A prospective nested cohort study was conducted to determine the effect of caffeine consumption during pregnancy on low birth weight. One-day nonconsecutive 24-hour recall was done to collect data related with caffeine for all pregnant mothers. In addition to this, 24-hour recall method was repeated for 21% pregnant mothers. The study found that 26.2% of pregnant women had a daily caffeine consumption more than or equal to 200 mg/day. The median caffeine consumption in unexposed was 79mg (IQR = 86) per day with minimum zero and maximum of ninety nine. In addition to this, the median caffeine intake in exposed group was 307 mg (IQR = 102) per day with minimum of two hundred one and maximum 478 mg/day.
After adjustment for possible confounder, caffeine consumption, height and wealth status were significant associated factors for low birth weight.
The risk of low birth weight was four times more likely to occur in exposed than unexposed group (< 200 mg a day).
The postulated mechanism by which caffeine consumption result in low birth weight were, caffeine absorbed immediately (after 45minutes) from gastrointestinal and passes placenta across freely (9). Additionally, fetuses don’t metabolize it well (10) and caffeine has been increasing catecholamine (11) which may causes utero-placental vasoconstriction and then fetal hypoxia, which possibly cause fetal growth and increases cellular cyclic adenosine mono-phosphate which may affect cell development and result in low birth weight (17).
Based on Bradford hill criteria there were effect of caffeine consumption on low birth weight. It fulfills some of the criteria, causality like dose response relationship. The risk of low birth weight was three times more likely to occur in pregnant mothers who consumed caffeine 151-300mg/day than (0-150mg/day) (ARR = 3.10; 95%CI: 1.12, 8.57). In similar manner, The risk of low birth weight was ten times more likely to occur in pregnant mothers who consumed caffeine greater or equal to 300mg/day than (0-150mg/day) (ARR = 9.52,95%CI:- 3.68–24.58). From this dose response relationship, we can conclude that as the dose of caffeine consumption increase the probability to have low birth weight neonate also increase.
Concerning with temporality, the cause is caffeine, outcome is low birth weight. There were many studies with different study design and setting which had consistent finding. There was strong association between caffeine and low birth weight. The biological plausibility of caffeine effect on low birth weight was caffeine passes placenta and form vasoconstriction which limit nutrient passing from mother to fetus, then resulted in low birth weight. This study was not fulfilling the criteria of specificity, because there were other factors which result in low birth weight. Caffeine was not the sole risk factor to low birth weight.
Based on literatures, 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 (18–23). According to a reports from literatures, a higher maternal caffeine intake (more than 50 mg per day) during pregnancy was associated with a higher risk of delivering low birth weight infants compared to no intake or very low intake (21, 23). This risk appears to increase linearly as caffeine intake increases (24, 25).
Other consistent reports from observational studies, the risk of having low birth weight was high for high caffeine consumption compared to moderate and low consumption. It has been established that each 100-mg/day increase in maternal caffeine intake (about one cup of coffee) was associated with 13%greater risk of having low birth weight (26).
Study done in united states shows, When comparison was made with women who had no caffeine exposure, the relative risks of low birth weight after adjustment for confounding factors were 2.3 (95% CI 1.1–5.2) for 151–300 mg/day. Excessive daily caffeine intake( > = 200 mg/day) has been associated with an increased risk of birth to SGA or LBW (< 2500 g) babies (27).
On the other hand, the recommendation of Marches of Dimes, American college of obstetrics and gynecology, American pregnancy association, Food and drug administration ,cable news network’s and American food safety which proposed greater than 200mg/day caffeine result in low birth weight so that caffeine should be limited to less than 200mg/day.
However, systematic review was done by WHO on effect of caffeine consumption on pregnancy outcome specifically on low birth weight. Based on this review, it developed context-specific recommendation guideline and generate three categories of certainty evidence level. These were very low, low and moderate certainty evidence level. Based on this certainty evidence level, very low certainty evidence level shows that less than 150mg per day of caffeine consumption during pregnancy may be associated with fewer low birth weights (5 none randomized studies). In similar manner low certainty evidence level indicated between 150-300mg/day caffeine consumption probably associated with low birth weight (7 none randomized studies). On the other hand, moderate certainty evidence level revealed caffeine consumption greater than 300mg/day associated with low birth weight. The developed guideline revealed that greater than or equal to 300mg/day of caffeine consumption during pregnancy associated with low birth weight with moderate certainty evidence level. According to WHO recommendation, only moderate certainty evidence level is considered until high certainty evidence level will be updated. In accordance with this guideline development standards, this recommendation will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.
Furthermore, different studies which were done at different western country didn’t find out any associations between caffeine consumption and low birth weight for daily caffeine consumption greater than 200mg/day, this may be due to studies measured birth weight at four week after delivery, this may be increase birth weight (28). In addition to this study used food frequency questionnaire for caffeine consumption, this might be lead to recall bias.
Additionally, the risk of low birth weight was two times more likely to occur in short stature pregnant mothers than normal height. Maternal height might be associated with LBW even though it is not completely understood how. This may be contributed by both genetic and environmental factors. Short-statured women are more likely to pass on to their fetus a genetic predisposition for smaller growth (29). Anatomical factors may also play a role in the risk, as short stature can be associated with a smaller uterus, and can therefore impose physical limitations (30) on the uterine, placenta and fetuses growth. Furthermore, height is correlated to pelvic size, and therefore, a short-statured woman may have a smaller pelvis, which may result in its earlier filling(29). Maternal short stature may also be associated with a lack of nutrients, resulting in decreased fetal growth or duration of gestation, (30).
Concerning about wealth status, the risk of developing low birth weight were four, five and five times more likely to occur in middle, rich and richest pregnant mothers than poorest wealth status respectively. As woman wealth status increases, the chance of buying coffee and consuming caffeinated beverages might increase. In other hand, developing countries, women of low socioeconomic status are likely to be shorter and thinner and to consume fewer calories and other nutrients during pregnancy and result in prematurity or IUGR and low birth weight(31).
Regarding the overall implication of this study, excessive caffeine (> 200mg per day) consumption result in low birth weight. Caffeine in coffee alone would account for 4% of cases of low birth weight (32). In Ethiopia neonatal death associated by low birth weight was high (3.63%) of all death (33). Therefore, greater than two hundred milligram per day caffeine consumption could be addressed in order to prevent neonatal death associated with low birth weight.
Strengths
As strengths, since it was community based prospective cohort study, the finding of the study could detect cause-effect relationship for effect of caffeine consumption on low birth weight and also generalize able to all pregnant women living in the study area. All days of the week were considered in order to control days of the week effect. In addition, around twenty (21%) percent was repeated 24-hour recall which is the recommended methods for the assessment of exposure with in risk assessment processes was done to control within person variation of caffeine intake. Regarding data collection tools this study was used different methods like structured questionnaires, anthropometry measurement, and biochemical measurement. Fourthly, first trimester ultrasound was used to estimate gestational age which was appropriate than second and third trimester ultrasound.
Limitations
The study findings should be interpreted and utilized by considering the following limitations. First, the level of caffeine concentration was obtained from previously done researches. However, the concentration of caffeine may vary based on the roasting and brewing process. Due to these reasons it might not give a perfect estimation of daily caffeine intake. Second, substances use such as alcohol and tobacco use are considered as taboo in the study area. As a result, the respondent might not report their consumption and this might introduce social desirability bias and this might not be enables researcher to control confounder’s effect of alcohol and tobacco on low birth weight. Third, physical activity and dietary Assessment of the pregnant women was not controlled for confounder.