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PLOS One logoLink to PLOS One
. 2020 May 8;15(5):e0232712. doi: 10.1371/journal.pone.0232712

Caffeine, alcohol, khat, and tobacco use during pregnancy in Butajira, South Central Ethiopia

Alehegn Aderaw Alamneh 1,*, Bilal Shikur Endris 2, Seifu Hagos Gebreyesus 2
Editor: Yael Abreu-Villaça3
PMCID: PMC7209255  PMID: 32384102

Abstract

Background

The use of excessive caffeine and consumption of alcohol, cigarette, and khat during pregnancy can result in adverse health effects on the fetus. The World Health Organization (WHO) recommends a daily caffeine intake not exceeding 300 mg. Likewise, pregnant women are recommended to avoid alcohol, khat and tobacco use. However, the prevalence’s of the use of substances among pregnant women were not well studied in developing countries such as Ethiopia. Therefore, the study aimed to estimate the prevalence of caffeine and alcohol consumption, khat chewing, and tobacco use during pregnancy and identify key factors associated with excess caffeine consumption.

Methods

We conducted a community based cross-sectional study and used a random sampling technique to recruit 352 pregnant women. We adapted a questionnaire from Caffeine Consumption Questionnaire-Revised (CCQ-R), Alcohol Use Disorder Identification Test (AUDIT), Global Adult Tobacco Survey (GATS), and Ethiopian Demographic Health Survey 2016 for caffeine, alcohol consumption, tobacco use, and khat chewing assessment, respectively. We conducted non-consecutive two days 24-hour recall to determine the habitual intake of caffeine from caffeinated beverages and foods. Prevalence with 95% confidence interval was estimated for excess caffeine intake per day, alcohol consumption, khat chewing, and passive tobacco smoking. We ran a multivariable binary logistic regression model to identify factors associated with excess caffeine intake.

Results

Almost all pregnant women (98.2%) consumed caffeine as estimated using the 2 days 24-hour average. The median daily caffeine intake was 170.5 mg and ranged from 0.00 mg to 549.8 mg per day. In addition, 17.6% (95% CI: 13.9%, 22.0%) of them had a daily caffeine consumption of 300 mg and above exceeding the WHO recommended daily caffeine intake during pregnancy. The prevalence of alcohol consumption and Khat chewing were 10.0% (95% CI: 7.2%, 13.7%) and 35.8% (95% CI: 30.8, 41.0%) respectively. None of the pregnant women were active tobacco smokers. However, 23.2% (95% CI: 19.0, 28.0%) were passive tobacco smokers. We found that pregnant women in the richest wealth quintile (AOR = 3.66; 95% CI: 1.13, 11.88), and the first trimester of pregnancy (AOR = 4.04; 95% CI: 1.26, 13.05) had higher odds of consuming excessive caffeine.

Conclusions

The study showed a considerable magnitude of substance use among pregnant women in the study area. Given this findings, we recommend, programs and services focusing on pregnant women to consider addressing substance use.

Introduction

Substance use is defined as the inappropriate consumption of medicines, drugs, or other materials including prescription drugs, over-the-counter drugs, street drugs, alcohol and tobacco [1]. Caffeine is a stimulant substance found in coffee, tea, cocoa (chocolate), and kola nuts (cola), soft drinks, energy drinks, and some over-the-counter medications [2]. Coffee is one of the most popular consumed beverages in the world and the most common sources of high caffeine [2].

Even though caffeine contains several chemical components that may provide health benefit in reducing dementia [3], insulin resistance, type 2 diabetes mellitus [4, 5], Parkinson disease [5], cirrhosis and advanced hepatic fibrosis [611], excess intake is not recommended; especially during pregnancy [12]. This is for the fact that caffeine can cross the placenta into the amniotic fluid and fetus and results in adverse pregnancy outcomes. The American Pregnancy Association and March of Dimes recommends that a pregnant woman should not take more than 200mg caffeine per day, which is around 355 milliliters coffee [13]. In 2003, Experts in Canada conducted a systematic review to evaluate the effects of caffeine on human health and recommended that a reproductive age woman should not take 300 mg and above caffeine per day. In addition, the World Health Organization (WHO) recommends that daily caffeine intake should not exceed 300 mg during pregnancy [12, 14].

Alcoholic beverages are drinks containing ethyl alcohol or ethanol which is an intoxicating ingredient. Alcohol is a central nervous system depressant and can cross the placenta. Therefore, since there is no safe amount of alcohol, a pregnant woman is advised to avoid drinking alcohol during pregnancy [15].

Globally, 9.8% of women consume alcohol while they are pregnant [16]. In the Eastern Africa WHO region, the estimated prevalence of alcohol consumption during pregnancy among the general population ranged from 3.4% in Seychelles to 20.5% in Uganda. In Ethiopia, the magnitude of alcohol consumption during pregnancy ranged from 7.9% to 34% [17, 18].

Alcohol consumed during pregnancy is the leading preventable cause of developmental disabilities and birth defects. According to the World Health Organization report, 1 in 100 babies is estimated to be born with alcohol-related damage [19]. One of the problems is Fetal Alcohol Spectrum Disorder (FASD), which is an umbrella term that covers all alcohol-related diagnoses [20].Besides, heavy alcohol consumption during pregnancy increases the risks of low birth weight, preterm birth [21], small for gestational age [22] and childhood leukemia in young children [23].

Globally, 8% of women aged 15 years and above were tobacco smoker. The tobacco epidemics continue to shift from high-income countries to low- and middle-income countries, with a recent increase in the prevalence of tobacco smoking among women, which is expected to rise to 20% by 2025 [24]. Based on the 2011and 2016 Ethiopian Demographic Health Survey (EDHS), the overall prevalence of tobacco use among reproductive age women was 0.8% [25, 26]. Different chemicals from cigarette smoking impair the structure and function of the placenta [27]. Therefore, smoking during pregnancy has been associated with preterm birth, restricted fetal growth and low birth weight [28, 29], and this leads to a higher risk of childhood obesity and non-communicable diseases in later life [30, 31].

Khat refers to the leaves and the young shoots of the plant Catha edulis Forsk, a species belonging to the plant family Celastraceae. Khat contains many different compounds such as cathinone [32]. As a result, khat chewing during pregnancy may reduce placental blood flow [33]. The WHO Expert Committee on Drug Dependence (ECDD) critical review result showed that khat chewing during pregnancy may have different obstetric effects like low birth weight, stillbirths, and impaired lactation [32]. In 2008, a community-based cross-sectional study in Yemen showed that about 40.7% of women reported chewing khat while pregnant [34].

Different factors were identified as risk factors for substances use during pregnancy. Younger age, white ethnicity, not being religious, low socio-economic status, being nonimmigrant, performing less frequent antenatal consultation, null parity, husband alcohol consumption, previous history of alcohol and other illicit drugs use, unplanned pregnancy, lack of awareness about the harmful effects of alcohol on the fetus and peer pressure were the identified factors associated with alcohol consumption [3538]. Being divorced, unemployed, younger age, low educational level and low socio-economic status, living with smoker, criminal history, working in receipt of social services, alcohol and illicit drug use, being fair to poor in perceived health, being previous heavy smoker, having at least one chronic disease and mental illness, and not having a regular medical doctor were the identified factors associated with cigarette smoking during pregnancy [35, 3942]. Old age, living in mountainous region, being Islamic follower, and being smoker were identified as a risk factor for khat chewing during pregnancy [34, 43, 44].

Despite the considerable effect of substances use with birth defects and developmental disabilities, the current magnitude of caffeine and alcohol consumption, cigarette smoking and khat chewing during pregnancy were not studied in Ethiopia. Therefore, this study was aimed to estimate the prevalence of caffeine and alcohol consumption, khat chewing, and tobacco use during pregnancy and identify factors associated with excessive caffeine consumption.

Materials and methods

Study area

The study was conducted in kebeles covered by Butajira Rural Health Program (BRHP) which is found in Meskan and Mareko districts of Gurage Zone, SNNP region, South Central Ethiopia. BRHP is located 130 km South of Addis Ababa which is the capital city of Ethiopia. Butajira Rural Health Program is a Health Demographic Surveillance System (HDSS) Site for Addis Ababa University. It covers the selected kebeles of Meskan and Mareko district. The BRHP comprises one urban and nine rural kebeles (the smallest administrative unit in Ethiopia).

Study design, period and population

A community based cross-sectional study was employed from April 12 to May 15, 2018. The source population of the study was all pregnant women living in kebeles covered by Butajira Rural Health Program. Pregnant women living in the study area were included in the study. None of the pregnant women was excluded.

Sample size determination and sampling procedure

The sample size was determined by using single population proportion formula and based on the following assumptions; 5% of margin error (d) (except for alcohol use where d = 4.5%, and tobacco use where d = 1.6%) and with 57% expected prevalence of caffeine intake during pregnancy [45], 34% expected prevalence of alcohol consumption [18], 3% expected prevalence of cigarette smoking [24] and 40.7% expected prevalence of khat chewing [34]. After adding a 5% non-response rate and population correction, a final sample of 352 pregnant women were required.

A stratified sampling technique was used to select pregnant women as the accessibility of substances might vary based on residence and agro-ecological zones. First, the BRHP kebeles were stratified as urban and rural. Second, the rural kebeles were stratified as lowland, midland, and highland while the urban kebele is found in the midland agro-ecological zone. Third, the total number of pregnant women during the data collection period was obtained from the Butajira Rural Health Program database. A sampling frame was prepared for each stratum and the samples were assigned for each stratum proportional to the number of pregnant women. Finally, pregnant women were selected from each stratum by using a simple random sampling (SRS) technique.

Data collection tool and procedure

We adapted a questionnaire from Caffeine Consumption Questionnaire-Revised (CCQ-R) [46] for caffeine consumption assessment, Alcohol Use Disorder Identification Test (AUDIT) [47] and EDHS 2016 (26) for alcohol consumption assessment, the Global Adult Tobacco Survey (GATS) [48] and EDHS 2016 (26) for tobacco use assessment and from published literatures [43] and EDHS 2016 (26) for khat chewing assessment.

Interviewer-administered face to face data collection method was employed to collect data from each pregnant woman. The overall data collection process was supervised by the two coordinators of Butajira Rural Health Program.

Measurement of study variables

Caffeine measurement

We conducted a repeated 24-hour recall was to assess the habitual intake of caffeine. To control days of the week’s variation, data was collected on 2 non-consecutive days of the week, i.e. one from week days and one from weekend days. All days of the week were considered in the sample to make the selection representative.

We asked participants to report their last 24-h consumption of caffeine from different caffeinated beverages (coffee, tea, Coca-Cola, Pepsi cola, and energy drinks), caffeinated foods (e.g., chocolate, candy bars, and baked goods) but not from medicines. The data collectors asked respondents to show the serving size for each caffeinated item. If the material was not available at home, a picture of calibrated serving size was shown to the mother to help estimate the amount consumed. Then, the participants were asked to indicate how many of each size of the beverages consumed in the last 24-hr. The daily 24-hr recall consumption data were transformed in to a standard unit (ml). The data were multiplied by the content of caffeine per unit of each caffeine source. The amount of caffeine from coffee (0.5309 mg/ml) was obtained from a study conducted in Ethiopia [49]. The caffeine concentration for tea (0.359 mg/ml) and coca cola (0.113mg/ml) was obtained from the International Food Information Council Foundation (IFICF) critical review on clarifying the controversies of caffeine and health [50].

To obtain the caffeine amount from coffee with milk, the portion of coffee in the drink (coffee with milk) was first estimated by conducting a pilot study before the actual data collection period. Based on the pilot study we conducted on 12 households, the estimated proportion of coffee in the drink of coffee served with milk was 0.7365. Then, the caffeine level was computed based on the caffeine level estimation in coffee as shown above.

The caffeine intake from each source was added to obtain the daily caffeine intake. The total level of caffeine consumption for two days was obtained by adding caffeine intake from each 24-h recall. The two days’ consumption was divided by 2 to obtain the average caffeine intake of the pregnant woman per day. If the daily caffeine consumption was greater than or equal to 300mg, the woman labeled as excessive caffeine consumer.

Alcohol consumption measurement

The participants were asked to report their alcohol consumption during pregnancy using the 3 consumption questions from Alcohol Use Disorder Identification Test (AUDIT) [47]. If a woman reported as consuming at least one unit of alcohol from any sources (Tella, Teje, Areqe, Beer, Wine, and Distilled sprites) during the current pregnancy, she was labeled as alcohol consumer. If she consumed five or more alcohol drinks in one session (one sit) during the current pregnancy, she was labeled as a binge alcohol consumer.

Cigarettes smoking assessment

The pregnant woman was asked to respond to close-ended questions concerning cigarette smoking. First, the woman was asked a question to assess whether or not she smoked cigarette during the current pregnancy. If she responded “yes”, the woman was labeled as a smoker and number of cigarettes smoked per day, awareness and source of information about the effects of cigarettes on the fetus, and secondary exposure at home, workplaces and public places were asked. If the pregnant woman exposed to tobacco at home during current pregnancy or work place in the last one month of the interview or public places in the last 7 days, she was labeled as a passive tobacco smoker.

Khat chewing assessment

The pregnant woman was asked to respond to a close-ended questions concerning khat chewing. First, the woman was asked a question to assess whether or not she chewed khat during the current pregnancy. If a woman responded “yes”, she was labeled as a consumer and frequency of chewing, awareness, and source of information about the effects of khat chewing on the fetus were asked.

Data quality assurance

To assure the quality of caffeine data, the locally available serving sizes of caffeinated products were calibrated and standardized before the data collection. In addition, two days training was given to the data collectors and supervisors to minimize an introduction of information bias. A pretest was conducted at neighboring kebele on 21 pregnant women before the actual data collection to check the consistency, any ambiguity in the language and to evaluate the skill of the interviewers. During pretest, new locally available serving sizes of caffeinated beverages were found and calibrated. Moreover, the questionnaire was modified based on the input from the pretest.

In addition, the consistency, completeness, and clarity of the data was checked by the data collectors before leaving the respondent and also checked by the supervisor and investigator on daily bases.

Data management, analysis and presentation

The collected data was compiled, checked for any inconsistency and missed value, coded, and entered using Epi-data version 3.1 Software and exported into Stata 14 for data management and analysis. The data were cleaned for missing values by running frequencies, and crosstabs.

The normality of age and caffeine data was checked using histogram with normal curve, and Shapiro Wilk test p-value. For caffeine data, the minimum and maximum, and median with interquartile range were analyzed. Prevalence’s were estimated for excess caffeine intake per day, alcohol consumption, khat chewing, passive smoking and overall substances use during pregnancy. Chi-square test statistics was run to test whether the proportion of excess caffeine consumption significantly differ across trimesters.

Principal Component Analysis was done to construct wealth index based on household data such as ownership of household including household fixed assets, type of house and its building materials, agricultural land ownership, animal ownership, source of drinking water, ownership and type of toilet facility, having domestic servant, and saving account. Assets owned by less than 5% or more than 95% of households were excluded from wealth index construction.

Bivariate and multivariate binary logistic regression was run to identify risk factors for excess daily caffeine intake among pregnant women. Those variables with p-value of less than 0.25 in bivariate logistic regression model were entered into the multivariate logistic regression model. Statistically significant association was declared at p value of less than 0.05.

Ethical consideration

An ethical clearance as well as support letter was obtained from the Research Ethics Committee of School of Public Health (SPH), College of Health Sciences (CHS) of Addis Ababa University. An informed verbal consent was obtained from each respondent after explaining the information sheet of the study. The verbal consent was documented by the interviewer on the prepared consent form attached with the questionnaire. The obtained information from each respondent kept confidential.

Results

A total 352 pregnant women approached for the study. Among these, we had a response rate of 96.9% (341 women). Table 1 shows the socio-demographic and economic characteristics of respondents. The majority of the respondents (79.2%) were rural residents. The median age of respondents in years was 28 (IQR = 6). The majority of respondents (61.9%) were within the age group of 25–34 years. In addition, the majority of respondents (83.9%) were Muslims and almost all (99.1%) were married.

Table 1. Socio-demographic and economic characteristics of pregnant women in Butajira, South Central Ethiopia, 2018.

Variables Frequency Percent (%)
Residence
Rural 270 79.2
Urban 71 20.8
Climatic Zone
Highland 98 28.7
Midland 124 36.4
Lowland 119 34.9
Age
15–24 96 28.2
25–34 211 61.9
35 and above 34 10.0
Religion
Muslim 286 83.9
Orthodox Christian 42 12.3
Protestant 13 3.8
Educational status
No formal education 148 43.4
Primary Level 150 44.0
Secondary level and above 43 12.6
Marital status
Married 338 99.1
Separated/widowed 3 0.9
Occupation
House wife 276 80.9
Government Employee 7 2.1
Merchant 45 13.2
Others* 13 3.8
Wealth status
Poorest 77 22.6
Poor 76 22.3
Middle 63 18.5
Rich 63 18.5
Richest 62 18.2

*Includes (farmer, daily laborer, tea/coffee sellers, free service, lumbering & hair making)

Prevalence and sources of caffeine consumption

The major sources of caffeine for pregnant women in the study are were coffee, coffee with milk, tea and Coca-Cola. Specifically, 88.9% of pregnant women (95% CI: 85.0, 91.8%) consumed coffee during the current pregnancy, 35.8% (95% CI: 30.8, 41.0%) consumed coffee with milk, 24.9% (95% CI: 20.6, 29.8%) consumed tea and 0.6% (95% CI: 0.1, 2.3%) consumed Coca-Cola. However, Pepsi cola, energy drinks and chocolates were not the sources of caffeine among pregnant women in the study area.

Almost all pregnant women (98.2%; 95% CI: 96.1%, 99.2%) consumed caffeine as estimated using the 2 days 24-hour recall average. Table 2 shows the median, range, and prevalence of excess caffeine intake among pregnant women by trimester of pregnancy. The daily caffeine intake among pregnant women ranges from 0.00–549.8 mg per day. The median daily caffeine intake during pregnancy was 170.5 mg (IQR = 135.1). Across the sample, 17.6% (95% CI: 13.9%, 22.0%) of the pregnant women consumed 300 mg and above caffeine per day. The proportion of excess caffeine (≥300mg/day) consumption was significantly different across the trimesters of pregnancy (p<0.001). The highest proportion of excess caffeine consumption was observed at the first trimester of pregnancy (50%; 95% CI: 27.2, 72.8). About 41.9% (95% CI: 36.8%, 47.3%) of the pregnant women consumed 200 mg and above caffeine per day.

Table 2. Estimated caffeine intake among pregnant women based on the non-consecutive repeated 24 hours recall average, by trimester of pregnancy, Butajira, South Central Ethiopia, 2018.

Trimester of pregnancy No. Median Caffeine intake (IQR)
mg/day
Range of caffeine intake
mg/day
Prevalence excessive caffeine intake (≥300mg/day*)
percent (95% CI)
1st Trimester 20 298.5 (199.1) 39.5–549.8 50.0 (27.2, 72.8)
2nd Trimester 133 169.9 (133.4) 0.0–525.0 15.8 (10.0, 23.1)
3rd Trimester 188 165.6 (125.0) 0.0–505.4 15.4 (10.6, 21.4)
Total 341 170.5(135.1) 0.0–549.8 17.6 (13.9, 22.0)

IQR = Inter Quartile range; CI = Confidence Interval

*300mg/day the maximum daily caffeine intake limit for pregnant women

Prevalence of alcohol consumption during pregnancy

Table 3 shows the prevalence of alcohol consumption among pregnant women. From a total of 341 pregnant women, 11.1% (95% CI: 8.2%, 15.0%) of the pregnant women consumed alcohol in the last 3 months before current pregnancy and 10.0% (95% CI: 7.2%, 13.7%) consumed alcohol during the current pregnancy. Moreover, 4.4% (2.7, 7.2%) of pregnant women were binge drinkers (consumed five or more drinks at a single occasion). Among women who consumed alcohol during the current pregnancy, the majority (76.8%) consumed alcohol with a frequency of monthly or less than monthly, and almost all (94.1%) of them consumed 1–2 drinks on a typical day whenever they drink.

Table 3. The prevalence of alcohol consumption among pregnant women in Butajira, South Central Ethiopia, 2018.

Variables Frequency Percent (95%CI)
Woman ever consumed alcohol
Yes 45 13.2 (10.0, 17.2)
No 296 86.8 (82.8, 90.0)
Woman consumed alcohol 3 months before pregnancy
Yes 38 11.1 (8.2, 15.0)
No 303 88.9 (85.0, 91.8)
Alcohol intake during current pregnancy
Yes 34 10.0 (7.2, 13.7)
No 307 90.0 (86.3, 92.8)
Frequency of alcohol consumption (n = 34)
Monthly or less 26 76.8
Two to four times a month 7 20.6
Two to three times a week 1 2.9
Number of drinks on a typical day (n = 34)
1–2 32 94.1
3–4 2 5.9
Frequency of drinking five or more drinks in one occasion (n = 34)
Never 19 55.9
Monthly 3 8.8
Less than monthly 11 32.4
Weekly 1 2.9
Binge drinking (n = 341)
Yes 15 4.4 (2.7, 7.2)
No 326 95.6 (92.8, 97.3)
Obtained information to stop drinking alcohol (n = 34)
Yes 5 14.7
No 29 85.3

Prevalence of khat chewing during pregnancy

Table 4 shows the prevalence, frequency and amount of khat chewing among pregnant women. A total of 122 (35.8%; 95% CI: 30.8, 41.0%) of pregnant women chewed khat during the current pregnancy. Among these, 36 (29.5%) chewed khat two to three times a week while 6.6% of them chewed khat more than four times a week.

Table 4. The prevalence, frequency and amount of khat chewing among pregnant women in Butajira, South Central Ethiopia, 2018.

Variables Frequency Percent (95%CI)
Woman chewed khat before the current pregnancy
Yes 147 43.1 (37.9, 48.4)
No 194 56.9 (51.6, 62.1)
Woman ever chewed khat during current pregnancy
Yes 122 35.8 (30.8, 41.0)
No 219 64.2 (59.0, 69.2)
Frequency of khat chewing (n = 122)
Monthly or less 47 38.5
Two to four times a month 30 24.6
Two to three times a week 36 29.5
Four or more times a week 8 6.6
Daily 1 0.8
Woman chewed khat in the last 30 days of interview (n = 341)
Yes 115 33.7 (28.9, 38.9)
No 226 66.3 (61.1, 71.1)
Informed to stop chewing (n = 122)
Yes 6 4.9
No 116 95.1

Prevalence of active and passive tobacco smoking during pregnancy

Table 5 shows the proportion of pregnant women exposed to tobacco smoke at home, work and public places. None of the pregnant women was active tobacco smokers. However, 9.7% (95% CI: 6.9, 13.3%) of pregnant women exposed to tobacco smoke at home. Of them, the majority (75.8%) of pregnant women exposed to tobacco smoke daily. Overall, 23.2% (95% CI: 19.0, 28.0) of pregnant women were passive smokers.

Table 5. The prevalence of passive smoking among pregnant women in Butajira, South Central Ethiopia, 2018.

Variables Frequency Percent (95% CI)
Exposure to smoking at home
Yes 33 9.7 (6.9, 13.3)
No 308 90.3 (86.7, 93.1)
Frequency of another person smoked at home (n = 33)
Daily 25 75.8
Weekly 4 12.1
Monthly 2 6.1
Less than monthly 2 6.1
Exposure to smoking at work places in the last 30 days
Yes 2 0.6 (0.1, 2.3)
No 339 99.4 (97.7, 99.9)
Exposure to smoking at Public places in the last 7 days
Yes 52 15.2% (11.8, 19.5)
No 289 84.8% (80.5, 88.2)
Overall passive smoking
Yes 79 23.2 (19.0, 28.0)
No 262 76.8 (72.0, 81.0)

Overall prevalence of substances use during pregnancy

Table 6 shows the summary of substances use during pregnancy. The overall prevalence of substance use during pregnancy is defined by exposure at least to one of the four substances i.e. caffeine more than or equal to 300 mg, alcohol intake or khat chewing or tobacco smoke during current pregnancy. Based on this, the overall substance use during the current pregnancy was 60.1% (95% CI: 54.8%, 65.2%).

Table 6. The summary of substances uses among pregnant women in Butajira, South Central Ethiopia, 2018.

Variables Affirmative response Frequency Percent (95% CI)
Excess caffeine intake Yes 60 17.6 (13.9, 22.0)
Alcohol intake Yes 34 10.0 (7.2, 13.7)
Khat chewing Yes 122 35.8 (30.8, 41.0)
Passive smokers Yes 79 23.2 (19.0, 28.0)
At least one substances use Yes 205 60.1 (54.8, 65.2)

Factors associated with excess caffeine consumption

Table 7 shows the result of a multivariate logistic regression analysis fitted to identify risk factors for excess caffeine consumption. After adjustment for possible confounders such as maternal age, educational status, wealth status, gestational age, antenatal care, awareness about the effects of coffee/tea consumption on the fetus and khat chewing during pregnancy, we found that the poor, rich and richest wealth status and first trimester pregnancies were significantly associated with excess caffeine consumption among pregnant women. The odds of excessive caffeine consumption is approximately four times higher among pregnant women at poor wealth status compared to the odds among the pregnant women at the poorest wealth status (AOR = 3.63; 95% CI: 1.16, 11.32). Similarly, as compared to the odds of excessive caffeine consumption among the pregnant women at the poorest wealth status, the odd of excessive caffeine consumption was approximately four times higher among pregnant women at the rich wealth status (AOR = 3.74; 95% CI: (1.17, 11.88). In addition, the odds of excessive caffeine consumption is approximately four times higher among pregnant women at richest wealth status compared to the odds of excessive caffeine consumption among the pregnant women at the poorest wealth status (AOR = 3.66; 95% CI: 1.13, 11.88).

Table 7. The multivariable logistic regression analysis to identify factors associated with excess caffeine consumption among pregnant women in Butajira, South Central Ethiopia, 2018.

Variables Excess Caffeine Intake COR (95% CI) +AOR (95% CI)
No
Count (%)
Yes
Count (%)
Age
15–24 85 (88.5) 11 (11.5) 1.00 1.00
25–34 177 (83.9) 34 (16.1) 1.48 (0.72, 15.36) 0.88 (0.38, 2.04)
35 and above 19 (55.9) 15 (44.1) 6.10 (2.42, 15.36) *** 2.98 (0.97, 9.14)
Educational status
No formal education 111 (75.00) 37 (25.00) 2.06 (0.80, 5.26) 0.85 (0.29, 2.48)
Primary 133 (88.70) 17 (11.30) 0.79 (0.29, 2.14) 0.39 (0.13, 1.16)
Secondary and above 37 (86.00) 6 (14.00) 1.00 1.00
Wealth status
Poorest 72 (93.5) 5 (6.5) 1.00 1.00
Poor 62 (81.6) 14 (18.4) 3.25 (1.11, 9.54) * 3.63 (1.16, 11.32) *
Middle 50 (79.4) 13 (20.6) 3.74 (1.26, 11.17) * 2.35 (0.72, 7.69)
Rich 49 (77.8)) 14 (22.2) 4.11 (1.39, 12.16) * 3.74 (1.17, 11.88) *
Richest 48 (77.4) 14 (22.6) 4.20 (1.42, 12.42) ** 3.66 (1.13, 11.88) *
Trimester
1st 10 (50.0) 10 (50.0) 5.48 (2.10, 14.34) ** 4.54 (1.38, 15.00) *
2nd 112 (84.2) 21 (15.8) 1.03 (0.56, 1.89) 0.82 (0.41, 1.64)
3rd 159 (84.6) 29 (15.4) 1.00 1.00
Antenatal care Follow up
Yes 256 (85.0) 45 (15.0) 1.00 1.00
No 25 (62.5) 15 (37.5) 3.41 (1.67, 6.97) *** 2.25 (0.94, 5.36)
Awareness on excess caffeine effect on the fetus
Yes 71 (92.2) 6 (7.8) 1.00 1.00
No 210 (79.5) 54 (20.5) 3.04 (1.26, 7.38) * 2.36 (0.92, 6.05)
Khat chewing
Yes 91 (74.6) 31 (25.4) 2.23 (1.27, 3.93) ** 1.71 (0.90, 3.25
No 190 (86.8) 29 (13.2) 1.00 1.00

*p value <0.05

** p value <0.01

*** p value <0.001

COR: Confidence Interval, COR: Crude Odds ratio, AOR: Adjusted odds ratio

+Adjusted for maternal age, educational status, wealth status, gestational age, ANC, awareness about the effects of coffee/tea consumption on the fetus and khat chewing during pregnancy

Moreover, the odds of excessive caffeine consumptions is four times higher among pregnant women at the first trimester of pregnancy compared to the odds among the pregnant women at third trimester (AOR = 4.04; 95% CI: 1.26, 13.05).

Discussions

We conducted a community based cross sectional study to determine the prevalence of excess caffeine, alcohol consumption, khat chewing, and tobacco use during pregnancy and identify factors associated with excessive caffeine consumption. The study found that 17.6% of pregnant women had a daily caffeine consumption more than or equal to 300 mg. In addition, one in ten and nearly four in ten pregnant women consume alcohol and chew khat during pregnancy respectively. We also found that two in ten pregnant women are passive tobacco smokers. Additionally, after adjustment for possible confounders, richest wealth status, and first trimester pregnancy were significantly associated with excess caffeine consumption among pregnant women.

The current study showed that the prevalence of excessive caffeine consumption (more than or equal to 300 mg per day) among pregnant women was 17.6%. The prevalence of caffeine consumption more than or equal to 200 mg per day among pregnant women was 41.9%. A great proportion (50.0%) of pregnant women in the first trimester of pregnancy consumed excessive caffeine compared to the pregnant women at the second and third trimester of pregnancy. This finding is not in line with the previous literature. According a study in 2004, 96% of subjects decreased or quit drinking coffee during first trimester pregnancy [51]. The possible reason for this discrepancy and high prevalence of excess caffeine intake during first trimester of pregnancy needs further investigation.

Based on the existing literature, high levels of caffeine intake during pregnancy can result in miscarriage, low birth weight, growth restriction, stillbirth, and increases the risk of health problems in later life [5259]. This implies that pregnant women were at risk of experiencing spontaneous abortion, stillbirth and low birth weight baby, which need an intervention.

This study found that 10.0% of pregnant women consumed alcohol during the current pregnancy. This figure is comparable to the global (9.8%) (16) and national (7.9%) prevalence of alcohol consumption among pregnant women (17). However, this finding was lower compared to a study from Ireland (60%), Belarus (47%), Denmark (46%), United Kingdom (41%), Russian Federation (37%) (20), South Eastern Nigeria (22.6%) (38), and Ethiopia at Bahirdar (34%) (18).

Maternal alcohol intake during pregnancy results in direct and indirect consequences on fetal development. Directly, alcohol readily crosses the placenta and blood-brain barriers and rapidly diffuses into any aqueous compartment of the body, such as the neurons or lipid membranes [60]. Exposure to alcohol during fetal development has been reported to reduce up to 12% of total brain weight, defined as microcephaly, due to decreased protein synthesis, which leads to decreased DNA translation [61]. Indirectly, alcohol induces maternal hypoxia, oxidative stress, and altered metabolism, affecting the growth and development of the fetus [62].

In addition, many alcoholics do not consume a balanced diet considering alcoholic beverages as part of their normal diet and acquire a certain number of calories from alcohol in substitution of calories from other nutrients. Moreover, alcohol consumption can interfere with the absorption of nutrients, impairing the quality and quantity of proper nutrient and energy intake, resulting in malnutrition especially of micronutrients such as vitamins, omega–3, folic acid, zinc, choline, iron, copper, and selenium [63]. When maternal nutritional status is compromised by alcohol the supply of essential nutrients are not available for the fetus; this can result in fetal abnormalities like Intrauterine Growth Restriction, Fetal Alcohol Spectrum Disorder [64], low birth weight (21), and small for gestational age (22). This indicated the need of alcohol consumption intervention program among pregnant women to prevent these adverse pregnancy outcomes.

In the current study the prevalence of khat chewing during the current pregnancy was 35.8% which is higher compared to the national khat chewing prevalence among the general population in Ethiopia (44). This difference might be due to the accessibility of khat in the current study area since khat grows as a cash crop in Butajira [65]. Moreover, low awareness on the harmful effects of substances use on the fetus as evidenced by this study might be the other possible reason. However figure is lower compared to a community based study finding in Yemen (34).This might be due socio-cultural variation.

Khat chewing during pregnancy may have different obstetric effects like low birth weight, stillbirths, impaired lactation, and embryo toxic as well as teratogenic properties. A study on rats in 1994 revealed that khat had retarded fetal growth and teratogenic effect and this developmental toxicity of khat is dose-related [66]. A case-control study conducted in 2015 at Bale Hospital of South East Ethiopia showed that maternal history of khat chewing was associated with low birth weight [67]. Another case-control study in 2017 obtained similar finding [68].

In addition, khat chewing during pregnancy associated with restrictive dietary behavior which results in Anemia. According to a study in 2013, the risk of anemia was 29% higher in the women who chewed khat daily than those who chewed sometimes or never did so [69]. These indicated that the need of khat chewing intervention program to prevent maternal anemia and adverse pregnancy outcomes.

In the current study, none of the pregnant women was active tobacco smokers. However, the prevalence of passive smoking was 23.2%. This figure is lower as compared to the findings of a study conducted in Shanghai, China (2016) where it was 34.8% [70]. Though the figure was lower, active or passive tobacco smoke exposure during pregnancy has adverse health effects on the fetus, as well as the mother. The adverse health effect of cigarette smoke on the fetus includes, an increased risk of strabismus in the offspring [71], clubfoot [72], low birth weight for gestational age (LBWGA), low birth weight, preterm births (28, 29), increased odds of elevated levels of antisocial behaviors during adolescence and adulthood, as well as violent and nonviolent outcomes [73], an increased risk of wheeze in children [74], and almost 3 times increased risk of congenital heart defects [75]. Moreover, tobacco smoke during pregnancy increases the prevalence of depressive symptoms during pregnancy [76]. This indicated the need of tobacco smoking intervention at home, work and public places to improve fetal, maternal and societal health.

The current study showed that the odds of excessive caffeine consumption was approximately four times higher among pregnant women at the poor, rich and richest wealth status compared to the odds of excessive caffeine consumption among pregnant women at the poorest wealth status. Likewise, the odd of excessive caffeine consumptions is four times higher among pregnant women at first trimester of pregnancy compared to the odds among the pregnant women at the third trimester of pregnancy. As women wealth status increases, the chance of buying coffee and consuming caffeinated beverages might increase. Due to this woman at the poor, rich and richest wealth status might consume excess caffeine compared to woman at the poorest wealth status. The reason why pregnant women at first trimester of pregnancy consume excess caffeine needs an investigation.

The findings of the study should be interpreted with the following strengths and limitations. Since we the study employed a random sampling methods, the findings could be generalizable to pregnant women living in the study area and similar settings. All days of the week were considered in order to control days of the week effect. In addition, non-consecutive 2 days repeated 24-hour recall which is the recommended method for the assessment of exposure within risk assessment processes was done to control with in person variation of caffeine intake.

However, the study has the following limitations. First, the level of caffeine concentration was obtained from previously conducted researches. However, the concentration of caffeine may vary based on the roasting and brewing process. Moreover, the strength of coffee was not considered as weak, medium and strong. Due to these reasons, the reported estimates of caffeine intake might be under or over estimated. Second, the study was conducted during the non-fasting season. In Ethiopia, coffee is traditionally consumed under coffee ceremony and the ceremony is a minimum of three times a day. In each ceremony, a person will take three cups of coffee [77]. Hence during fasting time, the number of ceremony decreases and this alter the daily coffee consumption. To the contrary, the frequency of coffee consumption increases during non-fasting season. Due to this reason our study might overestimate the prevalence of excessive caffeine consumption. Third, substances use such as alcohol and tobacco use are considered as non-religious and taboo in the study area. As a result, some respondents might not report consumption of alcohol and khat. These factors could underestimate the prevalence of alcohol and tobacco use among pregnant women. Fourth, there was no follow up of pregnant women. Due to this, the study could not assess exist of correlation between substance use and birth weight.

Conclusions

In conclusion, the prevalence of excess caffeine consumption, khats chewing as well as passive tobacco smoking were high among pregnant women. However, the prevalence of alcohol consumption was comparable to the global and national prevalence. The richest wealth status and first trimester pregnancy were significantly identified risk factors associated with excess caffeine consumption among pregnant women. Therefore, interventional programs that addresses caffeine and alcohol consumption, khat chewing and Tobacco smoke exposures among pregnant women are needed. Moreover, further research is also needed to examine the effect of substance use on birth outcomes.

Supporting information

S1 Dataset

(DTA)

Acknowledgments

First, we would like to acknowledge SPH, CHS of AAU for giving us an ethical clearance and writing a support letter to the study area. Second, our acknowledgment goes to Butajira Rural Health Program Staffs for provided us all the necessary information about the study area. At last but not least, we are grateful to all respondents for their voluntariness and participation.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Yael Abreu-Villaça

7 Feb 2020

PONE-D-19-29554

Caffeine, Alcohol, Khat, and Tobacco Use during Pregnancy in Butajira, South Central Ethiopia

PLOS ONE

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2. Please address the following:

- Please ensure you have thoroughly discussed any potential limitations of this study within the Discussion section. For example, the lack of follow-up with these participants does not allow for correlations to be made between substance use and birth weight.

- Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. In addition, please provide further details on the pre-testing of this questionnaire - i.e. how many participants were involved and from where were they recruited.

- Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified how verbal consent was documented and witnessed.

- Please provide further details of your pilot study. This is mentioned in the text with no further information or reference to a published work.

Thank you for your attention to these queries.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear author,

The following issues regarding Introduction, Methods, and Discussion sections must be addressed:

a. I think the study objective should be assess the prevalence of caffeine and alcohol consumption, khat chewing, and tobacco and predictors of caffeine consumption among pregnant pregnant women in South Central Ethiopia rather than "determine the magnitudes of caffeine and alcohol consumption, khat chewing, and tobacco use during pregnancy and identify factors associated with excess caffeine consumption".

b. The introduction is very long, some data are redundant. I suggest shortening and reviewing some paragraphs. Also, the last paragraph on page 5 would be better suited to the discussion.

c. The discussion should focus on the physiological and sociodemographic factors that may contribute to the increase in maternal caffeine intake. The study results should be confronted with others in the literature. However, the discussion has a strong focus on the adverse effects of maternal habits on the fetus and child that I consider to be more suitable for the introduction.

d. Was the design effect used for sample calculation?

e. Was the questionnaire validated?

f. It was not possible to quantify the concentration and the brand of caffeine products in this study. The author did not consider the strength of coffee as commonly consumed (weak, medium, or strong coffee). These limitations need to be included in the discussion.

g. Could the lack of information about some medications to underestimate the amount of caffeine ingested by pregnant women?

h. The literature report that social factors such as the family history of alcoholism, occupation of the head of the family, and higher parity are positively associated with high caffeine consumption. The author should comment on these limitations in the discussion.

i. Please define ANC follow up abbreviation (antenatal care).

j. Page 6: The sentence "The study was conducted in Butajira Rural Health Program (BRHP) site, which is found in Meskan and Mareko districts of Gurage Zone, SNNP region, South Central Ethiopia" is confusing. This needs to be more clearly described. Is the author saying the study was conducted in areas (kebeles) covered by BRHP?

k. Page 6: I think the sentences "Butajira Rural Health Program is a Health Demographic Surveillance System (HDSS) Site for Addis Ababa University" and "BRHP comprises one urban and nine rural kebeles (a kebele is the smallest administrative unit in Ethiopia)" are confusing. Does the Butajira Rural Health Program is a Health Demographic Surveillance System (HDSS) site? Does the BRHP cover selected kebeles of the Meskan and Mareko district? Please clarify it.

l. Page 7: "The source population of the study was all pregnant women living at BRHP". I’m not sure of what you mean "living at BRHP". Please, clarify it.

m. Page 7: "The list of pregnant women were obtained from the BRHP database". How about the recruitment process? How were they initially contacted? Was there a visit to the participant’s home? How about the exclusion or inclusion criteria?

n. Page 11: I think the sentence "After data collection, the data were entered using Epi-data version 3.1 software to avoid an introduction of error while data entry" is redundant. This information is described in the next paragraph.

o. Page 14: "However, Pepsi cola, energy drinks, and chocolates were not sources of caffeine among pregnant women in the study area pregnancy" I’m not sure of what you mean " sources of caffeine among pregnant women in the study area pregnancy ". Please, clarify it.

p. Page 22: The sentence “The possible reason for this high prevalence of excess caffeine intake during the first trimester of pregnancy needs further investigation” should be discussed. The literature report that in the first-trimester, behavioral changes occur aiming at enhancing personal care, and symptoms such as nausea or aversion to the coffee smell or taste can be quite common during pregnancy, reducing coffee consumption.

q. Page 25: The statement “ The current study showed that the odds of excessive caffeine consumption is approximately… at the richest wealth status compared to the odds among pregnant women at the poorest wealth status” seems no make much sense. Positive associations with poor women were seen. Besides, no significant association between middle income and coffee consumption were observed.

r. Page 25: “Due to this woman with richest wealth status might consume excess caffeine compared to woman with the poorest wealth status” and “As women wealth status increases, the chance of buying coffee and consuming caffeinated beverages might increase.” Poor people of rural areas do not consume coffee? Is coffee expensive in the studied areas? Does the studied area plant coffee?

s. Page 26: I’m not sure I understand this statement “Second, the study was conducted during the non-fasting season, and our report might overestimate the prevalence of excess caffeine consumption.” Is the author saying that women consume more caffeine because, in the fasting season, they can't do it? Please, clarify this statement.

t. The conclusion should be re-evaluated according to the considerations addressed in this review.

Reviewer #2: The manuscript’s issue is the excessive use of caffeine, and the consumption of alcohol, cigarette, and khat during pregnancy, and their adverse effects on the fetus's health. The theme is relevant and actual once it is a public health problem in many countries in the world. It is more critical in developing countries, in which many other socioeconomic risk factors can impact the pregnancy so, it is important to produce scientific information specifically from these countries.

The authors present global statistical data that strengthen the importance of the issue.

The abstract summarizes the arguments in an adequate way.

Method: the study area, study population, and sample size determination and sampling procedure are well described. A pilot study and a pretest were conducted and, a “two days training” was done to the data collectors and supervisors before the accomplishment of the study.

The authors considered that “the accessibility of substances might vary based on residence and agro-ecological zones”. It could be interesting to add information about how this accessibility could vary and which are the characteristics of these zones and their impact on drug use that could justify this division. Additionally, there are no comments about this point in the Results or Discussion sessions.

The results are well described, and the Discussion encompasses the main findings. The Conclusion is pertinent.

Reviewer #3: In the submitted manuscript the authors investigated the prevalence of caffeine, alcohol, khat, and tobacco use among 352 pregnant women in Ethiopia. They also investigated the main factors associated with the excess of caffeine intake among those women. The consumption of these substances during pregnancy may pose a risk to the health of mothers and newborns. Since information on the use of these substances during pregnancy in developing countries like Ethiopia is very scarce, this manuscript can bring new findings to the subject. However, to be published this manuscript needs some improvements.

MAJOR COMMENTS

The authors could have moved forward and, in addition to assess the use of caffeine, alcohol, khat, and tobacco during pregnancy, they could also have investigated the association between the use of these substances and adverse birth outcomes in the studied population. Although this association has been extensively studied, very few is known about this relationship under the socioeconomic conditions expected to be found in developing countries like Ethiopia.

English needs major revision.

MINOR COMMENTS

Page 3, line 54: The definition of "substance use" was retrieved from a website. I recommend that the authors search for a definition on a paper or book. In addition, I believe that authors meant to define substance abuse, not use.

Page 3, line 63: This submitted version still shows (ref), which I assumed as a missing reference.

The authors obtained the amount of caffeine intake from several sources through a two-24-hr recall survey, one in a weekday and another on a weekend day. Then, they calculated an average intake by summing the two-24-hr, and dividing by 2. Did authors test for differences in the caffeine intake between weekdays and weekend days for the different sources?

The authors found that the factors significantly associated with excess consumption of caffeine were the richest wealth status and the first trimester of pregnancy. However, they failed to describe that, compared with the poorest, the poor wealth status was also associated with excess of caffeine intake. In addition, crude odds ratios also suggested that age and antenatal care follow up may also be associated with the outcome. Although such associations were not statistically significant in the adjusted analyses, they were borderline and deserve to be mentioned in the results’ section.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Armando Meyer

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

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PLoS One. 2020 May 8;15(5):e0232712. doi: 10.1371/journal.pone.0232712.r002

Author response to Decision Letter 0


13 Mar 2020

PONE-D-19-29554

Caffeine, Alcohol, Khat, and Tobacco Use during Pregnancy in Butajira, South Central Ethiopia

PLOS ONE

Responses to the Academic Editor

Dear Academic Editor,

Thank you for your valuable questions and suggestions. We have tried to respond the queries you raised on the method and limitation sections line by line as follow:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response:

• Thank you! We have prepared our manuscript as per the PLOS ONE’s guideline.

2. Please address the following:

- Please ensure you have thoroughly discussed any potential limitations of this study within the Discussion section. For example, the lack of follow-up with these participants does not allow for correlations to be made between substance use and birth weight.

Response:

• Dear academic editor Thank you! We incorporated it as “There was no follow up of pregnant women. Due to this, the study could not assess exist of correlation between substance use and birth weight” (Check on discussion section, page 29, lines 468-470).

- Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. In addition, please provide further details on the pre-testing of this questionnaire - i.e. how many participants were involved and from where were they recruited.

Response:

� Regarding the issues raised on the questionnaire, we did not develop a questionnaire. The questionnaire was adapted from Caffeine Consumption Questionnaire-Revised (CCQ-R), Alcohol Use Disorder Identification Test (AUDIT), and Global Adult Tobacco Survey (GATS), EDHS 2016 for caffeine, alcohol consumption, tobacco use and khat chewing assessment, respectively (Check on materials and methods section, page 8, lines 152-156).

� Concerning the pre-test, it was done on 21 pregnant women who recruited from out of the actual study area (Check on materials and methods section, page 11, lines 213-218).

- Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified how verbal consent was documented and witnessed.

Response:

� Regarding the verbal consent, the verbal consent was documented by the interviewer on the prepared consent form attached with the questionnaire (Check on materials and methods section, page 12, lines 245 & 246).

- Please provide further details of your pilot study. This is mentioned in the text with no further information or reference to a published work. Thank you for your attention to these queries.

Response:

� Dear editor thank you! We conducted a pilot study before the actual data collection period to obtain the portion of coffee in the drink of coffee with milk. We recruited 12 households for the pilot study. Based on the pilot study we conducted, the estimated proportion of coffee in the drink of coffee served with milk was 0.7365 (Check on materials and methods section, page 9, lines 178-181).

Response to Reviewer #1

Dear Reviewer,

Thank you for your valuable questions and suggestions. We have tried to address the queries you raised on the introduction, result, method and discussion sections as follow:

a. I think the study objective should be assess the prevalence of caffeine and alcohol consumption, khat chewing, and tobacco and predictors of caffeine consumption among pregnant women in South Central Ethiopia rather than "determine the magnitudes of caffeine and alcohol consumption, khat chewing, and tobacco use during pregnancy and identify factors associated with excess caffeine consumption".

Response:

• Thank you for your suggestion! It was corrected as “To assess the prevalence of caffeine and alcohol consumption, khat chewing, and tobacco use during pregnancy and identify factors associated with excess caffeine consumption” (Check on the abstract section, page 2, line 27-29).

b. The introduction is very long, some data are redundant. I suggest shortening and reviewing some paragraphs. Also, the last paragraph on page 5 would be better suited to the discussion.

Response:

• Thank you for your suggestion! To make the introduction more informative, it becomes somehow long as you said. If we shorten it, it will not be informative. That is why we obliged to narrate it as such. Nevertheless, we have tried to make it short.

c. The discussion should focus on the physiological and sociodemographic factors that may contribute to the increase in maternal caffeine intake. The study results should be confronted with others in the literature. However, the discussion has a strong focus on the adverse effects of maternal habits on the fetus and child that I consider to be more suitable for the introduction.

Response:

• Thank you for your insight! We have discussed those factors which are significantly associated with excess caffeine intake. In addition, we incorporated the effects of caffeine intake to show the implication of excess caffeine intake during pregnancy on the fetus (Check on discussion section, page 28, line 444-452).

d. Was the design effect used for sample calculation?

Response:

• Because we have used stratified sampling technique, design effect was not considered during sample size determination.

e. Was the questionnaire validated?

Response:

� Dear reviewer, we did not develop a questionnaire. The questionnaire was adapted from Caffeine Consumption Questionnaire-Revised (CCQ-R), Alcohol Use Disorder Identification Test (AUDIT), and Global Adult Tobacco Survey (GATS), EDHS 2016 for caffeine, alcohol consumption, tobacco use and khat chewing assessment, respectively (Check on materials and methods section, page 8, lines 152-156).

f. It was not possible to quantify the concentration and the brand of caffeine products in this study. The author did not consider the strength of coffee as commonly consumed (weak, medium, or strong coffee). These limitations need to be included in the discussion.

Response:

• Thank you! We incorporated it as a limitation (Check on discussion section, page 29, line 459-462).

g. Could the lack of information about some medications to underestimate the amount of caffeine ingested by pregnant women?

Response:

• Yes, it underestimates the amount of caffeine consumption among pregnant women. Some drugs such as Aspirin contain caffeine as an ingredient. But, pregnant women mainly not took those drugs during pregnancy.

h. The literature report that social factors such as the family history of alcoholism, occupation of the head of the family, and higher parity are positively associated with high caffeine consumption. The author should comment on these limitations in the discussion.

Response:

• Dear reviewer, thank you for your insight. We have tried to search factors associated with excess caffeine consumption during pregnancy. But we could not find any study conducted on factors associated with excess caffeine consumption during pregnancy.

i. Please define ANC follow up abbreviation (antenatal care).

Response:

• Thank you! ANC follow up corrected as “antenatal care follow up” (Check on Result section, page 23, Table 7, between line 261 & 262).

j. Page 6: The sentence "The study was conducted in Butajira Rural Health Program (BRHP) site, which is found in Meskan and Mareko districts of Gurage Zone, SNNP region, South Central Ethiopia" is confusing. This needs to be more clearly described. Is the author saying the study was conducted in areas (kebeles) covered by BRHP?

Response:

• Yes and it is corrected as “The study was conducted in Kebeles covered by Butajira Rural Health Program (BRHP) which is found in Meskan and Mareko districts of Gurage Zone, SNNP region, South Central Ethiopia.” (Check on materials and methods section, page 6, line 123-125).

k. Page 6: I think the sentences "Butajira Rural Health Program is a Health Demographic Surveillance System (HDSS) Site for Addis Ababa University" and "BRHP comprises one urban and nine rural kebeles (a kebele is the smallest administrative unit in Ethiopia)" are confusing. Does the Butajira Rural Health Program is a Health Demographic Surveillance System (HDSS) site? Does the BRHP cover selected kebeles of the Meskan and Mareko district? Please clarify it.

Responses:

• Yes, Butajira Rural Health Program is a Health Demographic Surveillance System (HDSS) site (Check on materials and method, page 6 & 7, line 125-127).

• Yes, BRHP covers the selected kebeles of Meskan and Mareko district and clarified as suggested (Check on materials and method section, page 6 & 7, line 125-127).

l. Page 7: "The source population of the study was all pregnant women living at BRHP". I’m not sure of what you mean "living at BRHP". Please, clarify it.

Response:

• Thank you! It is corrected as “The source population of the study was all pregnant women living at Butajira Rural Health Program” (Check on materials and method section, page 7, line 131 & 132).

m. Page 7: "The list of pregnant women was obtained from the BRHP database". How about the recruitment process? How they were initially contacted? Was there a visit to the participant’s home? How about the exclusion or inclusion criteria?

Responses:

How about the recruitment process?

• The total number of pregnant women during the data collection period was 466 as obtained from the Butajira Rural Health Program data base. Sampling frame was prepared for each stratum and the samples were assigned for each stratum proportional to the number of pregnant women. Then, study subjects were selected from each stratum by using simple random sampling (SRS) technique (Check on materials and method section, page 7, line 142-150).

How they were initially contacted?

• The sampling frame was obtained from the Butajira Rural Health Program site. They continuously updated the database. Once we select the samples, the interview conducted at the respondents’ house (Check on materials and method section, page 7, line 145&146).

Was there a visit to the participant’s home? How about the exclusion or inclusion criteria?

• There was a visit to the participant’s home during the data collection time.

• Pregnant women living in the study area were included in the study. None of the pregnant women was excluded (Check on materials and method, page 7, line 132 & 133).

n. Page 11: I think the sentence "After data collection, the data were entered using Epi-data version 3.1 software to avoid an introduction of error while data entry" is redundant. This information is described in the next paragraph.

Response:

• Thank you! The statement “After data collection, the data were entered using Epi-data version 3.1 software to avoid an introduction of error while data entry” is removed as suggested (Check on materials and methods section, page 11, line 121).

o. Page 14: "However, Pepsi cola, energy drinks, and chocolates were not sources of caffeine among pregnant women in the study area pregnancy" I’m not sure of what you mean "sources of caffeine among pregnant women in the study area pregnancy ". Please, clarify it.

Response:

• Thank you! It is corrected as “However, Pepsi cola, energy drinks and chocolates were not the sources of caffeine among pregnant women in the study area” (Check on result section, page 15, line 275 & 276).

p. Page 22: The sentence “The possible reason for this high prevalence of excess caffeine intake during the first trimester of pregnancy needs further investigation” should be discussed. The literature report that in the first-trimester, behavioral changes occur aiming at enhancing personal care, and symptoms such as nausea or aversion to the coffee smell or taste can be quite common during pregnancy, reducing coffee consumption.

Response:

• Thank you for your insight! We discussed as “This finding is not in line with the previous literature. According a study in 2004, 96% of subjects decreased or quit drinking coffee during first trimester pregnancy. The possible reason for this discrepancy and high prevalence of excess caffeine intake during first trimester of pregnancy needs further investigation” (Check on discussion section, page 25, line 381-383).

q. Page 25: The statement “The current study showed that the odds of excessive caffeine consumption is approximately… at the richest wealth status compared to the odds among pregnant women at the poorest wealth status” seems no make much sense. Positive associations with poor women were seen. Besides, no significant association between middle income and coffee consumption were observed.

Response:

• Thank you for your point of view! Though, there was a positive associations between excess caffeine consumption among poor women and excess caffeine consumption and no significant association between middle income and excess caffeine consumption were seen, the odds of excessive caffeine consumption is approximately four times higher among pregnant women at the richest wealth status as compared to the odds among pregnant women at the poorest wealth status. That is why we narrate and discussed it as such (Check on result section, page 22, line 342-347).

r. Page 25: “Due to this woman with richest wealth status might consume excess caffeine compared to woman with the poorest wealth status” and “As women wealth status increases, the chance of buying coffee and consuming caffeinated beverages might increase.” Poor people of rural areas do not consume coffee? Is coffee expensive in the studied areas? Does the studied area plant coffee?

Responses:

� We are not saying that poor people of rural areas do not consume coffee.

� Yes, coffee is expensive in the study area. It is around 3 dollar per kg.

� The studied area does not plant coffee.

s. Page 26: I’m not sure I understand this statement “Second, the study was conducted during the non-fasting season, and our report might overestimate the prevalence of excess caffeine consumption.” Is the author saying that women consume more caffeine because, in the fasting season, they can't do it? Please, clarify this statement.

Responses:

• They can drink it during the fasting season. But, the authors want to say that the frequency of drinking coffee per day becomes decrease during the fasting season and increase during the non-fasting season. Due to this the intake of excess caffeine consumption may underestimated during the fasting period. While it may be overestimated during the non-fasting period (Check on discussion section, page 29, line 463-465).

Response to Reviewer #2

Dear Reviewer,

Thank you for your valuable suggestions. We have tried to address the queries you raised on the method section as follow:

� The manuscript’s issue is the excessive use of caffeine and the consumption of alcohol, cigarette, and khat during pregnancy, and their adverse effects on the fetus's health. The theme is relevant and actual once it is a public health problem in many countries in the world. It is more critical in developing countries, in which many other socioeconomic risk factors can impact the pregnancy so, it is important to produce scientific information specifically from these countries. The authors present global statistical data that strengthen the importance of the issue.

Response:

• Thank you!

• The abstract summarizes the arguments in an adequate way.

Method: the study area, study population, and sample size determination and sampling procedure are well described. A pilot study and a pretest were conducted and, a “two days training” was done to the data collectors and supervisors before the accomplishment of the study.

Response:

• Thank you!

• The authors considered that “the accessibility of substances might vary based on residence and agro-ecological zones”. It could be interesting to add information about how this accessibility could vary and which are the characteristics of these zones and their impact on drug use that could justify this division. Additionally, there are no comments about this point in the Results or Discussion sessions.

Response:

• Dear reviewer thank you for your comment! The accessibility of substances at rural and urban areas may not be the same. For instance: Tobacco may not be accessible at rural areas as such to the urban areas. In addition, Khat grows mainly in highland than lowlands. Due to these reasons, the accessibility of substances use may vary based on residence and agro ecological zones (Check on materials and method, page 7, line 142 & 143).

• The results are well described, and the Discussion encompasses the main findings. The Conclusion is pertinent.

Response:

• Thank you!

Response to Reviewer #3

Reviewer #3 comments

In the submitted manuscript the authors investigated the prevalence of caffeine, alcohol, khat, and tobacco use among 352 pregnant women in Ethiopia. They also investigated the main factors associated with the excess of caffeine intake among those women. The consumption of these substances during pregnancy may pose a risk to the health of mothers and newborns. Since information on the use of these substances during pregnancy in developing countries like Ethiopia is very scarce, this manuscript can bring new findings to the subject. However, to be published this manuscript needs some improvements.

Dear Reviewer,

Thank you for your valuable questions and suggestions. We have tried to address the major and minor comments you raised as follow:

Response to Major Comments:

� The authors could have moved forward and, in addition to assess the use of caffeine, alcohol, khat, and tobacco during pregnancy, they could also have investigated the association between the use of these substances and adverse birth outcomes in the studied population. Although this association has been extensively studied, very few is known about this relationship under the socioeconomic conditions expected to be found in developing countries like Ethiopia.

Response:

• Thank you! We appreciate your point of view. In fact we did not assess the data related with adverse pregnancy outcomes. Due to this we cannot investigate any association between the use of these substances and adverse birth outcomes in the studied population. We mentioned this as a limitation in the discussion section (Check on discussion section, page 29, line 468-470).

� English needs major revision.

Response:

• Thank you! We have revised the entire document.

Response to Minor comments

� Page 3, line 54: The definition of "substance use" was retrieved from a website. I recommend that the authors search for a definition on a paper or book. In addition, I believe that authors meant to define substance abuse, not use.

Response:

• Thank you for your recommendation. It would be nice if the source is from paper or book. But, we could not found any definition from book or paper. It is a medical dictionary definition, thus we decided to use as it is.

• The authors mean to define substance use. Because, during pregnancy even substances use has an effect on the developing fetus.

� Page 3, line 63: This submitted version still shows (ref), which I assumed as a missing reference.

Response:

• Thank you! We incorporated the missed reference (Check on introduction section, page 4 line 64).

� The authors obtained the amount of caffeine intake from several sources through a two-24-hr recall survey, one in a weekday and another on a weekend day. Then, they calculated an average intake by summing the two-24-hr, and dividing by 2. Did authors test for differences in the caffeine intake between weekdays and weekend days for the different sources?

Response:

• We did not test for differences in the caffeine intake between weekdays and weekend days for the different sources.

� The authors found that the factors significantly associated with excess consumption of caffeine were the richest wealth status and the first trimester of pregnancy. However, they failed to describe that, compared with the poorest; the poor wealth status was also associated with excess of caffeine intake. In addition, crude odds ratios also suggested that age and antenatal care follow up may also be associated with the outcome. Although such associations were not statistically significant in the adjusted analyses, they were borderline and deserve to be mentioned in the results’ section.

Response:

• Thank you! We described it as you suggested (Check on result section, page 22, lines 345-347).

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Yael Abreu-Villaça

3 Apr 2020

PONE-D-19-29554R1

Caffeine, Alcohol, Khat, and Tobacco Use during Pregnancy in Butajira, South Central Ethiopia

PLOS ONE

Dear Mr. Alamneh,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please note that one, as detailed below, of the reviewers still has concerns regarding your statistical analysis and, as a consequence,  the results presentation and interpretation.

Please also modify the materials and method section, page 7, line 131 & 132 to make it clear that the population of the study was "all pregnant women living in kebeles covered by BRHP".

We would appreciate receiving your revised manuscript by May 18 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

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  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

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We look forward to receiving your revised manuscript.

Kind regards,

Yael Abreu-Villaça, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #3: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear author,

The vast majority of issues were adequately answered. However, there are some issues described below that must be taken into account in the interpretation of some results:

1) Page 25: “The current study showed that the odds of excessive caffeine consumption is approximately… at the richest wealth status compared to the odds among pregnant women at the poorest wealth status”. According to manuscript Table 7, the adjusted OR for excessive caffeine consumption according to wealth status was:

Poor woman vs poorest one (OR: 3.63, 95%CI: 1.16, 11.32)

Rich woman vs poorest one (OR: 3.74, 95%CI: 1.17, 11.88)

Richest woman vs. poorest one (OR: 3.66, 95%CI: 1.13, 11.88)

Looking at the CIs, if the author hypothetically conducts the same study with a different sample, the true value (OR) of excessive intake of caffeine for women poor in relation to the poorest may be between 1.16 and 11.32. For rich women compared to the poorest one, the true odds may be between 1.17 and 11.88, and for the richest women than the poorest woman, this true value might be between 1.13 and 11.88.

Regarding the issues raised above, is the Odds ratio from 3.63 different from 3.66 and different from 3.74?

Besides, an OR of 2 means there is a 100% increase in the odds of an outcome with a given "exposure". In relation to the paper results, in terms of magnitude, is an increase of 263% different from 274% and different from 266%? Please explain why only the result for the richest woman group compared to the poorest ones were highlighted and discussed.

2) Page 26: “...the authors want to say that the frequency of drinking coffee per day decreases during the fasting season and increases during the non-fasting season.”

During the fasting period, the types of food and drinks and their frequencies are changed (Masood et al. 2018). But I did not find any literature that states that religious fasting alters food patterns after fasting. Please, include references that support your statement.

Masood, S. N., Saeed, S., Lakho, N., Masood, Y., Ahmedani, M. Y., & Shera, A. S. (2018). Pre-Ramadan health seeking behavior, fasting trends, eating pattern and sleep cycle in pregnant women at a tertiary care institution of Pakistan. Pakistan journal of medical sciences, 34(6), 1326.

Reviewer #3: I have carefully reviewed my comments and suggestions sent to the authors. I'm satisfied with the authors' answers.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: Yes: Armando Meyer, M.P.H, Ph.D

Professor of Occupational and Environmental Health

Public Health Institute

Federal University of Rio de Janeiro

ORCID: https://orcid.org/0000-0002-5258-8016

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 May 8;15(5):e0232712. doi: 10.1371/journal.pone.0232712.r004

Author response to Decision Letter 1


14 Apr 2020

Response to the Academic Editor

Dear Academic Editor,

We have tried to address the points raised on result presentation and interpretation during the review process line by line.

Comment 1:

� Please modify the materials and method section, page 7, line 131 & 132 to make it clear that the population of the study was "all pregnant women living in kebeles covered by BRHP".

Response:

� Thank you for your suggestion! We have modified it as “The source population of the study was all pregnant women living in kebeles covered by Butajira Rural Health Program” (Check on Material and Method section, page 7, line 139 & 140).

Response to Reviewer #1

Dear Reviewer,

Thank you for your invaluable concern. We have addressed the raised concerns on the result presentation and interpretation sections as follow:

1) Page 25: “The current study showed that the odd of excessive caffeine consumption is approximately… at the richest wealth status compared to the odds among pregnant women at the poorest wealth status”. According to manuscript Table 7, the adjusted OR for excessive caffeine consumption according to wealth status was:

Poor woman vs poorest one (OR: 3.63, 95%CI: 1.16, 11.32)

Rich woman vs poorest one (OR: 3.74, 95%CI: 1.17, 11.88)

Richest woman vs. poorest one (OR: 3.66, 95%CI: 1.13, 11.88)

Looking at the CIs, if the author hypothetically conducts the same study with a different sample, the true value (OR) of excessive intake of caffeine for poor women in relation to the poorest, may be between 1.16 and 11.32. For rich women compared to the poorest one, the true odds may be between 1.17 and 11.88, and for the richest women than the poorest woman, this true value might be between 1.13 and 11.88.

Regarding the issues raised above, is the Odds ratio from 3.63 different from 3.66 and different from 3.74? Besides, an OR of 2 means there is a 100% increase in the odds of an outcome with a given "exposure". In relation to the paper results, in terms of magnitude, is an increase of 263% different from 274% and different from 266%? Please explain why only the result for the richest woman group compared to the poorest ones were highlighted and discussed.

Response:

� Dear reviewer, we really thank you for your insight! We have admitted your concern. Thus, we have described the odds ratio of excessive caffeine consumption among women in the poor wealth quintile as compared to the women in the poorest wealth quintile (Check on result section, page 23, lines 360-369).

� In addition, we have revised the discussion section (Check on discussion section, page 29, lines 464-466 and lines 470 & 471).

2) Page 26: “...the authors want to say that the frequency of drinking coffee per day decreases during the fasting season and increases during the non-fasting season.”

During the fasting period, the types of food and drinks and their frequencies are changed (Masood et al. 2018). But I did not find any literature that states that religious fasting alters food patterns after fasting. Please, include references that support your statement.

Masood, S. N., Saeed, S., Lakho, N., Masood, Y., Ahmedani, M. Y., & Shera, A. S. (2018). Pre-Ramadan health seeking behavior, fasting trends, eating pattern and sleep cycle in pregnant women at a tertiary care institution of Pakistan. Pakistan journal of medical sciences, 34(6), 1326.

Response:

� Dear reviewer, sure, the authors want to say that the frequency of drinking coffee per day decreases during the fasting season and increases during the non-fasting season. Because, in Ethiopia, coffee is traditionally consumed under coffee ceremony and the ceremony is a minimum of three times a day. In each ceremony, a person will take three cups of coffee (Yoseph, 2013). Hence during fasting time, the number of ceremony decreases and this alter the daily coffee consumption. To the contrary, the frequency of coffee consumption increases during non-fasting season. Due to this reason our study might overestimate the prevalence of excessive caffeine consumption (Check on discussion section, page 30, lines 484-490).

Response to Reviewer #3:

Comment: I have carefully reviewed my comments and suggestions sent to the authors. I'm satisfied with the authors' answers.

� Response: Dear reviewer, we are thankful for your invaluable contribution in the improvement of this manuscript.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Yael Abreu-Villaça

21 Apr 2020

Caffeine, Alcohol, Khat, and Tobacco Use during Pregnancy in Butajira, South Central Ethiopia

PONE-D-19-29554R2

Dear Dr. Alamneh,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Yael Abreu-Villaça, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear author,

I am fully satisfied with the corrections. The presentation of the data is clear, and the overall quality of the manuscript seems adequate for publication in the PLOS ONE.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Acceptance letter

Yael Abreu-Villaça

29 Apr 2020

PONE-D-19-29554R2

Caffeine, Alcohol, Khat, and Tobacco Use during Pregnancy in Butajira, South Central Ethiopia

Dear Dr. Alamneh:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof. Dr. Yael Abreu-Villaça

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Dataset

    (DTA)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.


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