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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study associates TCR exposure with some NDs in children.
Geier
David A
DA
The Institute of Chronic Illnesses, Inc., Silver Spring, MD 20905, USA.
Mumper
Elizabeth
E
Gladfelter
Bambi
B
Coleman
Lisa
L
Geier
Mark R
MR
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000209:etiology*; D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood / Q000209:etiology*; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects; D012189:Retrospective Studies; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000502:physiology*; D018029:Rho(D) Immune Globulin / Q000009:adverse effects*; D012307:Risk Factors; D013849:Thimerosal / Q000009:adverse effects
D011310:Preservatives, Pharmaceutical; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; D013849:Thimerosal