Placenta and fetal membranes. Physiological changes during pregnancy. Diagnosis of Pregnancy
1. Chaudhary Anishka
2. Osmonova Gulnaz Zhenishbaevna
(1. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Teacher, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
The physiological adaptation of the female organism during gestation represents a complex biological orchestration designed to support fetal development while maintaining maternal homeostasis. Central to this process are the placenta and fetal membranes, transient organ systems that facilitate nutrient transport, gas exchange, metabolic regulation, immunological tolerance, and endocrine signaling. Concurrently, maternal organ systems undergo extensive anatomical, biochemical, and hemodynamic adaptations to accommodate the metabolic demands of the developing conceptus. Timely and accurate diagnosis of pregnancy relies on a synthesis of clinical history, physical examination findings, biochemical markers such as human chorionic gonadotropin, and sonographic evaluation. Understanding the intricate interplay between placental physiology, maternal adaptation, and diagnostic modalities is essential for advancing prenatal care, optimizing clinical outcomes, and identifying gestational pathologies at the earliest stages.
Introduction
Pregnancy represents a unique physiological state characterized by profound adaptations across virtually every organ system in the female body. These changes are driven by complex neuroendocrine signals and metabolic alterations designed to establish a suitable environment for fertilization, implantation, organogenesis, and fetal growth. At the core of maternal-fetal biology is the placenta, a highly specialized, transient organ formed from both embryonic and maternal tissues. Together with the fetal membranes—the amnion and chorion—the placenta serves as the essential physiological interface that mediates metabolic exchange, immunological protection, and endocrine signaling between the mother and the developing fetus.
The functional integration of the maternal-placental-fetal unit requires systemic maternal physiological adaptations. Cardiovascular, respiratory, renal, hematologic, gastrointestinal, and metabolic systems undergo marked adjustments early in gestation, often before fetal growth becomes clinically apparent. These maternal changes are essential to ensure adequate uteroplacental perfusion, satisfy the high metabolic requirements of the conceptus, and prepare the maternal body for parturition and lactation. Missteps in these adaptive processes can lead to significant obstetric complications, including preeclampsia, intrauterine growth restriction, gestational diabetes, and preterm labor.
Accurate and early diagnosis of pregnancy is the critical gateway to gestational healthcare management. Diagnostic techniques have evolved significantly over the past century, progressing from crude biological assays to highly sensitive biochemical markers and high-resolution imaging modalities. Today, clinical diagnosis relies on a combined assessment of early gestational symptoms, physical diagnostic signs, qualitative and quantitative assays for human chorionic gonadotropin, and obstetric ultrasonography. A detailed understanding of placental development, maternal gestational physiology, and modern diagnostic standards forms the foundation of modern obstetrics and maternal-fetal medicine.
Methods
This academic review was compiled through a comprehensive synthesis of contemporary literature, clinical practice guidelines, and fundamental physiological concepts in obstetrics, reproductive biology, and maternal-fetal medicine. Literature searches were conducted across medical databases including PubMed, Scopus, and Google Scholar, using search terms related to placental development, fetal membrane histology, maternal physiological adaptation during pregnancy, and diagnostic modalities for early pregnancy detection.
Relevant studies, clinical trials, and meta-analyses were evaluated for methodological rigor, clinical relevance, and alignment with established physiological models. Particular emphasis was placed on recent advancements in placental signaling pathways, microvascular adaptation, maternal hemodynamic changes, and high-sensitivity bioassays for gestational biomarkers. The synthesized information was structured into an integrated narrative detailing organ system changes, functional histology, and diagnostic workflows, adhering strictly to a formal academic exposition format without relying on schematic representations or bulleted enumerations.
Results and Discussion
1. Placental Development, Structure, and Function
Placentation begins shortly after blastocyst implantation, a process typically occurring six to seven days post-fertilization. The outer cell layer of the blastocyst, the trophoblast, differentiates into two distinct layers: an inner layer of mononuclear cytotrophoblasts and an outer multinucleated layer termed the syncytiotrophoblast. The syncytiotrophoblast displays invasive characteristics, penetrating the maternal uterine epithelium and underlying endometrial stroma through the secretion of proteolytic enzymes such as matrix metalloproteinases. As implantation progresses, fluid-filled spaces called lacunae form within the expanding syncytiotrophoblast mass. These lacunae enlarge and coalesce, eventually anastomosing with eroded maternal endometrial capillaries. This critical event establishes the primitive uteroplacental circulation, allowing maternal blood to fill the lacunar network and bathe the nascent trophoblastic processes.
Subsequent structural organization gives rise to the chorionic villi, which undergo three distinct stages of development. Primary villi consist of central cores of proliferating cytotrophoblasts covered by an outer layer of syncytiotrophoblast. Secondary villi are formed when extraembryonic mesoderm invades the central core of the primary villi. By the end of the third post-conception week, embryonic blood vessels differentiate within this mesodermal core, transforming the structures into tertiary villi. These villous vascular networks connect directly to the embryonic cardiovascular system via the umbilical vessel network. Cytotrophoblasts located at the distal tips of the anchor villi continue to proliferate and extend laterally through the syncytiotrophoblast, forming a continuous cytotrophoblastic shell that anchors the chorionic sac to the maternal decidua.
Remodeling of maternal spiral arteries represents a crucial physiological adaptation during early placentation. Specialized extravillous cytotrophoblasts migrate away from the villi and invade the decidua and the proximal third of the myometrium. These endovascular cytotrophoblasts degrade the endothelial lining and smooth muscle layer of the maternal spiral arteries, replacing the vascular wall with fibrinoid material and trophoblastic cells. Consequently, high-resistance, low-capacity spiral arteries are transformed into high-capacity, low-resistance, large-caliber conduits. This vascular remodeling ensures a steady, high-volume flow of maternal blood into the intervillous space, independent of maternal systemic vasomotor reactivity. Inadequate or incomplete spiral artery remodeling leads to reduced placental perfusion and ischemic injury, serving as the core pathophysiology in conditions such as preeclampsia and fetal growth restriction.
The fully developed human placenta is a discoid organ featuring a hemochorial interface, meaning maternal blood comes into direct contact with fetal chorionic tissue without intervening maternal capillary walls. Morphologically, the mature placenta presents two surfaces: the maternal surface, characterized by fifteen to twenty raised cotyledons separated by decidual septa, and the fetal surface, covered by the translucent amnion through which the umbilical blood vessels converge toward the umbilical cord. The placental barrier separates maternal and fetal circulations and consists of four layers in early pregnancy: the syncytiotrophoblast, cytotrophoblast layer, extraembryonic mesodermal stroma, and fetal capillary endothelium. As pregnancy advances toward term, the barrier undergoes thinning to facilitate efficient gas and nutrient exchange. The cytotrophoblast layer becomes discontinuous, the mesodermal core thins, and syncytial knots form, leaving a thin syncytiovascular membrane where the syncytiotrophoblast lies in direct apposition to the fetal capillary basement membrane.
Functionally, the placenta executes complex metabolic, respiratory, excretory, immunological, and endocrine tasks. Respiratory gas exchange occurs via simple passive diffusion down partial pressure gradients. Oxygen transfers efficiently from maternal hemoglobin to fetal hemoglobin due to the higher oxygen affinity of fetal hemoglobin, the double Bohr effect, and the relatively high concentration of fetal hemoglobin. Carbon dioxide diffuses rapidly from fetal to maternal circulation, aided by the double Haldane effect, which enhances carbon dioxide release as maternal blood absorbs oxygen. Nutrient transport across the placental barrier utilizes diverse transport mechanisms: simple diffusion for water and small electrolytes; facilitated diffusion via specific GLUT transporters for glucose; active transport via membrane-bound pumps and amino acid transporters for amino acids, calcium, and iron; and pinocytosis for larger macromolecules such as maternal immunoglobulin G, which provides passive immunity to the fetus.
The placenta functions as a robust endocrine organ, producing polypeptide and steroid hormones vital for maintaining pregnancy and coordinating maternal physiological adaptations. Human chorionic gonadotropin, synthesized by the syncytiotrophoblast, maintains the corpus luteum during early pregnancy, ensuring continuous progesterone production until the luteo-placental shift occurs around eight to ten weeks of gestation. Human placental lactogen, also known as human chorionic somatomammotropin, modulates maternal carbohydrate and lipid metabolism. It promotes maternal insulin resistance, lipolysis, and free fatty acid release, thereby conserving glucose and amino acids for preferential fetal transfer. Progesterone synthesized by the placenta inhibits uterine smooth muscle contractility, maintains endometrial integrity, and suppresses maternal cell-mediated immune responses. Estrogen, primarily estriol synthesized from fetal adrenal androgen precursors, enhances uteroplacental blood flow, promotes myometrial growth, and prepares the mammary glands for lactation.
2. Fetal Membranes and Amniotic Fluid Physiology
The fetal membranes, comprising the inner amnion and outer chorion, constitute the gestational sac enclosing the fetus and amniotic fluid. The chorion laeve, formed from the smooth non-villous portion of the chorion, fuses with the underlying decidua parietalis as the amniotic sac expands to fill the uterine cavity. Structurally, the chorion contains a connective tissue layer lined by residual cytotrophoblasts. It provides mechanical stability to the gestational sac and participates in local signaling cascades involving prostaglandins and cytokines near term. The amnion is an avascular, flexible membrane composed of a single layer of cuboidal epithelial cells resting on a basement membrane and a compact collagenous stroma. Despite its thin structure, the amnion exhibits remarkable tensile strength attributable to its organized interstitial collagen lattice, shielding the fetus from mechanical trauma and ascending pathogens.
Amniotic fluid performs critical protective, developmental, and homeostatic functions throughout gestation. In early pregnancy, amniotic fluid is predominantly an ultrafiltrate of maternal blood plasma and fluid secreted across the fetal skin and amniotic epithelium. As fetal development progresses and keratanization of the fetal skin occurs around nineteen to twenty weeks of gestation, the primary sources of amniotic fluid shift dramatically. In the second half of pregnancy, fetal urine output becomes the primary constituent of amniotic fluid volume, supplemented by fetal lung fluid secretions. Amniotic fluid resorption occurs principally through fetal swallowing and intramembranous pathway absorption, wherein fluid moves across the amnion into the fetal microcirculation traversing the fetal surface of the placenta.
The composition and volume of amniotic fluid undergo continuous changes throughout gestation. Amniotic fluid volume expands progressively from approximately thirty milliliters at ten weeks to a peak of eight hundred to one thousand milliliters at thirty-four to thirty-six weeks, after which it gradually declines toward term. Chemically, the fluid is composed of ninety-eight to ninety-nine percent water, alongside electrolytes, proteins, carbohydrates, lipids, urea, creatinine, hormones, and desquamated fetal cells. Amniotic fluid provides a cushioned environment that prevents mechanical cord compression, allows symmetrical fetal musculoskeletal growth, protects against external kinetic impacts, maintains a constant thermal environment, and exhibits intrinsic antimicrobial activity through peptides such as beta-defensins and lactoferrin.
Derangements in amniotic fluid volume—namely oligohydramnios and polyhydramnios—serve as major clinical indicators of underlying fetal, placental, or maternal pathology. Oligohydramnios, characterized by an amniotic fluid index of less than five centimeters or a maximum vertical pocket under two centimeters, may result from placental insufficiency, premature rupture of membranes, maternal dehydration, or fetal renal tract anomalies such as bilateral renal agenesis or posterior urethral valves. Prolonged severe oligohydramnios in early or mid-gestation can cause pulmonary hypoplasia, fetal compression deformities, and Potter sequence. Conversely, polyhydramnios, defined as an amniotic fluid index exceeding twenty-four centimeters or a maximum vertical pocket over eight centimeters, frequently stems from maternal diabetes mellitus, fetal gastrointestinal obstructions preventing swallowing, neuromuscular disorders, twin-to-twin transfusion syndrome, or congenital cardiac arrhythmias.
3. Maternal Physiological Adaptations During Pregnancy
Maternal physiology undergoes widespread functional restructuring designed to satisfy the metabolic demands of the fetus while preserving maternal systemic stability. The cardiovascular system undergoes some of the most profound early adaptations. Systemic vascular resistance falls dramatically due to the low-resistance vascular bed of the placenta and the vasodilatory effects of circulating progesterone, nitric oxide, and relaxin. To compensate for reduced systemic vascular resistance and maintain adequate tissue perfusion, cardiac output increases by forty to fifty percent above pre-pregnancy baselines. This elevation in cardiac output is achieved through increases in both stroke volume and heart rate. Stroke volume rises significantly in early pregnancy due to enhanced ventricular preload, while heart rate increases gradually by ten to fifteen beats per minute by the third trimester.
Maternal arterial blood pressure changes dynamically throughout gestation. Systolic and diastolic blood pressures decrease during the first trimester, reaching a nadir in the mid-second trimester, where diastolic pressure drops by as much as ten to fifteen millimeters of mercury. Blood pressure gradually returns toward baseline levels as term approaches. Anatomically, the heart undergoes mild eccentric ventricular hypertrophy to accommodate increased volumetric workloads. Apical displacement, prominent physiological S3 gallop sounds, and benign systolic ejection murmurs along the left sternal border are common normal clinical findings resulting from structural and kinetic heart changes. Position-dependent venous compression by the gravid uterus on the inferior vena cava in the supine position reduces venous return, stroke volume, and cardiac output, producing supine hypotensive syndrome characterized by dizziness, pallor, and diaphoresis.
Hematologic adjustments are characterized by a massive expansion of intravascular fluid volume. Plasma volume increases by forty to fifty percent, whereas red blood cell mass expands by only twenty to thirty percent under the stimulation of renal erythropoietin. This disproportionate increase in plasma volume relative to red cell volume produces a physiological hemodilution, commonly referred to as the physiological anemia of pregnancy. This physiological decrease in blood viscosity reduces vascular resistance and improves microvascular perfusion in the placental bed. Leukocyte counts rise moderately, mainly due to neutrophilia, while platelet counts may show a mild, physiological decline termed gestational thrombocytopenia. Pregnancy is a hypercoagulable state characterized by increased concentrations of clotting factors, particularly fibrinogen, factor VII, factor VIII, factor X, and von Willebrand factor, alongside suppressed fibrinolytic activity and decreased protein S levels. This hypercoagulability limits maternal hemorrhage during third-stage labor but significantly increases the risk of venous thromboembolism.
Respiratory adaptations compensate for increased maternal metabolic demands and elevated fetal oxygen consumption. Progesterone acts as a direct central respiratory stimulant, increasing tidal volume by forty to fifty percent without altering the baseline respiratory rate. Consequently, minute ventilation increases proportionally, leading to a mild primary respiratory alkalosis characterized by a decreased arterial partial pressure of carbon dioxide, typically ranging between twenty-seven and thirty-two millimeters of mercury. Renal excretion of bicarbonate compensates for this alkalosis, maintaining arterial pH within a narrow physiological range of 7.40 to 7.45. Anatomical changes caused by the enlarging uterus displacing the diaphragm superiorly lead to a decrease in functional residual capacity and expiratory reserve volume, though total lung capacity is largely preserved due to a compensatory enlargement of the transverse chest diameter.
The renal system experiences structural and functional modifications driven by endocrine signaling and mechanical displacement. Renal plasma flow and glomerular filtration rate increase by fifty to eighty percent above pre-pregnancy values early in the first trimester. This elevation accelerates the renal clearance of serum creatinine, blood urea nitrogen, and uric acid, resulting in lower physiological baseline concentrations for these parameters in pregnant individuals. Glomerular hyperfiltration exceeds the tubular reabsorptive capacity for certain solutes, frequently causing physiological glucosuria and mild aminoaciduria. Progesterone-mediated smooth muscle relaxation, combined with mechanical compression of the ureters by the enlarged uterus at the pelvic brim, leads to physiological hydronephrosis and hydroureter, which are more pronounced on the right side due to dextrorotation of the uterus and cushioning of the left ureter by the sigmoid colon.
Gastrointestinal and metabolic adaptations meet the nutritional requirements of fetal development while altering maternal metabolism. Progesterone-induced smooth muscle relaxation reduces lower esophageal sphincter tone, predisposing to gastroesophageal reflux, and decreases intestinal motility, leading to delayed gastric emptying and constipation. High circulating estrogen levels alter hepatic protein synthesis, increasing thyroid-binding globulin, corticosteroid-binding globulin, and sex hormone-binding globulin. Glucose metabolism is altered to ensure a continuous transplacental glucose supply to the fetus. Early pregnancy is an anabolic phase characterized by enhanced maternal insulin sensitivity and fat storage. In contrast, late pregnancy shifts into a catabolic state driven by human placental lactogen, prolactin, and cortisol, inducing peripheral maternal insulin resistance. This state maintains elevated postprandial maternal plasma glucose levels, facilitating passive transfer across the placenta, while maternal energy needs are increasingly met through lipolysis and fatty acid oxidation.
4. Clinical, Biochemical, and Sonographic Diagnosis of Pregnancy
The clinical diagnosis of pregnancy relies on a comprehensive history and physical examination, supplemented by validated diagnostic tests. Symptoms of early pregnancy include secondary amenorrhea, morning nausea and vomiting, fatigue, urinary frequency, and breast tenderness. Physical signs emerge progressively as gestation advances. Chadwick sign, visible by six to eight weeks, presents as a bluish discoloration of the cervix, vagina, and vulva resulting from increased pelvic vascular congestion. Goodell sign denotes a distinct softening of the vaginal portion of the cervix, while Hegar sign describes softening of the uterine isthmus, identifiable on bimanual examination. As the uterus enlarges, it becomes palpable above the pubic symphysis by twelve weeks of gestation, reaches the umbilicus by twenty weeks, and approaches the xiphoid process by thirty-six weeks.
Biochemical diagnosis centers on detecting human chorionic gonadotropin in maternal urine or serum. Human chorionic gonadotropin is a heterodimeric glycoprotein composed of an alpha subunit, shared with luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone, and a unique beta subunit that confers biological and immunologic specificity. Secreted by the syncytiotrophoblast, human chorionic gonadotropin enters the maternal circulation shortly after implantation and can be detected in maternal serum approximately eight to eleven days post-conception. Qualitative urine pregnancy tests utilize enzyme-linked immunosorbent assays targeting the beta subunit, achieving diagnostic sensitivity at concentrations between ten and twenty-five milli-international units per milliliter. Serum quantitative assays provide precise measurement of circulating hormone levels, doubling approximately every forty-eight to seventy-two hours during the first six to eight weeks of normal intrauterine pregnancy, peaking around ten to eleven weeks before declining to a lower, stable plateau for the remainder of gestation.
Continuous quantitative tracking of human chorionic gonadotropin levels is indispensable in evaluating early pregnancy viability and diagnosing ectopic or failing pregnancies. In a normal intrauterine pregnancy, serum human chorionic gonadotropin concentrations rise exponentially; a failure to achieve a minimum minimal rise over forty-eight hours raises suspicion for an abnormal gestation, such as a spontaneous abortion or an extrauterine implantation. When interpreted alongside transvaginal ultrasonography, the concept of the discriminatory zone becomes clinically paramount. The discriminatory zone refers to the serum human chorionic gonadotropin threshold—typically between one thousand five hundred and two thousand milli-international units per milliliter—above which a normal intrauterine gestational sac should consistently be visualized by transvaginal ultrasound.
Obstetric ultrasonography provides definitive confirmation of pregnancy, establishes gestational age, confirms viability, and verifies intra-uterine localization. Transvaginal ultrasonography is superior to transabdominal imaging in early pregnancy due to its higher frequency transducers and proximity to pelvic organs. The earliest sonographic evidence of pregnancy is the visualization of a gestational sac, appearing as a small, round, anechoic fluid collection surrounded by an echogenic rim within the thickened endometrium at approximately four to five weeks of gestation. Confirmation of a true intrauterine pregnancy requires identification of the double decidual sac sign or the intradecidual sign, distinguishing an authentic gestational sac from a pseudogestational sac associated with an ectopic pregnancy.
As gestation progresses, sequential developmental landmarks become sonographically visible. The yolk sac appears as a distinct, hyperechoic ring with an anechoic center within the gestational sac at approximately five to five and a half weeks of gestation, providing definitive proof of an intrauterine pregnancy. The embryonic pole, adjacent to the yolk sac, can typically be identified by five and a half to six weeks, at which point cardiac motion can be detected using real-time motion mode ultrasound. Measurement of the crown-rump length during the first trimester provides the most accurate sonographic method for gestational age assignment, carrying a margin of error of plus or minus five to seven days. In later trimesters, gestational age estimation shifts to a composite evaluation of fetal biometry, including biparietal diameter, head circumference, abdominal circumference, and femur length.
Conclusion
The physiological transformations characterizing human pregnancy reflect a complex adaptation designed to support fetal morphogenesis and development. The placenta and fetal membranes function not merely as passive conduits for metabolic exchange, but as active, highly regulated organs that mediate endocrine signaling, immunological protection, and vascular adaptation. These fetal structures induce sweeping modifications across maternal cardiovascular, hematologic, respiratory, renal, and gastrointestinal systems, establishing a dynamic physiological baseline specific to gestation.
Prompt and accurate diagnosis of pregnancy forms the cornerstone of high-quality obstetric management. Integrating clinical signs, quantitative biochemical assays of human chorionic gonadotropin, and high-resolution sonographic imaging allows clinicians to confirm pregnancy, establish precise gestational dating, verify fetal viability, and identify pathological deviations early in development. A thorough understanding of maternal-fetal physiology and diagnostic frameworks enables healthcare professionals to optimize maternal and neonatal outcomes across the continuum of prenatal care.
References
1. Burton, G. J., & Jauniaux, E. (2018). Development of the human placenta and fetal membranes. Fertility and Sterility, 109(2), 194–203. https://doi.org/10.1016/j.fertnstert.2017.11.026
2. Cole, L. A. (2012). Biological functions of hCG and hCG-related molecules. Reproductive Biology and Endocrinology, 10(1), 16. https://doi.org/10.1186/1477-7827-10-16
3. Davies, S., Byrn, F., & Cole, L. A. (2003). Human chorionic gonadotropin testing for early pregnancy viability and complications. Clinics in Laboratory Medicine, 23(2), 257–264. https://doi.org/10.1016/s0272-2712(03)00026-x Cited by: 68
4. Doubilet, P. M., Benson, C. B., Bourne, T., & Blaivas, M. (2013). Diagnostic criteria for nonviable pregnancy early in the first trimester. New England Journal of Medicine, 369(15), 1443–1451. https://doi.org/10.1056/NEJMra1302417
5. Gridelet, V., Tsampalas, M., Berndt, S., & Geenen, V. (2020). Human chorionic gonadotrophin: New pleiotropic functions for an "old" hormone during pregnancy. Frontiers in Immunology, 11, 503079. https://doi.org/10.3389/fimmu.2020.503079
6. Knöfler, M., Haider, S., Saleh, L., Pollheimer, J., Gamage, T. K., & James, J. L. (2019). Human placenta and trophoblast development: Key molecular mechanisms and model systems. Cellular and Molecular Life Sciences, 76(18), 3479–3496. https://doi.org/10.1007/s00018-019-03104-6
7. Lain, K. Y., & Roberts, J. M. (2002). Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA, 287(24), 3183–3186. https://doi.org/10.1001/jama.287.24.3183
8. Mani, S., & Suresh, S. (2020). Amniotic fluid dynamics and its clinical significance. Journal of Fetal Medicine, 7(3), 189–196. https://doi.org/10.1007/s40556-020-00260-2
9. Morton, J. S., & Davidge, S. T. (2013). Maternal cardiovascular adaptations to pregnancy. Comprehensive Physiology, 3(1), 421–447. https://doi.org/10.1002/cphy.c110045
10. Powe, C. E., Levine, R. J., & Karumanchi, S. A. (2011). Preeclampsia, a disease of the maternal endothelium: The role of antiangiogenic factors and implications for later cardiovascular disease. Circulation, 123(24), 2856–2869. https://doi.org/10.1161/CIRCULATIONAHA.109.853127
11. Rodgers, S. K., Chang, C., DeBardeleben, J. T., & Horrow, M. M. (2015). Normal and abnormal US findings in early first-trimester pregnancy: Review of the Society of Radiologists in Ultrasound 2012 consensus panel recommendations. RadioGraphics, 35(7), 2135–2148. https://doi.org/10.1148/rg.2015150092 Cited by: 92
12. Sanghavi, M., & Rutherford, J. D. (2014). Cardiovascular physiology of pregnancy. Circulation, 130(12), 1003–1008. https://doi.org/10.1161/CIRCULATIONAHA.114.009029
13. Schiffer, V., Evers, L., de Haas, S., Ghossein-Doha, C., Al-Nasiry, S., & Spaanderman, M. (2020). Spiral artery blood flow during pregnancy: A systematic review and meta-analysis. BMC Pregnancy and Childbirth, 20(1), 1–12. https://doi.org/10.1186/s12884-020-03150-0 Cited by: 51
14. Soma-Pillay, P., Nelson-Piercy, C., Tolppanen, H., & Mebazaa, A. (2016). Physiological changes in pregnancy. Cardiovascular Journal of Africa, 27(2), 89–94. https://doi.org/10.5830/CVJA-2016-021
15. Underwood, M. A., Gilbert, W. M., & Sherman, M. P. (2005). Amniotic fluid: Not just fetal urine anymore. Journal of Perinatology, 25(5), 341–348. https://doi.org/10.1038/sj.jp.7211290