Prenatal and perinatal factors linked to later psychosis onset

Paolo Fusar-Poli

Researchers have uncovered several prenatal and perinatal factors associated with later psychosis onset, according to results of a systematic review and meta-analysis published in The Lancet Psychiatry.

“If psychosis originates early in life, early detection of this condition is the most promising way not only to improve treatment for it, but also to prevent it," Paolo Fusar-Poli, MD, PhD, of the department of psychosis studies at King’s College London, told Healio Psychiatry. "Prevention of psychosis would mean restoring the lives of many young people and producing substantial benefits for their families, careers and for the whole society."

Prospective studies conducted since 2002 have shown long-term consequences of prenatal and perinatal hazards on exposed infants. Umbrella reviews established that numerous prenatal and perinatal risk factors are associated with psychosis, as well as with a range of neurological and cognitive abnormalities and other neurodevelopmental and psychiatric disorders. Further, neuroimaging studies revealed that when exposed infants reached adulthood, they exhibited an excess of brain structural and dopaminergic abnormalities similar to those of patients with schizophrenia.

Fusar-Poli and colleagues sought to fill the 2-decades gap in comprehensive, meta-analytical research on the association between prenatal or perinatal risk and protective factors and psychotic disorders. In a database search, they identified cohort and case-control studies that analyzed associations between prenatal and perinatal factors and any ICD or DSM nonorganic psychotic disorder with a healthy comparison group. They extracted variables including study type, sample size, publication year, type of psychotic diagnosis and diagnostic instrument, measure of association and the risk or protective factor.

Their analysis included 152 studies that related to 98 risk or protective factors. Significant risk factors included the following:

• maternal age younger than 20 years (OR = 1.17) and 30 to 34 years (OR = 1.05);

• paternal age younger than 20 years (OR = 1.31) and older than 35 years (OR = 1.28);

• any paternal (OR = 2.73) or maternal (OR = 4.6) psychopathology;

• maternal psychosis (OR = 7.61) and affective disorder (OR = 2.26);

• three or more pregnancies (OR = 1.3);

• herpes simplex 2 (OR = 1.35);

• maternal infections not otherwise specified (OR = 1.27);

• suboptimal number of antenatal visits (OR = 1.83);

• winter (OR = 1.05) and winter to spring (OR = 1.05) season of birth in the Northern Hemisphere;

• maternal stress not otherwise specified (OR = 2.4); and

• famine (OR = 1.61).

The researchers reported various other risk factors, including maternal hypertension and definite obstetric complications not otherwise specified.

Significant protective factors included the following:

• maternal ages 20 to 24 years (OR = 0.93) and 25 to 29 years (OR = 0.92);

• nulliparity (OR = 0.91); and

• birth weights of 3,500 to 3,999 g (OR = 0.9) or more than 4,000 g (OR = 0.86).

Fusar-Poli and colleagues corrected the results for publication biases and confirmed the robustness of these findings for most factors using sensitivity and meta-regression analyses.

“This knowledge advances understanding of psychosis, will facilitate multivariable risk prediction profiling and can help to inform future preventive strategies,” the researchers wrote.

In a related editorial, Mary Cannon, MD, PhD, FRCPsych, of the department of psychiatry at Royal College of Surgeons in Ireland, and colleagues noted a potential intervention strategy for this patient population.

“Although many of the obstetric risk factors for psychosis outlined by Davies and colleagues are not malleable to intervention, there are several possible avenues for preventive strategies,” they wrote. “Improving the number of antenatal care visits would appear to be an achievable goal using tools such as incentivized or outreach prenatal care.” – by Joe Gramigna

Disclosures: Fusar-Poli reports advisory consultancy fees from Lundbeck outside of the submitted work.The other authors report no relevant financial disclosures. The editorial authors report no relevant financial disclosures.