Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 25–36

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Best Practice & Research ClinicalObstetrics and Gynaecology

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Diabetes and obesity in pregnancy

David Simmons, MA, MB BS, FRCP, FRACP, MD, Diabetes Specialist,Professor a,b,*aWolfson Diabetes and Endocrinology Clinic, Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust,Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UKbDepartment of Rural Health, University of Melbourne, Shepparton, Victoria, Australia

Keywords:obesitypregnancygestational diabeteslifestyleexercise

* Wolfson Diabetes and Endocrinology Clinic, InsTrust, Addenbrookes Hospital, Hills Road, Cambrid

E-mail address: dsworkster@gmail.com.

1521-6934/$ – see front matter � 2010 Elsevier Ltdoi:10.1016/j.bpobgyn.2010.10.006

An epidemic of obesity is affecting growing numbers of women intheir childbearing years increasing their risk of obstetric complica-tions including diabetes, hypertension, pre-eclampsia, some mal-formations, macrosomia and the need for obstetric intervention.There is growing evidence that maternal obesity may increase therisk of obesity and diabetes in the offspring. Obesity and diabetes inpregnancy have independent and additive effects on obstetriccomplications, and both require management during pregnancy.Management of obesity including weight loss and physical activityprior to pregnancy is likely to be beneficial for mother and baby,although the benefits of bariatric surgery remain unclear at thistime. Limiting gestational weight gain to 5–9 kg among pregnantobese women is likely to improve obstetric outcomes, but how toachieve this remains an active area of research. If gestational dia-betes develops, there is good evidence that clinical managementreduces the risk of adverse pregnancy outcomes.

� 2010 Elsevier Ltd. All rights reserved.

The pandemic of obesity and obesity in pregnancy

Obesity and downstream, type 2 diabetes have increased spectacularly over the last 50 years. Apictorial display of the increase in obesity (body mass index (BMI) �30 kgm�2) across USA from 1985,when no state had an obesity prevalence >15%, to the current picture of increasing numbers of stateswith a prevalence of adult obesity >30% can be found on the Centers for Disease Control andPrevention (CDC) website http://www.cdc.gov/obesity/data/trends.html#State (accessed 29 April

titute of Metabolic Science, Cambridge University Hospitals NHS Foundationge CB2 2QQ, UK. Tel: þ44 01223 216 913; Fax: þ44 0 1223 217 080.

d. All rights reserved.

D. Simmons / Best Practice & Research Clinical Obstetrics and Gynaecology 25 (2011) 25–3626

2010). This trend of increasing prevalence is occurring across the world.1 The extent of obesity is suchthat there are now three grades (usingWorld Health Organization criteria) of severity: grade I BMI 30–34.9 kgm�2, grade II BMI 35–39.9 kgm�2 and grade III with BMI 40þ kgm�2. Overweight is defined asa BMI 25–29.9 kgm�2.

The obesity epidemic is affecting not only adults, but also children, adolescents and young adults.Naturally, this means there are a growing number of obese women, who are becoming pregnant. Thereare now a large number of studies showing the increasing prevalence of obesity in pregnant and pre-pregnant women in different countries and different sub-populations.2 Fig. 1 shows the prevalence ofobesity in pregnancy in a selected number of studies from the six continents by year.3–9 Only a limitednumber of studies emanate from the developing world, but those that do report an increasing prev-alence of obesity in pregnancy, reflecting the changing socioeconomic circumstances, the growingurbanisation and the underlying ethnic and geographical features. However, in these countries,undernourishment often remains a significant health problem, which runs in parallel with the obesityepidemic.10

Ethnicity is an important consideration when interpreting the major measure of obesity currentlyused around the world (BMI).11 Some ethnic groups have more fat for a given BMI (e.g., South Asians)and others (e.g., Polynesians) have a lower proportion of total fat mass.12 These ethnic differencesreflect variation in lean body mass (i.e., largely muscle and bone) and/or different adipose distribution(i.e., more centralised vs. overall).12 Central fat, rather than peripheral adiposity, is more associatedwith resistance to insulin, a predisposing factor to gestational diabetes mellitus (GDM) and type 2diabetes.13 The increasingly routine clinical measure to assess central fat distribution in non-pregnantadults (waist circumference), is generally not available in later pregnancy, hence the reliance on BMI inmost studies.

Ethnicity is associated with different prevalence rates of obesity even in the same geographicallocation, but this relationship is often confounded by socioeconomic status, for example. It is thereforeimportant to understand that any given national or local prevalence of obesity in pregnancy willchange over time, not only in relation to any underlying secular trends in obesity, but also with anydemographic shifts. However, the growth in obesity in pregnancy is clearly across all subgroups,suggesting some fundamental change in lifestyle and/or ecology underpinning the current epidemic.

In England, the growing prevalence of obesity among women of childbearing age has tracked theincreasing prevalence of obesity in the general population,6 as shown in Fig. 2.

Although the reasons for the obesity epidemic are, to an extent, explained by the increase inavailability and consumption of energy-dense foods and a reduction in physical activity, the scientificevidence that this explains the entire explosion in obesity prevalence is incomplete.14 Table 1 lists otherputative contributing factors to the obesity epidemic.14

The purpose in showing these putative contributors is, first, not to imply that detrimental lifestylechoices are not major contributors, or that attempts to address these are inappropriate, but toemphasise that the rapidity in the growth in the epidemic could suggest that one or more additionalaccelerators and amplifiers are operating. Second, several of these putative factors operate through

Fig. 1. Prevalence of maternal obesity (BMI 30þ) at booking during pregnancy in different years in selected studies in differentcontinents (3–9).

Fig. 2. The growing prevalence of obesity among women of childbearing age in the UK.

Table 1Other putative contributors to the obesity epidemic besides unhealthy diet and insufficient exercise

Putative cause Description

Reduction in smoking Stopping smoking is associated with weight gainMicro-organisms There is a close interaction between adipose tissue and the immune system.

Obesity promoting viruses (eg Canine distemper) and adiposityenhancing gut flora do exist

Epigenetics There is evidence for maternal obesity having an intrauterine effect on theoffspring through epigenetic mechanisms. Other epigeneticeffects could also be happening

Increasing maternal age The age at which women have their babies has been increasing. Mothers ofobese children. Co-morbidities could confound. Possible mechanismshave been found in animals

Greater fecundity amongpeople with higher adiposity

Evidence exists that the BMI correlates with the number of offspringproduced-there are a number of confounders and which isfirst needs more research

Assortative mating for adiposity Spousal resemblance does occur, but could be due to a range of factorsafter mate selection. Some studies have shown correlation before marriageand cohabitation. Animal studies suggest an impact on bodyweight can occurwithin one generation

Sleep debt The amount of sleep has reduced over the last 40 years. Sleep deprivationis associated with obesity

Endocrine disruptingchemicals (EDCs)

Exposure to several EDC’s is increasing. Some EDC’s interfere with oestrogenand androgen signaling-this could be associated with body fat and weight

Pharmaceutical iatrogenesis Pharmaceutical use is increasing, some pharmaceuticals (eg antipsychotics,tricyclic antidepressants, beta blockers) are associated with weight gain

Reduction in variability ofambient temperatures

Temperature control use (eg air conditioning) has increased and could beassociated with increase in obesity

Intrauterine andintergenerational effects

A range of non-epigenetic mechanisms have been proposed that increase therisk of adiposity (and diabetes) in the offspring

From: McAllister EJ, Dhurandhar NV, Keith SW, Aronne LJ, Barger JBM, Benca RM, Biggio J, Boggiano MM, Eisenmann JC, ElobeidM, Fontaine KR, Gluckman P, Hanlon EC, Katzmarzyk P, Pietrobelli A, Redden DT, Ruden DM,Wang C, Waterland RA, Wright SM,Allison DB. Ten Putative Contributors to the Obesity Epidemic. Critical Reviews in Food Science and Nutrition 2009;49:868–913.

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reproductive behaviours and/or the intrauterine milieu, matters of importance for those involved withobesity and diabetes in pregnancy. These are particularly important when considering interventions toarrest and reverse the current epidemic. Finally, it needs to be appreciated that while the genomemayhave remained relatively unaltered (beyond the hypothetical mechanisms in Table 1), the gene–environment interaction has clearly changed, emphasising the need to understand the underlyinggenetic mechanisms behind obesity and diabetes.

The pandemic of diabetes and diabetes in pregnancy

Following the obesity epidemic is a diabetes pandemic including growing numbers of womenwithGDM and type 2 diabetes in pregnancy (including undiagnosed type 2 diabetes).15 A meta-analysis16

across studies relating the risk of GDM to obesity identified 20 studies which included:

� obesity measures prior to any significant pregnancy weight gain;� a comparison group of normal-weight women; and� quantitative data.

The prevalence of GDM ranged from 1.3% to 19.9%, using a variety of diagnostic and screeningcriteria. The meta-analysis showed that the risk of developing GDM was 2.14 (95% confidence interval(CI) 1.82–2.53)-fold higher if overweight, 3.56 (3.05–4.21)-fold higher if obese and 8.56 (5.07–16.04)-fold higher if severely obese compared with normal-weight pregnant women. Interestingly, theserelationships were not affected by publication date, study location, parity, rate of GDM or type of datacollection. The impact of different screening approaches and diagnostic criteria were not investigated.

Since these studies, the International Association of Diabetes and Pregnancy Study Groups (IADPSG)has proposed new criteria for the diagnosis of GDM, based on the Hyperglycaemia and AdverseOutcomes Study (HAPO).17 The criteria use a 75-g oral glucose tolerance test (OGTT) without priorglucose challenge and diagnose GDM if the fasting glucose is �5.1 mmol l�1 and/or the 1-h post-loadglucose is�10.0 mmol l�1 and/or the 2-h post-load glucose is�8.5 mmol l�1.With the greater numberswith GDM, it will be interesting to see if there is an alteration in the relationship with obesity.

‘Diabesity’ and pregnancy outcomes-untangling diabetes and obesity

The adverse outcomes from both diabetes in pregnancy without obesity, and obesity in pregnancywithout diabetes overlap substantially. There are obviously some complications, such as diabeticketoacidosis, which are virtually only associated with type 1 diabetes, and others such as diabeticretinopathy only associated with pre-existing diabetes (mainly type 1 and type 2 diabetes includingundiagnosed type 2 diabetes). However, there is also clearly a gradient in fetal exposure to hyper-glycaemia from type 1 diabetes, to type 2 diabetes down to GDM. It is with GDM that the discussion ofthe impact of obesity and GDM on the foetus and mother often becomes circular, as the majority ofthose with GDM are obese and a significant proportion of those who are obese have GDM. Studies onthe impact of obesity on obstetric and foetal outcomes often do not systematically screen for anddiagnose GDM (which can develop later in pregnancy after initial screening). Furthermore, HAPO hasclearly shown that the impact of hyperglycaemia on the foetus is at a much lower glucose (particularlyfasting glucose) concentration than previously thought.18 This would mean that many of the studiesshowing an impact of obesity on foetal adiposity included a significant number of women withhyperglycaemia. Finally, a few studies also include the assessment of the supply of other fuels thatcould be increased, such as fatty acids, to the foetus. For example, maternal triglyceride concentrationsare also associated with macrosomia.19

Notwithstanding the overlap, Table 2 compares the relative impact of diabetes, overweight andobesity on different pregnancy outcomes in a range of studies.20–31 Naturally, in pre-existing diabetesand GDM, pregnancy outcomes also depend upon the intensity of the treatment, clinical targets set, thesuccess in achieving the targets and thewider obstetric management. Type 1 diabetes is included in thetable as a largely ‘insulin deficiency-related hyperglycaemia only’ effect. However, it needs to be

Table 2Risk of Adverse Pregnancy Outcomes with different types of diabetes, obesity and being overweight vs normal pregnancies 20–31

Pre-existing diabetes T1DM alone GDM Obese Overweight

Macrosomia/LGA 4.91 (4.28–5.63) 4.5 (4.0–5.1) 1.65 (1.57–1.72)–3.27 (1.44–7.45) 1.5 (1.1–2.2)–4.5 (2.3–8.7) 1.2 (1.0–1.6)–1.6 (1.3–2.0)Hypertension 14.16 (10.94–18.29) 1.53 (1.18–1.99) 2.70 (2.33–3.13) 3.8 (1.7–9.1)–10.6 (5.0–22.5) 1.9 (1.0–3.7)–2.6 (1.5–4.6)Pre-eclampsia 3.97 (3.36–4.69) 4.47 (3.77–5.31)–12.1 (9.0–16.1) 1.61 (1.39–1.86)–1.69 (1.47–1.95) 2.1 (1.9–2.5)–3.9 (2.4–6.4) 1.3 (0.8–2.0)–2.0 (1.4–3.0)TED ? ? ? 1.5 (0.8–2.7) 1.4 (0.9–2.2)Labour induction 1.52 (1.35–1.72) 1.54 (1.49–1.60) 2.2 (1.7–2.81)–2.6 (1.7–3.9) 1.2 (0.8–1.8)–LSCS 2.37 (2.05–2.75) 4.83

(4.25–5.48–before labour)3.7 (3.2–4.2)–5.31 (4.97–5.69) 1.47 (1.40–1.55)–1.88 (1.45–2.43) 1.5 (1.1–2.0)–2.5 (1.6–3.9) 1.2 (0.8–1.8)–1.5 (1.4–1.7)

Pre-term delivery 2.54 (2.18–2.95) 4.5 (3.8–5.3)–7.0 (6.3–7.6) 1.28 (1.20–1.36)–2.18 (1.24–3.84) 0.9 (0.9–1.0)–2.1 (1.4–3.1) 0.8 (0.8–0.9)–1.1 (0.9–1.3)Stillbirth 2.90 (1.81–4.60) 3.34 (2.46–4.55)–4.7 (3.2–7.0) 1.17 (0.88–1.54) 1.2 (0.6–1.2)–2.4 (1.3–4.3) 1.2 (0.6–2.6)–1.5 (0.9–2.7)Perinatal death 3.29 (2.50–4.33)–4.1 (2.9–5.6) 1.0 (0.4–2.2)–2.7 (1.2–6.1) 1.0 (0.2–1.3)–1.8 (0.6–6.0)Intensive care 5.45 (4.51–6.58) 1.41 (1.27–1.57)–4.11 (2.37–7.10) 1.3 (1.0–1.6)–1.4 (1.2–1.6) 0.9 (0.7–1.2)–1.2 (1.1–1.4)Hypoglycaemia 56.8 (50.53–63.81) 2.75 (1.01–7.52)–15.07 (14.38–15.80) 0.9 (0.5–1.8)–2.6 (1.4–4.8) 0.8 (0.4–1.7)–1.2 (0.6–2.1)Malformationsa 1.7 (1.3–2.2)–3.4 (2.4–4.8) 1.7 (1.34–2.15) obese 3.11

(1.75–5.46) very obese1.22 (0.99–1.49)

Maternal mortality 60.0 (14.3–249.6)Jaundice 1.68 (0.71–4.01)–3.87 (2.64–5.67) 1.0 (0.9–1.1)–1.0 (0.6–1.7) 1.0 (0.6–1.8)

Gaps mean studies showing actual hazard ratios were not found.a Neural Tube defects in obesity/overweight. 31

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remembered that increasing numbers of those with type 1 diabetes now have weight-managementissues, and, that a proportion will have been predisposed to GDM and type 2 diabetes through obesityand other causes of insulin resistance/insulin deficiency, had they not developed type 1 diabetes. BothGDM and type 2 diabetes can be seen as amix of both insulin deficiency and insulin resistance, with theexpected excess supply of both glucose and fats. Type 2 diabetes has been included in the ‘pre-existingdiabetes’ column because of the relatively small numbers and lack of separation in many studies(probably as a reflection of the speedwithwhich the burden of type 2 diabetes inpregnancy has grown).

The table includes 95% CIs, but the studies are in different populations and health services; hence,comparisons are difficult without a full meta-analysis. The data suggest that, overall, pregnanciescomplicated by pre-existing diabetes (including type 1 diabetes) have generally worse outcomes thanobese or overweight women, especially in caesarean section, pre-term delivery, stillbirth, perinataldeath, intensive care admission and neonatal hypoglycaemia. The risk is greater for obese than over-weight women. Where there appears to be comparability (i.e., worse risk in obese women is compa-rable to some risks for womenwith pre-existing diabetes), this may be due to ethnic or service deliverydifferences (including differences in the management of diabetes in pregnancy).

There are differences between women with GDM and obese women in pregnancy, with womenwith GDM possibly having greater macrosomia (even after treatment), greater pre-term delivery,admission to intensive care but possibly less pre-eclampsia and induced labour. There is clearly fargreater neonatal hypoglycaemia and jaundice among the offspring of women with GDM than thosefrom obese women, but this observation and the other data have to be interpreted with caution assome women may have had undiagnosed pre-existing diabetes.

In ATLANTIC DIP (Atlantic Diabetes in Pregnancy),32 obese women without GDM (i.e., a fastingglucose <5.6 mmol l�1 and 2-h glucose <7.8 mmol l�1) were shown to be 1.4 (1.10–1.77)-fold morelikely to have a history of miscarriage and 2.47 (1.09–5.60)-fold more likely to have a baby witha malformation. In a meta-analysis of 12 studies investigating the relationship between obesity andneural tube defects, obese women were more likely to have a neural tube defect (see Table 2).31

Unfortunately, measures of glycaemia were not considered, and the authors admit that there couldhave been women with for example, undiagnosed type 2 diabetes. Nevertheless, in view of theincreased risk of neural tube defects in obesity, folic acid replacement therapy (4–5 mg) is now rec-ommended,33 just as it is in pre-existing diabetes.34

Long-term effect upon the offspring

Malformations clearly can have a devastating effect on the future life and family of the offspring;however, evidence is now growing that intrauterine exposure to a ‘diabetic milieu’, increases thechance of the offspring developing diabetes and/or obesity in the future.35–41 There is some observa-tional evidence that more intensive treatment with insulin in GDM might be associated with lessadiposity in the offspring by 2 years 8 months,42 and that untreated GDM may be associated witha twofold risk of increased weight at 5–7 years.43 However, a randomised controlled trial of themanagement of GDM showed that treatment of GDM reduced macrosomia at birth, but did not showa reduction in BMI at age 4–5 years.44 It has been proposed that BMImight not reflect any differences inlean and fat mass, and that differences may not be detectable until 9 years of age.44

Although no intervention studies have yet been reported, there is growing evidence that maternalobesity and maternal gestational weight gain are associated with obesity in the offspring.45,46 In onestudy among largely non-obese women,46 there was an increasing risk of obesity of 1.08 (1.03–1.14)-fold per kg of gestational weight gain in the offspring after 42 years.

Are the effects of glucose and obesity independent?

The interpretation of studies relating glycaemia and obesity to birth weight, as one outcomemeasure, among women with and without GDM can be made more difficult with the variable pene-tration and impact of modern management of GDM.47,48 A continuum of risk for macrosomia withglycaemia exists below the criteria for GDM.49,50 However, there have been a number of studies toassess whether the effects of obesity and glycaemia are independent. Early work among all nulliparous

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women proposed that glycaemia and obesity were not independent risk factors for macrosomia andhypertensive disorder in pregnancy, and that of the two, hyperglycaemiawasmore significantly relatedto adverse outcomes.51 Another article among women with GDM suggested that it was maternalobesity that was the strong risk factor for macrosomia, and that only fasting glycaemia between 32 and35 weeks was associated with macrosomia.52 A further article including women with and withoutGDM suggested that obesewomenweremore likely to develop hypertension andmacrosomia, but thatgestational hyperglycaemia was associated with caesarean section.53 Larger studies have shown anindependently increased risk of caesarean section with maternal obesity (pregravid BMI 1.1 (1.04–1.06)-fold greater risk per kgm�2), pre-existing diabetes (3.4 (2.3–5.2)-fold greater risk), diet-treatedGDM (odds ratio (OR) 1.4 (1.01–2.1)-fold greater risk) and insulin-treated GDM (OR 2.0 (1.2–3.4)-foldgreater risk).54 A comparable analysis showed the risk of macrosomia to also be independentlyincreased with maternal obesity (pregravid BMI 1.039 (1.031–1.047)-fold greater risk per kgm�2), pre-existing diabetes (4.06 (2.81–5.86)-fold greater risk), diet-treated GDM (OR 2.7 (CI 2.09–2.73) (prob-ably an error in CI) greater risk) and insulin-treated GDM (OR 2.94 (1.85–4.67) greater risk).55 Ona population basis in Spain, the upper quartile of BMI (>26.1 kgm�2) independently accounted for 23%of macrosomia, 9.4% of caesarean section, 50% of pregnancy-induced hypertension and 17.6% of large-for-gestational-age newborns. In the same study, after adjusting for maternal BMI, GDM by NationalDiabetes Data Group (NDDG) criteria accounted for only 3.8% macrosomia, 9.1% of pregnancy-inducedhypertension and 3.4% of pre-term births.56 However, the NDDG criteria do not include some womenwith GDM (HAPO). In a multiethnic group of women in New Zealand, with women with GDM diag-nosed by the Australasian Diabetes in Pregnancy (ADIPS)-New Zealand criteria excluded, maternalweight of 84þ kg accounted for 12.9%, 16.4% and 27.2% of babies weighing 4þ kg among European,Maori and Pacific women, respectively. In the same analysis, a 1-h glucose on the glucose challenge testof 6.3þmmol l�1 accounted for 16.7%, 17.0% and 18.7% of babies weighing 4þ kg among European,Maori and Pacific women, respectively, independent of maternal weight.57

In summary, the impact of maternal obesity and maternal hyperglycaemia would appear to beindependent and additive.

Weight gain and adverse outcomes

One important confounder in the studies of the impact of weight and glycaemia on pregnancyoutcomes is weight gain. The Institute of Medicine58 recommends that weight gain is limited in view ofits association with adverse pregnancy outcomes. These recommendations take into account thepotential for adverse effects from weight gain in the long term, taking into account the relationshipbetween reduced foetal growth and long-term risk of heart disease and other chronic diseases (such ashypertension and type 2 diabetes).59,60 Table 3 shows their recommendations for weight gain inpregnancy. More specifically, gestational weight gain has been associated with macrosomiawith an ORof 1.08 (95% CI 1.03–1.12) per kg gained.53 Among obese Danish women with normal glucose toler-ance,61 gestational weight gain of 10.0–14.9 kg, compared with a weight gain <5 kg, was associatedwith a 3.6 (1.3–9.8)-fold increase in hypertension, 3.0 (1.4–6.4)-fold increase in risk of caesareansection, 2.8 (1.3–5.9)-fold increase in risk of induction of labour and 2.2 (1.0–4.7)-fold increase in risk ofa baby with a birth weight of 4000þ g. Gestational weight gain of 15.0þ kg was associated with a 4.8(1.7–13.1)-fold increase in hypertension, 3.6 (1.6–7.8)-fold increase in risk of caesarean section, 3.7(1.7–8.0)-fold increase in risk of induction of labour and 4.0 (1.8–9.0)-fold increase in risk of a babywitha birth weight of 4000þ g.

Table 3Institute of Medicine Recommendations for weight gain in pregnancy

Pre-pregnancy BMI Total weight gainRange in kg

Rates of weight gain 2nd and 3rd trimesterMean (range) in kg/week

Underweight (<18.5 kg/m2) 12.5–18 0.51 (0.44–0.58)Normal weight (18.5–24.9 kg/m2) 11.5–16 0.42 (0.35–0.50)Overweight (25.0–29.9 kg/m2) 7–11.5 0.28 (0.23–0.33)Obese (�30.0 kg/m2) 5–9 0.22 (0.17–0.27)

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Weight gain during pregnancy is also associated with greater retention of weight after birth,resulting in a greater likelihood of overweight/obesity in any subsequent pregnancy.62–64 Unfortu-nately, excessive gestational weight gain is becoming more common.65

Can the adverse effects of obesity in pregnancy be prevented?

There are now a number of trials investigating the combined impact of lifestyle interventions, moreintensive obstetric care and insulin therapy, where indicated, which show substantial beneficialimpacts on maternal and neonatal outcomes in GDM,47,48 and these will not be described here. A rangeof interventions is possible to reduce the adverse effects of maternal obesity on pregnancy – these canoccur either before or during pregnancy.

Interventions during pregnancy

Weight loss is not recommended during pregnancy.58 However, with the association betweenexcess weight gain and adverse pregnancy outcomes, a number of studies have attempted bettermanagement of gestational weight gain,66 and enhancements in physical activity and/or nutrition. Inview of the different lifestyle choices that are often made in pregnancy in any case, and with thechanging advice that is often given during pregnancy, only a randomised controlled format is likely togive reliable information. A few such studies have been undertaken among obese women.

One randomised controlled trial has provided important information and warrants furtherdetail.67 The trial included 50 non-smoking obese (mean BMI 35 kgm�2) Danish pregnant women,recruited in early pregnancy, of whom 23 were randomised to 10 1-h sessions with a dietician, withthe goal of limiting gestational weight gain to 6–7 kg (30% fat, 15–20% protein and 50–55% carbo-hydrate). Self-reported dietary total energy intake and proportion of energy as fat were lower, but theproportion of energy as carbohydrate and proteinwas higher. Changes in physical activity and ketosisare not described. Weight gain was 6.6� 5.5 kg overall, 0.26 kg week�1 to 36 weeks and –4.5 kg 4weeks post-partum in the intervention group compared with a gain of 13.3�7.5 kg, 0.44 kg week�1

and þ2.4 kg 4 weeks post-partum in the control group. The study was not powered to differentiatebirth outcomes, and although mean birth weight was 138 g lower in the intervention, neitherintrauterine growth restriction (IUGR) nor macrosomia rates were presented. However, GDM (0% vs.10%), pregnancy-induced hypertension (4% vs. 15%) and pre-eclampsia (0% vs. 4%) were non-signif-icantly less.

As a reflection of the difficulties and nuances in such trials, a randomised controlled trial ofa brochure, active education and control among 195 obese women in Belgium had no effect ongestational weight gain or physical activity.68 Similarly, a controlled trial of dietary and physical activitycounselling in primary care among 132 (105 completing) primigravid women (9.5% overweight orobese) had no impact on gestational weight gain.69 Of interest was a reduction in babies weighing4þ kg (15% controls vs. 0% in the intervention group; p¼ 0.006).

Trials of exercise to help manage obesity in pregnancy are also limited, although several areunderway. The 2006 Cochrane review included 11 trials, which were “small and not of high meth-odologic quality.”70 They concluded “Regular aerobic exercise during pregnancy appears to improve (ormaintain) physical fitness. Available data are insufficient to infer important risks or benefits for themother or infant. Larger and better trials are needed before confident recommendations can be madeabout the benefits and risk of aerobic exercise in pregnancy.” Since the Cochrane review, a number oftrials of physical activity in pregnancy have been published. One of resistance training amongsedentary women included only 8.5% obese women (another 19.7% overweight) and found nosignificant impact on maternal weight or neonatal outcomes.71 Offspring with a birth weight of 4þ kgwere non-significantly less prevalent with the intervention (1.4% vs. 10%).

There are few randomised trials of different nutritional regimens in pregnancy. The use of theglycaemic index has been attempted in GDM with a reduction in large-for-dates babies.72 A keynutritional issue emerging at the moment is the observation that many obese women are serologicallyVitamin D deficient. As a result, it has now been recommended in the UK that Vitamin D supple-mentation be provided for all women with a pre-pregnancy BMI of 30þ kgm�2.33

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Interventions before pregnancy for maternal obesity

Surprisingly few pre-pregnancy intervention studies for maternal obesity have been published.73

For women with a BMI of 35þ kgm�2 and who already have obesity-related co-morbidities, bari-atric surgery (alongside a healthy lifestyle) is an option which is increasingly becoming available. Forexample, one early study of laparoscopic adjustable gastric banding (LAGB) in 44 women compared 48pregnancies after LAGB with 31 prior pregnancies.74 After LAGB, GDM was reduced by 19% with lesswomen prescribed insulin therapy and hypertension was non-significantly reduced by 14.5%, but theoccurrence of either GDM or hypertension was much lower (52% vs. 20.4%). Weight gain during theindex pregnancy was less than previous pregnancies (3.7 kg vs. 15.6 kg).

A recent comprehensive review of reproductive outcome after bariatric surgery has beencompleted.75 There are no randomised controlled trials and, hence, bias in any comparisons is a realpossibility. Different procedures might be associated with different outcomes. Furthermore, theimpact of GDM (undiagnosed or under-managed) could also influence comparisons. In view of this,no estimates of impact are shown. Although the rates of GDM and hypertension do appear to be lessafter the different kinds of bariatric surgery, the incidence of caesarean section and prematurity donot appear to be reduced, and the reports on spontaneous miscarriage, neonatal deaths andcongenital malformations are mixed. These may be related to the temporal proximity to the surgery.Mean birth weight has usually been found to be lower, but the incidence of IUGR appears (usually) tobe higher. Even the extent of gestational weight gain appears to vary, with the lesser the weight gainthe longer the duration from the actual procedure. Complications from the surgery can occur, such asband migration leading to vomiting, severe dehydration, electrolyte disturbance and band leakageand band removal may be required.74 Intestinal obstruction has been reported infrequently (e.g., fromadhesions). Mild nutritional deficiencies can occur, some of which are severe enough to requireparenteral nutrition. On the other hand, there is evidence to suggest that obesity surgery-associatedweight loss may be linked to less obesity in the offspring.76

Summary

Obesity and diabetes are growing problems in pregnancy. Both are associated with adverse preg-nancy outcomes including malformations, increased hypertension, increased accelerated foetalgrowth, increased instrumental intervention and increased risk of obesity in the offspring. Gestationalweight gain is a particular problem in pregnancy. Detecting and managing GDM is essential. Advice toeat for two77 are inappropriate, and there are now updated recommendations that obese womenshould gain a maximum of 5–9 kg over the whole pregnancy. The development of lifestyle interven-tions are at an early stage. Preventing gestational weight gain, increasing physical activity and somequalitative dietetic changes may be of benefit both during the pregnancy and for the offspring in thelonger term. Folic acid treatment to prevent malformation and Vitamin D supplementation are newlyadded interventions to address the increase in foetal neural tube defects and maternal Vitamin Ddeficiency, respectively.

Practice points

� Weight gain in obese women should be limited to 5–9 kg.� All obese women should be tested for GDM.� Obese women should receive folic acid 5 mg day�1 up to 12 weeks.� Obese women should take 10 mg of vitamin D daily throughout pregnancy and during breast-feeding.

� Obese women should receive dietetic advice early in pregnancy and preferably while plan-ning pregnancy.

Research agenda

� Mechanisms behind macrosomia in pregnancies complicated by obesity.� Mechanisms behind macrosomia in pregnancies complicated by gestational weight gain.� Effect of vitamin D supplementation.� Efficacy of folate supplementation.� Efficacy of lifestyle interventions for reducing adverse obstetric outcomes and adiposity inthe offspring in the long term among obese women.

� Efficacy of lifestyle interventions to prevent GDM among obese women.

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