Physiology, Postpartum Changes


Introduction

The postpartum period is the period after delivery of conceptus when maternal physiological and anatomical changes return to the nonpregnant state. The postpartum period, also known as puerperium, starts following the expulsion of the placenta until complete physiological recovery of various organ systems. The postpartum period divides into three arbitrary phases, i.e., acute phase  - the first 24 hours after delivery of the placenta, early – up to 7 days, and late – up to 6 weeks to 6 months. Each phase has its unique clinical considerations and challenges.[1][2]

Organ Systems Involved

General Physiological Changes

There is generalized physical fatigue immediately after delivery. The pulse rate may be elevated a few hours after childbirth due to excitement or pain and usually normalizes on the second day. The blood pressure could be elevated due to pain or excitement but is generally in the normal range.[3] A significant decrease (> 20% below baseline) in blood pressure could be a sign of postpartum hemorrhage or septic shock.[4] Conversely, high blood pressure could be a sign of pain or pre-eclampsia.[5]

The temperature is slightly elevated up to 37.2C (99F) along with increased shivering, sweating, or diaphoresis in the first 24 hours and normalizes within 12 hours.[3][6] The temperature rise is attributable to the systemic absorption of metabolites accumulated due to muscle contractions. There could be a transient temperature rise (by 0.5C) on the third or fourth day due to breast engorgement. The respiratory rate also begins to fall back to the pre-pregnancy level within 2 to 3 days. A rise of temperature beyond the third day or over the upper limit is usually a sign of infection.[7][8][9][7] There is a weight loss of 5 to 6 kg due to the expulsion of products of gestation and accompanying blood loss. Further weight loss of 2 to 3 kg can be attributed to the brisk diuresis. The weight loss due to diuresis may continue up to 6 months after delivery.

Reproductive

Involution, a part of postpartum physiology, is the term given to the process of reproductive organs returning to their prepregnant state. Immediately following the delivery, the uterus, and the placental site contracts rapidly to prevent further blood loss. This rapid uterine contraction can lead to abdominal pain or cramps after childbirth. At this point, the uterus has an increased tone, feels firm, and weighs 1000 gms, and at the end of the first week, it weighs 500 gms, and by six weeks, it weighs approximately 50 gms. The female may complain. Initially, the contraction of the uterus is due to a substantial reduction in myometrial cell size; it constricts the blood vessels and limits the bleeding. The subsequent decrease in size is due to autolysis and infarction of uterine blood vessels.[10][11][12] The withdrawal of estrogen and progesterone leads to an increase in the activity of uterine collagenase and other proteolytic enzymes, accelerating the process of autolysis.[13] The intima and elastic tissues in the uterine blood vessels also undergo fibrosis and hyaline degeneration, leading to infarction and shedding of more uterine cells, which are removed by macrophages. The superficial and basal layers of the endometrium become necrotic and sloughed.[14] The endometrium is usually fully restored within 2 to 3 weeks.[15]

The lochia is the vaginal discharge that originates from the uterus, cervix, and vagina. The lochia is initially red and comprised of blood and fragments of decidua, endometrial tissues, and mucus and lasts 1 to 4 days. The lochia then changes color to yellowish or pale brown, lasting 5 to 9 days, and is comprised mainly of blood, mucus, and leucocytes. Finally, the lochia is white and contains mostly mucus, lasting up to 10 to 14 days. The lochia can persist up to 5 weeks postpartum. The persistence of red lochia beyond one week might be an indicator of uterine subinvolution. The presence of an offensive odor or large pieces of tissue or blood clots in lochia or the absence of lochia might be a sign of infection.[16][17][18] The cervix and vagina may be edematous and bruised in the early postpartum period and gradually heal back to normal.[19] 

Once the ovarian function resumes, rugae start to appear in the vagina, usually by the third week in females that are not breastfeeding. Similarly, the postpartum vaginal epithelium, which appears atrophic under the microscopic exam, is restored in 6 to 10 weeks, but the recovery delays in breastfeeding females due to low estrogen levels. The patient may develop perineal edema, lacerations, tears, or undergo an episiotomy in the immediate postpartum period that may lead to discomfort and pain.[20][21]

Lactation

The secretion from the breasts called colostrum increases after childbirth. Colostrum is rich in protein, vitamins and immunoglobulins, and other humoral factors (lactoferrin) and provides an immunological defense to the newborn.[22] The mammogenesis or preparation of breasts for lactation starts during pregnancy and entails ductal and lobuloalveolar hyperplasia and hypertrophy.[23] The high levels of estrogen and progesterone make the breast tissue unresponsive to prolactin. Still, as their levels decrease the following childbirth dramatically, the prolactin begins its milk secretory activity in mammary glans. The lactogenesis or milk secretion starts the third or fourth day postpartum. The neural arch of lactation involves ascending afferent impulses from nipple and areola, activated by suckling or stimulation of nipples, which pass via thoracic sensory nerves to the paraventricular and supraoptic nuclei of the hypothalamus, promoting the synthesis and secretion of Oxytocin from the posterior pituitary. Oxytocin affects the contraction of myoepithelial cells, leading to galactokinesis or milk expression from the mammary ducts. This release is also known as "milk ejection," or milk let down reflex." The milk ejection reflex can be inhibited by pain, anxiety, depression, breast engorgement, or depression. Prolactin maintains galactopoiesis, defined as the maintenance of effective and continuous lactation. A healthy mother secretes 500-800 ml of milk per day, which requires 700kcal/ day. The fat stores of up to 5 kg gained during pregnancy can provide enough calories to make up for any nutritional deficit during lactation. It is not unusual to develop nipple soreness, mastitis during this phase.[24][25]

Endocrine

The onset of the first menstrual period following delivery is variable and depends if the mother is lactating or not. If the mother is not breastfeeding, then the menstrual function returns by the sixth to eighth week postpartum in most of the cases. The duration of anovulation depends on the frequency and intensity of breastfeeding and is attributed to high serum prolactin levels associated with suckling.[24] Elevated serum prolactin levels inhibit the ovarian response to the follicular stimulating hormone, suppress the release of luteinizing hormone, suppressing the secretion of gonadotropins even further. This approach offers a natural method of contraception to the lactating female. In lactating females, menstruation usually reappears in 4 to 5 months, and in some cases, can be as late as 24 months. However, ovulation can commence in the absence of menstruation, and pregnancy can occur.[25][26][27] Non-lactating mothers should use contraceptive measures after three weeks, and lactating mothers after three months of delivery.[28] The level of human chorionic gonadotropin that mimics stimulating thyroid hormone falls dramatically after delivery. Consequently, the thyroid gland volume regresses to the pre-pregnant state by 12 weeks, and the thyroid function returns to normal by four weeks postpartum.[29][30] The diabetogenic effects of pregnancy are due to the production of placental insulinase, corticotropin-releasing hormone, and human placental lactogen.[31] The insulin sensitivity begins to increase after delivery and becomes restored within 2 to 3 days following delivery.[32] However, in obese females, postpartum normalization of insulin sensitivity may take 15 to 16 weeks.[33]  

Renal

The bladder wall may become edematous, hyperemic, and the bladder might be overdistended without the urge to pass urine.[34] The retention of urine in the first few days after labor may be due to the laxity of the abdominal musculature, tone of pelvic floor muscles, atony of bladder, compression of urethra by edema or hematoma, reflex inhibition of micturition due to genitourinary trauma.[35][1][35] Conversely, urinary incontinence, especially urge incontinence, affects 30% of postpartum females and is attributed most commonly to psychological stress associated with childbirth.[36] The mother may complain of painful micturition or dysuria that could be due to tears, laceration of the cervix or vagina, or episiotomy. During pregnancy, the compressive forces of the gravid uterus and the progesterone-induced decrease in ureteral tone, peristalsis, and contraction pressure lead to the dilation of the calyceal system, increasing the volume of kidneys by 30% from the pre-pregnant state.[37][38][37] The dilated ureters and renal pelvis usually return to the pre-pregnant state within four-eight weeks. There is an increased risk of developing urinary tract infections. It is important to counsel the mother to void every 3 to 4 hours.[39] 

Fluids

There is a shift of fluid from extravascular to intravascular space, corresponding to 6 to 8 liters of total body water. Furthermore, the persistent activity of the renin-angiotensin-aldosterone system (RAAS) during pregnancy leads to an excess of 950 mEq of sodium.[40] In the postpartum period, there is increased serum levels of the atrial natriuretic peptide (1.5 times normal) that inhibits aldosterone, angiotensin II and vasopressin and promotes urinary sodium excretion. There is brisk diuresis in the first two weeks after childbirth, and it is not uncommon to have a urinary output of 3000 cc/day. The amount of loss is usually in line with the amount of fluid retained during pregnancy. The glomerular filtration rate returns to baseline at eight weeks postpartum.[39] Lactosuria is not uncommon on the third or fourth day of the start of lactation.[41]

Hematologic

The hematocrit may initially drop due to blood loss associated with delivery but starts to rise again plasma volume decreases due to diuresis and hemoconcentration.[42] The hematocrit values return to normal in 3-5 days postpartum as plasma volume starts to increase. The discrepancy in hemoglobin values in the postpartum phase is due to the variability in the plasma volume due to fluid shifts. Studies evaluating the longitudinal values of hemoglobin in the postpartum phase indicate that it takes at least 4-6 months to restore the pregnancy-induced dip in hemoglobin to non-pregnant states.[43] The patient may develop leucocytosis (approximately 25,000/mm^3) due to the stress associated with labor. The white blood cell count returns to pre-pregnant values within four weeks.[44] The gestational thrombocytopenia resolves in 4 to 10 days after delivery as platelet count increases in response to platelet consumption during delivery.[44][45] During pregnancy, the fibrinogen, factor VII, VIII, X, XII, von Willebrand's factor, and ristocetin activity increase significantly as gestation progresses to prepare for delivery and prevent excess blood loss.[46] In the early postpartum period, the fibrinogen levels are still high, and platelets begin to rise to normal values. The tissue plasminogen, an enzyme responsible for clot lysis, doesn't rise or normalize in the early postpartum period. During pregnancy, the hypercoagulable state resolves gradually after birth, as clotting factor levels normalize in 8 to 12 weeks postpartum.[47][48] The changes in the coagulation system confer an increased risk for thromboembolic phenomena that are approximately ten-fold during pregnancy and twenty-fold during the early postpartum period.[49][50] Furthermore, the in vitro tests to assess or predict the possibility of thromboembolism, such as d-dimer tests, fibrin degradation products assay, are less reliable in the immediate postpartum period.[51]

Cardiovascular

There are significant structural and hemodynamic alterations in the peripartum period. Cardiac output increases throughout pregnancy. However, in the immediate postpartum period, following delivery, there is an increase in circulating blood volume from the contraction of the uterus and an increase in preload from the relief of inferior vena cava obstruction, leading to an increase in stroke volume and heart rate leading to a 60 to 80% rise in cardiac output, which rapidly declines to pre-labor values in 1 to 2 hours following delivery and to pre-pregnancy values in two weeks postpartum.[52][53] An increase in serum levels of progesterone and relaxin, a peptide hormone produced by corpus luteum and placenta, promotes systemic vasodilation leading to a progressive decrease in systemic vascular resistance (SVR). SVR decreases by 35 to 40% during pregnancy and increases to pre-pregnant levels in 2 weeks postpartum. There is also a decrease in systemic blood pressure by 5 to 10 mm Hg during pregnancy. Diastolic blood pressure decreases more than systolic blood pressure. The systemic blood pressures start to rise during the third trimester and return to prepregnant values at 16 weeks postpartum.[54] Heart rate increases in a linear fashion during pregnancy by 10 to 20 bpm over baseline and returns to pre-pregnant levels 6 weeks postpartum.[55][55] There is ventricular remodeling during pregnancy, and left ventricular wall thickness and mass increase by 28% to 52% above pre-pregnancy values. A few recent studies also report an increase in right ventricular volume and mass by 40% during pregnancy. The physiological hypertrophy of the ventricular system reverts to the pre-pregnant state in 4 weeks postpartum.[56][57] Cardiac contractility and ventricular ejection fraction don't undergo any significant change during the entire peripartum period.[55] 

Gastrointestinal

The mother may develop flatulence or constipation due to intestinal ileus (induced by pain or presence of placental hormone relaxin in the circulation), loss of body fluids, laxity of abdominal wall, and hemorrhoids.[58][59] The postpartum constipation is due to the progesterone-induced decrease in gastrointestinal transit time.[58] The compressive effects of the gravid uterus on the stomach, a decrease in lower esophageal sphincter tone due to high progesterone levels, and hypersecretion of acid due to high gastrin levels cause an increase in the incidence of acid reflux during pregnancy. After delivery, the levels of progesterone and gastrin drop within 24 hours, and the acid reflux and associated symptoms resolve in the next three to four days.[60][61][62][63]

Integumentary

Hyperpigmentation is the most commonly reported skin change during pregnancy, affecting 85% to 90% of females.[64] The hypothesis is that melanocytes are sensitive to elevated levels of estrogen, progesterone, and endorphins during pregnancy. Humoral factors produced by the placenta lead to the upregulation of tyrosine kinase, promoting further melanin synthesis.[65][66] The pigment changes accompanying pregnancy (melasma and linea nigra) usually disappear by 6 to 8 weeks.[67] Elevated estrogen during pregnancy can lead to telangiectasis and spider angiomata.[68] Venous dilation and increased hydrostatic pressure due to the gravid uterus can lead to nonpitting edema and varicosities in lower extremities, which returns to baseline in the postpartum period.[69] The nails undergo symmetrical, uniform hyperpigmentation during pregnancy that fades away in the postpartum period.[70] The abdominal muscles are overstretched during pregnancy and strained during labor and are slow to regain their normal tone and elasticity, returning to pre-pregnancy levels by 6 to 8 weeks. The patient may have divarication of recti, and the striae or stretch marks over the abdomen and legs might not disappear.[66]

Clinical Significance

Human physiology is significantly altered during pregnancy and in the postpartum period. The physician should be aware of the physiological changes associated with the postpartum period. The clinician should be able to tell the difference between healthy and abnormal to effectuate a diagnostic and therapeutic algorithm, especially in cases of acute emergencies such as postpartum hemorrhage, sepsis, amniotic fluid embolism, or uterine inversion. Furthermore, one should be aware of the hormonal changes related to the puerperium and lactation to formulate an effective contraception plan in the postpartum period. Thromboprophylaxis in the postpartum period is a constant topic of debate due to the high incidence of venous thromboembolism in the postpartum period, and females are risk-stratified into low-risk, medium-risk and, high-risk. Females with a history of no coagulation anomalies or low-risk don't require any thromboprophylaxis. Intermediate-risk females should be instituted thromboprophylaxis after delivery up to 7 days of puerperium. The females that are high risk receive thromboprophylaxis throughout pregnancy and up to 7 days of postpartum. The conduct of anesthesia for surgery also varies according to the timeline post-delivery. Patients undergoing surgery under general anesthesia within 48 hours of delivery should be treated as full stomach and should receive anti-aspiration measures, including non-particulate antacid and rapid sequence induction of anesthesia.


Article Details

Article Author

Gaurav Chauhan

Article Editor:

Prasanna Tadi

Updated:

11/21/2021 11:02:16 PM

References

[1]

Romano M,Cacciatore A,Giordano R,La Rosa B, Postpartum period: three distinct but continuous phases. Journal of prenatal medicine. 2010 Apr;     [PubMed PMID: 22439056]

[2]

Brown JS,Posner SF,Stewart AL, Urge incontinence: new health-related quality of life measures. Journal of the American Geriatrics Society. 1999 Aug;     [PubMed PMID: 10443860]

[3]

Bystrova K,Matthiesen AS,Vorontsov I,Widström AM,Ransjö-Arvidson AB,Uvnäs-Moberg K, Maternal axillar and breast temperature after giving birth: effects of delivery ward practices and relation to infant temperature. Birth (Berkeley, Calif.). 2007 Dec;     [PubMed PMID: 18021144]

[4]

Nathan HL,El Ayadi A,Hezelgrave NL,Seed P,Butrick E,Miller S,Briley A,Bewley S,Shennan AH, Shock index: an effective predictor of outcome in postpartum haemorrhage? BJOG : an international journal of obstetrics and gynaecology. 2015 Jan;     [PubMed PMID: 25546050]

[5]

Matthys LA,Coppage KH,Lambers DS,Barton JR,Sibai BM, Delayed postpartum preeclampsia: an experience of 151 cases. American journal of obstetrics and gynecology. 2004 May;     [PubMed PMID: 15167870]

[6]

Benson MD,Haney E,Dinsmoor M,Beaumont JL, Shaking rigors in parturients. The Journal of reproductive medicine. 2008 Sep;     [PubMed PMID: 18839822]

[7]

Alekseev NP,Vladimir II,Nadezhda TE, Pathological postpartum breast engorgement: prediction, prevention, and resolution. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2015 May;     [PubMed PMID: 25774443]

[8]

Woodd SL,Montoya A,Barreix M,Pi L,Calvert C,Rehman AM,Chou D,Campbell OMR, Incidence of maternal peripartum infection: A systematic review and meta-analysis. PLoS medicine. 2019 Dec;     [PubMed PMID: 31821329]

[9]

Hamadeh G,Dedmon C,Mozley PD, Postpartum fever. American family physician. 1995 Aug;     [PubMed PMID: 7625327]

[10]

Negishi H,Kishida T,Yamada H,Hirayama E,Mikuni M,Fujimoto S, Changes in uterine size after vaginal delivery and cesarean section determined by vaginal sonography in the puerperium. Archives of gynecology and obstetrics. 1999 Nov;     [PubMed PMID: 10728621]

[11]

Mulic-Lutvica A,Bekuretsion M,Bakos O,Axelsson O, Ultrasonic evaluation of the uterus and uterine cavity after normal, vaginal delivery. Ultrasound in obstetrics     [PubMed PMID: 11844171]

[12]

Sokol ER,Casele H,Haney EI, Ultrasound examination of the postpartum uterus: what is normal? The journal of maternal-fetal     [PubMed PMID: 15209115]

[13]

Cyganek A,Wyczalkowska-Tomasik A,Jarmuzek P,Grzechocinska B,Jabiry-Zieniewicz Z,Paczek L,Wielgos M, Activity of Proteolytic Enzymes and Level of Cystatin C in the Peripartum Period. BioMed research international. 2016;     [PubMed PMID: 26904684]

[14]

Anderson WR,Davis J, Placental site involution. American journal of obstetrics and gynecology. 1968 Sep 1;     [PubMed PMID: 5672474]

[15]

SHARMAN A, Post-partum regeneration of the human endometrium. Journal of anatomy. 1953 Jan;     [PubMed PMID: 13022577]

[16]

Sherman D,Lurie S,Frenkel E,Kurzweil Y,Bukovsky I,Arieli S, Characteristics of normal lochia. American journal of perinatology. 1999;     [PubMed PMID: 10772198]

[17]

Oppenheimer LW,Sherriff EA,Goodman JD,Shah D,James CE, The duration of lochia. British journal of obstetrics and gynaecology. 1986 Jul;     [PubMed PMID: 3755355]

[18]

Chi C,Bapir M,Lee CA,Kadir RA, Puerperal loss (lochia) in women with or without inherited bleeding disorders. American journal of obstetrics and gynecology. 2010 Jul;     [PubMed PMID: 20417483]

[19]

McLAREN HC, The involution of the cervix. British medical journal. 1952 Feb 16;     [PubMed PMID: 14896142]

[20]

Christianson LM,Bovbjerg VE,McDavitt EC,Hullfish KL, Risk factors for perineal injury during delivery. American journal of obstetrics and gynecology. 2003 Jul;     [PubMed PMID: 12861171]

[21]

Albers L,Garcia J,Renfrew M,McCandlish R,Elbourne D, Distribution of genital tract trauma in childbirth and related postnatal pain. Birth (Berkeley, Calif.). 1999 Mar;     [PubMed PMID: 10352050]

[22]

Thapa BR, Health factors in colostrum. Indian journal of pediatrics. 2005 Jul;     [PubMed PMID: 16077241]

[23]

Lamote I,Meyer E,Massart-Leën AM,Burvenich C, Sex steroids and growth factors in the regulation of mammary gland proliferation, differentiation, and involution. Steroids. 2004 Mar;     [PubMed PMID: 15072917]

[24]

Crowley WR, Neuroendocrine regulation of lactation and milk production. Comprehensive Physiology. 2015 Jan;     [PubMed PMID: 25589271]

[25]

The World Health Organization Multinational Study of Breast-feeding and Lactational Amenorrhea. II. Factors associated with the length of amenorrhea. World Health Organization Task Force on Methods for the Natural Regulation of Fertility. Fertility and sterility. 1998 Sep;     [PubMed PMID: 9757874]

[26]

Campbell OM,Gray RH, Characteristics and determinants of postpartum ovarian function in women in the United States. American journal of obstetrics and gynecology. 1993 Jul;     [PubMed PMID: 8333476]

[27]

Campino C,Ampuero S,Díaz S,Serón-Ferré M, Prolactin bioactivity and the duration of lactational amenorrhea. The Journal of clinical endocrinology and metabolism. 1994 Oct;     [PubMed PMID: 7962307]

[28]

Jackson E,Glasier A, Return of ovulation and menses in postpartum nonlactating women: a systematic review. Obstetrics and gynecology. 2011 Mar;     [PubMed PMID: 21343770]

[29]

Gaberšček S,Osolnik J,Zaletel K,Pirnat E,Hojker S, An Advantageous Role of Spectral Doppler Sonography in the Evaluation of Thyroid Dysfunction During the Postpartum Period. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2016 Jul;     [PubMed PMID: 27208199]

[30]

Stagnaro-Green A,Abalovich M,Alexander E,Azizi F,Mestman J,Negro R,Nixon A,Pearce EN,Soldin OP,Sullivan S,Wiersinga W, Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid : official journal of the American Thyroid Association. 2011 Oct;     [PubMed PMID: 21787128]

[31]

Sonagra AD,Biradar SM,K D,Murthy D S J, Normal pregnancy- a state of insulin resistance. Journal of clinical and diagnostic research : JCDR. 2014 Nov;     [PubMed PMID: 25584208]

[32]

Ryan EA,O'Sullivan MJ,Skyler JS, Insulin action during pregnancy. Studies with the euglycemic clamp technique. Diabetes. 1985 Apr;     [PubMed PMID: 3882502]

[33]

Sivan E,Chen X,Homko CJ,Reece EA,Boden G, Longitudinal study of carbohydrate metabolism in healthy obese pregnant women. Diabetes care. 1997 Sep;     [PubMed PMID: 9283800]

[34]

Rogers RG,Leeman LL, Postpartum genitourinary changes. The Urologic clinics of North America. 2007 Feb;     [PubMed PMID: 17145356]

[35]

Snooks SJ,Swash M,Mathers SE,Henry MM, Effect of vaginal delivery on the pelvic floor: a 5-year follow-up. The British journal of surgery. 1990 Dec;     [PubMed PMID: 2276018]

[36]

Viktrup L,Lose G,Rolff M,Barfoed K, The symptom of stress incontinence caused by pregnancy or delivery in primiparas. Obstetrics and gynecology. 1992 Jun;     [PubMed PMID: 1579319]

[37]

Au KK,Woo JS,Tang LC,Liang ST, Aetiological factors in the genesis of pregnancy hydronephrosis. The Australian     [PubMed PMID: 3869447]

[38]

Beydoun SN, Morphologic changes in the renal tract in pregnancy. Clinical obstetrics and gynecology. 1985 Jun;     [PubMed PMID: 4017319]

[39]

Cheung KL,Lafayette RA, Renal physiology of pregnancy. Advances in chronic kidney disease. 2013 May;     [PubMed PMID: 23928384]

[40]

Ogueh O,Clough A,Hancock M,Johnson MR, A longitudinal study of the control of renal and uterine hemodynamic changes of pregnancy. Hypertension in pregnancy. 2011;     [PubMed PMID: 21740248]

[41]

Andria M,Vargiu N, [Lactosuria in pregnancy and the puerperium]. Minerva ginecologica. 1968 May 15;     [PubMed PMID: 5738768]

[42]

Nicol B,Croughan-Minihane M,Kilpatrick SJ, Lack of value of routine postpartum hematocrit determination after vaginal delivery. Obstetrics and gynecology. 1997 Oct;     [PubMed PMID: 9380307]

[43]

Taylor DJ,Lind T, Red cell mass during and after normal pregnancy. British journal of obstetrics and gynaecology. 1979 May;     [PubMed PMID: 465384]

[44]

Chandra S,Tripathi AK,Mishra S,Amzarul M,Vaish AK, Physiological changes in hematological parameters during pregnancy. Indian journal of hematology     [PubMed PMID: 23997449]

[45]

Shehata N,Burrows R,Kelton JG, Gestational thrombocytopenia. Clinical obstetrics and gynecology. 1999 Jun;     [PubMed PMID: 10370851]

[46]

Clark P,Brennand J,Conkie JA,McCall F,Greer IA,Walker ID, Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thrombosis and haemostasis. 1998 Jun;     [PubMed PMID: 9657443]

[47]

de Boer K,ten Cate JW,Sturk A,Borm JJ,Treffers PE, Enhanced thrombin generation in normal and hypertensive pregnancy. American journal of obstetrics and gynecology. 1989 Jan;     [PubMed PMID: 2521425]

[48]

Eichinger S, D-dimer testing in pregnancy. Pathophysiology of haemostasis and thrombosis. 2003 Sep-2004 Dec;     [PubMed PMID: 15692237]

[49]

Jackson E,Curtis KM,Gaffield ME, Risk of venous thromboembolism during the postpartum period: a systematic review. Obstetrics and gynecology. 2011 Mar;     [PubMed PMID: 21343773]

[50]

Tepper NK,Boulet SL,Whiteman MK,Monsour M,Marchbanks PA,Hooper WC,Curtis KM, Postpartum venous thromboembolism: incidence and risk factors. Obstetrics and gynecology. 2014 May;     [PubMed PMID: 24785851]

[51]

Gherman RB,Goodwin TM,Leung B,Byrne JD,Hethumumi R,Montoro M, Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstetrics and gynecology. 1999 Nov;     [PubMed PMID: 10546719]

[52]

Robson SC,Hunter S,Boys RJ,Dunlop W, Serial study of factors influencing changes in cardiac output during human pregnancy. The American journal of physiology. 1989 Apr;     [PubMed PMID: 2705548]

[53]

Soma-Pillay P,Nelson-Piercy C,Tolppanen H,Mebazaa A, Physiological changes in pregnancy. Cardiovascular journal of Africa. 2016 Mar-Apr;     [PubMed PMID: 27213856]

[54]

Nama V,Antonios TF,Onwude J,Manyonda IT, Mid-trimester blood pressure drop in normal pregnancy: myth or reality? Journal of hypertension. 2011 Apr;     [PubMed PMID: 21178781]

[55]

Grindheim G,Estensen ME,Langesaeter E,Rosseland LA,Toska K, Changes in blood pressure during healthy pregnancy: a longitudinal cohort study. Journal of hypertension. 2012 Feb;     [PubMed PMID: 22179091]

[56]

Umar S,Nadadur R,Iorga A,Amjedi M,Matori H,Eghbali M, Cardiac structural and hemodynamic changes associated with physiological heart hypertrophy of pregnancy are reversed postpartum. Journal of applied physiology (Bethesda, Md. : 1985). 2012 Oct 15;     [PubMed PMID: 22923507]

[57]

Hill JA,Olson EN, Cardiac plasticity. The New England journal of medicine. 2008 Mar 27;     [PubMed PMID: 18367740]

[58]

Glazener CM,Abdalla M,Stroud P,Naji S,Templeton A,Russell IT, Postnatal maternal morbidity: extent, causes, prevention and treatment. British journal of obstetrics and gynaecology. 1995 Apr;     [PubMed PMID: 7612509]

[59]

Shin GH,Toto EL,Schey R, Pregnancy and postpartum bowel changes: constipation and fecal incontinence. The American journal of gastroenterology. 2015 Apr;     [PubMed PMID: 25803402]

[60]

Blouw R,Scatliff J,Craig DB,Palahniuk RJ, Gastric volume and pH in postpartum patients. Anesthesiology. 1976 Oct;     [PubMed PMID: 973697]

[61]

Lam KK,So HY,Gin T, Gastric pH and volume after oral fluids in the postpartum patient. Canadian journal of anaesthesia = Journal canadien d'anesthesie. 1993 Mar;     [PubMed PMID: 8467543]

[62]

O'Sullivan GM,Sutton AJ,Thompson SA,Carrie LE,Bullingham RE, Noninvasive measurement of gastric emptying in obstetric patients. Anesthesia and analgesia. 1987 Jun;     [PubMed PMID: 3578862]

[63]

Vanner RG,Goodman NW, Gastro-oesophageal reflux in pregnancy at term and after delivery. Anaesthesia. 1989 Oct;     [PubMed PMID: 2589605]

[64]

Bieber AK,Martires KJ,Stein JA,Grant-Kels JM,Driscoll MS,Pomeranz MK, Pigmentation and Pregnancy: Knowing What Is Normal. Obstetrics and gynecology. 2017 Jan;     [PubMed PMID: 27926637]

[65]

Bieber AK,Martires KJ,Driscoll MS,Grant-Kels JM,Pomeranz MK,Stein JA, Nevi and pregnancy. Journal of the American Academy of Dermatology. 2016 Oct;     [PubMed PMID: 27646736]

[66]

Tyler KH, Physiological skin changes during pregnancy. Clinical obstetrics and gynecology. 2015 Mar;     [PubMed PMID: 25517755]

[67]

Motosko CC,Bieber AK,Pomeranz MK,Stein JA,Martires KJ, Physiologic changes of pregnancy: A review of the literature. International journal of women's dermatology. 2017 Dec;     [PubMed PMID: 29234716]

[68]

Fernandes LB,Amaral WN, Clinical study of skin changes in low and high risk pregnant women. Anais brasileiros de dermatologia. 2015 Nov-Dec;     [PubMed PMID: 26734862]

[69]

Engelhorn CA,Cassou MF,Engelhorn AL,Salles-Cunha SX, Does the number of pregnancies affect patterns of great saphenous vein reflux in women with varicose veins? Phlebology. 2010 Aug;     [PubMed PMID: 20656957]

[70]

Erpolat S,Eser A,Kaygusuz I,Balci H,Kosus A,Kosus N, Nail alterations during pregnancy: a clinical study. International journal of dermatology. 2016 Oct;     [PubMed PMID: 27097299]