Energy balance in pregnancy and lactation

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Pregnancy and lactation present many physiological challenges to the mother, which leads to physiological adaptations involving metabolism and hormone regulations to support foetal growth, parturition and lactation. Hormonal changes seem to occur in anticipation and preparation of increased energy expenditure and high metabolic demands of late pregnancy and lactation. In combination with increased in food intake (hyperphagia) during pregnancy is a decrease in energy expenditure and increase of fat mass.

Obesity is a modern epidemic which has been associated with several increased health risks from developing diabetes mellitus to cardiovascular problems. There is an increased probability of pregnancy leading to obesity in women. It is now realised that foetal pre-programming is affected by maternal obesity which can in turn increase the probability of the offspring being obese when older. Other complications during the antepartum, intrpartum and postpartum pregnancy stages have also been categorised in association with obesity and pregnancy.

An individual’s requirement for essential nutrients corresponds to the amount of food they consume in relation to his/her energy needs and a woman will have very different energy metabolism and energy requirements during pregnancy . When a woman becomes pregnant. she should have a consistent long-term good body size and composition, and should gain weight at a rate consistent with good health for herself and her child. The recommendations for energy intake for women vary depending on their background (population-specific) as they differ in body size and lifestyles. For example, the energy requirements are different for well-nourished women from developed countries compared to shorter women from developing countries.

Energy Metabolism

During pregnancy, women gain weight which comprises of the products of conception (foetus, placenta, amniotic fluid), the increases of various maternal tissues (uterus, breasts, blood, extracellular extravascular fluid), and the increases in maternal fat stores. Therefore the energy cost of maintenance (also known as the basal metabolic rate, BMR), as well as physical activity, increases as a result of the increased tissue mass.

This anabolic situation leads to a positive energy balance, although some pregnant woman may also have a negative energy balance. This is due to the numerous metabolic adjustments that occur during pregnancy and lactation to support both foetal growth and milk synthesis without disrupting maternal homeostasis which requires retention of fat and protein in the mother and foetus. These adjustments ensure that a constant supply of glucose and amino acids reach the foetus. Adjustments also occur for lactation ensuring the mammary gland is the main area of nutrient utilization.

Energy expenditure in pregnant vs nonpregnant women. Adapted from (Forsum 2007)

Energy is needed to synthesise the correct amount of fat and protein in new tissue and this consists of two components: 1. The energy in fat and protein retained in the body 2. The energy needed to synthesise these components. As it has been shown in figure 1 the total energy expenditure in pregnancy consists of four components including the energy costs for synthesizing the fat and protein retained.

Recent information on BMR has found that the average increase during the first, second and third trimesters was 4%, 10% and 24% respectively, although different women vary considerably. Women from developing countries showed a much smaller increase in BMR than those from developed countries, furthermore women with high prepregnant BMI values showed larger increases in BMR which indicates a possible increase in metabolic activity of adipose tissue in pregnancy. Data therefore show that a change in BMR during pregnancy is largely a function of maternal nutritional status.

Availability of substrates to the foetus

To sustain the foetus’ growth, the mother must continuously supply it with nutrients; most importantly, glucose and amino acids. Although the placenta is almost impermeable to lipids, other than free fatty acids and ketone bodies, lipid metabolism is highly affected during pregnancy. There are two key stages during gestation; the first corresponds to the first 2/3 of the pregnancy when the foetal growth is minimal and the mother stores a great proportion of the nutrients consumed, which along with her increased food intake causes fat store accumulation. The last trimester is when the foetus grows very rapidly which is sustained through nutrient transfer through the placenta which means the mother switches to a catabolic condition. Lipid stores in particular are broken down, and glucose is the most abundant nutrient that crosses the placenta at this point.

Energy requirements

The definition of energy requirements during pregnancy can be paraphrased as "The energy requirement of a pregnant woman is the level of energy intake from food that will balance her energy expenditure when the woman has a body size and composition and level of physical activity consistent with good health, and that will allow for the maintenance of economically necessary and socially desirable physical activity. In pregnant women the energy requirement includes the energy needs associated with the deposition of tissue consistent with optimal pregnancy outcome."

Changes of hormone interactions and appetite regulators during pregnancy and lactation

The mechanisms involved in appetite regulation during pregnancy and lactation appear to involve different neuronal pathways. Research involving hormone regulation of appetite during lactation is particularly vague. During pregnancy, changes in the expression of the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-like protein (AgRP), and induced leptin resistance contribute to increased appetite, while other mechanisms associated with offspring stimulation are thought to maintain hyperphagia during lactation .

Changes in orexigenic and anorectic neuropeptides during pregnancy

Research by Makarov et al. (2010) showed that both NPY and AgRP mRNA expression increases during pregnancy and decreases again after parturition. While NPY mRNA expression levels remained constant during the end of pregnancy, AgRP mRNA expression was shown to increase at the end of pregnancy, which may be responsible for constant increase in food consumption . During pregnancy, central injections of α-MSH do not decrease food intake, suggesting that a α-MSH resistant state is also maintained during pregnancy Studies using NPY knock-out (KO) mice showed that these mice have normal food intake during lactation . Mechanisms involved in increased food consumption during lactation appear to be stimulated by the suckling action of offspring. There is an observed connection between the PVN of the hypothalamus and the nipples, which suggests that neuronal activity received by the PVN from the nipples, activates appetite stimulating neuronal pathways . These orexigenic neuropeptide levels are shown to increase even in presence of elevated leptin during pregnancy.

Development of leptin and insulin resistance during different reproductive states

As previously stated, a beneficial adaptation of the female during pregnancy is to increase energy reserves which are needed to help meet the increased metabolic demands of foetal development and lactation . As a result of increased adiposity in the body, plasma leptin levels are elevated. Drattan et al. (2007) have shown that increased leptin levels during pregnancy are unable to suppress food intake via orexigenic neuropeptides in pregnant rats . Recorded increases in leptin levels during pregnancy is now thought to be necessary for regulating foetal growth and development . After parturition, leptin levels decrease and leptin sensitivity is recovered. Leptin insensitivity has been shown to develop during pregnancy as studies using pregnant rats at the beginning of gestation show a decrease in food intake in response to direct leptin infusion . Thus initial hyperphagia, induced by pregnancy, is thought to be caused by other hormonal changes which occur in the early stages of pregnancy. As obesity can be caused by leptin insensitivity and resistance within the hypothalamus, pregnancy may provide a new unique, leptin resistance model to investigate the underlying mechanisms of leptin resistance associated with obesity. As there is no evidence of a down regulation of leptin receptors in the arcuate nuclease during pregnancy, leptin resistance may be caused by an increase in specific sex hormones during early pregnancy.

Roles of prolactin, progesterone and placental lactogen in leptin resistance

Increases in food intake occur very early in pregnancy when the energy demands of the foetus are still low. This observation has lead to the investigation of the roles of sex hormones in leptin resistance and hyperphagia . It has been suggested that progesterone stimulates appetite and food intake in pregnant females, even in the presence of leptin . Prolactin surges during early pregnancy stimulate initial orexigenic responses which are thought to include the stimulation of progesterone secretion. Placental lactogen is then thought to maintain hyperphagia by increasing leptin levels. Recorded elevated leptin levels in the pregnant female are too slow to induce leptin resistance, hence it is assumed that prolactin and placental lactogen induce leptin resistance during pregnancy, although these mechanisms of action on leptin response are unknown . Studies using pseudopregnant rats have demonstrated that chronic prolactin infusion, used to mimic placental lactogen patterns during pregnancy, inhibit the action of leptin to suppress food intake .

The effects and problems associated with obesity during pregnancy

It is now well established that obesity has become a modern day epidemic throughout the developed and developing world. Obesity represents a major risk factor in pregnant and lactating women and has documented adverse effects on both pregnancy and the fetus. Alarmingly 35% of the women who died from maternal death had a BMI >30 according to the 'Confidential Enquiries into Maternal Deaths' . This section will examine the effects of obesity on each stage of pregnancy and lactation post-birth lactation.

The pathological effects of obesity on pregnancy and fetal outcome. Adapted from (Smith et al 2008)

Antepartum Implications

Antepartum refers to the period of pregnancy before birth. Obesity has numerous implications on this stage of pregnancy. General physiological examination, namely ultrasound and blood pressure measurement, is difficult to perform due to excess fat tissue. This lead to difficulties in assessing the state of fetus . Obesity has also been shown to irregulate menstrual cycles making estimation of delivery date difficult. Further complexities arise when performing preinvasive tests such as amiocentesis. Risk of miscarriage increases greatly after such tests in obese women. It was reported that fetal loss was 4.4% in women with BMI >25 compared to 1% in women with BMI <20 . Studies comparing normal weight women with obese women have also shown that there is an increased risk of neural tube defect in the fetuses of the obese mothers. This leads to increased incidence of cleft palate. . Pre-eclampsia is also tripled when BMI >30 due to the association of obesity with chronic inflammation, oxidative stress and insulin resistance . A further, well documented implication of obesity on the antepartum phase is increased incidence of gestational diabetes. The risk increases significantly with an increase in BMI due to increased impaired glucose intolerance. Moreover gestational diabetes develops earlier in pregnancy in obese mothers, resulting in delayed diagnosis and treatment. Incidence of gestational diabetes can be up to twenty times greater in women with BMI >30

Intrapartum Implications

The intrapartum phase of pregnancy refers to the period of giving birth. Like in the antepartum phase, physical examination is difficult in obese women. In obese women an ultrasound is usually performed to assess the presentation of the fetus prior to birth. In normal weight women this is done far more efficiently through abdominal assessment. Monitoring the heart rate of the fetus during birth, an essential procedure, is also challenging in obese mothers and involves the use of a fetal scalp electrode. This will immobilise the pregnant mother and increase the risk of thromboembolism. As a result obese women must adopt preventative measures for thromboembolism . The gestation period is often longer than forty weeks in obese women and this leads to increased rates of induced labour compared to normal weight women. Perhaps the greatest implication of obesity concerns contractions during childbirth. In vitro studies have indicated the myometrium of obese women is less contractile than in normal weight women. This is due to inhibition of contractions by leptin, which is released by increased adipose tissue . The inhibitory effect of leptin during childbirth leads to reduced frequency and amplitude of myometrium contractions and therefore an increased necessity for caesarean section in obese women. Rates of caesarean section have been reported as 31% in obese women compared to 22% in normal weight women . Performing a caesarean section on obese women is technically very challenging due to physiological reasons. These include the need for a deeper incision, difficulty in accessing the lower segment and a larger panniculus . Leptin inhibition could also explain the aforementioned need for increased induced labour in obese women. Obesity in pregnant women can lead to anaesthetic problems during childbirth. Cutaneous veins are often obstructed in obese women and this makes intravenous access either difficult. Longer needles are also required to reach the spinal and epidural space. These technical challenges mean an experienced senior anaesthetist is usually required .

Postpartum Implications

Emergency procedures, including caesarean section, are much more common in obese women compared to normal weight women. Post operative complications and increased morbidity following such procedures are linked strongly to obesity . Although rare, one of the greatest risks of pregnancy and puerperium (6 weeks following birth) is venous thromboembolism. Studies have shown that obese women are at a much greater risk of developing deep vein thrombosis and pulmonary embolism. Obese women must therefore undertake measure to prevent venous thromboembolism after giving birth during the puerperium period. Measures may include TED stockings and administration of low molecular weight heparin .

Implications of obesity on lactation

The impact of obesity on lactation is poorly understood in comparison to pregnancy. However it is established that obese women are much less likely to initiate lactation, that they have delayed lactogenesis II and are far more prone to early cessation of breastfeeding compared to normal weight woment . Interestingly black women, who have the highest obesity rates, possess the shortest duration of breastfeeding and lowest rates compared to white and hispanic mothers .

Conclusion

Numerous metabolic adjustments occur during pregnancy and lactation to support fetal growth and milk synthesis without jeopardizing maternal homeostasis. These changes ensure the correct nutrients reach the fetus during pregnancy. During lactation, these mechanisms promote preferential use of nutrients by the mammary glands.

The mechanisms involved in metabolic adjustments during pregnancy and lactation appear to engage neuronal pathways affecting appetite. Orexigenic NPY and AgRP mRNA expression increase during pregnancy and decreases again after parturition meeting these increased metabolic demands. Furthermore the high leptin levels during pregnancy are thought to be necessary for regulating foetal growth and development. This results in leptin resistance which is thought to be induced by prolactin and placental lactogen during early pregnancy.

Obesity has become wide spread and is a major risk factor in pregnant and lactating women and has also been shown to have adverse effects on the fetus. Difficulty estimating delivery date due to irregular menstrual cycles, problems performing preinvasive tests such as amniocentesis, increased incidence of cleft palate and a much increased risk of miscarriage are just some of the problems obese pregnant women might face. Furthermore, post pregnancy, obese women are much less likely to initiate lactation.