Objective:

To identify those perinatal parameters and characteristics predisposing children to an increased risk of overweight during infancy and preschool years.

Design:

The analyses were performed using data from the Growth, Exercise and Nutrition Epidemiological Study In preSchoolers.

Subjects:

A representative sample of 2374 Greek preschoolers 1–5 years old.

Measurements:

Anthropometric data, such as body weight, recumbent length and standing height, were obtained by using standard procedures and measuring equipment. Structured interviews were conducted with both parents to collect information on anthropometric, demographic, medical and behavioral data. Finally, children's anthropometric data at birth, 6 and 12 months of age were recorded from their birth certificates and medical records.

Results:

Children born large for gestational age were 4.59 and 2.19 times more likely for being overweight at 6 and 12 months of age, respectively, than children born appropriate for gestational age. On the other hand, children that were exclusively breastfed were 0.49 and 0.54 times less likely for being overweight at 6 and 12 months of age, respectively, than children that were exclusively formula fed. Furthermore, 3- to 5-year-old children born to mothers who were both active and passive smokers during pregnancy were 1.79 times more likely of being overweight compared to children born to nonsmoking mothers. Finally, having an overweight father significantly increased the likelihood of childhood overweight at 12 months, 1–3 and 3–5 years of age.

Conclusion:

Our findings showed that some of the perinatal parameters and characteristics examined in the current study predict overweight at infancy, while others at preschool years. Priority should be given to size at birth, breastfeeding, maternal smoking during pregnancy and parental overweight, when developing public health strategies to reduce the prevalence of childhood overweight and related chronic disease later in life.

Introduction

Obesity represents the most frequent public health problem globally.¹ In many developed countries childhood overweight and obesity has reached epidemic proportions,² as these have been doubled in the past 20 years.³ Overweight children already show related signs of morbidity, including elevated blood pressure, cholesterol, triglycerides and insulin levels.⁴ Furthermore, overweight children have a high risk for being overweight in adulthood^{4, 5, 6} and to experience typical obesity-related morbidity. Recent research showed that several of the major chronic diseases of adult life including cardiovascular disease, hypertension and type 2 diabetes mellitus originate in early childhood. Thus, prevention of pediatric overweight and obesity is very important for the long-term prevention of chronic disease. The higher cost and the mixed effectiveness of therapeutic approaches⁷ emphasize the need for both population- and individual-oriented preventive measures, which ideally should begin very early in life. Additional reasons that emphasize prevention in early childhood include adipocyte physiology, adiposity rebound and the limited potential for reversing metabolic changes associated with obesity in later life.⁷

Although several efforts have been made to better understand the causes of obesity, still little is known on the exact causes or the best way to stop this adverse public health problem from expanding. Combined with the fact that diet and activity patterns cannot fully predict the increased rates of overweight in early life stages (that is, infancy and preschool years) several experts were led to the hypothesis that adverse influences in earlier life might also play an important role.^{8, 9} In addition to social and genetic predisposition both intrauterine and early postnatal environment have been reported to exert a significant effect on several metabolic, nervous and endocrine adaptations that increase the odds for obesity in later life.^{10, 11, 12} Therefore, the search for obesity predisposing factors should extend beyond the child's current lifestyle, to its perinatal environment (that is, fetal and postnatal).

Several national epidemiological studies have been conducted in Europe and the United States, aiming to assess perinatal parameters predisposing to overweight in early childhood.^{13, 14, 15} Regarding Greece there are no data with respect to perinatal correlates of overweight during infancy and preschool years. The Growth, Exercise and Nutrition Epidemiological Study In preSchoolers (GENESIS) represents the first large-scale epidemiological study in Greece, attempting among others to evaluate the aforementioned association.

Specifically, the objective of the current study was to identify those perinatal parameters and parental characteristics predisposing children of the GENESIS cohort to an increased risk of overweight during infancy and preschool years. Bearing in mind that the prevalence of childhood overweight in Greece is considerably high,¹⁶ the identification of the exact risk factors and of the exact life stages when these risk factors predispose infants and/or preschool children to overweight could be an important knowledge for public health authorities in designing and implementing appropriate obesity prevention programs by intervening very early in life.

Methods

Sampling

The study was carried out from April 2003 until July 2004 and was conducted with a population of Greek preschool children 1–5 years old. Initially, a representative number of randomly selected public and private nurseries as well as day care centers within municipalities in five counties (namely Attica, Aitoloakarnania, Thessalonica, Halkidiki and Helia) were invited to participate in the study. All nurseries invited to participate responded positively. Furthermore, an extended letter explaining the aims of the current study and a consent form was provided to each parent having a child in these nurseries. Those parents agreed to participate in the study had to sign the consent form and provide their contact details. Signed parental consent forms were collected for 2518 children, aged 1–5 years (that is, 12–60 months) (response rate 75%). From the total number of positive responses complete data became available for 2374 children with participation rate varying from 54 to 95%, reaching the highest rates in rural areas and the lowest ones in urban areas. More information on the sampling procedures and the representativeness of the understudy population are presented elsewhere.¹⁶ Approval to conduct the study was granted by the Ethical Committee of Harokopio University of Athens and by all municipalities invited to participate in the study.

Anthropometric measurements

Anthropometric data were obtained by using standard procedures and measuring equipment in all study sites. This information has been presented in details previously.¹⁶ In summary, body weight was recorded to the nearest 10 g with the use of a digital scale (Seca, Hamburg, Germany) and with subjects standing without shoes in the minimum clothing possible, that is, underwear. Recumbent length was measured for all subjects to the nearest 0.1 cm with a portable measuring wooden board that had a stationary head piece, a sliding vertical foot piece and a horizontal back piece with a measure tape mounted on it. In addition to recumbent length, standing height was also measured to the nearest 0.1 cm, with the use of a commercial stadiometer (Leicester Height Measure). The measurement of height was conducted without shoes and with children keeping their shoulders in a relaxed position, their arms hanging freely and with their head aligned in Frankfurt plane.¹⁷ Body mass index (BMI) was calculated by dividing weight (kg) with height squared (m²).

Data obtained by parents and birth certificates

A structured interview was conducted with both parents, to collect additional and retrospective information regarding: (1) parental educational level—both parents were asked to report total years of their education. Precisely up to 9 years of education, which is the time of compulsory education in Greece, corresponds to having a junior high school degree; 9–12 years of education corresponds to having a high school degree and more than 12 years of education corresponds to having a college or a university degree; (2) parental weight status—both parents were asked to report their weight in kg and their height in cm. BMI was then calculated by dividing weight by height squared; (3) maternal medical history of gestational diabetes mellitus; (4) maternal active and passive smoking as well as alcohol consumption patterns during pregnancy; (5) mother's age at birth; (6) birth rank (first-born vs not first-born child) and (7) children's feeding patterns from birth to 6 months of age, that is, breastfeeding, use of formula and age when formula was first initiated in the child's feeding—based on the collected information and on criteria provided by the World Health Organization¹⁸ with respect to the definition of breastfeeding and formula feeding the following three categories were created: exclusive breastfeeding, exclusive formula feeding and mixed feeding with concurrent use of breast milk and formula.

Furthermore, parents were asked to bring with them their child's birth certificate and medical record from which the following data were obtained: (1) birth date—this data was used for the estimation of the exact age of each subject and for grouping children into the following two age subsets: 1–3 years (that is, 12–36 months) and 3–5 years (that is, 37–60 months); (2) birth weight, length and gestational age—according to the collected data on birth weight we created the following three categories of children born: small for gestational age (SGA, <10th percentile), appropriate for gestational age (AGA, 10th–89th percentile) and large for gestational age (LGA, 90th percentile) and (3) child's weight and recumbent length at 6 and 12 months of age.

Definition of overweight

The Nutstat module of EpiInfo¹⁹ was used to determine children's age and sex-specific percentiles for weight, length and BMI. The US Center for Disease Control age- and sex-specific growth charts and relative cutoff points were used for the definition of overweight.²⁰ More specifically, the weight-for-length growth chart was used to classify children up to 24 months of age as 'overweight' (95th percentile), while children older than 24 months were classified as 'at risk of overweight' (85th and <95th percentile) and 'overweight' (95th percentile) using the BMI-for-age growth chart. Furthermore parental BMI values were used to categorize parents as 'normal weight' (25 kg m^-2) and as 'overweight' (BMI>25 kg m^-2).

Statistical analysis

All variables used in the current analysis were categorical to facilitate clinical interpretation and application. To test the effect of the factors under investigation on being overweight univariate logistic regression analyses were performed and data were modeled using multivariate logistic regression analyses. The primary outcome variable was 'overweight' defined as weight-for-length 95th percentile at 6, 12 months and 1–2 years of age and as BMI-for-age 85th percentile at 2–3 and 3–5 years of age. Multivariate analysis was performed using as predictors of overweight those independent variables that were found to be significantly (P<0.05) associated with childhood overweight in at least one age group in the univariate analyses. Odds ratio (OR) with 95% confidence intervals (CI) were computed. Statistical significance was set at 0.05. All analyses were conducted using STATA statistical software (version 6.0).

Results

Table 1 presents the prevalence of children being at risk of overweight and overweight. Totally the prevalence of overweight was 16.2% (weight-for-length 95th percentile for children up to 2 years of age and BMI-for-age 95th percentile for children older than 2 years) and the prevalence of being at risk of overweight (BMI-for-age 85th and <95th percentile) in children older than 2 years of age was 16.4%. More specifically, in children 1–2 years old the prevalence of overweight was 13.5%. In children 2–3 years old the prevalence of being at risk of overweight was 17.4% and the prevalence of overweight was 13.6%. At 3–5 years of age the prevalence of being at risk of overweight was 17.6% and the prevalence of overweight was 17.3%. Based on the retrospectively collected data provided from the medical records, the prevalence of overweight when children were 6 and 12 months old was estimated to be 9 and 5.6%, respectively.

Table 1 - Prevalence of being 'at risk of overweight' and 'overweight' by age group.

Full table

Table 2 summarizes data on parental characteristics and perinatal parameters. Almost 30% of the children were 1–3 years old (that is, 12–36 months) and the rest 70% were 3–5 years old (that is, 37–60 months). The majority of children were born to mothers who were 26–35 years old (71.8%), while 57.9% of mothers had a college or a university degree. Most children (43.2%) had an overweight father but a normal weight mother, while only 8.1% of children had a normal weight father but an overweight mother. Furthermore, 11.6 and 7.8% of children were born to mothers who admitted being either active or both active and passive smokers during their pregnancy. Nearly 30% of children were ever breastfed while 20.4% of children were exclusively breastfed for the first 6 months after birth. Finally, the percentage of children born SGA was 9.1%, while the rate of children born to mothers with gestational diabetes mellitus was 1.5%.

Table 2 - Parental characteristics and perinatal parameters of the study population, presented by age groups.

Full table

The multivariate analysis revealed that overweight at 6 months of age was significantly associated with gender, birth weight and postnatal feeding patterns (Table 3). Specifically, female infants and infants born LGA were 1.47 and 4.59 times more likely for being overweight at 6 months of age than male infants and infants born AGA, respectively. On the other hand infants that were born SGA and were exclusively breastfed for the first 6 months of their life were 0.19 and 0.49 times less likely for being overweight at 6 months of age than AGA and exclusively formula-fed infants, respectively. At 12 months of age both birth weight and breastfeeding remained significantly associated with overweight, while maternal age at birth and parental weight status were also found to exert a significant effect. Specifically, infants born LGA and having a normal weight mother and an overweight father were 2.19 and 1.84 times more likely of being overweight than infants born AGA and having normal weight parents, respectively. On the opposite infants that were exclusively breastfed for 6 months after birth and were born to mothers older than 35 years were 0.54 and 0.23 times less likely for being overweight than children that were exclusively fed with formula and were born to mothers younger than 20 years old, respectively.

Table 3 - Adjusted odds ratios (95% confidence intervals, CI) for being overweight in infants 6 and 12 months old.

Full table

At 1–3 years of age the only variable that predicted childhood overweight was parental weight status, since children with a normal weight mother and an overweight father were 1.43 times more likely of being overweight than children with normal weight parents (Table 4). At 3–5 years of age there were several parental characteristics and perinatal parameters found to predict childhood overweight, such as maternal educational level, smoking during pregnancy, birth weight and parental weight status. Precisely, children born to mothers who were both active and passive smokers during pregnancy and had an overweight father or both their parents overweight were 1.79 and 1.53 or 2.31 times more likely of being overweight compared to children born to nonsmoking mothers and having normal weight parents. On the contrary, children born SGA and born to mothers that had a college or a university degree were 0.56 and 0.58 less likely to be overweight than children born AGA and children born to mothers having a junior high school degree, respectively.

Table 4 - Adjusted odds ratios (95% confidence intervals, CI) for being at risk of overweight and overweight in preschool children 1–3 and 3–5 years old.

Full table

Discussion

The GENESIS study was the first large-scale epidemiological study ever conducted in Greece attempting to identify certain perinatal parameters and characteristics that predispose children to a higher risk of overweight at early years of life (Tables 2 and 3). Our findings revealed a dramatic increase of overweight from infancy to preschool years (from 9 and 5.6% at 6 and 12 months of age to 16.2% at 1–5 years of age, respectively). The magnitude of this adverse trend in Greece can be best judged via a comparison with the prevalence of childhood overweight in other developed countries, such as in the United States, where it has been reported to range from 11.6% at 6–23 months to 10.4% from 2–5 years of age.^{3, 21} These rates indicate that currently the magnitude of overweight in early childhood in the two countries is almost comparable and considerably high. However, none of the public health initiatives attempted so far has prevented the problem from expanding, since in both countries childhood overweight has been doubled over the past two decades.^{21, 22, 23} In sight of this unfavorable trend and bearing in mind the hypothesis that the presence of several environmental factors during specific critical periods of early development (that is, intrauterine or postnatal environment) seems to increase the risk of obesity in later life,^{9, 10} the current study attempted to reveal several such factors predisposing infants and children to a higher risk of overweight.

Our findings showed that some of the parental characteristics and parameters examined in the current study predict overweight at infancy, while others at preschool years. Specifically, size at birth and exclusive breastfeeding appear to exert a significant effect both at 6 and 12 months of age, while paternal overweight is a common predictor of childhood overweight both at 1–3 and 3–5 years of age. Furthermore, some risk factors became nonsignificant (for example, breastfeeding) whereas others became significant with age (for example, maternal smoking during pregnancy). However, most of the parameters and characteristics examined were significantly associated with overweight in children aged 3–5 years old (that is, maternal smoking during pregnancy, size at birth, maternal educational level). Although the presence of different parental and perinatal predictors of overweight at infancy and preschool years could be attributed to different statistical power, still the sample sizes in all age groups examined in the present study were adequate to achieve statistical power greater than 0.90 at a=0.05. Furthermore, there are no data available in the literature with regard to biological mechanisms explaining this different effect. There are only theoretical mechanisms proposed, which in the case of perinatal parameters are mainly based on the 'thrifty phenotype' hypothesis.²⁴ This hypothesis suggests that the effect of certain environmental factors during specific, critical periods of early development can lead to permanent physiological and metabolic adaptations that although serve the purpose of improving the chances of fetal and postnatal survival, may become detrimental in the long term and may be expressed at different life stages in the presence of certain environmental influences.^{25, 26} Thus, adaptations occurring due to a poor intrauterine nutritional environment may also lead to an altered postnatal metabolism that can consequently result to obesity when food intake is abundant.

Similar to the current study other recent studies have also confirmed a link between perinatal parameters and overweight in preschool years.^{11, 14, 27, 28} However, only the present study has examined the effect of these parameters simultaneously and during different developmental stages in early years of life (that is, infancy and preschool childhood). Our data revealed a positive relationship between size at birth and overweight at infancy and preschool years. Precisely, children born SGA were less likely of being overweight at 6 months and 3–5 years of age, while children born LGA were more likely of being overweight at 6 and 12 months of age than children born AGA. In agreement with our findings several other studies have shown that high birth weight is an important risk factor for later overweight.^{11, 29, 30} However, there are a number of studies reporting a 'U'-shaped relationship between birth weight and childhood overweight, thus suggesting a more complex association between fetal size at birth and adiposity in later life.^{31, 32} Irrespective of the exact association of the above parameters and as fetal size at birth is known to reflect the product of the nutritional and hormonal milieu in which the fetus develops,²⁵ better control of the trajectory of fetal growth via the optimization of maternal nutrition and health status during pregnancy is fundamental.

Evidence in the literature regarding whether breastfeeding is associated with a reduction in the risk of childhood overweight has been contradictory.^{13, 27, 33, 34, 35, 36, 37, 38} The findings of the current study showed that exclusive breastfeeding for the first 6 months of life reduced the risk of overweight at 6 and 12 months of age, but was not found to have any subsequent positive effect from 1 to 5 years of age. The positive link between long-term breastfeeding and lower rates of overweight could operate through several possible biological mechanisms. It has been suggested that breastfeeding compared to formula feeding allows the infant to respond to hunger and satiety cues and exert more control over breastfeeding initiation and termination.³⁹ Also, breast- and bottle-fed infants show a different hormonal response to feeding, as formula feeding stimulates a greater insulin response, possibly resulting in earlier fat deposition.⁴⁰ Furthermore, bioactive factors in breast milk might modulate growth factors, which inhibit adipocyte differentiation in vitro.^{41, 42} Finally, it has been suggested that exclusively breastfed infants adapt more readily to new foods such as fruits and vegetables, thus influencing the subsequent caloric density of their diet.⁴³ Considering its many benefits to mother, child and society, exclusive breastfeeding is the recommended practice of infant feeding for the first 6 months of life,⁴⁴ and ongoing efforts to support breastfeeding should continue regardless of whether it is an important factor protecting against childhood overweight.

In consistency to recent evidence,^{11, 14, 45} the present study indicates that children having an overweight father were 1.4–1.8 times more likely for being overweight at almost all age groups. A positive family history of overweight and obesity is an important indicator of the genetic risk for being overweight in childhood.^{46, 47} However, besides inheritance of genes that confer susceptibility to obesity, parental overweight is also a proxy for shaping the postnatal eating and activity environment of their child. In most cases overweight parents create and sustain an 'obesogenic' environment (that is, high-caloric diets and physical inactivity) for themselves and their children.¹⁴ Although other similar studies have reported a much stronger and significant risk relationship between maternal and childhood overweight,^{14, 48} such an association was not observed in the present study. This could be attributed to a higher underreporting of body weight by children's mothers than fathers and is reflected to the much higher percentage of children having an overweight father than children having an overweight mother (43.2 vs 8.1%), thus representing a limitation of the present study. Indeed, based on several recent findings adult women are more likely to underreport their actual body weight compared to adult men.^{49, 50}

In good keeping with the findings of the current study, several other recent epidemiological studies have also confirmed a link between maternal smoking during pregnancy and overweight in preschool years.^{14, 15, 43, 51, 52, 53} The underlying mechanism of this association still remains unclear. One explanation could be the fact that maternal smoking in pregnancy is another proxy for factors present in the child's postnatal environment, including diet and activity behaviors, while smoking during pregnancy is not, in itself, directly causal for childhood overweight.^{14, 43} Furthermore, mothers who smoked during pregnancy were more likely to be less educated, to have a slightly lower age and less likely to breastfeed than nonsmokers.⁵⁴ However, in the Bavarian school entry health examination study the association between maternal smoking during pregnancy and childhood overweight at 5–7 years of age remained significant even after adjusting for a wide range of potential confounders and known lifestyle risk factors for overweight.¹⁵ This observation indicates that maternal smoking in pregnancy may also be an independent risk factor for overweight in children at school entry, as it has been suggested to affect the appetite regulation system in the developing brain.^{55, 56}

The association between maternal education and childhood overweight at 3–5 years of age observed in the present study accords with the findings from other similar studies.^{15, 46, 57, 58} In all these studies preschoolers born to mothers having a higher education (usually with a college or a university degree) were less likely to be overweight than children born to mothers with lower education (usually with a junior high school degree). Higher maternal educational level in most cases reflects higher socioeconomic status of the family, which has been associated with healthier dieting, physical activity and weight control practices compared to families with lower socioeconomic status.⁵⁷

In conclusion, the findings of the current study indicate that there are certain perinatal parameters and characteristics that protect or predispose children to overweight at different stages during infancy and preschool years. On this basis, special attention should be given to large size at birth, exclusive breastfeeding, smoking during pregnancy and maternal educational level. The fact that these perinatal parameters have implications for health later in life prompts their reevaluation by future research that will need to identify the exact biological mechanisms that might underlie the epidemiological associations found. Such an approach may allow us to use the information outlined here in developing public health strategies to reduce the prevalence of childhood overweight and related chronic disease later in life.

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Acknowledgements

The GENESIS study was supported with a research grant from Friesland-Foods Hellas. We thank Evdokia Oikonomou, Vivian Detopoulou, Anastasia Anastasiadou, Christine Kortsalioudaki, Elina Ioannou, Margarita Bartsota, Thodoris Liarigkovinos, Manolis Birbilis, Katerina Kondakis, Elina Dimitropoulou, Nikoleta Vidra, Theodoros Athanasoulis, Pari Christofidou, Lilia Charila, Sofia Tzitzirika and Christos Vassilopoulos for their contribution to the completion of the study.