Discussion

In our study, there was no direct association between maternal and fetal element levels and fetal birth defects when evaluated collectively. Copper and magnesium levels were significantly different (p < 0.03 and p < 0.01, respectively) based on the geographic locations of mothers and offspring in the Jackson, MS, area.

Fetal birth defects affect approximately 3% of all pregnancies, accounting for 20% of all infant deaths [9]. The suspected factors causing these birth defects range from genetic to environmental causes. Many prior studies have examined the relationship between essential and toxic elements and long-term neurodevelopmental outcomes; however, studies involving environmental exposure and structural birth defects are less robust. Zeyrek et al. aimed to evaluate the relationship between serum micronutrient concentration and occurrence of neural tube defects and found a significantly higher mean copper concentration in the maternal and umbilical cord blood samples of their study participants with known neural tube defects [11]. Elevated concentrations of molybdenum may also be associated with a reduced risk for orofacial clefts [12]. Increased cobalt levels are associated with a decreased risk for neural tube defects, as well as decreased risk with increased levels of the six essential trace elements, suggesting a protective effect [13]. Numerous animal studies have shown teratogenicity with maternal cadmium exposure and orofacial clefts in the offspring [10,14,15]. Environmental exposure can also lead to DNA damage, with Wang et al. demonstrating a correlation between folate deficiency and DNA damage in chromium workers [15].

Heart defects are one of the most common congenital birth defects, and a recent meta-analysis found significant associations between arsenic, cadmium, mercury, and lead exposure during pregnancy and an increased risk of congenital heart defects [10]. The analysis included 13 studies, and pooled odds ratios for arsenic, cadmium, mercury, and lead were 2.12, 1.30, 1.22, and 2.30, respectively, for total congenital heart defects.

Importantly, heavy metals have been shown to not only cause birth defects but also contribute to other adverse pregnancy outcomes. Consistent with prior studies, Bommarito et al concluded that trace urinary metals may disrupt placentation and be associated with preeclampsia [2]. Likewise, lead and cadmium exposure is associated with a higher incidence of preterm birth [9].

Regarding geographic incidence in the Jackson, MS metropolitan area, there are no prior studies examining birth defects and environmental factors. A prior study at our institution did demonstrate an increased incidence of the fetal birth defect gastroschisis between 2000 and 2008, but a suspected cause for this increase was not hypothesized by the authors [16]. Overwhelmingly, the evidence indicates a need for further research into birth defects and adverse pregnancy outcomes associated with prenatal exposure to essential and toxic elements. While some of these factors are non-modifiable, it is thought that environmental exposure may serve as a point of intervention in the prevention of both maternal and neonatal morbidity and mortality [17].

This study is the first in our geographic area to evaluate trace and toxic element exposure on the development of fetal birth defects. The study was strengthened by the prospective nature of the study, as prenatal birth defects were identified in utero. The limitations of the study include its small sample size and the wide variety of birth defects that we evaluated due to an overall low prevalence of fetal malformations. Another limitation is the collection of maternal and neonatal blood samples after the period of organogenesis. In future studies, the measurement of these essential and toxic elements would ideally be analyzed during the period of organogenesis.