Ziaee and colleagues24 used HR-SF-ICPMS, as we did in this study, to measure the mean concentrations of cobalt and chromium ion levels in 10 maternal and umbilical cord blood samples in women with Birmingham MOM hip-resurfacing prostheses (Smith & Nephew, Warwick, United Kingdom). Nine of those patients had a unilateral resurfacing and 1 patient had bilateral-resurfacing prostheses. The mean maternal age was 31 years, and mean duration between hip resurfacing and delivery was 53 months. Ten normal controls were also tested with a mean maternal age of 30.9 years. The authors found that the mean cord blood level of cobalt in the study patients was 0.83 ng/mL, significantly higher (P < .01) than cobalt levels in the control group, which measured 0.33 ng/mL. The mean cord blood levels of chromium in the study and control groups were 0.37 ng/mL and 0.19 ng/mL, respectively. No children were reported to have evidence of congenital anomalies. Similar to our findings, they noted a modulatory effect on the transfer of metal ions across the placenta in patients with MOM prostheses.24 They reported the relative levels of cobalt and chromium in offspring to be 60.4% and 29.4% of the maternal ion levels, respectively. Control-group infants had mean cobalt and chromium levels that were 98.5% and 97.2% of mean maternal levels, respectively.
The transfer of metal ions across the placenta in control subjects is an expected finding because cobalt and chromium are essential trace elements required by the developing fetus. Rudge and colleagues25 estimated a transplacental transfer rate of 45% for cobalt in a series of 62 paired samples of maternal and cord blood. DeSouza and coauthors26 reported a series of 3 patients with MOM hip resurfacings who had the prosthesis in situ during pregnancy and found no teratogenic effects of metal ion transfer across the placenta. Umbilical cord blood chromium levels were less than 25% of the maternal serum levels and cord blood cobalt levels were approximately 50% that of maternal blood.26 In an animal experiment, Wallach and Verch18 also reported that maternal chromium levels can be decreased because of placental uptake.
Ziaee and colleagues24 tested metal ion levels using whole blood in contrast to serum, as we did in the present study. Daniel and coauthors16, who reported on the validity of serum levels as a surrogate measure of systemic exposure to metal ions in hip replacement, suggested that serum and whole blood metal ion levels cannot be interconverted because metal within cells are not in dynamic equilibrium with extracellular levels. They concluded that serum metal ion concentrations are not a useful surrogate measure of systemic metal ion exposure based on the wide variability seen in normalized and Bland-Altman scatterplots.16 However, it is important to note that Bland-Altman plots are user-dependent in determining significance, and results can vary based on the parameters tested. A high correlation does not automatically imply that there is a good agreement between 2 methods because a widespread sample could influence results. Whole blood analysis requires more processing steps, thus providing an increased chance of contamination and variability compared with serum metal level analysis. In our experiences, serum metal ion analysis has been shown to have accurate and reproducible results in clinical situations.2,4
While there is insufficient literature that specifically studies the effects of elevated metal ion levels on maternal and fetal subjects, there have been no reported negative effects in human babies even when maternal ion levels are elevated enough to be associated with ALTR. A case report by Fritzsche and colleagues27 reported a mother with bilateral MOM THA, a recurrent pseudotumor, and high blood levels of chromium (39 ng/mL) and cobalt (138 ng/mL) at 12 weeks gestation. The child was born at 38 weeks gestation with cord blood chromium and cobalt levels of 2.1 ng/mL and 75 ng/mL, respectively. The infant’s metal ion levels remained elevated at age 8 weeks with a chromium level of 2.5 ng/mL and cobalt level of 13 ng/mL and no signs of toxicity by age 14 weeks. In an animal model, Saxena and colleagues28 found that chromium in the hexavalent form passed through the placenta in mice and rats that were fed high doses of potassium dichromate. Trivalent chromium was not found to cross the placenta. In a follow-up study, Junaid and coauthors29 investigated the effects of elevated chromium levels in female mice given potassium dichromate in drinking water on days 14 to 19 of pregnancy. Animals receiving high-dose chromium had significantly higher incidences of postimplantation loss along with subdermal hemorrhagic patches and reduced ossification.29 Cobalt has not been shown to be teratogenic or cause fetotoxicity in a rat animal model given daily doses of as much as 100 mg/kg cobalt (II) chloride on days 6 to 15 of gestation.30