Materials and methods

A prospective case-control study involving 23 patients was conducted to measure maternal and fetal serum concentrations of essential and toxic elements. The study was approved by the Institutional Review Board at the University of Mississippi Medical Center (approval number: 2016-0328). The collection of samples occurred between December 12, 2018, and April 3, 2019. Patients delivering at the University of Mississippi Medical Center in Jackson, MS, with prenatally diagnosed birth defects (N = 18) were recruited and consented in writing before delivery. Control participants with no prenatally diagnosed birth defects (N = 5) who underwent fetal anatomic survey at our institution were selected, recruited, and consented in writing for comparison. These controls were screened and consented while on labor and delivery when presenting for delivery after it was confirmed that a normal fetal anatomic survey was performed at 18-22 weeks of gestation. All study participants had fetal anatomic surveys performed via ultrasound by maternal-fetal medicine specialists and delivered at the University of Mississippi Medical Center, Jackson, MS.

Inclusion criteria for all patients included term gestation and collection of maternal venous blood and fetal umbilical cord blood. Exclusion criteria were non-collection of cord blood or inadequate collection. Inclusion criteria for controls included term gestational age with a completed anatomy scan. Exclusion criteria included known chromosomal abnormalities (birth defect or BD group), multi-fetal gestation, pre-existing chronic medical condition, preterm gestational age (control), inadequate prenatal care (no anatomy scan), and intravenous magnesium infusion.

Demographic information was extracted from each patient’s electronic medical record. Maternal and fetal serum concentrations of essential and toxic elements were measured at delivery and analyzed for associations with fetal birth defects, geographic location, patient demographics, and perinatal outcomes.

Essential elements that were measured included calcium, copper, lithium, magnesium, manganese, molybdenum, selenium, strontium, and zinc. Toxic elements that were measured included arsenic, barium, cadmium, cobalt, lead, mercury, nickel, platinum, thallium, and uranium. Umbilical cord blood was analyzed for 20 inorganic elements by The Great Plains Laboratory, Inc., located in Lenexa, KS. According to the lab protocol, The Great Plains Laboratory analyzes the elements in whole blood by inductively coupled plasma mass spectroscopy following specimen digestion with nitric acid in a closed-containing microwave oven system. The procedure measures the total concentration of an element in whole blood, regardless of biochemical form or partitioning of the element in blood fractions.

Comparisons and p-values between element levels and development of fetal birth defects were evaluated using the Mann-Whitney U test using R Software, version 3.3.1 (R Foundation for Statistical Computing, Vienna, Austria). Secondarily, baseline values of the essential and toxic elements for gravid mothers in the metro Jackson, MS, area and surrounding areas were compared between the groups.