• Supporting Scientific Evidence
• Helpful Actions

Research has already identified a link between pre-natal/birth complications and increased risk of developing schizophrenia in offspring, particularly for those who may carry genetic susceptibility. Some studies have suggested that maternal-fetal Rh incompatibility, which arises when a mother with Rh negative blood type produces antibodies against the Rh proteins in her Rh-positive fetus's blood, may be a specific complication that can increase risk of schizophrenia, possibly by increasing risk of hypoxia (oxygen shortage) to the developing fetal brain.

Hollister et al (1996) found a 2-fold increased rate (2.1% prevalence) of schizophrenia in a retrospective study of RH incompatible infants, as compared to an expected rate of 0.8% schizophrenia in RH-compatible subjects. This 2-fold risk was recently replicated by Insel et al (2005); however, their calculated risk was only stastically significant for male babies.

Other authors who have studied this relationship (Kraft et al, 2004) point out that the risk increases with number of births, as a woman who is Rh negative will start producing antibodies during the first exposure (pregnancy with an Rh-positive fetus), but will only build up sufficient antibody numbers for an immune response against subsequent Rh-positive fetuses. These authors, re-analyzing data collected by a previous study, found: "[the]relative risk of schizophrenia in the second- and later-born RHD MFG-incompatible children is 1.7, consistent with earlier estimates."

--risk higher for male babies

--incompatibility risk (and therefore schizophrenia risk) increases in the later, of a series, of births (Kraft et al 2004).

--risk seems to be caused be "adverse prenatal environment" rather than a close association/linkage between RHD gene locus and any gene implicated in schizophrenia onset (Palmer et al 2002).

-Hollister et al (1996) found a 2-fold increased rate (2.1% prevalence) of schizophrenia in a retrospective study of RH incompatible infants, as compared to an expected rate of 0.8% schizophrenia in RH-compatible subjects

Helpful Actions: If you have a history of schizophrenia in your family, it may be wise to know whether you are RH positive or negative, and whether your partner is RH positive or negative. Only women who are RH negative, and who have an RH positive fetus (more likely if the father is RH positive), has the possibility of reacting to her fetus with antibodies, known as Rh-sensitization.

If you are Rh negative and you have a history of schizophrenia in your family (or you have another reason to suspect you or your offspring are susceptible), talk with your doctor about preventative measures you can take to avoid an Rh sensitization immune reaction during pregnancy.

See 'Rh Sensitization' from the Blue Shield of California for more information on identification, screening, and preventative measures.

Supporting Research (a sample):

• Maternal-fetal blood incompatibility and the risk of schizophrenia in offspring. Schizophr Res. 2005 Jul 7
• RHD maternal-fetal genotype incompatibility and schizophrenia: extending the MFG test to include multiple siblings and birth order.
  Eur J Hum Genet. 2004 Mar;12(3):192-8.
• RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility. Am J Hum Genet. 2002 Dec;71(6):1312-9. Epub 2002 Nov 18
• Rhesus incompatibility as a risk factor for schizophrenia in male adults. Arch Gen Psychiatry. 1996 Jan;53(1):19-24