Patrick Catalano, MD

Obesity has become so pervasive that it is now considered a major health concern during pregnancy. Almost 56% of women aged 20-39 years in the United States are overweight or obese, based on the World Health Organization’s criteria for body mass index (BMI) and data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Moreover, 7.5% of women in this age group are morbidly obese, with a body mass index (BMI) greater than 40 kg/m² (JAMA 2012;307:491-7).

Obesity in pregnancy not only increases the risk of spontaneous abortions and congenital anomalies, it also increases the risk of gestational diabetes (GDM), hypertensive disorders, and other metabolic complications that affect both the mother and fetus.

Of much concern is the increased risk of fetal overgrowth and long-term health consequences for children of obese mothers. Obesity in early pregnancy has been shown to more than double the risk of obesity in the offspring, which in turn puts these children at risk for developing the metabolic syndrome – and, as Dr. Thomas Moore pointed out in September’s Master Class – appears to program these offspring for downstream cardiovascular risk in adulthood.

Mean term birth weights have risen in the United States during the past several decades. In Cleveland, we have seen a significant 116 g increase in mean term birth weight since 1975; this increase encompasses weights from the 5th to the 95th percentiles. Even more concerning is our finding that the ponderal index in our neonatal population has increased because of decreased fetal length over the last decade.

Some recent studies have suggested that the increase in birth weight in the United States has reached a plateau, but our analyses of national trends suggest that such change is secondary to factors such as earlier gestational age of delivery. Concurrently, an alarming number of children and adolescents – 17% of those aged 2-19 years, according to the 2009-2010 NHANES data – are overweight or obese (JAMA 2012;307:483-90).

How to best treat obesity for improved maternal and fetal health has thus become a focus of research. Studies on lifestyle interventions for obese women during pregnancy have aimed to prevent excessive gestational weight gain and decrease adverse perinatal outcomes – mainly macrosomia, GDM, and hypertensive disorders.

However, the results of this recent body of research have been disappointing. Lifestyle interventions initiated during pregnancy have had only limited success in improving perinatal outcomes. The research tells us that while we may be able to reduce excessive gestational weight gain, it is unlikely that we will be successful in reducing fetal overgrowth, GDM, or preeclampsia in obese women.

Moreover, other studies show that it is a high pregravid BMI – not excessive gestational weight gain or the development of GDM – that plays the biggest role in fetal overgrowth and fetal adiposity.

A paradigm shift is in order. We must think about lifestyle intervention and weight loss before pregnancy, when the woman’s metabolic condition can be improved in time to minimize adverse perinatal metabolic outcomes and to maximize metabolic benefits relating to fetal body composition and metabolism.

Role of prepregnancy BMI

In 2008, the Institute of Medicine (IOM) and National Research Council reexamined 1990 guidelines for gestational weight gain. They concluded that excessive weight gain in pregnancy was a primary contributor to the development of obesity in women. In fact, according to the 2009 IOM report, “Weight Gain During Pregnancy: Reexamining the Guidelines” (Washington: National Academy Press, 2009), 38% of normal weight, 63% of overweight, and 46% of obese women had gained weight in excess of the earlier guidelines.

Helping our patients to gain within the guidelines is important. Excessive gestational weight gain is a primary risk factor for maternal postpartum weight retention, which increases the risk for maternal obesity in a subsequent pregnancy. It also has been associated with a modest increased risk of preterm birth and development of type 2 diabetes.

Interestingly, however, high gestational weight gain has not been related to an increased risk of fetal overgrowth or macrosomia in many obese women. Increased gestational weight gain is a greater risk for fetal overgrowth in women who are of normal weight prior to pregnancy (J. Clin. Endocrinol. Metab. 2012;97:3648-54).

Our research has found that in overweight and obese women, it is maternal pregravid BMI – and not gestational weight gain – that presents the greatest risk for fetal macrosomia, and more specifically, the greatest risk for fetal obesity. Even when glucose tolerance levels are normal, overweight and obese women have neonates who are heavier and who have significant increases in the percentage of body fat and fat mass (Am. J. Obstet. Gynecol. 2006;195:1100-3).

In an 8-year prospective study of the perinatal risk factors associated with childhood obesity, we similarly found that maternal pregravid BMI – independent of maternal glucose status or gestational weight gain – was the strongest predictor of childhood obesity and metabolic dysfunction (Am. J. Clin. Nutr. 2009;90:1303-13).

Other studies have teased apart the roles of maternal obesity and GDM in long-term health of offspring. This work has found that maternal obesity during pregnancy is associated with metabolic syndrome in the offspring and an increased risk of type 2 diabetes in youth, independent of maternal diabetes during pregnancy. A recent meta-analysis also reported that, although maternal diabetes is associated with an increased BMI z score, this was no longer significant after adjustments were made for prepregnancy BMI (Diabetologia 2011;54:1957-66).

Maternal pregravid obesity, therefore, is not only a risk factor for neonatal adiposity at birth, but also for the longer-term risk of obesity and metabolic dysfunction in the offspring – independent of maternal GDM or excessive gestational weight gain.

Interventions in Pregnancy

Numerous prospective trials have examined lifestyle interventions for obese women during pregnancy. One randomized controlled study of a low glycemic index diet in pregnancy (coined the ROLO study) involved 800 women in Ireland who had previously delivered an infant weighting greater than 4,000 g. Women were randomized to receive the restricted diet or no intervention at 13 weeks. Despite a decrease in gestational weight gain in the intervention group, there were no differences in birth weight, birth weight percentile, ponderal index, or macrosomia between the two groups (BMJ 2012;345:e5605).

Another randomized controlled trial reported by a Danish group involved an intervention that consisted of dietary guidance, free membership in a fitness center, and personal coaching initiated between 10 and 14 weeks of gestation. There was a decrease in gestational weight gain in the intervention group, but paradoxically, the infants in the intervention group also had significantly higher birth weight, compared with controls (Diabetes Care 2011;34:2502-7).

Additionally, there have been at least five meta-analyses published in the past 2 years looking at lifestyle interventions during pregnancy. All have concluded that interventions initiated during pregnancy have limited success in reducing excessive gestational weight gain but not necessarily to within the IOM guidelines. The literature contains scant evidence to support further benefits for infant or maternal health (in other words, fetal overgrowth, GDM, or hypertensive disorders).

A recent Cochrane review also concluded that the results of several randomized controlled trials suggest no significant difference in GDM incidence between women receiving exercise intervention versus routine care.

Just this year, three additional randomized controlled trials of lifestyle interventions during pregnancy were published. Only one, the Treatment of Obese Pregnant Women (TOP) study, showed a modest effect in decreasing gestational weight gain. None found a reduction in GDM or fetal overgrowth.

Focus on prepregnancy

Obesity is an inflammatory condition that increases the risk of insulin resistance, impaired beta-cell function, and abnormal adiponectin concentrations. In pregnancy, maternal obesity and hyperinsulinemia can affect placental growth and gene expression.

We have studied lean and obese women recruited prior to a planned pregnancy, as well as lean and obese women scheduled for elective pregnancy termination in the first trimester. Our research, some of which we reported recently in the American Journal of Physiology , has shown increased expression of lipogenic and inflammatory genes in maternal adipose tissue and in the placenta of obese women in the early first trimester, before any phenotypic change becomes apparent (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).

Specifically, hyperinsulinemia and/or defective insulin action in obese women appears to affect the placental programming of genes relating to adipokine expression and lipid metabolism, as well as mitrochondrial function. Altered inflammatory and lipid pathways affect the availability of nutrients for the fetus and, consequently, the size and body composition of the fetus. Fetal overgrowth and neonatal adiposity can result.

In addition, our research has shown that obese women have decreased insulin suppression of lipolysis in white adipose tissue, which during pregnancy results in improved lipid availability for fetal fat accretion and lipotoxicity.

When interventions aimed at weight loss and improved insulin sensitivity are undertaken before pregnancy or in the period between pregnancies, we have the opportunity to increase fat oxidation and reduce oxidative stress in early pregnancy. We also may be able to limit placental inflammation and favorably affect placental growth and gene expression. By the second trimester, our research suggests, gene expression in the placenta and early molecular changes in the white adipose tissue have already been programmed and cannot be reversed (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).

In studies by our group and others of interpregnancy weight loss or gain, interpregnancy weight loss has been associated with a lower risk of large-for-gestational-age (LGA) infants, whereas interpregnancy weight gain has been associated with an increased risk of LGA. Preliminary work from our group shows that the decrease in birth weight involves primarily fat and not lean mass.

The 2009 IOM guidelines support weight loss before pregnancy and state that overweight women should receive individual preconceptional counseling to improve diet quality, increase physical activity, and normalize weight. Multifaceted interventions do work: In obese nonpregnant individuals, lifestyle interventions, which include an exercise program, diet, and behavioral modification have been shown to be successful in improving insulin sensitivity, inflammation, and overall metabolic function.

According to the IOM report, preconceptional services aimed at achieving a healthy weight before conceiving will represent “a radical change to the care provided to obese women of childbearing age.” With continuing research and accumulating data, however, the concept is gaining traction as a viable paradigm for improving perinatal outcomes, with long-term benefits for both the mother and her baby.

Dr. Catalano reports that he has no disclosures relevant to this Master Class.

Obesity has become so pervasive that it is now considered a major health concern during pregnancy. Almost 56% of women aged 20-39 years in the United States are overweight or obese, based on the World Health Organization’s criteria for body mass index (BMI) and data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Moreover, 7.5% of women in this age group are morbidly obese, with a body mass index (BMI) greater than 40 kg/m² (JAMA 2012;307:491-7).

Obesity in pregnancy not only increases the risk of spontaneous abortions and congenital anomalies, it also increases the risk of gestational diabetes (GDM), hypertensive disorders, and other metabolic complications that affect both the mother and fetus.

Of much concern is the increased risk of fetal overgrowth and long-term health consequences for children of obese mothers. Obesity in early pregnancy has been shown to more than double the risk of obesity in the offspring, which in turn puts these children at risk for developing the metabolic syndrome – and, as Dr. Thomas Moore pointed out in September’s Master Class – appears to program these offspring for downstream cardiovascular risk in adulthood.

Mean term birth weights have risen in the United States during the past several decades. In Cleveland, we have seen a significant 116 g increase in mean term birth weight since 1975; this increase encompasses weights from the 5th to the 95th percentiles. Even more concerning is our finding that the ponderal index in our neonatal population has increased because of decreased fetal length over the last decade.

Some recent studies have suggested that the increase in birth weight in the United States has reached a plateau, but our analyses of national trends suggest that such change is secondary to factors such as earlier gestational age of delivery. Concurrently, an alarming number of children and adolescents – 17% of those aged 2-19 years, according to the 2009-2010 NHANES data – are overweight or obese (JAMA 2012;307:483-90).

How to best treat obesity for improved maternal and fetal health has thus become a focus of research. Studies on lifestyle interventions for obese women during pregnancy have aimed to prevent excessive gestational weight gain and decrease adverse perinatal outcomes – mainly macrosomia, GDM, and hypertensive disorders.

However, the results of this recent body of research have been disappointing. Lifestyle interventions initiated during pregnancy have had only limited success in improving perinatal outcomes. The research tells us that while we may be able to reduce excessive gestational weight gain, it is unlikely that we will be successful in reducing fetal overgrowth, GDM, or preeclampsia in obese women.

Moreover, other studies show that it is a high pregravid BMI – not excessive gestational weight gain or the development of GDM – that plays the biggest role in fetal overgrowth and fetal adiposity.

A paradigm shift is in order. We must think about lifestyle intervention and weight loss before pregnancy, when the woman’s metabolic condition can be improved in time to minimize adverse perinatal metabolic outcomes and to maximize metabolic benefits relating to fetal body composition and metabolism.

Role of prepregnancy BMI

In 2008, the Institute of Medicine (IOM) and National Research Council reexamined 1990 guidelines for gestational weight gain. They concluded that excessive weight gain in pregnancy was a primary contributor to the development of obesity in women. In fact, according to the 2009 IOM report, “Weight Gain During Pregnancy: Reexamining the Guidelines” (Washington: National Academy Press, 2009), 38% of normal weight, 63% of overweight, and 46% of obese women had gained weight in excess of the earlier guidelines.

Helping our patients to gain within the guidelines is important. Excessive gestational weight gain is a primary risk factor for maternal postpartum weight retention, which increases the risk for maternal obesity in a subsequent pregnancy. It also has been associated with a modest increased risk of preterm birth and development of type 2 diabetes.

Interestingly, however, high gestational weight gain has not been related to an increased risk of fetal overgrowth or macrosomia in many obese women. Increased gestational weight gain is a greater risk for fetal overgrowth in women who are of normal weight prior to pregnancy (J. Clin. Endocrinol. Metab. 2012;97:3648-54).

Our research has found that in overweight and obese women, it is maternal pregravid BMI – and not gestational weight gain – that presents the greatest risk for fetal macrosomia, and more specifically, the greatest risk for fetal obesity. Even when glucose tolerance levels are normal, overweight and obese women have neonates who are heavier and who have significant increases in the percentage of body fat and fat mass (Am. J. Obstet. Gynecol. 2006;195:1100-3).

In an 8-year prospective study of the perinatal risk factors associated with childhood obesity, we similarly found that maternal pregravid BMI – independent of maternal glucose status or gestational weight gain – was the strongest predictor of childhood obesity and metabolic dysfunction (Am. J. Clin. Nutr. 2009;90:1303-13).

Other studies have teased apart the roles of maternal obesity and GDM in long-term health of offspring. This work has found that maternal obesity during pregnancy is associated with metabolic syndrome in the offspring and an increased risk of type 2 diabetes in youth, independent of maternal diabetes during pregnancy. A recent meta-analysis also reported that, although maternal diabetes is associated with an increased BMI z score, this was no longer significant after adjustments were made for prepregnancy BMI (Diabetologia 2011;54:1957-66).

Maternal pregravid obesity, therefore, is not only a risk factor for neonatal adiposity at birth, but also for the longer-term risk of obesity and metabolic dysfunction in the offspring – independent of maternal GDM or excessive gestational weight gain.

Interventions in Pregnancy

Numerous prospective trials have examined lifestyle interventions for obese women during pregnancy. One randomized controlled study of a low glycemic index diet in pregnancy (coined the ROLO study) involved 800 women in Ireland who had previously delivered an infant weighting greater than 4,000 g. Women were randomized to receive the restricted diet or no intervention at 13 weeks. Despite a decrease in gestational weight gain in the intervention group, there were no differences in birth weight, birth weight percentile, ponderal index, or macrosomia between the two groups (BMJ 2012;345:e5605).

Another randomized controlled trial reported by a Danish group involved an intervention that consisted of dietary guidance, free membership in a fitness center, and personal coaching initiated between 10 and 14 weeks of gestation. There was a decrease in gestational weight gain in the intervention group, but paradoxically, the infants in the intervention group also had significantly higher birth weight, compared with controls (Diabetes Care 2011;34:2502-7).

Additionally, there have been at least five meta-analyses published in the past 2 years looking at lifestyle interventions during pregnancy. All have concluded that interventions initiated during pregnancy have limited success in reducing excessive gestational weight gain but not necessarily to within the IOM guidelines. The literature contains scant evidence to support further benefits for infant or maternal health (in other words, fetal overgrowth, GDM, or hypertensive disorders).

A recent Cochrane review also concluded that the results of several randomized controlled trials suggest no significant difference in GDM incidence between women receiving exercise intervention versus routine care.

Just this year, three additional randomized controlled trials of lifestyle interventions during pregnancy were published. Only one, the Treatment of Obese Pregnant Women (TOP) study, showed a modest effect in decreasing gestational weight gain. None found a reduction in GDM or fetal overgrowth.

Focus on prepregnancy

Obesity is an inflammatory condition that increases the risk of insulin resistance, impaired beta-cell function, and abnormal adiponectin concentrations. In pregnancy, maternal obesity and hyperinsulinemia can affect placental growth and gene expression.

We have studied lean and obese women recruited prior to a planned pregnancy, as well as lean and obese women scheduled for elective pregnancy termination in the first trimester. Our research, some of which we reported recently in the American Journal of Physiology , has shown increased expression of lipogenic and inflammatory genes in maternal adipose tissue and in the placenta of obese women in the early first trimester, before any phenotypic change becomes apparent (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).

Specifically, hyperinsulinemia and/or defective insulin action in obese women appears to affect the placental programming of genes relating to adipokine expression and lipid metabolism, as well as mitrochondrial function. Altered inflammatory and lipid pathways affect the availability of nutrients for the fetus and, consequently, the size and body composition of the fetus. Fetal overgrowth and neonatal adiposity can result.

In addition, our research has shown that obese women have decreased insulin suppression of lipolysis in white adipose tissue, which during pregnancy results in improved lipid availability for fetal fat accretion and lipotoxicity.

When interventions aimed at weight loss and improved insulin sensitivity are undertaken before pregnancy or in the period between pregnancies, we have the opportunity to increase fat oxidation and reduce oxidative stress in early pregnancy. We also may be able to limit placental inflammation and favorably affect placental growth and gene expression. By the second trimester, our research suggests, gene expression in the placenta and early molecular changes in the white adipose tissue have already been programmed and cannot be reversed (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).

In studies by our group and others of interpregnancy weight loss or gain, interpregnancy weight loss has been associated with a lower risk of large-for-gestational-age (LGA) infants, whereas interpregnancy weight gain has been associated with an increased risk of LGA. Preliminary work from our group shows that the decrease in birth weight involves primarily fat and not lean mass.

The 2009 IOM guidelines support weight loss before pregnancy and state that overweight women should receive individual preconceptional counseling to improve diet quality, increase physical activity, and normalize weight. Multifaceted interventions do work: In obese nonpregnant individuals, lifestyle interventions, which include an exercise program, diet, and behavioral modification have been shown to be successful in improving insulin sensitivity, inflammation, and overall metabolic function.

According to the IOM report, preconceptional services aimed at achieving a healthy weight before conceiving will represent “a radical change to the care provided to obese women of childbearing age.” With continuing research and accumulating data, however, the concept is gaining traction as a viable paradigm for improving perinatal outcomes, with long-term benefits for both the mother and her baby.

Dr. Catalano reports that he has no disclosures relevant to this Master Class.

Obesity has become so pervasive that it is now considered a major health concern during pregnancy. Almost 56% of women aged 20-39 years in the United States are overweight or obese, based on the World Health Organization’s criteria for body mass index (BMI) and data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Moreover, 7.5% of women in this age group are morbidly obese, with a body mass index (BMI) greater than 40 kg/m² (JAMA 2012;307:491-7).

Obesity in pregnancy not only increases the risk of spontaneous abortions and congenital anomalies, it also increases the risk of gestational diabetes (GDM), hypertensive disorders, and other metabolic complications that affect both the mother and fetus.

Of much concern is the increased risk of fetal overgrowth and long-term health consequences for children of obese mothers. Obesity in early pregnancy has been shown to more than double the risk of obesity in the offspring, which in turn puts these children at risk for developing the metabolic syndrome – and, as Dr. Thomas Moore pointed out in September’s Master Class – appears to program these offspring for downstream cardiovascular risk in adulthood.

Mean term birth weights have risen in the United States during the past several decades. In Cleveland, we have seen a significant 116 g increase in mean term birth weight since 1975; this increase encompasses weights from the 5th to the 95th percentiles. Even more concerning is our finding that the ponderal index in our neonatal population has increased because of decreased fetal length over the last decade.

Some recent studies have suggested that the increase in birth weight in the United States has reached a plateau, but our analyses of national trends suggest that such change is secondary to factors such as earlier gestational age of delivery. Concurrently, an alarming number of children and adolescents – 17% of those aged 2-19 years, according to the 2009-2010 NHANES data – are overweight or obese (JAMA 2012;307:483-90).

How to best treat obesity for improved maternal and fetal health has thus become a focus of research. Studies on lifestyle interventions for obese women during pregnancy have aimed to prevent excessive gestational weight gain and decrease adverse perinatal outcomes – mainly macrosomia, GDM, and hypertensive disorders.

However, the results of this recent body of research have been disappointing. Lifestyle interventions initiated during pregnancy have had only limited success in improving perinatal outcomes. The research tells us that while we may be able to reduce excessive gestational weight gain, it is unlikely that we will be successful in reducing fetal overgrowth, GDM, or preeclampsia in obese women.

Moreover, other studies show that it is a high pregravid BMI – not excessive gestational weight gain or the development of GDM – that plays the biggest role in fetal overgrowth and fetal adiposity.

A paradigm shift is in order. We must think about lifestyle intervention and weight loss before pregnancy, when the woman’s metabolic condition can be improved in time to minimize adverse perinatal metabolic outcomes and to maximize metabolic benefits relating to fetal body composition and metabolism.

Role of prepregnancy BMI

In 2008, the Institute of Medicine (IOM) and National Research Council reexamined 1990 guidelines for gestational weight gain. They concluded that excessive weight gain in pregnancy was a primary contributor to the development of obesity in women. In fact, according to the 2009 IOM report, “Weight Gain During Pregnancy: Reexamining the Guidelines” (Washington: National Academy Press, 2009), 38% of normal weight, 63% of overweight, and 46% of obese women had gained weight in excess of the earlier guidelines.

Helping our patients to gain within the guidelines is important. Excessive gestational weight gain is a primary risk factor for maternal postpartum weight retention, which increases the risk for maternal obesity in a subsequent pregnancy. It also has been associated with a modest increased risk of preterm birth and development of type 2 diabetes.

Interestingly, however, high gestational weight gain has not been related to an increased risk of fetal overgrowth or macrosomia in many obese women. Increased gestational weight gain is a greater risk for fetal overgrowth in women who are of normal weight prior to pregnancy (J. Clin. Endocrinol. Metab. 2012;97:3648-54).

Our research has found that in overweight and obese women, it is maternal pregravid BMI – and not gestational weight gain – that presents the greatest risk for fetal macrosomia, and more specifically, the greatest risk for fetal obesity. Even when glucose tolerance levels are normal, overweight and obese women have neonates who are heavier and who have significant increases in the percentage of body fat and fat mass (Am. J. Obstet. Gynecol. 2006;195:1100-3).

In an 8-year prospective study of the perinatal risk factors associated with childhood obesity, we similarly found that maternal pregravid BMI – independent of maternal glucose status or gestational weight gain – was the strongest predictor of childhood obesity and metabolic dysfunction (Am. J. Clin. Nutr. 2009;90:1303-13).

Other studies have teased apart the roles of maternal obesity and GDM in long-term health of offspring. This work has found that maternal obesity during pregnancy is associated with metabolic syndrome in the offspring and an increased risk of type 2 diabetes in youth, independent of maternal diabetes during pregnancy. A recent meta-analysis also reported that, although maternal diabetes is associated with an increased BMI z score, this was no longer significant after adjustments were made for prepregnancy BMI (Diabetologia 2011;54:1957-66).

Maternal pregravid obesity, therefore, is not only a risk factor for neonatal adiposity at birth, but also for the longer-term risk of obesity and metabolic dysfunction in the offspring – independent of maternal GDM or excessive gestational weight gain.

Interventions in Pregnancy

Numerous prospective trials have examined lifestyle interventions for obese women during pregnancy. One randomized controlled study of a low glycemic index diet in pregnancy (coined the ROLO study) involved 800 women in Ireland who had previously delivered an infant weighting greater than 4,000 g. Women were randomized to receive the restricted diet or no intervention at 13 weeks. Despite a decrease in gestational weight gain in the intervention group, there were no differences in birth weight, birth weight percentile, ponderal index, or macrosomia between the two groups (BMJ 2012;345:e5605).

Another randomized controlled trial reported by a Danish group involved an intervention that consisted of dietary guidance, free membership in a fitness center, and personal coaching initiated between 10 and 14 weeks of gestation. There was a decrease in gestational weight gain in the intervention group, but paradoxically, the infants in the intervention group also had significantly higher birth weight, compared with controls (Diabetes Care 2011;34:2502-7).

Additionally, there have been at least five meta-analyses published in the past 2 years looking at lifestyle interventions during pregnancy. All have concluded that interventions initiated during pregnancy have limited success in reducing excessive gestational weight gain but not necessarily to within the IOM guidelines. The literature contains scant evidence to support further benefits for infant or maternal health (in other words, fetal overgrowth, GDM, or hypertensive disorders).

A recent Cochrane review also concluded that the results of several randomized controlled trials suggest no significant difference in GDM incidence between women receiving exercise intervention versus routine care.

Just this year, three additional randomized controlled trials of lifestyle interventions during pregnancy were published. Only one, the Treatment of Obese Pregnant Women (TOP) study, showed a modest effect in decreasing gestational weight gain. None found a reduction in GDM or fetal overgrowth.

Focus on prepregnancy

Obesity is an inflammatory condition that increases the risk of insulin resistance, impaired beta-cell function, and abnormal adiponectin concentrations. In pregnancy, maternal obesity and hyperinsulinemia can affect placental growth and gene expression.

We have studied lean and obese women recruited prior to a planned pregnancy, as well as lean and obese women scheduled for elective pregnancy termination in the first trimester. Our research, some of which we reported recently in the American Journal of Physiology , has shown increased expression of lipogenic and inflammatory genes in maternal adipose tissue and in the placenta of obese women in the early first trimester, before any phenotypic change becomes apparent (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).

Specifically, hyperinsulinemia and/or defective insulin action in obese women appears to affect the placental programming of genes relating to adipokine expression and lipid metabolism, as well as mitrochondrial function. Altered inflammatory and lipid pathways affect the availability of nutrients for the fetus and, consequently, the size and body composition of the fetus. Fetal overgrowth and neonatal adiposity can result.

In addition, our research has shown that obese women have decreased insulin suppression of lipolysis in white adipose tissue, which during pregnancy results in improved lipid availability for fetal fat accretion and lipotoxicity.

When interventions aimed at weight loss and improved insulin sensitivity are undertaken before pregnancy or in the period between pregnancies, we have the opportunity to increase fat oxidation and reduce oxidative stress in early pregnancy. We also may be able to limit placental inflammation and favorably affect placental growth and gene expression. By the second trimester, our research suggests, gene expression in the placenta and early molecular changes in the white adipose tissue have already been programmed and cannot be reversed (Am. J. Physiol. Endocrinol. Metab. 2012;303:e832-40).

In studies by our group and others of interpregnancy weight loss or gain, interpregnancy weight loss has been associated with a lower risk of large-for-gestational-age (LGA) infants, whereas interpregnancy weight gain has been associated with an increased risk of LGA. Preliminary work from our group shows that the decrease in birth weight involves primarily fat and not lean mass.

The 2009 IOM guidelines support weight loss before pregnancy and state that overweight women should receive individual preconceptional counseling to improve diet quality, increase physical activity, and normalize weight. Multifaceted interventions do work: In obese nonpregnant individuals, lifestyle interventions, which include an exercise program, diet, and behavioral modification have been shown to be successful in improving insulin sensitivity, inflammation, and overall metabolic function.

According to the IOM report, preconceptional services aimed at achieving a healthy weight before conceiving will represent “a radical change to the care provided to obese women of childbearing age.” With continuing research and accumulating data, however, the concept is gaining traction as a viable paradigm for improving perinatal outcomes, with long-term benefits for both the mother and her baby.

Dr. Catalano reports that he has no disclosures relevant to this Master Class.