R E S E A R C H A R T I C L E P r e v a l e n c e o f D e v e l o p m e n t a l D e l a y i n In f a n t s w h o a r e H I V P o s it iv e A B S T R A C T : The p resence o f developm ental delay in children who are H IV p o sitive has been w ell described. International studies have iden tified 25 - 40% o f H IV infected infants to have developm enta l delay. This study a im ed to establish the prevalence o f developm en tal delay in H IV p ositive infants in South Africa. The study w as condu cted a t C oronation H ospital, G auteng, South Africa. Infants u nd er 12 m on ths o f age atten ding an o u t-p a tien t fo llo w -u p clin ic were a ssessed f o r developm ental delay using the N eurodevelop m ent A ssessm en t Score. Inform ed w ritten consen t w as obta in ed fr o m the caregivers p r io r to assessm ent. The results fr o m 30 H IV p ositive a n d 30 H IV n egative infants were analysed. D escrip tive analyses were u sed to analyse m o st o f the data. D a ta were su m m arised using m eans f o r continu ous variables a n d fre q u e n c ie s and pro p ortio n s f o r ca teg orical variables. The tw o groups w ere w ell m a tch ed f o r age, w eight a n d so cio-econom ic status. F orty p e rc e n t o f the H IV p o sitive sam p le p resented w ith develop m ental delay co m pared to 13% o f the H IV negative sam ple. The caregivers o f the H IV in fected children expressed a n eed f o r su p p ort g roups a nd education on H IV a n d how to care f o r th eir infants. The results o f this study sup port the fin d in g s o f international studies on develop m en tal d elay in H IV infected infants. F urtherm ore this study identifies the need f o r cost effective, innovative p ro g ra m m es to address the long term needs o f H IV infected infants a n d th eir caregivers. K E Y W O R D S : N E U R O D E V E L O P M E N T A L DELAY, H IV PO SITIVE, INFANTS. POTTERTON JL (MSc)'; EALES CJ (PhD)' 1 Department o f Physiotherapy, University o f the W itw atersrand. INTRODUCTION At present there are approxim ately one million children in Sub-Saharan Africa infected with H IV (LINAIDS Report, 2000). In South A frica young women betw een 20 and 30 have the highest prevalence rates o f HIV infection in the country (H IV /AID S/STD Strategic Plan for South A frica 2000 - 2005, 2000). As more young women o f child­ bearin g age becom e infected w ith HIV, so the num ber o f infants born with vertically transm itted HIV will continue to rise. The health care costs for these children are largely borne by the state as the m ajority are unable to afford private health care. D espite the fact that the num ber of HIV infected infants in South Africa continues to grow, no research on the prevalence o f neurological com plica­ tions in HIV infected children in South Africa could be found. Unless an effort is made to identify the m agnitude o f this particular aspect o f paediatric HIV in South A frica we are not going to be able to plan appropriate and affordable intervention program m es for the patients in our care. The purpose o f this study was to establish w hether developm ental delay presented in the first 12 m onths in infants with vertically transm itted HIV infection and, to ascertain the prevalence o f developm ental delay in HIV infected infants under 12 m onths o f age. This study fu rth e r u ndertoo k to establish w hether a need exists for regular devel­ opm ental screening and the develop­ m ent o f a hom e program m e for HIV infected infants. M any questions rem ain as to how and when m other to child transm ission o f HIV occurs, the rate o f the vertical transm ission ranges from 14% - 40% (Quinn e ta l, 1994). The tim ing o f infec­ tion o f a foetus varies and depends on a num ber o f factors largely related to the m o th er’s disease status (Tardieu, 1998). In co n trast to w hat w as orig in ally believed, international trials have shown no significant difference in,transm ission rates betw een infants d eliv ered by caesarian section and those delivered vaginally (Falloon et al, 1989; Quinn et al, 1994). The diagnosis o f HIV in infants under 15 - 18 m onths o f age is com plicated by the possible presence o f m aternal an tib o d ies in in fa n ts’ b lo o d stream s which may lead to false positive results if serologic testing is done, this includes the E L ISA and W estern B lot tests which are com m only used in developing countries (Falloon et al, 1989). A more accurate test is the Polym erase Chain Reaction which tests the infants leuco­ cytes for the presence o f HIV DNA (Falloon et al, 1989). The PCR is a specialised and expensive test and is therefore not routinely used in South A frican hospitals. Central nervous system involvem ent was recognized in children infected with HIV soon after AIDS was first identi­ fied in the early 1980s (Belm an, 1992). The neurological syndrom e described, CORRESPONDENCE TO: JL Potterton D epartm ent o f Physiotherapy 7 York Road, Parktown 2193 South Africa Tel: (01 1 )4 8 8 -3 4 5 0 Fax: (01 1 )4 8 8 -3 2 1 0 SA J o u r n a l o f P hysiotherapy 2001 V o l 57 No 3 11 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 3. ) to g eth e r w ith the neuro p ath o lo g ical fin d in g s, co n firm ed the h ypothesis that HIV was a neurotropic retrovirus (Belm an, 1992). The m ost frequently infected cells within the brain are the m acrophages (Tardieu, 1998). M acro­ phages in the white matter, the basal ganglia and around the blood vessels are the m ost vulnerable to infection. M onocytes, lym phocytes and astrocytes may also becom e infected but to a lesser degree (Tardieu, 1998). T he discrepancy between the severity o f the ensuing encephalopathy and the relatively sm all viral load in the CNS suggest that factors other than direct cellular dam age may play a role. Falloon et al (1989) suggest that this allow s for hope that antiretrovirals may reverse the encephalopathy to a certain extent, while Tardieu (1998) takes a more pessi­ mistic view that m uch o f the dam age may in fact take place prenatally and be irreversible. A characteristic encephalopathy has been described in a num ber o f studies related to infants and children infected with HIV (Belman et al, 1996; European C ollaborative Study, 1990). E ncephalo­ pathy may be the first clinical sign o f HIV infection (Falloon et al, 1989), it usually initially presents with develop­ mental delays, loss o f m ilestones and a d eterioration in intellectual abilities. The developm ental delay usually pro­ gresses to include pyram idal tract signs, ataxia, abnorm al m uscle tone and pseudobulbar palsy (Falloon et al, 1989; Tardieu, 1998). A cquired m icrocephaly is com m on in infants (Falloon et al, 1989). U ltim ately the encephalopathy may result in spastic quadriparesis with dystonic posturing and regression in m otor m ilestones (Tardieu, 1998). The developm ent o f severe encephalopathy in infancy has been correlated with serious sym ptom atic disease and an increased and early m ortality (Belm an, 1992). METHOD This study was conducted in the unit follow -up clinic o f Coronation Hospital, Gauteng, South Africa. Children who have had an adm ission to one o f the m edical wards at Coronation Hospital attend this clinic for out-patient follow- up a p p o in tm en ts after h aving been discharged. Patients attending the clinic are drawn from sim ilar sociol-econom ic backgrounds. Prior to the com m encem ent o f this study, ethical clearan ce from the C o m m ittee fo r R esearch on H um an S ubjects o f the U n iv ersity o f the W itw atersrand was obtained. All infants under one year o f age attending the unit follow -up clinic at C oronation Hospital were identified by checking their date o f birth in the clinic booking book. Inform ed consent was obtained from the caregivers o f the child prior to any assessment being performed. Inclusion criteria for the experim ental sam ple included; infants betw een six weeks and 12 m onths o f age who tested HIV p o sitive on P o ly m erase C hain R eaction (PC R ) testin g o r infants between six weeks and 12 m onths o f age who tested HIV positive on ELISA and m anifested clinical signs and sym ptom s o f HIV infection as stipulated by the Centre for Disease control. HIV was to have been perinatally acquired. Only subjects who were deem ed fit for devel­ opm ental assessm ent by the exam ining doctor were assessed. Exclusion criteria for participation in the study included; gestational age of less than 36 weeks, any infant with a history o f brain dam age due to perinatal factors or acquired post-natally; children w ho w ere resident in an institution and therefore did not have a single primary caregiver. The control group was selected from infants aged between six weeks and 12 months who attended the sam e follow- up clinic. The infants in the control group had not tested HIV positive nor had clinical signs and sym ptom s suggestive o f HIV infection. This inform ation was obtained from the infants file once the assessm ent had been perform ed. T hirty H IV positive and 30 HIV negative infants were assessed. The children all cam e from Coronationville, the western outskirts o f Soweto, Brixton and Crosby. The fam ilies from these areas have sim ilar socio-econom ic and educational backgrounds. Cultural beliefs about child rearing may vary slightly in the different racial groups represented. The vast m ajority o f the sam ple were black or coloured infants w ith only one w hite and one Ind ian in fan t being assessed. T he N eu ro d e v elo p m en tal A sse ss­ m ent Score (NDS) was used to assess developm ental delay. The N eurodevel­ opm ental A ssessm ent Score was chosen as a m easuring tool as it was developed using a sim ilar population to the study sample. It is a screening tool and is quick and easy to adm inister and to score. Taking contextual factors into account the NDS was thought to be an adequate assessm ent tool which would provide internal sam ple coherence. T he NDS has been validated for assessing children from six weeks to 12 m onths o f age. The scale assesses 12 areas o f m otor developm ent namely: moro reflex, protective reactions, ATNR, eye contact, head control, hand function, neck and sh o u ld er retractio n , prone function, sitting, rolling, standing and h o rizontal and o b liq u e su spension (G oodm an et al, 1985). All infants under one year o f age atten d in g the follo w -u p clinic at Coronation hospital were assessed by means o f the NDS. The infant and the caregiver/guardian were taken from the w aiting area to a private room w here the study was explained to them and their participation requested. The caregiver was given the inform ation sheet to read. The nursing staff were always available to assist w ith translating if necessary. O nce w ritten c o n se n t had been obtained from the caregiver the infant was assessed by the researcher. The infants perform ance in each o f the 12 areas was evaluated by the researcher and com pared to the age specific norms o f the assessm ent sheet. The sheet was m arked with a ‘0 ’ if the infant was func­ tioning at, or above an age appropriate level and was m arked with a ‘ I ’ if the infant was functioning below an age appropriate level. A score out o f 12 was then d eterm ined and the infant was assigned to NDS category I, II or III depending on its score. Category: I - Norm al ie NDS 0 - 4 II - D evelopm entally delayed ie NDS 5 - 9 111- N eurologically im paired in NDS 1 0 - 12 12 SA J o u r n a l o f Physiotherapy 2001 V o l 57 No 3 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 3. ) Table 1: Summary of Demographic Data of the Experimental and Control Groups HIV Positive HIV Negative Mean Age (months) 7 , 5 5 Female 1 5 1 3 Male 1 5 1 7 Caesarian Section (%) 1 6 ,5 ( 5 / 3 0 ) 2 0 ( 6 / 3 0 ) Below 50th Percentile (%) 7 3 ( 2 2 / 3 0 ) 5 0 ( 1 5 / 3 0 ) Table 2: Classification of Subjects According to Their NDS Category NDS Category HIV Positive HIV Negative 1 6 0 % ( 1 8 / 3 0 ) 8 7 % ( 2 6 / 3 0 ) II 3 3 % ( 1 0 / 3 0 ) 1 3 % ( 4 / 3 0 ) III 7 % ( 2 / 3 0 ) 0 % T he fo llo w in g info rm atio n was obtained from the child’s file gestational age, method o f delivery, sex o f the infant and the infant’s w eight in kilogram s as recorded on that day by the clinic sisters. M any o f the caregivers were eager to d iscu ss th eir c h ild ’s co n d itio n and spoke at length to the researcher. These spontaneous, informal conversations were docum ented and three case scenarios will be discussed further. The infant’s weight was classified as being above or below the 50th percentile using the growth charts routinely used in South African hospitals. Infants identified as being d ev elo p m en tally d elayed or neurologically im paired were referred to the physiotherapy departm ent at C orona­ tion hospital for further assessm ent and managem ent. All the data collected was analysed by Dr P B ecker o f the M edical Research Council o f South Africa. Data were sum m arised using means for continuous variables and frequencies and proportions for categorical variables. D escriptive analyses were used to evaluate m ost o f the data. HIV positive and HIV negative infants were com pared w ith respect to their NDS classification using the Two Sam ple Proportion Test. The software used was STATISTIX for Windows V2:0. A p-value o f less than 0,05 was con­ sidered to indicate statistical signifi­ cance in this research report. RESULTS The two groups were well m atched in term s o f age, sex, mode o f delivery and w eigh t. T here w as no statistica lly significant difference between the two groups for any o f these param eters. The dem ographic data o f the two groups are sum m arised in Table 1. Forty percent (12/30) o f the HIV positive group could be classified as either developm entally delayed or neu­ rologically im paired w hereas only 13% (4/30) o f the HIV negative group were assigned this category. U sing the Two Sam ple Proportion test a p-value of p = 0,0195 was obtained. This is statis­ tically significant. The NDS classifi­ cation o f the study sam ple is presented in Table 2: Further analysis o f the NDS o f the HIV positive infants was done to deter­ mine on w hich areas o f the assessm ent the infants perform ed worst. It was found that the areas w here HIV positive infants consistently failed to perform ed at an age appropriate level were: - Pull to sitting (14/30) - Prone (16/30) - Sitting (14/30) - Rolling (11/30) - Horizontal and oblique suspension (13/30) M any o f the caregivers who consented to have their infants assessed spoke at length about the problem s facing them and their fam ilies and their need for inform ation and support. The infants assessed in this study were too young to attend a specific HIV clinic as these clinics only cater for children over two years old. Three case histories have been cho­ sen, they represent a m icrocosm o f the problem s caregivers are experiencing and h ig h lig h t the need fo r sup port system s for caregivers o f young infants with HIV. Case 1 M r A brought his nine month old son to be assessed. His wife passed away when the baby was eight weeks old due to an AIDS related illness. The baby was initially looked after by his maternal grandm other w ho is 76 years old. By the tim e the baby was four m onths old it had been hospitalised three times for gastroenteritis and was severely m al­ nourished. At this point M r A took a m onth’s leave from his clerical jo b and brought the baby to live with him. The child has since flourished and scored very well on the NDS. At present he attends a creche during the day and lives alone with his father. In his own w ords M r A says he is ‘clu e le ss’ about norm al developm ent and worries w hether he is feeding his baby properly. He asked w hether the researcher knew any other fathers rais­ ing HIV infected children on their own whom he could meet. He also asked w hether he could see the researcher on a regular basis to have his b ab y ’s develop­ mental progress monitored. As he was leaving he turned to the researcher and asked: “If my wife died o f AIDS and my boy has AIDS, should I also go and have an AIDS test?” M r A had obviously never been coun­ selled about having a HIV test, or if he had he had certainly not com e to terms with the fact that, in all likelihood, he was also HIV positive. Case Two Ms B brought a three month old girl to be assessed. She looked very young and I thought she may be the b ab y ’s sister. W hen asked w hat her relationship to the child was, she burst into tears and said that the researcher m ust not be angry with her. She is a 15 year old girl who was raped by one o f her teachers when she was in grade eight. She left school as SA J o u r n a l o f P hysiotherapy 2001 V o l 57 No 3 13 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 3. ) soon as it becam e apparent that she was pregnant. She tested HIV positive when she w ent to the ante-natal clinic when she was six m onths pregnant. She now sits at hom e w ith her baby. She says she is too asham ed to contact h er old school friends and can not get a jo b because she has no skills. Her m other continues to support her and the baby. It is highly unlikely that M s B will ever be financially independent o f her mother. She is conscious o f being ‘a b urden’ to mother. M s B said that she felt lonely and depressed and showed little insight or interest in her b aby’s condition. She said it felt good to talk to som eone and asked for a phone num ber w here she could contact the researcher. Case Three M s C is m arried with three children. She brought her youngest child to be assessed - a daughter o f eight months. M rs C watched with interest as the researcher assessed her baby and com ­ m ented that she had noticed that the baby was ‘lazier’ than her previous two children and had w ondered w hether this was because the baby had HIV. She also asked the researcher to show her w hat she could do at hom e to help her baby sit better. As she was dressing her baby M rs C turned to the researcher and said there was one thing she did not understand and that was how could her baby be HIV positive if she was HIV negative. She had one HIV test when she attended the ante-natal clinic at the hospital which had been negative, her baby tested positive on Polym erose C hain Reaction. M rs C had not been advised about being retested and did not know about the ‘w indow ’ period or the possibility o f a false negative result. DISCUSSION The prevalence o f developm ental delay in the study sam ple was relatively high at 40%. The prevalence o f develop­ m ental delay or neurological involve­ m ent in other studies varies from 9,52% (E m odi and O kafor, 1998) to 90% (Spiegel and M ayers, 1991). It is very difficult to com pare the results o f pre­ vious studies done due to the fact that they often have very different inclusion criteria, use different assessm ent tools and draw their subjects from very dif­ feren t so c io -eco n o m ic and cu ltu ral back-grounds. The study sam ple in this case is a biased one. Due to the fact that PCRs are not routinely done and that clinical signs\and sym ptom s had to be present along \w ith a positive ELISA test in order to confirm diagnosis, means that the infants assessed had already all had a hospital adm ission. T hese infants who present with clinical signs o f HIV infec­ tion at an early age generally have a less favourable prognosis that those who rem ain healthy for longer (Quinn et al, 1994; Falloon et al, 1989). The results o f this study can therefore not be taken to be representative o f all HIV positive infants under a year o f age, but only fo r those w ith clin ical ev id en ce o f HIV infection. A sim ilar bias is present in m any o f the studies review ed and is d ifficu lt to avoid w ith o u t incu rrin g significant laboratory expenses (Emodi and Okafor, 1998; Vetter et al, 1996; M sellati et al, 1993). One may argue that the mere fact that the children have been ill and have been hospitalized could have a negative im pact on the norm al developm ental progress o f a child (Spiegel and M ayers, 1991). Spiegel and M ayers (1991) report that a controlled study found that envi­ ronm ental factors such as hospitaliza­ tion and social isolation did not account for the developm ental delays seen in children with HIV infection. It is interesting to note that the areas in w hich the infants were most delayed ie pull to sit, sitting, prone, rolling and horizontal suspension, are all activities which require proxim al m uscle strength as well as co-ordination o f movem ent. It is im possible to say w hether the infants found these activities difficult due to m uscle w eakness and the effects o f their chronic illness or w hether it is a result o f inco-ordination o f m uscle acti­ vity due to a central nervous system deficit. The developmental delay evident in this study can therefor not be attri­ buted to CNS involvem ent alone. M ore in-depth lo n g itu d in al neu ro lo g ical assessm ents would be needed to draw conclusive results. A part from the Bayley Scales o f Infant D evelopm ent, w hich is costly and tim e-consum ing to adm inister, there is no one assessm ent tool which has been consistently used in previous studies. The NDS was developed from a num ber o f sources and was validated against the G riffith ’s M ental D evelopm ent Scale (G oodm an et al, 1985). An assessm ent tool that was quick to adm inister was needed as the study was conducted in a busy out-patient clinic. Caregivers would be reluctant to spend another hour in the clinic w hile their infants were assessed. For many caregivers, attending the clinic requires leaving w ork and losing pay for the hours lost. In retrospect whilst the NDS was easy to adm inister and to score, it failed to give in-depth inform ation about the child’s developm ent. The NDS is also exclusively a gross m otor test and therefore does not detect fine m otor or speech involvem ent. T he need for su p port g ro ups for caregivers o f HIV positive infants was expressed by a num ber o f caregivers and m any asked for follow -up appointm ents with the researcher to have their infants reassessed. T he better inform ed care­ givers are about their ch ild ’s illness the m ore in control they feel, this reduces anxiety (Spiegel and M ayers, 1991). Support groups do not necessarily need to be run by a health care professional. A m ore cost effective m ethod would be to facilitate the form ation o f groups organised by the caregivers themselves. Spiegel and M ayers (1991) found that inform al support groups w ere perceived as being less threatening by the care­ givers. Spiegel and M ayers (1991) identified the im portance o f m aintaining a degree o f self-esteem for caregivers. They claim that this can be achieved by helping the caregivers to develop a sense o f com petence w hen dealing with their child. The have found that the regular use o f a p h y sio th erap y p ro g ram m e w ithin the hom e provides a sense o f pur­ pose and com petence for the caregivers. In addition to this, when the child does die the caregivers derive com fort from the fact th at they w ere p erso n ally involved in the ch ild ’s health care. T he South African governm ent has identified com m unity and hom e based 14 SA J o u r n a l o f P hysiothera py 2001' V o l 57 No 3 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 3. ) care o f HIV infected individuals as a key strategy to be im plem ented by 2005 (H IV /A ID S /S T D S trateg ic Plan for South Africa: 2000 - 2005, 2000). They pro pose th at the fu n ding fo r such p ro g ram m es should com e from the departm ents o f H ealth and Welfare, as well as from Non Governm ental O rgani­ zations. H om e based program m es can reduce costs for hospitals by reducing the num ber o f out patient visits and by reducing the direct contact time with health care professionals. Costs incurred by the patients can also be reduced in term s o f transport to the hospital as well as tim e o ff work. M odels used success­ fully in other developing countries e.g. U ganda need to be appraised for pos­ sible im plem entation in South Africa. Budgetary constraints are a very real issue and any program m e im plem ented w ould have to prove cost effective. Ethically we cannot continue to w ith­ hold clinical and em otional support from HIV infected infants and their caregivers. The lim itations o f this study are that the sam ple was a biased one and the results can therefore only be said to apply to this particular group o f infants who have already m anifested signs of HIV infection. The NDS proved to be an insensitive assessm ent tool and there­ fore the results o f this study lack depth. D espite the lim itations o f this study, the results obtained do confirm the fact that children who are HIV positive are predisposed to developm ental delay, and that these developm ental problem s may m anifest very early on in the child’s life. As the num ber o f HIV positive chil­ dren adm itted to hospital continues to escalate at an alarm ing rate, physiothe­ rapists need to be fully aware o f the p ossib le clin ical c o m p licatio n s w ith which these children m ay present. A h o listic m u lti-d iscip lin a ry approach w hich could address the em otional and educational needs o f the caregivers as well as the therapeutic needs o f the children needs to be investigated. Models from other parts o f the world, and espe­ cially from other A frican countries, need to be evaluated. Based on the results o f this study the fo llo w in g rec o m m en d atio n s can be made: - Infants diagnosed as being HIV posi­ tive should be routinely screened for neurological com plications. - Physiotherapists should play a more active role in the long term m anage­ m ent o f infants who are HIV positive, in term s o f developing appropriate home program m es and m onitoring developm ental progress. - A need exists for support groups for the parents o f HIV positive chil­ dren o f all ages. These groups should encom pass an educational com ponent as well as addressing the em otional needs o f the parents. - Future studies should m ake use of the a more com prehensive assess­ m ent tool e.g. Bayley Scales o f Infant D evelopm ent. - A p ro sp ectiv e lo n g itu d in al study would yield useful inform ation on the natural progression o f neurological involvem ent o f children who are HIV positive. CONCLUSION The findings o f this study confirm that developm ental delay is a com m on find­ ing in infants with HIV infection. It may m anifest in the first y ear-o f the ch ild ’s life. The severity o f developm ental delay varies from loss of, or failure to attain milestones, to severe neurological impair­ m ent resulting in m ultiple handicaps. A need exists for physiotherapists to becom e involved in the long term m anagem ent o f infants who are HIV positive. This involvem ent needs to be appropriate and cost effective in keeping with budget and staff constraints. The em otional and ed u catio n al needs o f caregivers o f HIV infected infants are not currently being met. Holistic support groups may help to address these issues. The fin d in g s drawn from this study cannot be extrapolated to include infants who are HIV positive but rem ain asym p­ tomatic, nor those who are older than 12 months. 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