May 18, 2024

Postpartum Period- Physiology

Introduction

As soon as the placenta is separated from the uterine wall and is expelled, major maternal physiological changes occur. Right away estrogen and progesterone levels plummet precipitously. A protein hormone, oxytocin surges along with another hormone, prolactin. The uterine muscles strongly contract. These contractions constrict the placental bed containing blood vessels that had penetrated into the uterus and close them so that there is no hemorrhage. Since there three muscle layers----longitudinal, circular and oblique these contractions close the vessels from all directions. If the uterus does not contract the organ relaxes and serious hemorrhage occurs leading to a significant blood loss in short time frame. If this hemorrhage cannot be controlled death will happen. Thus, doctors and midwives pay close attention to how contracted the uterus is and often message the uterus to make certain that it stays firm and tight.

In the past it was thought that all physiological alternations of pregnancy changed to the prepregnant by six to eight weeks after birth. Now we know that this is not what happens normally. The postpartum period lasts much longer and it will be as long  as six months to a year before all body systems are back to a completely non-pregnant state. This postpartum period has three distinct phases (1). The first phase begins at delivery when estrogen and progesterone levels drop, the second phase ends three to six weeks later while a delayed phase ends when all the organ systems return to their prepregnant state. What follows is a short summary of  some of these changes.

Uterine involution

During pregnancy the uterus increases to 500 times from its prepregnant state. Recall that the uterus undergoes hypertrophy meaning that the muscle cells become larger as well as hyperplasia where the cells themselves proliferate by cell division. The extracellular matrix, the substance between all cells the hold them together, grows by the secretion and accumulation of new molecules, particularly collagen, elastin and glycosaminoglycans. In order to involute to a normal size the uterus must eliminate much of this accumulated extracellular matrix. This happens because an influx of leukocytes, monocytes and macrophages into the uterus occurs. Multiple enzymes are released to degrade the not needed cells and extracellular proteins. This influx of cells is a tissue remodeling inflammatory reaction. It is not an infectious process but one that remodels tissue by breaking it down and allowing for the elimination  of the breakdown products by autophagy (2) or in some species by apoptotic cell death (3). In humans several studies indicate that this elimination occurs by autophagy while in other species such as the rat it occurs by apoptosis. Usually, this process is completed by the sixth week postpartum,  However, it many individuals it will occur over a longer time frame. And there are differences between first and subsequent pregnancies. Uterine involution can be evaluated by ultrasound methods (4,5).

Onset of lactation

The human breast becomes functionally and anatomically mature at the end of pregnancy (6).  The process of lactation causes changes in maternal metabolism. During gestation the breast ducts proliferate and glands enlarge. The first stage of lactogenesis occurs in the second half of pregnancy (6). Often colostrum, the first breast secretion may be produced in small amounts during this time. After birth the second stage of lactation is initiated. Colostrum is the first secretion of the breast and contains immunoglobulins, growth factors, antimicrobial factors and antioxidants that promote the newborn’s immunity as well as providing nutrients during the first days after birth. Colostrum is secreted for the first two to three days and is then replaced by milk. Human milk composition changes from day to day to respond to the nutritional needs of the infant. The percentage of milk protein and fat, important components of milk vary from day to day. The second stage of lactogenesis  is under hormonal and mechanical stimuli (6). The immediate decrease in progesterone levels accompanied by an increase in prolactin, cortisol and insulin simulate the breast to secrete milk (7.) Prolactin is produced and released by the anterior pituitary gland. Oxytocin, secreted by the posterior pituitary gland is responsible for the letdown reflex or milk ejection reflex whereby the milk fills the breast and flows out. Milk production is maintained by nipple stimulation and suckling of the newborn. The suckling of the infant stimulates sensory nerves in the nipple and the areolar area surrounding the nipple, leading to the further secretion of prolactin and oxytocin (6). Other factors involved in the physiology of milk  production are human placental lactogen and human chorionic gonadotropin.

For lactation to occur properly mastitis (infection), plugged ducts, and nipple pain that occurs if the infant has not latched onto the breast correctly must be prevented. For this reason, new breastfeeding mothers need to have a person experienced in how to successfully breastfed available to help and teach prevention of these problems and how to treat them if they occur. When the time comes to wean the infant the processes in the body leading to milk production cease. It is wise to carry out weaning gradually by slowly eliminating feedings. For those who do not desire to breast feed or who cannot do so for work or other reasons, the milk production  will cease fairly rapidly. The metabolic demands of breastfeeding are such that the mother needs at least 500 additional calories daily. The levels of hormones in the blood often do not return to the prepregnant state until the end of breastfeeding.

Please be aware, it is possible for transgendered men to become pregnant after female to male transition and to produce milk to feed their infants. The community calls this chest feeding rather than breastfeeding. That is appropriate. In carrying  for pregnant transgender men, it is important to refer to pregnant people. As a clinician that is how I would refer to a transgendered man who chooses to have a pregnancy and birth.  At the same time, we need to be sensitive that there are many individuals who are not comfortable with this terminology and it is equally important to understand that.  For this reason, I often chose to use the term pregnant woman when writing public educational articles.

Postpartum Thyroid Alterations

During pregnancy thyroid homeostasis is altered. There is a very large decrease in the serum concentration of thyroid binding globulin that occurs following the rise in estrogen. As a consequence, triiodothyronine (TT3) and tetraiodothyronine (TT4) increase. Thyroid stimulating hormone (TSH decreases in the first trimester due to the presence of human chorionic gonadotropin (HCG).  Free T3 and free T4 decrease in the first trimester but rise in the second and third trimester. After birth these alterations slowly return to nonpregnant levels. This is not a rapid transition but takes place over around a six-week period.  However, after birth, or in other situations such as miscarriage, somewhere between five to ten percent of individuals will develop antithyroid antibodies that will cause postpartum thyroiditis. Risk factors for the development of postpartum thyroiditis are type 1 diabetes and/or a history of thyroid conditions previously or among family members. Postpartum thyroiditis usually is seen in three phases. The first phase occurs one to three months after the end of pregnancy and is a hyperthyroid state. The symptoms are anxiety, weight loss, hair loss and a rapid heart rate. Treatment to counteract these symptoms should be given. With time, usually in four to eight months, a hypothyroid state is seen. During this time fatigue, weight gain, dry skin, constipation muscle pain and cold intolerance along with depression occur.  If breastfeeding, lactation is diminished. During this stage thyroid hormone replacement is prescribed. Finally, in phase three the thyroid function becomes normal in eighty percent of persons with postpartum thyroiditis. Roughly twenty percent or perhaps more will have persistent hypothyroidism and will need long-term thyroid replacement therapy. The diagnosis of thyroid disease in the postpartum year can be subtle. Sometimes individuals or their family attribute their symptoms to simply the normal physiology of the postpartum year with the result of not seeking care.  One of the symptoms is depression which is a serious condition and must not be ignored (8).

Postpartum Cardiovascular Changes

Right after birth the circulatory blood volume increases due to the fact that the uterus strongly contracts, closing off the placental bed vessels as noted previously. The birth of the infant relieves the pressure of the fetus on the maternal inferior vena cava. Thus, the cardiac stroke volume increases and maternal heart rate rises resulting in a sixty to eighty percent increase in cardiac output.(9) The rapid increase in these parameters will decrease to pre-labor values within one to two hours following birth. By two weeks after birth these are reduced to prepregnant levels. During pregnancy systemic vascular resistance decreases with a return to prepregnant levels two weeks after birth. The decrease in systemic blood pressure observed in pregnancy begins to rise in the third trimester, but non pregnant levels do not occur until 16 weeks postpartum. Maternal heart rate which increases over time during pregnancy to as much as 20 beats per minute higher than before gestation returns to its pregnant rate by 6 weeks. Finally current research finds that a physiological cardiovascular hypertrophy returns to its original state by the 4th weeks postpartum (9).  A serious but rare complication – peripartum cardiomyopathy causes heart failure. No other cause of this heart failure is found except for the pregnancy. The symptoms are fatigue, shortness of breath, swelling of hands and feet, cough, chest tightness. With treatment, most individuals recover. A rare few may need long term treatment (10).

Respiratory Tract

As the uterus enlarges as pregnancy advances it pushes the diaphragm up causing alterations in respiration. The chest increases in size from front to back. The functional reserve capacity of the lungs is decreased. Oxygen consumption and carbon dioxide production increase sixty percent while the respiratory rate is a bit more rapid than before pregnancy. Because the respiratory tract mucous membranes become more vascular and edematous they are easily irritated. (11). The changes in breathing occurs rapidly after birth, while it can take eight weeks for oxygen consumption to return to prepregnant levels.

Urinary Tract

Urinary output increases right after birth as fluid accumulated in pregnancy is excreted causing  the urine volume at each void to go up to 500 ml or sometimes as much a 1000 ml. In some situations, urine is retained. However, in most situation this resolves with the first day. Some women might develop urinary incontinence or leakage of urine when they cough or sneeze. This condition is a risk factor for developing urinary incontinence years later. Many factors are involved in the incontinence associated with pregnancy and birth. Preventive measures are: not smoking prior to and during pregnancy; maintaining appropriate weight for height prior to pregnancy and regaining prepregnancy weight; avoidance of constipation; practicing pelvic floor muscle exercises (Kegel). Cesarean births are not a preventive measure (12). Renal function returns to a prepregnant state by three months.

Immune Changes

During gestation tremendous alternations in the immune system occur. These are necessary to allow implantation of the blastocyst. It is ”foreign” to mother and without the changes in the immune system, the blastocyst would be rejected. Changes in the immune system are designed to keep pathogens out and yet protect the embryo/fetus. To add to the complexity the immune system alterations are integral in the process of labor and birth(13). These alterations are restored to normal in about two to three months.

Brain Plasticity

During the postpartum period hormonal changes especially the release of prolactin and oxytocin as well as the sensory interactions the newborn are correlated with complex structural and functional alterations of the brain. The brain pathways that promote mother infant bonding and nurturing are enlarged. Prolactin related brain changes are also vital to maternal sense of well-being. Pioneering studies using brain scans reveal this brain plasticity.  Interestingly, the alterations note in a healthy postpartum period are not observed in the situation of postpartum depression which is a very serious disease that can lead to death of the mother or infant by suicide or infanticide. This terrible condition is also associated with postpartum dysfunction of the thyroid gland in up to twenty percent of those diagnosed with postpartum depression (14-17).

References

(1)Romano M, Cacciatore A, Giordano R, La Rosa B. Postpartum period: three distinct but continuous phases. J Prenat Med. 2010 Apr;4(2):22-5. PMID: 22439056; PMCID: PMC3279173.

(2) Hsu SK , Pan H-A, Hsu Y-Y, Wu  C-M, Chung W-J, Huang S-C  Enhanced myometrial autophagy in postpartum uterine involution

(3) Takamoto, N., Leppert, P. C., & Yu, S. Y. (1998). Cell Death and Proliferation and Its Relation to Collagen Degradation in Uterine Involution of Rat. Connective Tissue Research, 37(3–4), 163–175. https://doi.org/10.3109/03008209809002436

(4) Covali R, Socolov D, Carauleanu A, Pavaleanu I, Akad M, Boiculese LV, Socolov RV. The Importance of the Novel Postpartum Uterine Ultrasonographic Scale in Numerical Assessments of Uterine Involution Regarding Perinatal Maternal and Fetal Outcomes. Diagnostics (Basel). 2021 Sep 21;11(9):1731. doi: 10.3390/diagnostics11091731. PMID: 34574072; PMCID: PMC8469620.

(5) Paliulyte V, Drasutiene GS, Ramasauskaite D, Bartkeviciene D, Zakareviciene J, Kurmanavicius J. Physiological Uterine Involution in Primiparous and Multiparous Women: Ultrasound Study. Obstet Gynecol Int. 2017;2017:6739345. doi: 10.1155/2017/6739345. Epub 2017 May 7. PMID: 28555159; PMCID: PMC5438840.

(6) Lawerence, R. (2022) Breastfeeding, (9th edition). 58-92pp. Elsevier, Amsterdam.

(7) Pillay J, Davis TJ. Physiology, Lactation. StatPearls, Jan 2024 StatPearls Publishing, Treasure Island  Florida.

(8) https://my.clevelandclinic.org/health/diseases/15294-postpartum-thyroiditis  accessed May 13, 2024.

(9 Chautan, G, Tadi P. Physiology, Postpartum Changes. StatPearls, November 2022. StatPearls  Publishing, Treasure Island, Florida

 (10) American Heart Association. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/peripartum-cardiomyopathy-ppcm accessed May 14, 2024.

(11) Stanford University.  https://www.stanfordchildrens.org/en/topic/default?id=the-lungs-in-pregnancy-90-P02468  accessed May 15,2024

(12) Wesnes, S.L., Lose, G. Preventing urinary incontinence during pregnancy and postpartum: a mental health. Arch Womens Ment Health. 2019 Apr;22(2):289-299. doi: 10.1007/s00737-018-0889-z. Epub 2018 Jul 14. PMID: 30008085; PMCID: PMC6440938.13) Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal Immunological Adaptation During Normal Pregnancy. Front Immunol. 2020 Oct 7;11:575197. doi: 10.3389/fimmu.2020.575197. PMID: 33133091; PMCID: PMC7579415.

(13) Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal Immunological Adaptation During Normal Pregnancy. Front Immunol. 2020 Oct 7;11:575197. doi: 10.3389/fimmu.2020.575197. PMID: 33133091; PMCID: PMC7579415.

(14) Barba-Müller E, Craddock S, Carmona S, Hoekzema E. Brain plasticity in pregnancy and the postpartum period: links to maternal caregiving and mental health. Arch Womens Ment Health. 2019 Apr;22(2):289-299. doi: 10.1007/s00737-018-0889-z. Epub 2018 Jul 14. PMID: 30008085; PMCID: PMC6440938.

(15) Šebela A, Hanka J, Mohr P. Etiology, risk factors, and methods of postpartum depression prevention. Ceska Gynekol. 2018 Winter;83(6):468-473. English. PMID: 30848154.

(16) Brummelte S, Galea LA. Postpartum depression: Etiology, treatment and consequences for maternal care. Horm Behav. 2016 Jan;77:153-66. doi: 10.1016/j.yhbeh.2015.08.008. Epub 2015 Aug 28. PMID: 26319224.0

(17) Konstantakou P, Chalarakis N, Valsamakis G, Sakkas EG, Vousoura E, Gryparis A, Sakkas GE, Papadimitriou G, Zervas I, Mastorakos G. Associations of Thyroid Hormones Profile During