Introduction

The term "Failure to Thrive" (FTT) has historically been used widely to describe the situation in which infants and young children fail to achieve expected growth by measurements of weight and height. In recent times the term FTT has been criticized as pejorative, with parents perceiving themselves to be failures, rather than the child's growth, and they can feel as if they are to blame for a child's inadequate intake.1 Although the term FTT is still used by many health professionals, other terms such as "slow weight gain" and "under nutrition" have been suggested as alternatives, with the term "faltering growth" (FG) being accepted and used more commonly in recent times.1

Faltering growth results from an imbalance in energy intake versus energy expenditure. This can arise from an insufficient intake of calories due to a child not being offered enough or not taking enough, or a child's current intake of calories being insufficient to meet the increased requirements associated with a medical condition. Faltering growth can also occur due to a loss of calories through malabsorption associated with a number of medical conditions such as celiac disease or cystic fibrosis.2

Faltering growth has traditionally been described as either organic or non-organic. Organic FG is associated with an acute or chronic illness which increases the child's energy requirements and/or leads to decreased calorie intake. Non-organic FG is psycho-social in nature and may arise from abuse or neglect, difficulties in establishing the mother-infant bond or significant family stressors. In practice, most FG has both an organic and non-organic basis.3

Faltering growth is a symptom of under nutrition rather than a diagnosis.2 There is a lack of consensus in current literature on the definition of FG, with a number of definitions described in the literature.4 Common anthropometric criteria used for diagnosing FG include body mass index (BMI), weight velocity, weight for age or length for age less than the 5th percentile, weight less than the 75th percentile of median weight for age, or weight for length,5 with the most accepted definition being weight falling through two or more percentile bands.6

Faltering growth is not uncommon in the developed world, and is seen in 5-10% of infants and toddlers in primary care settings7 and 3-5% of infants and toddlers in the hospital setting.8 Children who experience FG in infancy are lighter and shorter,9 and have a lower IQ10 than their age matched counterparts, therefore prevention and treatment of FG are imperative.

Small for gestational age (SGA) refers to infants born at less than -2 standard deviations from the mean, or weight below the 10th percentile.11 The prevalence of SGA is difficult to determine as birth weights and gestational age are not often recorded in most national databases. One study estimated that in 2010, 32.4 million babies were born SGA in low- and middle-income countries, constituting 27% of all live births.12 Similar to those who experience FG, children who are born small for gestational age are also more likely to be shorter,13 with reduced intellectual capacity compared to their age matched counterparts.14

Preterm birth refers to birth occurring before 37 weeks of gestation and has a global incidence of 9.6%.15 Children born very premature are also shorter and thinner16 and can suffer cognitive problems later in life.17

Catch-up growth refers to growth at a rate which exceeds normal expectations for age and occurs after a period of impaired growth.18 Catch-up growth and rapid weight gain in infants identified with FG can prevent the detrimental effects of FG, such as muscle wasting, infection, gastrointestinal dysfunction, developmental delay and deficits in cognition and social and emotional competence.19 In infants born SGA, catch-up growth during infancy can prevent deficits in final adult height13 as well as suboptimal intellectual and psychological performance.20 Interventions employed to facilitate catch-up growth and achieve rapid weight gain depend on the age of the child, method of feeding and severity of growth impairment. Common interventions include more frequent breastfeeding and lactation support, formula to supplement breastmilk intake, concentrated formula for formula-fed infants, and food fortification with energy dense foods for children on solids.4

While catch-up growth and achieving adequate growth rates is recognized as an important determinant of health, recent attention has focused on the longer term consequences of catch-up growth and rapid weight gain in infancy.21 The association between rapid weight gain in the first year of life and the development of overweight and obesity later in life is now well established,22 with those born small for SGA at an increased risk of both obesity and increased fat mass later in life.11 Other reported metabolic consequences of rapid weight gain or catch-up growth experienced in infancy include cardiovascular disease,23 hypertension24 and insulin resistance.25 This creates a dilemma in that for infants with FG and born premature or small for gestational age, catch-up weight gain may result in both short-term benefits and long-term risks.26 Currently, the diverse range of populations studied in the literature (including term infants, SGA and premature infants) and range of outcomes measured make it difficult to determine appropriate growth targets for infants and toddlers, particularly for those who experience FG. A search in MEDLINE, Embase, JBI Database of Systematic Reviews and Implementation Reports and the Cochrane Library in December 2016 did not identify any systematic reviews currently on this topic. This review aims to provide clarity to this discussion, and evaluate the metabolic outcomes of rapid weight gain and catch-up growth experienced in infancy across those born term, prematurely or SGA. It is hoped that the results of this review provide clear information to direct dietetic practice in infants requiring catch-up growth.

Inclusion criteria

Participants

This review will consider studies that include participants three years and over who experienced any type of rapid weight gain or catch-up growth in the first two years of life. Studies that include infants with a specific medical condition known to impair growth, including, but not limited to, kidney disease, a cardiac condition and coeliac disease, will be excluded.

Exposure

This review will consider studies that evaluate the impact, risk or association between rapid weight gain or catch-up growth in the first two years of life and future metabolic outcomes. For the purposes of this review, catch-up growth and rapid weight gain are defined as any weight above what is normally expected for age.

Outcomes

This review will consider studies that include the following outcomes:

* Overweight and obesity - measured by a BMI score.

* Hypertension - measured by blood pressure.

* Hyperlipidemia - measured by serum cholesterol and triglycerides.

* Cardiovascular disease (CVD) - measured by presence of coronary heart disease.

* Type 2 diabetes and insulin resistance - measured by blood glucose levels.

* Body composition - measured by waist circumference, percentage fat mass, abdominal fat distribution and/or visceral adiposity.

This review will not include studies that investigate non-metabolic outcomes including but not limited to cancer, type-1 diabetes mellitus, asthma and cognitive ability.

Types of studies

This review will consider both experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies and interrupted time-series studies. In addition, analytical observational studies including prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies will be considered for inclusion.

Methods

Search strategy

The search strategy will aim to find both published and unpublished studies. An initial limited search of MEDLINE and Embase has been undertaken to identify articles on this topic, followed by analysis of the text words contained in the titles and abstracts, and of the index terms used to describe these articles. This informed the development of a search strategy including identified keywords and index terms which will be tailored for each information source. The reference list of all studies considered for this review will be screened for additional studies. The full search strategy is detailed in Appendix I.

Initial search terms to be used include:

* Infant^* or toddler^* or child^* or babies or small for gestational age or neonat^* or premature or newborn^*

* faltering growth or failure to thrive or malnourish^* or intrauterine growth restriction or IUGR

* ((rapid^* or catchup or catch-up or accelerat^* or velocit^* or fast or faster) adj6 (weight or growth or adipos^*)).

* (metaboli^* or obesity or overweight or adiposity or blood pressure or hypertensi^* or hyperlipidemia or type 2 diabetes or cvd or coronary heart disease or body composition or body mass index or percentage mass fat or abdominal fat distribution

Information sources

The Ovid platform will be used to conduct the literature search. The databases to be searched include MEDLINE and Embase.

The trial registers to be searched include Cochrane Register of Controlled Trials.

Studies published in English will be included. No date limits will be stipulated in this review.

Study selection

Following the search, all identified citations will be collated and uploaded into Endnote (Clarivate Analytics, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two or more independent reviewers for assessment against the inclusion criteria for the review. Studies that meet, or could potentially meet, the inclusion criteria will be retrieved in full and their details imported into the Joanna Briggs Institute's System for the Unified Management, Assessment and Review of Information (JBI SUMARI) (Joanna Briggs Institute, Adelaide, Australia). The full text of selected citations will be retrieved and assessed in detail against the inclusion criteria by at least two independent reviewers. Full text studies that do not meet the inclusion criteria will be excluded and reasons for exclusion provided in an appendix in the final systematic review report. Included studies will undergo a process of critical appraisal. The results of the search will be reported in full in the final report and presented in a PRISMA flow diagram. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.

Assessment of methodological quality

Selected studies will be critically appraised by two independent reviewers at the study level for methodological quality using standardized critical appraisal instruments from the Joanna Briggs Institute for experimental and quasi-experimental studies, cohort studies, case-control studies and analytical cross-sectional studies.27 Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. The results of critical appraisal will be reported in narrative form and in a table.

All studies, regardless of the results of their methodological quality, will undergo data extraction and synthesis (where possible).

Data extraction

Data will be extracted from papers included in the review using the standardized data extraction tool available in JBI SUMARI by two independent reviewers.27 The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and objectives. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer. Authors of papers will be contacted to request missing or additional data where required.

Data synthesis

Where possible, papers will be pooled in statistical meta-analysis using JBI SUMARI or Cochrane's Review Manager. Effect sizes will be expressed as either odds ratios (for dichotomous data) and weighted (or standardized) mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard chi-squared and I² tests. The choice of model (random or fixed effects) and method for meta-analysis will be based on the guidance by Tufanaru et al. 2015.28 Subgroup analyses will be conducted where there is sufficient data to investigate. Participants may be stratified by population or metabolic outcome, including but not limited to term, SGA or preterm infants, and obesity, CVD or high blood pressure respectively. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Assessing certainty in the findings

A Summary of Findings using GRADEPro GDT software will be developed (McMaster University, ON, Canada). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for grading the quality of evidence will be followed.29 The Summary of Findings will present the following information where appropriate: absolute risks for the treatment and control, estimates of relative risk, and a ranking of the quality of the evidence based on the risk of bias, directness, heterogeneity, precision and risk of publication bias of the review results. All outcomes will be included in the Summary of Findings.

Appendix I: Search strategy

Search strategy for Ovid MEDLINE

References