Are early childhood stunting and catch-up growth associated with school age cognition?-Evidence from an Indian birth cohort.

BACKGROUND: Millions of children worldwide especially in the Asian subcontinent are vulnerable to early childhood stunting. There are contradictory reports of the association between catch-up growth in childhood and school age cognition.
METHODS: A community-based birth cohort recruited between 2010 and 2012 from urban slums in Vellore, India was followed up until 9 years of age. From regular anthropometric measurements, stunting status for each individual child was calculated at 2, 5 and 9 years. Cognition was assessed at 9 years of age using the Malin's Intelligence Scale for Indian Children (MISIC). Children were divided into groups based on stunting at each time point as well as catch-up growth, and a regression model was utilised to evaluate their association with cognition at 9 years.
RESULTS: Among 203 children included in this analysis, 94/203 (46.31%) children were stunted at 2 years of age, of whom 39.36% had a catch-up growth at 5 years of age, and 38.30% at 9 years. Around 10% of the cohort remained stunted at all time points. In the multivariable analysis, children who were stunted at 2, 5 and 9 years had a significantly lower verbal and total intelligence quotient (IQ) scores by 4.6 points compared to those who were never stunted. Children with catch up growth following stunting at 2 years had higher cognition scores than those who were persistently stunted throughout the childhood.
CONCLUSIONS: This study showed persistent stunting in childhood was associated with lowering of 4-5 IQ points in childhood cognition at 9 years of age. Recovery from early life stunting in children with catch up growth prevented further lowering of cognition scores in these children compared to persistently stunted children. Nutritional supplementation during late infancy and early toddlerhood in addition to continuing nutritional supplementation programmes for preschool and school children can improve childhood stunting and cognitive abilities in vulnerable populations.

Introduction

The sustainable development goal (SDG) 4 of achieving quality education by 2030 [1] is vulnerable to ongoing early childhood risks. Twin risks of early childhood stunting, and absolute poverty have caused over 200 million young children worldwide, majority of them in the low- and middle-income countries (LMIC), to have suboptimal developmental potential [2-4]. Around 150 million under-five children globally are stunted, defined as height for age z scores (HAZ) < -2 Standard Deviation (SD) on WHO growth charts [5], with more than half belonging to the Asian continent [6]. A sub-national analysis of child malnutrition in India found average child stunting to be 39.3%, with states having low socio-demographic index of development being disproportionately more affected [7]. Children globally have similar growth potential in life, as evidenced by comparable growth performance of affluent Indian children to that in developed countries [8]; but those growing up in vulnerable environments are exposed to early childhood risks affecting not just their linear growth, but also developmental potential.

The first 1000 days of life are critical for optimal developmental potential as brain development happens during this period through neurogenesis, neuronal migration, axonal and dendritic growth, synaptogenesis, myelination, and synaptic pruning [9], and any disruption to this neuronal process can affect long-term structural and functional capacity of the brain [2]. Children exposed to early childhood risk factors thus have not just stunting, but also developmental, cognitive and learning difficulties. Stunting has been identified as a major public health priority due to its association with an individual’s morbidity, mortality, and reduced developmental, learning and economic potential, and its propagation of ‘intergenerational cycle of poverty’ [3, 10]. Meta analyses have shown consistent relationship between early childhood stunting with child cognitive and motor development [11] and later adult height, but an inconclusive association with adult educational potential and achievement [12].

Human growth and development are continuous processes throughout the whole lifespan, and periods beyond the first 1000 days of life are also vital to optimise an individual’s potential [13]. Longitudinal studies have shown that catch-up growth can happen between 24 months and mid-childhood and during adolescence years [14]. There are contradictory findings in the literature on the extent of cognition recovery due to catch-up in linear growth, with some studies reporting no association with cognition or development [15-17], while others reporting catch-up growth even in late childhood improving cognitive deficits in stunted children [18, 19]. These contradictory findings may be due to differing definitions and time periods studied [20, 21]. Absolute catch-up is defined as a child growing up to match the mean healthy reference sample height to narrow the height-for-age difference (HAD), while a relative catch-up is an improvement in the HAZ score [20, 21]. Catch-up growth can be also defined by stunting status at each time point where children once stunted grow up to attain HAZ scores within normal limits (≥ -2 SD) in subsequent follow-up [18, 22–24].

In this context, birth cohort studies, especially in LMIC settings such as India, can help in our understanding of the pattern of undernutrition and recovery from birth throughout the childhood, and its impact on cognition in the childhood. Birth cohort studies can also compare different growth trajectories through childhood and thus providing an opportunity to plan for timing of interventions to improve overall growth capacity and in turn economic and human potential. The objective of the current study was to evaluate the association of stunting and catch-up growth with childhood cognition at 9 years in an urban slum birth cohort setting in India.

Materials and methods

Study population and methodology

The current study population was a birth cohort originally enrolled for the ‘Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development’ (MAL-ED) Network, a longitudinal prospective multinational, cohort study conducted in eight countries across the world [25]. The Indian study site was in Vellore, South India and consisted of eight adjacent densely populated urban slum dwellings [26]. Details about study population, recruitment process, exclusion criteria and follow-up are already published [26-29].

The initial birth cohort recruitment was conducted between March 2010 and February 2012 and recruited 251 new-borns. Children were subsequently followed up at 2, 3, 5, 7 and 9 years of age. The original birth cohort recruitment and subsequent follow-ups were approved by the Institutional Review Board and Ethics committee of Christian Medical College Vellore, and children were recruited at each stage after written informed parental consent with additional child assent at 9 years of age.

Measures

Length of children was measured to the nearest cm using infantometer until 2 years of age. Stadiometer was used for further height measurements after 2 years of age. Weight was measured using an electronic weighing scale to the nearest 10 grams. Head circumference was measured using a non-stretchable tape by a trained person to the nearest 0.1 cm. All machines underwent periodic recalibration, and personnel had periodic retraining as per the MAL-ED protocol. For follow-ups separate training was conducted for all personnel involved. To calculate z-scores for height/weight for age, Multicentre Growth Reference Study (MGRS) standards was used for measurements done under-5 years and WHO AnthroPlus software for measurements performed at 9 years [5]. Stunting was defined as HAZ < -2 on WHO growth curves [5] and catch-up in growth defined as HAZ within normal SDs on WHO charts after previous instance/s of stunting [20]. Current definition used for catch-up growth using stunting status at each time points has been widely used in other cohort studies from similar LMIC settings for growth trajectory modelling [15, 21–24]. Advantage of use of this definition based on HAZ scores, would be that HAZ is a relative measure accounting for variability in growth in the reference population, compared to measures based on HAD, which is an absolute measure for growth.

The Malin’s Intelligence Scale for Indian Children (MISIC)

The Malin’s Intelligence Scale for Indian Children (MISIC) [30] is the Indian adaptation of the Wechsler Intelligence Scale for Children (WISC). This test can be administered to children from 6 years to 16 years.

Verbal sub-scales measure the range of factual information in terms of vocabulary, and the ability to comprehend and reason by logical and deductive thinking. The verbal scale has subtests of Information, Similarities, Arithmetic, Vocabulary, Comprehension and Digit Span. Performance sub-scales measure visual perception, spatial organization and co-ordination. The performance scale has subtests of Picture Completion, Coding, Picture Arrangement, Block Design and Object Assembly. This measure was administered in a distraction-free environment in the community clinic setting by a single psychologist. Raw scores were converted into standardized scores and corresponding quotients were computed using mental and chronological ages. Verbal intelligence quotient (VIQ) was derived from verbal subscales, performance intelligence quotient (PIQ) from performance sub-scales and total intelligence quotient (IQ) using all subscales.

The WAMI measure for socio-economic status

Socio-economic status (SES) was measured in the MAL-ED study using a composite measure with components of access to improved Water and sanitation, Assets, Maternal education and total household Income (WAMI) [31]. A trained field worker visited the home and administered the translated and piloted WAMI measure.

Raven’s progressive matrices

The Raven’s progressive matrices measures non-verbal reasoning ability and can be used as culture-fair measure [32]. A single trained psychologist administered this measure to all mothers at 6–8 months of child’s age, as per the MAL-ED study protocol, to assess maternal cognition [33]. We used raw scores for our analysis.

Data entry and analysis

Completed paper forms were validated by field supervisor before data entry. Information from the paper forms were entered into electronic database using a double entry database system managed by the Data Co-ordinating Centre of the MAL-ED study [25].

Statistical analysis

Categorical variables including sociodemographic characteristics and anthropometric measurements were expressed as percentages and compared across the time-points between birth and 9 years of age. Families of children with WAMI scores less than 33rd percentile were classified as low for socioeconomic status and those who scored 33rd percentile and above were classified as high.

Based on their stunting status at 2, 5 and 9 years of age, children were grouped into four categories–i) children who were never stunted, ii) children stunted at 2 years with a catch-up at 5 years, iii) children stunted at 2 and 5 years, with a catch-up at 9 years, and iv) children stunted at 2, 5 and 9 years. Continuous variables such as mother’s cognition, cognitive assessment scores in children using MISIC scale were expressed as mean and standard deviation. Statistical significance of verbal IQ, performance IQ and total IQ between the groups was tested using Analysis of variance (ANOVA). Simple linear regression analysis was used to model the association of stunting on cognition scores analysed at 9 years. Having the children who were never stunted as the reference category, effect of stunting at one or more time points on cognition scores, under verbal and performance domain, was assessed separately after adjusting for mother’s cognition and socioeconomic status at 2 years of age in the multivariable model. Beta co-efficients along with 95% confidence interval were reported. Model fit was assessed using R2 values and p-value < 0.05 was considered as the level of significance. Stata version 13 (StataCorp. 2013. Stata Statistical Software. Release 13. College Station, TX: StataCorp LP) software was used for the statistical analysis.

Results

Between 2010 and 2012, 301 pregnant mothers residing in the study area were screened for recruiting 251 new-borns in the original birth-cohort. Details about study population, recruitment, exclusion criteria and follow-up are already published [26–29, 34]. There were 228 (90.84%), 212 (84.46%) and 205 (81.67%) children available for follow-up at 2, 5 and 9 years respectively (Fig 1). Families moving out of the study area was documented as the predominant reason for loss to follow-up in the study and this finding from the same birth-cohort has already been published [29]. The 9-year recruitment was planned between February 2019 and February 2021. Due to the Covid-19 pandemic, recruitment was paused for > 6 months in 2020. Anthropometric and cognitive assessments for all children were completed by April 2021.

Fig 1

Flowchart depicting the follow-up of the birth cohort.

This birth-cohort was established in urban settlements of Vellore and families of children in this cohort had their adults working as predominantly unskilled labourers. Access to safe water and sanitation facility was sub-optimal for the study families and 17% of babies weighed less than 2.5 kg at birth. Cohort characteristics at enrolment, 2, 5 and 9 years were similar with respect to sex distribution and SES characteristics (Table 1). Mothers’ mean cognition raw score (SD) was 43.91 (10.49) on Raven’s matrices. Proportion of children who were stunted (101/228–44.5%) and under-weight (81/228–35.7%) was highest by 2 years of age and this declined by 5 years and more so by 9 years (Table 1 and Fig 2).

Table 1

Comparison of cohort characteristics at birth enrolment, years 2, 5 and 9 of follow-up of MAL-ED cohort.

	Enrolment (At birth) n = 251 (%)	2 years n = 228*(%)	5 years n = 212 (%)	9 years n = 205#(%)
Gender
Male	113 (45)	105 (46.05)	98 (46.23)	96 (46.83)
Female	138 (55)	123 (53.95)	114 (53.77)	109 (53.17)
Socioeconomic status (SES)
Low (WAMI < 33rd percentile)	71 (30.2)	71 (31.14)	65 (30.66)	-
High (WAMI ≥ 33rd percentile)	164 (69.79)	157 (68.86)	147 (69.34)
Height-for-age Z scores (HAZ)
≥ - 2 SD	210 (83.67)	126 (55.51)	150 (70.75)	183 (89.27)
< - 2 to ≥ - 3 SD	31 (12.35)	69 (30.40)	50 (23.58)	20 (9.76)
< -3 SD	10 (3.98)	32 (14.10)	12 (5.66)	2 (0.98)
Weight-for-age Z scores (WAZ)
≥ - 2 SD	194 (77.29)	146 (64.32)	149 (70.28)	146 (73)
< - 2 to ≥ - 3 SD	41 (16.33)	61 (26.87)	52 (24.53)	34 (17)
< -3 SD	16 (6.37)	20 (8.81)	11 (5.19)	20 (10)

Only 227 children had information on WAZ and HAZ scores at 2 years of follow-up.

#Only 205 children had information on WAZ scores at 9 years of follow-up.

MAL-ED—Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development; IQ–Intelligence Quotient.

Fig 2

Proportion of children stunted at 0, 2, 5 and 9 years of age in MAL-ED cohort.

About 203/251 children in the cohort had complete information on stunting at all time points. However, to study the association between early childhood stunting with/without a catch-up at later ages and cognition at 9 years, only 200/203 were considered for analysis. Remaining 3/203 children were not included in the analysis, as 2/3 children were stunted only at 5 years and the other child only at 9 years, with normal growth parameters at other time-points. 91/203 children were stunted at 2 years of age, of whom 34/91 (37.36%) had a catch-up growth at 5 years of age, 36/91 (39.56%) remained stunted at 5 years and had a catch-up growth by 9 years, and 21/91 (23.08%) continued to remain stunted at 5 and 9 years (Table 2) The mean HAZ score of the cohort measured at birth, 2, 5 and 9 years of age was -0.97, -1.89, -1.55 and -0.73 respectively. Children in all groups showed the lowest HAZ score at 2 years of age with subsequent improvements at 5 and 9 years of age.

Table 2

Grouping of children in MAL-ED cohort based on stunting* status at 2, 5 and 9 years (n = 200).

Groups	n (%)	Mean (SD) HAZ scores at birth	Mean (SD) HAZ scores at 2 years	Mean (SD) HAZ scores at 5 years	Mean (SD) HAZ scores at 9 years
Children who were never stunted	109 (54.50)	-0.65 (0.91)	-1.20 (0.58)	-0.93 (0.63)	-0.26 (0.76)
Children stunted at 2 years and catch-up at 5 years	34 (17)	-1.20 (1.05)	-2.30 (0.21)	-1.52 (0.34)	-0.79 (0.46)
Children stunted at 2 and 5 years, and, catch-up at 9 years	36 (18)	-1.32 (0.84)	-2.88 (0.56)	-2.47 (0.36)	-1.06 (1.87)
Children stunted at 2, 5 and 9 years	21 (10.50)	-1.67 (1.3)	-3.32 (0.75)	-3.00 (0.46)	-2.48 (0.38)

Children with height-for-age z scores < - 2SD were classified as stunted.

#Of 203 children who had complete information on stunting at all three time points, 200 (98.52%) were included in one of the above groups. The remaining 3/203 (1.48%) children who were not included in any of the above groups, two were stunted only at 5 years, with their HAZ scores at 2 and 9 years ≥ 2 SD, and, another child was stunted only at 9 years, followed by HAZ scores ≥ 2 SD at 2 and 5 years.

The mean VIQ, PIQ and total IQ (SD) scores of children at 9 years of age were 94.03 (9.71), 91.49 (13.01) and 92.76 (10.26) respectively. Distribution of cognition scores across the groups based on stunting status of children at one or more time points is presented in Table 3. Children who were never stunted scored high in VIQ and total IQ assessment with mean (SD) scores of 95.19 (9.51) and 94.37 (9.75) respectively, compared to those who were stunted at one or more time points. In the multivariable analysis (Table 4), after adjusting for mother’s cognition scores and socioeconomic status at 2 years, children who were stunted at 2, 5 and 9 years had significantly lower verbal IQ scores by 4.6 points lesser than those who were never stunted (VIQ—89.15 vs 95.19 respectively; adjusted beta co-efficient (95% CI): -4.61 (-8.86 - -0.36)). In performance domain, children who were stunted at 2 years, but recovered later had lesser IQ scores by 5.8 points when compared to those of who were never stunted during the follow-up (PIQ– 87.88 vs 93.54 respectively; adjusted beta co-efficient (95% CI): -5.77 (-10.51 - -1.03)). R2 values for models based on verbal and performance outcome was 14.88% and 13.96% respectively. Children who were stunted at 2, 5 and 9 years had significantly lesser total IQ scores by 4.6 points compared to those who were never stunted (IQ– 88.16 Vs 94.37; adjusted beta co-efficient (95% CI): -4.62 (-9.07 - -0.17)).

Table 3

Distribution of verbal, performance and total cognition raw scores, and IQ at 9 years in children who were stunted at various time points of follow-up in MAL-ED cohort (N = 200).

Groups, n	Verbal scores, mean (SD)			Performance scores, mean (SD)			Total scores, mean (SD)
	Raw scores	IQ	P value *	Raw scores	IQ	P value *	Raw scores	IQ	P value *
Children who were never stunted (n = 109)	475.96 (47.56)	95.19 (9.51)	0.024	467.64 (61.87)	93.54 (12.40)	0.051	943.60 (97.48)	94.37 (9.75)	0.036
Stunted at 2 years and catch-up at 5 years (n = 34)	474.18 (47.93)	94.85 (9.54)		439.41 (83.67)	87.88 (16.73)		913.59 (122.65)	91.36 (12.27)
Stunted at 2 and 5 years, and, catch-up at 9 years (n = 36)	457.75 (49.88)	91.55 (9.98)		452.36 (59.68)	90.47 (11.94)		910.11 (101.13)	91.01 (10.11)
Stunted at 2, 5 and 9 years (n = 21)	445.76 (45.77)	89.15 (9.15)		435.79 (51.51)	87.16 (10.30)		881.55 (84.86)	88.16 (8.49)

#200/203(98.52%) children who had complete information on stunting at all three time points were included in this analysis.

*Statistical significance between the groups for verbal IQ, performance IQ and total IQ was tested using ANOVA.

Table 4

Association of stunting status at 2, 5 and 9 years and verbal, performance and total IQ scores at 9 years of age using regression analysis (n = 200).

Predictors	Adjusted beta co-efficient (95% CI)
	Verbal IQ	Performance IQ	Total IQ
Stunting
Children who were never stunted	1	1	1
Stunted at 2 years and catch-up at 5 years	-0.20 (-3.70–3.29)	-5.77 (-10.51 - -1.03)	-3.00 (-6.65–0.66)
Stunted at 2 and 5 years, and, catch-up at 9 years	-1.79 (-5.27–1.69)	-0.88 (-5.60–3.85)	-1.33 (-4.97–2.31)
Stunted at 2, 5 and 9 years	-4.61 (-8.86 - -0.36)	-4.64 (-10.41–1.14)	-4.62 (-9.07 - -0.17)
Socio economic status at 2 years
Low (<33rd percentile of WAMI)	1	1	1
High (> = 33rd percentile of WAMI)	5.13 (2.27–7.98)	4.91 (1.04–8.79)	5.02 (2.04–8.01)
Mother’s IQ scores	0.18 (0.06–0.31)	0.33 (0.16–0.49)	0.26 (0.13–0.38)

IQ–Intelligence Quotient; WAMI–Water, Assets, Maternal Education and Income

#200/203(98.52%) children who had complete information on stunting at all three time points were included in this analysis.

Bolded values have significant p-values

R2 values for regression models with following outcomes -verbal, performance and total IQ scores were 14.88%, 13.96% and 17.06% respectively.

Discussion

The present study evaluated childhood catch-up growth after early childhood stunting and its association with cognition at 9 years of age in a LMIC urban slum setting in India. Proportion of stunting in cohort children was noted to be the highest at 2 years of age with subsequent catch-up growth at 5 and 9 years of age. Children who were never stunted had better intelligence by 4–5 IQ points than those stunted throughout childhood. Children who were stunted at 2 years and had a catch up later had higher cognition scores compared to persistently stunted children. For verbal cognition, a graded response was seen where children whose height improved earlier performed better than those who caught up later.

In this birth cohort study, maximum stunting was observed at 2 years of age, where more than 40% of the cohort children were stunted. All 5 birth cohorts in the ‘Consortium on Health Orientated Research in Transitional Societies’ (COHORT) study was noted to have a similar nadir at 2 years of age [35]. In the current study, more than 75% of children who were stunted at 2 years caught up by 9 years of age, with only 10% of the original cohort being stunted at all time points. This is similar to another study published from Kerala where 50% children who were stunted at 0–4 years of age caught up by 7–11 years [36], but the percentage of children who caught up in linear growth in the current study is higher. Our finding is in discordance with the COHORT study follow-up, where longitudinal growth catch-up was noted by childhood in other birth cohorts, but not in the Indian site [37]. However, the HAZ at 2 years in the Indian COHORT study site was -1.9 [35], which is similar to what is reported in the current study. The COHORT study was conducted in New Delhi in north India in the 1980s and the Kerala study the beginning of 2010–20 decade. The present study has followed children for 9 years in the 2010–20 decade, spilling over to the current one. It is possible that national nutrition intervention schemes for children through preschool programmes such as Balwadis and school midday noon meal schemes are better implemented currently to provide the catch-up growth as seen in this study. Balwadi program initiated in 1970–71 by the Government of India caters to health, nutritional and educational needs of preschool children aged 3 years onwards, while midday meal schemes support one wholesome meal for school going children [38, 39]. It is also imperative that such nutritional support schemes should continue for school going children as evidence from the Young Lives study show that linear growth faltering and catch-up also happen in late childhood and adolescent years between 8 and 15 years of age [18].

Early childhood stunting has been shown to be associated with childhood cognitive and motor abilities [11]. The Benin Demographic and Health Survey (BDHS) in Benin, Africa [40], Indian, Ghana and Peruvian studies [41-43] and the MAL-ED study conducted across 8 countries [44] have shown detrimental association of early childhood stunting on early childhood development in preschool years itself. The Cebu Longitudinal Health and Nutrition Study in Philippines [23, 45], the Pelotas birth cohort in Brazil, Birth to 20 plus cohort in South Africa [46, 47] and studies in Peru [48] and Thailand [49] provided evidence of early stunting being associated with poor later childhood cognition. The COHORT study done in Brazil, Guatemala, India, Philippines, and South Africa [50] and the Pelotas birth cohort study in Brazil [47] have shown that early stunting was associated with poor educational achievement in adulthood, though a subsequent meta-analysis showed inconclusive evidence [12]. A unit increase in HAZ at < 2 years of age resulted in 0.22 SD increase in cognitive ability in the childhood (5–11 years) in another meta-analysis [11]. The current study concurs with the existing literature that persistent childhood stunting is associated with lower verbal, performance and full cognition scores in mid-childhood and shows a lower cognition score of 0.3 SD (4–5 IQ points) in children who were persistently stunted. Stunting represents chronic undernourishment during early years of life in children, when rapid neurodevelopmental process takes place. It has been documented in human as well as animal studies that undernourishment during early childhood affects the neurodevelopment process such as neuronal growth, synaptogenesis and myelination process. In addition to undernutrition, literature has shown that there is an interplay of factors such as micronutrients intake, child’s interaction with external environment, caregiver’s behaviour, and timing and recovery from undernutrition, which holistically determine cognitive development process in children [51, 52]. Common and intersecting risks and causative pathways can affect both child growth and cognition, but stunting is generally recognised as the best surrogate for overall child health especially in resource poor settings [10].

Differing definitions of linear growth catch-up and time points utilised have given conflicting reports of its benefit in the literature [20]. As 2 years is the culmination of the first 1000 days of life including the gestational period, utilising this time point is more appropriate as done in the current analysis. The Young Lives study done in Ethiopia, India, Peru, and Vietnam showed that the catch-up growth between 1 and 8 years of age was associated with better receptive vocabulary, reading comprehension and mathematic achievement [53] and between 8 and 15 years was associated with better cognition and schooling outcomes in adolescence [18]. However, a study done in north India reported no relationship between linear growth change from early to late childhood and cognition in late childhood [54], but this study recruited children initially at an age range between 6–30 months. Another Indian study evaluating catch-up growth showed that school-level nutritional interventions caused better growth, but not the corresponding cognitive ability [17], probably due to an earlier onset insult to brain growth and cognition, as well as the short nature of intervention (6 months). Contrastingly, a rural Malawian study reported that late childhood growth was related to better cognition during the adolescence [55]. However, the present study showed that stunted children with catch-up growth between 2 and 9 years of age had relatively higher cognition scores than the persistently stunted children, highlighting that earlier recovery after toddlerhood stunting prevented further lowering of cognition scores in these children compared to those who were persistently stunted. Thus, catch-up in growth in this period did not overcome all cognitive deficits due to early childhood stunting and is concurrent with other published literature [19, 23]. Another finding from our study that children who were stunted at 2 years and recovered by 5 years had a significantly lower performance IQ scores compared to children who were never stunted, highlights the fact that interventions to prevent early life stunting are not substitutable. Thus, our study adds to the evidence that consequence of early deprivation is not fully reversible, and it is important to identify nutritional deficiencies, in terms of calorie, protein and micronutrient requirements during the first 1000 days of life in children with appropriate, corrective interventions at the earliest, so as to maximize the gain in human capital.

Limitations of the current study include comparatively smaller sample size and some minimal loss to follow-up due to migration of families outside the study area. Strengths of the MAL-ED India cohort are strong range of data availability for early childhood, good follow-up rates at 2, 5 and 9 years of the cohort, standardised assessments with good quality control, and India-specific cognitive assessment in childhood.

Conclusions

The current study showed persistent stunting in childhood was associated with a 0.3 SD lowering in childhood cognition attainment at 9 years of age and an early catch-up before 5 years prevented further lowering of cognition scores, although the cognitive deficits as a result of early nutritional deprivation persisted. Continuing nutritional supplementation programmes for preschool and school children can help in improving overall growth parameters as well as optimal education as envisaged in the SDG 4 [1]. Additional nutritional supplementation during late infancy and early toddlerhood can improve the stunting nadir seen at 2 years of age, and this has to be complemented with policy measures improving overall socioeconomic status of the family and improving educational attainment among mothers. Extending Balwadi or community support to this group with provision of home delivery of nutritional supplements might help this cause.

(XLS)

Click here for additional data file.

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

27 Sep 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Seo Ah Hong, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following in the Acknowledgments/ Financial Support Section of your manuscript:

a. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequence for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill and Melinda Gates Foundation, the Foundation for the NIH and the National Institutes of Health/Fogarty International Center (Grant number – GR-681)

b. The 9-year follow-up of the Mal-ed India cohort was supported by an Intermediate clinical and public health research fellowship awarded by the DBT/Wellcome Trust India Alliance to Dr. BK. (Fellowship grant number IA/CPHI/19/1/504611)

Sponsors/Funders had no role in the study design, data collection and analysis, decision to publish or preparation of manuscript.

Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

a. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequence for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill and Melinda Gates Foundation, the Foundation for the NIH and the National Institutes of Health/Fogarty International Center (Grant number – GR-681)

BK, LMK, RS, VRM, SJ, GK - GK lead

Sponsor/Funder had no role in the study design, data collection and analysis, decision to publish or preparation of manuscript.

b. The 9-year follow-up of the Mal-ed India cohort was supported by an Intermediate clinical and public health research fellowship awarded by the DBT/Wellcome Trust India Alliance to Dr. BK. (Fellowship grant number IA/CPHI/19/1/504611).

Sponsor/Funder had no role in the study design, data collection and analysis, decision to publish or preparation of manuscript.

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

3. Thank you for stating the following in your Competing Interests section:

No competing interests exist

Please complete your Competing Interests on the online submission form to state any Competing Interests. If you have no competing interests, please state "The authors have declared that no competing interests exist.", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now

This information should be included in your cover letter; we will change the online submission form on your behalf.

4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is an interesting paper and is potentially a very useful addition to the literature. The cohort, while small, has a high level of retention and a number of informative measures. It is great, for example, that there is data on maternal cognition.

My concern with this paper is that the authors have not critically engaged with some of the key issues in the literature, despite mentioning a number, and these have significant implications for the interpretation of their results.

-The authors note that the definition of catch up is a point of dispute in the literature, but do not explain why they selected the one that they used. The one used is a rather weak definition - children can be defined as having caught up even when falling behind in terms of CM deficits. Nonetheless, it is a commonly used definition and its use could be justified, but it does need to be justified and not used without question.

-Stunting does not cause cognitive impairment, impairment and stunting are both indicators of malnutrition and possibly of lack of stimulation (and possible the combination of the two). As a result, any association between them needs to be carefully interpreted. The authors do not adequately cover this topic, which hinders the subsequent discussion of the results.

-If the authors are going to make the case that their results imply that nutrition programmes are needed, then a fuller discussion of the adequacy of the controls in the regression is needed. As mentioned, the association with stunting may be a result of smaller children being protected by parents leading to under stimulation - this may not be resolved by a nutrition program. Similarly, smaller children may be held back from school entry as parents do not think they are ready. The association between stunting and cognitive performance may be a result of less exposure to schooling.

-Do the authors think that catch up growth could indicate a recovery from earlier malnutrition leading to a similar catch up in cognition? Or that those who catch up avoid falling further behind, while those who remain stunted continue to fall behind? Their results could support either argument, but which argument is correct has important policy implications and this should be discussed.

The authors from time to time slip into causal language, this should be avoided.

The discussion on the importance of the first 1,000 days is a little unclear and could be improved. It is the pace and foundational nature of development in that period which is critical and this does not come through enough.

Overall the paper is well written, but there are a few places which would benefit from a careful edit.

Minor comments:

Why report weight if you don't use it? Just for context?

The top third based on WAMI can hardly be called high SES given the selection process. Would relatively high not be better?

When was the WAMI measure taken? What the implications of only using one time point? Did those who exhibited catch up also see an improvement in their SES which might explain the better cognitive scores?

Reviewer #2: Thank you for a very interesting study. Overall, the study is well conducted. There are a few comments and editorial as below.

1. Table 4: on the PIQ, it is shown that stunting at 2 y, though with a catch-up at 5 y had 5.77 PIQ less than normal children, but the children who stunted at 2 & 5 who only caught-up at 9 had much better PIQ than normal, than children who were already catch-up since 2y and those persisted till 9 y. What could explain such a pattern? Please add discussion.

2. Lines 365-366 & reference 17: Did children who received intervention were during older childhood (e.g., early school-age) and hence, the damage on cognition could have occurred since early age, aside from possible short duration of intervention? Please consider.

3. Editorial errors:

a. Line 116, Introduction: ‘…. (HAZ) <2 on WHO…’, should this read ‘…. (HAZ) <-2 SD…’?

b. Line 351 ‘A unit increase in HAZ <2 Y…’, suggest to read, ‘A unit increase in HAZ at <2 y of age..’

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Pattanee Winichagoon

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

12 Nov 2021

KINDLY SEE THE ATTACHED FILE

To

The reviewers

PLOS One

Re: PONE-D-21-21418 - Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort

Dear reviewers,

Thank you for reviewing our manuscript titled “Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort”. Author’s responses are provided below

Comments Authors’ response Page number; line number

Academic Editor

1. Additionally, regarding line 137-138, “These contradictory findings may be due to differing definitions and time periods studied [20],” although the authors discussed it in the discussion, you are requested to address in the introduction in terms of what your study add to the literature. Thank you. Suggested change has been made.

6; line 142-147

2. Also the potential to recover from undernutrition to neurocognitive development need to be addressed.

Refer to the response to comment no. 1 6; line 142-147

3. In Table 1, “Weight-for-age Z scores (HAZ)” needs to be changed to “Weight-for-age Z scores (WAZ)”

Thank you. Changed to WAZ Table 1

4. Financial statement Deleted from Title page section Cover letter

5. Competing interest No competing interest

Deleted from Title page section Cover letter

6. Data Minimal anonymized data set is uploaded Supplementary file

7. Ethics statement – Mention only in manuscript Deleted from Title page section

Reviewer 1

8. The authors note that the definition of catch up is a point of dispute in the literature, but do not explain why they selected the one that they used. The one used is a rather weak definition - children can be defined as having caught up even when falling behind in terms of CM deficits. Nonetheless, it is a commonly used definition and its use could be justified, but it does need to be justified and not used without question. Thank you. Suggested changes have been incorporated and corresponding references have been added. 7, Lines 175-178

9. -Stunting does not cause cognitive impairment, impairment and stunting are both indicators of malnutrition and possibly of lack of stimulation (and possible the combination of the two). As a result, any association between them needs to be carefully interpreted. The authors do not adequately cover this topic, which hinders the subsequent discussion of the results.

Thank you. Suggested changes have been incorporated and corresponding references have been added. 19, Lines 365-372

10. If the authors are going to make the case that their results imply that nutrition programmes are needed, then a fuller discussion of the adequacy of the controls in the regression is needed. As mentioned, the association with stunting may be a result of smaller children being protected by parents leading to under stimulation - this may not be resolved by a nutrition program. Similarly, smaller children may be held back from school entry as parents do not think they are ready. The association between stunting and cognitive performance may be a result of less exposure to schooling. Thank you. Our analysis showed that apart from early childhood stunting, other factors such as poor socioeconomic status and lesser IQ of the mother, were predictors for poor cognitive performance at 9 years in children. Also, our study showed that recovery from stunting at later years in children, who were stunted at 2 years, also to be a factor for better cognitive performance at 9 years. Thus, we would summarize that cognition at 9 years is because of interplay of multiple factors during the childhood period, which is inclusive of nutrition, timing of catch up growth, socioeconomic status and caregiver’s IQ. Changes have been made in the conclusion. 20, lines – 404-406

11.Do the authors think that catch up growth could indicate a recovery from earlier malnutrition leading to a similar catch up in cognition? Or that those who catch up avoid falling further behind, while those who remain stunted continue to fall behind? Their results could support either argument, but which argument is correct has important policy implications and this should be discussed.

Findings from our study support the evidence that children who catch up perform better in cognition tests at 9 years, when compared to children, who have been persistently stunted between 2 and 9 years. This has been discussed in the lines 350-371 -

11 The authors from time to time slip into causal language, this should be avoided.

Thank you and this has been addressed -

12. The discussion on the importance of the first 1,000 days is a little unclear and could be improved. It is the pace and foundational nature of development in that period which is critical and this does not come through enough.

Thank you and this has now been addressed. 19, lines 364-371, &

20, 391-393

13. Why report weight if you don't use it? Just for context?

Yes, weight for age scores have been provided to give a complete picture of anthropometric measurements of children in the cohort. -

14. The top third based on WAMI can hardly be called high SES given the selection process. Would relatively high not be better?

Thank you. We have used this nomenclature of high and low, having 33rd percentile as cut-off consistently in the previous papers published from the same cohort. Hence, we would like to retain the same nomenclature.

Mohan VR, Sharma S, Ramanujam K, Babji S, Koshy B, Bondu JD, John SM, Kang G. Effects of elevated blood lead levels in preschool children in urban Vellore. Indian Pediatr. 2014 Aug;51(8):621-5.

Koshy B, Srinivasan M, Zachariah SM, Karthikeyan AS, Roshan R, Bose A, Mohan VR, John S, Ramanujam K, Muliyil J, Kang G. Body iron and lead status in early childhood and its effects on development and cognition: a longitudinal study from urban Vellore. Public Health Nutr. 2020 Aug;23(11):1896-1906. -

15. When was the WAMI measure taken? What the implications of only using one time point? Did those who exhibited catch up also see an improvement in their SES which might explain the better cognitive scores? WAMI measures were available for the MAL-ED study, until 5 years of age and there were no WAMI measurements, thereafter. In the current study, WAMI scores measured at 2 years was considered, since we were interested to see, if SES status post-infancy continued to have effect on cognition scores measured at later childhood.

Further, subgroup analysis showed that there is no significant improvement in SES status between the children who were stunted at 2 years and recovered at 5 years vs. those who were stunted both at 2 and 5 years. To substantiate this, we would provide following data. Of 95 children, who were stunted at 2 years, 37 (38.9%) recovered from stunting, with 58 (61.1%) of them, continued to be stunted at 5 years. 4/37 (10.8%) children who recovered from stunting had the improvement in SES from low to high by 5 years; compared to 5/58 (8.62%) who continued to be stunted at 5 years and had a similar improvement in SES status from low to high. -

Reviewer 2

16. Table 4: on the PIQ, it is shown that stunting at 2 y, though with a catch-up at 5 y had 5.77 PIQ less than normal children, but the children who stunted at 2 & 5 who only caught-up at 9 had much better PIQ than normal, than children who were already catch-up since 2y and those persisted till 9 y. What could explain such a pattern? Please add discussion Thank you. We are unable to substantiate this pattern of regression co-efficients obtained between stunting with/without catch-up in early childhood and PIQ measurements at 9 years. The probable reason would be smaller sample size within the subgroups, that could have limited meaningful inference of the data. Having a smaller sample size in this study has already been highlighted as one of the limitations within the Discussion section. 20, line 394

17. . Lines 365-366 & reference 17: Did children who received intervention were during older childhood (e.g., early school-age) and hence, the damage on cognition could have occurred since early age, aside from possible short duration of intervention? Please consider.

Thank you. We have added this into the Discussion. 19, Line 383-384

18. 23. Editorial errors:

a. Line 116, Introduction: ‘…. (HAZ) <2 on WHO…’, should this read ‘…. (HAZ) <-2 SD…’?

b. Line 351 ‘A unit increase in HAZ <2 Y…’, suggest to read, ‘A unit increase in HAZ at <2 y of age..’ Thank you.

Corresponding changes made

a. Page 5; line 117

b. Page 18; line 361

Thanking you

Yours sincerely

Authors

Submitted filename: Reply to editor and reviewers final.docx

Click here for additional data file.

1 Dec 2021

14 Dec 2021

Separate copy is uploaded

To

The reviewers

PLOS One

Re: PONE-D-21-21418 - Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort

Dear reviewers,

Thank you for reviewing our manuscript titled “Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort”. Author’s responses are provided below

Comments Authors’ response Page number; line number

1. The authors have not substantially engage with a number of key issues raised in the previous review. Most notably, they have not justified their definition of catch up growth other than to say that other people use it, so it must be okay. They do not even mention what the other definitions are and how these could explain the contradictory findings that they also seek to explain. Thank you.

Different definitions have been included in the introduction – page 6, lines 126-128.

Justification for current approach is included in methodology – page 8, lines 163-166

6; 126-128

8; 163-166

2. They also do not engage with the possibility that their results are endogenous - i.e. growth and cognition both have common causes. This links to perhaps the most serious problem - the authors use causal language throughout. Growing taller will not make you smarter. Growing taller may indicate that your environment has improved and that this environment now better facilitates cognitive development. This mechanism is not explained or referenced when interpreting findings. The absence of this explanation (understanding?) may explain why the conclusions are over stated. It may also explain why the results from the literature discussed are also over interpreted as showing a causal link. Thank you.

We completely agree with the lack of causalilty and have used the word ‘association’ throughout manuscript.

We are happy to edit/modify if this is not clear in the manuscript.

Another statement also has been added to highlight common and intersecting risks and causative pathways for both growth and cognition in early childhood. 20; 360-362

3. Finally, the authors ignored the need to differentiate between catch up in cognition and a slowing of the rate at which children are falling behind. If children who remain stunted are falling behind at a faster rate than those who have 'caught up', then a significant result in their regression may not be indicating catch up in cognition in the latter group. This is a critical point - it speaks to the extent to which inputs in different life stages are or are not substitutable. Thank you.

That is a valid observation and we agree with you.

We have added further information in Table 2 to show that children in all groups improved in HAZ between 2 and 9 years of age.

Table 2

Thanking you

Yours sincerely

Authors

Submitted filename: Reply to editor and reviewers.docx

Click here for additional data file.

23 Dec 2021

27 Jan 2022

To

The reviewers

PLOS One

Re: PONE-D-21-21418 - Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort

Dear editor and reviewers,

Thank you for reviewing our manuscript titled “Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort”. Author’s responses are provided below

Comments Authors’ response Page number; line number

(Track version of the manuscript)

Further, there are several miner things which the authors should correct.

Table 3 showed the scores among 4 categories of stunting and catch up status of children and the coefficient of the rest three group, compared to the “never stunted group” were shown in Table 4. However, the authors used causal languages as the reviewer #1 mentioned. Thank you for the comment and the category ‘never stunted’ in table 2, 3 and 4 is replaced with ‘children who were never stunted’ Table 2, 3 and 4

Thus, the uses of “reduction” or “decline” are not appropriate. You may use “lower score” instead. Please revise throughout the manuscript. Thank you and this correction has been made in the Abstract, Results and Conclusions section. Page 4 and lines 83 and 88

Page 15 and lines 284, 287 and 291

Page 22 and lines 406 - 410

Reg “Catch-up growth was associated with higher verbal intelligence as well total cognition, but not the performance component.” higher verbal intelligence as well as total cognition than what? you mean “never catch up group”? Please clarify the sentences Thank you and this sentence has been rephrased.

Page 18 and lines 318-319

The authors did not discuss why the second group (catch up at 5 years) are negatively associated with performance IQ. Thank you and this change has been made in the Discussion Page 21 and lines 392-395

Make some efforts on it, and reduce the length of “good follow-up rate of your cohort study” and add after the limitation of your study” to highlight the significance of your study in the discussion. Thank you and this change has been made in the Discussion Page 21 and lines 402-403

Lastly, put the acronym in parentheses after the full term, if you use the term the first time. For example, IQ in the abstract, SD in the introduction and ANOVA in the method section. Thank you and these suggestions have been incorporated in the Abstract, Introduction and Methods. Page 4 and line 84

Page 5 and line 103

Page 10 and lines 214-215

There are still come remnants of causal language, such as 'reduction' and 'decline', but they are not serious and could easily be left Thank you and this correction has been made throughout the manuscript. Page 4 and lines 83 and 88

Page 15 and lines 284, 287 and 291

Page 20 and line 360

The justification of the definition use is weak, it mentions only the advantages and fails to consider the limitations (of which there are many). But as mentioned, previously, the definition is often used and so I guess its unquestioned use here is acceptable. Thank you and the justification for the use of definition based on HAZ scores in this study has been provided in Methods section. Page 8 and lines 170 - 173

The one remaining issue which I would like to see addressed relates to the failure to engage with the comment I made that there may be no catch up in cognition. The additions to the table to show that the z-score increased don't help and add little. The definitions of the categories already provided the outline of this information. Besides, the question was not about growth but cognition. Perhaps my explanations have not been clear, so I will try with an example.

Three people enter a race (Tom, Fred and Joann). At the half way mark, Tom and Fred are 50meters behind Joann. When Joann crosses the finish line, Fred is still 50meters behind, but Tom is now 100meters behind. Can you say that Fred caught up? They all moved forward and he stopped falling behind, but he did not catch up.

This is a critical point, because if that 50meters at half way is lost forever and all you can do post the half way mark is prevent someone falling further behind, interventions in the first half of the race are not substitutable. This does not mean that interventions in the second half to prevent further falling behind are not important, but there should not be any suggestion that we can wait to the second half and catch up all the way.

In my mind, the possibility that there was no catch up in cognition should be mentioned. And this should be carried through to the conclusions, i.e. that the consequences of early deprivation on cognition may not be reversible, but we can act to prevent children from falling further behind. Thank you and we agree with this suggestion and corresponding changes have been made throughout in the manuscript. Use of ‘Catch up in cognition’ in children who recovered from early life stunting has been replaced as the attainment of higher cognition scores in these children compared to persistently stunted children in relevant sections. Page 4 and lines 85-86, 89-91

Page 18 and lines 318-319

Page 21 and lines 385-389

Page 22 and line 408-410

Thanking you

Yours sincerely

Authors

Submitted filename: Reply to editor and reviewers.docx

Click here for additional data file.

2 Feb 2022

Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort

PONE-D-21-21418R3

Dear Dr. Koshy,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Seo Ah Hong, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for addressing all the issues reviewers raised. Copy editing is strongly recommended to improve readability before submitting the final version since some errors were found. For example, change from “height for age SD scores (HAZ) < -2 SD on WHO growth charts” to “height for age z scores (HAZ) < -2 Standard Deviation (SD) on WHO growth charts”

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The changes made in this revision are very helpful. The causal language has been removed and the interpretation of the findings has been improved. The paper makes a useful contribution to the literature.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

8 Feb 2022

PONE-D-21-21418R3

Are early childhood stunting and catch-up growth associated with school age cognition? – Evidence from an Indian birth cohort

Dear Dr. Koshy:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof. Seo Ah Hong

Academic Editor

PLOS ONE