**2.4 Aetiology of cerebral palsy: historical vs. current perspectives and well-resourced/high income countries (HICs) vs. low & Medium Income countries (LMICs)**

Historically, William J. Little and Sigmund Freud made significant contributions to the understanding of the aetiology of CP [20]. In brief, Little first described spastic diplegia (Little's disease) and causally related it to difficult delivery, preterm birth and birth asphyxia—a conception that has survived centuries [5, 20]. However, Freud was the first to state that CP could result solely from antenatal or intrauterine factors (in utero abnormalities of brain development) or combined with birth complications [5, 20]. This assertion which was at variance with that of Little derived from

**Figure 1.** *Casual pathway from prematurity to CP.*

**Figure 2.**

*Causal pathway from maternal genitourinary tract infection to CP.*

his observations that children with CP had many other neurological disorders and children with birth asphyxia could be completely normal [5, 20]. Nevertheless, the contribution of the perinatal period to CP causation (Little's view) has also been supported by subsequent research [16]. But this is indeed much less frequent than previously thought.

Current understanding of the aetiology of CP support more of Freud's views since epidemiological studies [9, 10] notably the National Collaborative Perinatal Project [9] *Aetiology and Pathophysiology of Cerebral Palsy DOI: http://dx.doi.org/10.5772/intechopen.106685*

**Figure 3.** *Casual pathway from twinning to CP.*

**Figure 4.** *Casual pathway from placental pathology to CP.*

brought to the fore that less than 10 percent of CP were causally related to birth asphyxia but rather most predictors of CP were antenatal factors [10]. Thus, the debate on causation and timing has moved from intrapartum events (birth asphyxia, birth trauma/ complications, Little's view) to antenatal factors or antecedents (cerebral dysgenesis, genetics, maternal infection, Freud's view) [4, 9, 10]. Further support for the significant role of antenatal factors or "antecedents" in CP causation is the fact that the reduction in perinatal asphyxia by improved perinatal and obstetric care in well-resourced countries (HICs) of Europe and America did not lower the prevalence of CP [21]. Recent studies involving neuroimaging and inflammatory markers [22–25] which continue to debunk Little's view of birth asphyxia as a major cause of CP abound in literature from developed countries of Europe and America. However, studies from low and middle income

countries (LMICs) of Africa continue to implicate preventable perinatal and postnatal aetiological factors in CP (perinatal asphyxia, kernicterus, meningitis, cerebral malaria) [26]. Majority of these studies are of low-quality with simple cross-sectional design and lacking appropriate control groups for proper assessment of risk factors [26]. The studies involving neuroimaging and inflammatory markers are rare in LMICs due to financial constraints, unavailability of equipment and lack of expertise. Therefore, the type and quality of studies on aetiological factors in CP seen in well-resourced countries are needed in developing countries (LMICs) to harmonize the spectrum of aetiological factors and timing of insults in CP worldwide.

As regards the relative contribution of individual risk factors to CP causation, variations also exist between HICs and LMICs. It is well known that in HICs, improved preventive measures, use of guidelines and better management of neonatal jaundice have resulted in a significant reduction of cases of CP attributed to kernicterus [27]. Moreso, prolonged obstructed labour and breech delivery with its attendant increased risk of intracranial haemorrhage/injury are currently rare in HICs owing to the high rates of planned caesarean deliveries [19]. Furthermore, congenital rubella infection and meningitis caused by *Haemophilus influenzae* Type B (HIB) and Neisseria meningitidis have been significantly reduced through effective immunization programmes in HICs while the recent introduction of the malaria vaccine is expected to reduce the relative contribution of cerebral malaria to brain damage in malaria-endemic regions [27]. The reducing incidence and severity of CP associated with prematurity has been reported in some HICs [28]. Further reduction in the prevalence of CP among children with low birth weight is expected with the implementation in many HICs of guidelines recommending administration of magnesium sulphate (MgSO4) for neuroprotection in imminent preterm delivery at <32–34 weeks of gestation (pre-eclampsia and preterm labour) [19, 28].
