Maternal obesity is of major consequence, affecting every aspect of maternity care including both short- and long-term effects on the health of the offspring. Obese mothers are at a higher risk of developing gestational diabetes and pre-eclampsia, potentially exposing the foetus to an adverse intrauterine environment. Maternal obesity is linked to foetal macrosomia, resulting in increased neonatal and maternal morbidity. Foetal macrosomia is a result of a change in body composition in the neonate with an increase in both percentage fat and fat mass. Maternal obesity and gestational weight gain are associated with childhood obesity, and this effect extends into adulthood. Childhood obesity in turn increases chances of later life obesity, thus type 2 diabetes, and cardiovascular disease in the offspring. Further clinical trials of lifestyle and, potentially, pharmacological interventions in obese pregnant women are required to determine whether short- and long-term adverse effects for the mother and child can be reduced.
Highlights
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Maternal obesity results in increased neonatal and maternal morbidity.
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Foetal macrosomia alters body composition, increasing percentage fat and body fat mass.
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Maternal obesity and gestational weight gain infer an increased risk of childhood obesity.
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Childhood obesity imposes an increased risk of cardiovascular disease in adult life.
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Educating young women on the dangers of obesity per se and in pregnancy is paramount.
Obesity: the scale of the problem
Obesity has become an epidemic throughout the world, and is considered one of the leading causes of death and disease in the industrialised world . Maternal rates of obesity are no different to rates of obesity in the general population doubling over a decade . In some parts of the UK, >20% of women of childbearing age are obese and the prevalence of obesity amongst pregnant women is spiralling, placing an unanticipated burden on health-care resources . Maternal obesity is of major consequence in obstetrics and affects every aspect of maternity care including long-term effects on the future health of the offspring ( Table 1 ). The purpose of this chapter is to highlight some of the key impacts of maternal obesity, both short and long term, on the offspring.
| Obstetric complication | Increased risk associated with obesity | References |
|---|---|---|
| Pre-eclampsia Systematic overview (16 studies) of rates in women categorised by prepregnancy BMI | RR 0.54% [0.27–0.80] | O’Brien et al., 2003 |
| Gestational Diabetes Meta-analysis (20 studies) of pregnancy complications including gestational diabetes: overweight, obese and severely obese vs non obese women | OR 2.14 [1.82–2.53] (overweight) OR 3.56 [3.05–4.21} (obese) OR 8.56 [5.07–16.04] (severely obese) | Ch SY et al., 2007 |
| Preterm labour (nulliparous elective preterm delivery) | OR R 1.15 [1.03–1.27] (overweight) OR 1.52 [1.31–1.77] (obese) OR 2.13 [1.75–2.58] (severely obese) | Smith et al., 2007 |
| Macrosomia | OR 2.1 [1.6–2.6] | Jolly et al., 2003 Usha et al., 2005 |
| Adverse Perinatal Outcome Results from an observational based population study of 60,167 deliveries over a 9 year period. | shoulder dystocia OR 2.9 [1.4–5.8] NNU admission OR 1.5 [1.09–2.3] Birth trauma (skin grazes, bruises, fractures, nerve palsies, muscle haematomas, cephalohaematomas) OR 1.5 [1.1–2.1] | Usha et al., 2005 |
| Miscarriage Meta-analysis (16 studies) of miscarriage rate in women who conceived by spontaneous pregnancy or assisted conception with BMI>25. | RR 1.67 [1.25–2.25] (including all miscarriages <20 weeks) | Metwally et al., 2008 |
| Congenital anomalies Systematic review (39 studies) and meta-analysis (18 studies) of congenital anomaly rates by group and subtype: obese vs non-obese women | Neural tube defects RR 1.87 [1.82–2.15] Spina bifida RR 2.24 [1.86–2.69] Cleft lip/palate RR 1.20 [1.03–1.40] Hydrochephaly RR 1.68 [1.19–2.36] Cardiovascular anomalies RR 1.30 [1.12–1.64] | Stothard et al., 2009 |
Short-term impact of maternal obesity on the offspring
Birthweight and foetal macrosomia
It is well recognised that birthweight is, in part, dependent on maternal nutrition , maternal pre-gravid weight and weight gain during the pregnancy.
Studies have shown positive correlations between maternal pre-pregnancy weight and gestational weight gain with the birthweight of the neonate and associated health risks . The Institute of Medicine (ISOM) published guidelines on recommended weight gain in pregnancy based on pre-pregnancy body mass index (BMI) and several studies have examined the influence on maternal weight gain on birthweight. A Danish study investigated the association of maternal weight gain and birthweight in 2248 singleton term pregnancies and found that in normal-weight women there was an increased risk of birthweight <3000 g (OR 2.3 (1.5–3.7)) if the maternal weight gain in pregnancy was below recommended levels, and almost double the risk of birthweight ≥4000 g (OR 1.9 (1.5–2.5)) when the women gained more than what was recommended . Excessive weight gain in obese women is also associated with increased birthweight in neonates . Obese women are at a higher risk of excessive weight gain in the antenatal period . Given excessive weight gain in pregnancy per se is independently associated with birthweight and adiposity in the offspring, the neonate of lean women with excess gestational weight gain also may be at risk .
Macrosomia is known to be associated with diabetes in pregnancy. As highlighted in Chapter 5 of this book, given that obesity and pregnancy combined both confer a state of insulin resistance to the mother, it is not surprising that obese women are four times more likely and severely obese women are nine times more likely to develop gestational diabetes than lean women . Evidence suggests that even modest fasting hyperglycaemia (4.2–5.6 mmol/l) is linearly associated with adverse outcome, such as increased birthweight and neonatal hypoglycaemia . A study by Pettitt el al. assessed the risk of foetal macrosomia by maternal weight gain and glucose levels. Amongst their population of 80,000 mothers and newborns, they found that foetal macrosomia increased linearly with increasing maternal glucose levels, amongst women with a normal glucose tolerance test. Furthermore, they found that excessive gestational weight gain increased the risk of macrosomia across increasing levels of maternal glucose including gestational diabetes mellitus (GDM) .
Foetal macrosomia is linked not only to the absolute size of the foetus but also to the change in the actual body composition, with an increase in percentage fat and fat mass in the offspring of overweight and obese mothers . Similar results were found in a study by Sewell et al., which demonstrated significant increases in percent body fat (11.6% (±4.7%) vs. 9.7 (±4.3%); p = 0.003) and fat mass (420 g (±220 g) vs. 380 g (±170 g); p = 0 .01) in neonates of overweight/obese women versus lean/average weight women .
Furthermore, Catalano et al. have published a series of studies comparing the body composition analysis of infants to women with normal glucose tolerance (NGT) tests and GDM within 48 h of birth. There was no significant difference in the actual birthweight (GDM 3398 g (±550 g) vs. NGT 3337 g (±549 g), p = 0.26) or fat-free mass (GDM 2962 g (±405 g) vs. NGT 2975 g (±408 g), p = 0.74); however, there was a significant increase in fat mass (GDM 436 g (±206 g) vs. NGT 362 g (±198 g), p = 0.0002) and percentage body fat (GDM 12.4 g (±4.6 g), p = 0.0001) in the infants born to GDM mothers .
Short-term impact of maternal obesity on the offspring
Birthweight and foetal macrosomia
It is well recognised that birthweight is, in part, dependent on maternal nutrition , maternal pre-gravid weight and weight gain during the pregnancy.
Studies have shown positive correlations between maternal pre-pregnancy weight and gestational weight gain with the birthweight of the neonate and associated health risks . The Institute of Medicine (ISOM) published guidelines on recommended weight gain in pregnancy based on pre-pregnancy body mass index (BMI) and several studies have examined the influence on maternal weight gain on birthweight. A Danish study investigated the association of maternal weight gain and birthweight in 2248 singleton term pregnancies and found that in normal-weight women there was an increased risk of birthweight <3000 g (OR 2.3 (1.5–3.7)) if the maternal weight gain in pregnancy was below recommended levels, and almost double the risk of birthweight ≥4000 g (OR 1.9 (1.5–2.5)) when the women gained more than what was recommended . Excessive weight gain in obese women is also associated with increased birthweight in neonates . Obese women are at a higher risk of excessive weight gain in the antenatal period . Given excessive weight gain in pregnancy per se is independently associated with birthweight and adiposity in the offspring, the neonate of lean women with excess gestational weight gain also may be at risk .
Macrosomia is known to be associated with diabetes in pregnancy. As highlighted in Chapter 5 of this book, given that obesity and pregnancy combined both confer a state of insulin resistance to the mother, it is not surprising that obese women are four times more likely and severely obese women are nine times more likely to develop gestational diabetes than lean women . Evidence suggests that even modest fasting hyperglycaemia (4.2–5.6 mmol/l) is linearly associated with adverse outcome, such as increased birthweight and neonatal hypoglycaemia . A study by Pettitt el al. assessed the risk of foetal macrosomia by maternal weight gain and glucose levels. Amongst their population of 80,000 mothers and newborns, they found that foetal macrosomia increased linearly with increasing maternal glucose levels, amongst women with a normal glucose tolerance test. Furthermore, they found that excessive gestational weight gain increased the risk of macrosomia across increasing levels of maternal glucose including gestational diabetes mellitus (GDM) .
Foetal macrosomia is linked not only to the absolute size of the foetus but also to the change in the actual body composition, with an increase in percentage fat and fat mass in the offspring of overweight and obese mothers . Similar results were found in a study by Sewell et al., which demonstrated significant increases in percent body fat (11.6% (±4.7%) vs. 9.7 (±4.3%); p = 0.003) and fat mass (420 g (±220 g) vs. 380 g (±170 g); p = 0 .01) in neonates of overweight/obese women versus lean/average weight women .
Furthermore, Catalano et al. have published a series of studies comparing the body composition analysis of infants to women with normal glucose tolerance (NGT) tests and GDM within 48 h of birth. There was no significant difference in the actual birthweight (GDM 3398 g (±550 g) vs. NGT 3337 g (±549 g), p = 0.26) or fat-free mass (GDM 2962 g (±405 g) vs. NGT 2975 g (±408 g), p = 0.74); however, there was a significant increase in fat mass (GDM 436 g (±206 g) vs. NGT 362 g (±198 g), p = 0.0002) and percentage body fat (GDM 12.4 g (±4.6 g), p = 0.0001) in the infants born to GDM mothers .
Macrosomia, birth injuries and neonatal unit admission
Foetal macrosomia contributes to significant challenges at delivery and in the immediate neonatal period. A UK-based cohort of 350,311 completed singleton pregnancies found macrosomia to be associated with prolonged labours, operative deliveries, shoulder dystocia, other birth traumas including nerve palsies and fractures, perinatal asphyxia and neonatal unit (NNU) admissions . These findings have been replicated . In a Welsh population-based cohort study of uncomplicated singleton term infants, they found adverse perinatal outcomes to be higher in the obese compared with the non-obese mothers including macrosomia (OR 2.1 (1.6–2.6)), shoulder dystocia (OR 2.9 (1.4–5.8)), NNU admission (OR 1.5 (1.09–2.3)) and birth trauma (including skin grazes, bruises, fractures, nerve palsies, muscle haematomas and cephalohaematomas) (OR 1.5 (1.1–2.1)) Interestingly, mothers with pregnancy complications (e.g., diabetes) were excluded. Given that obesity has a strong association with conditions such as diabetes and pre-eclampsia, the adverse perinatal outcome of infants born to obese mothers is likely to be under-represented .
There is a well-established association between maternal obesity and neonatal admission to the NNU . A recent study by Blomberg showed that the risk of adverse neonatal outcomes rises with increasing BMI regardless of the mode of delivery. Infants born to mothers of class 3 obesity had a twofold increased risk of skeletal birth injuries and respiratory distress. Furthermore, they had a threefold added risk of bacterial sepsis, convulsions, birth asphyxia, feeding difficulties and a fourfold increased risk of birth injuries to the peripheral nervous system and hypoglycaemia .
Obese mothers are less likely to labour spontaneously, more likely to have an induced labour, less likely to deliver vaginally and more at a risk of caesarean section . This also impacts on higher rates of admission to the NNU for the management of transient tachypnea of the newborn secondary to retained lung fluid following caesarean section, especially a planned caesarean section .
Maternal obesity and breastfeeding
The benefits of breastfeeding to both the mother and baby are well established. The immediate postnatal period is thought to be crucial in programming long-term body weight and metabolism. It has been demonstrated that rapid weight gain in the neonatal period is a significant risk factor for developing obesity. Interestingly, it has been shown that for every increase in body weight by 100 g in the first week of life, even in babies born to non-obese mothers, the risk of obesity in adulthood rises by 28% .
The perinatal diet is thought to influence weight regulatory centres, by either promoting or reducing excessive weight gain. The findings of studies, however, are conflicting and confounding factors such as socioeconomic class and lifestyle factors may influence this. There is evidence, however, suggesting that infants who are exclusively breastfed are provided with a potential protective effect against obesity. Infants formula fed have been shown to exhibit faster weight gain than their breastfed counterparts and are at an increased risk of obesity in later life . There are certain fatty acids (FA) contained in breast milk that are thought to possibly be protective against obesity. Such a FA supply, however, is supplied via the maternal diet, being found in meat and organic dairy products . Conjugated linoleic acid (FA) isomers have been shown in animal studies to reduce fat gain and maintain insulin sensitivity in mice being given a high-fat diet. It is believed they increase energy expenditure and reduce body fat . Furthermore, conjugated linoleic acid suppresses inflammation within the human body and promotes the production of natural anti-inflammatory agents .
In terms of obesity, there is evidence that maternal obesity is associated with reduced initiation, establishment and maintenance of breastfeeding. It is plausible that other confounding factors may influence this risk; however, this link still exists when corrected for age, parity, smoking status and educational level . Maternal obesity is also a recognised risk factor for delayed lactogenesis that is compounded by an increased incidence of prolonged labour, operative deliveries and gestational diabetes that are all independently associated with poor lactogenesis .
Furthermore, in obese mothers, there is a mechanical difficulty in encouraging the infant to attach to heavier breasts and separation of the infant and mother soon after birth, due to higher risk of neonatal complications, with increased formula supplementation to treat neonatal hypoglycaemia .
Overall, it can be concluded that there are a number of factors which likely interplay and affect successful lactogenesis in obese mothers. The end result is of increased formula feeding, which may confer a risk of obesity to the neonate in childhood.
Maternal obesity and prematurity
Preterm birth/labour (PTL), defined as delivery under 37 weeks gestation, is the leading cause of neonatal morbidity and mortality, and this risk increases with decreasing gestation. Globally, an estimated 15 million babies are born prematurely annually, accounting for 11% of all live births. Approximately >1 million of these babies die as a result of morbidities related to prematurity. The concept of PTL is a complex one and clearly will be affected by a number of different factors involving the mother, foetus and intrauterine environment .
PTL can be either spontaneous or iatrogenic. Cohort studies have demonstrated that obese mothers are more at risk of iatrogenic delivery than spontaneous PTL . A recent study by Cattingius et al. investigated the link between BMI category and preterm delivery by gestation. They found that all classes of preterm delivery (i.e., 22–36 weeks) increased with BMI and the risks related to obesity were highest for the extremely preterm infants (i.e., 22–27 weeks) . Furthermore, a large retrospective record linkage study in Scotland investigated pregnancy outcomes for 187,290 women based on BMI. The study found there were statistically significant interactions between nulliparity and BMI for overall preterm deliveries, spontaneous preterm deliveries and elective preterm deliveries, with all p values <0.001. The risk of elective preterm delivery in nulliparous women increased with BMI in a linear fashion (BMI 25–29.9, OR 1.15 (1.03–1.27); BMI 30–34.9, OR 1.52 (1.31–1.77); BMI >35, OR 2.13 (1.75–2.58)). This association did exist but to a much lesser extent with parous women. A common reason for planned preterm delivery within the nulliparous women with a BMI >35 was pre-eclampsia, with 40.2% of women delivered being diagnosed with it, this compared to 18% in the multiparous group ( p < 0.01). Spontaneous preterm delivery occurred less with increasing BMI (BMI < 20, OR 1.46 (1.32–1.62); BMI 25–29.9, OR 0.89 (0.73–0.99); BMI 30–34.9, OR 0.85 (CI 0.73–0.99); BMI > 35, OR 0.81 (0.63–1.04)). This protective effect against spontaneous preterm labour was stronger for multiparous women . Overweight and obese mothers are known to be at an increased risk of maternal complications antenatally, including gestational diabetes, gestational hypertension, thromboembolism and pre-eclampsia . Pre-eclampsia (PET) risk in pregnancy doubles for every 5–7 kg/m 2 increase in BMI . The risk is doubled with a BMI of 26 and almost trebled when the BMI is > 30 compared to that of 21 . Maternal and foetal complications arising from diabetes and pre-eclampsia often necessitate early delivery .
Finally, obesity is related with intrauterine growth restriction as well as macrosomia and if detected may warrant preterm delivery .
Long-term impact of maternal obesity
Childhood obesity
Maternal obesity has been linked to long-term adverse effects on the offspring . Over the last 20 years, there has been a childhood epidemic of obesity . It is now estimated that 42 million children under the age of 5 years are now overweight and children born to obese mothers are more likely to be obese themselves . Furthermore, childhood obesity has been identified as a risk factor for obesity in adolescent and adult life independent of lifestyle, genetic and environmental factors . As we have previously discussed, infants born to obese mothers are more at risk of being macrosomic and have increased body fat and fat mass compared to their average weight counterparts. In obese pregnancies, as a result of the in utero environment of relative maternal hyperglycaemia, the neonate is born hyperinsulinaemic and it has been hypothesised this hyperinsulinaemic state may exert long-term effects on the body by means of increasing adipocyte size and/or number thus potentially contributing to childhood and adolescent obesity . A study that measured amniotic fluid insulin levels, a surrogate marker of foetal insulin production, supported this hypothesis by demonstrating that higher levels of insulin correlated with adolescent obesity in infants born to diabetic mothers . Additionally, a study amongst PIMA Indians showed that siblings born to mothers who concurrently were diabetic had a higher BMI between the ages of 9 and 24 years than those born to the same mothers who were not diabetic during that index pregnancy . An American study interestingly found that for every 1-kg increase in the birthweight of term infants, there was approximately a 50% increased chance of obesity in these adolescents between the ages of 9 and 14 years . Importantly, it is not only absolute BMI but also maternal weight gain in pregnancy which is relevant to the long-term risk of obesity in the offspring. A cohort study investigating the relationship of weight gain in pregnancy and pre-pregnancy maternal obesity found that a maternal weight gain of >7 kg increased the risk of adolescent obesity and abdominal obesity by 1.5-fold. Furthermore, this risk increased by fourfold if the mother had a pre-pregnancy BMI of >30 kg/m 2 compared with those of normal BMI .
The reasons for a potential long-term effect on childhood obesity is multifactorial and not yet fully understood, but one of the key proposed mechanisms may be through foetal programming when exposed to an unfavourable metabolic milieu in utero. Experimental evidence from both animal and human studies investigating the effects of a maternal high-fat diet on the offspring have shown that it leads to insulin resistance, hyperinsulinaemia and increased fat accumulation in the offspring . Such effects are associated with the altered programming of “central reward pathways” leading to an increase in the rewarding nature of food and the preference for high-fat and saturated foods . The hypothalamus is thought to be key to regulating body weight and metabolism. It is under hormonal control and leptin is thought to be one important hormone implicated in hypothalamic development. Leptin is derived from adipocytes and is a satiety hormone, which acts centrally in the arcuate nucleus of the hypothalamus to attenuate hunger and increase energy expenditure . Furthermore, leptin contributes to the development of central pathways that regulate feeding and metabolism . In animal models, excess or an absence of leptin at crucial times during development, whether due to over- or under-nutrition, have been shown to interrupt the development of the circuit . Animal studies have shown alterations to maternal diet during pregnancy or lactation can affect the magnitude and onset of the leptin surge, leading to long-term alternations in body weight regulation . Babies carried by obese mothers may be exposed to high levels of leptin too soon and expose the immature hypothalamus prematurely to a leptin surge, to which it cannot respond appropriately . If the hypothalamic centres are interrupted during their crucial period of development, the regions responsible for food intake may be altered resulting in an excessive hunger state contributing to obesity . The leptin theory of promoting obesity is clearly complex and leptin in humans is produced from other sources in addition to adipocytes .
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