Summary: Over 30 prenatal and postnatal environmental risk factors have been identified for the development of psychosis in offspring. The factors have been split into four categories, including parental and familial, pregnancy, labor and delivery, and fetal growth and development. Significant protective factors are lower maternal age, first-time mothers, and babies with higher birth weights.
Source: NIHR Maudsley Biomedial Research Center
More than 30 significant risk factors have been identified for the development of psychotic disorders in offspring in research led by the NIHR Maudsley BRC. It is the first comprehensive meta-analysis of pre- and perinatal risk factors for psychosis in nearly 20 years.
These prenatal and perinatal environmental risks, meaning risks during pregnancy and seven days after birth, have a significant effect on the likelihood of their child developing psychosis. As a result, researchers suggest women at risk should be screened early on in their pregnancy so that those with these identified risks can be given additional support. The findings have been published in Lancet Psychiatry.
Gathering data from 152 studies published between 1977 and July 2019 and looking at 98 factors, researchers identified 30 significant risk factors and five protective factors.
Psychotic disorders are severe mental illnesses which cause abnormal thoughts, such as hallucinations or delusions, but they can affect each person in different ways. In 2014, a survey found the 6% of people in England said they had experienced at least on symptom of psychosis.
Factors can be split into four categories; parental and familial, pregnancy, labour and delivery, and foetal growth and development. Significant protective factors were mothers being aged between 20 – 29, first time mothers and higher birthweights in babies.
For risk factors, previous mental health conditions in either parents, nutritional deficiencies, low birthweight and giving birth in the colder months were found to increase the probability of a child developing psychosis. Age related risk factors were either parent being under 20, mothers between 30-34 and fathers over 35. Researchers also found that a lack of prenatal care visits poses a risk and marked this as a potential risk factor to combat with outreach campaigns.
This study confirmed the importance of factors during labour and delivery, such as a fetus’ brain being deprived of oxygen and ruptured membranes, which are historically among the most consistently implicated risk factors. Conversely, despite previous studies focusing on infections during pregnancy causing psychosis, this study found significant associations only for HSV-2 and maternal infections ‘not otherwise specified’ and found that influenza had no indication of a significant effect.
This study will help guide future research in the field of psychosis, as well as form the basis for psychosis risk prediction models which could advance preventative strategies.
Dr Paolo Fusar-Poli, Reader in Psychiatry and Youth Mental Health at Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London said: ‘This study is confirming that psychotic disorders originate in the early phases of life with the accumulation of several environmental risk factors during the perinatal and prenatal phases. The results of this study will advance our ability to detect individuals at risk of developing psychosis, predict their outcomes and eventually offer them preventive care.’
Whilst this study focused on the environmental factors there may also be genetic or epigenetic risks factors that are implicated in the onset of psychosis.
Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis
Background Prenatal and perinatal insults are implicated in the aetiopathogenesis of psychotic disorders but the consistency and magnitude of their associations with psychosis have not been updated for nearly two decades. The aim of this systematic review and meta-analysis was to provide a comprehensive and up-to-date synthesis of the evidence on the association between prenatal or perinatal risk and protective factors and psychotic disorders.
Methods In this systematic review and meta-analysis, we searched the Web of Science database for articles published up to July 20, 2019. We identified cohort and case-control studies examining the association (odds ratio [OR]) between prenatal and perinatal factors and any International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) non-organic psychotic disorder with a healthy comparison group. Other inclusion criteria were enough data available to do the analyses, and non-overlapping datasets. We excluded reviews, meta-analyses, abstracts or conference proceedings, and articles with overlapping datasets. Data were extracted according to EQUATOR and PRISMA guidelines. Extracted variables included first author, publication year, study type, sample size, type of psychotic diagnosis (non-affective psychoses or schizophrenia-spectrum disorders, affective psychoses) and diagnostic instrument (DSM or ICD and version), the risk or protective factor, and measure of association (primary outcome). We did random-effects pairwise meta-analyses, Q statistics, I 2 index, sensitivity analyses, meta-regressions, and assessed study quality and publication bias. The study protocol was registered at PROSPERO, CRD42017079261.
Findings 152 studies relating to 98 risk or protective factors were eligible for analysis. Significant risk factors were: maternal age younger than 20 years (OR 1·17) and 30–34 years (OR 1·05); paternal age younger than 20 years (OR 1·31) and older than 35 years (OR 1·28); any maternal (OR 4·60) or paternal (OR 2·73) psychopathology; maternal psychosis (OR 7·61) and affective disorder (OR 2·26); three or more pregnancies (OR 1·30); herpes simplex 2 (OR 1·35); maternal infections not otherwise specified (NOS; 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 NOS (OR 2·40); famine (OR 1·61); any famine or nutritional deficits in pregnancy (OR 1·40); maternal hypertension (OR 1·40); hypoxia (OR 1·63); ruptured (OR 1·86) and premature rupture (OR 2·29) of membranes; polyhydramnios (OR 3·05); definite obstetric complications NOS (OR 1·83); birthweights of less than 2000 g (OR 1·84), less than 2500 g (OR 1·53), or 2500–2999 g (OR 1·23); birth length less than 49 cm (OR 1·17); small for gestational age (OR 1·40); premature birth (OR 1·35), and congenital malformations (OR 2·35). Significant protective factors were maternal ages 20–24 years (OR 0·93) and 25–29 years (OR 0·92), nulliparity (OR 0·91), and birthweights 3500–3999 g (OR 0·90) or more than 4000 g (OR 0·86). The results were corrected for publication biases; sensitivity and meta-regression analyses confirmed the robustness of these findings for most factors.
Interpretation Several prenatal and perinatal factors are associated with the later onset of psychosis. The updated knowledge emerging from this study could refine understanding of psychosis pathogenesis, enhance multivariable risk prediction, and inform preventive strategies.