Proposed mechanisms for the effect of maternal obesity on the onset of lactogenesis II
Emma Sickles, Kinsey Michael, Moriyah Cope
Department of Food Science & Human Nutrition; Colorado State University Fort Collins, CO
Objectives
Introduction and Background
Proposed Mechanisms
Implications and Conclusions
Related Nutrients
Re
Abstract
Spring 2018
Women who are obese prior to entering pregnancy may have increased adipose tissue and insulin resistance. This results in hormone imbalances which disturb the onset of lactogenesis II, or copious milk production.1,2,3,4,5 The delay in milk production causes many mothers to feed their infant with formula instead of breast milk. The benefits of breastfeeding for both mother and infant have been well documented.6 Thus, it is important for health care providers to encourage women to achieve a healthy pre-pregnancy weight in order to breastfeed for the recommended amount of time. The purpose of the poster is to inform readers of the proposed mechanisms behind the observed delay of lactogenesis II in obese mothers, to explain the importance of achieving healthy pre-pregnancy body weight, and to reiterate why breastfeeding is beneficial for the mother and infant.
The significant results and evidence from our research indicate that hormonal imbalances and insulin resistance are the major proposed mechanisms for delayed milk production in obese mothers. There is an observed decrease in the prolactin response to suckling in obese mothers, and a decrease in the gene expression of cells in mammary glands which are important for milk production.7,5 The evidence suggests that the delay of milk production in obese mothers results in using formula exclusively instead of breast milk, which is not as beneficial for the mother or infant.3,6 More research should be done to explore other potential physiological mechanisms for the delay of lactogenesis II, as well as the impact of underlying psychological and social factors on milk production.
Many obese mothers have delayed onset of milk production (lactogenesis II), resulting in decreased duration and initiation of breastfeeding and increased supplementation with infant formula.3,8 Breastfeeding has been proven to be beneficial for both the mother and the child. The World Health Organization (WHO) and the American Association of Pediatrics recommend exclusive breastfeeding for at least six months postpartum.6,9 Breast milk provides micronutrients and macronutrients that the child needs to thrive. It also provides powerful antibodies to fight infection, and may reduce the child’s risk of having asthma or allergies.9 Breastfeeding also provides many benefits for the mother. It can help the mother expend more energy to return to prepregnancy weight and is protective against both breast and ovarian cancers.10,11
The prevalence of obesity among women of reproductive age has been increasing worldwide. According to the 2014 National Vital Statistic Reports for the United States, 25.6 % of these women were overweight and 24.8% were obese.12 Obesity can have many adverse side effects on the mother and child. The mother is at an increased risk for developing gestational diabetes, preeclampsia, heart disease, and hypertension. The child is at increased risk for stillborn birth, congenital abnormalities and future obesity and heart disease.13 Thus, entering pregnancy at a healthy weight encourages better health outcomes for mothers and their children.
Studies show that lactogenesis II can be delayed by physiological mechanisms related to obesity.2 A delay is considered to be no sign of milk production or breast “fullness” for more than 72 hours after birth.1 In normal weight women the onset of lactogenesis II is triggered by the reduction of progesterone in the body, and increases in the hormone prolactin. Progesterone normally falls about 24-40 hours after birth, allowing for increased and sustained concentrations of prolactin.4 Prolactin is released from the anterior pituitary to stimulate milk production in response to suckling by the infant. The posterior pituitary releases another hormone, oxytocin, which stimulates contraction of the cells in the alveoli to release milk from the breast [Figure 1].14 Another hormone involved in milk production is insulin, which regulates the genes expressed in mammary glands.5 In obese mothers, the hormones in this system become either imbalanced or improperly regulated due to decreased prolactin response to suckling and insulin resistance, which are thought to be the main causes for the delay in copious milk production.
A pre-pregnancy BMI of ≥ 30 kg/m2 is considered obese and can lead to many unfavorable outcomes during and after pregnancy such as delivery complications, development of type II diabetes, heart disease, and adverse health impacts on the infant.23 One of the negative outcomes of entering pregnancy with a pre-pregnancy BMI of ≥ 30 kg/m2 is the delay of lactogenesis II. The delay in the onset of copious milk production makes exclusive breastfeeding difficult and increases the risk that the infant will receive supplemental formula. The American Association of Pediatrics recommends that infants are breastfed exclusively for the first 6-months of life without supplementation from formula for optimal health outcomes.9 The CDC recommends that women thinking about becoming pregnant reach a healthy weight through proper diet and exercise before becoming pregnant.23 Attaining a healthy pre-pregnancy BMI will promote better health outcomes for the mother and infant.
In order to reach a healthy pre-pregnancy BMI, women who are overweight or obese should follow recommendations from the 2015-2020 Dietary Guidelines for Americans and the 2008 Physical Activity Guidelines for Americans. Key recommendations from the Dietary Guidelines include eating a variety of fruits and vegetables, whole grains, lean proteins, healthy fats, and low-fat dairy products. The guidelines also suggest limiting calories from added sugars and saturated fat.24 It is best to consult with one’s doctor before drastically changing your level of activity to ensure your health and safety. Generally, adults should engage in muscle-training activities twice a week, intense aerobic activities for at least 75 minutes per week, and moderate aerobic activities for at least 2.5 hours per week.24 The CDC recommends an average weight loss of 1-2 lbs per week until a healthy weight is reached (BMI 18.5-24.9).23 Talk with your doctor and/or dietitian about your plan to make diet and exercise changes before implementing any of them.
During lactation, women can promote healthy breastfeeding through nutrition. It is recommended that women consume an extra 330 calories/day during the first 6 months of breastfeeding. Women should also eat 1.1g/kg of body weight of protein per day. It is important to consume adequate amounts of DHA, EPA, and 3.8 L/day of water.26 Other vitamins and minerals can be obtained in adequate amounts through a varied diet.27
The incidence of overweight and obesity in women of reproductive age is concerning for many reasons. Obesity is linked to adverse maternal and infant health outcomes.12,13 Women who enter pregnancy at a BMI of ≥ 30 kg/m2 are at an increased risk for gestational diabetes mellitus, preeclampsia, hypertension, and delivery complications.28 The reason we have most thoroughly discussed in this analysis is the observed delay of lactogenesis II in obese mothers. Increasing incidence of overweight and obesity could indicate that more mothers will experience a delay in lactogenesis II in the future.
Multiple mechanisms have been proposed to explain this phenomenon. Obese mothers experience decreased prolactin concentrations in response to infant suckling compared to mothers of healthy weight.7 In obese women, excess adipose tissue may concentrate progesterone in the body, which may block the signal to synthesize and release prolactin. There is inconclusive evidence about whether the progesterone concentrations between obese and normal weight women differ, so more research should be conducted to determine if progesterone plays a part in inhibiting the prolactin response. Another mechanism that might disrupt lactogenesis II is obesity-related insulin resistance. Insulin resistant individuals have been shown to have a disruption in the inulin signaling pathway which results in failure to stimulate gene expression in the mammary glands. The disruption in gene expression causes delayed milk production and decreased output.5,17,18
Due to the obesity-related delay of lactogenesis II, many women will initiate formula feeding as it is necessary to quickly feed the infant after birth.29 Obese mothers are often unable to initiate breastfeeding for more than three days after they give birth, while women who enter pregnancy at a healthy body weight are often able to initiate breastfeeding between 50-72 hours after delivery.3,8 Formula feeding does not provide the numerous benefits of breastfeeding for the infant or the mother. In terms of maternal health, lactation increases energy expenditure which supports postpartum weight loss for obese and overweight mothers.11 In addition to this, it is known that breastfeeding decreases the mother’s long-term risk for breast and ovarian cancers.10
Although more research should be done to fully understand and identify the mechanisms which cause the observed delay of lactogenesis II in obese individuals, maintaining a healthy weight before pregnancy decreases the risk that breast milk production will be delayed. While the CDC recommendations and dietary guidelines can be used as a guide, consumers are encouraged to visit their healthcare provider or dietitian for the best recommendations for attaining a healthy body weight before entering pregnancy.
References
Proposed Mechanism 2: Insulin
Another proposed mechanism for the delay in lactogenesis II in obese mothers relates to the hormone insulin. Obesity is known to cause insulin resistance; this resistance may be one of the causes of delayed onset of lactogenesis II. Insulin and the insulin signaling pathway are thought to be involved in the regulation of genes expressed in mammary glands during lactation. It has been shown that mice without insulin receptors in their mammary glands experienced downregulation of genes involved in differentiation of mammary cells and milk synthesis.5,17 In 2013, the PTPRF gene, the gene that codes for the enzyme protein tyrosine phosphatase receptor-F, was found to be overexpressed in the mammary glands of mothers with decreased insulin sensitivity.18 Similarly, other studies found that obese, insulin resistant individuals had increased expression of PTPRF.19,20 PTPRF is a protein that is involved in inhibiting the insulin signaling pathway; it inhibits the activation of the insulin receptor through dephosphorylation of the tyrosine kinase domain (located on the insulin receptor).21 In healthy individuals, PTPRF plays an important role in the regulation of the body’s response to insulin. In insulin resistant individuals, the PTPRF gene has been shown to be upregulated. Overexpression of the PTPRF gene is thought to contribute to the pathogenesis of insulin resistance [Figure 3].22,21 Insulin resistance may disrupt the transcription of genes regulated by the insulin signaling pathway that are important for milk production.5,17 This disruption results in a slower and decreased milk output in response to the stimulus of a suckling infant.
Figure 3: PTPRF is an insulin-signaling pathway inhibitor. The insulin signaling pathway is important for the stimulation of gene expression, cell survival, and protein synthesis. The diagram above depicts the consequence of the overexpression of the PTPRF gene. When the gene is upregulated, there is an increase in the presence of PTPRF which is thought to inhibit the insulin signaling pathway which disrupts the aforementioned cell functions.
Citation: de Lorenzo C, Greco A, Fiorentino TV, Mannino GC, Hribal ML. Variants of insulin-signaling inhibitor genes in type 2 diabetes and related metabolic abnormalities. Int J Genomics. 2013;2013:376454.
Proposed Mechanism 1: Prolactin
Prolactin is one of the main hormones needed to produce milk when breastfeeding. During pregnancy, it is suppressed by the high concentrations of progesterone secreted by the placenta. When levels of these hormones decrease due to excretion of the placenta at birth, lactogenesis II can begin.7,2,15,16 One study found that obese mothers had decreased prolactin concentrations in response to suckling 48 hours after birth [Figure 2].7 The study showed that by seven days after birth, the mothers’ prolactin levels returned to normal; however, the first few days are shown to be the most important for initiating milk production.7 In fact, it is known that milk removal by the infant should occur by day three in order for the continuation of milk production.16 The lower prolactin concentrations were thought to be caused by increased adipose tissue in obese women.7,2 Adipose tissue is thought to concentrate progesterone; it was proposed that the higher concentrations of progesterone delay prolactin’s ability to stimulate milk production. However, when the progesterone concentrations between normal weight and obese women were measured, they were not significantly different between two and seven days.7 Thus, the reason that obese women have decreased prolactin responses to suckling remains unknown. However, the distinct hormonal imbalances caused by obesity are thought to be one of the reasons for delayed milk production and secretion.
Figure 2: Compares the prolactin response in ng/ml to suckling at two and seven days postpartum between normal-weight and overweight/obese women. They observed lower prolactin concentrations in response to suckling obese women compared to normal-weight women at 48 hours. There was still some difference at 7 days, but the response had normalized some.
Citation: Rasmussen KM, Kjolhede CL. Prepregnant overweight and obesity diminish the prolactin response to suckling in the first week postpartum. Pediatrics. 2004;113:465–71.
Figure 1: Depicts the signalling pathway which results in milk production and ejection.
Citation: VanPutte C, Regan J, Russo A. Lactation. brainkart.com. http://www.brainkart.com/article/Lactation_22009/. Published June 8, 2017. Accessed March 6, 2018.