Environmental and dietary exposure to persistent toxic substances (PTS) and trace elements in pregnancy and birth outcomes

Persistent organic pollutants (POPs) and toxic metals are recognised as having effects on health and development in children. These substances are also known to be transferred from the mother to the foetus and neonates through the umbilical cord and breast feeding respectively. In this regard, the growing foetus and new born child are at a greatest risk of the toxic effects of these substances as they are still in their developmental stages. On the other hand, deficiency or excess levels of some trace elements during pregnancy has also been linked to adverse health effects. In this regard, the levels of these contaminants in maternal blood during pregnancy give an indication of the potential risk to the developing foetus.\nMost of the monitoring and studies on effects of persistent toxic substances among pregnant women in relation to reproductive health are conducted in temperate regions, mostly in Europe and America. One important contributor is the Arctic Monitoring and Assessment Programme (AMAP). AMAP started in 1991 and includes monitoring of PTS in eight arctic countries namely Canada, Denmark, Finland, Iceland, Norway, Russia, Sweden and the USA. At the later stage, these studies were also expanded to a few countries in the southern hemisphere. The data on these substances and possible associations with adverse reproductive health effects are scarce, especially in the African settings that include other low- and middle-income countries. POPs (including Polyand Perfluoroalkyl Substances (PFAS) toxic and trace elements have been used in Malawi for a long time. However, to our knowledge, studies on exposure to these environmental pollutants by susceptible groups like pregnant women and its associations on reproductive health outcomes are limited.\nThis thesis is based on data from a cross-sectional study of pregnant women and their offspring in southern Malawi. The study aimed at assessing the predictors for concentrations of POPs (including PFAS) toxic as well as trace elements in pregnant women. Furthermore, this study assessed associations between maternal serum concentrations of these substances and birth outcomes. Data on pregnant women socio-demographic characteristics and neonatal birth outcomes were collected using a questionnaire administered by a trained research nurse. Non fasting venus blood samples were collected using a glass red top vacutainer for POPs analyses.\nSimilarly dark blue vacutainer was used for the collection of a blood sample for toxic and trace elements analyses. Maternal serum PFAS concentrations were analyzed by ultrahigh pressure liquid chromatography tandem-quadrupole mass-spectrometry (UHPLC-MS/MS) and POPs by gas chromatography atmospheric pressure ionisation coupled to tandem mass spectrometers (GCAPI-MS/MS). Inductively coupled plasma mass-spectrometry (ICP-MS) technique was used for maternal blood analyses.\nMaternal age, level of education and parity were the main determinants of exposure to PFAS and POPs. Although the Malawi government banned the use and distribution of DDT over forty years ago, some traces of DDT and its metabolites were still detected in some serum samples; notably, with high concentrations detected in maternal serum samples from urban areas as compared to rural settings. The p, p’-DDE: p, p’-DDT concentration ratio found in this study suggests diet as the main route of exposure for these compounds to pregnant women. \nIn general, Maternal age and area of residence were the main determinants of the concentrations of toxic and trace elements in maternal blood. Furthermore, concentrations of most toxic elements detected in pregnant women were either low or similar if compared to similar studies conducted around the globe. The geometric mean or median concentration of Pb were higher than studies conducted in Ushuaia city in Argentina, Colombia, USA, Canada, Spain, Norway and Japan. Inverse associations were observed between As and Pb versus head circumference and birth length.\nMost of the associations with birth outcomes were relatively weak. Higher concentrations of trans-Nonachlor (t-NC) (p = 0.04), Oxychlordane (Oxy-CD) (p = 0.01) and cis- Nonachlor (cis-NC) (p = 0.05) were associated with smaller neonatal head circumferences. Similarly, increased Perfluorooctanoate (PFOA) (p = 0.04) and Perfluorononanoate (PFNA) (p = 0.001) concentrations were also associated with smaller neonatal head circumferences. However, high concentrations of Perfluorohexane sulfonate (sumPFHxS) (p = 0.05) were associated with bigger neonatal head circumferences. High maternal serum concentrations of PFNA (p = 0.005) and Perfluorooctane sulfonate (sumPFOS) (p <0.001) were associated with a shorter gestational age. Increased concentrations of PFOA (p <0.001) and PFNA (p = 0.005) were associated with reduced birth length, as was SumPFHxS (p = 0.01) with birth weight. The results on PFAS highlight the need to investigate SumPFHxS further as it follows a pattern that is different to similar compounds and cohorts. High maternal blood concentrations of Ni showed weak significance for birth weight, birth length, head circumference and gestational age, all p-values around 0.3-0.5. Increased concentrations of As were associated with smaller head circumference (p <0.001). Similarly, higher maternal blood Pb concentrations were associated with smaller head circumference (p =0.002) and birth length (p =0.016).\nThe results from this study may be used in the identification of specific lifestyles that are associated with increased maternal POPs, PFAS and toxic and trace elements concentrations of women of child-bearing age. Published data from studies on maternal POPs as well as toxic and trace elements concentrations in relation to reproductive health outcomes from the northern hemisphere cannot be directly used in the context of the southern hemisphere. Therefore, assessing the extent of exposure to these substances during pregnancy and its association to reproductive health outcomes in Malawi and other countries in the southern hemisphere is of public health importance.

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