Systematic review of the effectiveness of aromatherapy in labor

Background Clinical practice with aromatherapy has become an expanding area for nursing, and is considered one of the most popularly used complementary treatments. However, there is insu�cient evidence about the bene�ts of aromatherapy for pain management and other related discomforts in labor. We aimed to evaluate the effects of aromatherapy for women during delivery particularly for pain relief. Methods AMED, ClinicalTrials.Gov, CINAHL, Cochrane Library, EMBASE, MEDLINE, PubMed, and WHO ICTRP were searched in August 2017. For updates, these databases were searched from July 2017 to July 2018. This study included randomized controlled trials (RCTs) and quasi-RCTs for normal pregnancy women who were experiencing labor onset, and compared aromatherapy with standard care or control. Results Six RCTs from six reports, and four quasi-RCTs from �ve reports were included (1238 pregnant women). The trials found signi�cant difference between groups for the primary outcomes of pain relief on the latent (MD -1.56, 95%CI: -2.45 to -0.67, low certainty of evidence) and early active phase (MD -1.69, 95%CI: -2.50 to -0.89, low certainty of evidence). However, there were no signi�cant differences for the primary outcomes of pain relief on the late active phase, and anxiety relief on the early and late active phases. Conclusions This meta-analysis found evidence that the use of inhalation aromatherapy for term pregnancy women is associated with reduction of labor pain. However, there is insu�cient evidence to con�rm pain relief on the late active phase, anxiety relief, and other outcomes following aromatherapy. Trial registration We registered the study protocol with PROSPERO (CRD42017077617).


Background
Although labor and birth are considered to be a natural process, laboring women experience a signi cant amount of discomfort and pain as well as a variety of other challenging sensations [1].Women in labor experience pain caused by uterine contractions, expansion of the lower uterus, and the dilation of the cervix.Moreover, pain is produced by the stretching of the vagina and pelvic oor to accommodate the baby.These complexes of pain can lead to complications such as a compromised immune system, reactive hypoglycemia, delayed wound healing, increased myocardial oxygen consumption, paralytic ileus, and reduced respiratory function [2].This pain possibly exerts its effects in the form of psychological distress to both the mother and the baby.Perceptions of labor pain vary by the individual and are in uenced by a variety of physiologic, psychologic, emotional, socio-cultural, and environmental factors [1].Labor, without using drugs or invasive methods such as an epidural, is often sought by many women and they usually turn to complementary therapies such as aromatherapy to help reduce their pain perception [3].
Aromatherapy is the use of essential oils from plants such as owers, trees or herbs.These essential oils improve physical, mental, and spiritual well-being.The clinical practice with aromatherapy has become an expanding area for nursing and is considered one of the most popularly used complementary therapies [4].Aromatherapy during labor and delivery may provide relaxation and reduce pain [5].Several essential oils used in aromatherapy have been suggested to have antistressor, antidepressive, and relaxation effects [6].In addition to reducing pain, aromatherapy may also decrease symptoms such as anxiety, nausea, vomiting and other labor-related conditions [6].
To date, there has been inconclusive evidence regarding the bene ts of aromatherapy for the management of pain and other related discomforts in labor, as well as for the improvement of maternal and neonatal outcomes.A previous Cochrane systematic review on aromatherapy published in 2011 could not clearly show evidence of its effects on pain relief during deliveries [3].The most recent systematic review, which was published in 2019, reported the anxiolytic effects of aromatherapy, and suggested positive effects on anxiety during the rst stage of labor [7].This 2019 review analyzed the e cacy of individual aroma essence oils in the rst stage of labor, and it included studies of aromatherapy intervention using other care methods such as massage.We concluded that aromatherapy results may be in uenced by other factors.
We believe that a meta-analysis is needed to de nitively evaluate the e cacy of inhalation aromatherapy in terms of all its outcomes, particularly for pain management by excluding cointervention, which may affect its e cacy.The purpose of this systematic review is to evaluate the e cacy of aromatherapy for women in all stages of labor.

Methods
We followed the Cochrane Handbook [8] and Cochrane's MECIR [9] for conducting the search, PRISMA guidelines [10] for reporting the search, and PRESS guidelines for peer-reviewing the search strategies [11].We registered the study protocol with PROSPERO (CRD42017077617).

PICOS and selection criteria
We included all types of randomized controlled trials (RCTs) involving pregnant women of 37-42 gestation weeks and with labor onset.The included RCTs only focused on inhalation of any kind of aroma essence compared with the standard care or placebo.We included multiple arms and cointervention, which wereto compare the e cacy of aromatherapy.The primary outcomes were pain relief and anxiety relief during labor.The secondary outcomes were duration of delivery, duration of contraction, spontaneous or operative delivery, and Apgar score (Appendix S1).

Search strategy
In August 2017, we searched AMED, ClinicalTrials.Gov, CINAHL, Cochrane Library, EMBASE, MEDLINE, PubMed, and WHO ICTRP with no date/time, language, document type, and publication status limitations.For the present review, these databases were searched from July 2017 to July 2018.The PubMed search strategy is shown in the Appendix S2, and we adapted the search terms for every database.We also hand searched Google scholar in August 2018.Data extraction KS, MK, and HS independently screened and con rmed study eligibility.When there were con icts of eligibility, each study was discussed with HS and EO for resolution.We found several papers written in Persian, and we attempted to contact to the authors.However, we received no reply.From each study, KS extracted information on characteristics of participants, study design, numbers of participants, interventions, and outcome data.Data were extracted by HS and checked by MK.Risk of bias was assessed as recommended in the Cochrane Handbook [8], and MK and HS independently assessed each trial.Discrepancies were resolved through discussion.MK and HS also contacted the authors of three RCTs [12][13][14] to request unpublished outcome data, where trial reports implied that relevant data might be available.However, replies were not forthcoming.

Statistical analysis
We performed meta-analysis to analyze pooled outcome data.We estimated weighted mean difference (MD) when the outcomes were measured similarly between trials.We also used standardized mean difference (SMD) to combine trials that measured the same outcome with different methods, and 95% con dence interval (CI) for continuous outcomes.If multiple intervention arms were reported, we combined the data of aromatherapy intervention groups and calculated mean and standard deviation (SD).When cointervention was used, we analyzed the compared data of aromatherapy and controlled to avoid the effects of other interventions.For binary outcomes (e.g., response, remission, and dropouts), we estimated risk ratio (RR) and 95% CI for each comparison using the numbers randomly assigned and numbers of events.We used intention-to-treat (ITT) data in this analysis, as ITT data are less biased and address a more pragmatic and clinically relevant situation.To address missing data, we used the number randomized minus any participants for the denominator for each outcome in each trial.We used general inverse variance method (GIVM) when the included studies reported only the difference between the means for the two groups and the standard error of this difference.We included outcome data from quasi-RCTs.We carried out sensitivity analysis to explore the effect of trial quality assessed by quasi-RCTs, concealment of allocation and incomplete outcome data, or more than one, with quasi-RCT studies being excluded from the analysis to assess whether this makes any difference in the overall result.
Heterogeneity was assessed using I 2 statistic.We considered I 2 ≥ 60% as high, then we used random effects meta-analysis.For low to moderate heterogeneity (I 2 < 60%), we used xed effects meta-analysis.
We performed all analyses using Review Manager (RevMan) [15].We used GRADE [16] to judge the certainty of evidence for the effectiveness of aromatherapy for the primary outcomes such as labor pain relief and anxiety relief through all the stages of labor.

Trial characteristics
We screened 254 titles and abstracts (Fig. 1), and identi ed six individual RCTs from six reports [18, 19,22,[25][26][27] and four quasi-RCTs from ve reports [17,20,21,23,24] for inclusion in the nal review.We excluded the trials with massage and bathing as these have other effects.Eight studies that were included mentioned that blinding of participants was not possible because of the diffusion of oil molecules in the air [17,[19][20][21][22][25][26][27].For this reason, ve reports [17,20,21,23,24] had performed interventions on randomly allocated days with the aromatherapy days and the placebo days.Although we considered these four trials as quasi-RCTs, we included these four trials from the nature of the intervention.
For the measurement of outcomes, labor pain severity was measured using the Visual Analogue Scale (VAS) chart and the Numerical Rating Scale (NRS) [17-21, 24, 26, 27].Both scales have a score range of 0 to 10 [28, 29].One trial reported the pain score changes from baseline therefore we performed GIVM for the meta-analysis [26].In three studies, Spielberger's State-Trait Anxiety Inventory (STAI) was used to determine the level of anxiety of the participants [18, 23,25].STAI questionnaires consist of 40 questions in which the scores ranged from 20 to 80. Higher scores indicate greater anxiety [30].The reliability of STAI has a Cronbach's alpha of 0.90 [25].One study used the Visual Analog Scale for Anxiety (VASA) [22].
The scale ranges from 0 to 10 with 0 indicating no anxiety and 10 greatest anxiety [31].

Aromatherapy interventions
Table 1 presents details of the aromatherapy interventions administered in each trial.All trials evaluated inhalation of aroma essence in labor.Two studies had a three-arm design with intervention arms [21,22].One study used two kinds of aroma essence (Jasmin and Salvia essence), and we combined them into one group and used the calculated data which is the combined mean ±SD [21].Another study carried out interventions by inhalation of aroma essence using a footbath, only footbath, and routine care [22].We included inhalation of aroma essence with footbath as the intervention group, and only footbath as the control group to exclude the effect from footbath.Moreover, one study performed inhalation of aroma essence with breath technique as the intervention, and breath technique alone as the control [19].

Labor pain relief
For the measurement of labor pain, all of the studies used VAS or NRS [17-21, 24, 26, 27].As one trial reported interquartile range we used score change reports [26].For this reason, we calculated MD with GIVM for the analysis of labor pain.Eight studies found that aromatherapy signi cantly reduced labor pain intensity compared with control in the latent phase (MD -1.56, 95% CI -2.45 to -0.67, p = 0.0006, I 2 =97%, eight trials, 1,005 women, low certainty of evidence; Fig 3).Six studies reported that aromatherapy intervention signi cantly reduced labor pain compared with control in the early active phase (MD -1.69, 95% CI -2.50 to -0.89, p < 0.0001, I 2 = 96%, six trials, 689 women, low certainty of evidence; Fig. 4).These studies also reported that aromatherapy signi cantly reduced labor pain in the late active phase (MD -1.52, 95% CI -2.33 to -0.71, p = 0.0002, I 2 = 97%, six trials, 689 women, very low certainty of evidence; Fig.

Sensitivity analysis
Due to the high heterogeneity, we performed sensitivity analysis by excluding quasi-RCTs and high risk of random sequence [17,20,21,23,24].For labor pain relief, it still showed signi cant differences during the latent and early active phase.(Appendix.Fig. S13, S14).However, there were no signi cant differences in pain relief during the late active phase, and anxiety relief during all of the active stages (Appendix.Fig. S15-S17).For secondary outcomes, there was no signi cant difference in the labor length of the 1 st stage (Appendix.Fig. S18).

Discussion
We found evidence that using inhalation aromatherapy for term pregnancy women was associated with reduction of labor pain on the latent and early active phase.This is most likely the rst review showing evidence of pain relief with the use of aromatherapy in labor, and the rst study to evaluate the e cacy of aromatherapy in all the stages of labor.The Cochrane systematic review included two RCTs [32,33].However, the researchers could not perform a meta-synthesis owing to the differences in the comparison methods, and they reported each trial result individually.This previous review could not identify any evidence of the effects of aromatherapy on pain relief in labor because the number of included studies were not su cient.Furthermore, the searches were conducted in 2010 [3].In the present review, there was insu cient evidence regarding the effect of reducing anxiety of the participants using inhalation aromatherapy during labor.Ghiasi et al. reported the systematic review on the anxiolytic effect of aromatherapy during the rst stage of labor [7].They suggested a positive effect on anxiety with a qualitative analysis of the bene t from individual aroma essence oils in the rst stage of labor.This previous review also did not perform a meta-analysis, thus this review was not conclusive [7].Moreover, Ghiasi et al. included trials of aromatherapy intervention with massage.In the present review, we excluded data that may exert any effect on the evaluation of the genuine e cacy of aromatherapy.Thus, our hypothesis that the use of aromatherapy during labor reduces labor pain was found to be effective in pregnant women on the latent and early active phase, and we considered a low certainty of evidence from the GRADE assessment (Table 2).The Cochrane review reported outcomes of assisted vaginal delivery, cesarean delivery, spontaneous delivery, augmentation, and admission to NICU, and there was no evidence of effect due to the lack of power [3].Taken together, there were no signi cant differences in the secondary outcomes, such as duration of contraction, labor length, Apgar score, types of delivery, labor augmentation in our present review.Moreover, there was no report about adverse events of aromatherapy in the included studies.However, people have different preferences of smell, and pregnant women are particularly more sensitive.The choice of essential oils depends on the women's preference.
Overall, the risk of bias about blinding allocation of the included studies were high.Blinding allocations of the participants and care providers are di cult because of the smell of the aroma essence.This setting downgrades the level of evidence.Four trials of random sequence also had a high risk of bias.We conducted sensitivity analysis to adjust for the effects of this high risk of bias of randomization.The results showed high heterogeneities overall in the outcomes of pain as well as reduction of anxiety.In another review, labor pain intensity was also reported with high heterogeneity [34].Pain and anxiety are subjective senses, and these outcomes were assessed by self-report questionnaires.Additionally, it is predictable that there are various individual differences in sensitivity to labor pain.These various differences may provoke a high heterogeneity status.
We did not specify the kinds of aroma essence although eight kinds of essences were used in the included studies.We cannot de ne the speci c e cacy of aromatherapy in this present review.It is possible that what in uenced the reduction in the subjective labor pain was the e cacy of relaxation brought about by the inhalation of pleasant smells of the aroma essence.A women's internal experience of labor pain is affected by the environment, and this factor includes the person's verbal and nonverbal communications [35].Relaxation may have a role in reducing pain, increasing satisfaction with pain relief, and reducing the rate of assisted vaginal delivery [36].Creating an environment with less stress and providing relaxation to parturient women are needed to reduce pain intensity.
Moreover, there is a strong association between anxiety and pain in the latent phase of labor [37].Although we could not nd su cient evidence of reducing anxiety by aromatherapy, the results showed a tendency for aromatherapy to be slightly more effective than the control group.From this point of view, even if we could not reach de nitive evidence of anxiety relief in this present review, there were still bene ts of using aromatherapy in labor.
For women, natural pain and anxiety interventions are in more demand than medical interventions.Aromatherapy is a noninvasive method with a low risk and low cost for reducing labor pain.

Strength and Limitations
This present review has several strengths.Almost all included studies used genuine branded aroma oils for women in labor, thus it is su cient to say that most of the outcomes are reliable in terms of their e ciency.Only one study had an unclear attrition bias [22].This included study reported the number of assigned participants, but not the number of randomized participants.However, other included reports all had a low risk of bias in incomplete outcome data, and also other bias was low in this review.From this status, we considered that the quality of evidence in the present review was kept from attrition bias.This systematic review provides the results of all outcomes following aromatherapy in all stages of labor.
Although we could not assess the differences in the e cacies of individual essential oils, Ghiasi et al. reported the e cacy of aromatherapy on anxiety for each aroma oil [7].Investigating differences in the effectiveness of essential oils on labor pain should also be considered.Despite these strengths, several limitations were found in the present review.Firstly, the nine of the 10 studies for inclusion in the nal review were conducted in Iran.The results of these studies might be impacted by its bias.Secondly, all studies could not maintain blinding of participants because the essential oil fragrance naturally spreads in the air and prevents from complete blinding of the participants.Additionally, this study was able to examine the effectiveness of aromatherapy, and found a possible effect for reducing women's labor pain.Although there was a positive result for pain relief, it is very di cult to evaluate this objectively because the perception of pain is very subjective and results from various internal experiences.Women in labor experience a signi cant amount of discomfort rather than labor pain, but the included studies were not focused on those unpleasant symptoms such as nausea, excessive physical sensitivity, vomiting, and other discomforts.Future research is needed not only in terms of physiological labor pain but also psychological e cacy (e.g., stress response changes or anxiety).The former Cochrane review concluded that the e cacy and effectiveness of aromatherapy have not yet been established owing to the limited the number of trials [3].Our included studies were comparatively new, and we updated the e cacy for pain reduction.
Further research of the evaluation of aromatherapy about these three points are needed.Firstly, the included studies were concentrated in Iranian settings, and future research should be investigated in other various settings.Secondly, the types of aroma essence were not speci ed in this review, and future research should assess the e cacy of the speci c kinds of aroma oils.Thirdly, future research should investigate additional outcomes such as nausea, excessive physical sensitivity, vomiting, and other discomforts.Anxiety and discomforts, which are experienced during labor, may be related to psychological status.Future research is needed to focus on the psychological e cacy of aromatherapy.

Conclusions
The of aromatherapy during labor and delivery has continued to expand in practice settings.There was a low certainty of evidence of subjective labor pain reduction by inhalation aroma essence on the latent and early active phase.However, other outcomes such as pain relief on the late active phase, anxiety relief, duration of contraction, labor length, types of delivery, labor augmentation, and the Apgar score of infants could not reach the level of evidence indicating the de nitive effectiveness of aromatherapy.Some discomforts during child birth are related to pain, and this feeling of pain may be reduced following aromatherapy.