a Department of Paediatrics,
b Clinical Trials Centre, Faculty of Medicine,
c Department of Statistics and Actuarial Sciences, University of Hong Kong.
Prof. JPE Karlberg, Department of Paediatrics, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, PR China. E-mail: jpekarl{at}hkucc.hku.hk
Abstract
Background Studies have often compared the postnatal motor development of small versus normal newborns. Not much is known about the associations between a broad spectrum of size at birth and motor development. The effect of early postnatal growth on motor development is little researched. Growth failure in terms of shortness and thinness should be differentiated, but not many studies have the data for this analysis.
Methods This is a longitudinal study of infants born in Lahore, Pakistan, between 1984 and 1987. Age at commencement of independent walking and age at building a 3-cube tower were taken as indicators of gross and fine motor development, respectively. Size at birth was captured by length and thinness as continuous variables; postnatal growth from birth to 6 months of age was measured by changes in length and thinness. Adjustment for covariates and handling of censored cases were performed by generalized log gamma regression.
Results Thinness at birth and postnatal stunting and wasting had a linear, inverse association with gross motor development (each P < 0.05). Birth length had a non-linear, inverse association with this outcome (P < 0.05). Birth length, thinness at birth and postnatal wasting had a linear, inverse association with fine motor development (each P < 0.05).
Conclusion Both fetal and early postnatal growth over a broad spectrum may affect infants' motor development. It is not just the babies who were very small at birth that suffered. Birth length appeared to be more influential than other anthropometric indicators.
KEY MESSAGES
Keywords Growth, body height, thinness, motor development
Accepted 3 April 2000
Psychomotor development in infants is often measured in terms of age at achievement of developmental milestones. While developmental milestones have been investigated extensively in developed countries, not many studies can be found in developing countries.16 Yaqoob et al.6 compared the profile of developmental milestones of Pakistani children and children in Europe and North America. Pakistani children born into upper-middle class families had psychomotor development similar to their western counterparts; the rest had a considerable delay in the achievement of most milestones. The reasons for developmental delay were largely unexplored in the paper.
The effect of size at birth on psychomotor development has been studied frequently in the last two decades. However, most previous studies compared normal controls with extreme cases, most often very low or extremely low birthweight babies, using various cut-off points for the classification.712 Not much is known about the association between a broad spectrum of size at birth and developmental delay. In addition, birthweight is a crude indicator of nutrition and growth since small newborns consist of a heterogeneous group.13 It has been suggested that newborns thin at birth have suffered from growth retardation during the last trimester of pregnancy, whereas short newborns have suffered prolonged intrauterine growth retardation.1416 The latter is a more important public health issue in developing countries.16
Postnatal growth faltering during the first 2 years of life is common in developing countries.17 The influence of postnatal growth on psychomotor development is a relatively unexplored area. Again, previous studies mainly consisted of low birthweight babies.15,18 Growth velocity of the human brain has a positively skewed distribution, centring in the perinatal period and skewed towards the postnatal period.19 Humans are more postnatal brain developers than prenatal brain developers; the growth velocity of the human brain is particularly high in the first 6 months of life. Studies in animals have also shown that the cerebellum, which manages motor co-ordination, is the part of the brain most susceptible to early postnatal insults.20 As such, growth faltering in the first 6 months of life may be a potentially important factor influencing motor development.
This is a longitudinal study of gross and fine motor development in Pakistani children. Basic findings on psychomotor development from this Pakistani cohort were reported previously.6 The present study aims to investigate the association between size at birth, postnatal growth in the first 6 months of life, and gross and fine motor development. Instead of dichotomizing infants as small or normal, this paper operationalizes body growth as a continuous phenomenon.
Materials and Methods
Study design
This is a longitudinal study of a population of 1476 infants born between 1984 and 1987 in four different areas of Lahore, Pakistan. The four areas were: a typical village about 40 km from Lahore, a periurban slum on the periphery of Lahore, a typical urban slum area in the city, and an upper-middle class group scattered over the city. The infants were examined monthly during home visits by the doctors of the research project. Details of the research design have been reported elsewhere.6,21
Variables
At each visit weight and supine length were taken to the nearest 100 g and 0.1 cm, respectively. The measuring equipment were checked weekly and maintained by a trained technician. The standard procedures set out by Cameron were followed and used in the training of field staff.22 The independent variables included indicators of length and thinness at birth and indicators of postnatal changes in length and thinness. Due to the cultural practice of not allowing strangers to see a mother immediately after delivery, weight and length at birth could not be measured on the spot. Instead they were measured as early as possible after delivery; babies not measured within 1.5 months of birth were not included in the analysis. Length at first measurement was age and sex standardized according to a WHO recommended international reference.17 This was used as a proxy measure of birth length standard deviation score (SDS). A weight for length SDS proposed by Karlberg and Albertsson-Wikland23 was used to measure thinness. The procedure was to calculate weight for height value = weight SDS-0.7 x height SDS, and then divide it by the standard deviation. This index has the advantage of being roughly independent of height throughout the paediatric years. For brevity, body size at first measurement is referred to as body size at birth. Changes in length SDS and weight for length SDS from birth to age 6 months were used as indicators of postnatal growth. The values represented the SDS at 6 months minus the SDS at birth. They are referred to as postnatal stunting and postnatal wasting.
Covariates adjusted for in multiple regression analysis included residential area, mother's education, incidence of diarrhoea from birth to age 6 months, medical diagnosis at first examination, gestational age and sex. Subjects in the four residential areas had different socioeconomic profiles.24 The periurban slum and village samples had a lower socioeconomic background and poorer housing than the other two groups. Mother's education was classified as none, primary and above primary. At each home visit the number of episodes of diarrhoea in the last month was enumerated. Diarrhoea was defined separately for breastfed and non-breastfed babies.25 The variable used in statistical analysis was the average number of episodes per month from birth to age 6 months. At the first visit the infants were examined by a physician for any medical condition, including congenital abnormalities. The outcome was dichotomized as presence or absence of at least one medical condition. Gestational age was determined using Dubowitz estimates for 56% of the babies;26 the rest were determined by last menstrual period facilitated by a local events calendar. Gestational age was specified as having a linear term and a quadratic term.
At each monthly follow-up several milestones were observed by teams consisting of a field doctor and a woman health visitor. The teams were initially trained to test the milestones and were retrained every 3 months. Independent walking was selected from the Denver Developmental Screening Test as an indicator of gross motor development.27 It was defined as taking about 10 steps without support. Building a tower of 3 cubes was selected from the Developmental Screening Inventory as an indicator of fine motor development.28 The testing involved three demonstrations and three trials. In comparison with other gross and fine motor milestones assessed during the first 2 years of life, the two chosen indicators were achieved at older ages.6 They not only represented relatively long-term outcomes of size at birth, but also allowed an examination of the effect of postnatal catch-up growth, which usually take place in the first 6 months of life. When the child achieved a milestone, age at onset of that milestone was taken as the average of age at this follow-up and age at the previous follow-up. Chronological age was used in the main analysis. Age corrected for gestational duration,29,30 i.e. chronological age plus (gestational age 40 weeks), was calculated and used in subsidiary sensitivity analyses.
Statistical analysis
There were two sources of unobserved outcomes (censoring): losses to follow-up before achievement of milestones, and not having achieved the milestones by the last follow-up at age 24 months. The latter phenomenon was rare for independent walking (n = 5), but fairly common for cube tower building (n = 90). We therefore used a survival analysis approach to handle the censoring. Graphical examination of the observed age at achievement of milestones suggested that the distributions were positively skewed and looked roughly log normal. The analysis was based on a generalized log gamma model, which is very flexible in shape and includes the log normal as its special case.31 The regression coefficients represented differences in age at achievement of milestones on the log scale. The exponentiated regression coefficients were interpreted as time ratios (TR). For example, a time ratio of 0.9 meant that one-unit increase in the variable was associated with a 10% reduction (younger) in average age at achievement of a milestone. The variables were forced entries in the multiple regression models in a pre-specified manner. The exceptions were quadratic terms for the four anthropometric variables, whose inclusion or exclusion was based on significance tests. Interactions were examined by the likelihood ratio test. Deviance residuals were examined by graphical means. To give a more clinical feel of the impact of fetal and postnatal growth, we estimated the median ages at achieving the two milestones for subjects at 2 and +2 standard deviations of each anthropometric variable, using the medians and time ratios from the regression models. Similarly, the differences for the extreme values of other significant variables were also estimated. In a sensitivity analysis we repeated the survival models excluding infants not measured for size on the first day of birth.
Results
In all, 212 subjects were not measured for body size within 1.5 months of birth, among them 33 died and 8 migrated out of the research area before 1.5 months. The median age at first measurement was 2 days. The medians for the two socioeconomically disadvantaged areas, i.e. the village and periurban slum, were 1 and 4 days, respectively; the medians for the urban slum and city groups were 3 and 2 days, respectively. Two hundred and fifteen subjects were not measured for body size around 6 months of age, among them 91 died and 51 migrated before 6 months. Thirty-five subjects had missing or extreme values (<5 SDS or >5SDS in anthropometric variables; >44 weeks of gestational age). The number of subjects in the analyses was 1014.
Table 1 shows the distribution of the categorical variables. Table 2
summarizes the distribution of the continuous variables. The infants were 0.4 SDS thinner and shorter than expected. From birth to age 6 months the infants experienced considerable stunting, i.e. a decline of about 0.8 SDS. Mean gestational age was 39 weeks. Only 20 (3%) infants were pre-term (<37 weeks). The mean onset of independent walking was 14 months of age. Correction for gestational duration slightly reduced this average to 13.8 months. The mean age at building a 3-cube tower was 18 months (17.8 months after correction for gestational duration).
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No significant interaction was found between growth and residential area and mother's education (each P > 0.05), or between residential area and mother's education (each P > 0.05). In a sensitivity analysis, we substituted gestation-corrected age at achieving the milestones into the survival models. In another sensitivity analysis, we included only the infants who were measured for size on the first day of birth (n = 415). The results were almost identical to Table 4 (details not shown).
Discussion
Relatively few previous studies have examined the impact of a broad spectrum of size at birth, and few have investigated the impact of early postnatal growth. Information on birth length was not often collected in either routine health information systems or research projects. Thus it is sometimes difficult to say whether it is birthweight or birth length that has an impact on development. This study of Pakistani infants has the advantage of investigating both length and thinness at birth, as well as postnatal changes in them.
Due to cultural reasons, body size was not measured immediately after birth. We had to use the measurements from the first visit as indicators of size at birth, and we excluded subjects not measured within the first 1.5 months of birth. However, half of the infants were measured within 2 days of birth so the first measurement should give reasonable estimates of size at birth. The first measurements were made earlier in the village and city groups; earlier or later measurements did not concentrate in the two disadvantaged areas. Residential areas had also been adjusted for as a categorical variable in the analysis. A sensitivity analysis showed that excluding all subjects not measured on the first day would give virtually identical results. It is debatable whether chronological age or age corrected for gestation is a more valid and clinically useful measure of child development.29,30 Nevertheless, this debate did not concern us as the two measures were highly correlated and sensitivity analysis showed no practical difference in the regression outcomes.
In bivariate correlation analysis, shortness and thinness at birth were inversely associated with postnatal growth. This suggested some postnatal catch-up growth. Since the size at birth and postnatal variables were correlated, multiple regression analysis was used to reveal a clearer picture. In multiple regression analysis, residential area and mother's education were related to age at onset of independent walking and/or cube tower building. Medical conditions at first examination and incidence of diarrhoea did not show any statistical significance. Confounding due to congenital anomalies and infection seemed unlikely. Briend maintained that the impact of diarrhoea on growth was probably exaggerated.32 Children caught-up in nutritional status after an episode of diarrhoea; the effect of the disease on growth was only transient.32,33 The same reason may explain the lack of association between diarrhoea and the two markers of motor development. With adjustment for covariates, both shortness and thinness at birth and their postnatal changes were related to age at commencement of independent walking. Length SDS at birth showed a non-linear relation with the outcome. The residual plot suggested that, in the 3 SDS to 1.5 SDS range, the form of relation was adequately captured by a quadratic function. The model overestimated the outcome for those born with length above 2 SDS. This is the typical end effect of using natural polynomials in regression analysis.34 The quadratic function imposed a spurious upturn at the upper end of the curve. However, it is not important in the present study since only a few babies fall in that range. For infants born shorter than the average (zero SDS) of the international reference, the regression coefficients implied a roughly linear dose-response relation. The effect of birth length levelled off among average and above average values. Zero SDS appeared to be a threshold of birth length effect on delayed gross motor development. Other aspects of fetal and early postnatal growth had a linear, inverse association with the gross motor development outcome. Length SDS at birth, thinness at birth and postnatal wasting were significantly associated with the fine motor milestone. The relations were inverse and linear.
Shortness and thinness at birth indicate growth failure at different stages of pregnancy. The former is an indication of fetal undernutrition with an onset in the second trimester; a prevalent problem in developing countries.16 Since the short or thin infants might include some normal infants whose small body size was due to genetic reasons, the present estimates of relationship may be somewhat underestimated. The true importance of fetal and early postnatal growth failure on motor development should in that case be slightly higher. Among the four factors, length SDS at birth stood out as being the most influential on both aspects of motor development. Previous studies have tended to focus on birthweight. Our findings called for more emphasis on the investigation of birth length and its implications. The findings also suggest that it is not just those very small babies who suffered delayed gross and fine motor development. Rather, in the Pakistani context, the larger is usually the better, with the exception that babies of above average birth length did not enjoy extra gain in gross motor development. While improving the health of some very small babies is important in clinical settings, improving the health of many slightly small babies would be more important for the promotion of a healthy population.35 Moreover, postnatal growth was also inversely related to motor development. It is not that clear whether poor postnatal growth and under-nutrition lead to developmental delay, or whether infants may adapt to those problems by reducing interaction with the environment. However, both situations are undesirable. Interventions to improve fetal and postnatal growth may be helpful in facilitating child motor development. Whether the two aspects of motor development are powerful in predicting later/adult performance is not well known at the moment. To elucidate this, studies with long-term follow-up are warranted.
Acknowledgments
The authors are grateful to the comments of the referees, which improved the clarity of this paper. This study is made possible by grants from the Swedish Agency for Research Cooperation with Developing Countries (SAREC), and from the Faculty of Medicine, University of Hong Kong. Professor F Jalil, Kings Edward Medical College, Pakistan, was the principal investigator on the Pakistani side for the SAREC project.
References
1 Bhandari A, Ghosh BN. A longitudinal study on child development in relation to socioeconomic factors. Ind J Med Res 1980;72:67784.[ISI][Medline]
2 Freeman HE, Klein RE, Townsend JW, Lechtig A. Nutrition and cognitive development among rural Guatemalan children. Am J Public Health 1980;70:127785.[Abstract]
3 Lejarraga H, Krupitzky S, Gimenez E et al. The organization of a national survey for evaluating child psychomotor development in Argentina. Paediatr Perinat Epidemiol 1997;11:35973.[ISI][Medline]
4 Ojofeitimi EO, Elegbe I, Jinadu MK, Oladipo CA. Factors affecting delayed walking skill in malnourished children. Child Abuse Neglect 1984;8:36972.[ISI][Medline]
5 Upadhyay SK, Saran A, Agarwal DK, Singh MP, Agarwal KN. Growth and behavior development in rural infants in relation to malnutrition and environment. Ind Pediatr 1992;29:595606.
6 Yaqoob M, Ferngren H, Jalil F, Nazir R, Karlberg J. Early child health in Lahore, Pakistan: XII. Milestones. Acta Paediatr 1993;390(Suppl.): 15157.
7 Nickel RE, Bennett FC, Lamson FN. School performance of children with birth weights of 1,000 g or less. Am J Dis Child 1982;136:10510.[Abstract]
8 Ornstein M, Ohlsson A, Edmonds J, Asztalos E. Neonatal follow-up of very low birthweight/extremely low birthweight infants to school age: a critical overview. Acta Paediatr Scand 1991;80:74148.[ISI][Medline]
9 Robson A, Cline B. Developmental consequences of intrauterine growth retardation. Infant Behavior Dev 1998;21:33144.[ISI]
10 Smedler AC, Faxelius G, Bremme K, Lagerstrom M. Psychological development in children born with very low birth weight after severe intrauterine growth retardation: a 10-year follow-up study. Acta Paediatr 1992;81:197203.[ISI][Medline]
11 Tenovuo A, Kero P, Korvenranta H, Piekkala P, Sillanpaa M, Erkkola R. Developmental outcome of 519 small-for-gestational age children at the age of two years. Neuropediatr 1998;19:4145.
12 Williamson WD, Wilson GS, Lifschitz MH, Thurber SA. Nonhandicapped very-low-birth-weight infants at one year of age: developmental profile. Pediatr 1990;85:40510.[Abstract]
13 Beattie RB, Johnson P. Practical assessment of neonatal nutrition status beyond birthweight: an imperative for the 1990s. Br J Obst Gyn 1994;101:84246.[ISI][Medline]
14 Barker DJP. Mothers, Babies and Health in Later Life. Edinburgh: Churchill Livingstone, 1998.
15 Tudehope DI, Burns Y, O'Callaghan M, Mohay H, Silcock A. The relationship between intrauterine and postnatal growth on the subsequent psychomotor development of very low birth weight (VLBW) infants. Aust Paediatr J 1983;1:38.
16 Villar J, Altobelli L, Kestler E, Belizan J. A health priority for developing countries: the prevention of chronic fetal malnutrition. Bull World Health Organ 1986;64:84751.[ISI][Medline]
17 WHO Working Group. Use and interpretation of anthropometric indicators of nutritional status. Bull. World Health Organ 1986;64:92941.[ISI][Medline]
18 Connors JM, O'Callaghan MJ, Burns YR et al. The influence of growth on development outcome in extremely low birthweight infants at 2 years of age. J Paediatr Child Health 1999;35:3741.[ISI][Medline]
19 Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Human Dev 1979;3:7983.[ISI][Medline]
20 Lynch A, Smart JL, Dobbing J. Motor coordination and cerebellar size in adult rats undernourished in early life. Brain Res 1975;83:24959.[ISI][Medline]
21 Jalil F, Lindblad BS, Hanson LA et al. Early child health in Lahore, Pakistan: I. Study design. Acta Paediatr 1993;390(Suppl.):316.
22 Cameron N. The methods of auxological anthropometry. In: Falkner F, Tanner JM (eds). Human Growth. New York: Plenum Press, 1986, Vol.2, pp.820.
23 Karlberg J, Albertsson-Wikland K. Nutrition and linear growth in childhood. In: Bindels JG, Coedhart AC, Visser HKA (eds). Recent Development in Infant Nutrition. Dordrecht, The Netherlands: Kluwer, 1996, pp.11227.
24 Hagekull B, Nazir R, Jalil F, Karlberg J. Early child health in Lahore, Pakistan: III. Maternal and family situation. Acta Paediatr 1993; 390(Suppl.):2737.
25 Mahmud A, Jalil F, Karlberg J, Lindblad BS. Early child health in Lahore, Pakistan: VII Diarrhoea. Acta Paediatr 1993;82(Suppl.390): 7986.
26 Dubowitz LM, Dubowitz V, Goldberg C. Clinical assessment of gestational age in the newborn infant. Pediatr 1970;77:110.[Abstract]
27 Frankenburg WK, Dodds JB. The Denver developmental screening test. J Pediatr 1967;71:18191.[ISI][Medline]
28 Knobloch H, Pasamanick B. (eds). Gesell and Amatruda's Developmental Diagnosis: The Evaluation and Management of Normal and Abnormal Neuropsychologic Development in Infancy and Early Childhood. New York: Harper & Row, 1974.
29 Allen MC, Alexander GR. Gross motor milestones in preterm infants: correction for degree of prematurity. J Pediatr 1990;116:95559.[ISI][Medline]
30 Den-Ouden L, Rijken M, Brand R, Verloove-Vanhorick SP, Ruys JH. Is it correct to correct? Developmental milestones in 555 normal preterm infants compared with term infants. J Pediatr 1991;118: 399404.[ISI][Medline]
31 Cox DR, Oakes D. Analysis of Survival Data. London: Chapman & Hall, 1984.
32 Briend A. Is diarrhoea a major cause of malnutrition among the under-fives in developing countries? A review of available evidence. Eur J Clin Nutr 1990;44:61128.[ISI][Medline]
33 Briend A, Hasan KZ, Aziz KMA, Hoque BA. Are diarrhoea control programmes likely to reduce childhood malnutrition? Observations from rural Bangladesh. Lancet 1989;ii:31922.
34 Royston JP, Altman D. Using fractional polynomials to model curved regression relationships. Stata Tech Bull Rep 1995;4:11027.
35 Rose GA. The Strategy of Preventive Medicine. Oxford: Oxford University Press, 1992.