Neurodevelopmental disorders, maternal Rh-negativity, and Rho(D) immune globulins: a multi-center assessment

Many formulations of Thimerosal (49.55% mercury by weight)-containing Rho(D) immune globulins (TCRs) were routinely administered to Rh-negative mothers in the US prior to 2002.

It was hypothesized: (1) if prenatal Rho(D)-immune globulin preparation exposure was a risk factor for neurodevelopmental disorders (NDs) then more children with NDs would have Rh-negative mothers compared to controls; and (2) if Thimerosal in the Rho(D)-immune globulin preparations was the ingredient associated with NDs, following the removal of Thimerosal from all manufactured Rho(D)-immune globulin preparations from 2002 in the US the frequency of maternal Rh-negativity among children with NDs should be similar to control populations.

Maternal Rh-negativity was assessed at two sites (Clinic A-Lynchburg, VA; Clinic B-Rockville and Baltimore, MD) among 298 Caucasian children with NDs and known Rh-status. As controls, maternal Rh-negativity frequency was determined from 124 Caucasian children (born 1987-2001) without NDs at Clinic A, and the Rh-negativity frequency was determined from 1,021 Caucasian pregnant mothers that presented for prenatal genetic care at Clinic B (1980-1989). Additionally, 22 Caucasian patients with NDs born from 2002 onwards (Clinics A and B) were assessed for maternal Rh-negativity.

There were significant and comparable increases in maternal Rh-negativity among children with NDs (Clinic: A=24.2%), autism spectrum disorders (Clinic: A=28.3%, B=25.3%), and attention-deficit-disorder/attention-deficit-hyperactivity-disorder (Clinic: A=26.3%) observed at both clinics in comparison to both control groups (Clinic: A=12.1%, B=13.9%) employed. Children with NDs born post-2001 had a maternal Rh-negativity frequency (13.6%) similar to controls.

This study associates TCR exposure with some NDs in children.