The present study used data from the first two phases of a prospective cohort study entitled “A population-based prospective cohort study to identify contributors of mother and child health in suburban communities” in Bandar Abbas city, which is abbreviated as Bandar Abbas Pregnancy Cohort (BAPC). The study protocol was ethically approved and financially granted by the National Institute for Medical Research Development (NIMAD) with the approval code of 943607 and ethical code of N. IR.NIMAD.REC.1396.205. Since 2014, BAPC investigates the effects of lifestyle and environmental factors on child wellbeing and growth in Bandar Abbas city, the capital of Hormozgan Province in the south of Iran. The BAPC was designed to recruit and follow-up 1,000 pregnant women through door-by-door inquiry. Inclusion criteria defined as ages between 16-50 years, being pregnant, and being resident of the three most socially and economically vulnerable neighborhoods of Bandar Abbas. Exclusion criteria defined as inability to communicate in Farsi, unwillingness to participate or migration from the study area. Following a signed informed consent form, data from the subjects and their babies are gathering through four visits in pregnancy, 1, 6, and 12 months after birth. The details of the cohort methodology have been published elsewhere(14).
The present paper used the data of 897 subjects who completed the second visit of the BAPC (participation rate: 92%, response rate: 95.42%) during September 2016 to May 2018. The second visit was conducted during post-partum period (0-42 days post-delivery) by a visit to the mother`s home or by telephone interview based on the subject`s preference. The following cohort subjects were further excluded from the present analysis: pregnancies that ended up with miscarriage (n=24, 2.55%), stillbirth or multiple pregnancies (n=8, 0.85%), and pregnant subjects with self-reported cigarette smoking during pregnancy (n=4, 0.44%). Therefore, data of 861 live singleton pregnancies (mean +SD gestational age at recruitment: 22.62+9.66 weeks) was included in the analysis (Figure 1). The main outcome of the study was LBW, defined as birth weight below 2,500 grams (1). The main exposures were water pipe smoking and caffeine intake during pregnancy both were measured on the first phase of the BAPC. Water pipe smoking during pregnancy (Yes regular/Yes often/No) was measured by a checklist recommended by the WHO (15) and was merged into Yes/No answers. The checklist was validated by a group of healthcare professionals and epidemiologists while the reliability was checked on a subset of BAPC subjects (n=25, Cronbach`s alpha=0.78). The checklist also contained additional information on age at smoking initiation, smoking duration, and number of water pipe sessions per day, and Environmental Tobacco Smoking (ETS). Due to the unavailability of a standard checklist to measure dietary caffeine intake, Bunker categorization of caffeine content of beverages was used as a guideline(16). Accordingly, a checklist was designed and validated by a team of nutritionist, epidemiologist and gynecologist to measure dietary intake of caffeine. The checklist contained a set of questions on daily intake of any type of caffeinated beverages available in the local market (including black coffee, instant coffee, black tea, green tea, hot chocolate, soft drinks) and caffeinated medications (e.g. painkillers). The reliability was further checked on a subset of BAPC subjects (n=15, Cronbach`s alpha=0.64). The cumulative daily dose of caffeine was then dichotomized to normal (0-99 mg/day) and high (>100 mg/day) groups (17). Based on the recommendations to receive at least nine prenatal visits by the national guideline for pregnancy healthcare package, prenatal care visit was defined as number of prenatal visits to healthcare center and/or gynecologist office to receive care (regular/irregular). Monthly expenditure as a proxy of socio-economic status was defined as average monthly of usual expenses of household during the last six months on housing, food, clothing, and healthcare.
Confounder selection was based on the Change-In-Estimate (CIE) strategy. The CIE selects covariates on the basis of how much their control changes exposure effect estimates, i.e. amount of confounding by the covariate. CIE strategy is recommended over the classic significance testing of the covariate coefficient since 1970 (18). Suppose RRa and RRu denote the estimated risk ratio with and without adjustment for the covariate; then RRa/RRu is traditionally used to judge change importance. By this strategy, an "important covariate" was determined as whether the change in the exposure effect estimate from adjusting for the covariate falls outside an interval of practical equivalence; e.g., 0.91 < RRa/RRu < 1.1 (which is the 10%-change rule for the risk ratio modified to be proportionally symmetric) (19). Based on the CIE strategy, duration of water pipe smoking, maternal education, intake of iron supplement, infant sex, preterm birth, history of LBW infant, and monthly expenditure were included in the final regression model. RRa for the effects of the main exposures on LBW were calculated using Modified Poisson regression models (20). The Miettinen formula was applied to calculate PAFs for caffeine intake and water pipe smoking (12, 21). Accordingly, we estimated the PAF from the estimated RRa derived from the modified Poisson regression model for the exposure of interest (water pipe smoking and caffeine intake, both as dichotomous variables). The prevalence of exposure among cases (pc) was estimated as 22.3% for water pipe smoking and 67.63% for caffeine intake equal or more than 100 mg/day. The PAF finally estimated as: PAF = pc(1 −1/RR)(12).
GIFs were calculated using the following formula:
Where, Pi denoted the proportion of the population in exposure category i (fact) (8.59% for water pipe, 56.98% for high caffeine intake). Pi` denoted the proportion of the population in exposure category after an intervention or other change (counter fact). Therefore, Pi` for water pipe was set as 3% as the estimated national prevalence of water pipe. To set Pi` for caffeine intake, we used the recommended dose of 100 mg/day caffeine in pregnancy by the world health organization as the safe threshold; hence, we hypothesized that an effective intervention would successfully decrease the proportion of women with high intake of caffeine to 14.9%. Finally, RRa denoted adjusted relative risk derived from the modified Poisson regression model (13). GIFs were calculated based on a series of proposed action plans for: a) decrease caffeine intake to less than 100 mg/day in subjects with excessive intake of caffeine; and b) decrease prevalence of water pipe smoking to the estimated national prevalence (i.e. 3% among 25-54 years old Iranian women(7)). All the analyses were performed using Stata version 13 (Stata Corp., College Station, TX, USA). P-values less than 0.05 were considered statistically significant for the final model.