B. Diderholm - Academia.edu (original) (raw)

Papers by B. Diderholm

Research paper thumbnail of Supplementary Material for: The Risk of Necrotizing Enterocolitis following the Administration of Hyperosmolar Enteral Medications to Extremely Preterm Infants

<b><i>Introduction:</i></b> Necrotizing enterocolitis (NEC) is a disease ... more <b><i>Introduction:</i></b> Necrotizing enterocolitis (NEC) is a disease predominantly affecting preterm infants. The administration of hyperosmolar solutions could lead to the development of NEC. The objective of this study was to measure the osmolality of enteral medications used in clinical practice and to assess the risk of NEC following exposure to hyperosmolar medications. <b><i>Methods:</i></b> A retrospective cohort study in extremely preterm infants (gestational age &lt;28 weeks) born between 2010 and 2016 at a tertiary neonatal intensive care unit in Sweden. 465 infants were identified via the Swedish Neonatal Quality register. Data relating to enteral administrations received during a two-week period were collected from the medical records. The osmolalities of medications were measured using an osmometer. Logistic regression was used to calculate the odds ratio of developing NEC. <b><i>Results:</i></b> A total of 253 patients met the inclusion criteria. The osmolalities of 5 commonly used medications significantly exceeded the recommended limit of 450 mOsm/kg set by the American Academy of Paediatrics (AAP). Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found. <b><i>Conclusion:</i></b> The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC.

Research paper thumbnail of Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013

The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased ... more The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased during the last decades [1]. Infants born LGA are at increased risk for perinatal complications as well as metabolic disease later in life [2-4]. Maternal overweight and obesity are related to increased infant size [3]. During pregnancy several physiological alterations occur, one of which is a metabolic adaptation to ensure an optimal supply of glucose, amino acids and triacylglycerols to the fetus. The mechanisms behind this process, however, are yet to be elucidated. The adipokines, leptin and adiponectin, are of interest in this respect, given their involvement in satiety control, regulation of body fatness, insulin resistance and energy expenditure [5]. Several studies on the relationship between adipokines and body composition, energy expenditure, and insulin resistance during pregnancy have been performed, but so far no reports on the relationship between adipokines and maternal energy substrate

Research paper thumbnail of Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

Pediatrics, Nov 1, 2007

The authors have indicated they have no financial relationships relevant to this article to discl... more The authors have indicated they have no financial relationships relevant to this article to disclose.

Research paper thumbnail of 3 Increased Lipolysis in Large for Gestational Age Infants

Pediatric Research, Sep 1, 2004

Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect pos... more Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect post natal growth and development, but data in newborns are limited due to difficulties in sample collection. Methods: A new method for FA analysis in a drop of whole blood absorbed on a strip of Chromatography Paper (Marangoni et al, Anal Biochem 2004;326:267) was applied to a population of 110 infants, by analyzing blood samples collected from the heel within 72 h after delivery (37-41 wks post-conceptional age). Results:Comparisons with data from an unrelated, healthy adult population (100 subjects), analyzed with the same technique, showed lower levels of linoleic acid (LA) and alpha-linolenic acid (ALA) together with higher LCP (mainly arachidonic acid, AA, and docosahexaenoic acid, DHA, 22:6 n-3) levels, and markedly higher proportions of Ͼ 22 C FA of all FA families in the newborns, revealing major differences in FA intake, metabolism and incorporation in lipid pools between the two groups. Differences in FA profiles occurred also within the newborns, in relation with 1. gender (higher LA in females) 2. gestational age, with lower AA and DHA levels in the highest decile (10 s) for post-conceptional age at birth (41.2 weeks, SD 0.1) compared to the others 3. birth weight, with higher DHA levels in the lowest (10 s) vs the highest (12 s) decile (%: 4.2, SD 0.4, vs 3.4, SD 1.0, Mann-Whitney U test: P ϭ 0.002) and 4. maternal life style (higher 22:5 n-6/22:6 n-3 ratio in smoking vs non-smoking mothers). Conclusion: The new method of FA analysis provides valuable information on the FA status and biochemical features related to FA at very early stages of post natal development, an age that has not been adequately investigated so far.

Research paper thumbnail of 3 Increased Lipolysis in Large for Gestational Age Infants

Pediatric Research, 2004

Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect pos... more Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect post natal growth and development, but data in newborns are limited due to difficulties in sample collection. Methods: A new method for FA analysis in a drop of whole blood absorbed on a strip of Chromatography Paper (Marangoni et al, Anal Biochem 2004;326:267) was applied to a population of 110 infants, by analyzing blood samples collected from the heel within 72 h after delivery (37-41 wks post-conceptional age). Results:Comparisons with data from an unrelated, healthy adult population (100 subjects), analyzed with the same technique, showed lower levels of linoleic acid (LA) and alpha-linolenic acid (ALA) together with higher LCP (mainly arachidonic acid, AA, and docosahexaenoic acid, DHA, 22:6 n-3) levels, and markedly higher proportions of Ͼ 22 C FA of all FA families in the newborns, revealing major differences in FA intake, metabolism and incorporation in lipid pools between the two groups. Differences in FA profiles occurred also within the newborns, in relation with 1. gender (higher LA in females) 2. gestational age, with lower AA and DHA levels in the highest decile (10 s) for post-conceptional age at birth (41.2 weeks, SD 0.1) compared to the others 3. birth weight, with higher DHA levels in the lowest (10 s) vs the highest (12 s) decile (%: 4.2, SD 0.4, vs 3.4, SD 1.0, Mann-Whitney U test: P ϭ 0.002) and 4. maternal life style (higher 22:5 n-6/22:6 n-3 ratio in smoking vs non-smoking mothers). Conclusion: The new method of FA analysis provides valuable information on the FA status and biochemical features related to FA at very early stages of post natal development, an age that has not been adequately investigated so far.

Research paper thumbnail of Insulin and carbohydrate metabolism

Best Practice & Research: Clinical Endocrinology & Metabolism

Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by gl... more Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by glucose delivery from the mother during pregnancy. Maternal hyperglycaemia and gestational diabetes (GDM) are known to be detrimental to offspring, although defining the criteria for diagnosis of GDM is controversial. Recent data suggest that the risk of poor fetal outcome appears to be a continuous variable across the range of glucose control, and that the level of maternal blood glucose for a diagnosis of gestational diabetes needs to be reviewed. After birth, rapid adaptation is necessary for infants to be able to maintain independent glucose homeostasis. This adaptation is compromised in infants who are small for gestational age (SGA), premature, or large for gestational age (LGA). Interestingly, the infants who are born at the extremes of birth weight are also at increased risk of impaired glucose tolerance and diabetes in later life.

Research paper thumbnail of Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers

Diabetes Care, 2008

OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and... more OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS-Women in two unselected birth cohorts, one retrospective (n ϭ 3,158) and one prospective (n ϭ 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS-In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean Ϯ SEM) 2.1 Ϯ 0.8% (P ϭ 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 Ϯ 0.8% (P Ͻ 0.0001) rise in emergency cesarean delivery, a 3.1 Ϯ 0.7% (P Ͻ 0.0001) rise in elective cesarean delivery, and a 46 Ϯ 8 g (P Ͻ 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight Ͼ90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per ϩ1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per ϩ1 kg/m 2 [1.04-1.18]). The mother's higher fasting glycemia (P ϭ 0.004), lower insulin sensitivity (P ϭ 0.01), and lower insulin secretion (P ϭ 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P Ͻ 0.05). CONCLUSIONS-Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Research paper thumbnail of Effect of theophylline on glucose production and lipolysis in preterm infants (<= 32 weeks)

Pediatric Research

Apnea occurs commonly in preterm infants. Theophylline is used as prophylaxis and treatment. Apar... more Apnea occurs commonly in preterm infants. Theophylline is used as prophylaxis and treatment. Apart from improving ventilatory function, theophylline may also have metabolic effects, including an effect on glucose metabolism and lipolysis. No data are available on the effect of theophylline on glucose production and lipolysis in preterm infants at start of medication. Ten preterm infants with gestational ages of < or = 32 wk, postnatal ages of 16-84 h, and birth weights > 900 g were recruited. Hepatic glucose production and lipolysis were measured by use of gas chromatography/mass spectrometry after constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol tracers. Plasma glucose levels increased after theophylline administration (mean +/- SD, 4.0 +/- 1.9 mmol/L before and 4.7 +/- 2.1 mmol/L after start of therapy), whereas the rate of glucose production decreased (6.0 +/- 2.5 mg.kg-1.min-1 and 4.3 +/- 1.9 mg.kg-1.min-1, respectively). The plasma glycerol concentration did...

Research paper thumbnail of Independent associations between maternal rates of lipolysis and glucose production, estimated fetal size and birth weight

Research paper thumbnail of Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

PEDIATRICS, 2007

The authors have indicated they have no financial relationships relevant to this article to discl... more The authors have indicated they have no financial relationships relevant to this article to disclose.

Research paper thumbnail of Effect of Theophylline on Glucose Production and Lipolysis in Preterm Infants (≤32 Weeks)

Research paper thumbnail of Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies

Hormone Research in Paediatrics, 2010

During the last decades the number of large for gestational age infants delivered by nondiabetic ... more During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2-2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed. Median (range) glucose production rate was 805 (653-1,337) μmol/min and that of glycerol, reflecting lipolysis, was 214 (110-576) μmol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.

Research paper thumbnail of Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013

The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased ... more The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased during the last decades [1]. Infants born LGA are at increased risk for perinatal complications as well as metabolic disease later in life [2-4]. Maternal overweight and obesity are related to increased infant size [3]. During pregnancy several physiological alterations occur, one of which is a metabolic adaptation to ensure an optimal supply of glucose, amino acids and triacylglycerols to the fetus. The mechanisms behind this process, however, are yet to be elucidated. The adipokines, leptin and adiponectin, are of interest in this respect, given their involvement in satiety control, regulation of body fatness, insulin resistance and energy expenditure [5]. Several studies on the relationship between adipokines and body composition, energy expenditure, and insulin resistance during pregnancy have been performed, but so far no reports on the relationship between adipokines and maternal energy substrate

Research paper thumbnail of Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers

Diabetes Care, 2008

OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and... more OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS-Women in two unselected birth cohorts, one retrospective (n ϭ 3,158) and one prospective (n ϭ 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS-In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean Ϯ SEM) 2.1 Ϯ 0.8% (P ϭ 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 Ϯ 0.8% (P Ͻ 0.0001) rise in emergency cesarean delivery, a 3.1 Ϯ 0.7% (P Ͻ 0.0001) rise in elective cesarean delivery, and a 46 Ϯ 8 g (P Ͻ 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight Ͼ90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per ϩ1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per ϩ1 kg/m 2 [1.04-1.18]). The mother's higher fasting glycemia (P ϭ 0.004), lower insulin sensitivity (P ϭ 0.01), and lower insulin secretion (P ϭ 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P Ͻ 0.05). CONCLUSIONS-Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Research paper thumbnail of Insulin and carbohydrate metabolism

Best Practice & Research Clinical Endocrinology & Metabolism, 2008

Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by gl... more Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by glucose delivery from the mother during pregnancy. Maternal hyperglycaemia and gestational diabetes (GDM) are known to be detrimental to offspring, although defining the criteria for diagnosis of GDM is controversial. Recent data suggest that the risk of poor fetal outcome appears to be a continuous variable across the range of glucose control, and that the level of maternal blood glucose for a diagnosis of gestational diabetes needs to be reviewed. After birth, rapid adaptation is necessary for infants to be able to maintain independent glucose homeostasis. This adaptation is compromised in infants who are small for gestational age (SGA), premature, or large for gestational age (LGA). Interestingly, the infants who are born at the extremes of birth weight are also at increased risk of impaired glucose tolerance and diabetes in later life.

Research paper thumbnail of Decreased maternal lipolysis in intrauterine growth restriction in the third trimester

BJOG: An International Journal of Obstetrics and Gynaecology, 2006

Objective Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are... more Objective Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are many possible aetiologic factors of maternal, placental and/or fetal origin. Often there is no known explanation. The aim of this study was to investigate whether a reduction in maternal energy substrate production could be one of the factors involved in IUGR. Design Measurement of maternal energy substrate production and glucoregulatory hormones in women with growth-restricted fetuses.

Research paper thumbnail of Supplementary Material for: The Risk of Necrotizing Enterocolitis following the Administration of Hyperosmolar Enteral Medications to Extremely Preterm Infants

<b><i>Introduction:</i></b> Necrotizing enterocolitis (NEC) is a disease ... more <b><i>Introduction:</i></b> Necrotizing enterocolitis (NEC) is a disease predominantly affecting preterm infants. The administration of hyperosmolar solutions could lead to the development of NEC. The objective of this study was to measure the osmolality of enteral medications used in clinical practice and to assess the risk of NEC following exposure to hyperosmolar medications. <b><i>Methods:</i></b> A retrospective cohort study in extremely preterm infants (gestational age &lt;28 weeks) born between 2010 and 2016 at a tertiary neonatal intensive care unit in Sweden. 465 infants were identified via the Swedish Neonatal Quality register. Data relating to enteral administrations received during a two-week period were collected from the medical records. The osmolalities of medications were measured using an osmometer. Logistic regression was used to calculate the odds ratio of developing NEC. <b><i>Results:</i></b> A total of 253 patients met the inclusion criteria. The osmolalities of 5 commonly used medications significantly exceeded the recommended limit of 450 mOsm/kg set by the American Academy of Paediatrics (AAP). Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found. <b><i>Conclusion:</i></b> The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC.

Research paper thumbnail of Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013

The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased ... more The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased during the last decades [1]. Infants born LGA are at increased risk for perinatal complications as well as metabolic disease later in life [2-4]. Maternal overweight and obesity are related to increased infant size [3]. During pregnancy several physiological alterations occur, one of which is a metabolic adaptation to ensure an optimal supply of glucose, amino acids and triacylglycerols to the fetus. The mechanisms behind this process, however, are yet to be elucidated. The adipokines, leptin and adiponectin, are of interest in this respect, given their involvement in satiety control, regulation of body fatness, insulin resistance and energy expenditure [5]. Several studies on the relationship between adipokines and body composition, energy expenditure, and insulin resistance during pregnancy have been performed, but so far no reports on the relationship between adipokines and maternal energy substrate

Research paper thumbnail of Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

Pediatrics, Nov 1, 2007

The authors have indicated they have no financial relationships relevant to this article to discl... more The authors have indicated they have no financial relationships relevant to this article to disclose.

Research paper thumbnail of 3 Increased Lipolysis in Large for Gestational Age Infants

Pediatric Research, Sep 1, 2004

Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect pos... more Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect post natal growth and development, but data in newborns are limited due to difficulties in sample collection. Methods: A new method for FA analysis in a drop of whole blood absorbed on a strip of Chromatography Paper (Marangoni et al, Anal Biochem 2004;326:267) was applied to a population of 110 infants, by analyzing blood samples collected from the heel within 72 h after delivery (37-41 wks post-conceptional age). Results:Comparisons with data from an unrelated, healthy adult population (100 subjects), analyzed with the same technique, showed lower levels of linoleic acid (LA) and alpha-linolenic acid (ALA) together with higher LCP (mainly arachidonic acid, AA, and docosahexaenoic acid, DHA, 22:6 n-3) levels, and markedly higher proportions of Ͼ 22 C FA of all FA families in the newborns, revealing major differences in FA intake, metabolism and incorporation in lipid pools between the two groups. Differences in FA profiles occurred also within the newborns, in relation with 1. gender (higher LA in females) 2. gestational age, with lower AA and DHA levels in the highest decile (10 s) for post-conceptional age at birth (41.2 weeks, SD 0.1) compared to the others 3. birth weight, with higher DHA levels in the lowest (10 s) vs the highest (12 s) decile (%: 4.2, SD 0.4, vs 3.4, SD 1.0, Mann-Whitney U test: P ϭ 0.002) and 4. maternal life style (higher 22:5 n-6/22:6 n-3 ratio in smoking vs non-smoking mothers). Conclusion: The new method of FA analysis provides valuable information on the FA status and biochemical features related to FA at very early stages of post natal development, an age that has not been adequately investigated so far.

Research paper thumbnail of 3 Increased Lipolysis in Large for Gestational Age Infants

Pediatric Research, 2004

Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect pos... more Background: Long Chain Polyunsaturated (LCP) Fatty Acid (FA) status in the newborn may affect post natal growth and development, but data in newborns are limited due to difficulties in sample collection. Methods: A new method for FA analysis in a drop of whole blood absorbed on a strip of Chromatography Paper (Marangoni et al, Anal Biochem 2004;326:267) was applied to a population of 110 infants, by analyzing blood samples collected from the heel within 72 h after delivery (37-41 wks post-conceptional age). Results:Comparisons with data from an unrelated, healthy adult population (100 subjects), analyzed with the same technique, showed lower levels of linoleic acid (LA) and alpha-linolenic acid (ALA) together with higher LCP (mainly arachidonic acid, AA, and docosahexaenoic acid, DHA, 22:6 n-3) levels, and markedly higher proportions of Ͼ 22 C FA of all FA families in the newborns, revealing major differences in FA intake, metabolism and incorporation in lipid pools between the two groups. Differences in FA profiles occurred also within the newborns, in relation with 1. gender (higher LA in females) 2. gestational age, with lower AA and DHA levels in the highest decile (10 s) for post-conceptional age at birth (41.2 weeks, SD 0.1) compared to the others 3. birth weight, with higher DHA levels in the lowest (10 s) vs the highest (12 s) decile (%: 4.2, SD 0.4, vs 3.4, SD 1.0, Mann-Whitney U test: P ϭ 0.002) and 4. maternal life style (higher 22:5 n-6/22:6 n-3 ratio in smoking vs non-smoking mothers). Conclusion: The new method of FA analysis provides valuable information on the FA status and biochemical features related to FA at very early stages of post natal development, an age that has not been adequately investigated so far.

Research paper thumbnail of Insulin and carbohydrate metabolism

Best Practice & Research: Clinical Endocrinology & Metabolism

Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by gl... more Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by glucose delivery from the mother during pregnancy. Maternal hyperglycaemia and gestational diabetes (GDM) are known to be detrimental to offspring, although defining the criteria for diagnosis of GDM is controversial. Recent data suggest that the risk of poor fetal outcome appears to be a continuous variable across the range of glucose control, and that the level of maternal blood glucose for a diagnosis of gestational diabetes needs to be reviewed. After birth, rapid adaptation is necessary for infants to be able to maintain independent glucose homeostasis. This adaptation is compromised in infants who are small for gestational age (SGA), premature, or large for gestational age (LGA). Interestingly, the infants who are born at the extremes of birth weight are also at increased risk of impaired glucose tolerance and diabetes in later life.

Research paper thumbnail of Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers

Diabetes Care, 2008

OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and... more OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS-Women in two unselected birth cohorts, one retrospective (n ϭ 3,158) and one prospective (n ϭ 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS-In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean Ϯ SEM) 2.1 Ϯ 0.8% (P ϭ 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 Ϯ 0.8% (P Ͻ 0.0001) rise in emergency cesarean delivery, a 3.1 Ϯ 0.7% (P Ͻ 0.0001) rise in elective cesarean delivery, and a 46 Ϯ 8 g (P Ͻ 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight Ͼ90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per ϩ1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per ϩ1 kg/m 2 [1.04-1.18]). The mother's higher fasting glycemia (P ϭ 0.004), lower insulin sensitivity (P ϭ 0.01), and lower insulin secretion (P ϭ 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P Ͻ 0.05). CONCLUSIONS-Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Research paper thumbnail of Effect of theophylline on glucose production and lipolysis in preterm infants (<= 32 weeks)

Pediatric Research

Apnea occurs commonly in preterm infants. Theophylline is used as prophylaxis and treatment. Apar... more Apnea occurs commonly in preterm infants. Theophylline is used as prophylaxis and treatment. Apart from improving ventilatory function, theophylline may also have metabolic effects, including an effect on glucose metabolism and lipolysis. No data are available on the effect of theophylline on glucose production and lipolysis in preterm infants at start of medication. Ten preterm infants with gestational ages of < or = 32 wk, postnatal ages of 16-84 h, and birth weights > 900 g were recruited. Hepatic glucose production and lipolysis were measured by use of gas chromatography/mass spectrometry after constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol tracers. Plasma glucose levels increased after theophylline administration (mean +/- SD, 4.0 +/- 1.9 mmol/L before and 4.7 +/- 2.1 mmol/L after start of therapy), whereas the rate of glucose production decreased (6.0 +/- 2.5 mg.kg-1.min-1 and 4.3 +/- 1.9 mg.kg-1.min-1, respectively). The plasma glycerol concentration did...

Research paper thumbnail of Independent associations between maternal rates of lipolysis and glucose production, estimated fetal size and birth weight

Research paper thumbnail of Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

PEDIATRICS, 2007

The authors have indicated they have no financial relationships relevant to this article to discl... more The authors have indicated they have no financial relationships relevant to this article to disclose.

Research paper thumbnail of Effect of Theophylline on Glucose Production and Lipolysis in Preterm Infants (≤32 Weeks)

Research paper thumbnail of Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies

Hormone Research in Paediatrics, 2010

During the last decades the number of large for gestational age infants delivered by nondiabetic ... more During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2-2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed. Median (range) glucose production rate was 805 (653-1,337) μmol/min and that of glycerol, reflecting lipolysis, was 214 (110-576) μmol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.

Research paper thumbnail of Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013

The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased ... more The number of large for gestational age (LGA) infants, born of non-diabetic women, has increased during the last decades [1]. Infants born LGA are at increased risk for perinatal complications as well as metabolic disease later in life [2-4]. Maternal overweight and obesity are related to increased infant size [3]. During pregnancy several physiological alterations occur, one of which is a metabolic adaptation to ensure an optimal supply of glucose, amino acids and triacylglycerols to the fetus. The mechanisms behind this process, however, are yet to be elucidated. The adipokines, leptin and adiponectin, are of interest in this respect, given their involvement in satiety control, regulation of body fatness, insulin resistance and energy expenditure [5]. Several studies on the relationship between adipokines and body composition, energy expenditure, and insulin resistance during pregnancy have been performed, but so far no reports on the relationship between adipokines and maternal energy substrate

Research paper thumbnail of Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers

Diabetes Care, 2008

OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and... more OBJECTIVE-We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS-Women in two unselected birth cohorts, one retrospective (n ϭ 3,158) and one prospective (n ϭ 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS-In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean Ϯ SEM) 2.1 Ϯ 0.8% (P ϭ 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 Ϯ 0.8% (P Ͻ 0.0001) rise in emergency cesarean delivery, a 3.1 Ϯ 0.7% (P Ͻ 0.0001) rise in elective cesarean delivery, and a 46 Ϯ 8 g (P Ͻ 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight Ͼ90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per ϩ1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per ϩ1 kg/m 2 [1.04-1.18]). The mother's higher fasting glycemia (P ϭ 0.004), lower insulin sensitivity (P ϭ 0.01), and lower insulin secretion (P ϭ 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P Ͻ 0.05). CONCLUSIONS-Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Research paper thumbnail of Insulin and carbohydrate metabolism

Best Practice & Research Clinical Endocrinology & Metabolism, 2008

Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by gl... more Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by glucose delivery from the mother during pregnancy. Maternal hyperglycaemia and gestational diabetes (GDM) are known to be detrimental to offspring, although defining the criteria for diagnosis of GDM is controversial. Recent data suggest that the risk of poor fetal outcome appears to be a continuous variable across the range of glucose control, and that the level of maternal blood glucose for a diagnosis of gestational diabetes needs to be reviewed. After birth, rapid adaptation is necessary for infants to be able to maintain independent glucose homeostasis. This adaptation is compromised in infants who are small for gestational age (SGA), premature, or large for gestational age (LGA). Interestingly, the infants who are born at the extremes of birth weight are also at increased risk of impaired glucose tolerance and diabetes in later life.

Research paper thumbnail of Decreased maternal lipolysis in intrauterine growth restriction in the third trimester

BJOG: An International Journal of Obstetrics and Gynaecology, 2006

Objective Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are... more Objective Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are many possible aetiologic factors of maternal, placental and/or fetal origin. Often there is no known explanation. The aim of this study was to investigate whether a reduction in maternal energy substrate production could be one of the factors involved in IUGR. Design Measurement of maternal energy substrate production and glucoregulatory hormones in women with growth-restricted fetuses.