Complex relationships between maternal metabolic environment of the developing fetus and the potential influence of postnatal life style and environment have complicated the efforts to study the effects of maternal programming of overeating in humans.
A proposal to explain the link between maternal obesity and child obesity is the “overeating hypothesis". It states that hyperglycemia, increased levels of free fatty acids and amino acids cause permanent changes in appetite control, neuroendocrine functioning and/ or energy metabolism in the developing fetus, leading to the emergence adiposity risk (with risks of metabolic and cardiovascular disease) later in life [7
It is well known that the events in the womb have long-term influences on the risk of disease later in life. This phenomenon, known as “early life programming", has been extensively studied in relation to low birth weight, with the adjustment of the developing fetus in the womb (for example due to maternal malnutrition), in order to maximize the immediate chance of survival [8
]. These adaptations include permanent changes in structural axes, physiological and hormonal phenomenon of down-regulation of growth resulting low birth weight [9
Maternal obesity and overeating are now recognized as “programming factors".
Intrauterine growth restriction (IUGR) is an important public health problem in both industrialized and developing countries, leading to perinatal morbidity and long-term sequelae and mortality. The correct identification of IUGR has a great importance as the low weight of the newborn determines the specific conduct, surveillance as well as antenatal and postnatal care.
Obesity during pregnancy increases the risk for a number of complications for both the mother and child.
The recommendation for weight gain during pregnancy is of 11.2 - 15.9 kg (0.5-2.0 kg for the first trimester and 0.35 - 0.50 kg per week for the second and third trimesters) (
WHO Recommendations for the weight gained during pregnancy
Although there are strict recommendations for overweight and obese pregnant women to keep their weight gain to a minimum, women who are overweight before pregnancy are more likely to exceed the recommendations and have a higher risk of complications [11
Maternal obesity is associated with an increased risk of perinatal mortality and the occurrence of genetic disorders. The most common complications are the death of the fetus in utero, genetic disorders, macrosomia and intrauterine growth restriction [12
Fetal death is a dramatic result of any pregnancy, especially when it occurs late in the pregnancy. An increase of up to five times the risk of intrauterine death and increased infant mortality in obese women was recorded in some studies [13
]. Also there seems to be a correlation between maternal BMI and infant mortality [14
An explanation of the increased incidence of congenital anomalies in fetuses of obese women could be represented by the difficulties of interpretation of blood serum indices and failure to display fetal anatomy on the ultrasound. However, there is data to justify a real association between maternal obesity and genetic disorders. Specifically, fetuses of obese mothers have a higher risk of developing neural tube defects such as spina bifida, heart defects and abdominal wall defects such as omphalocele. These abnormalities are more common in children with mothers with diabetes mellitus type 2 and folic acid deficiency, disorders that often coexist with obesity.
Numerous studies have established the association between maternal obesity and insulin resistance weight before pregnancy and fetal health, concluding that they affect fetal growth [15
Obesity and insulin resistance modify the placental function, in the last weeks of pregnancy, increasing the availability of glucose, fatty acids and amino acids to the fetus [16
]. The induced fetal hyperglycemia as a result of maternal hyperglycemia leads to hypertrophy/ hyperplasia of the pancreas and fetal hyperinsulinemia. Insulin has a direct effect on cell division, resulting in macrosomia. Therefore, women with diabetes have an increased risk of macrosomia. Given that the prevalence of obesity is about ten times larger than gestational diabetes, it is obvious that the lifestyle of the mother exerts a great influence on the incidence of fetal macrosomia [17
A common etiology of intrauterine growth restriction is the placental pathology including placental insufficiency, anatomical abnormalities, such as corioamnionitis, hemangiomas, placental tumors, single umbilical artery, placental abruption and placenta praevia.
Fetal etiopathogenic factors are genetic defects, chromosomal and cardiovascular abnormalities, congenital infections and metabolic diseases [18
Maternal obesity is also associated with a significantly increased risk of low Apgar score at birth [19
In a Swedish study conducted on a sample of 189,783 children, a higher maternal BMI was associated with a higher risk of asthma; children with obese mothers are more likely to require medication and hospitalization for asthma at age 8-10 [20
]. Also, a study conducted on a sample of 6945 Finnish adolescents found that a high prepregnancy BMI indicates an occurrence of wheezing and asthma in children aged 15-16 years [21
Maternal obesity has also been linked to impaired brain development and behavioral changes in children. A study involving a total of 1,004 children found that 67% of obese mothers were more likely to have a child with an autism spectrum disorder, diagnosed with standardized assessments, and twice as likely to have a child with a developmental delay [22,23
]. Another study conducted on a sample of 1714 children aged 5 years has shown that obese patients with obese mothers are more likely to develop symptoms of attention deficit hyperactivity disorder (ADHD), lack of concentration and difficulty regulatory emotionality as reported by kindergarten teachers and mothers using a list of DSM-IV symptom-derived [24,25
]. Further studies are needed to determine whether these possible negative effects of maternal obesity on brain function of children persist in adult life.
In any human study, although factors related to lifestyle, such as the current level of obesity, behavior, activity and diet are often considered as confounding factors in the statistical analysis, it is almost impossible to separate pre- and postnatal influences on children's outcomes [26-28
]. Also, common maternal genes that influence the risk of obesity of children should be considered.
Studies in siblings were used as an attempt to separate the intrauterine events from environment and genetic factors, and a recent study showed an independent influence of maternal obesity and weight gain during pregnancy on children, especially among women obese [29
The numerous studies conducted on different populations emphasize the association between intrauterine growth restriction and peri and postnatal evolution as differing depending on fetal sex. And, although intrauterine programming mechanisms are still unclear and the involvement of other factors and results of the studies are controversial, it seems that the female gender is more likely to develop intrauterine growth restriction [30
Perhaps, more evidence of maternal obesity on children's programming comes from a study that used a group of mothers who had undergone surgery for obesity [31
]. The authors were able to observe the long-term effects. Children born before their mothers had undergone biliopancreatic diversion (BPD) for obesity had significantly higher body weights at 12 and at 21 to 25 years than children born after surgery. Thus it supports the hypothesis that obesity has long-term influences on children's weight and BMI independent of genetic, environmental and lifestyle. However, it is likely that dietary changes made by these mothers have influenced postoperative diet and lifestyle of children born after surgery.
In conclusion, maternal obesity is a serious health risk for the fetus, the impact increasing according to the degree of obesity. A non-balanced diet during pregnancy not only contributes to the abnormal development of the fetus and the subsequent increase in the neonatal morbidity and mortality, but also to increased morbidity during childhood, adolescence and adulthood. Due to the difficulties in identifying, monitoring these fetuses, prenatal as well as postnatal, and because of the increased perinatal mortality and morbidity associated intrauterine growth restriction (IUGR) remains a serious multidisciplinary problem.
A systematic effort to reduce weight is imperative to avoid transmission of obesity from generation to generation. Achieving this goal will most likely result in a sharp decrease in fetal and neonatal morbidity and mortality and improve outcomes followers and future pregnancies.
Disclosure: None of the authors have a conflict of interest.
This paper is supported by the Sectoral Operational Programme Human Resources Development (SOP HRD) 2007-2013, financed from the European Social Fund and by the Romanian Government under the contract number POSDRU/107/1.5/S/82839.