**2.5 Comprehensive list of risk factors for CP**

A comprehensive list of risk factors for CP does not exist and a number of cases may be devoid of known risk factors. A plethora of epidemiological studies [3, 9–25] worldwide have been done to ascertain risk factors for CP and have reported countless risk factors for CP categorized as antenatal (prenatal), perinatal (natal) or postnatal (postneonatal) in timing. A meta-analysis [29] of 18 studies in China identified six major risk factors for CP during pregnancy namely: advanced maternal age (≥ 35 years), multiple pregnancy, medicine use in early pregnancy, harmful environment, recurrent vaginal bleeding during pregnancy and pregnancy-induced hypertension (pre-eclampsia). A systematic review [26] of 25 articles identified 10 consistent risk factors (statistically significant in each study) for CP in children born at term in wellresourced countries/HICs namely: placental abnormalities, major and minor birth defects, low birth weight, meconium aspiration, instrumental/emergency caesarean delivery, birth asphyxia, neonatal seizure, respiratory distress syndrome, hypoglycaemia and neonatal infections. Another systematic review of paediatric cerebral palsy in Africa [26] reported that the most common risk factors identified in African cohorts were birth asphyxia, kernicterus and neonatal infections. From the foregoing, it is already clear that there are numerous risk factors for CP with variations in the spectrum of risk factors for preterm and term babies (different gestation ages), HICs and LMICs and strength of associations (some strongly correlated and others weakly associated).

*Pre-pregnancy/maternal factors*: low socioeconomic status, maternal medical conditions (server maternal iodine deficiency/thyroid disorder, intellectual disability, epilepsy)

*Antenatal*: prematurity, genetic factors/mutations, congenital malformations/cerebral dysgenesis, placental pathology, infections (TORCH, maternal genitourinary infections), Intrauterine growth restriction (IUGR/ FGR/SGA), multiple births, antepartum haemorrhage

*Perinatal*: perinatal asphyxia/birth complications, neonatal encephalopathy, perinatal stroke, kernicterus

*Postnatal (postneonatal)*: meningitis/encephalitis (including cerebral malaria), kernicterus, traumatic head injuries, shaken baby syndrome, cardiopulmonary arrest (near drowning)

*TORCH syndrome refers to transplacental &/parturitional infections with Toxoplasmosis, Others (syphilis, HIV, EBV, Zika, varicella, enterovirus), Rubella, Cytomegalovirus, Herpes simplex. FGR = Foetal Growth restriction. SGA = Small for Gestational Age.*

#### **Table 1.**

*Risk factors for cerebral palsy.*

**Table 1** shows a list of risk factors for CP but the list is inexhaustive since many cases of CP have unidentifiable aetiological factors. Subsequently, a discussion of some of the risk factors with emphasis on their neuropathological substrates will follow.
