the study and provided written informed consent prior to any intervention procedures.

Intervention

Participants were randomly assigned to one of four arms using covariate adaptive randomization. All patients received a 10 mL roller ball applicator to be self-administered. The three active arms included essential oils diluted with avocado oil, while the placebo arm only included avocado oil. The three active arms contained one of the following essential oils: grapefruit, ginger, or peppermint. All essential oils were purchased from Eden Botanicals, an essential oil supplier in California. Purity and chemical composition were assessed via gas chromatography–mass spectrometry data provided by the distiller.

Grapefruit (Citrus paradisi) oil is cold pressed from the citrus rind, and was selected as a limonene-rich oil for its mild, fresh aroma. The grapefruit rollerball contained 60% white grapefruit oil and 40% avocado oil. Ginger (Zingiber officinale) oil is extracted from the rhizome of the herb, which is used in herbal medicine to alleviate nausea and vomiting. The ginger roller ball contained 25% fresh ginger oil and 75% avocado oil. Peppermint (Mentha x piperita) oil is extracted from the leaves of the plant, which are also used in herbal medicine to alleviate nausea and vomiting. The peppermint rollerball contained 15% peppermint oil and 85% avocado oil. The essential oil dilution ratio for each botanical was selected by professional aromatherapists based on a combination of factors including the current safety data for topical exposure to each oil and the aroma's strength.

Participants applied the rollerball of oil directly to the skin for seven days, every four to six waking hours, but not within a half an hour of a meal. For each application, oils were applied to the inside of the wrists and along the side of the face, from the temples to the jawline. This ensured frequent inhalation of the essential oil throughout the day.

A placebo arm was included in this study because the placebo effect is highly effective for the reduction of subjective symptoms, such as well-being and nausea, as compared to objective measures such as tumor size. Because this study is designed to evaluate the effects of an intervention on a subjective outcome, the placebo group distinguishes between the effects which can be attributed to the essential oils rather than the mere practice of an aroma-based intervention.

Outcomes

The prespecified primary endpoint to measure efficacy was the day 3 score on the Quantification of Emesis 24-hour scale (PUQE-24). The PUQE-24 scale was developed to quantify nausea and vomiting, rather than relying on subject perception and has been validated for use with pregnancy-related nausea and vomiting. This scale contains three questions which are ranked on a scale of 1–5. Collectively, these three questions produce a total PUQE score which ranges from 3 to 15. It also measures self reported sleep and subjective well-being.

A prespecified exploratory endpoint of the study was the effect any form of aromatherapy had on each of the PUQE-24 scores, as compared to the control group. For this analysis, all three intervention groups were combined into one group, which was compared directly with the placebo.

Safety was measured using monitoring for adverse events from the time of the first intervention until seven days after the study concluded. Participants were instructed to notify the research staff of any side effects and open-ended questions at the end of the study solicited additional information about the participant's experience, including any unwanted effects and subjective satisfaction with the intervention.

Sample Size

Sample size was established to identify a large effect size (F = 0.4) using four study arms. With a significance level of 0.05 and power of 0.8, the required sample size was 52 participants or 13 per group. Between 10% and 15% of pregnancies end in miscarriage, which often occurs in the first trimester.²⁷ To allow for loss of follow-up due to pregnancy loss, recruitment was increased by 20% to 62 participants.

Randomization and Blinding

To control for maternal age and parity, a covariate adaptive randomization approach was utilized. This ensures even distribution of patients in both groups based on these potentially confounding variables. Adaptive randomization sequences used the Covariate Adaptive Randomization software developed by Kang et al. to control for age and parity.²⁸

Rollerballs in all four arms were identical in appearance. These were prepackaged and consecutively numbered using the randomization protocol. Participants provided demographic information about themselves and were allocated to one of the four study arms by one member of the research team. After a patient provided informed consent, this member directed which rollerball number should be assigned.

Participants were blinded to intervention allocation. In an aromatherapy trial, due to the presence of a scent, successful blinding requires multiple strategies. This was accomplished by concealing the specific odors and anticipated strength of the aromatherapeutic interventions as well as controlling participant expectations. Success of blinding was evaluated through the use of open-ended questions regarding group assignment. No differences were found between the group responses regarding their perception of the assigned intervention group.

Statistical Analyses

The primary endpoint scores for nausea, vomiting, and retching, sleep, and overall well-being were assessed using analysis of covariance (ANCOVA) with baseline scores as the covariate. A total of five outcomes (nausea, vomiting, retching, sleep, subjective well-being) were assessed.

To ensure assumptions were met, descriptive statistics were conducted to check for skewness and kurtosis. Kolmogorov-Smirnov normality test assessed normality of the variables and Levene's test for equality of variances was conducted to assess for homogeneity. Post hoc corrections were made using Bonferroni adjustments. All statistical analyses were conducted using STATA version 16.

Exploratory Analysis

In addition to assessing each of the three aromatherapy arms individually, the aromatherapy participants were combined into a single “aromatherapy” group and contrasted with the placebo group. This allowed a comprehensive analysis of the overall effect of using scent to boost quality of life during pregnancy. This analysis was conducted using the same methods as the primary analysis.

Results

Participant Flow

Participants were recruited from January 2019 through October 2019. Prior to recruiting participants, the study protocol was reviewed and approved by a central IRB and registered at ClinicalTrials.gov. A total of 74 participants signed consent forms, received materials, and completed at least one day of the study. The participants were randomized into four groups using adaptive randomization to control for age and parity. Of the participants, six were withdrawn from the study due to pregnancy loss, adverse effects, or personal dislike of the aroma.

Three participants were withdrawn due to pregnancy loss. One loss occurred in the peppermint group, one in the ginger group, and one in the placebo group. The loss in the peppermint group began after baseline data collection, but before the start of the intervention. The loss in the ginger group occurred after recruitment, but before the start of the study. The loss in the placebo group began on the final day of the study. Because all three losses began prior to or in the absence of exposure to the essential oils, these participants were classified as withdrawals.

One adverse event was recorded. A participant in the placebo group withdrew on day 3 and reported that the treatment was causing “horrible headaches.” Additionally, two participants in the ginger group noted that they did not like the aroma; one continued despite not liking the aroma and the other withdrew.

An additional 15 participants were lost to follow-up, providing data for a total of 53 participants on day 3 for a modified intent-to-treat analysis. All patients for whom day 3 data were available were analyzed as randomized. The withdrawn participants and those lost to follow-up were evenly distributed among the groups, therefore the final sample size met the requirements of the power analysis.

Baseline Data

Participants were all in the first trimester and were between the ages of 21 and 43 years (M = 31.04, SD = 7.15). Over half (65.71%) of participants were on their first or second pregnancy, with mean gravidity being 1.40 (SD = 1.66). Most participants had a history of healthy pregnancies carried full term, with 67.14 experiencing 0 previous miscarriages and only 11.43% experiencing 2 or more miscarriages. There were no differences between groups on any baseline variables.

Nausea, Vomiting, and Retching

A one-way between-groups ANCOVA was conducted to compare the efficacy of the three essential oils with a placebo for nausea, vomiting, and retching on day 3, with the baseline score for each outcome as the covariate. Preliminary checks were conducted to ensure there was no violation of the assumptions of normality, linearity, homogeneity of variances, homogeneity of regression slopes and reliable measurement of the covariate.

After adjusting for baseline scores, there was no significant difference between any of the three intervention groups on nausea scores on day 3 (F(3,41) = 1.34, P = 0.275, partial eta squared = 0.089). Similarly, after adjusting for baseline scores, there was no significant difference between any of the three intervention groups on vomiting scores on day 3 (F(3,41) = 0.94, P = 0.432, partial eta squared = 0.064).

However, significant reductions in retching were identified on day 3 (F(3,41) = 3.53, P = 0.023, partial eta squared = 0.205). Post hoc analysis using a Bonferroni correction identifies that ginger essential oil is more effective than grapefruit, peppermint, or the placebo at reducing retching on day 3, with an extremely large overall effect size. Three days of aromatherapy intervention did not significantly reduce nausea or vomiting, but did have an extremely large reduction effect on retching (Table 1).

Table 1.

Retching Scores, Day 3

Source	df	SS	MS	F	P	η ²
Baseline score	1	8.11	0.197	40.53	<0.001	0.497
Treatment group	3	6.17	0.699	3.53	0.023	0.205
Error	41
Total	45
Adjusted R ² = 0.467

Sleep and Subjective Well-being

A one-way between-groups ANCOVA was conducted to compare the efficacy of the three essential oils with a placebo for the outcomes of sleep and subjective well-being on day 3, with the baseline score for each outcome as the covariate. Preliminary checks were conducted to ensure there was no violation of the assumptions of normality, linearity, homogeneity of variances, homogeneity of regression slopes and reliable measurement of the covariate.

After adjusting for baseline scores, there was no significant difference between any of the three intervention groups on sleep scores (F(3,41) = 0.97, P = 0.418, partial eta squared = 0.066) or subjective well-being on day 3 (F(3,60) = 2.72, P = 0.057, partial eta squared = 0.166). Three days of aromatherapy intervention did not significantly improve sleep or subjective well-being (Table 2).

Table 2.

Well-Being Scores, Day 2

Source	df	SS	MS	F	P	η ²
Baseline score	1	65.33	65.33	38.77	<0.001	0.447
Treatment group	3	18.50	6.17	3.66	0.019	0.186
Error	48
Total	52
Adjusted R ² = 0.467

Additional Analyses

To assess the overall effect of aromatherapy with essential oils as compared to a placebo, the three treatment groups were combined into a single aroma group for additional analysis. A one-way between-groups ANCOVA was conducted to compare the efficacy of aromatherapy use with a placebo for nausea, vomiting, and retching, with the baseline score as the covariate. Preliminary checks were conducted to ensure there was no violation of the assumptions of normality, linearity, homogeneity of variances, homogeneity of regression slopes and reliable measurement of the covariate.

Well-being scores were dramatically improved in the aromatherapy group. A significant difference was identified (F(1,50) = 6.85, P = 0.012, partial eta squared = 0.137), with an average improvement of 1.438 points on the 10-point well-being scale. Subjective well-being dramatically improved for those in aromatherapy groups as compared to those receiving a placebo.

Safety and Adverse Events

One participant withdrew from the study due to “horrible headaches” after application, reporting that she did not normally experience headaches. This participant was in the placebo group. Additionally, two individuals in the ginger aromatherapy group reported that they did not like the aroma, and one withdrew midway through the study as a result.

The use of essential oils during early pregnancy, especially in the form of a topical application or in high concentrations, is controversial among aromatherapists. This study provides evidence that the topical application of high concentrations of essential oils during pregnancy is safe, though certain aromas may be intolerable on a personal level. Because scent is a highly subjective experience, essential oils should be tested for personal preference prior to use in medicinal applications. This is particularly relevant during early pregnancy when shifts in preference of sensory experiences occur.²⁹

Discussion

Limitations

These findings are consistent with other studies, which produce mixed results when evaluating aromatherapy use for PINV. This study was powered to detect a large effect size. Therefore, it was not designed to detect a small or medium effect of aromatherapy on PINV. Larger studies would be required to be able to detect a smaller effect size, but the clinical relevance of a small effect size would be questionable.

Additionally, this study only evaluated data on patients after three days of essential oil usage. While this is consistent with other studies on the topic, it is possible that longer usage is required to achieve larger effect sizes. Future studies should examine the potential for different oils, doses, or durations to improve PINV scores.

Generalizability

This intervention utilized a range of different essential oils among pregnant individuals of all ages, with differing gravidity, and varying geographical locations, indicating that pregnant patients across a wide spectrum of ages and health histories may benefit from the use of ginger for retching or aromatherapy in general for improved well-being. Additionally, this study utilized potencies that are consistent with self-prescription of essential oils, which is often far more potent than what professional aromatherapists recommend during pregnancy. This design allows for real-world replication of the study findings.

Interpretation

Anecdotal reports of beneficial effects of aromatherapy are widespread, but little evidence exists comparing these effects to a placebo. This study provides evidence that a potent application of essential oils improves subjective well-being during early pregnancy, and that the use of ginger essential oil has the potential to reduce retching in early pregnancy. While this study did not find that essential oils of grapefruit, ginger, or peppermint reduce nausea and vomiting at levels that are large enough to achieve statistical significance, other essential oils, other doses, or longer durations may produce different results. Furthermore, this study did not find any intervention-related adverse effects of these essential oils, confirming that professionally-developed protocols for essential oil usage can be safe and potentially beneficial for pregnant patients in the first trimester.

Further studies should evaluate the role of the mind-body connection in aromatherapy to determine which of these effects can be attributed to the essential oils themselves and which are due to the practice of treatment with aromatherapy.

Conclusion

The use of inhalation aromatherapy with ginger, grapefruit, or peppermint, at constant levels through the use of topical application of essential oils in early pregnancy is safe and has the potential to improve subjective well-being among patients in the first trimester. Additionally, the use of ginger essential oil helps to reduce retching during the first trimester. While this study found that aromatherapy is also associated with a reduction in nausea, vomiting, and retching, these reduction effects were achieved using both essential oils and a placebo carrier oil.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was funded by the Franklin Health Research Foundation, a 501(c)(3) nonprofit foundation associated with the Franklin Health Research Center, which specializes in clinical and epidemiological research within the natural products industry.▪

References

Herrell

. Nausea and vomiting of pregnancy. Am Fam Physician, 2014; 89:965–970.

Lacroix

, Eason

, Melzack

. Nausea and vomiting during pregnancy: A prospective study of its frequency, intensity, and patterns of change. Am J Obstet Gynecol, 2000; 182:931–937.

Bustos

, Venkataramanan

, Caritis

. Nausea and vomiting of pregnancy—what's new?. Auton Neurosci, 2017; 202:62–72.

Hollyer

, Boon

, Georgousis

. The use of CAM by women suffering from nausea and vomiting during pregnancy. BMC Complement Altern Med, 2002; 2:1–6.

O'Brien

, Naber

. Nausea and vomiting during pregnancy: Effects on the quality of women's lives. Birth, 1992; 19:138–143.

Goodwin

. Hyperemesis gravidarum. Obstet Gynecol Clin North Am, 2008; 35:401–417.

Ding

, Leach

, Bradley

. The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: A systematic review. Women Birth, 2013; 26:e26–30.

Fejzo

, Trovik

, Grooten

, et al. Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nat Rev Dis Primers, 2019; 5:1–17.

Ozgoli

, Naz

MSG

. Effects of complementary medicine on nausea and vomiting in pregnancy: A systematic review. Int J Prev Med, 2018; 9.

10.

Illamola

, Amaeze

, Krepkova

, et al. Use of herbal medicine by pregnant women: What physicians need to know. Front Pharmacol, 2020; 10:1483.

11.

Frawley

, Adams

, Steel

, et al. Women's use and self-prescription of herbal medicine during pregnancy: An examination of 1,835 pregnant women. Womens Health Issues, 2015; 25:396–402.

12.

McFarlin

, Gibson

, O'Rear

, Harman

. A national survey of herbal preparation use by nurse-midwives for labor stimulation: Review of the literature and recommendations for practice. J Nurse Midwifery, 1999; 44:205–216.

13.

Sibbritt

, Catling

, Adams

, et al. The self-prescribed use of aromatherapy oils by pregnant women. Women Birth, 2014; 27:41–45.

14.

Wills

, Forster

. Nausea and vomiting in pregnancy: What advice do midwives give?. Midwifery, 2008; 24:390–398.

15.

Farrar

, Farrar

. Clinical aromatherapy. Nurs Clin North Am, 2020; 55:489–504.

16.

Gong

, Dong

, Tang

, et al. Effects of aromatherapy on anxiety: A meta-analysis of randomized controlled trials. J Affect Disord, 2020; 274:1028–1040.

17.

Safajou

, Shahnazi

, Nazemiyeh

. The effect of lemon inhalation aromatherapy on nausea and vomiting of pregnancy: A double-blinded, randomized, controlled clinical trial. Iran Red Crescent Med J, 2014; 16:e14360.

18.

Amzajerdi

, Keshavarz

, Montazeri

, Bekhradi

. Effect of mint aroma on nausea, vomiting and anxiety in pregnant women. J Family Med Prim Care, 2019; 8:2597.

19.

Joulaeerad

, Ozgoli

, Hajimehdipoor

, et al. Effect of aromatherapy with peppermint oil on the severity of nausea and vomiting in pregnancy: A single-blind, randomized, placebo-controlled trial. J Reprod Infertil, 2018; 19:32–38.

20.

Pasha

, Behmanesh

, Mohsenzadeh

, et al. Study of the effect of mint oil on nausea and vomiting during pregnancy. Iran Red Crescent Med J, 2012; 14:727.

21.

Ghani

RMA

, Ibrahim

ATA

. The effect of aromatherapy inhalation on nausea and vomiting in early pregnancy: A pilot randomized controlled trial. J Nat Sci Res, 2013; 3:10–22.

22.

Hall

, McKenna

, Griffiths

. Midwives' support for complementary and alternative medicine: A literature review. Women Birth, 2012; 25:4–12.

23.

Hughes

, Liddle

, Sinclair

, McCullough

. The use of complementary and alternative medicine (CAM) for pregnancy related low back and/or pelvic girdle pain: An online survey. Complement Ther Clin Pract, 2018; 31:379–383.

24.

Birdee

, Kemper

, Rothman

, Gardiner

. Use of complementary and alternative medicine during pregnancy and the postpartum period: An analysis of the National Health Interview Survey. J Womens Health, 2014; 23:824–829.

25.

Gagnier

, Boon

, Rochon

, e al. Reporting randomized, controlled trials of herbal interventions: An elaborated CONSORT statement. Ann Intern Med, 2006; 144:364–367.

26.

Moher

, Hopewell

, Schulz

, et al. CONSORT 2010 explanation and elaboration: Updated guidelines for reporting parallel group randomised trials. Int J Surg, 2012; 10:28–55.

27.

Andersen

AMN

, Wohlfahrt

, Christens

, et al. Maternal age and fetal loss: Population based register linkage study. BMJ, 2000; 320:1708–1712.

28.

Kang

, Ragan

, Park

. Issues in outcomes research: An overview of randomization techniques for clinical trials. J Athl Train, 2008; 43:215–221.

29.

Cameron

. Measures of human olfactory perception during pregnancy. Chem Senses, 2007; 32:775–782.