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Abstract
Background Early life growth trajectories of Indian small for gestational age (SGA) infants are sparse. This study aimed to compare longitudinal growth in appropriate for gestational age (AGA) and SGA infants during their first year of life.
Methods Apparently healthy term infants (52 SGA, 154 AGA) were recruited at birth and followed up till 1 year. Parental, sociodemographic characteristics and feeding patterns were recorded. Anthropometric measurements were assessed at birth, 3, 6, 9 and 12 months of age; Z scores and growth velocity at 3-month intervals were computed. Longitudinal measurements were compared between the two groups, using the two-way Friedmans test. Median regression with mixed effects was used to adjust covariates; p value <0.05 was considered statistically significant.
Result AGA infants had significantly higher median weight (kg) (2.87 (2.67, 3.04) vs 2.39 (2.25, 2.54)) at birth, (7.08 (6.50, 7.54) vs 6.49 (6.13, 6.78)) at 6 months, (8.64 (7.92, 9.14) vs 7.90 (7.36, 8.54)) at 12 months, median length (cm) ((48.10 (47.20, 49.30) vs 46.75 (45.43, 47.50)) at birth, (65.50 (64.23, 66.98) vs 63.33 (62.26, 65.28)) at 6 months, (73.30 (71.58, 74.66) vs 71.55 (70.00, 73.30)) at 12 months. SGA infants had comparable weight velocity at all intervals except 9–12 months (6.62 (6.45, 6.79) vs (6.70 (6.51, 6.85)), being significantly higher than AGA infants. Differences in skinfold thicknesses between groups were observed only at birth. Exclusivity of breast feeding was significantly higher at 3 months in AGA, compared to SGA infants (80.9% vs 57.8%). Length velocity was comparable at all ages between groups. Sexual dimorphism was observed in the growth velocities of both groups.
Conclusion SGA infants grew in parallel to AGA infants, having significantly lower anthropometric measurements at all time points. However, growth velocities were similar; SGA infants had significantly higher weight velocity from 9 to 12 months. Longitudinal studies beyond 1 year of age, using body composition are needed to determine the quality of growth in Indian infants.
- Growth
- Breastfeeding
- Infant
Data availability statement
Data are available upon reasonable request. Kindly email the corresponding author (RK), for data that supports the findings of the present study.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
SGA neonates have increased risk of morbidity, stunting, poor linear growth in early life along with increased risk of later life morbidity.
WHAT THIS STUDY ADDS
Novel data on the growth trajectories of Indian AGA and SGA infants; SGA infants grew in parallel to AGA infants having significantly lower anthropometric measurements from birth to 1 year of age.
Weight velocity of SGA infants was significantly higher at the 9 to 12 month age interval. Skinfold measurements of SGA infants were lower only at birth and caught up with AGA infants.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This study emphasises the importance of monitoring early life growth in Indian infants and providing energy recommendations based on their growth patterns.
Findings of the present study along with follow-up beyond 1 year of age, with additional body composition measurements can help inform policy makers on the quality of growth in infants born with low weight, thereby provide appropriate dietary interventions to promote optimal growth, yet prevent childhood obesity.
Introduction
Small for gestational age (SGA) infants have birth weight <10th percentile of sex-based reference standard1; prevalence rate in India is 36.5%.2 SGA infants exhibit increased risk of delayed neurodevelopment and poor linear growth,2 3 with term and preterm SGA infants being more likely to be stunted in childhood than appropriate for gestational age (AGA) term infants.3 On the other hand, the intrauterine programming and genetic modulation resulting in SGA can increase the risk of morbidity in later life, predisposing these infants to higher risk of insulin resistance, obesity, dyslipidaemia and hypertension in adulthood.4–6
SGA infants often experience early-life catch-up growth (CUG). CUG is described as the upward crossing of centiles observed in infants born low birth,7 and also defined as an increase in Z score of >0.67 between two-time points.8 CUG aids in improved neurodevelopment, enhanced immune function, supports survival in early life and in achieving final adult height.9 However, the CUG can also initiate a cascade of metabolic risk factors.9–11 Excessive CUG in weight of SGA infants from the USA and UK,12 13 was associated with higher abdominal fat mass, elevated blood pressure and high fasting glucose.12–14 Indian infants with lower birth weight showed higher CUG, which was associated with higher adiposity at 1 and 2 years.7 Term SGA Chinese children with CUG, had higher insulin resistance (HOMA-IR), when compared with SGA children who did not show CUG and AGA children,14 suggesting that early CUG may be associated with higher adiposity and metabolic alterations.15
Growth and body composition trajectories of Indian infants, particularly SGA infants are limited. In Pune, Maharashtra, children born SGA showed relatively poor growth and were stunted between 0.5 and 5 years, when compared with AGA infant16; SGA children from the lower socio-economic strata were more stunted.16 A study from Delhi, estimating body composition using deuterium dilution technique, observed term SGA infants to have similar fat mass index (FMI; kg/m2) and per cent fat mass (% FM) at 2 years compared with AGA infants, despite lower weight and fat-free mass index (FFMI; kg/m2).17 Understanding longitudinal growth changes that occur during early life in SGA infants, is particularly relevant in Indian infants who are postulated to be of ‘thin yet fat’ phenotype.18 Thus, the primary objective of the present study was to accurately measure and compare longitudinal growth (weight and linear growth) from birth to 1 year of life in SGA and AGA infants from South India. The secondary objective is to compare longitudinal growth velocities of SGA and AGA infants stratified by sex, from birth to 1 year. The hypothesis of the study was that SGA and AGA infants exhibit differences in their patterns of growth and growth velocities from birth to 1 year of life.
Methods
Participants
Term infants (37+0 to 41+6 weeks of gestational age), born to apparently healthy mothers from singleton pregnancy were recruited from St. John’s Medical College Hospital, Vani Vilas Hospital and Anganwadi Centres in Bengaluru between July 2018 and April 2022. Infants with birth defects, congenital anomalies and those requiring intensive hospital care were excluded. Details on recruitment and follow-up are detailed in figure 1. The gestational age was determined based on mother’s last menstrual period and the infants were classified as SGA or AGA.1
Strengthening the Reporting of Observational Studies in Epidemiology diagram of the present study.*Observations that had missing follow-up visit after the 3-month visit were deleted from the final analysis.AGA, appropriate for gestational age; SGA, small for gestational age.
Sample size
Sample size was calculated using an average difference of 1.4 cm in length over the five-time points, with anticipated correlation coefficient of 0.3 and an SD of 3.3 cm between term AGA and SGA infants,17 with 80% power, 95% CI, and 20% inflation for data skewness, 30% attrition and expecting 30% of the infants to be SGA. Thus, a minimum sample of 46 SGA and 132 AGA infants were estimated to be enrolled to complete the study in the cohort.
Sociodemographic and parental details
A semi-structured questionnaire was administered to capture sociodemographic details. Obstetric history and pre-pregnancy weight were obtained from hospital records. Maternal gestational weight gain was calculated as the difference in maternal body weight between first and third trimesters (measured at the last antenatal visit). Parental anthropometry was measured using standard methodology.19
Infant anthropometry
Measurements were performed on infants at birth (≤7 days after birth) and subsequently at 3, 6, 9 and 12 months of age. Infant body weight was measured using a calibrated paediatric electronic weighing scale, with an accuracy of 10 g (Salter 914, Delhi, India) and length using an infantometer (SECA 417, Hamburg, Germany) at St. John’s Research Institute using standard protocol.20 Weight-for-age Z (WAZ), height-for-age Z (HAZ) and weight-for-height Z (WHZ) scores were computed.21 Birth weight was obtained from hospital records. Circumferences of head and mid-upper arm were measured using non-stretchable fibreglass tape (ADC 396, Hauppauge, New York) to the nearest 0.1 cm.20 Triceps, biceps, suprailiac and subscapular skinfold thicknesses were measured using Holtain Calliper (Holtain, UK 610ND)20 on the left side of the infant’s body in triplicates and the mean of three readings were taken. All measurements were performed by three trained personnel and the interobserver/intraobserver difference was ≤1%.
Assessment of feeding practices
Infant’s feeding history was recorded at each visit and exclusivity of breast feeding was defined.22 Details on the complementary feeding practices were captured at 7, 10 and 12 months of infant’s age by trained nutritionists, using a 3-day, 24-hour recall, using standardised volume measures. The nutrient composition was computed using nutritive value of raw foods from databases23 24 and the average of 3-day food intake was considered. The adequacy of the dietary intake was evaluated for assessing infant and young child feeding (IYCF) practices.25
Statistics
Assumption of normality were tested using Shapiro-Wilk’s test (p<0.05). Continuous outcomes were presented as mean±SD or median (IQR) and categorical variables as frequency and percentages. Infants with no follow-up visits after the second visit were deleted and infants with minimum of three visits were included in the analysis. Growth velocity for the anthropometric measurements and Z scores were calculated at 3-month intervals, as the difference between two consecutive measurements and the given time (3–0, 6–3, 9–6, 12–9 months). Friedman’s two-way analysis of variance with time and group interaction (SGA/AGA) was used to compare the parameters (both group and sex-stratified), and complementary food intake between two groups at all ages since the data was not normally distributed. Median regression with mixed effects was used to adjust the summaries of growth velocity variables for maternal age, maternal weight and gender (except Z scores to prevent overadjustment) using the qrLMM package. Pairwise comparisons were performed using the Dwass-Steel-Critchlow-Flinger pairwise comparison tests at each time point. The estimated median with IQR of the anthropometric measurements and growth velocity adjusted for gender and maternal factors were reported. Pearson’s χ2 test or Fisher’s exact test were used to test the association between AGA and SGA infants for categorical variables such as maternal pre-pregnancy body mass index (BMI), mode of delivery, parental education, income, gender and exclusivity of breast feeding. The one sample median test was used for comparison of anthropometric velocities with WHO Multicentre Growth Reference Study (MGRS).21 P<0.05 was considered statistically significant and all statistical analyses were performed using RStudio V.4.4.2.
Results
The general characteristics of the study population are presented in table 1. Only maternal and paternal weight of AGA infants were significantly higher (~6 kg), compared with SGA infants. The birth weight and percentage of boys were significantly lower in SGA infants.
Parental and infant characteristics at birth
Longitudinal anthropometric measurements of infants from birth to 1 year of age
Figure 2 and table 2 compare the anthropometric measurements of AGA and SGA infants at different time points. The missingness of data for the anthropometric variables ranged from 3% to 15% over the longitudinal measurements. AGA infants had significantly higher measurements at all ages, except for WHZ score which was significantly higher at birth, 9 and 12 months. The skinfold measurements were similar at all ages, except at birth.
Longitudinal changes in anthropometry and Z scores between AGA and SGA infants from birth to 12 months.Panels represent the comparison of the different anthropometric and growth indicators of SGA and AGA infants. (A) Median weight (kg); (B) median length (cm); (C) median head circumference (cm); (D) median WAZ; (E) median HAZ; (F) median WHZ.Bold black line represents AGA group; dotted black line represents SGA group.*Significant difference between the two groups at that age interval.P value <0.05 was considered significant (Friedman’s two-way analysis of variance and median regression with mixed effects (with time and group interaction) and pairwise comparisons by the Dwass-Steel-Critchlow-Flinger test).AGA, appropriate for gestational age; HAZ, height for age Z score; SGA, small for gestational age; WAZ, weight for age Z score; WHZ, weight for height Z score.
Longitudinal anthropometric measurements of AGA and SGA infants from birth to 12 months
Growth velocity of anthropometric parameters at 3-month intervals
The comparison of velocities between the infant groups at 3-month intervals are depicted in figure 3 and online supplemental table 2. The weight velocity (g/d) was comparable between AGA and SGA infants at all time points, except for the 9–12 months interval, where the SGA infants had a significantly higher velocity compared with AGA infants. The length velocity (cm/d) and WAZ score was comparable at all time intervals. Velocities of other measurements were significantly higher in AGA infants at a few age intervals, while SGA infants had higher WHZ score velocity per month, at 0–3 months age interval.
Supplemental material
Comparison of velocities of anthropometric and growth indicators between AGA and SGA infants at 3-month intervals from birth to 12 months.Panels represent the comparison of the velocities of different anthropometric and growth indicators of SGA and AGA infants. (A) Weight velocity (g/d); (B) length velocity (cm/d); (C) head circumference velocity (cm/d); (D) WAZ velocity (per month); (E) HAZ velocity (per month); (F) WHZ velocity (per month).Bold black line represents AGA group; dotted black line represents SGA group.*Significant difference between the two groups at that age interval.P value <0.05 was considered significant (Friedman’s two-way analysis of variance and median regression with mixed effects (with time and group interaction) and pairwise comparisons by the Dwass-Steel-Critchlow-Flinger test) adjusted for gender, maternal age and maternal weight).AGA, appropriate for gestational age; HAZ, height for age Z score; SGA, small for gestational age; WAZ, weight for age Z score; WHZ, weight for height Z score.
Growth velocity stratified by sex at 3-month intervals
Sexual dimorphism in growth velocities was observed within and between the groups of infants (figure 4 and online supplemental table 3). In AGA infants, boys had significantly higher weight velocity compared with girls across all age intervals, whereas in SGA infants, boys showed significantly higher weight velocity only at 0–3 months, while girls had higher weight velocity at 9–12 months interval. Length velocity was significantly higher in boys at 0–3 months and 9–12 months interval compared with girls. The head circumference, HAZ and WHZ velocities/months were comparable between sexes in both groups at all age intervals. WAZ velocity/months was comparable between sexes in both groups at all ages except at 6–9 months interval, where AGA boys were significantly higher when compared with girls. However, WAZ velocity/months of SGA boys were comparable with girls at all ages (online supplemental table 3). Growth velocities of AGA and SGA infants from the present study were observed to be significantly lower in both sexes, at all age intervals compared with WHO MGRS standards.21
Comparison of velocities of anthropometric and growth indicators stratified by sex in AGA and SGA infants at 3-month interval from birth to 12 months.Panels represent the comparison of the velocities of different anthropometric and growth indicators stratified by sex (boys and girls) in SGA and AGA infants. (A) Weight velocity (g/d); (B) length velocity (cm/d); (C) head circumference velocity (cm/d); (D) WAZ velocity (per month); (E) HAZ velocity (per month); (F) WHZ velocity (per month).Bold black line represents AGA group; dotted black line represents SGA group.*Significant difference within sex, between the two groups at that age interval.P value <0.05 was considered significant (Friedman’s two-way analysis of variance and median regression with mixed effects (with time and group interaction) and pairwise comparisons by the Dwass-Steel-Critchlow-Flinger test) adjusted for gender, maternal age and maternal weight).AGA, appropriate for gestational age; HAZ, height for age Z score; SGA, small for gestational age; WAZ, weight for age Z score; WHZ, weight for height Z score.
Infant and child feeding practices
Exclusive breast feeding (EBF) rates were significantly lower at 3 months in SGA (57.8%) compared with AGA (80.9%) infants, but comparable at 6 months, with only 11.5% of AGA and 12.0% of SGA infants being EBF. Nutrient intake patterns (online supplemental table 1) were similar between groups, except at 7 months and 12 months where SGA infants had significantly higher energy intake (kcal/kg body weight) and AGA infants had higher vitamin A (IU) intake at 12 months. All indicators of IYCF practices,25 were comparable at all ages between the groups, except for vegetable and fruit intake at 7 months, where SGA infants had significantly higher consumption.
Discussion
This present study which accurately tracked growth in South Indian infants from birth to 12 months suggests that SGA infants grew in parallel to AGA infants at almost all time points; however, the growth velocities were similar, with SGA infants having a significantly higher weight velocity (g/d) at 9–12 months age interval. Sexual dimorphism was observed with boys having higher anthropometric measurements and growth velocities at most age intervals. Similar findings were observed in Filipino/Chinese SGA infants who had rapid growth in the first months of life, followed by minimal CUG thereafter.26 27
Early CUG has been associated with risk of being overweight in childhood/adolescents. CUG in infants born SGA from UK, aged between 4 and 7 years, was associated with higher abdominal fat mass, blood pressure and glycaemia between 4 and 7 years.13 Although weight and FFMI were lower at 2 years, in Indian infants born SGA, when compared with AGA infants, the FMI was similar, suggesting that catch-up in adiposity may occur earlier than lean mass in Indian SGA infants.17 The findings of our study showed that SGA infants had significantly higher weight velocity at 12 months, and similar skinfold thickness measurements when compared with AGA infants. Accelerated growth in weight in early life has been associated with increased risk of obesity, metabolic syndrome and cardiovascular disease.28 29 Monitoring infants born SGA should start from the neonatal period and extend into adulthood, in order to attenuate the long-term impact on health and disease.
The SGA infants of the present study, had significantly lower length at all time points when compared with AGA infants, being consistent with previous literature,11 emphasising the need for appropriate interventions to prevent later life stunting in infants born SGA. Similar to findings of previous studies, sexual dimorphism was observed in both groups of infants for all anthropometric velocities, with male infants having higher values at most age intervals, .26 27 30 Various factors such as hormonal differences, genetic, nutritional, socioeconomic and cultural factors could play a role.31
The growth velocities of both SGA and AGA infants in the present study were significantly lower at all ages when compared with the WHO MGRS velocity standards,22 which could be due to differences in socioeconomic status, maternal nutritional, environmental exposures and genetic factors between the study populations. Reduced postnatal growth velocity, progressively leads to growth faltering, increasing the burden of childhood morbidity, mortality and future non-communicable disease risk.32 This is relevant in Indian infants postulated to be of the ‘thin-fat phenotype’. Targeted nutritional interventions covering the first 1000 days are important since maternal nutritional and at-birth characteristics of the infant are important determinants of growth faltering during the first 2 years of life.32
In our study, parental body weight was significantly different between the infants born AGA and SGA. Studies have suggested intergenerational relationship between parental and infant size for gestational age status and preterm birth.9 33 34 Additionally, rapid CUG was observed in SGA infants whose parents were taller or had higher BMI.7 35 Hence, parental nutritional and birth outcomes should be considered when assessing the biological and environmental risk factors contributing to infant size for gestational age status.7 36
Breast feeding practices and morbidity are the key determinants of postnatal growth in term SGA infants, particularly in low/middle-income countries.37 In our study, only 57.8% of SGA infants were EBF at 3 months, which was significantly lower than AGA infants (80.9%). Studies indicate that EBF infants grew better than formula fed peers,36 however mothers of SGA may face more challenges concerning infant’s size, often leading to supplement infant’s diet with formula milk. The complementary feeding intake in both AGA and SGA infants of the present study were similar, except for the SGA infants having significantly higher energy intake (kcal/kg body weight) at 7th and 12th months, which may have contributed to the higher weight velocity in SGA infants at the 9–12 months age interval. While previous literature on SGA infants is not available, the AGA infants from the present study had better dietary intake, when compared with similar Indian mother-infant cohorts at 12 months of age assessed by IYCF indicators.38
The limitations of the present study were lack of details on maternal smoking, water, sanitation and hygiene practices. The COVID-19 pandemic and lockdowns resulted in loss to follow-up in the cohort. Body composition estimates and certain biomarkers could have provided additional insights. This study may also lack power, for growth velocity comparison between sexes. Despite these limitations, this well-conducted study adds valuable data to the scanty literature of early-life growth trajectories of SGA and AGA infants in India. Infants born with low weight are often advised increased energy intake, without considering its long-term health effects. Thus, identifying population specific growth patterns will help inform adequate energy intake for optimal growth, while simultaneously preventing excessive energy intake leading to childhood obesity.
The findings of the study suggest SGA infants grew in parallel to AGA infants. Growth velocities were similar, except for SGA infants showing higher weight velocity at 9–12 months interval. Sexual dimorphism existed in both groups. Further longitudinal follow-up beyond 1 year of age with body composition measurements and cardio-metabolic characterisation will help understand the quality of growth and in planning targeted interventions to prevent long-term disease outcomes in Indian infatns born with low weight.
Data availability statement
Data are available upon reasonable request. Kindly email the corresponding author (RK), for data that supports the findings of the present study.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Institutional Ethical Review Board, St. John’s Medical College Hospital, Bengaluru, India. IEC Study reference number: 162/2017. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
The authors acknowledge the entire study team for their involvement in data collection. We are grateful to all the mothers and their neonates who participated in the study.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
SRP and RP are joint first authors.
SRP and RP contributed equally.
Contributors SRP and RP contributed equally to this work and are joint first authors. RK designed the research (project conception, overall research plan and study oversight). SRP and RP wrote the initial drafts of the manuscript, RK critically reviewed the draft. RP, SK, JVA and DP were involved in the recruitment and data collection. SRPN and SKJ facilitated the recruitment of neonates into the study; AK performed the statistical analysis; SRP, RP, AK and RK were involved in the interpretation of results; RK is the guarantor and has full responsibility for the work, conduct of the study, access to data and overall content. All authors have read and approved the final manuscript.
Funding This research work was supported by the Department of Biotechnology, Ministry of Science and Technology, India (Grant Number: BT/PR20575/PFN/20/1304/2017) through funds to Rebecca Kuriyan.
Competing interests None to declare.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.