This work investigated patient’s consumption habits in regards of food and beverages from plastic packaging within the CGATE cohort, aiming on the specification of EDC exposure during pregnancy and the associations with changes of fetal birthweight and pregnancy duration.
BPA and phthalates are known for causing epigenetic modifications of fetuses and germ cells and thus might lead to negative fetal programming (16, 17). Moreover, phthalates affect thyroid metabolism and influence urine thyroxine levels. Johns et al. found an inverse correlation between 11 measurable phthalate metabolites in urine and the concentrations of fT3 and fT4, which was increasing with duration of pregnancy (2). Hypothyroidism might lead to mental retardation with potentially severe disability and spasticity of the child, but might also result in an increase of birthweight (18, 19).
The EARTH study including 346 patients examined pre-conceptual and prenatal urine samples in concerns of their bisphenol A and S concentration and observed an inverse relationship between bisphenol concentration and birthweight; high bisphenol levels in pre-conceptual urine were associated with an average weight reduction of 119 g (95% CI: -212; -27) and increased bisphenol concentrations in prenatal urine revealed a decrease of 75 g (95% CI:-153; 2) (20).
Within the ALSPAC study 447 mother-daughter dyads were investigated. Elevated maternal serum concentrations of perfluorooctanoate and perfluorohexane sulfonate were correlated with 133 g (95% CI: -237; 30) or 108 g (95% CI: -206; 10) lower birthweights of girls (10).
Controversially, a study from Spain analyzing data of 488 mother-child pairs from the INMA-Sabadell birth cohort found that with increasing urine concentrations of mono-benzyl phthalate femur length was increasing by 3.7% (95% CI: 0.75; 6.63) within 20 to 34 weeks of gestation. Additionally, birthweight among boys was 48 g (95% CI: 6; 90) higher. Interestingly an inverse correlation with birthweight of girls (–27 g, 95% CI: –79; 25, interaction p = 0.04) was observed (5). However, our results didn’t reveal a statistical significant change of birthweights among individuals with increasing plastic consumption habits during pregnancy.
Further statistical analyses of CGATE data regarding the correlation of increasing food and beverage consumption from plastic packaging or cans with pregnancy duration did not show a significant association, besides Tetra Pak with a statistically significant pregnancy prolongation, highlighting that pregnancy duration might though had been affected by exposure to EDCs.
In German supermarkets, many dairy products, fruit juices and even drinking water are retailed in paperboard boxes referred as Tetra Pak. The inner layer of these beverage cartons is laminated with a thin plastic film (21). A Chinese study by Huang et al. including 207 patients analyzed the concentrations of 15 different phthalates in the cord blood after delivery and found, that an exposure to phthalates (except to dicyclohexyl phthalate) was statistically significant associated with a decrease of pregnancy duration and with PTB (6). Padmanabhan et al. investigated 40 patients in Michigan and found no association between maternal EDC levels and pregnancy duration (11), which is in accordance with a study from Wolff et al. including a cohort of 367 patients from New York City (22). Within a collective of 60 individuals from Mexico City, Cantonwine et al. found, that elevated BPA urine concentrations during pregnancy had an odds ratio of 2.5 (95% CI: 1.1; 6.0) for occurrence of PTB before 37 weeks of gestation (23). Another study by Cantonwine et al. investigated 130 PTB cases and 352 term controls in Birmingham and Boston. Mother's urine was tested for BPA concentration at four time points during pregnancy and had no significant association with PTB (OR = 1.21, 95% CI: 0.79; 1.85). However, stratified analyses of sexes revealed a significant correlation of BPA with PTB in girls (OR = 1.8, p-value = 0.04, 95% CI: 1.02, 3.13) (12).
Controversially, a study from 2009 by Adibi et al. examining 300 patients in the United States found an association between phthalate concentration and longer duration of pregnancy. They observed a pregnancy prolongation by 1.1 to 1.3 days. This association was even stronger, when comparing the concentrations of phthalate metabolites in individuals at the 75th percentile and the 25th percentile (2.3 days, CI: 1.4; 3.3) (24).
Based on the CGATE data it can be stated, that there was no median "excessive" consumption of food from cans and plastic packaging, which becomes evident after statistical analysis of question 2 in the pregnancy diary, where option "(almost) never" was chosen most often. Thus, the overall exposure of our patient collective to EDCs might rather have been intermediate to low. Accordingly, change of fetal birthweight was not statistically significant within this study population.
Two Italian research groups investigated bisphenol concentrations of most popular beverages packed in cans, plastic containers, glass bottles and Tetra Pak in Campania province (Italy) and detected, that 100% of milk products contained BPA, whereas BPA was only found in 57% of carbonated and 50% of non-carbonated drinks. Interestingly, dairy products showed the highest BPA levels, which might be explained by precipitation of bisphenols through presence of milk lipids. Within the groups of carbonated and non- carbonated beverages cans showed highest BPA concentrations, followed by plastic packaging and Tetra Pak. Liquids from glass bottles were never contaminated with bisphenols (25-27). Consequently, beverages packed in Tetra Pak seem to have lowest EDC concentrations among all frequently used plastic packaging materials. This might be an explanation for observed pregnancy prolongation within the group of frequent Tetra Pak use in CGATE, as this subgroup regularly consumed liquids from a more “harmless” packaging source.
Limitations of this study are missing analyses of maternal urine/serum or fetal cord blood and shortage of the patient questionnaire to exactly determine EDC exposure. Strengths are the prospective cohort design, the high number of participating individuals, simplicity of the patient questionnaire, and especially the “freedom” to keep a pregnancy diary to avoid unnecessary and stressful study visits.