**6. Long-term effects of fetal environment for offspring**

32 From Preconception to Postpartum

industrialized countries is not, in all probability, a result of environmental factors such as periodic food shortages and malnutrition; therefore, one must consider it an expression of constitutional low weight or a result of cosmetically induced starvation. Excessive thinness has been glamorized among reproductive aged women, and unhealthy dieting to lose weight has become a popular practice in that age group. Body image in younger women is susceptible to societal influence through mass media, such as television, movies, and

Low prepregnancy BMI and low GWG have been associated with the delivery of smaller infants. There is strong evidence for an association between weight gains below the IOM guidelines and the risk of having an SGA infant ( Nielsen et al., 2006; Park et al., 2011). In a study undertaken of 26,028 women in California, those with gestational weight gains below the IOM guidelines had a significantly higher risk of SGA infants when compared with women with a weight gain above IOM guidelines, adjusting for prepregnancy BMI (Park et

Similar results were also observed in a study among Swedish women with singleton fullterm births. The risks for SGA were higher when gaining <8 kg (95% CI: 1.68-2.35) and lower when gaining >16 kg (95% CI: 0.50-0.61) (Cedergren, 2006). Merchant et al. (1999) reported lower mean birth weights of newborns among Pakistani women with prepregnancy BMI<19 kg/m2 who gained >12.5 kg compared to those who gained 12.5 kg. Women in the lowest quartile for both prepregnancy BMI and GWG were 5.6 times more likely to have intrauterine growth restriction (IUGR) infants, compared to women in the upper quartile (Naidu & Rao, 1994). The research among 3,071 Japanese women who gave birth to single-term infants found that underweight women were 1.7 times and 1.5 times more likely to give birth to a SGA or LBW infant, respectively (Watanabe et al., 2007).

Current evidence indicates that GWG, particularly during the second and third trimesters, is an important determinant of fetal growth (Althuizen et al., 2006; Kaiser et al., 2008). Inadequate weight gain during these trimesters is associated with an increased risk of LBW or IUGR. Health care providers should give women individual graphs of their weight gains at each antenatal check up, having viewed valuable sources of information on diet and nutrition.

The mean birth weight has continuously increased in United States, Canada, Europe, and Asia (Kramer et al., 2002). In Australia, LGA births have increased from 9.2% to 10.8% in male infants and from 9.1% to 11% in female infants from 1990 to 2005 (Hadfield et al., 2009). The 25% to 36% increase in maternal BMI over the past decade has translated to approximately a 25% increase in the incidence of newborns with high birth weight (Surkan et al., 2004). The possible reason may be increased maternal body weight and/or excess weight gain during pregnancy beyond the recommended IOM guideline. Strong evidence confirms the association

However, an increase in GWG eliminated or reduced the incidence of SGA.

between excessive GWG and increased birth weight in all BMI categories.

infants IOM and

**5. Influence of prepregnant BMI and GWG on birth weight** 

magazines.

**5.1 SGA infant** 

al., 2011).

**5.2 LGA infant** 

Many animal models have demonstrated that altering the environment in utero leads to lifelong consequences, such as high blood pressure (Mamun et al, 2009), impaired glucose tolerance (Fraser et al., 2010), insulin resistance (Ozanne & Hales, 1999), and altered hepatic architecture and function (Ozanne et al., 2001). Population-based prospective cohort studies starting from different geographical regions in the preconception period or in early fetal life and following the offspring from early fetal life until young adulthood seem to be the most suitable epidemiological design (Geelhoed & Jaddoe, 2010; Jaddoe & Witteman, 2006) (Fig. 3).

There is now increasing evidence supporting the effect of the in utero environment on the development of obesity and risk factors for adult diseases (Ong, 2006; Pettitt & Jovanovic, 2007). Epidemiological studies confirm that the relationships between human birth weight and adult obesity, hypertension, or insulin resistance are U-shaped curves rather than inverse linear associations over a full range of birth weight distributions (Barker, 1998) (Fig. 4). That is, children born at both the lower - classified as SGA - and the upper – classified as LGA – ends of the birth weight spectrum are at risk of obesity and, subsequently, a range of adult diseases in later life.

Source; Reference [Geelhoed & Jaddoe, 2010; Jaddoe & Witteman, 2006]

Fig. 3. Models for studying the fetal origins of adult diseases hypotheses in epidemiological studies.

The Effect of Prepregnancy Body Mass Index and Gestational Weight Gain on Birth Weight 35

High birth weight and LGA infants are prone to induce neonatal complications (Das & Sysyn, 2004) and to developing insulin resistance (Giapros et al., 2007), obesity, and diabetes in later life (Boney et al., 2005; Dietz, 2004). LGA infants have increased fat mass at birth compared with AGA infants (Armitage et al., 2008). McCance et al. (1994) examined birth weight and diabetes in later life among Pima Indians. Diabetes rates among persons with high birth weight (≥4500 g) were almost twice as high as among those with a birth weight between 2,500 and 4,500 g. Similar findings were observed in a meta-analysis where infants with high birth weight (>4,000 g) had 1.36 times higher (95%CI: 1.07-1.73) incidence of type

Furthermore, a recent study has shown that obese women have a high risk for gestational diabetes mellitus, providing a future risk for type 2 diabetes mellitus (Catalano et al., 2009). Diabetes in pregnancy that results in high birth weight and early onset of diabetes in the offspring represents a vicious cycle (Knowler et al, 1990), with the offspring of women who had diabetes during pregnancy being very likely to have already developed diabetes by the time they reach their childbearing years. Boney et al. (2005) conducted a longitudinal cohort study to determine whether children who were LGA at birth and offspring of mothers with or without gestational diabetes mellitus were at increased risk for developing the metabolic syndrome in childhood at age 6 to 11 years. They found that children who were LGA at birth and exposed to an intrauterine environment of either diabetes or maternal obesity

Birth weight is an important predictor in infant mortality and morbidity, growth, development, and wellbeing in adult life. Women with a normal prepregnancy BMI and within the adequate range of GWG associated with minimal risk for SGA and LGA have better pregnancy outcomes in both mothers and infants, for short- and long-term health. However, nearly two thirds of reproductive-aged women are currently overweight or obese. On the other hand, the number of women with BMI below 18.5 has increased in some countries. In addition, only 28% of women actually adhere to the guidelines for optimum

Prepregnancy BMI and pregnancy weight gain reflect maternal nutritional status before and during pregnancy; this status plays a crucial role in creating an optimal intrauterine environment. Understanding the relationship between maternal nutrition and birth outcomes may provide a basis for developing nutritional interventions that will improve birth outcomes and long-term quality of life. All women of reproductive age should be encouraged to follow the government recommendations and eat a well-balanced diet. A critical goal for women is to make behavior changes to achieve good nutritional status

Althuizen, E.; van Poppel, M.N.; Seidell, J.C.; van der Wijden, C. & van Mechelen, W. (2006).

Design of the New Life (style) study: a randomized controlled trial to optimize maternal weight development during pregnancy. *BMJ Public Health*, Vol. 6: 168.

before, during, and after conception, which may lead to improved birth outcomes.

2 diabetes in later life than normal birth weight (2,500-4,000 g) infants did.

were at increased risk of developing metabolic syndromes.

birth weight; over half gain in excess of the recommended weight gain.

**7. Conclusion** 

**8. References** 

**6.2 The consequence of being LGA** 

Source; Reference [Barker DJ, 1998]

Fig. 4. Hypothesized U-shaped relationship between offspring birth weight and risk for postnatal adverse health outcomes

#### **6.1 The consequence of being SGA**

LBW and SGA infants are at risk for hypertension, cardiovascular disease, insulin resistance, and diabetes mellitus type 2 in adult life (Saenger, 2007). A recent systematic review of the literature relating to the birth weight/type 2 diabetes relationship noted that for every onekg increase in weight at birth, the risk of diabetes in adulthood decreased by 25% (OR 0.75, 95%CI: 0.70-0.81) (Whincup et al., 2008). In an Indian study of young adults, which followed up at birth and every six months until the age of 21 years, plasma glucose concentrations and insulin resistance were inversely related to birth weight, and impaired glucose tolerance and diabetes were associated with lower weight and BMI at the age of 1 year, after adjusting for adult BMI (Bhargava et al., 2004).

Studies linking birth weight to kidney disease and hypertension in adulthood have also been reported. LBW infants have lower kidney weight with a decreased number of nephrons, which indicates that hypertensive patients have lower nephron numbers (Hughson et al., 2003). A histomorphometric study observed a 13% decrease of nephron number in LBW infants (Manalich et al., 2000). Schmidt et al. (2005) investigated kidney length or volume in early life in SGA infants compared to AGA infants. They found that being SGA was associated with small kidneys at birth and impaired kidney growth in early childhood. Hotoura et al. (2005) compared SGA infants with a gestational age of 31 to 36 weeks with a control group of AGA infants. They reported that SGA infants had shorter kidney length at birth compared with AGA infants. Similar findings were observed in the SGA term infant, but the association disappeared in later childhood (Giapros et al., 2006).

In addition, a recent study reported that SGA was associated with adult psychological disorders. Children born full term but weighing 2,475 g had increased psychological distress in later life, and a 1SD decrease in birth weight for gestational age was associated with increased psychological distress in adulthood ( Wiles et al., 2005).

#### **6.2 The consequence of being LGA**

34 From Preconception to Postpartum

Fig. 4. Hypothesized U-shaped relationship between offspring birth weight and risk for

LBW and SGA infants are at risk for hypertension, cardiovascular disease, insulin resistance, and diabetes mellitus type 2 in adult life (Saenger, 2007). A recent systematic review of the literature relating to the birth weight/type 2 diabetes relationship noted that for every onekg increase in weight at birth, the risk of diabetes in adulthood decreased by 25% (OR 0.75, 95%CI: 0.70-0.81) (Whincup et al., 2008). In an Indian study of young adults, which followed up at birth and every six months until the age of 21 years, plasma glucose concentrations and insulin resistance were inversely related to birth weight, and impaired glucose tolerance and diabetes were associated with lower weight and BMI at the age of 1 year, after adjusting

Studies linking birth weight to kidney disease and hypertension in adulthood have also been reported. LBW infants have lower kidney weight with a decreased number of nephrons, which indicates that hypertensive patients have lower nephron numbers (Hughson et al., 2003). A histomorphometric study observed a 13% decrease of nephron number in LBW infants (Manalich et al., 2000). Schmidt et al. (2005) investigated kidney length or volume in early life in SGA infants compared to AGA infants. They found that being SGA was associated with small kidneys at birth and impaired kidney growth in early childhood. Hotoura et al. (2005) compared SGA infants with a gestational age of 31 to 36 weeks with a control group of AGA infants. They reported that SGA infants had shorter kidney length at birth compared with AGA infants. Similar findings were observed in the SGA term infant, but the association disappeared in later childhood

In addition, a recent study reported that SGA was associated with adult psychological disorders. Children born full term but weighing 2,475 g had increased psychological distress in later life, and a 1SD decrease in birth weight for gestational age was associated with

increased psychological distress in adulthood ( Wiles et al., 2005).

Source; Reference [Barker DJ, 1998]

postnatal adverse health outcomes

**6.1 The consequence of being SGA** 

for adult BMI (Bhargava et al., 2004).

(Giapros et al., 2006).

High birth weight and LGA infants are prone to induce neonatal complications (Das & Sysyn, 2004) and to developing insulin resistance (Giapros et al., 2007), obesity, and diabetes in later life (Boney et al., 2005; Dietz, 2004). LGA infants have increased fat mass at birth compared with AGA infants (Armitage et al., 2008). McCance et al. (1994) examined birth weight and diabetes in later life among Pima Indians. Diabetes rates among persons with high birth weight (≥4500 g) were almost twice as high as among those with a birth weight between 2,500 and 4,500 g. Similar findings were observed in a meta-analysis where infants with high birth weight (>4,000 g) had 1.36 times higher (95%CI: 1.07-1.73) incidence of type 2 diabetes in later life than normal birth weight (2,500-4,000 g) infants did.

Furthermore, a recent study has shown that obese women have a high risk for gestational diabetes mellitus, providing a future risk for type 2 diabetes mellitus (Catalano et al., 2009). Diabetes in pregnancy that results in high birth weight and early onset of diabetes in the offspring represents a vicious cycle (Knowler et al, 1990), with the offspring of women who had diabetes during pregnancy being very likely to have already developed diabetes by the time they reach their childbearing years. Boney et al. (2005) conducted a longitudinal cohort study to determine whether children who were LGA at birth and offspring of mothers with or without gestational diabetes mellitus were at increased risk for developing the metabolic syndrome in childhood at age 6 to 11 years. They found that children who were LGA at birth and exposed to an intrauterine environment of either diabetes or maternal obesity were at increased risk of developing metabolic syndromes.
