The Impact of Myo-Inositol Supplementation on Sleep Quality in Pregnant Women: A Randomized, Double- Blind, Placebo-Controlled Study

Research Article

Austin J Sleep Disord. 2020; 7(1): 1036.

The Impact of Myo-Inositol Supplementation on Sleep Quality in Pregnant Women: A Randomized, Double- Blind, Placebo-Controlled Study

Mashayekh-Amiri S1, Delavar MA2*, Bakouei F2, Faramarzi M2 and Esmaeilzadeh S2

¹Student Committee Research, Babol University of Medical Sciences, Babol, Iran

²Department of Midwifery, Babol University of Medical Sciences, Babol, Iran

*Corresponding author: Mouloud Agajani Delavar, Department of Midwifery, Babol University of Medical Sciences, Babol, Iran

Received: May 29, 2020; Accepted: October 09, 2020; Published: October 16, 2020

Abstract

Myo-inositol, a glial marker which plays a critical role in some brain regions, can supposedly affect sleep processes. The aim of randomized controlled trial was to evaluate the impact of myo-inositol supplementation on sleep quality in pregnant women. This study enrolled 60 women with low risk singleton pregnancies, with a gestational age of at least 14 weeks, in Iran. The participants were block randomized to receive myo-inositol supplementation powder containing 2000 mg of myo-inositol and 200 μg of folic acid or placebo (400μg of folic acid) for 10 weeks from the gestational age of 14 to 24. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). The primary outcome was the change in sleep quality from the first trimester to the second trimester (24-28 week). The results of ANCOVA boot strapped demonstrated that the mean deference of the total sleep quality score between the two groups was -1.537; 95% CI: -3.050 to -0.024, p=0.047) in the second trimester. Also, there were significant mean differences in subjective sleep quality, sleep duration and habitual sleep efficiency between the two groups at different times (-0.427; 95% CI: -0.725 to -0.128, p=0.006, (-0.427; 95% CI: -0.725 to -0.128; p=0.006 -0.670; 95% CI: -1.240 to -0.101; p=0.022, and 8.066; 95% CI: 1.077 to 15.054; p=0.025, respectively). The research confirmed that myo-inositol supplementation can improve pregnant women’s global sleep quality, subjective sleep quality, and sleep duration. Therefore, these findings applied to minimize the rate of poor sleep quality in pregnant women.

Keywords: Dietary supplements; Iinositol; Pregnant women; Sleep; Sleep hygiene

Abbreviations

PSQI: Pittsburgh Sleep Quality Index; ASSM: The American Academy of Sleep Medicine; SHI: Sleep Hygiene Index; BDI: Beck Depression Inventory; PSS: Perceived Stress Scale

Introduction

It is generally assumed that pregnancy is one of the most important events in a woman’s life. It is a natural process, accompanied by physiological and psychological changes, which can lead to changes in the pattern of sleep [1]. Sleep is presumably a physiological process to restore physical vitality and energy [2]; hence, people spend about one-third of their lives sleeping [3]. Poor sleep patterns in terms of quality and short sleep in terms of duration is the two common phenomena during pregnancy [4]. The quality and duration of sleep are commonly affected by several factors such as hormonal, physical, physiological, and behavioral changes during pregnancy [5]. A study conducted in Iran indicated that 87.2% of pregnant women suffered from sleep-related problems [6].

It is presumed that sleep-related problems could have negative consequences for both mother and fetus during pregnancy. These complications include daily dysfunction, maternal fatigue, obesity, gestational hypertension, preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, low birth weight, and preterm birth. It could also be associated with caesarean section, prolonged labor, and the use of delivery instruments, depression during pregnancy, and postpartum depression [7-11].

It is also thought that pharmacological and non-pharmacological therapies can improve the quality of sleep. Due to the potential risks of drugs on the fetus and the limited number of both pharmacological and non-pharmacological methods, pregnant women are commonly recommended to use other methods such as acupressure, exercise, auricular therapy, massage or relaxation therapy, mindful meditation and yoga, and cognitive behavioral therapy (CBT) to promote the quality of sleep during their pregnancies [12].

The concept of sleep hygiene, applied to regulate sleep problems, was first used by Peter Hauri [13]. The midwives’ role is to maintain the physical and psychological health of pregnant women in prenatal care. One of the important needs of pregnant women is to promote sleep quality through sleep hygiene education and counseling regarding the normal sleep pattern, total sleep time, and sleep alternation during pregnancy [14]. The American Academy of Sleep Medicine (ASSM) [15], and a clinical guideline in the Journal of Clinical Sleep Medicine [16], do not recommend sleep hygiene education as an independent treatment due to the lack of sufficient evidence for sleep problems.

It is assumed that inositol has nine isomers, and that myo-inositol is one of the commonest stereoisomer of C6 sugar alcohol [17,18]. The myo-inositol is one of the secondary messengers in the signal transmission pathways, which can examine the metabolism of fats and sugar in the nerve cells and regulate the secretion of some glands [19,20]. Myo-inositol is also regarded as a glial marker. Generally, the glial brain cell is known as asytrocytes, which can regulate a number of vital functions in the brain [21,22].

In the same vein, animal studies have also found acute changes in sleep variables in animals with the dysfunction of asytrocytes cells, although glial function related to sleep in humans has not been examined yet [23]. The researchers speculate that glial function may have a critical role in brain regions involved with sleep processes [23,24]. Therefore, we hypothesized that myo-inositol, as a glial marker, could have a positive effect on sleep quality in pregnant women. To this end, the aim of this study was to determine the impact of myo-inositol supplementation on sleep quality in pregnant women.

Materials and Methods

Study Design

This study was a randomized, double-blind, placebo-controlled trial attempt to investigate the impact of myo-inositol supplementation on sleep quality. The study was conducted in prenatal clinics of Babol University of Medical Sciences, Babol, Iran from April 2018 to March 2019.

The inclusion criteria were as follows: conscious written consent, pregnant women with singleton pregnancy, age above 18, the gestational age of at least 14 weeks, the absence of chronic diseases such as diabetes, hypertension and cardiovascular diseases, no history of taking prenatal drugs before pregnancy, no history of sleep disorders before pregnancy, employed women without night shifts, no smoking, no alcohol use, no history of psychiatric problems, and no abortion in previous pregnancies. It is worth noting that women with severe depression or severe stress, those with the death experience of one of their first-class relatives during pregnancy, and those with changes in sleep patterns due to travel were excluded from the study.

The primary outcome was to measure sleep quality in the second trimester (24-28 weeks) between the intervention and control groups. The secondary outcome was to measure the score of sleep quality in the third trimester (37-38weeks), the side effects of drugs, and maternal and neonatal conditions at delivery.

Instruments

The tools for the implementation of this research included such socio-demographic characteristics and reproductive history as age, educational level, occupation, family income, monthly cost, the total number of pregnancies, and the total number of birth. We also used Pittsburgh Sleep Quality Index (PSQI), Sleep Hygiene Index (SHI), the Beck Depression Inventory (BDI), and perceived stress scale (PSS) in this study.

PSQI: It is assumed to be one of the most common methods of assessing the sleep status and quality [25]. This questionnaire included 19 items in seven different components including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, the use of sleeping medication, and daytime dysfunction. The sum of seven component scores gives the total PSQI score. The response of each self-rated question scored between 0 and 3 according to the symptom frequency. The total score has a value in the range of 0-21. High values indicate a poor sleep quality. Having a total score below 5 (0-4 points) indicates that sleep quality is good, and a score of 5 or greater (5-21 points) indicates poor sleep quality. The Cronbach’s alpha of PSQI was reported 0.73 [26]. In Iran, Hossein Abadi et al. (2008), estimated the reliability (r = 0.88) and the reliability of the questionnaire via retest (r = 0.84) [27]. In addition, the Cronbach’s alpha of PSQI was calculated to be 0.75 in our study. The PSQI has a Cronbach’s alpha of 0.83.

SHI: It is a 13-item, self-report questionnaire, which measures sleep hyigene. Each item is graded based on a 5-point Likert’s scale ranging from 0 (never) to 4 (always). The total score ranges from 0–52, with a higher score representing lower sleep hygine. The SHI has been shown to have adequate reliability and validity in sleep hygiene research [28]. In a study by Chehri et al. (2015), the reliability of the Persian version of this questionnaire was established with a Cronbach’s alpha coefficient of 0.83. The Persian version of SHI has been used as a reliable and valid tool to assess sleep hygiene among Iranian women [29]. The a coefficient of sleep hygiene index was 0.66 in our study.

PSS: This scale was developed by Cohen et al. It is a 14-item selfreport questionnaire, which evaluates a person in terms of stress during the past months. It has a good validity, reliability, and stability over time. It is a 5-point Likert’s scale ranging from 0 (never) to 4 (very often). The maximum score in this test is 56, and the least is zero. The scale yielded a single score with high scores indicating higher levels of stress and lower levels indicating lower levels of stress [30]. PSS was translated into Iranian version and validated by [31]. Finally, the internal consistency of the PSS in our study was calculated at 0.86 using Cronbach alpha.

BDI: It is a 13-items self-report questionnaire, which is widely used in numerous studies designed to measure physical, behavioral, and cognitive symptoms of depression. Each item is rated on a fourpoint scale ranging from 0 to 3 point. The sum of 13 items gives the total score ranging from 0 to 39, and sets various degrees of depression from mild to severe (no=0-4, mild=5-7, moderate=8-15, severe=16-39) [32]. Rajabi et al. has shown that this questionnaire is a reliable and valid scale for screening depression among samples with psychiatric outpatients in Iran [33]. The a coefficient of the questionnaire in the current study was calculated to be 0.75.

Participants

Around 63 healthy pregnant women that met the inclusion criteria were asked to sign the written informed consent forms. At first, the women were instructed to complete the Beck Depression Inventory (BDI) and Perceived Stress Scale (PSS). The participants with severe depression (scored greater than 15) and severe stress (scored greater than 28) were excluded from the study.

Finally, 60 pregnant women with low risk singleton pregnancies with a gestational age of at least 14 weeks were requested to complete the socio-demographic questionnaire, PSQI, and SHI according to the instructions provided. Then, all participants received a sleep hygiene education, which was delivered to them through training and a booklet. The evidence regarding sleep hygiene education was collected through multiple databases and search engines. The content of the sleep hygiene, which was taken from academic search engine and several library databases, included such areas as maintaining regular hours of bedtime and arising, keeping the bedroom cool, dark, and quite, maintaining a regular exercise schedule, having a light dinner before bedtime, not drinking tea, coffee or caffeine consumption before sleep, and not using alcohol, cigarette, etc.

The participants were then randomly assigned into intervention and control groups. Randomization was accomplished through blocked randomization with a block size of 4 for the two groups (A, B). At first, blocks containing 4 of 2 treatments (myo-inositol and placebo) were written with different possible combinations, and each one was assigned a number. The sachets for the two groups, which were identical in appearance, were prepared by a single laboratory. The envelops were sealed and a number was assigned to each. Then, using a random number table, after the coding procedure (A or B), 70 sachets were placed in a box for each participant. The sachets were then given to the researcher and the randomization page was hidden. The researcher was unaware of the contents of the sachets, and the identities of the sachets were available only to the pharmacist. It should be noted that both the researchers and participants were blinded to the whole process (double-blind). Breaking blinding was possible in two cases: after the delivery and in case of severe side effects encountered. The women in the intervention group received a myo-inositol supplementation powder (the Inofulic commercial name, LO.LI. Pharma, Rome, Italy) containing 2000 mg of myoinositol and 200 μg of folic acid once daily before sleep per night (one hour a sachet is dissolved in a glass of water) for 10 weeks from the gestational age of 14 to 24 weeks. The control group received placebo containing 2000 mg of wheat flour and 200 μg of folic acid, identical in color, flavor and texture to the myo-inositol powder to be taken in the same dose and for the same duration of time. According to the World Health Organization protocol, all samples should receive one tablet containing 60 mg elemental iron (as 300 mg ferrous sulphate) from 14-16th week of gestation and should continue it until birth. Text messages or telephone calls were considered by the researcher to ensure the use of supplements during the study. Participants were also requested to bring the supplements box at each visit.

Sleep quality was evaluated through Pittsburgh Sleep Quality Index (PSQI) in the second trimester, in weeks [24-28], and in the third trimester, in weeks. In addition, the pregnancy outcomes and the occurrence of side effects caused by treatments such as the presence of nausea/vomiting, diarrhea, headache, uterine contractions, tiredness and flatulence were assessed during the follow-up visits. Maternal outcomes included: weight gain during pregnancy (expressed as kilogram based on cutoff 12), gestational age at delivery (expressed as the number of patients who delivered before ‘37 weeks’ and ‘37- 42 weeks’ of gestation), the mode of delivery (expressed as vaginal delivery and caesarean section incidence), gestational hypertension (defined as a systolic pressure of at least 140 mm Hg or a diastolic pressure of at least 90 mm Hg, and preterm delivery (expressed as number of participants delivered before 37 weeks’ gestation completed). Fetal and neonatal outcomes included: the birth weight expressed by grams and percentile, macrosomia (birth weight >4 kg), admission to Neonatal Intensive Care Unit (NICU), and shoulder dystocia. The participant drop-out rate was 4 (3 participants in myoinositol group and 1 in palacebo group) (Figure 1).