Incredible pharmaceutical residues in human milk in a cohort study from Şanlıurfa in Turkey

https://doi.org/10.1016/j.etap.2020.103502Get rights and content

Highlights

  • Almost all breastmilk samples had some unexpected veterinary drug residues.

  • Tolfenamic acid residues were seen in more than half of the breast milk samples.

  • Beta-lactam and quinolone antibiotics were the most frequently detected residues.

  • Pharmaceutical use in all veterinary and agricultural areas should be supervised.

Abstract

Maternal milk is essential for optimum growth and development of an infant. The aim was to examine the presence of pharmaceutical residuals in breastmilk. This cohort study enrolled 90 healthy mother-infant pairs at 5−14 days after delivery and a control examination was performed 4–8 weeks later. Milk samples were taken at both visits. RANDOX Infiniplex kit performed residual analysis. More than half of mothers (54.4 %) had anti-inflammatory drug residues in at least one milk sample: those were 52.2 % for tolfenamic acid and 2.2 % for meloxicam and 1.1 % for metamizole. The most frequent residue group included the beta-lactam antibiotic group, which was detected in 93.3 % of mothers’ milk. The second one was the quinolone group (81.1 %). One-third of mothers expressed nitroxynil and one-fifth polymyxin in at least one sample. Almost all mothers had some unexpected drug residues in their milk. Additional studies from other countries can display maternal environmental exposures.

Introduction

After the application of drugs for therapeutic or prophylactic purposes or feed additives in animal husbandries, the trace amount of drugs is shown to deposit in animal tissues and pass to their milk and eggs in unaltered or metabolized form(Leeman et al., 2007; Prescott, 2017; Sachi et al., 2019). These unexpected drug residues in foodstuffs pose a potential threat to global public health, such as antibiotic resistance, hypersensitivity, teratogenicity, and changes in the intestinal microbiota of the exposed living organisms(Bacanli and Basaran, 2019; Beyene, 2016; Ortelli et al., 2018). Therefore, a withdrawal time is recommended in veterinary medicine (Chevance et al., 2017). However, the characteristics of hosts which pharmaceuticals are given (age, sex, and health status such as renal or hepatic failure), the dosage, physicochemical properties of pharmaceuticals, the interaction with other chemicals, and the administration route can influence withdrawal time and residual content (Beyene, 2016; Chevance et al., 2017; EU, 2019; Leeman et al., 2007; Zeng et al., 2017). Out-of-counter and extra label drug use is also a problem for the residuals (Hajjar et al., 2007; Yazıcı et al., 2007). Therefore, supervising food and feed for animal consumption is recommended (Gıda Tarım ve Hayvancılık Bakanlığı, 2017; WHO, 2018). Despite all this, each pharmaceutical preparation given may also contaminate the environment and can reach the human by polluting the soil and groundwater (Charuaud et al., 2019). And, pharmacopollution is a global public health problem (EFSA Panel on Biological Hazards, 2017; Pereira et al., 2017). Finally, it was shown that pregnant women and lactating women could transmit a trace amount of their contaminants to their fetuses and infants through the placenta and human milk (Dursun et al., 2016; García-Lino et al., 2019).

Due to the possibility of transfer of pollutants encountered by the nursing mother, human milk is a valuable matrix for assessing the mother’s environment (García-Lino et al., 2019; Yalcin et al., 2020). There are some studies evaluating pollutants in breastmilk in Turkey (Dursun et al., 2016; Memis and Yalcin, 2019; Yalcin et al., 2020, 2015). Besides, studies from Ankara in West Anatolia Region and from Eskişehir in the East Marmara region in Turkey reported unexpected veterinary drug residues in human milk (Dinleyici et al., 2018; Ergen and Yalcin, 2019). However, the status in Şanlıurfa from the South-eastern part of Turkey is not known. In addition, there is no published longitudinal study evaluating changes in the presence of drug residues in breast milk during the lactational period. The contents of maternal milk, which meet all the needs of her own baby, change both during the same day and with lactational age (Eriksen et al., 2018). It is hypothesized that maternal exposure may vary with lactational age and there may be intra-individual differences in contaminants. The aim of this study is to examine the presence of pharmaceutical residuals both on Day 5−14 after birth and 4–8 weeks later in Şanlıurfa, South-eastern part of Turkey. By this way, types of residues and changes in expression of drug residuals between early- and mid-lactational stages can be evaluated.

Section snippets

Methods

The cohort study covered lactating mothers with single newborns at 5−14 days after delivery from Özel Şan Hospital in Şanlıurfa between August 2017 and March 2018. Voluntary mothers who wanted to continue breastfeeding up to 4 months postpartum and give two-breastmilk samples on admission and at 5−10 weeks after birth were enrolled for the study. Mothers who had taken any medication such as antibiotics or anti-inflammatory drugs for the last 10 days at weeks 5−10 were excluded from the study.

Results

The mean age was 27.9 ± 5.3 years for mothers and 7.1 ± 2.1 days for infants on admission. Overall, 90 volunteer lactating mothers were enrolled at 5−14 days after delivery. Three mothers had gestational diabetes, and two mothers had hypothyroidism, and five mothers had anemia during the gestational period. Nearly half of the mothers reported either smoking or environmental smoke exposure during the study period (Table 1).

Almost all mothers had taken antibiotics (ampicillin-sulbactam or

Discussion

The results of this study showed that almost all human milk samples were contaminated with unpredictable drug residuals in Şanlıurfa. Maternal drug intake had no role in the drug residuals as recorded in maternal history. This condition might be due to maternal environmental contaminants. A systematic review from China showed very high antibiotic detection rates of nearly 100 % for soil, surface water, and coastal water (Lyu et al., 2020). The dominant antibiotics observed were tetracyclines,

Conclusions

Although mothers had no history of drug use, almost all mothers showed some unexpected drug residues in their milk. Besides, some residues even belonged to pharmaceuticals which were not permitted for human use. Remnants of some pharmaceuticals were present in one or both samples of mothers’ milk during follow-up period. Intra-individual changes in human milk contaminants showed differences in exposures during follow-up period. Further human milk studies with maternal food consumption and

Funding

Financial support for test kits and materials of milk multidrug residues were made possible by Hacettepe University Scientific Research Projects Coordination Unit (project no. THD-2017−15742). But this organization was not involved in designing the concept of this study, analysis, interpretation of data and in preparation of the manuscript draft. This organization also did not cover any fund for publication.

Authors’ contributions

SSY contributed to the conception or design of the work. BG contributed to the acquisition of data. SY contributed to the analysis and interpretation of data for the work. SSY prepared the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

Ethical approval

Ethics Board of Non-Interventional Clinical Research from Hacettepe University approved the protocol. All procedures in the study complied with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent was obtained from the mothers included in the study.

Availability of data and materials

For access to the files, please send an e-mail request to [email protected].

Declaration of Competing Interest

The authors report no declarations of interest.

Acknowledgements

The authors are grateful to all volunteers for participating in this study.

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