1Ninety-eight percent of the 3.7 million neonatal deaths per year occur in developing countries; the majority of these deaths occur during the first week of life (Lawn et al 2009). Globally, the major direct causes of neonatal death are preterm birth (28%), severe infections (26%), and birth asphyxia (23%) (Lawn et al 2005) (Figure 1).
2Mortality and morbidity from birth asphyxia disproportionately affect infants in low and low-middle income countries, particularly those from the lowest socioeconomic groups (Lawn 2009). It is estimated that an equal or larger proportion of survivors suffer brain damage resulting in mental retardation and cerebral palsy. In a multicenter prospective study in eight countries in eastern, central, and southern Africa, the primary cause of neonatal mortality was identified as birth asphyxia (Kinoti, 1993). Thus birth asphyxia has a large impact, especially in low resource countries.
3Although little work has been done on neuro-developmental outcomes of babies surviving birth asphyxia in developing countries (Halloran, 2009), Ramey and colleagues in the ‘Abecedarian Project’ demonstrated that intensive early intervention could enhance the development of many high-risk babies (Ramey, 1992). Their EIP resulted in an IQ of 105 compared to the control average of 85 at three years.
4In most developed countries, infants who are at risk for developmental delay (genetic factors, prematurity, congenital infections, and birth asphyxia) are routinely followed up. Appropriate early intervention programs are instituted to allow the child to develop to maximum potential. However, this is uncommon in low resources countries. Only a few studies have evaluated the feasibility and efficacy of EIP in these settings. In a study by Badr et al (2006), developmental outcomes in response to EIP were evaluated at 2 months, 6 months, and 8 months on infants with brain injury using the Bayley Scale of Infant Development (BSID). There were minimal positive effects on Mental Development Index (MDI) and Physical Development Index (PDI) of infants in the EIP group when compared to the control group. The attrition rate was 31% (Badr et al, 2006). In the randomized trial by Zhang et al (2007), infants in the intervention group received early intervention guidance and follow up after discharge from Neonatal Intensive Care Unit (NICU) in China. The developmental outcome was evaluated based on MDI and PDI at 1 year. The MDI and PDI scores of the group with high compliance were markedly higher than in the less compliant group. This study showed that early intervention can improve the neurodevelopmental outcome of preterm infants at 1 year of age. Thus, there are some encouraging findings from studies of high risk infants in low resource countries that their development can be enhanced through early intervention.
5However, the effects of an EIP on early child development for infants with birth asphyxia in low resource countries have not been evaluated sufficiently to determine if these interventions would be effective. We are aware of only one such study. A small single centre randomized controlled trial in mainland China (Bao et al 1997) evaluated the effects of EIP in 64 infants with birth asphyxia who were randomized to EIP (n=34) or conventional care (n=30), At 18-24 months of age, using a modified BSID, MDI was 105 +/- 15 in the early intervention group vs 91 +/- 11 in the conventional care group (p<0.0001) and 100 +/- 13 in the normal term infants who received conventional care. PDI did not differ significantly between the groups.
6Our study was conducted to identify infants at risk for neuro-developmental disorders and to evaluate the feasibility of implementing an innovative trial of home-based, parent-delivered early developmental stimulation intervention in Lusaka, Zambia (Figure 2). The intention was to inform a larger trial evaluating the efficacy of EIP in low resources countries that could follow.
Figure 2. Socioeconomic characteristics of Zambia (source: WHO 2011).
7Lusaka is the capital and largest city of Zambia. It has a population of about 1.7 million (ZHDS, 2007). It is a commercial centre as well as the centre of government and dominates the country’s urban system accounting for 32 percent of the total urban population in the country. About 70 percent of Lusaka’s population lives in poor, unplanned settlements comprising 20 percent of the city’s residential land. Urban poverty is reflected by the fact that informal settlements are expanding faster than the rest of the city. All of these mushrooming informal settlements are similar in that they lack adequate shelter, essential infrastructure as well as inadequate access to water and sanitation facilities. Thus, the situation in the unplanned urban settlements makes its residents vulnerable to epidemics. The housing, health, and environmental conditions in the growing informal settlements of city consequently are extremely poor. Road accessibility is almost impossible during the rainy reason which starts from November to March as most of the roads are washed away.
8Eighty live born infants weighing > 1500 g were recruited from delivery centers in Lusaka. The babies had birth asphyxia defined by the inability to initiate or sustain breathing at birth (WHO definition) (WHO, 1997) and needed resuscitation with bag and mask. Mothers/babies pairs were randomized into control (n=40) and intervention group (n=40).
9Starting at 8 weeks, college-trained physiotherapists and nurse health counselors gave parents in both groups WHO health messages (Appendix 1) at home on a bi-weekly basis up to 8 months of age. Messages emphasized exclusive breastfeeding, infant feeding, immunizations, etc. The intervention group parents were trained in engaging their babies in stimulating developmentally appropriate activities, following the Partners for Learning Curriculum (Sparling & Lewis, 1984). This is a home-based parent provided model which allows the intervention to occur in the family context for a child aged 0-3 years. A home-based, parent-implemented EDI model was chosen because the home is the foremost natural environment for learning to occur for a child aged 0-3 years, and the parent (or the equivalent) is one of the limited numbers of caring persons with whom the infant or toddler is attached (Ramey & Ramey, 1998). This approach supports the parent in the role as the first teacher of the child and provides opportunities for strengthening the parent-child bond. This model is also especially well suited for low-resource settings because it requires relatively little infrastructure and resources to implement, compared to alternative models, such as center-based interventions.
10Partners for Learning has several components that are transmitted via a trainer who visits parents in the children’s homes. During each visit, lasting about 45 minutes, the trainer presents playful interactive learning activities, which are depicted on cards. Each activity targets a developmentally appropriate competence. Cycles of use allow the parent to implement several activities for a while, but then move on to new activities as the child masters each competence. This progression is guided by the trainer, who selects activities to match and enhance the child’s developmental competences. Partners for Learning covers a full spectrum of 23 developmental skill areas, organized into the four areas: (1) cognitive and fine motor, (2) social and self-help, (3) gross motor, and (4) language skills. The trainer encourages the parent to apply the targeted activities until the next home visit by integrating them into daily life with the child. The activities can thus enrich care routines such as diapering, feeding, dressing and special one-to-one times. By applying these activities and observing how the child changes and acquires these competences, general principles gradually emerge that enable the parent to gain a deeper understanding of early child development. With this understanding, the parent can appreciate her own important contribution to the child’s development, thereby gaining enhanced efficacy in the parenting role and becoming empowered as an important agent in the child’s life.
11Six health workers (3 physiotherapists and 3 nurses) were trained by two senior child development experts for a period of one week. This included lectures and practical sessions both at the institution and in the community (Figure 3).
Figures 3. Health workers being trained by child development experts.
12The assessment was matched to the developmental period with an upper limit of 2 weeks. The sessions in the control group lasted for 45 minutes and 75 minutes in the intervention group.
13Stringent methods were put in place to trace babies. Researchers would look for mothers who changed location by interviewing neighbors and looking up these mothers at their new addresses. When found, mothers were encouraged to continue to receive the parent trainer during scheduled home visits. To compare compliance with EIP to another health intervention, we obtained the rates of attendance at immunization clinics of babies born during the same time as the study population.
14Data were entered locally and transmitted electronically to the data coordinating center (RTI International, Research Triangle Park, NC, USA) where edits and data analyses were performed.
15Human Subjects Protection
16This study was approved by the University of Zambia’s Research Ethics Committee and the University of Alabama at Birmingham’s Institutional Review Board.
17A total of 99 mother/babies pairs were screened, with birth weight > 1500g. One baby (1.0%) had notable severe mental/physical impairments. All lived within the study area in rented accommodations (Table 1).
Table 1. Screening information
|
Total
|
Total number screened (N)
|
99
|
Speaks English - n/N (%)
|
57/95 (60)*
|
Baby > 1500 g at Birth - n/N (%)
|
98/99 (99)
|
Severe mental/physical impairment - n/N (%)
|
1/99 (1)
|
Lives in study area - n/N (%)
|
98/99 (99)
|
Consent obtained - n/N (%)
|
80/99 (80)
|
*4 missing
18Consent was obtained from the participants and 80 were enrolled into the study. Mother’s mean age was 23.7, median 22.0 with a standard deviation of 5.6. All the mothers were African, and 67 (83.8%) were married and 13 (16.3%) were single. The mean for years completed at school was 8.8, median 9.0, standard deviation of 3.0 (Table 3).
Table 2. Study completion information
|
Number
|
%/mean + std
|
Total number enrolled
|
80
|
100%
|
Completed study
|
42
|
52.5%
|
Did not complete study
|
34
|
42.5%
|
(Reasons for not completing the study)
|
|
|
Loss to Follow up
|
14
|
41.2%
|
Withdrew
|
16
|
47.1%
|
Died
|
3
|
8.8%
|
Other
|
1
|
2.9%
|
Table 3. Demographic information
|
Statistic
|
Total
|
Total number enrolled
|
N
|
80
|
Mother’s age
|
N
|
78
|
|
Mean
|
23.7
|
|
Median
|
22.0
|
|
Std Dev
|
5.6
|
|
Min – Max
|
15 - 38
|
Mother’s race
|
N
|
80
|
African - n/N (%)
|
n (%)
|
80/80 (100)
|
|
|
|
Marital Status
|
N
|
80
|
Married
|
n/N (%)
|
67/80 (84)
|
Single
|
n/N(%)
|
13 (16)
|
|
|
|
Years of School Completed
|
N
|
79
|
|
Mean
|
8.8
|
|
Median
|
9.0
|
|
Std Dev
|
3.0
|
|
Min – Max
|
0 – 15
|
Table 4. Pregnancy History
|
Statistic
|
Total
|
Total number enrolled
|
N
|
80
|
Gravida
|
N
|
80
|
|
Mean
|
1.9
|
|
Median
|
1.0
|
|
Std Dev
|
1.6
|
|
Min – Max
|
1 - 7
|
Parity
|
N
|
73
|
|
Mean
|
2.0
|
|
Median
|
1.0
|
|
Std Dev
|
1.7
|
|
Min – Max
|
1 - 7
|
Number of children (excluding this one)
|
n
|
35
|
|
Mean
|
1.8
|
|
Median
|
1.0
|
|
Std Dev
|
1.6
|
|
Min – Max
|
0 - 5
|
Pregnancies lost at or before birth - n/N (%)
|
n
|
6/80 (8)
|
Number of preterm babies that died at or bbebefore birth
|
n
|
4
|
|
Mean
|
0.8
|
|
Median
|
1.0
|
|
Std Dev
|
0.5
|
|
Min – Max
|
0 - 1
|
Number of term babies that died at or before birth
|
n
|
5
|
|
Mean
|
1.4
|
|
Median
|
1.0
|
|
Std Dev
|
1.5
|
|
Min – Max
|
0 - 3
|
19Most of the mothers had an average of 2 children (Table 4). Multiple births (twins) occurred in 7 (8.8%) of the mothers, and 98.8 % of the mothers attended antenatal care. The mean gestation age at delivery was 36.8, median 36.0 with a standard deviation of 2.6. The mean age at first visit was 4.6 weeks, median 4.0, standard deviation of 2.1 (Table 5).
Table 5. Current pregnancy information
|
Statistic
|
Total
|
Total number enrolled
|
n
|
80
|
Current pregnancy is multiple births - n/N (%)
|
n
|
7/80 (9)
|
Number of fetuses - n/N (%)
|
n
|
7
|
2
|
n (%)
|
7/7 (100)
|
Mother had prenatal care for current - n/N (%) (%)pregnancy
|
n
|
79/80 (99)
|
Number of prenatal visits
|
n
|
59
|
|
Mean
|
4.2
|
|
Median
|
4.0
|
|
Std Dev
|
1.8
|
|
Min – Max
|
1 - 10
|
GA at first prenatal visit (weeks)
|
n
|
8
|
|
Mean
|
14.3
|
|
Median
|
16.0
|
|
Std Dev
|
5.7
|
|
Min – Max
|
2 - 20
|
GA at delivery (weeks)
|
n
|
79
|
|
Mean
|
36.8
|
|
Median
|
36.0
|
|
Std Dev
|
2.6
|
|
Min – Max
|
26 - 44
|
Age of child at visit (weeks)
|
n
|
79
|
|
Mean
|
4.6
|
|
Median
|
4.0
|
|
Std Dev
|
2.1
|
|
Min – Max
|
2 - 10
|
20Completion in this study was defined as infants followed up at bi-weekly intervals by the research assistants and assessed at 4 months and 8 months of age. Of the 80 enrolled, 42 infants (52.5%) completed the study at 8 months (22 from intervention, and 20 from the control groups). Of the 38 (47.5%) who did not complete the study, reasons were as follows: 19 (50%) were lost to follow up, 16 (42.1%) withdrew, and 3 (7.8%) died (Table 2). The mean length for the EIP visits was 38.7 minutes; median was 40.8 with a standard deviation of 17.6 (Table 6).
Table 6. Study visit/assessment information
Variable
|
Statistic
|
Total
|
Total number enrolled
|
N
|
80
|
Total number of visits
|
N
|
512
|
Number of visits per participant
|
N
|
511
|
1-2
|
n/N(%)
|
125(24.5)
|
3-5
|
n/N( %)
|
154 (30.1)
|
6-8
|
n/N(%)
|
110 (21.5)
|
9-11
|
n/N(%)
|
76 (14.9)
|
12-14
|
n/N(%)
|
38 (7.4)
|
> 14
|
n/N(%)
|
8 (1.6)
|
|
|
|
Age of participant (months)
|
(N)
|
512
|
|
Mean
|
4.2
|
|
Median
|
4.0
|
|
Std Dev
|
2.0
|
|
Min-Max
|
1-8
|
|
|
|
Visit location
|
N
|
508
|
Home
|
n/N(%)
|
210 (41.3)
|
Clinic
|
n/N(%)
|
298 (58.7)
|
|
|
|
Visit type
|
N
|
506
|
EIP
|
n/N(%)
|
419 (82.8)
|
ASQ assessment
|
n/N(%)
|
18 (3.6)
|
EIP & ASQ assessment
|
n/N(%)
|
6 (1.2)
|
Control
|
n/N(%)
|
63 (12.5)
|
|
|
|
Age ASQ assessment completed (months)
|
N
|
21
|
4
|
n/N(%)
|
16 (76.2)
|
8
|
n/N(%)
|
5 (23.8)
|
|
|
|
Length of EIP visits (minutes)
|
N
|
405
|
|
Mean
|
38.7
|
|
Median
|
40.0
|
|
Std Dev
|
17.6
|
|
Min-Max
|
1-330
|
Rating of mother’s use of activities
|
N
|
182
|
1
|
n/N (%)
|
4 (2.2)
|
2
|
n/N(%)
|
9 (4.9)
|
3
|
n/N(%)
|
32 (17.6)
|
4
|
n/N(%)
|
53 (29.1)
|
5
|
n/N(%)
|
84 (46.2)
|
21Our study aim was to assess the feasibility of implementing EIP in an urban, poorly resourced setting. In the study, 52.5% of the enrolled infants completed the study to 8 months; 22 from the intervention group and 20 from the control group. This study used the Partners for Learningcurriculum which is a home-based parent provided model that allows the intervention to occur in the home, a natural environment for learning to occur for a child aged 0-3 years. One advantage of this model is that it relies on tools/materials normally found in the home. It was envisaged that by training eight health workers in administering the Partners in Learning Curriculum, these would become Trainer of Trainers in conducting EIP. This model could then be used not only for infants surviving from birth asphyxia but in other high risk infants such as those with very low birth weight.
22Developmental assessments of babies who survive birth asphyxia also serves as an audit for those performing resuscitation, as an increase in mental handicap following birth asphyxia would warrant a review of skills of birth attendants. Strategies such as WHO Essential Newborn Care have been or are being rolled out to reduce neonatal deaths from birth asphyxia in developing countries. However there is some concern that the survivors may end up with minor to major developmental problems. It is therefore important that well designed control follow-up studies of babies at risk be conducted to assess neuro-developmental outcomes of these interventions (Wallander et al 2010).
23However, in our study there was a high loss to follow-up in comparison with the relatively high compliance for immunization visits, which have a similar schedule (Appendix 2). The immunization coverage for measles was 84 % (WHO 2006). One difference that may account for the better compliance rate is that immunization has been a long and pro-active campaign in educating parents on the need to have infants immunized. It also requires parents to take their children to a specified location. The immunizations are done at the health centres where families can also access treatment for their babies. EIP in contrast is a novel concept in this culture. The message conveying the rationale and benefits of EIP would need careful development to match well this cultural context.
24In order to improve follow up for implementation of an EIP in families living in urban slums there needs to be a careful evaluation of resources (human and financial) required for an effective program. In our study, follow-up of these children in their homes on a bi-weekly basis was expensive both in time and human resources for the health workers. In most developing countries such as Zambia, there is a shortage of healthcare workers, who are needed to attend to the high disease burden. Most of the health workers therefore deal with life threatening illnesses at the health facilities. Diverting health workers to long-term prevention programs may not be preferable under these conditions. Community based interventions using trained non-professional individuals and creation of mother support groups may improve not only the survival of children (through health care messages given at home) (WHO 2006), but also may improve the neuro-developmental outcomes. In a study by Bang et al (Bang 1999) village health workers trained in neonatal care made home visits and managed birth asphyxia, premature birth or low birth weight, hypothermia, and breast-feeding problems. This package of home-based care included the management of neonates with septicemia, meningitis, and pneumonia. Neonatal and infant mortality was reduced by nearly 50% among the malnourished, illiterate, rural study population.
25The parent trainer sessions in the intervention group in our study lasted about 45 minutes per session on a bi-weekly basis, raising questions to sustainability and success in implementation. This may be too much to expect from mothers given the various demands they face. Among the majority of rural and low-income urban dwellers, women perform all domestic tasks, while many also farm and trade. They are also responsible for the care of other children (most participants had more than one child at home), the sick and the elderly, in addition to performing essential social functions within their communities. This poses a challenge for improving neurodevelopmental outcomes through home-based programs where women are overburdened by multiple family chores (Manuh 1998). It is envisaged that exploring new ways of implementing EIP such as the use of trained community based workers and shortening the parent training session may result in a higher compliance rate.
26Studies in developed countries and a few in developing countries have shown that EIP can improve a child’s development (Bennett et al. 1991, Wasik et al. 1990, Brooks-Gunn et al. 1994, McCarton et al. 1997, Reynolds 1994, Bonnie 2008). Follow-up evaluations as long as 18 years have shown significant positive effects for those who received EIP during the first two years of life on measures of intelligence, reading comprehension, mental health, and self-esteem (Walker et al 2005). Empirical data are now available from a small-scale single center trial that suggests that low-cost home-based parent-provided early interventions can improve developmental outcomes in infants with asphyxia also in developing countries (Bao et al. 1997). However, its suitability to the varying conditions among low resources countries must be evaluated.
27To be successful as the immunization programs, interventions to implement neuro-developmental programs for children who have suffered birth asphyxia need further development, taking the social conditions of each setting into consideration.
28In this study we achieved a follow up rate of 52% at 8 months. There is need to conduct further EIP studies to determine ways to improve follow up rates of children surviving birth asphyxia. Integrating early intervention programs with the existing immunization programs may improve follow up rates in the first year of life. It is also important to consider that community based trained interventionists become the core group to spearhead EIP as this would be cost-effective and sustainable due to the shortage of health workers.
29The National Institute of Child Health and Development, under a cooperative agreement with the grantees, provided funding for the study. National Institute of Child Health and Development staff participated in the study design, study conduct, interpretation of the data, and editing of the manuscript.