Clinical profile, predisposing factors, and associated co-morbidities of children with cerebral palsy in South India.

INTRODUCTION: Cerebral palsy (CP) is the most common physical disorder of children. Causes like jaundice and birth injury though are decreasing; complications resulting from the survival of low birth weight babies are replacing some of the older etiologies. Hence, this study was planned.
OBJECTIVES: The objective was to study the clinical patterns, predisposing factors, and co-morbidities in children with CP.
MATERIALS AND METHODS: The present study is a hospital based prospective study conducted from January 2012 to January 2013 in children presenting to neurodevelopmental clinic at a tertiary care teaching hospital in India. Hundred cases with clinical features suggestive of CP were included in the study. Cases were evaluated by history, clinical examination, and necessary investigations.
RESULTS: Results of the study showed 81% of spastic, 12% of hypotonic, 5% of dystonic, and 2% of mixed CP cases. The mean age of presentation was 2 year, 2 month, and male to female ratio of 1:2. Pregnancy-induced hypertension (PIH) was the most common antenatal complication observed in 6%. Four percent had neonatal sepsis and 19% were born premature. Associated co-morbidities were mental retardation (55%), seizure disorder (46%), visual problems (26%), hearing problems (19%), and failure to thrive (47%). DISCUSSION: Sex distribution observed in our study was male to female ratio of 1.2, which was comparable with a multicenter study in Europe. PIH was observed in 6% of cases, which was comparable with prior studies. Birth asphyxia was observed in 43% of cases. Eighty-one percent of the cases constituted a spastic variety of CP which was comparable to other studies.
CONCLUSION: Perinatal asphyxia was the important etiological factor. We found preventable intranatal causes (60%) and antenatal causes (20%) forming a significant proportion. Co-morbidities were significantly observed in our study.

Introduction

The developmental disabilities are a group of disorders differentiated by the pattern of delay among the developmental streams. The four streams of development include language, problem solving, motor, and social. Cerebral palsy (CP) is a disorder of development in which motor function abnormalities are the key features. It is the most common physical disorder in children first described by William John Little in 1861.

Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitations that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of CP are often accompanied by disturbances of sensation, perception, cognition, communication, behavior, epilepsy, and by secondary musculoskeletal problems.[12345678910] The definition and classification of CP, April 2006 document is offered for international consensus and adoption, with the intent of providing a broad spectrum of audience with a common conceptualization about CP.[5]

Because of the wide variety of causes of CP, the exact numbers from different studies do not completely match. However, there is a remarkable similarity in the prevalence across the world, from Sweden in the 1980s with a prevalence of 2.4 per 1000[11] and 2.5 per 1000 in the early 1990s,[12] 2.4 per 1000 from Malta,[13] 2.5 per 1000 from Finland,[14] and 1.6 per 1000 in China.[15] Considering the difficulty in making a specific diagnosis, and especially finding mild cases, these numbers probably reflect much more variation in counting than clear differences in prevalence.

Ravn et al. reported the total CP birth prevalence has been significantly decreasing since the birth period 1983–1986 with 3.0 per 1000 live births until the period 1995–1998 with 2.1 per 1000 live births. The overall decrease was seen in preterm infants (<31 weeks) as well as in term infants and despite a simultaneous fall in perinatal and early neonatal mortality in the preterm group. Analyzing the subtypes of CP we found a significant increase in the numbers as well as the rate of unilateral CP with a simultaneous fall in the numbers as well as the rate of bilateral CP.[16]

Cerebral palsy prevalence is remarkably similar in developed countries. Nineteen of the 27 reports show prevalence between 1.5 and 2.5 per 1000 live births or child survivors, and all studies show prevalence between 1.2 and 3.0 per 1000 live births.[17] For CP at all birth weights, the overall impression is stability over time, but with a slight increase in prevalence in the 1980s. There is a suggestion that this increase may be on the decline. CP prevalence per 1000 live born infants who weigh <1500 g exhibited a sharp increase in the 1980s which seems to be on the decline. A similar, but slightly less pronounced trend was found in infants who weigh between 1500 g and 2499 g. The time trend for infants who weigh more than 2500 g shows an up-and-down pattern with no obvious trend.[17] It also is apparent that the slight increase in CP prevalence that is seen in all infants reflects the increase in CP in very low birth weight (VLBW) infants, which is entirely a consequence of their increasing survival. The decline in CP in such infants recently may reflect improvements in care of VLBW infants that are beginning to affect rates of CP or it simply may be sample variance, only time will tell.[17]

Causes like jaundice and birth injury are decreasing and on the other hand complications resulting from the survival of more low birth weight (LBW) babies are replacing some of the older etiologies. Prematurity and the factors responsible for the same, natal causes like intra-partum asphyxia, birth injury and the factors responsible for those, postnatal causes like infections, kernicterus, and other metabolic impairments constitute preventable etiologies of CP. If we are able to reduce the incidence of CP in future, the area's most amenable to intervention are those related to preventing postnatal brain injury in infants and those reducing preterm births. The present study intends to look into the present spectrum, etiology, risk factors, and co-morbidities of CP.

Materials and Methods

All children presenting with clinical features suggestive of CP to the neurodevelopmental clinic at Indira Gandhi Institute of Child Health over a period of 1-year (January 2012 to January 2013) were enrolled. History and a clinical examination using systematically designed forms were taken. MRI of brain was done to find out the cause and severity of brain injury. Intelligent quotient and associated behavioral problems like autistic features, hyperactivity was done by a clinical psychologist. Visual evaluation was done by a pediatric ophthalmologist and visual evoked potentials. Hearing assessment was done by an audiologist with brain stem auditory evoked potentials. Electroencephalogram was done to detect convulsions in children with a history of epilepsy. Following cases were included: Cases of developmental delay with neurological examination consistent with CP; nonprogressive brain malfunction manifested early in life. Progressive neurological disorders were excluded.

Results

Our study group composed of 100 cases. Age of presentation at the first diagnosis was <1-year (28%), 1–4 year (65%), 5–10 year (6%), and more than 10 year (1%) [Table 1]. Male to female ratio of 1.2:1 was noted. Fifty percent were each from urban and rural regions. Distribution of cases as per socio-economic status (as per modified Kuppuswamy classification) observed was upper-middle - 11%, lower middle - 53%, upper lower - 36%. Common age of mother at birth of affected children was 19–25 year (72%) [Table 1]. Sixty-four percent of children were born to nonconsanguineous and 36% to consanguineously married couples (32% second degree and 4% third degree). Similar history of CP in family was observed in 5 cases (1 case with cerebral malformation, 2 cases secondary to prematurity, and two cases of perinatal asphyxia).

Table 1

Risk factors and types of cerebral palsy

Birth order and gestational age of the affected children are shown in Table 1. Prematurity was a predominant finding (50%) in spastic diplegia. Extreme prematurity was observed in dystonic CP (severe form). Birth weights of the affected children are shown in Table 1. Extremely LBW was observed in cases of spastic diplegia. LBW was observed in 30% of our cases.

Antenatal complications observed are depicted in Table 1. The modes of delivery observed in our study were: Vaginal delivery (81%), instrumentation (3%), caesarean section (12% - the indications being: 3 cases of transverse lie, 9 cases of nonprogression of labor). The places of delivery observed were: Institutional 94% (primary health center - 46%, referral [secondary/tertiary center] - 48%), home - 6%. Forty percent of them required resuscitation at birth. No data about APGAR score is available in our study. Postnatal complications observed in our study are shown in Table 1.

Various risk factors observed in our study are shown in Table 2. Encephalopathy after birth was observed in 49% of bilateral spastic CP cases. Genetic causes or malformations were observed in 50% of hypotonic CP cases. Classifications of CP and the associated problems are shown Table 2.

Table 2

Etiology, classification and associated co-morbidities

Discussion

The mean age of presentation of CP cases observed in our study was 2 year and 2 month and the median age of presentation was 2 years. More severe forms of CP presented earlier and an exception being dystonic CP in our study, and that might be as a result of small number of dystonic CP seen in our study. The presenting age in our study was when concerns regarding standing, walking, talking, and communication were at their peak. Sex distribution observed in our study was male to female ratio of 1.2 which was comparable with a multicenter study in Europe (2002) in which male to female ratio of 1.33 was observed.[18] No sex predisposition was seen. Consanguinity was observed in 36% of our cases which was comparable with few Turkish studies who have noted a high number of marriages between relatives (21% of all marriages).[1920] The increased frequency of consanguinity among parents of children with CP, and the strong association with a positive family history suggests the role of genetic factors in the pathogenesis of CP in this environment.[21]

Region of distribution of cases was equal among urban and rural population. In urban scenario, increasing antenatal risk factors and increased morbidity secondary to improved neonatal care were significant, whereas inadequacy of efficient obstetric care was the risk factor observed in the rural scenario.

In our study, socio-economic status of the study population was 53% Class III and 36% Class IV as per modified Kuppuswamy classification. A population-based study in Ireland[22] reported a significantly higher risk of CP, particularly diplegia, among children born to families of unskilled manual workers. We did not observe a significant correlation with socioeconomic status and diplegia in our study.

Birth order of the affected child in our study showed 65% being first born and 23% were second born which was comparable to previous studies.[2324] Incidence of CP was less in higher order birth because of improved knowledge, attitude, and practice of parents in seeking obstetric and perinatal care.

History of CP in the family was observed in 5% of cases in our study. It was 2.5% in Sharma et al.,[24] and 2% in Hughes and Newton study.[25] Higher incidence observed in our study might be because of the high incidence of consanguinity observed in our study.

Gestational age of the affected children observed in our study was term gestation in 81%, late preterm (34–36 week) in 4% and preterm (<34 week) in 15%. Six out of the 19 preterms (32%) had spastic diplegia. Periventricular leukomalacia is most commonly observed in prematurity. Dystonic CP was observed in extreme prematurity (<28 week), as they are susceptible for global ischemia. LBW was observed in 30% of our cases, but prematurity was seen in 19% indicating that 11% of term children were intrauterine growth retardation in our study. Prior studies have noted that diplegia is the dominant type of CP (39.8%) and most of those cases (71.6%) were preterm. Children with spastic diplegia are almost universally appropriate for gestational age.[1426] In agreement with few prior studies,[27] suggesting a relation between tetraplegic phenomena and small-for-gestational age term infants, 72.9% of cases of tetraplegia in a Turkish study were seen in term infants of whom 66% were small for gestational age.[19]

In terms of the type of CP, a prior study found that the spastic type of CP was the predominant form in preterm and term infants.[28] In our study also, we noticed spastic CP most common type of CP.

Cerebral palsy in children with normal birth weight was mainly caused by global ischemia secondary to perinatal asphyxia, cerebral malformation, intracranial bleed, and postnatal infections. This was comparable with other studies.[1829]

Cerebral palsy cases were equally observed from primary health centers and referral center (secondary/tertiary). Lack of timely intervention or referral at primary centers was observed. At referral center, more high risk cases had been delivered and very sick newborns had been managed resulting in neurological morbidity and CP.

All variants of spastic CP were observed in extremes of maternal age in our study. Pregnancy-induced hypertension (PIH) was observed in 6% of cases, which was comparable with previous studies[24] [Table 3]. Antenatal risk factors like PIH, infection, and drugs were predominantly known to cause vascular insult and thereby hypoxia resulting in spastic CP.

Table 3

Comparison of incidence of risk factors and etiologies of cerebral palsy

Birth asphyxia (hypoxic ischemic encephalopathy) was observed in 43% of cases and LBW in 30% cases which were comparable with a previous study[24] [Table 3]. Prematurity was observed in 15% of cases compared to 25.4% seen in Sharma et al., might be secondary to increased survival of morbid premature infants in their study.[24] Causes of prematurity could be extremes of age, maternal infections, familial, PIH, twinning, etc. Instrumentation was observed in 3% of cases compared to 7.5% in Sharma et al. study.[24] CP seen in 81% of vaginal deliveries might be due to lack of timely intervention in the perinatal period and nonavailability of appropriate obstetric and postnatal care.

Neonatal sepsis was observed in 4% of cases. Incidence of pyogenic meningitis and tubercular meningitis was 8% and 2%, respectively, which was comparable with Sharma et al. study.[24] Intracranial bleed during infancy was observed in 6% of cases and resulted in a unilateral form of CP (hemiplegia).

Classification of diagnosis

Eighty-one percent of the cases constituted a spastic variety of CP, which was comparable to Sharma et al.[24] and few international studies[1819] [Table 4]. Bilateral spastic CP was the predominant type comparable to Sharma et al.[24] and few international observations.[1819] Diplegia observed in 13% of cases compared to 54% in Sharma et al.[24] and 22% in few international studies[1819] [Table 4]. Unilateral spastic CP constituted 9% in contrast with few international observations[1819] [Table 4]. Hypotonia was observed in 12% of cases comparable with both Sharma et al.[24] and few international observations.[1819] Dystonia in 5% of cases and mixed CP in 2% of cases, both were comparable with Sharma et al. and few international observations[181924] [Table 4].

Table 4

Comparison of types of cerebral palsy

Intellectual sub-normality (IQ <70) was observed in 55% of cases. Other co-morbidities observed were, speech abnormalities in 38%, visual problems in 26% (strabismus, nystagmus, cataract, amblyopia, and cortical blindness), hearing impairment in 11% (sensorineural hearing loss), seizures in 46%, feeding problems in 19%, and undernutrition in 47% of cases. These were similar to Sharma et al.[24] [Table 5].

Table 5

Comparison of associated co-morbidities in cerebral palsy

Intellectual subnormality and feeding problems were predominantly observed in bilateral spastic and hypotonic CP children [Table 5]. That was secondary to global cerebral involvement and cerebral malformations. Seizures were observed in 52% of bilateral spastic CP cases, 25% of spastic diplegic cases, 45% of unilateral spastic CP cases, and 50% of hypotonic CP cases, respectively. Lesser prevalence of seizures in spastic diplegia is probably because of the cortical sparing of the pathological events resulting in diplegia.[30] Our data is not representative of the community as it was done in a referral hospital. This is a limitation of our study.

Conclusion

Bilateral spastic CP was the most common clinical form of CP observed in our study mostly secondary to global ischemia during the perinatal period, which are mostly preventable. This is in contrast to the international observation of predominant unilateral spastic CP, which is mostly secondary to nonmodifiable intrauterine vascular insult.

Perinatal asphyxia is the important etiological factor in our study. We found preventable intranatal causes (60%) and antenatal causes (20%) formed a significant proportion of our study group. Hence, timely obstetrical intervention and immediate newborn care can still play a major role in preventing CP hence; there is an urgent need to further strengthen the existing maternal and child health services.

Co-morbidities are significantly observed in cases of CP. Appropriate screening and management of co-morbidities especially vision, hearing, speech, seizures, and nutrition improve the overall prognosis in cases of CP. Seizures add a dimension of uncertainty to the otherwise relatively static problem of CP.

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Nil.

Conflict of interest

There are no conflict of interest.