This prospective cohort study was conducted at All India Institute of Medical Sciences, New Delhi during 2013-2016 after approval from the ethics committee. Healthy term singleton infants were enrolled at birth after informed consent from the parents. Infants with birthweight <1800 gram and >4000 gram, any illness requiring neonatal intensive care unit stay or intravenous fluid therapy for >48 hours, maternal inability or contraindication to breastfeeding, families belonging to lower socio-economic strata, and large family size (more than three alive siblings) were excluded.

Gestational age was calculated based on last menstrual period. Infants were classified into small, appropriate and large for gestational age (SGA, AGA and LGA, respectively) using Indian intrauterine growth curves [11]. Socioeconomic status was determined based on the income, education and occupation of head of the household [12]. Maternal serial weights were noted from her antenatal records, and weight of father was measured with a bathroom scale. Height of both parents was measured using stadiometer to an accuracy of 0.5 cm.

Nude weight of infant was measured at birth by electronic weighing balance with a sensitivity of 10 gram (Seca 354, Seca GmbH). Length and skinfold thicknesses at biceps, triceps, subscapular and supra-iliac sites were measured within 48 hours of birth using infant measuring board (Seca 417, Seca GmbH), and Holtain calipers (Holtain Ltd), respectively. All measurements were made in duplicate and averaged. Anthropometric equipment were calibrated regularly. Percentage body fat (BF%) was calculated from the sum of skinfolds using the equations given by Weststrate and Deurenberg [13]. Weight and length were converted to z-scores using World Health Organization (WHO) Anthro plus software. Anthro-pometric measurements (weight, length and skinfold thicknesses) were repeated at 3.5 months (±2 weeks), 1 year (±1 month), and 2 years (±2 month) of age. Standing height was measured for all children at 2 years. If the age of the child was less than completed 24 months, 0.7 cm was added to the standing height before calculation of z-score to make it equivalent to supine length. Feeding of infants was assessed using infant and young child feeding (IYCF) questionnaire [14], and detailed dietary intake was recorded at 1 year and 2 year visits using a one-month semi-quantitative food frequency question-naire. Caloric intake was calculated by a qualified dietician.

Catch-up growth and catch-down growth were defined as an increase or decrease in z-score of > 0.67 between two time points [4]. This approximately represents the width of each major percentile band on standard growth charts (e.g., 10th to 25th or 25th to 50th), and therefore can be considered clinically significant.

Sample size was estimated as 225 taking prevalence of weight catch-up between birth and 2 years as 30% [4], with precision of 6%. Considering the possibility of upto 15% attrition of the cohort, 262 infants were enrolled.

Statistical analyses: The proportion of infants who experienced catch-up growth and catch-down growth during the different time periods was calculated. The anthropometric measurements, adiposity and caloric intake were compared between infants with and without catch-up growth. Factors that could affect the increment in weight for age z-score between birth to 3.5 months, birth to 1 year and birth to 2 year, including parents’ height and BMI, maternal parity, socio-economic status, and infants’ birthweight, gender and feeding were evaluated by linear regression. P <0.05 was considered as significant.

A total of 262 newborns (150 boys) were enrolled. The baseline characteristics of the cohort are shown in Table I and study flow chart is presented in Fig. 1. Table II summarizes the anthropometric parameters as absolute values, z-scores, and proportion of infants with z-scores < -2 at birth and follow-up. At 2 years, 11 (4.9%) children had BMI z-score > +2, of whom 4 were born LGA while the rest were born AGA.

In this contemporary birth cohort, median weight and length z-scores were close to –1 at birth, improved by one year of age and again declined during the second year. Body fat percentage increased maximally between birth to 3.5 months, and then showed a small decline.

Both catch-up growth and catch-down growth in weight were common in this cohort. Infants with birthweight close to the median birthweight of Indian infants (approximately 2.9 kg) had a steady growth pattern while those with lower and higher birthweights showed catch-up growth and catch-down growth patterns, respectively. A similar pattern was noted for length, with the median length of infants with steady growth being about 48.5 cm, which is close to our national average. Catch-up growth and catch-down growth are considered as target-seeking patterns that bring babies with fetal growth restriction and excessive fetal growth, respectively, towards their normal growth channels [10]. Thus, the present study suggests that the birthweight and length of Indian babies, although low as compared to the international median [1], may be physiologically normal for our population. Similar conclusions were drawn in a previous study from southern India that noted that birthweight distribution of Indian infants is shifted to the left, and the risks associated with being LGA were present at lower weights [17].

The weight trajectories of infants born in the lowest and highest tertile of WAZ converged at 2 years like narrowing of a funnel, similar to observations in Bangla-deshi infants [18]. In the present study, LAZ at 2 years but not at birth correlated with the height of both parents. Thus, CUG and CDG in length served to align the length of the infants to their genetic potential. About two-thirds of infants cross length centiles in the first 2 years in order to reach their mid-parental height centiles [19].

In the present study, weight CUG between birth and 3.5 month, 1 year and 2 year was chiefly driven by lower birthweight. Previous studies have also emphasized that lower birthweight is the exclusive determinant of CUG in first six months [20]; and growth during infancy should be assessed not just by comparing with reference charts, but also taking infants’ birthweights into account [21]. In the present study, it was observed that while catch-up growth was commoner than catch-down in the first year, the reverse was true in the second year; and change in weight z-score between 1-2 year was positively correlated with caloric intake. An earlier Indian study [22] reported an inverse association between duration of exclusive breastfeeding and weight gain between birth to 2 years, similar to the present study, reiterating that optimal feeding between birth to 2 years is important to avoid growth faltering as well as accelerated weight gain.

The mean values of body fat percentage in the present study were similar to those reported from the Western countries [15,16]. An overall trend for improvement in nutritional status was observed in this study, more marked for BMI than length.

Infants who had catch-up growth in first 3.5 months had higher BMI z scores and body fat at 2 years compared to those without catch-up growth. The median LAZ remained nearly the same, indicating that early weight catch-up growth does not improve statural growth but may contribute to obesity in later childhood. These findings were in consonance with our earlier study where early catch-up growth (in first 6 to 12 weeks) in term low birth infants was associated with higher body fat at 7 months [23]. Rapid weight gain in early infancy may contribute to later adiposity, obesity and cardiometabolic diseases [2-7].

This study used WHO z-scores for presenting the anthropometric data, which takes into account the variations in the exact age at the time of anthropometric measurements as well as gender, and makes international comparisons easier. The study had low attrition, and we also measured body fat. The limitations were that the findings cannot be extrapolated to infants with birth weights outside the 1800-4000 g range, the effect of catch-up growth and catch-down growth on neurodevelop-ment, risk of infections, blood pressure and metabolic parameters was not assessed, and longer follow-up of this cohort was not done.

To conclude, catch-up and catch-down growth in weight and length are very common in the first 2 years of life, which may represent physiological adjustments towards the median and the genetically determined growth trajectory in the majority. Infants’ feeding may also contribute to growth acceleration/deceleration. Early increase in weight z-score was associated with higher adiposity at the age of 1 and 2 years. We recommend that the determinants and consequences of CUG and CDG in infancy should be studied further in larger cohorts followed up for a longer duration.

Acknowledgments: Babita Upadhyaya, dietician, for help with dietary assessment, and Anuj Kumar and Naveen Kumar for technical help with acquisition of data.

Ethics clearance: AIIMS Ethics Committee; No. IEC/NP-127/2012 and RP-21/2012, dated April 27, 2012.

Contributors: VJ: conceptualized and designed the work, supervised data acquisition and analysis, interpreted the data and drafted the paper; BK, SK: acquired the data and helped with analysis and writing. All authors have given final approval to the version to be published.

Funding: Department of Biotechnology, Government of India (Grant No. BT/PR3884/Med/97/03/2011).

Competing interests: None stated.