Health & Research

Maternal Obesity and its Relative Contribution to offspring Obesity

Gestational Diabetes & High Risk of Pregnancy

Abstract:

Obesity is rising globally, reaching to epidemic levels and becoming a great threat with time for the people of all age groups. Maternal obesity is a potent risk factor for adverse pregnancy outcomes. Various researchers have explored the relationship between obesity and increased gestational weight gain, gestational Diabetes Mellitus, Large for Gestational Age, macrosomia and caesarean delivery. There are strong evidences that such obstetric conditions independently lead to offspring obesity.

There is increasing interest in hypothesis that maternal obesity is associated with lifelong obesity and related metabolic consequences in off spring because “the obesity epidemic could accelerate through successive generations independent of further genetic or environmental factors. This article suggests that increasing trends of maternal weight may generate an inter generational vicious cycle of obesity.

Obese mothers give birth to heavier daughters, who are at increased risk to be obese themselves during their reproductive years, thus perpetuating the cycle. Obesity engenders obesity and the need to put an end to this vicious cycle is imperative.

Introduction:

Obesity is rising epidemically throughout the world and has been more than doubled between 1980 and 2014 (WHO 2016). In 2014, more than 1.9 billion adults (18 years and older) were overweight and 600 million were obese in them, if the current rate of rise in obesity continues, the number of obese and overweight people will become 1.12 billion and 2.16 billion respectively till 2030 (Lim et al., 2014).

A large proportion of the world`s population is being affected by obesity, the proportion of adults with a body-mass index (BMI) of >25 kg/m² has increased between 1980 and 2013 from 28·8% to 36·9% in men, and from 29·8% to 38·0% in women (Marie et al., 2014).

According to WHO estimates, about 205 million men and 297 million women above the age of 20 are obese (WHO 2013). Like all other regions of world, Pakistan is also suffering from epidemic of obesity that is affecting almost all age groups (Tanzil and Jamali 2016). Obesity was first recognized as a disease by the World Health Organization (WHO) in 1948 (International Journal of Obesity 2008).

There is lack of knowledge among people, about the risks and detrimental effects associated with increased weight gain and obesity (Brooten et al., 2012; Groth et al., 2012). Due to the burden of non-communicable diseases caused by obesity, it contributes to more than 36 billion of DALYs (Disability adjusted life years) globally in addition to 2–6 percent total health expenditure of health (Swinburn et al., 2011). Obesity is a BMI (Body Mass Index) greater than or equal to 30 kg/m2 (WHO 2016).

BMI (Body Mass Index):

BMI is a simple index commonly used to classify overweight and obesity in adults as the weight in kilograms divided by the squared height in meters (kg/m2).

Risk factors of obesity:

A complex interaction of factors influence obesity (Haerens et al., 2010). Life during early childhood is very critical period during which the eating habits and energy balance is regulated with lifelong consequences of risks of obesity (Reilly et al., 2005). The age during 10–14 years is considered as a “crucial age” at which children are at greater risk for unnecessary weight gain (Haerens et al., 2010). The reduced physical activity, socioeconomic status, television use, and diet are mainly associated with overweight and obesity (Little et al., 2016).

Diet is an important factor playing role in developing obesity, as Consumption of fats and sugars is also increasing with time by snack foods (Zhang et al., 2015). Intake of such foods, macro-nutrients, and micronutrients is seemed to have greater associations with BMI, overweight, and obesity (Little et al., 2016).

The micronutrients such as zinc, iron, vitamin C and vitamin A may have an important role in fat deposition and the pathogenesis of obesity (Garcia et al., 2012). Several studies have been done on the dietary patterns which shows the associations of general and abdominal obesity with specific dietary patterns especially among women (Boggs et al., 2011). Children of higher socioeconomic status are at lower risk for obesity than children of lower socioeconomic status (Ogden et al., 2010).

Families with lower socioeconomic status are different in their lifestyle—including dietary and physical activity patterns—thus increasing the obesity risk (Little et al., 2016). However, in Pakistan, obesity seems to be associated with higher socioeconomic status, whereas among the children of lower socioeconomic status undernutrition is more likely to be present (Warraich et al., 2009).

Globally, changing food patterns and eating habits, unhealthy life style, rapid industrialization, physical inactivity and urbanization are the key factors that are contributing in increasing burden of obesity (Tanzil and Jamali 2016). Similarly among Pakistani women socio-economic and environmental risk factors play remarkable role in increasing obesity, these factors include sedentary lifestyle, lack of awareness, higher rates of urbanisation and shift in dietary pattern from high-fibre diet to low-fibre, and high-calorie diet (Mehboob et al., 2016). High intake of meat in food is also a risk factor for developing obesity in Pakistan (Warraich et al., 2009). Obesity during childhood is itself a risk factor for obesity in adolescence as it persist longer in adolescence (Zahnd et al., 2015).

Effects of obesity:

There is lack of knowledge about the risks and detrimental effects associated with increased weight gain and obesity (Brooten et al., 2012, Groth et al., 2012). According to the WHO most of the world’s population live in countries where overweight and obesity kills more people than underweight. Overweight and obesity are linked to more deaths worldwide than underweight.

Obese people have low social support and less satisfaction with life (Zutven et al., 2014). In addition to this these individual may self-stigmatize themselves which also contribute to poor health outcomes like negative eating habits, depression, anxiety, and poor functioning (Hilbert et al., 2013 and Pearl et al., 2013).Obesity also throw a great impact over psychosocial functioning as it is markedly associated with psychosocial impairment among obese people (Zutven

et al., 2014).

Obesity during childhood persist longer in adolescence and they have higher risk of developing chronic conditions like cancers, cardiovascular problems and diabetes (Zahnd et al., 2015). Maternal obesity also increases risk of schizophrenia (Khandaker et al., 2012) as well as diabetes (Hussen et al 2015) in the offspring. Obesity is also considered to be associated with poor cognitive outcomes (Zavodney, 2013). Evidence also suggest that obese encounter more emotional and behavioural issues (Griffiths et al., 2011).

Obesity among the females of reproductive age:

Girls from all age groups are considerably more obese than boys (Tanzil and Jamali 2016). According to the World Health Organization obesity is a pandemic issue, with a higher prevalence in females than males (Satpathy et al., 2008). The prevalence of obesity among women of reproductive age is rising around the world during the last few decades (Krause et al., 2011). In the National Health and Nutrition Examination Survey (NHANES), the prevalence of obesity in women aged 20-49 years continues to be high, exceeding 30% after 1999 (Flegal et al., 2010). Data from (NHANES) 2011-2012 indicates that 58.5% women of reproductive age between 20-39 years are classified as overweight or obese (Ogden et al., 2014).

There is also an evidence of high prevalence of an overweight and obesity among Pakistani females (Pakistan demographic health survey 2013). A study, carried out in Islamabad, showed females are at more risk to gain extra weight than males and so are more prone to complications (Bilal et al., 2005). The quality of life (QOL) is affected by obesity among both males and females but the major impact of obesity over males is seen on their work life, but among African and American women it has a great impact over their reproductive life (Wee et al., 2015).

Concerning with the reproductive life, females with obesity are at greater risk of infertility and pregnancy associated complications (Schliep et al., 2014). Obesity is associated with reduced fertility, coronary artery disease, and type ii diabetes mellitus, osteoarthritis, gallbladder disease, hypertension, and some cancers including breast and colon. (Endres et al., 2015). Females with higher BMI are seemed to have more ovulation problems and tubal disease (Schliep et al., 2014).

 

Obesity during pregnancy:

The prevalence of obesity and weight gain is increasing with time among the females who enter in pregnancy, this is diverting the public health care concern towards pre pregnancy obesity as well as the weight gain during pregnancy (Whitaker et al., 2015). The burden of obesity is rising among pregnant females, In the United States, more than half of pregnant women are overweight or obese which is putting them at a greater risk for pregnancy-associated complications (ACOG Committee opinion no. 549).

More than one-third of all pregnant women have BMI greater than 25kgm−2 at the time of conception (McIntyre et al., 2012). In 2009 1 in 5 pregnant women were obese when they became pregnant and its prevalence is increasing continuously with time (Fisher et al., 2013). Approximately 50% of the women are exceeding the weight gain guidelines, given by institute of medicine (IOM), during pregnancy (National research council and institute of medicine; Whitaker et al., 2015; Simas et al., 2011).

Obesity increases the risk of obstetrical complications including recurrent miscarriages, still birth, intra uterine fetal death, congenital malformations, (Gardosi et al., 2013) GDM, preeclampsia, dysfunctional labour so more than half of the maternal deaths either by direct or indirect causes are seen among the females with obesity (Lim et al., 2014). Obesity and overweight status of women at the beginning of pregnancy increases the risk of adverse pregnancy outcomes (Castano et al., 2013).

Obesity is becoming a great threat, especially for the women of childbearing age, as it is associated with adverse pregnancy outcomes (Hemond et al., 2016), including congenital disorders (Gilboa et al., 2010), neural tube defects (Stothard et al., 2009), cardiovascular diseases, macrosomia (Ehrenberg et al., 2004), large for gestational age (LGA) (Vesco et al., 2014; Black et al., 2013), childhood obesity (Susan and Erin 2015) and many more.

A higher proportion of obese women are observed who die in pregnancy/postpartum (Scott et al., 2013). An enquiry on reviewing maternal deaths to make motherhood safer (2003-2005) reported that maternal deaths incidence in obese women was 27% (Mander et al., 2010). Maternal obesity causes an increased risk of stillbirth, according to a study on still birth about 25% of all stillbirths were associated with maternal obesity, they showed that as the BMI increases, risk for still birth also increases from 1.36 for overweight women to 3.16 for women with BMI of greater than 50 kg/m2 (Yao et al., 2014).

A recent study from Sweden showed an increase in infant mortality from 2.4 per 1000 for normal-weight women to 5.8 per 1000 for women with BMI>40kg/m2 among 2 million new-borns (Johansson et al., 2014). There is 35% increased risk of premature death of fetus from any cause in obese pregnant females compared with the normal weight mothers (Reynolds et al., 2013).

The risk of gestational hypertension, gestational diabetes, and LGA infants increases with maternal obesity (Shin et al., 2014). Increased prepregnancy body mass index (BMI) is associated with adverse neonatal outcome including a higher incidence of fetal and neonatal macrosomia (birth weight ‡4,000g), shoulder dystocia, and caesarean delivery (Gaudet et al., 2012).

Obese women were found more prone to have labour induction, failure of the labour to progress, meconium stained amniotic fluid, malpresentation and caesarean section than non-obese women (Sheiner et al., 2005).

Fig. 3: Complications of obesity in females

Obesity among children:

Obesity during early life is becoming a serious health problem (Lobstein et al. 2004). It is reaching to the epidemic levels throughout the world (Ogden et al., 2010). In the past 30 years childhood obesity is more than doubled (Ogden et al., 2014). In 2009-2010, the prevalence of obesity in children and adolescents was 16.9%; this was not changed compared with 2007-2008 (Ogden et al., 2012).

According to the data from International Association for the Study of obesity Pakistan is having an estimated prevalence of childhood obesity between 15-20%. There is increasingly high burden of overweight and obesity among children living in an urban area of Pakistan (Ahmed et al., 2013).

It is observed that obesity during childhood persist longer in adolescence and these children have higher risk of developing health problems like cancers, cardiovascular problems and diabetes (The Surgeon General’s Vision for a Healthy and Fit Nation). Children who are obese in their early life are more likely to remain obese in their adolescence (Ogden et al., 2014).

A recent study carried out on the incidence of childhood obesity in united states showed that one third of children who were overweight were obese by eighth grade, and almost every obese child remained obese as an adult (Cunningham et al., 2014).

Maternal factors that lead to childhood obesity:

Maternal in utero environment have a great impact over the development of the fetus and influence the offspring’s risk for having obesity and type 2 diabetes later in life (Dabelea and Crume 2011). Scholars from various disciplines have established that pregnancy is a critical time for children’s development and uterine environment have considerable effects on birth and later life outcomes (Susan and Erin 2015, Almond and Currie, 2011).

Most common Risk factors associated with childhood obesity are determined during their intrauterine life they include maternal obesity before pregnancy (Yu et al, 2013), excess gestational weight gain (Mamun et al., 2014), smoking during pregnancy (Oken et al., 2008), low maternal vitamin D levels (<64 nmol/L) (Crozier et al., 2012; Krishnaveni et al., 2011) and short duration of breastfeeding (none or <1 mo) (Owen et al., 2011).

Greater the number of risk factors a child have greater is the risk for developing early childhood obesity (Robinson et al., 2014). Children having 1 or more of these risk factors have 29% prevalence of obesity as compared with 6% of children who had none of these risk factors, this difference is seemed to be persist in later life till the age 7 to 10 years (28% compared with 4%) (Gillmen et al., 2013).

Fig. 4:  Maternal factors that lead to childhood obesity.

1). Maternal obesity:

Maternal obesity is an important contributor towards obesity in the next generation (Boyle et al., 2016). Numerous studies have been done using observational data that shows a strong correlation between maternal obesity (either pre-pregnancy or excess pregnancy weight gain) and childhood obesity (e.g. Salsberry et al., 2007; Whitaker, 2004; Oken et al., 2007; Oken, 2009; Ja¨a¨skela¨inen et al., 2011; Branum et al., 2011; Yu et al., 2013; Ludwig et al., 2013). Maternal obesity is now a strongest predictor of childhood obesity at age 6-11 years (Catalano et al., 2009).

Maternal obesity before pregnancy has been associated with a 5-fold risk of infant obesity (Gaillard et al., 2013; Yu et al., 2013). The children of obese mothers have higher BMI as compared to the children of non-obese mothers and theses children also have higher body and abdominal fat mass (Gaillard et al., 2014). Maternal BMI before pregnancy is a universally recognized factor that have a great effect over fetal growth (Yu et al., 2013).

A large literature confirms that mother’s pre pregnancy obesity greatly results in obesity in her children (Susan and Erin 2015). According to HAPO study carried out in 2010 higher pre pregnancy BMI, is associated with greater likelihood of caesarean delivery and higher infant birth weight and body fat (Valsamakis et al., 2015). Maternal obesity or diabetes causes fetal over nutrition that can lead to postnatal obesity and related chronic diseases (Gluckman et al., 2008).

Maternal obesity leads to the umbilical cord mesenchymal stem cells adipogenesis, which is correlated with offspring adiposity (Boyle et al., 2015). Several Epidemiological studies suggest that these relationships between maternal obesity and offspring adiposity are not limited to neonatal life but aslo affect the offspring throughout the life span, independent of lifestyle factors after birth (Pirkola et al., 2010).

 

Table 2: Complications of maternal obesity and its effects on fetus.

PeriodEffect on foetusReferences
Antenatal1.      Congenital malformations

·         Neural tube defects

·         Congenital heart defects

·         Cleft lip and palate

 

Stothard et al., 2009

Gilboa et al., 2010

 

 

 

 

 

2.      Still birthYao et al., 2014

 

3.      Miscarriage

 

Gardosi et al., 2013
Intra partum1.      Fetal macrosomiaAlberico et al., 2014; Ehrenberg et al., 2004; Gaudet et al., 2014

 

2.      Shoulder dystocia,Gaudet et al., 2012
3.      LGAVesco et al ., 2014, Black et al., 2013,  Simas et al., 2012, Gaillard et al., 2013. Morrens et al., 2016, Navid et al., 2013
 

4.      Birth injury

 

 Lim et al., 2014
Post partum
1.      Obesity in childhood and adolescenceHillier et al., 2016, Gaillard et al., 2013, Valsamakis et al., 2015. Logan et al., 2016
2.      Poor cognitive outcomeZavodney, 2013
3.      Early menarche in girlsLim et al., 2014

 

4.      Psychosocial problemsWee et al., 2015; zutven et al., 2014;

Griffiths et al., 2011

5.      DiabetesHussen et al., 2015
6.      Metabolic syndromeBoney et al ., 2005
 

7.      Low 5 minute apgar score

 

Vesco et al., 2011

 

8.      SchizophreniaKhandaker et al., 2012

 

Placental weight and size:

Placenta of the mother is a organ that transports nutrients from the mother to fetus during intrauterine life (Lisboa et al., 2012). Maternal obesity, excessive GWG, and GDM are the predictors of maternal “over-nutrition” (Hillier et al., 2008), they are seemed to be associated with large size of placenta (Ouyang et al., 2013).

Increased nutrients or glucose present in obese and diabetic mothers affect the placental growth and therefore placental transport efficiency (Higgins et al., 2011). According to the study carried out on effects of maternal obesity, GWG and GDM on placental growth the Placental weight was an independent predictor of childhood obesity, their study suggested a long-term effect of the placenta on the risk of developing childhood obesity (Ouyang et al., 2016).

Mothers with high pre-pregnancy BMI and those who have excessive amounts of gestational weight gain have more fat and thus deliver greater concentrations of glucose and fatty acids to their developing fetus (Lawlor et al., 2011). The placenta is found to serve as potential sources for the transmission of intrauterine microbiota from mothers to the fetus (Aagaard et al., 2014). Excess maternal weight gain during pregnancy becomes a potent risk factor for her baby to become obese (Ayub et al., 2015).

Gestational diabetes mellitus (GDM):

Gestational diabetes mellitus (GDM) is defined as ‘carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy (Collier et al., 2016). GDM is seemed affecting up to 14 % of pregnancies (Lim et al., 2014). Diabetes in pregnancy is increasing and currently affects up to 5% of women in the U.K. (National Institute for Health and Care Excellence 2015) and up to 9.2% in the U.S. (DeSisto et al., 2014).

Approximately 87.5% of cases are gestational diabetes mellitus (National Institute for Health and Care Excellence 2015).  Obesity and GDM are highly associated with each other in a way that obese females are more likely to develop GDM regardless of having any previous history of diabetes (Hemond et al., 2016).

Obesity increases the risk of GDM as it is increased 2.1 times in overweight, 3.6 times in obese and 8.6 times in severely obese women compared to normal weight women (Chu et al., 2007). Females who develop GDM usually encounter type ii diabetes later in their life after pregnancy (Bellamy et al., 2009).

GDM shows strong association between obesity, excessive gestational weight gain and adverse fetal outcomes like LGA (Morrens et al., 2016). Inter pregnancy weight reduction causes much fall in the risk of developing GDM (Lim et al., 2014). GDM is also associated with adverse pregnancy outcomes including congenital malformations, cardio metabolic derangement, overweight and obesity in adult life as well as perinatal complications of a Diabetic pregnancy includes macrosomia, hypoglycaemia, respiratory distress, etc.

And sudden infant death (Pratheepan et al., 2016). GDM also increases the risk of caesarean section as well as macrosomia and these children suffer increased risk of obesity as well as type ii diabetes (Hakanen et.al 2016, Kamana et al., 2015). So the Obese pregnant women with GDM are more likely to take insulin in order to get good glycaemic control and to prevent GDM related adverse pregnancy outcomes (Lim et al., 2014).

Fig. 5: The vicious cycle of obesity and diabetes

According to a retrospective cohort study Including 652 women out of which 163 with GDM and 489 controls, showed that women with GDM have higher gestational weight gain through 24 weeks in turn a gestational weight gain is a risk factor for GDM in overweight and obese patients, but not in women with normal weight before pregnancy (Gibson et al., 2012). Obesity is considered as the long term complication of GDM (Miao et al., 2016). Obesity and gestational diabetes (GDM) in pregnancy are recognized as potential and independent risk factors for adverse pregnancy outcomes, including caesarean section (CS), macrosomia and preeclampsia (Wahabi et al., 2014).

The risk of LGA new born associated with increased pregnancy BMI is seemed to be more pronounced in diabetic mothers (Sridhar et al., 2013). According to the one of the study the offspring of mothers with pre gestational diabetes and GDM were large for gestational age at birth, and, after about 5 years of age they were heavier than the offspring of nondiabetic mothers (Pettitt et al., 1993).

Table 3: Rates of gestational diabetes in obese and non-obese pregnant females:

DurationLocationTotal no. of obeseTotal no. of non-obeseObese patients with GDM Non obese patients with GDMReference
1st April 2010 till 31st March 2011.

 

Department of obstetrics and Gynaecology Lady Reading Hospital, Peshawar 

250

 

_

n%n% 

Syed 2014

51(20.4)   _   _
January 2006 to April 2008.Private Maternity Home at Karachi,1181184400Jaleel 2009
December 2008 to December 2009.Civil Hospital, Karachi from11011087.210.9Hashmi et al., 2012
June 2009 to June 2010Ziauddin Hospital and Kharader General Hospital Karachi12029251.720.6Ali and Lakhani 2011
1st Sep, 2010 to 31st May, 2011.Combined Military Hospital Quetta,494948.100Uzma et al., 2014
2004-

2011

 

Pregnancy Risk Assessment Monitoring System (PRAMS) 40 US states and New York City.4296311352369781674336.5Shin et al., 2014

 

Maternal obesity and maternal diabetes are the most potent, independent risk factors and powerful predictor for the obesity in next generation (Soderborg et al., 2016; Logan et al., 2016; Weng et al., 2013; Catalano et al., 2012) and there combination has a greater impact than either alone (Catalano et al., 2012). GDM leads to higher incidence of offspring obesity as shown by one of the studies carried out between the offspring of mothers with and without GDM and the association between GDM and overweight offspring was studied.

GDM offspring were more prone to be overweight at 5, 7 and 12 years of age (24.6%, 28.1%, 29.4%) than nondiabetic offspring (15.6%, 18.3%, 18.1%) (Hakanen et al., 2016). According to other study carried out by Gillman et al 9.7% children overweight at early adolescence were born to mothers with GDM compared with only 6.6% children born to non-diabetic mothers (Gillman et al., 2003).

Epi genetic changes taking place during intrauterine life of foetal development of the mother having GDM initiate foetal metabolic programming and create adverse metabolic memory that leads to childhood obesity, metabolic syndrome and Diabetes (Pratheepan et al., 2016).

Studies indicate that offspring born to mothers with diabetes or GDM are at increased risk of developing childhood obesity with highest growth velocity around puberty and glucose intolerance in their life than offspring not exposed to maternal diabetes (Crume et al., 2014; Crume et al., 2011). Maternal hyperglycaemia either due to GDM or excessive maternal weight gain is an independent risk factor for childhood obesity at the age of 2-5 years (Hillier et al., 2016).

Table 4: Obesity in offspring of gestational diabetic and non-gestational diabetic mother

Child age in years at outcomeTotal no. of offspring with maternalOverweight/obese children among women with maternal

 

OutcomeReference (population)

 

GDMNo GDM     GDMNo GDM
 

11

 

74

 

148

n%n% 

 

BMI ≥ 90th percentile

 

 

Boerschmann et al., 2010 (Germany)

 

2331.12315.5
1252063169418.1185629.4BMI ≥ 90th percentile

 

Hakanen et al., 2016

(Finland)

9-114065441230148122.6BMI > 85th percentileLawlor et al., 2010 (United Kingdom)
16846611821.411317.1BMI > 85th percentilePirkola et al., 2010 (Finland)
7-10631011930.22625.5BMI ≥ 85th percentileTam et al., 2009

(Hong Kong)

3511035713.7918.8BMI ≥ 95th percentileWright et al., 2009 (USA)
4-934108926.51715.7BMI > 95th percentileWroblewska-Seniuk et al., 2009

(Poland)

4-93410838.887.4BMI 85th–95th percentileWroblewska-Seniuk et al., 2009

(Poland)

 

10

23271252.2414.8BMI > 85th percentileBuzinaroetal., 2008 (Brazil)
10232714.300BMI > 95th percentileBuzinaroetal., 2008 (Brazil)
5-737076096417.392812.2BMI > 95th percentileHillier et al., 2007 (USA)

 Gestational weight gain:

Gestational weight gain (GWG) is defined as the amount of weight gained by a pregnant woman between the time of conception and the onset of labor (Viswanathan et al., 2008). The GWG is becoming an important issue and obesity is a potent risk factor for increasead GWG as shown by one of the studies the In obese women, the mean GWG was 10.4 kg compared with 12.6 kg (SD 5.7) in the normal BMI category (O ’ Dwyer et al., 2013). Excessive GWG is linked strongly with maternal obesity during and after pregnancy (Rasmussen et  al., 2010).

Increase GWG irrespective of maternal weight before pregnancy is very important factor leading to serious health problems for women as well as for her child (Jersey et al., 2015). Excessive gestational weight gain of a mother is associated with number of adverse outcome in off springs that include low 5 minute Apgar score, hypoglycaemia, LGA and future obesity compared to the mothers who gain weight with in the recommended levels during pregnancy (Vesco et al., 2011).

It is associated with increased risk of gestational diabetes, gestational hypertension, caesarean delivery, macrosomia and obesity in mothers (Hernandez et al., 2012). Maternal Obesity leads to increased GWG (Valsamakis et al., 2015; Hemond et al., 2016), that in turn increases the risk of fetal macrosomia (Hillier et al., 2016) which is itself a risk factor for childhood obesity (Ouyang et al., 2016). GWG is associated with an increase in the caesarean section rate among non-obese women, however, but not among obese women (Rasmussen et al., 2010).

Excessive gestational weight gain especially in early pregnancy is associated with increase in the risk of GDM (Morisset et al., 2011; Hedderson et al., 2010) women who gain weight beyond the IOM recommendations during pregnancy are at greater risk of becoming overweight or obese (Mamun et al., 2010) these females are then more prone to develop diabetes mellitus in later life (Mamun et al., 2013).

GWG is now considered a potential risk factor for childhood obesity (Lau et al., 2014). Excess maternal weight gain during pregnancy becomes a potent risk factor for her baby to become obese (Ayub et al., 2015; Sridhar et al., 2014). GWG are positively associated with off spring’s birth weight (Rode et al., 2007).

IOM (institute of medicine) 2009 recommendations for total weight gain during pregnancy, by pre-pregnancy BMI.

Pre gestational BMI (kg/m2)statusRecommended gestational weight gain(kg) Recommended GWG in lbsRates of Weight Gains kg/week
<18.5underweight12.5-18>350.51
18.5-24.9normal11.5-16>250.42
25-29.9over weight7.5-11.5>200.28
>30obese5-9>150.22

In one of the study carried out on the effects of maternal excessive GWG the data from 313 mother-child pairs showed that Increasing maternal pre-pregnancy BMI was associated with significantly worse childhood outcomes including body mass index (BMI), waist circumference (WC), subcutaneous (SAT) and visceral adipose tissue (VAT), HDL-cholesterol (HDL-c) and triglyceride (TG) levels (Kaar et al., 2014).

In one of the other study the prevalence of offspring obesity was 20% at 10 years and 22% at 16 years due to the increased maternal gestational weight gain (Diesel et al., 2015). Obesity among females leads to increased GWG (gestational weight gain) and GWG in turn increases the risk of fetal macrosomia (Hillier et al., 2008).

Obese women tend to gain weight at a higher rate as compared to non-obese pregnant female (Rasmussen et  al., 2010) most of these women then never lose the weight gained during a pregnancy, placing them at higher risk for subsequent overweight and obesity (Endres et al., 2015). There is association between maternal gestational weight gain and future obesity in the off springs (Lau et al., 2014; Whitaker et al., 2015). The rate of obesity increased in the children of mothers who gained 16kg during pregnancy compared with those children born to mothers with weight gain of less than 9kg during pregnancy (Morerio et al., 2007).

Graph 1: IOM (institute of medicine) 2009 recommendations for TOTAl weight gain in pregnancy in lb and kg

Macrosomia:

Fetal macrosomia is a term used to define new-borns who are significantly larger than average birth weight of ≥4,000g (Kamana et al., 2015). Maternal overweight or maternal obesity predominantly predict for risk for maternal and neonatal medical complications, including macrosomia that may contribute to breastfeeding initiation failure (Cordero et al., 2015). Macrosomia is a risk factor for major problems during labour and can cause increased neonatal morbidity as well as is associated with overweight and type 2 diabetes (Clausen et al., 2008).

It causes complications in about 10% of all pregnancies which include prolonged labour, instrumental delivery, shoulder dystocia, increased rate of caesarean delivery and postpartum haemorrhage (Vyas et al., 2008). Birth weight of a new born is influenced by a number of maternal, fetal, metabolic and genetic factors, out of which maternal factors throw a significant impact over the development of macrosomia, they include gestational age at the time delivery, maternal diabetes mellitus, maternal obesity, multiparity, previous macrosomic infant, maternal age, ethnicity and race, out of these Maternal obesity causes three to four fold increased risk of fetal macrosomia (Iftikhar 2007). In one of the meta-analysis, the prevalence rates of fetal macrosomia is 13.3% in obese pregnant women as compared to (8.3%) in non-obese women (Leddy et al., 2008).

Children who are born macrosomic or LGA are at a greater risk of having obesity in their life (Ouyang et al., 2016). Adverse pregnancy outcomes have been observed when both maternal obesity and fetal macrosomia is present than the pregnancy without maternal obesity (Gaudet et al., 2014). Maternal obesity is an independent risk factor for macrosomia (Ehrenberg et al., 2004). Maternal obesity is associated with increased fetal growth which in turns leads to the macrosomia (Gaudet et al., 2014).

According to the study, obese women are at 1.7-fold increased risk to develop offspring macrosomia, compared to normal weight women, this study also confirms that maternal obesity, excessive GWG and maternal diabetes are independent risk factors for new-born macrosomia (Alberico et al., 2014). By another study the incidence of macrosomia increases from 4.8% to 13% among overweight women with a normal gestational weight gain and overweight women with excessive weight gain (Di et al., 2012).

Children born to mothers with GDM and overweight/obesity are more likely to be macrosomic and large for their gestational age (Wahabi et al., 2014). Maternal diabetes and excessive maternal weight gain in obese pregnant women increase the risk of macrosomic babies (Hillier et al., 2008) and macrosomia is itself a risk factor for childhood and eventually adult obesity (Lau et al., 2011). The risk of macrosomia in the infants of mothers with gestational diabetes mellitus (GDM) is between 15 and 45% as compared to 12% in new-borns of non-diabetic mothers.

Those females who develop diabetes during gestation pass high levels of glucose through their placenta into their fetus, which ultimately results in increased insulin secretion leading to high levels of proteins and fat stores in fetus resulting macrosomia. In order to prevent maternal and fetal birth trauma elective caesarean section is of best choice (Kamana et al., 2015). The importance of macrosomia is that it increases the risk of infant and childhood obesity which is then associated with insulin resistance diabetes and hypertension over the long term development of child. Obesity and diabetes are common inter acting factors in pregnancies, related to fetal and neonatal macrosomia (Marshall et al., 2014).

Pregnant obese mothers are at the high risk of developing diseases like gestational hypertension, gestational diabetes (GDM) and abnormal excess of weight acquisition in her fetus (Fraser et al., 2011 and Suresh et al., 2012). Macrosomic neonates born to diabetic and over-weight mothers are more prone to develop young age obesity, as shown in study the rate of developing obesity is 17.1% compared to 14.2% in the non macrosomic control group at birth, and 9.7% compared to 6.6% at adolescence (Jovanovic et al., 1991). A meta-analysis showed that BW greater than 4000 g increases the risk by twofold for obesity, and this risk is increased up to about 2.5-fold when BW exceeds 90th percentile (Monasta et al., 2010).

Table 5: Comparison of rates of macrosomia in obese and non-obese pregnant females:

DurationLocationTotal no. of obeseTotal no. of non-obeseNo(%) of obese patients with macrosomiaNo(%) of non-obese patients with macrosomiaReference
14th March 2010 to 13th Sep 2010Nishtar hospital Multan. 

174

 

_

n%n% 

Fatima et al., 2012

5431 

_

 

_

January 2006 to April 2008.Private Maternity Home at Karachi,1181181616.266.1Jaleel 2009
January 2009 to Oct 2010.Sultan Welfare Hospital Karachi100100262644Fatima et al., 2011
 

_

 

_

100 

_

2626 

_

 

_

Khurram et al., 2006
June 2009 to June 2010Ziauddin Hospital and Kharader General Hospital Karachi1202923831.63913.3Ali and Lakhani 2011
April, 2010 till Mar 2011.Lady Reading Hospital, Peshawar250    _5522    _  _Syed 2015
June 5, 2011 to June 5, 2012.Benazir Bhutto Med College, Lyari General Hospital, Karachi.200   _  _20.5  _   _Rehman et al., 2012
December 1, 2007, and March

31, 2010.

 

Ottawa Hospital

Civic Campus

 

1328563224018.159510.6Gaudet et al., 2014

 

Large for gestational age:

Pre-pregnancy overweight and obesity account for a high proportion of LGA, even in the absence of GDM (Morrens et al., 2016). Most of studies show overweight mothers with a BMI of  greater than 25 kg/m2 and less than 30 kg/m2 have about 1.5 times more risk of delieverig a LGA baby (Hemond et al., 2016). Maternal obesity before pregnancy has been associated with a 3-fold risk of delivering LGA neonates (Gaillard et al., 2013; Yu et al., 2013). Women who are active throughout their pregnancy are at lower risk of delivering a LGA baby (Mudd et al., 2013).

Several studies confirm the association of pre-pregnancy obesity with the risk for high birth weight (HBW), large-for-gestational-age (LGA) neonates, macrosomia and subsequent offspring obesity (Valsamakis et al., 2015). If maternal weight gain is more than 11 kg it is strongly associated with the birth of large for gestational age baby (Lim et al., 2014). It shows that maetnal weight gain is highly associated with LGA and is collaborated by large body of literature (Vesco et al., 2014).

High placental weight is correlated with higher prevalence of LGA (Ouyang et al., 2016). In a retrospective study carried out on 9835 women, Overall, 5,851 (59.5%) women were overweight and 1,892 (19.2%) had GDM. High birth weight and LGA infants are prone to develop insulin resistance (Giapros et al., 2007), obesity, and diabetes in later life (Boney et al., 2005; Dietz, 2004). LGA infants have high body fat mass at birth compared with AGA (appropriate for gestational age) infants (Armitage et al., 2008). In Obesity there are high levels of leptin which have physiologic inhibitory effect on uterine contractions leading to prolonged pregnancy and LGA (Bhattacharya et al., 2007).

Corticotrophin releasing hormone (CRH) secreted by placenta helps inducing labour is inversely proportional with gestational weight gain, greater the weight gain lesser the (CRH) causing delayed labour and prolonged pregnancy. The metabolism of oestrogen by the maternal adipose tissue also changes the oestrogen progesterone ratio that affects the initiation of labour (Riley et al., 1991). LGA babies are at the risk of shoulder dystocia, fractured clavicle, erb palsy and other birth injuries. They also have at a greater risk of hypoglycaemia regardless of their mothers having GDM or not (Hemond et al., 2016).

 

Chart 1: Percentage of LGA babies in normal overweight and obese mothers

 

The prevalence of large-for gestational-age (LGA) infants was significantly higher for overweight and obese women compared with the normal-weight counterparts, It is reported that 12.7% babies from obese mothers were LGA compared with 10.8% babies of overweight mothers and the percentage of LGA babies from a normal weight mothers was 7.7% (Black et al., 2013). Healthy mothers with BMI <25kgm2 have 17% of LGA babies while overweight mothers with BMI of >25kgm2 have 28% of LGA babies (Jersey et al., 2014).

In one study carried out by Rehman et al 70% of obese women delivered between 37-40, 20% between 40-42 weeks and 10% beyond 42 weeks of gestation (Rehman et al., 2012). Other study showed delivery rate of 47.4% in between 37-39 weeks, 47.2% in 40-41 weeks and 5.4% at >42 weeks of gestation (Stotland et al., 2007). Similar results were shown by Denison et al which quoted 6.8% of post term deliveries (Denison et al., 2008).

Table 6: Comparison of rates post term/LGA pregnancy in obese and non-obese pregnant females:

DurationLocationTotal no. of obeseTotal no. of non-obeseObese patients with LGANon obese patients with LGAReference
    _Combined Military Hospital, Lahore 

100

 

100

 n%n%Naveed et al., 2013
32322525
February 2003 to 2007.The Aga Khan University, Karachi,10443691777.41433.8Munim and Maheen 2011
January 2009 to October 2010.Sultan Welfare Hospital Karachi10010024241414Fatima et al., 2011
30 October 2005 and

31 December 2010.

 

The Kaiser Permanente Southern California Medical Center

 

1915602824312.75419Black et al., 2013
2004-2011

 

Pregnancy Risk Assessment Monitoring System.42963113523614514.382317.25Shin et al., 2014

Caesarean delivery:

The widespread increase in the number of caesarean births is diverting the attention public health towards its effects over the off springs on later life (Hyde et al., 2012). In many countries, the rate of caesarean section has exceeded 15% (Gibbons et al., 2012). Obese women are considered at higher risk of delivering the baby via caesarean section irrespective of their past history of mode of delivery (Kubaisy et al., 2014). The rate of successful vaginal delivery decreases as maternal BMI increases (Leddy et al., 2008).

The increase in caesarean section rate is seem to be due to inability or slow progress in the first stage of labour or difficulty in descent in second stage of labour in obese mothers (Davies et al., 2010). High rates of caesarean sections associated with obesity is seen because of reduction in contractility of the obese uterus, this may be due to increased cholesterol deposits in the myometrium (Zhang et al 2007). During pregnancy changes occur in the gut microbiota of the mother (Koren et al., 2012).

There is a difference in the gut microbiota between the women with normal weight and obese mothers especially in the second half of pregnancy and this difference is in turn associated with increased neonatal birthweight (Santacruz et al., 2010).During the vaginal birth the new-borns are directly exposed to maternal vaginal and intestinal microbiota, whereas the new-borns by caesarean section are exposed to a totally different type of microbiota derived from maternal skin and environmental bacteria, this difference affects the development of offspring gut microbiota composition (Nicholson et al., 2012; Dogra et al., 2015). Caesarean section deprives the opportunity for the new-born to get exposed to maternal vaginal feces, the bacteria from which are a major source for the intestinal bacteria of the new-born (Neu et al., 2012; Blustein et al., 2013).

This change in the composition of microflora of the off spring lasts through out the life and may become the causative factor of obesity. Gut microbiome composition in new-borns plays a significant role in child development (Soderborg et al., 2016). New-born’s gut composition is correlated with microbiota colonisation in later life, suggesting that dysbiosis in infancy due to obesity exposure may have great impact on metabolic health of child (Koleva et al., 2015). Caesarean section also leads to obesity in childhood adolescence by affecting the inflammation, immune and endocrine function of baby (Huh et al., 2013). Caesarean section was associated with a reduced rate of early breastfeeding (Zanardo et al., 2010).

Table 7: Rates of caesarean section in obese pregnant females:

During yearLocationTotal no. of obeseObese patients with caesareanReference
1st April 2010 till 31st March 2011.

 

Lady Reading Hospital, Peshawar 

250

n%Syed 2014
7630.4
25th August 2010 to 25th November 2010.Lady Reading Hospital, Peshawar1263830Liaqat et al., 2014
from August 2010 to November 2011Kalsoom Maternity Hospital, Bannu Peshawar1363836.4Abrar et al.,2016
June 5, 2011 to June 5, 2012.Benazir Bhutto Med College, Lyari General Hospital, Karachi.2008844Rehman et al 2012
October 2008- April 2009Liaquat National Hospital Karachi2449739.8Shabab and Tahir et al., 2010

 

Several epidemiological studies have examined the association between caesarean section and later overweight/obesity in off springs (Ajslev et al., 2011 and Zhou et al., 2011; Manco et al., 2010). The risk of caesarean delivery is increased by 50% in overweight and more than doubled in obese women in comparison with normal weight pregnant women shown in A meta-analysis of 11 cohort studies (Poobalan et al., 2009; Valsamakis et al., 2015).

Caesarean delivery, one of the complication of maternal obesity and GDM is associated with a 46% increase in infant obesity risk at 7 years of age (Mueller et al., 2015).  There is a 20% increased risk in development of type 1 diabetes for the children born by ceasaren section compared with children born vaginally (Cardwell et al., 2008). In a prospective pre-birth cohort study Infants delivered by caesarean section showed two fold higher odds of childhood obesity, Out of 1255 deliveries 284 children (22.6%) were delivered by caesarean section. Out of 284, 15.7% children were obese compared with 7.5% of children born vaginally at age 3 years (Huh et al., 2013).

According to one of the study carried out on non-diabetic 736 women (22% with normal prepregnancy weight, 29% overweight, 23% obese, 14% very obese, and 12%  extremely obese) who delivered macrosomic infants, caesarean delivery increased from 20% among women of normal weight to 57% for extremely obese women. Conversely, vaginal deliveries declined from 80% to 43% from normal weight to extremely obese women (Cordero et al., 2015). Sherrard et al studied maternal anthropometric risk factors for caesarean delivery in a Canadian University Hospital and found that pre-pregnancy BMI >30 kg/m2 increases the risk in all women irrespective of age, parity, socio-economic factors, gestational diabetes, pregnancy induced hypertension and other obstetric factors (Sherrard et al 2007).

Table 8: Comparison of rates caesarean in obese and non-obese pregnant females:

During yearLocationTotal no. of obeseTotal no. of non-obeseObese patients with cNon obese patients with cReference
 

 

Combined Military Hospital, Lahore

 

100

 

100

n%n%Naveed et al., 2013
28282121
1st September, 2010 to 31st May, 2011.Combined Military Hospital Quetta,49491938.71020.4Uzma et al., 2014
January 2006 to April 2008.Private Maternity Home at Karachi,1181183636.42424.2Jaleel 2009
January 2009 to October 2010.Sultan Welfare Hospital Karachi10010043431414Fatima et al., 2011
February 2003 to 2007.The Aga Khan University, Karachi,1044369129027.886223.35Munim and Maheen 2011
December 2008 to December 2009.Civil Hospital, Karachi from1101103935.41715.5Hashmi et al., 2012
June 2009 to June 2010Ziauddin Hospital and Kharader General Hospital Karachi120292584810836.9Ali and Lakhani 2011

Fig 6: transgenerational cycle of obesity

Table 9: Maternal factors and their effects on offspring.

NameMaternal factorType of studyOutcomeSampleCountry
Ouyang et al., 2016Maternal obesity , gestational

weight gain and gestational diabetes mellitus

 

Prospective birth cohort study7.2% children had obesity follow up till 7 years old offspring of obese mothers33,893US
Karen et al., 2016Gestational diabetes mellitusProspective longitudinal studythe GDM group had significantly greater total AT (adipose tissue) volume at 10 weeks than control group infants86 infants (GDM group 42 infants; control group 44 infants)London
Hillier et al., 2016

 

Maternal glucose and gestational weigh gainPopulation studyChildhood overweight (>85%ile) and obesity (>95 %ile) between age 2–10 was 49.2 and 28.4 %, respectively.24,141 mothers and babiesNew York
Morrens et al., 2016Maternal diabetes and gestational weigh gainRetrospective analysisMacrosomia (>4Kg) was present in 16.2 % of

deliveries, LGA was present in 45.2 %

 

259Belgium
Hakanen et al., 2016Gestational diabetes mellitusLongitudinal cohort studyGDM offspring were overweight at 5, 7 and 12 years of age (24.6%, 28.1%, 29.4%) than nondiabetic offspring (15.6%, 18.3%, 18.1%)

 

6909 childrenFinland
Kaar et al., 2014Increased gestational weigh gainObservational historical prospective cohort studyIncreases off spring BMI, waist circumference, subcutaneous (SAT) and visceral adipose tissue (VAT), HDL-cholesterol and triglyceride (TG) levels313Colorado
Alberico

et al., 2014

Maternal obesity , gestational

weight gain and gestational diabetes

 

Prospective multicentre studyNew born macrosomia14109Italy
Diesel et al. 2015Increased gestational weigh gainProspective  pregnancy cohort studyOffspring obesity at 10 and 16 years of age514USA
Sridhar et al., 2014Maternal gestational

weight gain

Prospective cohort study46% increase in odds of having an overweight/obese child (odds ratio

[OR], 1.46; 95%

confidence interval [CI], 1.17-1.83)

4145 womenCalifornia
Black et al., 2013Maternal Overweight and Obesity, GWG and GDM

 

Retrospective study21.6% of

LGA infants with maternal overweight and obesity,

23.3% of LGA infants with GDM.

 

9,835 womenCalifornia
Oken et al., 2008Increased gestational weigh gainCohort studyoffspring obesity in adolescents aged 9–14 years11,994Boston
Catalano et al., 2009Maternal obesityCase control,Offspring of obese had greater % body fat(13.1vs11.6%,PZ0.0268 cases, 53 controlsUSA
Mesman et al.,2009Maternal obesityprospective cohortOne unit increase in maternal pre-pregnancy BMI associated with increase in child BMI of b 0.041(95% CI 0.03–0.053) kg/m2 at 2-4 years3171USA
Reynolds et al.,  (2009)Raised First trimester BMIBirth cohort,Greater percentage body fat in offspring of mothers with higher BMI (rising by 0.35% per kg/m2)276UK

Prevention:

Breast feeding:

Maternal obesity dramatically increase the long-term risk for obesity in the next generation, and lactation may be critical periods at which to aim primary prevention to break the obesity cycle (Soderborg et al., 2016). Breastfeeding has many established benefits to both mother and baby, including as another potentially modifiable way to reduce childhood obesity risk (Mayer et al., 2006).

Among the 302 women who answered questions about breastfeeding, the risk of developing obesity in their children was dramatically reduced among mothers that breastfed than those who did not. Children of women who breastfed had an obesity prevalence of 37 %, compared to 51 % for children of women who did not breastfed (p=0.006) (Division of Nutrition and Physical Activity 2007).

Exclusive breastfeeding can help in reducing the risk of paediatric obesity (Yan et al., 2014; Young et al., 2012) and that this can provide protection against offspring obesity in women with obesity for at least 6 months (Woo et al., 2015). A longer duration of breast-feeding is associated with reduced risk of developing later obesity; each month of breast-feeding was associated with a decrease of 4% in obesity risk (Harder et al., 2005). Breast-feeding is partly associated with slower rate of growth compared to formula-fed infants (Singhl et al., 2007).

Controlling glucose levels:

Advanced control of glucose levels in mothers with the family history of diabetes or previous GDM, as well as early identification and control of hyper glycaemia during pregnancy are the key strategies to improve outcomes in the offspring (Pratheepan et al., 2016). Obese pregnant women with GDM are more likely to take insulin in order to get good glycaemic control and to prevent GDM related adverse pregnancy outcomes (Lim et al., 2014).

 

Physical activity:

Pregnant women should also be physically active and incorporate at least 30 minutes of moderate-intensity activity into each day. However, women who did not exercise regularly before pregnancy should begin with no more than 15 minutes of continuous activity three times per week, gradually reaching a target of 30 minutes (NICE public health guidance, 2010).

Dietary regulation:

Moreover, dietary interventions are the most effective type of intervention in pregnancy in reducing gestational weight gain (Thangaratinam et al., 2012). Thus, following IOM recommendations, 45-65% of a pregnant woman’s energy intake should come from carbohydrates, 20-35% from fat and 10-35% from proteins (IOM 2002/2005).

According to the NICE (National Institute for Health and Care Excellence) guidelines, pregnant women should base their meals on starchy foods, eat at least five portions of vegetables and fruits each day and consume fibre-rich foods instead of foods rich in fat and sugar.

Future directions for research:

The effects of maternal over nutrition/diabetes/obesity exists as a vicious cycle for transgenerational transfer of obesity (fig. 5) and diabetes in next generation (Fig. 4) (Dabelea and Crume 2011). However, the specific likely mechanisms through which it operates remain unclear.

Studies and researches are necessary to understand the role and the pathways of maternal obesity that are involved in this cycle in developing offspring obesity. The effect of the postnatal environment and the interaction between fetal over nutrition and future obesity in childhood and adolescence also requires further study. Several longitudinal cohort studies starting from gestation and spanning through childhood and adolescence, such as ALSPAC (Lawlor et al., 2010), EPOCH (Crume et al., 2011), Project Viva (Oken et al., 2007) and the National Children’s Study (Landrigan et al., 2006) are needed to search and to provide the necessary platform for understanding and addressing these mechanisms and pathways related crucial questions.

Many randomized trials are needed to confirm the individual effect of each of the pregnancy associated medical conditions and their consequences on the offspring obesity. If this is achievable, it will help us in finding the ways to take interventions in breaking this vicious cycle of transgenerational obesity and probably result in reduction of the prevalence of obesity in the next generation (Dabelea and Crume 2011).

Conclusion:

Obesity has become one of the most attention seeking health challenges of the 21st century. The prevalence of adverse pregnancy outcomes is increased among overweight and obese women. Obese mothers give birth to heavier neonates who are more likely to be obese as children and are at greater risk of retaining this weight during adolescence. For all these reasons, it is very important that women should have normal weight when entering pregnancy and should keep an eye on their gestational weight gain within the recommended range according to the IOM guidelines of 2009. Obesity engenders obesity and the need to put an end to this vicious cycle is imperative. Nutritional counselling for establishment of a healthy and balanced diet, physical exercise and close monitoring of maternal weight pre conceptionally and throughout pregnancy can be useful weapons in our battle against the current epidemic of obesity.

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