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Being Born Large for Gestational Age: Metabolic and Epidemiological Studies
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is a major health problem in the Western world. Mean birth weight has increased during the last 25 years. One explanation is that the proportion of large for gestational age (LGA) infants has increased. Such infants risk developing obesity, cardiovascular disease and diabetes later in life. Despite the risk of neonatal hypoglycemia, their postnatal metabolic adaptation has not been investigated. Our data, obtained with stable isotope labeled compounds, demonstrate that newborn LGA infants have increased lipolysis and decreased insulin sensitivity. After administration of glucagon, the plasma levels of glucose and the rate of glucose production increased. The simultaneous increase in insulin correlated with the decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

We also demonstrated an intergenerational effect of being born LGA, since women born LGA, were at higher risk of giving birth to LGA infants than women not born LGA. Further, the LGA infants formed three subgroups: born long only, born heavy only, and born both long and heavy. Infants born LGA of women with high birth weight or adult obesity were at higher risk of being LGA concerning weight alone, predisposing to overweight and obesity at childbearing age. In addition we found that pregnant women with gestational diabetes were at increased risk of giving birth to infants that were heavy alone. This could explain the risk of both perinatal complications and later metabolic disease in infants of this group of women.

To identify determinants of fetal growth, 20 pregnant women with a wide range of fetal weights were investigated at 36 weeks of gestation. Maternal fat mass was strongly associated with insulin resistance. Insulin resistance was related to glucose production, which correlated positively with fetal size. The variation in resting energy expenditure, which was closely related to fetal weight, was largely explained by BMI, insulin resistance, and glucose production. Lipolysis was not rate limiting for fetal growth in this group of women. Consequently, high maternal glucose production due to a high fat mass may result in excessive fetal growth.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket , 2008. , p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 363
Keywords [en]
large for gestational, glucose production, lipolysis, insulin resistance, intergenerational, gestational diabetes mellitus, stable isotopes, pregnant women, newborn infant
National Category
Other Medical Sciences not elsewhere specified
Identifiers
URN: urn:nbn:se:uu:diva-9135ISBN: 978-91-554-7246-7 (print)OAI: oai:DiVA.org:uu-9135DiVA, id: diva2:172315
Public defence
2008-09-12, Rosénsalen, Akademiska Sjukhuset, Ingång 95/96, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-08-18 Created: 2008-08-18Bibliographically approved
List of papers
1. Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age
Open this publication in new window or tab >>Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age
2007 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 120, no 5, p. 958-965Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE. In addition to neonatal hypoglycemia, infants who are born large for gestational age are at risk for developing obesity, cardiovascular disease, and diabetes later in life. The aim of this study was to investigate glucose production, lipolysis, and insulin sensitivity in infants who were born large for gestational age to mothers without diabetes. The effect of glucagon administration on production of energy substrates was also investigated.

METHODS. Ten healthy term infants who were born large for gestational age to mothers without diabetes were studied 16 ± 8 hours postnatally after a 3-hour fast. Rates of glucose production and lipolysis were analyzed by gas chromatography–mass spectrometry following constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol. Insulin sensitivity was assessed by the Homeostasis Assessment Model. In 8 of the infants, the effect of an intravenous injection of 0.2 mg/kg glucagon was also analyzed.

RESULTS. Plasma glucose and glycerol averaged 3.8 ± 0.5 mmol/L and 384 ± 183 µmol/L, respectively. The glycerol production rate, reflecting lipolysis, was 12.7 ± 2.9 µmol/kg per min. Mean rate of glucose production was 30.2 ± 4.6 µmol/kg per min. Homeostasis Assessment Model insulin sensitivity corresponded to 82% ± 19%, β-cell function to 221% ± 73%, and insulin resistance to 1.3 ± 0.3. After glucagon administration, rate of glucose production increased by 13.3 ± 8.3 µmol/kg per min and blood glucose by 1.4 ± 0.5 mmol/L. Glycerol production decreased from 12.8 ± 3.0 to 10.7 ± 2.9 µmol/kg per min. Mean insulin concentration increased from 10.9 ± 3.0 to 30.9 ± 10.3 mU/L. There was a strong inverse correlation between the decrease in lipolysis and increase in insulin after glucagon administration.

CONCLUSIONS. Infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth. The simultaneous increase in plasma insulin correlated strongly with the noted decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

Keywords
LGA, glucose production, lipolysis, newborn infant, insulin sensitivity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97381 (URN)10.1542/peds.2007-0165 (DOI)000250618900004 ()17974732 (PubMedID)
Available from: 2008-08-18 Created: 2008-08-18 Last updated: 2017-12-14Bibliographically approved
2. Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants
Open this publication in new window or tab >>Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants
2007 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 3, p. 358-362Article in journal (Refereed) Published
Abstract [en]

Aim: To analyse if females born large for gestational age (LGA) have an increased risk to give birth to LGA infants and to study anthropometric characteristics in macrosomic infants of females born LGA.Methods: The investigation was performed as an intergenerational retrospective study of women born between 1973 and 1983, who delivered their first infant between 1989 and 1999. Birth characteristics of 47 783 females, included in the Swedish Birth Register both as newborns and mothers were analysed. LGA was defined as >2 SD in either birth weight or length for gestational age. The infants were divided into three subgroups: born tall only, born heavy only and born both tall and heavy for gestational age. Multiple logistic and linear regression analyses were performed.Results: Females, born LGA with regard to length or weight, had a two-fold (adjusted OR 1.96, 95% Cl 1.54-2.48) increased risk to give birth to an LGA infant. Females, born LGA concerning weight only, had a 2.6 (adjusted OR 2.63, 95%, 1.85-3.75) fold increased risk of having an LGA offspring heavy only and no elevated risk of giving birth to an offspring that was tall only, compared to females born not LGA. In addition, maternal obesity was associated with a 2.5 (adjusted OR 2.56, 95%, 2.20-2.98) fold increased risk of having an LGA newborn, compared to mothers with normal weight.Conclusion: Females, born LGA, have an increased risk to give birth to LGA infants, compared to mothers born not LGA. Maternal overweight increases this risk even further.

Keywords
Females born LGA, Intergenerational study, LGA, Newborn infants
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97382 (URN)10.1111/j.1651-2227.2006.00141.x (DOI)000244716300009 ()17407456 (PubMedID)
Available from: 2008-08-18 Created: 2008-08-18 Last updated: 2017-12-14Bibliographically approved
3. Gestational diabetes and offspring body disproportion
Open this publication in new window or tab >>Gestational diabetes and offspring body disproportion
Show others...
2010 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 1, p. 89-93Article in journal (Refereed) Published
Abstract [en]

Aim:   It has been demonstrated that females born large for gestational age   (LGA) in weight but not length are at increased risk of being obese at   childbearing age. We addressed the question whether women with   gestational diabetes mellitus (GDM) are at increased risk of giving   birth to such infants.   Methods:   Birth characteristics of 884 267 infants of non-diabetic mothers and   7817 of mothers with GDM were analysed. LGA was defined as birth weight   or birth length > 2 standard deviation scores for gestational age.   Multiple logistic regression analysis was performed.   Results:   The odds ratio (OR) for a woman with GDM to give birth to an LGA infant   that was heavy alone was four times increased (OR: 3.71, 95% CI:   3.41-4.04). Furthermore, in the population of mothers giving birth to   LGA infants, the proportion heavy alone was 68% in the group of women   with GDM compared with 64.4% in the group of non-diabetic women. The   risks were independent of gender of the foetus.   Conclusion:   Women with GDM have an almost four times higher risk of delivering an   LGA infant that is heavy alone. The noted disproportion between weight   and length in infants of such mothers may have an impact on the risk of   later obesity.

Keywords
Body disproportion, Gestational diabetes, Large for gestational age, Newborn and obesity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97383 (URN)10.1111/j.1651-2227.2009.01532.x (DOI)000272565800025 ()19814749 (PubMedID)
Available from: 2008-08-18 Created: 2008-08-18 Last updated: 2017-12-14Bibliographically approved
4. Maternal glucose production and resting energy expenditure determine fetal size
Open this publication in new window or tab >>Maternal glucose production and resting energy expenditure determine fetal size
Show others...
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-97384 (URN)
Available from: 2008-08-18 Created: 2008-08-18 Last updated: 2010-01-13Bibliographically approved

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