Tessa L. Crume

Maternal Environment and the Transgenerational Cycle of Obesity and Diabetes

The prevalence of obesity continues to increase worldwide and represents one of the most pressing public health issues due to its associated morbidity, mortality, and health care costs. Novel research is demonstrating that alterations of the maternal environment can impact the intrauterine development of the fetus and influence the offspring’s risk for obesity and type 2 diabetes over the lifecourse. This article reviews the epidemiological evidence with a focus on the fetal overnutrition hypothesis. We discuss potential mechanisms and suggest future directions for research. While postnatal lifestyle is the most immediate cause of obesity, the influence of the maternal in utero environment is evidenced in the U- or J-shaped relationship between birth weight and adult obesity and metabolic disease demonstrating that both a nutritionally limited or excessive in utero environment can lead to postnatal obesity and related chronic diseases. Developmental biology has taught us about the role of a mismatch between a constrained prenatal and a plentiful postnatal environment in the pathogenesis of obesity, i.e., a so-called thrifty obesity pathway (1). This is likely operating in developing countries and populations undergoing rapid transition. Another developmental pathway to obesity, which is likely more important in Western societies, is the fetal overnutrition pathway. This pathway reflects the effects of hypernutrition during fetal life and creates the conditions for the later pathophysiological effects of an obesogenic environment (1). Although these developmental mechanisms are likely distinct, they are both associated with an increased risk of obesity later in life. This article focuses on the fetal overnutrition pathway. Research in this field started with the hypothesis of fuel-mediated teratogenesis (2) and clinical studies suggesting that offspring exposed to diabetes in utero have greater birth weight and greater weight for length during childhood. Animal studies have demonstrated that the metabolic imprinting caused by the obese and …

Highly resistant Salmonella Newport-MDRAmpC transmitted through the domestic US food supply: a FoodNet case-control study of sporadic Salmonella Newport infections, 2002-2003.

BACKGROUND A new multidrug-resistant (MDR) strain of Salmonella serotype Newport, Newport-MDRAmpC, has recently emerged. We sought to identify the medical, behavioral, and dietary risk factors for laboratory-confirmed Salmonella Newport infection, including that with Newport-MDRAmpC. METHODS A 12-month population-based case-control study was conducted during 2002-2003 in 8 sites of the Foodborne Diseases Active Surveillance Network (FoodNet), with 215 case patients with Salmonella Newport infection and 1154 healthy community control subjects. RESULTS Case patients with Newport-MDRAmpC infection were more likely than control subjects to have taken an antimicrobial agent to which Newport-MDRAmpC is resistant during the 28 days before the onset of diarrheal illness (odds ratio [OR], 5.0 [95% confidence interval {CI}, 1.6-16]). Case patients with Newport-MDRAmpC infection were also more likely to have eaten uncooked ground beef (OR, 7.8 [95% CI, 1.4-44]) or runny scrambled eggs or omelets prepared in the home (OR, 4.9 [95% CI, 1.3-19]) during the 5 days before the onset of illness. International travel was not a risk factor for Newport-MDRAmpC infection but was a strong risk factor for pansusceptible Salmonella Newport infection (OR, 7.1 [95% CI, 2.0-24]). Case patients with pansusceptible infection were also more likely to have a frog or lizard in their household (OR, 2.9 [95% CI, 1.1-7.7]). CONCLUSIONS Newport-MDRAmpC infection is acquired through the US food supply, most likely from bovine and, perhaps, poultry sources, particularly among persons already taking antimicrobial agents.

Re-assessment of risk factors for sporadic Salmonella serotype Enteritidis infections: a case-control study in five FoodNet Sites, 2002-2003.

Active surveillance for laboratory-confirmed Salmonella serotype Enteritidis (SE) infection revealed a decline in incidence in the 1990s, followed by an increase starting in 2000. We sought to determine if the fluctuation in SE incidence could be explained by changes in foodborne sources of infection. We conducted a population-based case-control study of sporadic SE infection in five of the Foodborne Diseases Active Surveillance Network (FoodNet) sites during a 12-month period in 2002-2003. A total of 218 cases and 742 controls were enrolled. Sixty-seven (31%) of the 218 case-patients and six (1%) of the 742 controls reported travel outside the United States during the 5 days before the cases illness onset (OR 53, 95% CI 23-125). Eighty-one percent of cases with SE phage type 4 travelled internationally. Among persons who did not travel internationally, eating chicken prepared outside the home and undercooked eggs inside the home were associated with SE infections. Contact with birds and reptiles was also associated with SE infections. This study supports the findings of previous case-control studies and identifies risk factors associated with specific phage types and molecular subtypes.

The Impact of In Utero Exposure to Diabetes on Childhood Body Mass Index Growth Trajectories: The EPOCH Study

OBJECTIVE To examine associations between exposure to maternal diabetes in utero and body mass index (BMI) growth trajectories from birth through 13 years of age among a diverse cohort of youth. STUDY DESIGN Mixed linear effects models were constructed to assess differences in BMI and BMI growth velocity from birth through 13 years of age for 95 subjects exposed to diabetes in utero and 409 unexposed subjects enrolled in a retrospective cohort study. RESULTS The overall BMI growth trajectory (adjusted for sex and race/ethnicity) was not significantly different for exposed and unexposed subjects from birth through 26 months of age (P = .48). However, the overall growth trajectory from 27 months of age through 13 years differed by exposure status (P = .008), adjusted for sex and race/ethnicity. The difference was primarily due to a significantly higher BMI growth velocity among exposed youth between 10 and 13 years, increasing by 4.56 kg/m² compared with 3.51 kg/m² in the unexposed (P = .005). Control for demographic variables, socioeconomic factors, and maternal prepregnancy BMI did not alter the observed associations. CONCLUSIONS Exposure to maternal diabetes in utero accelerates BMI growth in late childhood, thus increasing long-term obesity risk.

Lactation and Neonatal Nutrition: Defining and Refining the Critical Questions

This paper resulted from a conference entitled “Lactation and Milk: Defining and refining the critical questions” held at the University of Colorado School of Medicine from January 18–20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond.

Long-Term Impact of Neonatal Breastfeeding on Childhood Adiposity and Fat Distribution Among Children Exposed to Diabetes In Utero

OBJECTIVE To evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero. RESEARCH DESIGN AND METHODS Retrospective cohort study of 89 children exposed to diabetes in utero and 379 unexposed youth with measured BMI, waist circumference, skinfolds, visceral (VAT) and subcutaneous (SAT) abdominal fat. A measure of breast milk–months was derived from maternal self-report and used to categorize breastfeeding status as low (<6) and adequate (≥6 breast milk–months). Multiple linear regression was used to model the relationship between exposure to diabetes in utero and offspring adiposity outcomes among youth stratified according to breastfeeding status. RESULTS Adequate (vs. low) breastfeeding status was associated with significantly lower BMI, waist circumference, SAT, and VAT at ages 6–13 years. Among youth in the low breastfeeding category, exposure to diabetes in utero was associated with a 1.7 kg/m2 higher BMI (P = 0.03), 5.8 cm higher waist circumference (P = 0.008), 6.1 cm2 higher VAT (P = 0.06), 44.6 cm2 higher SAT (P = 0.03), and 0.11 higher ratio of subscapular-to-triceps skinfold ratio (P = 0.008). Among those with adequate breastfeeding in infancy, the effect of prenatal exposure to diabetes on childhood adiposity outcomes was not significant. CONCLUSIONS Adequate breastfeeding protects against childhood adiposity and reduces the increased adiposity levels associated with exposure to diabetes in utero. These data provide support for mothers with diabetes during pregnancy to breastfeed their infants in order to reduce the risk of childhood obesity.

The long-term impact of intrauterine growth restriction in a diverse U.S. cohort of children: the EPOCH study

To explore the long‐term impact of intrauterine growth restriction (IUGR) among a diverse, contemporary cohort of US children.

The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero : the EPOCH Study

Objective:To evaluate the influence of breast-feeding on the body mass index (BMI) growth trajectory from birth through 13 years of age among offspring of diabetic pregnancies (ODP) and offspring of non-diabetic pregnancies (ONDP) participating in the Exploring Perinatal Outcomes Among Children Study.Subjects:There were 94 ODP and 399 ONDP who had multiple BMI measures obtained from birth throughout childhood. A measure of breast milk-months was derived from maternal self-report to categorize breast-feeding status as adequate (⩾6 breast milk-months) or low (<6 breast milk-months). Mixed linear-effects models were constructed to assess the impact of breast-feeding on the BMI growth curves during infancy (birth to 27 months) and childhood (27 months to 13 years).Results:ODP who were adequately breast-fed had a slower BMI growth trajectory during childhood (P=0.047) and slower period-specific growth velocity with significant differences between 4 and 6 years of age (P=0.03) and 6 to 9 years of age (P=0.01) compared with ODP with low breast-feeding. A similar pattern was seen in the ONDP, with adequate breast-feeding associated with lower average BMI in infancy (P=0.03) and childhood (P=0.0002) and a slower growth trajectory in childhood (P=0.0002). Slower period-specific growth velocity was seen among the ONDP associated with adequate breast-feeding with significant differences between 12–26 months (P=0.02), 4–6 years (P=0.03), 6–9 years (P=0.0001) and 9–13 years of age (P<0.0001).Conclusion:Our study provides novel evidence that breast-feeding is associated with long-term effects on childhood BMI growth that extend beyond infancy into early and late childhood. Importantly, these effects are also present in the high-risk offspring, exposed to overnutrition during pregnancy. Breast-feeding in the early postnatal period may represent a critical opportunity to reduce the risk of childhood obesity.

Identification of Minimal Clinically Important Difference Scores of the PedsQL in Children, Adolescents, and Young Adults With Type 1 and Type 2 Diabetes

OBJECTIVE To establish minimal clinically important difference (MCID) scores representing the smallest detectable change in quality of life (QOL), using the Pediatric Quality of Life Inventory (PedsQL) Generic Core and Diabetes Module among youth with diabetes and their parents, and to identify demographic and clinical correlates of QOL change over 1 year. RESEARCH DESIGN AND METHODS Participants in the SEARCH for Diabetes in Youth Study aged >5 years and parents of youth aged <18 years completed PedsQL surveys at their initial and 12-month study visits. MCIDs for each PedsQL module were calculated using one standard error of measurement. Demographic and clinical characteristics associated with QOL change were identified through multiple linear and logistic regression analyses. RESULTS The sample comprised 5,004 youth (mean age, 12.5 ± 4.7 years; mean diabetes duration, 3.4 ± 3.7 years). Of 100 possible points, PedsQL total score MCIDs for youth with type 1 and type 2 diabetes, respectively, were Generic Core, 4.88, 6.27 (parent) and 4.72, 5.41 (youth); Diabetes Module, 4.54, 6.06 (parent) and 5.27, 5.96 (youth). Among 1,402 youth with a follow-up visit, lower baseline QOL, male sex, private insurance, having type 1 diabetes, longer diabetes duration, and better glycemic control predicted improvements in youth- and parent-reported PedsQL total scores over 1 year. Clinically meaningful (≥1 MCID) improvements in total score for at least one PedsQL module were predicted by private insurance, lower BMI, and lower A1C at baseline. CONCLUSIONS These diabetes-specific reference points to interpret clinically meaningful change in PedsQL scores can be used in clinical care and research for youth with type 1 and type 2 diabetes.

Maternal obesity, gestational weight gain, and offspring adiposity: the exploring perinatal outcomes among children study.

OBJECTIVE To determine whether adequate vs excessive gestational weight gain (GWG) attenuated the association between maternal obesity and offspring outcomes. STUDY DESIGN Data from 313 mother-child pairs participating in the Exploring Perinatal Outcomes among Children study were used to test this hypothesis. Maternal prepregnancy body mass index (BMI) and weight measures throughout pregnancy were abstracted from electronic medical records. GWG was categorized according to the 2009 Institute of Medicine criteria as adequate or excessive. Offspring outcomes were obtained at a research visit (average age 10.4 years) and included BMI, waist circumference (WC), subcutaneous adipose tissue (SAT) and visceral adipose tissue, high-density lipoprotein cholesterol, and triglyceride levels. RESULTS More overweight/obese mothers exceeded the Institute of Medicine GWG recommendations (68%) compared with normal-weight women (50%) (P < .01). Maternal prepregnancy BMI was associated with worse childhood outcomes, particularly among offspring of mothers with excessive GWG (increased BMI [20.34 vs 17.80 kg/m(2)], WC [69.23 vs 62.83 cm], SAT [149.30 vs 90.47 cm(2)], visceral adipose tissue [24.11 vs 17.55 cm(2)], and homeostatic model assessment [52.52 vs 36.69], all P < .001). The effect of maternal prepregnancy BMI on several childhood outcomes was attenuated for offspring of mothers with adequate vs excessive GWG (P < .05 for the interaction between maternal BMI and GWG status on childhood BMI, WC, SAT, and high-density lipoprotein cholesterol). CONCLUSION Our findings lend support for pregnancy interventions aiming at controlling GWG to prevent childhood obesity.