The Eects of Aroma on Apnea Attacks and

Oxygen Saturation Among Preterm Infants: A

Systematic Review and Meta-Analysis

Sanaz Rustaee1, Rafat Rezapour-Nasrabad2, Masumeh Ghazanfarpour3, Saeedeh Piri4, Seyedeh Fatemeh Moosavi

Moqaddam5, Arian Behdarvandi6, Fatemeh Kafami Ladani7, Ahmad Rahmah8, Maryam Mirzaei9

1 Department of Nursing Internal Surgery, School of Nursing, Fasa University of Medical Sciences, Fasa, Iran

2 Department of Psychiatric Nursing and Management, School of Nursing and Midwifery, Shahid Beheshti University of Medical

Sciences, Tehran, Iran

3 Nursing Research Center, Kerman University of Medical Sciences, Kerman, Iran

4 Department of Nursing, Lorestan University of Medical Science, Shahid Madani Hospital, Khorramabad, Iran

 Department of Nursing, School of Nursing, Jahrom University of Medical Sciences, Jahrom, Iran

6 Department of Biology, Shahid Chamran University of Ahvaz, Ahvaz, Iran

7 Department of Nursing, Nursing Care Research Center, Iran University of Medical Sciences, Tehran, Iran

8 Department of Clinical Pharmacy, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq

9 Department of Obstetrics and Gynecology, Faculty of Medicine, Jiro University of Medical Sciences, Jiro, Iran

GMJ.2023;12:e2846

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 Correspondence to:

Maryam Mirzaei, Department of Obstetrics and Gyne-

cology, Faculty of Medicine, Jiroft University of Medi-

cal Sciences, Jiroft, Iran.

Telephone Number: +98983443262401

Email Address: m.mirzaei@kmu.ac.ir

Received 2022-11-27

Revised 2023-02-07

Accepted 2023-02-9

Abstract

Researchers and clinicians need to be aware of procedures that are more adaptable to new and

dierent environments in premature infants; therefore, it is important to conduct a compre-

hensive review of the eect of aromatherapy on apnea attacks and oxygen saturation (SpO2)

in premature newborns. In this review, databases such as PubMed, Scopus, Web of Science,

and Cochrane Library were systematically searched without language and time limitations up

to November 1, 2022. Initially, 153 studies were founded, and after duplicate removal, title

as well as full-text review, seven studies were enrolled in the nal analysis. Studies indicated

that aromatherapy with Rosa damascena, vanilla, and breast milk odors could signicantly re-

duce apneas in preterm infants and improve SpO2 levels. Hence, aromatherapy could consider

as an eective adjuvant treatment for the reduction of apnea attacks among preterm infants.

[GMJ.2023;12:e2846] DOI:10.31661/gmj.v12i0.2846

Keywords: Premature; Aromatherapy; Herbal; Infants; Oxygen Saturation

Introduction

Providing suitable environmental condi-

tions, especially in high-risk groups, in-

cluding children, women, the elderly [1-4],

and patients with life-threatening diseases, is

one of the most important duties of the med-

ical team [5-10]. Meanwhile, premature in-

fants and their mothers are among the most

critical groups receiving medical care [1-3].

Premature labor (before 37 weeks of gesta-

tion) increases the probability of fatality and

morbidity due to respiratory immaturity [11].

Apnea–a brief pause for more than 20 sec-

onds–is one of the most prevalent complica-

tions experienced by premature infants admit-

ted to the neonatal intensive care unit [12]. In

other words, apnea, pallor, bradycardia, and

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Rustaee S, et al. Eects of Aroma On Apnea and SpO2 of Preterm Infants

2GMJ.2023;12:e2846

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cyanosis [13] are reported in approximately

85% of infants with a gestational age equal to

or less than 34 weeks [14].

Also, apnea could lead to brain damage, hy-

potonia, hypotension, neurological disorders,

hydrocephalus, and even mortality [15].

The recurrent apnea and the need for mechan-

ical ventilation within the rst week of treat-

ment could be decreased using methylxan-

thines, such as aminophylline, theophylline,

and caeine [14, 16, 17].

However, they cannot completely prevent

apnea sequels, and additionally, several un-

desirable side eects such as hyperactivity,

irritability, sleep disorders, tachycardia, and

urinary disorders have been noticed in treated

infants [18]. As a natural treatment, aroma-

therapy uses aromatic essential oils extracted

from various parts of plants, such as leaves,

bark, fruits, stems, seeds, roots, and owers

[19].

The olfactory and gustatory receptors develop

by the eighth week of gestation and become

functional by the 24th and 17th weeks, respec-

tively [20]. Several studies showed the eects

of aromatherapy with vanilla [11, 15, 19, 21],

Rosa damascena [18], and breast milk odor

[13-15] on apnea attacks and oxygen satura-

tion (SpO2).

Hence, this study aimed to provide evidence

through a systematic review of the eects of

aromatherapy on apnea attacks and SpO2 in

preterm infants.

Materials and Methods

Search Strategies

This systematic review was conducted ac-

cording to the PRISMA 2020 Checklist [22].

A comprehensive literature search was con-

ducted in PubMed, EMBASE (via OVID SP),

Scopus, and Web of Science until November

2022. We used the medical subject heading

(MESH) and free text words for our search

in dierent combinations, such as ((Preterm

OR (Premature) AND (Odor OR Olfactory

OR Aroma OR aromatherapy OR Smell OR

odor) AND (Apnea OR oxygen saturation

OR Spo2). Search strategies were modied as

necessary for each specic database. The full

search strategies for each database are pre-

sented in Table-1.

All the articles found throughout our search

process were imported into Endnote X6

(Thomson Reuters, Philadelphia, PA, USA),

and duplicates were removed. The titles and

abstracts of identied studies were scrutinized

for eligibility by four reviewers (SR, MGH,

SP, and SFMM) in two groups independently,

and full-text versions of selected studies were

collected for further assessment.

Four reviewers in two dierent groups inde-

pendently examined the full texts, and rel-

evant articles were identied. The discrep-

ancies were examined and nalized by the

corresponding author (MM). Also, for better

coverage, reference lists of selected articles

and review papers were manually searched to

identify relevant articles.

Eligibility Criteria and Study Selection

We included all clinical trials that exanimated

the impact of aromatherapy on SpO2 and ap-

nea attacks among preterm infants (less than

37 weeks of gestation).

Also, non-clinical trials, non-human stud-

ies, reviews, letters to the editor, multi-sen-

sorial interventions, conference papers, and

non-published data were excluded.

Data Extractions

After selecting the relevant studies, data, in-

cluding rst author name, year of publication,

type of control, intervention interval, and aro-

ma dosage were entered in a pre-developed

form.

Quality Assessments

We used the modied Jadad tool, a checklist

that evaluated clinical trial studies [9]. Brief-

ly, Jadad consists of eight questions in ve

domains (e.i., description of randomization,

methods used to generate the sequence of

randomization, blinding, method of blinding,

description of withdrawals, and dropouts) that

scored separately.

The maximum score obtained from the Jadad

is equal to eight. Accordingly, studies were

categorized into three groups low-(score<4),

moderate- (score 4 to 6), and high- (score≥6)

quality.

Two authors (SR and MM) independently per-

formed the quality assessment, and a consen-

sus was made in the case of disagreement.

Eects of Aroma On Apnea and SpO2 of Preterm Infants Rustaee S, et al.

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Table 1.Table 1. The Search Strategies In the Di󰀨erent Databases The Search Strategies In the Di󰀨erent Databases

Database Search statement

PubMed

(((((“Infant, Premature”[Mesh] AND “Infant, Extremely Premature”[Mesh]) AND ( “Infant, Premature/blood”[Mesh] OR “Infant, Premature/cerebrospinal

uid”[Mesh] OR “Infant, Premature/growth and development”[Mesh] OR “Infant, Premature/immunology”[Mesh] OR “Infant, Premature/metabolism”[Mesh]

OR “Infant, Premature/physiology”[Mesh] OR “Infant, Premature/psychology”[Mesh] OR “Infant, Premature/urine”[Mesh] )) AND ( “Infant, Extremely

Premature/blood”[Mesh] OR “Infant, Extremely Premature/cerebrospinal uid”[Mesh] OR “Infant, Extremely Premature/growth and development”[Mesh] OR

“Infant, Extremely Premature/immunology”[Mesh] OR “Infant, Extremely Premature/metabolism”[Mesh] OR “Infant, Extremely Premature/physiology”[Mesh]

OR “Infant, Extremely Premature/psychology”[Mesh] OR “Infant, Extremely Premature/urine”[Mesh] )) AND ( “Aromatherapy/adverse eects”[Mesh]

OR “Aromatherapy/classication”[Mesh] OR “Aromatherapy/economics”[Mesh] OR “Aromatherapy/ethics”[Mesh] OR “Aromatherapy/history”[Mesh]

OR “Aromatherapy/instrumentation”[Mesh] OR “Aromatherapy/methods”[Mesh] OR “Aromatherapy/mortality”[Mesh] OR “Aromatherapy/nursing”[Mesh]

OR “Aromatherapy/psychology”[Mesh] OR “Aromatherapy/standards”[Mesh] OR “Aromatherapy/statistics and numerical data”[Mesh] OR “Aromatherapy/

trends”[Mesh] OR “Aromatherapy/veterinary”[Mesh] )) AND ( “Odorants/analysis”[Mesh] OR “Odorants/legislation and jurisprudence”[Mesh] OR “Odorants/

prevention and control”[Mesh] )) AND “Agnosia”[Majr]

Web of Science TI= (Infant * OR “Infant, Premature”) AND TI=(“Bariatric Surgery” OR “Preterm Infant” OR “Premature Newborn” OR “Preterm Neonate” OR “ Prematurity “)

AND TI=(“Aromatherapy*” OR “ Odor “ OR Smell *) AND TI=(“ Olfactometer *” OR “ Olfactory stimulation*”)

Scopus

(TITLE-ABS (Infant *) OR TITLE-ABS (“Infant, Premature “)) AND (TITLE-ABS(“Preterm Infant”) OR TITLE-ABS(“Preterm Newborn “) OR TITLE-

ABS(“Premature Newborn “) OR TITLE-ABS(Premature Neonate) OR TITLE-ABS(“Preterm Neonate “)) AND (TITLE-ABS(Prematurity *) OR TITLE-

ABS(“Aromatherapy “) OR TITLE-ABS(Odor) OR TITLE-ABS(Smell *)) AND (TITLE-ABS(Olfactometer *) OR TITLE-ABS(Olfactory stimulation *))

Cochrane

Library

Title Abstract Keyword Premature infant AND Title Abstract Keyword Prematurity AND Title Abstract Keyword odour AND Title Abstract Keyword Olfactory

stimulation AND Title Abstract Keyword Preterm infant AND Title Abstract Keyword odor AND Title Abstract Keyword Olfactometer AND Title Abstract

Keyword smell Title Abstract Keyword Premature infant OR Title Abstract Keyword Prematurity OR Title Abstract Keyword odour OR Title Abstract Keyword

Olfactory stimulation OR Title Abstract Keyword Preterm infant OR Title Abstract Keyword odor OR Title Abstract Keyword Olfactometer OR Title Abstract

Keyword smell

Embase

(‘Preterm infant’:ab,ti OR ‘Premature infant’:ab,ti OR ‘Preterm Newborn’:ab,ti OR ‘Premature Newborn’:ab,ti OR ‘ Premature Neonate’:ab,ti OR ‘Preterm

Neonate’:ab,ti OR ‘Premature baby’:ab,ti OR ‘Preterm baby’:ab,ti OR ‘ Preterm infant, Aromatherapy’:ab,ti OR ‘ Preterm infant; Aroma’:ab,ti OR ‘ Preterm infant,

Smell ‘:ab,ti AND ‘Aromatherapy’:ab,ti OR ‘Aroma’:ab,ti OR ‘Smell’:ab,ti OR ‘Odor’:ab,ti OR ‘odour’:ab,ti OR ‘Olfactometer’:ab,ti OR ‘Olfactory stimulation’:ab,ti)

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Rustaee S, et al. Eects of Aroma On Apnea and SpO2 of Preterm Infants

Statistical Analysis

The heterogeneity of studies was evaluated by

the Chi-squared and I2 tests.

The results were reported using a random-ef-

fects model, and the standardized mean dif-

ference (SMD) method was applied to the

intergroup comparisons at a 95% condence

interval (CI). Also, the “Metaprop” command

was used to perform meta-analyses of pro-

portions on STATA14 (Stata, College Station,

TX, USA).

Results

1. Characteristics of Studies

Our initial search identied 153 articles, and

after duplicate removal, as well as the title and

abstract screening, 13 articles were chosen for

full-text review. Finally, seven studies [11, 15,

19, 21, 23-25] were included in our review

(Figure-1).

The characteristics of included studies are

presented in Table-2. Totally, 463 preterm in-

fants were evaluated. Aromatherapy with va-

nilla, R. damascena, and breast milk odor was

performed in four [11, 15, 19, 21], one [25],

and four [11, 19, 23, 24] studies, respective-

ly. The Jadad score for included studies are

shown in Table-3.

2. Eect of Aromatherapy On Apnea Attacks

2.1. Vanilla

Although four studies [11, 15, 19, 21] as-

sessed the eect of aromatherapy with vanilla,

only three studies [15, 19, 21] indicated the

role of vanilla on the frequency of apnea at-

tacks (Table-2).

Edraki et al. [15] showed that receiving va-

nilla solution (2%) could signicantly reduce

apnea attacks compared to the control group

(Table-2).

Also, Kanbur et al. [19] reported a signicant

decrease in the frequency of apnea in preterm

neonates in the vanilla group compared to the

breast milk and control groups.

In Yaghoubi et al. study [21], the frequency

of apnea attacks changed after treatment with

cotton impregnated with 2ml of vanilla ex-

tract compared to the control group (P=0.016,

Table-2).

2.2. R. damascena

In a study by Aghagoli et al. [25], the num-

ber of apnea attacks was signicantly lowered

in the R. damascena group than in control

(P<0.05, Table-2).

3. Eect of Aromatherapy On SpO2

Overall, the SMD of SpO2 between the aro-

matherapy and the control group was -0.48

(95%CI: -0.708 to -0.25, I2=28.1%), which

indicates signicant dierences (P˂0.001,

Figure-2).

3.1. Vanilla

Regarding Figure-3, the SpO2 levels of the

vanilla group were signicantly dierent

compared to the control group (SMD: -0.43,

95%CI: -0.72 to -0.14, P=0.003; Figure-3).

In Yaghoubi et al. study [21], a signicant

dierence was observed in SpO2 levels of

premature neonates with apnea between the

vanilla group and the control (Table-2). Also,

Edraki et al. [15] reported a signicant dier-

ence in SpO2 between the vanilla group and

the control group (P=0.02, Table-2). In con-

trast, Neshat et al. [11] showed no signicant

dierences among preterm infants of vanilla

and control groups regarding SpO2 (Table-2).

3.2. R. damascena

In the study of Aghagoli et al. [25], decreased

SpO2 level was signicantly (P<0.05) im-

proved in the 10% R. damascena group than

in control (distilled water) among preterm in-

fants with apnea (Table-2).

3.3. Breast Milk

The SpO2 levels between breast milk and

the control groups were signicantly dier-

ent (SMD=-0.38, 95%CI: -0.66 to -0.105,

P=0.007, Figure-4)

Park et al. [23] demonstrated no signicant

dierences in SpO2 levels between the milk

odor and control groups (P=0.548, Table-2).

Also, Alemdar et al. [24] indicated that the

mean level of SpO2 was not signicantly dif-

ferent in breast milk odor groups compared to

mother voice and control groups (Table-2).

However, Neshat et al. [11] stated that the

breast milk odor group could signicantly

improve the SpO2 of premature infants com-

pared to the control group (P=0.014, Table-2).

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Eects of Aroma On Apnea and SpO2 of Preterm Infants Rustaee S, et al.

Table 2. Characteristics of Included Studies

Authors [Ref] Location Groups Dose/Interval Outcome(s)

Neshat et al. [11] Iran

-Vanilla (n=45)

-Breast milk (n=45)

-Control (n=45)

-Ten drops vanilla/ve minutes

before and 30 seconds after

sampling

Improvement SpO2 in the breast milk odor group

(P=0.014); however, no signicant change in the vanilla

group (P=0.16) in comparison with the control

Edraki et al. [15] Iran -Vanilla (n=18)

-Control (n=18) Solution 2%/every 12 hours A signicant dierence between the vanilla group and

control regarding SpO2 and apnea

Kanbur et al. [19] Turkey

-Breast milk (n=13)

-Vanilla (n=16)

-Control (n=13)

Not mentioned A signicant decrease in the frequency of apnea in the

vanilla group compared to the breast milk and controls

Yaghoubi et al. [21] Iran

-Vanilla (n=19)

-Control

(n=18)

A piece impregnated with 2ml in

approximately 20 cm from infants/

every 12 hours

The frequency of apnea attacks and SpO2 level changed

after treatment in vanilla extract (P=0.016) compared

with the control groups

Park et al. [23] Korea -Breast milk (n=14)

-Control (n=16)

A 2cc was placed 10 cm away from

the infants/ eight times per day for

three days

Signicant dierences in SpO2 levels between the milk

odor and control group

Alemdar et al. [24] Turkey

-Breast milk (n=30)

-Mother voice (n=30)

-Cover (n=31)

-Control (n=32)

Solution placed on gauze sponge

15 min before

Peripheral cannulation.

And up to 15 min after the

procedure.

The breast milk odor groups were not dierent from the

mother voice and control group in terms of mean SpO2

Aghagoli et al. [25] Iran -R. damascena (n=30)

-Control (n=30)

Two drops/every three hours for

three days

The number of apnea attacks and SpO2 levels was

signicantly lower in the R. damascena group than in the

control

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Rustaee S, et al. Eects of Aroma On Apnea and SpO2 of Preterm Infants

Table 3. The Quality of Included Studies Based on Jadad

Questions Edraki et al. Kanbur et al. Yaghoubi et al. Neshat et al. Park et al. Alemdar et al. Aghagoli et al.

Was the study descript as

randomized? 1 0 0 1 1 0 1

Were the methods of randomization

appropriate? 1 1 1 1 1 1 1

Was the study descript as blinded? 1 0 1 1 0 0 1

Was the methods of blinding

appropriate? 0 1 0 0 1 0 0

Was a description of withdrawals

and dropouts? 0 0 1 1 1 0 0

Was a clear description of inclusion

and exclusion criteria 1 1 0 1 0 1 0

Was the method used to assess the

adverse eects described? 1 1 1 0 0 1 1

Was the method of statistical analysis

described? 1 1 1 1 1 1 1

Total score 6 5 5 6 5 4 5

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Eects of Aroma On Apnea and SpO2 of Preterm Infants Rustaee S, et al.

Figure 1. PRISMA owchart of the study.

Figure 2. The e󰀨ects of aromatherapy on SpO2. The horizontal lines denote the 95% CI; ■ point estimate

(square size corresponds to its weight); ♦ combined overall e󰀨ect of treatment.

Rustaee S, et al. Eects of Aroma On Apnea and SpO2 of Preterm Infants

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Discussion

The current systematic review found that aro-

matherapy had both preventive [15] and ther-

apeutic eects [18] on apneas in preterm in-

fants. Ataei Nakhaei et al. [26] in a systematic

review, revealed that aromatherapy eectively

treats apnea in preterm infants. However, the

authors reiterated that their ndings should be

interpreted cautiously due to the small sample

size and the low number of studies [26]. Ev-

idence indicated that vanilla could impact on

apnea in some ways. Indeed, vanilla could be

absorbed via the nasal mucosa and enter the

brain through the bloodstream and improve

orbitofrontal blood ow [15]. Also, vanilla

helps newborns deal with stress and directly

aects the respiratory centers [18]. Hence,

it balances psychological and physiological

states [18].

Aromatherapy with the R. damascena could

be applied as an eective intervention for pre-

mature infants suering from apnea, followed

by routine therapy to reduce bradycardia and

improve SpO2 levels [25]. The extract of R.

damascena contains christin and kaempferol,

which has some benecial eects on the

nervous system [27] and reduces pain [28].

Moreover, the hydro-alcoholic extract of R.

damascena has a dilatory eect on respira-

tory airways [25, 28]; hence, it could reduce

anxiety as well as improve sleep quality, espe-

cially in premature infants hospitalized due to

apnea [29-31].

Although the current study involved more

studies compared to previous research [26],

there were some limitations. Indeed, the stud-

ies included in our systematic review had a

small sample size, and only one type of ap-

nea (i.e., the idiopathic apnea of prematurity)

was evaluated. Hence, further investigations

to verify the eectiveness of this non-pharma-

cological method in various types of apnea are

recommended.

Figure 3. The e󰀨ects of aromatherapy with vanilla. The horizontal lines denote the 95% CI; ■ point esti-

mate (size of the square corresponds to its weight); ♦ combined overall e󰀨ect of treatment.

Figure 4. The e󰀨ects of aromatherapy with breast milk odor on SpO2. The horizontal lines denote the 95%

CI; ■ point estimate (size of the square corresponds to its weight); ♦ combined overall e󰀨ect of treatment.

Conclusion

Aromatherapy with natural substances (e.g.,

R. damascena) and even articial ones can be

used as an additional treatment to improve the

breathing condition of premature infants with

apnea.

Conict of Interest

Authors declare there were no any conicts of

interest.

Eects of Aroma On Apnea and SpO2 of Preterm Infants Rustaee S, et al.

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