Background
There is strong evidence that fetal and early postnatal environment play an important role in fetal programming and in determining the risk for disease in adulthood such as obesity, diabetes and cardiovascular disease [
1,
2]. Proposed key underlying mechanisms include epigenetic influences on DNA expression, the intrauterine development of hormonal axes and the relative accretion of different tissues and body components [
3]. Body composition at birth may serve as a surrogate marker for the environment in-utero [
4].
Fetal growth and body composition at birth are influenced by numerous factors, some non-modifiable such as gender, gestational age and ethnic/genetic background, others modifiable such as maternal diet as well as weight gain and (metabolic) health during pregnancy. These modifiable prenatal factors may affect the health of the offspring throughout his/her entire life [
5,
6].
In a recently published meta-analysis including 477,620 children aged 2 to 13 years in Europe, the pooled prevalence of overweight and obesity ranged from 13 to 23% in various regions in the period between 2011 and 2016 [
7]. In a recent study on children and adolescents aged 2 to 19 years in the United States, the prevalence of obesity was 17.0% in 2011–2014 and that of extreme obesity was 5.8% [
8], indicating the increasing relevance of childhood obesity for public health. Obesity in children is associated with elevated blood pressure and abnormal fasting glucose concentrations [
9]. Furthermore, obese children are likely to become obese adults with an increased risk of obesity-related complications (e.g. diabetes and cardiovascular disease) and increased morbidity and mortality [
10‐
12].
Neonatal body composition parameters such as fat mass (FM), fat free mass (FFM) and the proportion of FM divided by total body mass (BF%), might be more sensitive markers of the in-utero environment and neonatal adiposity than birth weight and length alone, because variability in FM and FFM has been reported in newborns of similar weight and length [
13,
14], and anthropometric measures, albeit easy to determine, do not necessarily reflect variability in body composition.
Neonatal body composition can be determined by skinfold thickness, isotope dilution, dual energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and air displacement plethysmography (ADP), where the latter was shown to produce highly reproducible and accurate measurements and may be suitable for large epidemiological studies [
4,
15]. Furthermore, ADP has the advantages of not using ionizing radiation, a short examination time and comparatively low costs, hence ADP will likely be the method of choice for future studies.
To inform future studies, we performed a systematic review of the literature and meta-analysis for available measurements of body composition at birth in healthy, term, singleton infants using ADP. Our aim was to establish reference values for different ethnic groups and to investigate factors potentially influencing body composition.
Discussion
Aim of this meta-analysis was to summarize and compare the currently available data on neonatal body composition in healthy term infants determined by ADP to inform future studies. In the studies selected for meta-analysis, median BF% was 10.0% (SD 4.1%) and mean FFM 2883 (356) g. German infants showed values for BF% (10.6%) [
20] similar to those from other Europeean countries such as Portugal (11.3%) [
26], the Netherlands (10.3%) [
25], and Ireland (11.1%) [
21], but higher values than those from Australia (BF% 9.2) [
4] and the US (BF% 9–13.6%) [
18,
23,
27,
28].
Meta-analysis of eight studies enabled comparisons of different ethnic backgrounds and showed that Hispanic infants recruited in the USA had the highest BF% with 14.3%, followed by African-American infants with 11.2%. The lowest BF% was reported for East-African newborns (7.8%). FFM was highest in Caucasian infants with 2903 (363) g, followed by East-Africans with 2840 (310) g and lowest in African-Americans (2674 (N/A) g).
Differences in total body fat between populations of different ethnic background have already been reported in adults and children [
31,
32], but little data based on ADP exist in neonates. Paley et al. found a higher total FM in African–American, Asian and Hispanic males and African–American females compared to Caucasian males and females, respectively [
23]. Furthermore, an Australian study reported that infants of Caucasian mothers showed higher BF% and birthweight compared to infants of Asian mothers [
4]. In contrast, Ramel et al. measured body composition in preterm infants after hospital discharge in comparison to term infants and found no differences between „white “or „non-white “infants [
33]. The data from this systematic review seem to support that there are differences in body composition between neonates from different ethnic backgrounds, but it remains unclear whether these are genetically determined or due to socioeconomic factors (e.g., access to nutrition etc.). Furthermore, the absolute differences in FFM and BF% reported herein must be interpreted with caution because lack of data on SD precluded statistical analyses by ANOVA and t-test.
In a cross-sectional Australian study including 599 term infants, gender showed the strongest association with neonatal BF%, followed by maternal ethnicity [
4]. Consistent with this, the present study and meta-analysis confirmed differences in body composition between female and male neonates, with girls having a higher BF% (11.1% vs. 9.6%) and lower FFM (2827 g vs. 2979 g), which seems to remain true throughout life [
34,
35]. Gender is known to be a major determinant of body composition for term infants: males are heavier at birth and have a higher lean body mass, whereas females have more subcutaneous fat [
36]. Gender differences have been primarily attributed to the action of fetal sex steroid hormones, e.g. testosterone, which presumably enhances lean body mass growth in utero [
37].
Besides ethnic factors and gender, the quality of maternal diet and intake of macro- and micronutrients during pregnancy as modifiable factors have demonstrated significant impact on birth outcomes including body composition [
38,
39]. Therefore, maternal nutritional status during pregnancy is an important factor in fetal growth and development [
27,
38‐
42] and changed over the last years in industrialized as well as developing countries. The Healthy Start study demonstrated the influence of poor diet quality during pregnancy on neonatal adiposity with increases in BF% but no differences in FFM [
27]. It also reported that neonatal adiposity, but not birth weight, was independently associated with increased maternal intake of total fat and total carbohydrates [
40], indicating that maternal diet is an important factor impacting on neonatal body composition but not birth weight.
Sparkes et al. hypothesized that fetal FFM is primarily influenced by genetic factors, whereas fetal FM is influenced by the maternal metabolic and nutritional environment [
43]. This is consistent with our results indicating less variability in FFM compared to BF% across populations from industrialized countries. In the context of worldwide increasing public health challenges due to childhood obesity and later life metabolic dysregulation, interventions aiming at maternal nutritional exposure as well as maternal physical activity during pregnancy could be important [
44].
Healthy newborn infants typically loose about 6–7% of their initial birth weight in the first days after birth [
45,
46], and this weight loss is influenced by several factors (e.g., volume of feeding after birth, pre-delivery intravenous fluids, etc.). In a longitudinal study involving 28 exclusively breastfed, healthy, term infants during their first 5 postnatal days, Roggero et al. [
22] showed that body composition changes with early postnatal weight loss and that both BF% and FFM decreased postnatally. However, there was a greater loss in BF% compared to FFM initially. In this meta-analysis summarizing cross-sectional data, FFM decreased along with body weight during the first 4 days after birth – whereas BF% differed little, indicating that FFM and FM are lost in similar proportions during the early postnatal weight loss. Admittedly, the longitudinal study of Roggero with repeated measurements in the same cohort is better suited to evaluate which compartments are affected by postnatal weight loss than this meta-analysis.
Limitations of our analysis are the limited number of studies and their heterogeneous design. Data on various influencing factors (e.g. age at measurement) were not published for all study populations. Nonetheless, body composition was measured in an objective and reproducible fashion using the same technique in healthy term (and predominantly singleton) neonates. The relatively homogeneous results found for body composition in our meta-analysis suggest good generalizability to other industrialized countries.
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