Elke Rodekamp

Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome.

Pre‐ and neonatal overfeeding programmes a permanent obesity disposition and accompanying diabetic and cardiovascular disorders, by unknown mechanisms. We proposed that early overfeeding may alter DNA methylation patterns of hypothalamic promoter regions of genes critically involved in the lifelong regulation of food intake and body weight. We induced neonatal overfeeding by rearing Wistar rats in small litters (SL) and thereafter mapped the DNA methylation status of CpG dinucleotides of gene promoters from hypothalamic tissue, using bisulfite sequencing. Neonatal overfeeding led to rapid early weight gain, resulting in a metabolic syndrome phenotype, i.e. obesity, hyperleptinaemia, hyperglycaemia, hyperinsulinaemia, and an increased insulin/glucose ratio. Accompanying, without group difference to controls, the promoter of the main orexigenic neurohormone, neuropeptide Y, was methylated at low levels (i.e. < 5%). In contrast, in SL rats the hypothalamic gene promoter of the main anorexigenic neurohormone, proopiomelanocortin (POMC), showed hypermethylation (P < 0.05) of CpG dinucleotides within the two Sp1‐related binding sequences (Sp1, NF‐κB) which are essential for the mediation of leptin and insulin effects on POMC expression. Consequently, POMC expression lacked upregulation, despite hyperleptinaemia and hyperinsulinaemia. Accordingly, the extent of DNA methylation within Sp1‐related binding sequences was inversely correlated to the quotients of POMC expression/leptin (P= 0.02) and POMC expression/insulin (P < 0.001), indicating functionality of acquired epigenomic alterations. These data for the first time demonstrate a nutritionally acquired alteration of the methylation pattern and, consequently, the regulatory ‘set point’ of a gene promoter that is critical for body weight regulation. Our findings reveal overfeeding as an epigenetic risk factor of obesity programming and consecutive diabetic and cardiovascular disorders and diseases, in terms of the metabolic syndrome.

Breast-Feeding and Risk for Childhood Obesity: Response to Mayer-Davis et al.

We read with great interest the recent study by Mayer-Davis et al. (1) on the impact of breast-feeding on childhood obesity risk in the presence of maternal diabetes or obesity. The authors drew conclusions that seem to directly oppose previous observations from our group (2,3). However, we would like to deliver three arguments suggesting that the presented data can also be interpreted in a completely different manner and in no way exclude, but rather support, a …

Rapid neonatal weight gain increases risk of childhood overweight in offspring of diabetic mothers

Abstract Aim: Increased neonatal weight gain has been suggested as risk factor for later overweight. Offspring of diabetic mothers (ODM) have a long-term increased overweight risk. However, the role of early postnatal weight gain for later overweight has not been addressed so far in ODM. We investigated whether increased weight gain during the first 4 months is related to later overweight in ODM. Methods: Determinants of childhood overweight and neonatal weight gain were analyzed in 152 ODM from the Kaulsdorf Cohort Study by MANOVA and regression analyses. Results: Independent of birth weight, weight gain during the first 4 months was positively related to childhood relative body weight (P=0.001). Each 100 g-increase in weight during this period increased overweight risk by 65% (95%CI: 10–247%). ODM with rapid early weight gain had a more than six-fold increased risk of later overweight (OR: 6.77; 95%CI: 1.36–33.6). Early neonatal intake of breast milk from metabolically healthy mothers protected from rapid early weight gain (P=0.03). Conclusions: Increased weight gain during the first 4 months of life is a strong, independent risk factor for childhood overweight in ODM. Preventing nutritionally-induced rapid early weight gain in ODM might be a promising strategy to lower their long-term overweight risk.

Impact of breast-feeding on psychomotor and neuropsychological development in children of diabetic mothers: role of the late neonatal period.

Abstract Aim: Previous data from our Kaulsdorf Cohort Study (KCS) suggest that early neonatal ingestion (1st week) of breast milk from diabetic mothers (diabetic breast milk, DBM) may increase the risk of being overweight and delay speech development in offspring of diabetic mothers (ODM). Late neonatal DBM ingestion (2nd–4th week), however, not independently influenced the risk of overweight. We investigated whether late neonatal DBM ingestion might independently influence neuro-development. Methods: Achievement of developmental milestones according to late neonatal DBM intake was analyzed in 242 ODM. Results: No impact of DBM ingestion on psychomotor parameters was observed. In contrast, it negatively influenced onset of speaking (no DBM: median 44.0 weeks, range 31.0–72.0; some DBM: 48.0, 24.0–100.0; DBM only: 52.0, 28.0–84.0; P=0.037) and halved the probability of reaching this milestone at any time point (hazard ratio: 0.53, 95% confidence interval: 0.31–0.91). However, adjustment for DBM volume ingested during the early neonatal period weakened the hazard ratio towards non-significance. In the fully adjusted model, the hazard ratio was halved, but insignificant. Conclusions: Our results underscore that neonatal DBM ingestion, particularly during the first week of life, may delay speech development, an important indicator of cognitive development. Further studies are urgently recommended on consequences of breast-feeding for neurodevelopment in ODM.

Vasa praevia: risk-adapted modification of the conventional management--a retrospective study.

PURPOSE Undiagnosed vasa praevia carries an imminent risk of fetal death and increases with IVF. When diagnosed, the question arises as to whether the conventional prenatal management of routine steroid administration for fetal lung maturation and elective caesarean section in week 35 is generally justified in face of the risks involved. We present a retrospective study of a risk-adapted modification of the conventional management of vasa praevia. MATERIAL AND METHODS We analysed 11 years of records involving 18 cases of antenatally diagnosed vasa praevia at our perinatal centre. Each case was managed by a risk-adapted modification of the conventional treatment where both, the steroid administration and the timing of delivery, were dependent on the patient history and clinical signs for preterm birth. RESULTS There were no lethal fetal, neonatal, or maternal complications. The earliest caesarean section took place at 34 weeks 1 day, the latest at 37 weeks 1 day, and in more than half of the cases at ≥ 36 weeks. CONCLUSION Steroid application is generally recommended for pregnancies before 34 weeks carrying a risk for preterm birth. Thus, retrospectively, none of our cases required steroid administration. This supports our protocol of not obligatorily administering steroids. Delaying the caesarean section up to two weeks beyond the conventionally recommended date of 35 weeks in 78% of our cases resulted in no complications. This justifies the suitability of determining the timing of delivery based on our individual patient assessment. In conclusion, the following recommendations for a risk-adapted management of vasa praevia can be made: 1. weekly evaluation of risk factors for preterm delivery; 2. steroid administration only at risk for preterm birth; 3. admission to hospital with full obstetric and neonatal care facilities between 32 and 34 weeks; 4. elective caesarean section between 35 and 37 weeks, risk-adapted.

Prävention der kindlichen Adipositas während der Schwangerschaft

ZusammenfassungEine große Zahl von epidemiologischen und tierexperimentellen Befunden weist darauf hin, dass Einflüsse während der Schwangerschaft das lebenslange Risiko für die Entwicklung von Adipositas sowie Stoffwechsel- und Herz-Kreislauf-Erkrankungen programmieren können. Entscheidend für die Erkenntnis dieser Zusammenhänge waren Studien an Kindern von Müttern mit Diabetes mellitus während der Schwangerschaft sowie an Kindern mit einem verminderten Geburtsgewicht. Unter Fokussierung auf die Folgen eines mütterlichen Übergewichts/Diabetes mellitus während der Schwangerschaft sowie einer pränatalen Unterernährung wird anhand ausgewählter epidemiologischer und tierexperimenteller Daten der derzeitige Kenntnisstand zum Phänomen einer perinatalen Programmierung von adipogenen und diabetogenen Risiken diskutiert. Die hieraus erwachsenden weitreichenden Konsequenzen für die Primärprävention von chronischen Erkrankungen sowie der Modellcharakter dieser Hypothesen und Beobachtungen für das grundlegende Verständnis der Entwicklung von Gesundheit und Krankheit werden hervorgehoben.AbstractCurrently, epidemiological and experimental data are being intensively discussed which indicate that exposures during prenatal life have lifelong consequences for the risk of developing obesity and subsequent metabolic and cardiovascular diseases. In this context, observations in offspring of mothers with diabetes during pregnancy as well as studies in children with low birth weight were most influential. This paper illustrates the current knowledge on perinatal programming of obesity and associated diseases and discusses possible aetiopathogenic mechanisms, focussing on epidemiological and animal studies on the consequences of exposure to maternal obesity/diabetes and prenatal undernutrition. The resultant far-reaching potential for primary prevention of chronic diseases as well as the paradigmatic character of these hypotheses and observations for the general understanding of health and disease are highlighted.

Predictors of Overweight During Childhood in Offspring of Parents With Type 1 Diabetes: Response to Hummel et al.

We read with interest the article by Hummel et al. (1) regarding predictors of childhood overweight risk in offspring of type 1 diabetic parents. Beyond the reevaluation of large-for-gestational-age (LGA) status as a long-term risk factor for later overweight, it is important and became clear that in this study breast-feeding significantly decreased childhood overweight risk. Thus, the study provides new data supporting the promotion of breast-feeding, which is undoubtedly worth targeting. Moreover, the authors also confirmed that, of course, maternal type 1 diabetes is not a risk factor as such, but that tight metabolic control during pregnancy may optimize the short- …

Fetale Programmierung bei intrauteriner Milieustörung – grundlegende Mechanismen am Beispiel der Körpergewichts- und Stoffwechselregulation

Currently, epidemiological and experimental data indicate that exposures during prenatal and perinatal life may have lifelong consequences for the risk of developing obesity and metabolic and cardiovascular diseases. In this context, observations of the offspring of mothers with gestational diabetes as well as studies of children with low birth weight were most influential. This paper illustrates the current knowledge about perinatal programming of obesity and associated diseases and discusses possible etiopathogenic mechanisms, focussing on epidemiological and animal studies of the consequences of exposure to maternal diabetes and pre-/neonatal undernutrition. The resultant far-reaching potential for primary prevention of chronic diseases as well as the paradigmatic character of these hypotheses and observations for the general understanding of health and disease are highlighted.Currently, epidemiological and experimental data indicate that exposures during prenatal and perinatal life may have lifelong consequences for the risk of developing obesity and metabolic and cardiovascular diseases. In this context, observations of the offspring of mothers with gestational diabetes as well as studies of children with low birth weight were most influential. This paper illustrates the current knowledge about perinatal programming of obesity and associated diseases and discusses possible etiopathogenic mechanisms, focussing on epidemiological and animal studies of the consequences of exposure to maternal diabetes and pre-/neonatal undernutrition. The resultant far-reaching potential for primary prevention of chronic diseases as well as the paradigmatic character of these hypotheses and observations for the general understanding of health and disease are highlighted.

Birth Weight and Later Risk of Type 2 Diabetes

According to the ‘small baby syndrome hypothesis’, birth weight is claimed to show an inverse linear relation to later risk of type 2 diabetes. By looking into the literature 14 studies involving a t

Letter Regarding Article by Stettler et al, “Weight Gain in the First Week of Life and Overweight in Adulthood: A Cohort Study of European American Subjects Fed Infant Formula”

To the Editor: Recently, Stettler et al1 published exciting data from a large cohort of formula-fed infants on the association between weight gain in the first neonatal week and risk of overweight in adulthood. Suggesting that this early, short period has such a long-term impact on later health is fascinating and provoking. We have data strongly …