Figure 3.3 Association of Mediterranean diet score in pregnancy with child BMI z score in (a) pooled analysis, (b) only Project Viva, and (c) only Rhea pregnancy cohort studies. Results from generalized additive models adjusted for maternal age, pre‐pregnancy body mass index, race/ethnicity, education level, parity, smoking during pregnancy, and child sex and age at outcome assessment.
From Chatzi et al. [28] © 2017 World Obesity Federation. Reproduced with permission.
In a pooled analysis, for each 3‐point increment in the MDS, offspring BMI z‐score was lower by 0.14 units (95% CI: −0.15 to −0.13), waist circumference by 0.39 cm (95% CI: −0.64 to −0.14), and the sum of skin‐fold thicknesses by 0.63 mm (95% CI: −0.98 to −0.28). In addition, higher MDS was associated with lower offspring systolic (−1.03 mmHg; 95% CI: −1.65 to −0.42) and diastolic blood pressure (−0.57 mmHg; 95% CI: −0.98 to −0.16). These results support the hypotheses that maternal adherence to the Mediterranean diet during pregnancy was associated with lower child adiposity, adipokines, and blood pressure levels.
One mechanism by which excess sugar intake and lower adherence to a Mediterranean dietary pattern might act to influence health outcomes is via increasing systemic inflammation. The Dietary Inflammatory Index (DII)™ has been developed and validated to characterize and quantify the cumulative inflammatory potential of individual diets [61]. The DII score positively correlates with interval changes in high‐sensitivity C‐reactive protein (hsCRP), a marker of systemic inflammation, in nonpregnant adults and pregnant women [61,62]. The DII is not a dietary pattern in itself but a way to assess the pro‐ or anti‐inflammatory potential of any diet. In Project Viva, dietary inflammatory index in the highest quartiles during both pregnancy and early childhood, compared to the lowest quartiles, was associated with higher waist circumference (2.4 cm; 95% CI: 0.14, 4.6) in all children and higher BMI in boys (0.78 units; 0.34, 1.22) [63]. While intervention trials are needed to confirm these associations, it seems reasonable for health care providers to recommend healthy, less inflammatory dietary patterns such as the Mediterranean diet for pregnant women.
Environmental chemicals
Recent epidemiologic and experimental data have elucidated the role of environmental chemicals on the risk for obesity and related metabolic diseases. These organic and inorganic pollutants of human and natural origin have been termed “environmental obesogens” or “metabolism‐disrupting chemicals.”
Maternal smoking during pregnancy is one well‐characterized example of an environmental exposure that appears to persistently influence offspring body weight. While prenatal smoking causes reduced fetal growth, analyses from dozens of studies have consistently found associations with later offspring obesity. One meta‐analysis of 14 studies estimated that maternal smoking during pregnancy conferred 50% increased odds (adjusted OR 1.50; 95% CI: 1.36, 1.65) for offspring obesity across an age range of 3–33 years [64]. Adjustment for factors related to social and economic position did not markedly affect estimates, and publication bias did not appear to explain the finding, but residual confounding is still possible. A more recent independent patient data meta‐analysis included 26 identified studies, including a total of 238,340 mother–child‐pairs [65]. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increased per cigarette of 1.03 (95% CI: 1.02, 1.03); the OR flattened with higher cigarette use (Fig. 3.4) [65].
A similar pattern of association as for maternal prenatal smoking, with both lower fetal growth and rapid postnatal weight gain, is seen with traffic‐related air pollution [66], supporting the smoking‐obesity relationship by analogy. Further, animal studies have observed similar findings; one in rats indicated that nicotine administration in the puerperal period led to higher adiposity through early adulthood despite no differences in maternal weight gain or size at birth [67]. Nicotine‐exposed offspring had phenotypes similar to those associated with human obesity, including higher blood pressure and impaired glucose metabolism [68,69]. Interestingly, limited data suggest that these effects may be transgenerational – F2 offspring of F1 dams exposed to nicotine during their own intrauterine development had higher blood pressure, higher fasting insulin, and greater insulin response to a glucose load [70].
Figure 3.4 Association of maternal number of cigarettes smoked per day and risk of offspring overweight (including obesity), and obesity only stratified by sex. From Albers et al. [65] ©Nature Publishing Group.
Reproduced with permission. ____ = OR for the association between maternal number of cigarettes and offspring overweight/obesity; _ _ _ = 95% CI of the OR; the vertical dashes above the x axis indicate the density of the observations underlying the model.
Per‐ and polyfluorinated substances (PFAS) are another class of chemicals that have been studied in relation to programming of obesity [71]. PFAS are man‐made fluorinated chemicals used in stain‐resistant and water‐resistant coatings for textiles, non‐stick cookware, food containers, floor polish, fire‐fighting foam, and industrial surfactants. The strong carbon‐fluorine chemical bond makes PFAS extremely resistant to thermal, chemical, and biological degradation, which results in bioaccumulation and persistence in human tissues for years. Four PFAS – perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) – are almost universally detected in the serum of pregnant women, neonates, and children worldwide, which indicates that exposure is ubiquitous. Furthermore, these chemicals can cross the placenta [71]. A substantial body of evidence exists suggesting that prenatal exposure to PFAS could adversely affect fetal growth. In a systematic review and meta‐analysis, greater prenatal PFOA exposure was associated with a 19 g decrement in birth weight (95% CI: −8 to −30 g) [72]. These results in humans are similar to those observed in rodent studies [73]. Some human observational studies indicate an association of higher circulating concentrations of certain PFAS with weight gain or obesity in children and adults [74,75]. Additionally, some prospective cohort data show that prenatal PFAS exposure is associated with alterations in infant or child growth, increased adiposity during childhood and adulthood [76–78], although others have not shown associations [79,80].
Infant growth patterns and timing
Just like fetal growth, early postnatal growth is a strong predictor of later size. Because weight gain accompanies linear growth, weight gain in excess of linear growth is more interesting than weight gain alone. Obtaining accurate length measures is crucial for this effort [81]. Many studies, unfortunately, do not have accurate lengths and therefore resort to examining weight gain alone.
Independent of birth size, greater postnatal weight gain predicts later adiposity and related cardiometabolic risk [82,83]. Meta‐analyses have found that accelerated weight gain during the first weeks or months of life is associated with higher BMI or obesity later in life [84,85]. For example, Baird et al. [84] reviewed 10 studies that assessed the relationship of infant growth with subsequent obesity. Compared with other infants, among infants with more rapid growth the ORs and relative risks of later obesity ranged from 1.17 to 5.70. Associations were consistent for obesity at different ages and for people born over a period from 1927 to 1994.
Despite the seeming consistency of these studies, counterexamples exist. Among Finnish men, those who eventually developed coronary heart disease, compared with the cohort as a whole, appeared to have experienced declining height, weight, and BMI during the first year of life before increasing dramatically after the age of 2 years [86]. Gain in BMI in the first 2 years of life was associated with adult lean