REPD 372 Module 4 Content PDF

SECTION 01: MATERNAL AND FETAL TIMELINES 1.1 SECTION 01: MATERNAL AND FETAL TIMELINES Pregnancy is a unique state involving adaptations to the female body designed to accommodate and sustain the development of the fetus. In this section, you will explore the timeline of human pregnancy, learn the...

SECTION 01: MATERNAL AND FETAL TIMELINES 1.1 SECTION 01: MATERNAL AND FETAL TIMELINES Pregnancy is a unique state involving adaptations to the female body designed to accommodate and sustain the development of the fetus. In this section, you will explore the timeline of human pregnancy, learn the clinical terms that define maternal changes and fetal developmental changes that characterize pregnancy, as well as explore how this knowledge is used for monitoring the health of both mother and fetus. Before delving into the materials and concepts of this module, watch this TED talk that provides a visual overview of human development from conception to birth using high resolution 3D images. Notice the remarkable process by which embryonic structures form and the rapid growth of the fetus as it prepares to be brought into the world. 1.4 TRIMESTERS OF PREGNANCY The average human pregnancy, also known as gestation, is about 38-40 weeks (approximately 9 months), starting from the first day of a woman's last menstruation up until the date of delivery, and is traditionally divided into three trimesters, to facilitate clinical tracking. However, the real number of weeks within each trimester will vary slightly between individual women, so each trimester is defined as roughly 12-14 weeks, for a total duration of 40-42 weeks. Each trimester is characterized by specific maternal physiological changes and fetal developmental stages. FIRST TRIMESTER The first trimester lasts from the week of conception until about the 13th week of gestation. This is a period of rapid development in the embryo in which all organ systems are being developed. Note that these processes occur before the stage of their visible development. The mother's body undergoes significant changes during these weeks to accommodate the growing fetus; these include increasing its blood supply to carry more nutrients and oxygen, as well as an elevated heart rate. Circulating hormone levels also drastically change during this time. These changes result in some of the common early symptoms of pregnancy, which include but are not limited to: fatigue, morning sickness, headaches, and constipation. SECOND TRIMESTER The second trimester occurs between the 13th week to about 26th week of gestation. During this time, the uterus expands and the fetal organs continue developing. Around the 20th week of gestation, the hair, nails, and reproductive organs are fully developed. As such, the sex of the fetus can be determined during this trimester. Bones and teeth continue to harden, and the nervous system becomes functional. The fetus begins to make movements during this period, and most women feel the baby kick at around 20 weeks of gestation. Some symptoms that the mother may experience in this period include body aches, dizziness due to low blood pressure, and swelling of the hands and feet. THIRD TRIMESTER The third trimester lasts from around week 27 to the birth of the baby, which normally takes place between weeks 37 to 42. During this time the fetus begins to gain weight while simultaneously slowing its growth lengthwise. Some fetal systems such as the respiratory system begin to mature just before birth, which is why many premature babies have respiratory difficulties. At this point in the pregnancy, women will visit their healthcare provider every 2 weeks until the last month of pregnancy, where they will have weekly appointments until their delivery. During these appointments, maternal blood pressure and urine samples are taken to check for signs of urinary tract infections, as well as other potential problems. The physician will also check the mother's cervix and the baby's position to s see whether the baby is in the appropriate cephalic (head-down) position, or in the breech position (bottom-down) position which can complicate delivery. 1.6 FETAL VULNERABILITY The first trimester is the most vulnerable time for the fetus. Agents that have the ability to cause birth defects are called teratogens. Examples of teratogens include radiation, alcohol, or certain prescription medications. Because of this, miscarriages are also most common during the first trimester, with 80% of miscarriages occurring during this period. Miscarriages occur in approximately 10-25% of clinically recognized pregnancies. Causes of a miscarriage are varied, but those that occur in the first 13 weeks are most often due to chromosomal or genetic abnormalities of the embryo. Note that the critical developmental period occurs in the first 12-14 weeks of gestation. When thinking about gestational age, think about the length of pregnancy. When thinking about fetal age, think about the age of the embryo since it came to be at the moment of fertilization. **Teratogen:** Any agent that has the ability to cause birth defects in the developing embryo. **Miscarriage:** An event that results in the loss of a fetus in the first 20 weeks of pregnancy. **Clinically recognized pregnancies:** A pregnancy confirmed by ultrasound visualization. 1.7 TIMING OF DELIVERY When a pregnancy has lasted between 37 and 41 weeks, it is considered to be \"full term\" or carried \"to term\". Such pregnancies are associated with fewer complications and the optimal health outcomes for the baby. However, pregnancies can end before or after this period. **Preterm:** Pregnancies that result in birth before 37 weeks are considered preterm, because they are associated with maternal complications and worsening health outcomes for the baby the earlier childbirth occurs. **Full Term:** Pregnancies carried for 37 - 40 weeks are considered to be full term, which is considered the optimal time for delivery. Pregnancies carried for 41 weeks are considered late term. **Post term:** Pregnancies carried beyond 42 weeks are considered post-term, as the risks for complications increase significantly for both mother and fetus. Obstetricians will generally induce labour between weeks 41 and 42. The 6-week period immediately after pregnancy is known as the postnatal period or puerperium. This is a critical time during which the mother undergoes significant physical and psychological changes as the body returns to its pre-pregnancy condition. **Obstetricians:** Physicians specializing in the care of women and their reproductive health, specifically with pregnancy and birth. **Induce:** The act of starting labor via medical intervention, due to complications for either the mother or the baby. It can be done via mechanical or drug interventions. 1.8 WHY IT MATTERS: CALCULATING ESTIMATED DATE OF DELIVERY By measuring gestational age, the estimated date of delivery can be calculated using what is known as Naegele\'s Rule. Naegele\'s rule is a standard way of calculating the delivery date for a pregnancy under the common assumption of a gestational age of 280 days at childbirth. Using this rule, an estimated date of delivery can be calculated by following three simple steps. - Determine when was the first day of your last menstrual period (LMP) - Count back 3 calendar months from the previous date - Add 1 year and 7 days to that date On the next page you will have the opportunity to calculate the estimated date of delivery of a pregnant patient using Naegele's rule, which can be expressed using the equation: (Gestational Age) -- (3 Months) + (1 year and 7 days) = Estimated Date of Delivery Alt Text: Pregnancy wheels are often used to calculate the due date of delivery. 1.10 DEVELOPMENTAL TIMELINE The baby's development is divided into two major stages which encompass the process of growth and maturation in utero. The embryonic stage comprises the first 8 weeks of development (fetal age), and the developing offspring is called an embryo. It occurs during the first trimester of pregnancy and is characterized by major morphological changes, as all organ structures are being established. This stage was first studied and classified by Dr. Franklin P. Mall. The fetal stage begins after the 8th week of development (around 10 weeks gestation, after Carnegie stage 23), and the developing offspring is called a fetus. It occurs during the final weeks of the first trimester and extends until birth. It is characterized by growth and continued development of the structures established during the embryonic stage. Next you will learn the details of the embryonic and fetal stages. 1.10.1 THE CARNEGIE STAGES OF THE EMBRYONIC PERIOD Embryo development is difficult to track by chronological age or size. Embryologist Franklin P. Mall was the first person to stage the development of human embryos based on morphology. Using photographs of embryo specimens he began collecting in 1887, he and his collaborators categorized the morphological changes of the embryonic period into 23 stages known as Carnegie Stages, which continue to be the standard of embryo classification. These stages were named based on the studies performed at the Department of Embryology at the Carnegie Institution of Washington, D.C. (USA). 1.11 THE HUMAN EMBRYONIC PERIOD (WEEKS 1-8) As you have learned, the embryonic period is the stage of development in which all organ systems are established. **Weeks 0-2** *Carnegie stages 1-6* In the first two weeks of development (preimplantation), the zygote travels towards the uterine cavity and undergoes cleavage. By the time it reaches the uterus, it has become a blastocyst. After hatching from the zona pellucida, the blastocyst implants into the uterine wall and eventually develops the germ layers that will give rise to organ systems. **Weeks 3-4** *Carnegie stages 7-13* The body plan is established. The mesoderm layer begins its differentiation into muscle, kidneys, bones, and heart, the ectoderm into the nervous tissues and skin, and the endoderm into the digestive tract, lungs, and liver. Primordial germ cells begin to migrate towards the gonadal ridges. Wolffian and Müllerian ducts begin to form. Early blood vessels, red blood cells, and the primitive heart appear in week 3. By week 4, a primitive heart beats around 113 times per minute, becoming the first functioning organ of the embryo. **Week 5** *Carnegie stages 14-15* The four major chambers of the heart become visible (the primitive heart which begins beating in Week 3, consists of only two, joined, contractile tubes). Upper and lower limbs begin to bud from the embryo and grow. The future cerebral hemispheres become visible. **Week 6** *Carnegie stages 16-17* Primordial germ cells arrive at and invade the gonadal ridges. The heart and lungs begin to descend into the thorax. The heart starts to beat at a regular rhythm. **Weeks 7-8** *Carnegie stages 18-23* The embryo transitions into the fetal stage. Fingers become visible. Cartilage begins to be replaced by bone. The gonads differentiate. In males, primitive testes begin their slow descent. Genitals are undifferentiated until Week 9. Note: You don't need to memorize the Carnegie stages, but recognize the developmental milestones at each week of development, particularly the reproductive system (as learned in Module 1). 1.12 THE FETAL PERIOD (WEEKS 9 - BIRTH) According to Carnegie staging, the fetal stage begins after Carnegie stage 23, around week 9 of gestation, and continues until the moment of birth. This is a period of continued growth and development of the organs formed during the embryonic period; the fetus also grows rapidly in length and weight during this period. **Fetal Age: 8 weeks (kumquat)** At a fetal age of 8 weeks, the embryo tail disappears, and it is now called a fetus. The fetus is about 3 cm long and weighs roughly 35g. **Fetal Age: 11 weeks (lemon)** The fetus is now 6.5 cm long and weighs about 75g. All the major organs have formed. **Fetal Age: 14 weeks (avocado)** The fetus is now around 18 cm long and weighs approximately 150g. **Fetal Age: 21 weeks (grapefruit)** The fetus has grown to be 30 cm long and weighs about 560g. **Fetal Age: 29 weeks (coconut)** The fetus is now around 42 cm long and weighs roughly 1.4 k g. **Fetal Age: 38 weeks (watermelon)** Right before birth the fetus is approximately 52 cm long and weighs roughly 3.6 kg. 1.13 CLINICAL APPLICATION OF PREGNANCY TIMELINES Understanding the timing of maternal physiological changes as well as fetal developmental stages are key to the monitoring of maternal and fetal health during pregnancy. This knowledge has been used to inform current guidelines in maternal and fetal tests, optimal nutrition during pregnancy, and for the prevention and treatment of complications commonly experienced during pregnancy and preventative interventions for fetal complications. One specific example of a preventative measure that is suggested for all women before and during pregnancy is routine ultrasound monitoring. Most women get an ultrasound between 18 and 22 weeks of gestation. Based on what you know about the fetal developmental timeline, why is this an important period of time to perform an ultrasound? An ultrasound allows a clinician to visualize and evaluate specific fetal structures such as the heart, spine, brain, and kidneys, for the detection of abnormalities. The first trimester is a time of organ development when organ systems have not been established, so an ultrasound evaluation for detecting fetal abnormalities is most effective and accurate during the second trimester, after major organs have developed and can be assessed for anatomical abnormalities. Explore the reasons an ultrasound evaluation may be used. - **Confirm pregnancy and location:** Can be used to detect an ectopic pregnancy, which is highly dangerous for the mother. - **Confirm number of babies:** A multiple pregnancy may come as a surprise, thus an ultrasound can confirm the number of babies in the uterus. - **Determine gestational age:** Can be used to determine the due date of the baby and track important milestones. - **Evaluate fetal growth:** An ultrasound can determine if the fetus is growing at a normal rate. They can monitor movement, breathing, and heart rate. - **Evaluate placenta and fluid levels:** The placenta provides nutrients and oxygen-rich blood, while the amniotic fluid protects the fetus. Both are critical during pregnancy. - **Identify birth defects:** Some birth defects can be detected using an ultrasound. - **Determine fetal position before delivery:** A headfirst position is needed for delivery, so an ultrasound can confirm the baby's position to determine the delivery options. - **Other prenatal tests**: In case of an abnormality, other tests may be recommended based on the ultrasound results. **Amniotic fluid:** The fluid that surrounds the fetus in the uterus during pregnancy. SECTION 02: MATERNAL-FETAL CIRCULATION: DEVELOPMENT OF THE PLACENTA The placenta is the organ that acts as an interface between the mother and fetus. In this section, we will explore the process by which feto-maternal circulation is established via the formation of the placenta, we will learn the normal structure and physiology of the placenta, as well as its roles and functions in pregnancy. 2.2 THE PLACENTA As you have learned in Module 3, the embryo implants into the decidua and initially receives histiotrophic nutrition from the secretions of the uterine glands. To continue its growth, the developing embryo needs to quickly establish a link with the maternal circulation in order to receive nutrients and regulate other functions it cannot perform on its own. The placenta is a temporary organ that develops from both maternal and fetal tissues during pregnancy to help the development of the fetus by regulating its nutrient uptake, thermo-regulation, waste elimination, and gas exchange via the mother\'s blood supply. Switch between an illustration of the placenta and a plastinated human placenta. 2.3 IMPLANTATION AND PLACENTATION In humans, the process of implantation is highly invasive, as the embryo embeds itself completely into the maternal decidua. Thus, the human placenta is hemochorial, which is the most invasive type among placental mammals, based on the layers of separation between maternal and fetal circulation. Other species demonstrate varying degrees of placental invasiveness. **Epitheliochorial** The least invasive type, where maternal blood is kept separate from fetal tissues by three maternal tissue layers: endothelium, connective tissue, and epithelium. This placenta is observed in cows, pigs, and horses. **Endotheliochorial** Maternal blood is separated from the fetal membranes by a layer of maternal endothelium and some interstitial tissue. It can be observed in dogs and cats. **Hemochorial** The human placenta allows the fetal membranes to be bathed directly with maternal blood. We share this type of placenta with mice and rabbits, among others. 2.4 PRIMARY FUNCTIONS OF THE PLACENTA **Nutrient and Oxygen Exchange** A primary function of the placenta is to supply adequate nutrition to the growing fetus. As the interface between mother and fetus, it regulates the exchange of oxygen, carbon dioxide, and other nutrients. **Protection** The placenta acts as a barrier, reducing fetal exposure to xenobiotic substances that may be harmful to the fetus. **Hormone production** The placenta releases a number of key hormones into fetal and maternal circulation that regulate maternal metabolism, fetal growth, as well as other functions. **Excretion** Waste products from the fetus diffuse across the placenta to the maternal blood where they may be excreted through the mother's urine. **Attachment to Uterine Wall** All of the other functions of the placenta are made possible by the proper anchoring of the placenta to the uterine wall. **Xenobiotic:** A substance that is foreign to the body. 2.5 VIDEO: FORMATION AND DEVELOPMENT OF THE PLACENTA The placenta starts to form as soon as implantation starts. After the embryo survives the pre- implantation period and manages to form the initial attachment to the uterine wall, it begins to bury itself into the decidua. The invasion of the embryo marks the beginning of placental formation. 2.6 TROPHOBLAST INVASION Human placental formation begins with implantation, when the trophectoderm or trophoblast layer, the outer layer of cells that first appears during the blastocyst stage, initiates the attachment to the maternal decidua. As you saw in Module 03, around day 9 post-fertilization, the trophoblast cells grow and invade the decidua, anchoring and invading the uterine surface to try to reach and access the maternal blood vessels. After this initial invasion (about 7 days post fertilization), trophoblasts differentiate into two cell types, the cytotrophoblast and the syncytiotrophoblast, which develop concurrently to fulfill unique functions. 2.6.1 SYNCYTIOTROPHOBLAST The syncytiotrophoblast layer is composed of cytotrophoblast cells that fuse together into a multinucleated, continuous cell layer (without cell borders) known as a syncytium. It comprises the outermost layer of the trophoblast cells and it actively migrates and invades the decidua. The syncytiotrophoblast will go on to become the blood-placental barrier, helping regulate efficient nutrient/gas exchange, enabling the production of placental hormones, and regulating immune tolerance of the fetus by the maternal immune system. As the syncytiotrophoblast layer expands, hollow spaces begin to form called lacunae. These individual spaces will continue to grow and eventually fuse into a larger space known as the intervillous space. 2.6.2 CYTOTROPHOBLAST Cytotrophoblasts comprise the inner layer of trophoblast cells, which produce proteolytic enzymes to facilitate the invasion of the decidua. These cells replenish the cells of the outer syncytium layer, and are thus called germinal cells of the syncytium. These cells, unlike the cells of the syncytium, have a clear cell border and a single nucleus. 2.7 DIFFERENTIATION OF THE INNER CELL MASS The blastocyst invades the decidua until it becomes fully encased within the endometrium. While the outer trophoblast layer differentiates and invades the decidua, the inner structures of the blastocyst also develop. Recall from Module 1 that the inner cell mass forms a flattened bilayered embryonic disc consisting of the epiblast and hypoblast. At around day 9, the hypoblast gives rise to the extraembryonic mesoderm, a layer of cells between the outer cytotrophoblast layer and inner cell mass, which will later support the development of key structures, such as the amnion, the yolk sac, and the chorionic villi of the placenta, which you will learn about in the next pages. **Hypoblast:** The layer of the bilayered embryonic disc, derived from the inner cell mass, that faces the blastocyst cavity. This layer does not give rise to embryonic structures, but instead supports the development of the embryo. **Epiblast:** The layer of the bilayered embryonic disc, derived from the inner cell mass, that eventually gives rise to all embryonic structures. **Amnion:** A membranous sac that surrounds and protects the embryo. **Yolk sac:** The yolk sac is one of the three embryonic cavities (chorion, amnion, and yolk sac), that appears as of day 8 of human development. Hypoblast cells are considered the developmental origin of the human yolk sac. 2.8 FORMATION OF CHORIONIC VILLI Once implantation is complete, the cytotrophoblast layer continues to grow, and the cells form finger-like projections through the syncytium known as chorionic villi. Depending on their stage of development, chorionic villi can be classified as primary, secondary, or tertiary villi. These villous structures will be the ones in direct contact with the maternal blood. **Primary Villi** Primary villi form as the cytotrophoblast cells invade and protrude into the syncytiotrophoblast layer. They are small and avascular, with a cytotrophoblast core surrounded by a layer of syncytium, as depicted in the cross-sectional diagram. **Secondary Villi** Secondary villi are composed of an extraembryonic mesodermal core and are covered by a layer of cytotrophoblast cells and an outer syncytiotrophoblast layer. **Tertiary Villi** As the embryonic blood vessels develop in the mesodermal core of secondary villi, they become tertiary villi. Tertiary villi have an extraembryonic mesodermal core with villous capillaries and are covered by a cytotrophoblastic and syncytiotrophoblastic layer. **Avascular:** Lacking blood vessels. 2.9 FORMATION OF THE CYTOTROPHOBLASTIC SHELL As tertiary villi continue to grow, cytotrophoblasts will invade and pass through the syncytiotrophoblast layer to come in direct contact with the maternal decidua. At this point, the cytotrophoblasts begin to proliferate laterally and eventually form a cytotrophoblastic shell surrounding the syncytiotrophoblasts and the entire embryo. Large tertiary villi that connect this cytotrophoblastic shell to the chorionic plate are known as anchoring villi. These will grow villous branches known as floating villi. The space between the villi will become the intervillous space, between the chorionic shell and the chorionic plate. This is where the maternal circulation will pool and bathe the chorionic villi. Together, the shell and the chorionic plate surround the embryo and form the chorion. **Chorionic plate:** The base, the fetal side of the placenta, from which chorionic villi originate. **Chorion:** A double-layered membrane formed by the cytotrophoblastic shell and the chorionic plate. This structure forms the outermost covering of the embryo, amnion, and yolk sac, and will eventually give rise to the fetal side of the placenta. 2.10 ASYMMETRICAL VILLI DEVELOPMENT Although primary and secondary villi project practically uniformly from the entire surface of the chorionic plate, tertiary villi develop asymmetrically, growing specifically at the anchoring side of the embryo, where it faces the maternal decidua. This highly villous area becomes known as the chorion frondosum, the fetal side of the placenta. Any villi on the opposite side will atrophy, creating a smooth surface known as the chorion laeve. The side of the decidua where the chorion frondosum attaches and grows is called decidua basalis, while the other side of the decidua surrounding the embryo is called the decidua capsularis, as it does not interact with chorionic villi and will later become a smooth layer. 2.11 ADDITIONAL FETAL MEMBRANES The fetus will grow inside the extraembryonic membranes, which are the additional layers that project from the placenta and surround the fetus to protect and assist in its development. **Amnion** The innermost membrane that surrounds the embryo. It is a transparent membrane containing the amniotic fluid, which protects the embryo from mechanical stress and impact. **Yolk sac** A small sac on the ventral surface of the embryo. Its most important functions occur in early pregnancy, such as being the source of primordial germ cells and blood cells. It regresses in later stages of pregnancy. **Allantois** A hollow sac on the tail end of the yolk sac. It contributes to nutrition and excretion and helps form the umbilical cord. **Chorion** The outermost fetal membrane, it surrounds all other membranes and the embryo and forms the fetal side of the placenta. It includes the chorion frondosum and chorion laeve. **Extraembryonic coelom** The space between the amnion and the chorion. 2.12 SPIRAL ARTERY REMODELLING The blood vessels that supply the uterus are characterized as having a spiral shape, particularly in the basal layer of the endometrium (the side in contact with the myometrium). These are the arteries that will supply the placenta and the growing fetus. A highly invasive type of cytotrophoblast arises from the tips of anchoring villi, known as extravillous trophoblasts. These will migrate towards the maternal arteries (not the veins), and cause major modifications of their walls, a process known as spiral artery remodeling. This is a critical step in the establishment of the placenta, as these arteries will feed into the intervillous space, where the maternal blood comes into contact with the fetal membranes. 2.12.1 THE PROCESS OF SPIRAL ARTERY REMODELLING **1. Early Pregnancy** The extravillous trophoblasts proliferate from anchoring villi and invade the maternal decidua. **2. End of First Trimester** Extravillous trophoblasts differentiate into two types. Interstitial extravillous trophoblasts: these cells invade deeper into the decidua and surround the spiral arteries. Endovascular extravillous trophoblasts: these cells penetrate the lumen of the uterine spiral arteries. **3. Midgestation** Both types of extravillous trophoblasts are involved in the degradation of maternal vascular endothelium, and the replacement of smooth muscle and connective tissue of the arteries with fibrous material. As a result, maternal spiral arteries become wider, which decreases vascular resistance and allows a higher volume of blood flow compared to normal arteries. **4. 3rd Trimester** By the third trimester, the blood supply to the uterus and placenta has increased by a factor of 10 compared to the non-pregnant uterus as a result of spiral artery remodeling. 2.13 PLACENTAL CIRCULATION As the organ that permits the connection between mother and fetus, the placenta acts as the interface between two circulatory systems: the uteroplacental (maternal-placental) blood circulation, and the fetoplacental blood circulation. 2.13.1 FETOPLACENTAL CIRCULATION The fetus is attached to the placenta via the umbilical cord. Since the umbilical cord connects to the placenta and is not directly connected to the mother's circulatory system, it transports oxygen and nutrients to and from the mother's blood without allowing direct mixing. The umbilical cord contains three vessels. **One umbilical vein:** Carries oxygenated, nutrient-rich blood from the placenta to the fetus. **Two umbilical arteries:** Carries deoxygenated, nutrient-depleted blood from the fetus to the placenta. 2.13.2 UTEROPLACENTAL CIRCULATION Uteroplacental circulation begins around the end of the first trimester, although maternal blood vessels continue to be remodeled until the third trimester. Maternal blood flows from the uterine spiral arteries into the intervillous space, allowing for the exchange of oxygen and nutrients between maternal blood and the fetal blood vessels within the chorionic villi. The in-flowing maternal arterial blood pushes deoxygenated blood into the endometrial veins and back into the maternal circulation. 2.14 MATURATION OF THE PLACENTA The placenta continues to grow in thickness and circumference until the end of the fourth month of gestation. The increased thickness of placenta is the result of the lengthening and branching of the villi in the chorion frondosum, with an accompanying expansion of the intervillous space. After the fourth month, the placenta no longer increases in thickness, but as the fetus grows, the circumference of the placenta continues to increase throughout the remainder of the pregnancy. 2.15 THE PLACENTA AS AN IMMUNE BARRIER The fetus grows in an isolated environment created by the placenta and the extraembryonic membranes. All nutrients and molecules needed by the fetus come through the feto-placental barrier, which is created by the syncytiotrophoblasts that enclose the intervillous space. This barrier has two functions: 1. **Prevent maternal immune rejection:** The fetus is genetically different than the mother. The feto-placental (or blood-placental) barrier maintains the separation between maternal and fetal blood to prevent the mother's immune cells from detecting the fetal tissues and potentially rejecting them as a foreign body. Although not fully understood, there are changes to the maternal immune system that lead to immune tolerance. These are established in the early stages of placental development and will be discussed in Section 3. 2. **Protect the fetus from pathogens:** The feto-placental barrier also shields the fetus from potential pathogens or toxins that may have accessed the maternal circulation or the uterine cavity via the vaginal canal. However, there are pathogens capable of breaching this barrier. Although the exact mechanisms are not well understood, one of the potential mechanisms is the direct infection of trophoblast cells, which then allows the pathogen to spread to the fetus. 2.16 WHY IT MATTERS: CALCULATING ESTIMATED DATE OF DELIVERY The placenta is a fully formed, complex organ that develops exclusively for the survival of the fetus and it is disposed of at the end of the pregnancy. Understanding the normal anatomy of the placenta allows us to understand how to manage placental complications that can put maternal or fetal health at risk. You will cover some example placenta-related complications in Section 4. SECTION 03: MATERNAL ADAPTATIONS TO PREGNANCY 3.1 SECTION 03: MATERNAL ADAPTATIONS TO PREGNANCY Throughout pregnancy, the mother\'s body undergoes massive changes in order to accommodate and meet the demands of the developing fetus while also maintaining homeostasis. These changes are mostly orchestrated by a number of hormones whose production is stimulated by the fetus or produced by the fetus itself. In this section, you will learn about various hormonal physiological changes that occur in the reproductive system and other organs, and how these changes are regulated by fetal and maternal hormones. 3.2 HORMONES ARE EVERYTHING Recall from Module 02 that after ovulation, the corpus luteum will secrete estrogen and progesterone, the sex hormones that promote the remodeling of the uterine lining in preparation for pregnancy, among other physical changes. The corpus luteum will secrete hormones until around 10 days after which it will undergo involution. The declining levels of these hormones trigger menstruation will be triggered by the declining levels of these hormones. However, in the case of a pregnancy, the implanting embryo stimulates the survival of the corpus luteum for a few additional weeks via the release of human chorionic gonadotropin (hCG) hormone. Using what you learned in previous modules, predict which cells on the implanting embryo will produce hCG and what their function might be. Human chorionic gonadotropin (hCG) is a hormone produced by trophoblast cells, especially syncytiotrophoblasts, shortly after they develop and invade the decidua. The main function of hCG is to substitute the effects of LH in supporting the survival and function of the corpus luteum, inducing the corpus luteum to grow and continue to produce progesterone and estrogen. 3.3 WHY IT MATTERS: PREGNANCY TESTS Over-the-counter, hormonal pregnancy tests are one of the easiest and quickest methods to confirm a pregnancy. These tests are as accurate as the urine tests performed at the doctor's office. They work by measuring the hCG hormone levels in urine. HCG is only synthesized by the body after implantation, once the trophoblast cells have differentiated and developed sufficiently to begin producing hormones. A pregnancy test is most accurate when taken after the first missed menstrual cycle to ensure there are detectable levels of hCG, if present. A blood test is more sensitive and can detect a pregnancy up to a week earlier than a urine test. 3.4 SEX HORMONES DURING PREGNANCY Estrogen and progesterone are stimulated by the embryo but go on to be synthesized by the placenta. **First Trimester** Embryo implantation occurs around 5-6 days after ovulation. The corpus luteum begins to degrade around 10 days after ovulation. HCG must appear by the 10th day post ovulation (4 days after implantation) to stop the corpus luteum from degrading. **Second Trimester** After the 12th week of development, the placenta starts producing enough progesterone and estrogen to sustain the remainder of the pregnancy. The production of hCG by the embryo decreases and the corpus luteum degrades between the 13th and 17th week of gestation. **Third Trimester** Once the placenta takes over the production of progesterone and estrogen, the levels of estrogen and progesterone increase steadily until the end of the pregnancy. They are largely responsible for the many physiological changes observed during pregnancy. 3.5 OTHER HORMONAL CHANGES DURING PREGNANCY Other endocrine glands in the body undergo significant changes in their function during pregnancy. During pregnancy, the anterior pituitary gland undergoes a two- to three-fold enlargement. Although the sex hormones (progesterone and estrogen) supress the production of FSH and LH throughout pregnancy, the production of other pituitary hormones is enhanced, such as corticotropin (ACTH), thyrotropin (TSH) and prolactin (PRL). **Adrenal Cortex** Adrenocorticotropic hormone (ACTH) is involved in the stress response, so it regulates a wide range of functions from appetite suppression to feelings of anxiety. In pregnancy, it is responsible for determining the length of gestation and the timing of parturition. Some is produced by the placenta as well. **Thyroid Gland** Thyroid-stimulating hormone or thyrotropin (TSH) stimulates the thyroid gland, which in turn increases the production of thyroid hormones by 40 to 100 percent. These changes increase maternal metabolic rate, to meet the nutrient demands of the fetus. Also, maternal thyroxine can cross the placenta and is required by the fetus in the first 12 weeks of development, to maintain its thyroid function. **Mammary Glands** Prolactin (PRL) mainly stimulates the mammary glands to produce milk. Early in pregnancy, PRL stimulates the proliferation of glandular epithelial cells and presecretory alveolar cells of the breast, causing the breasts to grow. After birth, PRL is released in pulsatile bursts in response to suckling by the baby. **Ovary** As we learned, the placenta takes over the production of estrogen and progesterone, and their levels increase steadily through pregnancy. As such, FSH and LH are inhibited for the duration of the pregnancy, thus preventing ovulation from happening during this time. After birth, it takes between 2 months to a year for the hormonal cycle to be restored to its normal state and begin the cycle of ovulation. **Parturition:** The process of childbirth or labour. 3.6 PHYSIOLOGICAL CHANGES IN THE REPRODUCTIVE SYSTEM During pregnancy, major anatomical and physiological adaptations occur to the female reproductive system. 3.6.1 MAMMARY GLANDS Under the influence of estrogen, progesterone, and prolactin, the breasts increase in size throughout pregnancy. Vascular supply to the breasts increases. The ducts, alveoli, and mammary epithelium undergo hyperplasia in preparation for lactation. The first milk, called colostrum, appears in the alveoli of the acinar glands as early as the second trimester. However, milk production is inhibited until after childbirth. 3.6.2 UTERUS During pregnancy, the endometrial layer of the uterus is transformed by decidualization. Uteroplacental blood flow doubles by mid-gestation, due to spiral artery remodeling. The uterus is stretched to accommodate the fetus, placenta, and amniotic fluid, causing hypertrophy of the muscle cells of the myometrial layer. By the end of the pregnancy, the volume capacity of the uterus has increased 500 to 1000 times. 3.6.3 CERVIX Through pregnancy, the cervix softens due to undergoing connective tissue remodeling. This is necessary to permit a variety of functions such as maintenance of structural integrity to carry the pregnancy to term, but also allowing dilation during delivery and repair following parturition. Cervical glands double in number and create a mucus plug, that acts as a barrier to protect the uterine contents from infections. This plug is expelled shortly before delivery. 3.7 PHYSIOLOGICAL CHANGES IN OTHER SYSTEMS We will now explore some of the major physiological changes each bodily system undergoes in response to pregnancy. Remember that these changes are orchestrated via the complex hormonal pathways of pregnancy. 3.7.1 THE CIRCULATORY SYSTEM Pregnancy places significant demands on the cardiac metabolism. Cardiac output begins to increase as early as 5 weeks of gestation. Cardiac output increases as much as 50% by mid-pregnancy, as a result of an increase in heart rate and stroke volume. There is also an increase in blood volume and red blood cell mass. The increased blood flow to the placenta causes a drop in total vascular resistance. These changes begin to reverse as early as 2 weeks postpartum. **Cardiac Output:** the volume of blood being pumped by the heart per unit time. **Stroke Volume:** the volume of blood pumped from the left ventricle per heartbeat. It is one of the determinants of cardiac output. 3.7.2 THE METABOLIC SYSTEM The metabolic needs of the fetus peak in the third trimester, which is the phase of greatest growth. Because of this, maternal metabolism in early pregnancy is largely anabolic, storing nutrients for the upcoming demands. In late gestation, maternal metabolism becomes largely catabolic, directing nutrients to the rapidly growing fetus. Insulin resistance develops in early pregnancy, to limit maternal glucose consumption and direct most of it to the fetus. In late pregnancy, maternal adipose tissue releases fatty acids for use by the liver and muscle. The liver metabolizes fatty acids to make ketones that are usable by the brain, muscle, and fetus, but uses glycerol and amino acids to synthesize glucose for the fetus. **Anabolic:** involving metabolic pathways that build new molecules out of the products of catabolism, which are used to build and maintain cellular structures. **Catabolic:** involving metabolic pathways that breakdown molecules into usable forms; energy is either stored in energy molecules or released as heat. **Insulin Resistance:** when cells in muscle, fat, and liver become resistant to insulin signaling, which prevents proper uptake of glucose by cells. 3.7.3 THE MUSCULOSKELETAL SYSTEM The mother gains 10-15 k g of weight during pregnancy. About 3 k g of the weight gain is the fetus, 1.8 kg is amniotic fluid and fetal membranes, 1 kg is the overgrown uterus, 1 kg is in the breasts, and 1.3 kg can be attributed to fat accumulation. This weight gain causes a shift in the body's center of gravity, which requires a realignment of the spinal curvature and pelvic tilt that leads to lumbar lordosis. Additional biomechanical changes include increased joint mobility due to ligamentous laxity, particularly of the sacroiliac joints, which will facilitate delivery later on. Stretching of the abdominal ligaments results on diastasis recti. **Lumbar Lordosis:** Excessive inward curvature of the spine, in this case, the lumbar region. **Diastasis Recti:** The separation of the two sides of the rectus abdominis muscle. 3.7.4 THE IMMUNE SYSTEM To ensure fetal tolerance, trophoblast cells produce factors that suppress the maternal immune response. This immune tolerance prevents rejection of paternal antigens expressed by the fetus, but it also changes disease susceptibility, making women more susceptible to infectious diseases and less susceptible to inflammatory diseases. Immune cells are key for placenta development. During implantation, the decidua is populated by a large variety of immune cells. In the first trimester, 70% of these cells are uterine (or decidual) natural killer cells (uNK or dNK). uNK cells secrete factors that promote early vascular remodelling and help establish fetal tolerance. They are considered critical for the establishment of pregnancy. Their numbers begin to decline at mid-pregnancy, reaching normal levels at term. 3.7.5 THE RESPIRATORY SYSTEM With increased metabolic and cardiac needs, oxygen requirements also increases significantly during pregnancy. Oxygen consumption increases about 20 percent through pregnancy, and 40-60 percent during labour. The higher number of red blood cells increases the mother's oxygen-carrying capacity. Around the 6th month of gestation, the fetus begins to exert increasing pressure on the mother's diaphragm. This reduces lung capacity and causes an increase in minute ventilation. **Minute Ventilation:** The volume of gas inhaled or exhaled per minute. 4.1 SECTION 04: PARTURITION The process of childbirth, also known as parturition, is a stepwise process that involves a series of physiological changes that culminate in the moment of delivery and birth of the baby. In this module, you will learn the details of the process of parturition as well as the postpartum period, which is also key for the proper recovery of normal maternal physiology. 4.2 NORMAL PARTURITION: STAGES OF NORMAL LABOUR Parturition is the process by which childbirth occurs, also known as labour and delivery. Vaginal birth is the natural and most common way for childbirth to occur, and proceeds in three stages. 4.2.1 STAGE 1: ONSET OF LABOUR This is the stage preceding labour, characterized by the beginning of regular uterine contractions. It includes the latent phase and the active phase. Uterine contractions are controlled by a positive feedback loop known as the Ferguson reflex. Think back to 'Principles of Mammalian Physiology II' and review the steps involved in the positive feedback reflex of parturition. **Step 1** The pressure of the fetal head on the cervix causes stretching of the mother's cervix and also causes stretching of the uterine walls. **Step 2** In response to the stretching, nerve impulses are sent to the hypothalamus in the brain. **Step 3** The hypothalamus signals the posterior pituitary to release Oxytocin. **Step 4** The oxytocin released from the pituitary travels through the bloodstream to the muscular walls of the uterus, and causes smooth muscle contractions of the myometrium in the uterus. Myometrial contractions increase cervical dilation, further stimulating release of oxytocin and hence the cycle continues. This process is also known as cervical ripening, which allows the baby to fit through the cervix. **Latent Phase:** the time of the onset of labour when the mother starts experiencing regular contractions until the cervix is dilated to 3cm. **Active Phase:** the contractions become increasingly intense - more frequent, longer. Strong this continues from 3 cm until the cervix is fully dilated to 10 cm. **Cervical Pipening:** The softening of the cervix in preparation for labour, usually occurring before the onset of any contractions. 4.2.1 SIGNS AND SYMPTOMS FOR THE ONSET OF LABOUR Symptoms for the onset of labour vary between women, but can include: - Lightening, when the baby moves down from the rib cage and sits lower in the pelvis. Pregnant women may find breathing easier since lungs have more room for expansion, although this puts pressure on the bladder. - Experiencing regular uterine contractions, less than 10 minutes apart, accompanied by cervical effacement and dilation. - The amniotic sac may break at this point, releasing the amniotic fluid, a process commonly called the \"water break\". 4.2.2 STAGE 2: ACTIVE LABOUR During this stage, the cervix progressively dilates until it is fully dilated to 10 c m, to be able to fit the baby's head. This process of dilation and effacement of the cervix can last between 8 to 20 hours. As mentioned before, the increasing pressure on the cervix stimulates a positive feedback cycle in which the pressure on the cervix causes the release of oxytocin, which stimulates uterine contractions that then further increase pressure on the cervix. This is known as the Ferguson reflex or fetal ejection reflex. Eventually, this leads to the expulsion and delivery of the baby. 4.2.3 STAGE 3: DELIVERY OF THE PLACENTA The third stage of labour is the shortest stage and it starts immediately after fetal birth. The time for the delivery of placenta can range anywhere between 5 to 30 minutes. In order to help deliver the placenta, the physician will put pressure on the mother's abdomen, helping detach the placenta from the uterus. Signs that indicate placental separation include a firmer uterine fundus, a sudden gush of blood from the vagina, a lengthening of the umbilical cord, and a rise of the uterus into the abdomen. 4.2.4 STAGE 4: IMMEDIATE POSTPARTUM The immediate postpartum is clinically defined as the hour or two after delivery when the tone of the uterus is reestablished. During this time, the mother is monitored closely. The most common risk is that of postpartum hemorrhage, which can happen if the uterus does not contract properly following delivery. Uterine massage is commonly used to help the uterus contract. The mammary glands contain colostrum, which is the first form of breastmilk present after delivery. It contains immune cells and nutrients, which will provide the newborn with basic immunity within the first few hours after being born. The term postpartum is also used to refer to the following 6 weeks after birth, also known as the puerperium. During this time, the mother undergoes physical recovery. 4.3 WHY IT MATTERS: COMPLICATIONS OF PARTURITION Numerous complications can still develop at the moment of parturition. About 4% of women will have a breech birth, which happens when the baby is delivered bottom first rather than head first. If the baby is in breech position, the practitioner may order an external cephalic version to turn the baby into the appropriate position for birthing. If a complication develops that puts the mother or baby at risk, labour can be medically induced or a cesarean section can be performed, which is a surgical procedure where the baby is delivered via an incision on the abdomen and through the uterus. **External cephalic version:** A procedure to turn the fetus from the breech to cephalic presentation before labour begins. **Augmentation:** The process of stimulating the uterus to increase the frequency, duration and, intensity of contractions. It has commonly been used to treat delayed labour when uterine contractions are assessed to be insufficiently strong or inappropriately coordinated to dilate the cervix. Labour augmentation has traditionally been performed with the use of intravenous oxytocin infusion and/or artificial rupture of amniotic membrane. SECTION 05: PREGNANCY COMPLICATIONS Pregnancy is a unique and delicate period of time, due to the drastic physiological changes experienced by the mother and the critical state of development of the fetus. As such, health issues can arise during pregnancy and present significant risks for both mother and fetus. In this section, you will learn about pregnancy-related complications and how they impact the health of mother and fetus. Pregnancy pathology is a broad and complex field, so this section will focus on a few selected conditions and explore how abnormal placental function is involved in their development. 5.2 HEALTH DURING PREGNANCY A pregnancy complication is any health problem caused by pregnancy or occurring during the course of pregnancy that affects the wellbeing of the mother, the fetus, or both. The term \"pregnancy complication\" is generally used to denote the symptoms and complications being experienced by the mother, but it also encompasses the effect those issues will have on the developing fetus. Pregnancy complications can arise at any time point in the pregnancy, including the postpartum period, and they can be caused by factors of maternal or fetal origin. Due to the natural link between mother and fetus, most complications, regardless of the origin, end up affecting both mother and fetus. The severity and outcome of the complication will depend on the timing of onset (pre-pregnancy, first, second or third trimester, or postnatal), and the causes (genetic anomaly, placental abnormality, etc). 5.3 ROLE OF THE PLACENTA IN PREGNANCY PATHOLOGY Since the placenta is the organ that facilitates and regulates the feto-maternal link, the majority of pregnancy complications will involve some kind of disruption to placental function, which in turn will affect fetal growth and development. As such, you will explore some common pregnancy complications and the role of placental dysfunction on the development of these pathologies. This section will focus on conditions caused by intrinsic physiological factors and exclude those caused by extrinsic factors, such as infectious diseases or exposure to drugs or toxins. 5.4 COMPLICATIONS DURING PREGNANCY **First Trimester** Complications of early pregnancy or the first trimester are generally associated with disruptions in the process of implantation or early embryo development. Any disruption to normal maternal physiology has the potential to affect the establishment of the pregnancy. For example, if the mother has a preexisting condition (e.g. hypertension, diabetes), it will usually increase the risk of developing a pregnancy complication or will compound with any pregnancy issues that may arise later. However, embryo or fetal abnormalities can also disrupt the process. **Second Trimester** In the absence of an external cause, such as a viral infection or a toxin, disorders that arise in the second trimester are often the result of issues that were initiated in the first trimester. Women with preexisting conditions like hypertension or diabetes are commonly at a higher risk of developing mid-pregnancy complications. **Third Trimester** Complications during the third trimester are challenging as clinicians need to balance the concern for maternal well-being with the consequences of a premature delivery. The earliest that a baby can survive is at 22 weeks of gestation, with a 50% chance of survival. During this trimester, any health issues that arose during the second trimester can become worsened and lead to an early delivery. 5.4.1 MISCARRIAGE (1) A miscarriage or spontaneous abortion is the loss of an embryo or fetus before the 20th week of gestation. It is the most common human pregnancy disorder with 50% of all conceptions lost before or around implantation and another 20% lost between implantation and completion of the first trimester. The cause of placental abnormalities or other defects that lead to miscarriage is often unknown. Miscarriages most often occur as a natural response to the presence of an abnormality, to prevent a potentially unhealthy pregnancy from moving forward. A large portion of such defects is caused by fetal chromosomal abnormalities (aneuploidies), which as we have seen before, are highly prevalent in humans. In about two-thirds of early pregnancy failures, there is anatomical evidence of defective placentation, mainly featuring a thinner and fragmented trophoblast shell and reduced cytotrophoblast invasion of the endometrium. For example, an anembryonic pregnancy is a condition where the embryo does not develop, leaving only the gestational sac. The body typically eliminates the gestational sac naturally, resulting in a clinical miscarriage, even if no embryo is present. **Defective placentation:** Abnormal and/or insufficient development of the placenta. 5.4.3 PREECLAMPSIA Preeclampsia is the most severe hypertensive disorder of pregnancy, characterized by high blood pressure and proteinuria (excess presence of protein in urine) after 20 weeks of gestation. It affects between 3-6% of pregnancies and accounts for more than 75,000 maternal deaths a year worldwide. Its main danger is that it can evolve into eclampsia, which is the onset of seizures in a woman with preeclampsia and is considered a medical emergency. 5.4.4 PREECLAMPSIA IS ASSOCIATED WITH IMPAIRED PLACENTATION The cause of the condition is still unknown, but it is clearly associated with impaired placentation in the first trimester. During the process of placentation, the trophoblast invasion and remodeling of the uterine arteries is impaired, resulting in arteries that are smaller in diameter. As pregnancy continues, this leads to inadequate placental perfusion that in turn, results in placental ischemia. The immune system identifies this as a stress signal, leading to the local production of inflammatory signals that, over time, will induce changes to the cardiovascular profile of the mother. **Placental ischemia:** in insufficient or inconsistent oxygen and nutrient flow to the placental bed. 5.4.4 ANTEPARTUM HEMORRHAGE Antepartum hemorrhage is defined as bleeding that occurs after the twentieth week of gestation but before birth and it is considered a medical emergency. It is usually caused by abnormalities with the anatomy of the placenta. Some of the maternal and fetal life-threatening causes of antepartum bleeding include abruptio placenta and placenta previa. Management of the condition will depend on the cause of bleeding, but generally includes delaying delivery or inducing delivery if the bleeding is life threatening to the mother. Learn the two common examples of antepartum hemorrhage. 5.5 WHY IT MATTERS: HOW DO FETAL COMPLICATIONS AFFECT LONG -TERM HEALTH? Pregnancy complications pose significant risks to the fetus and can even affect their long-term health. There are many different pregnancy contraindications that can have these long-lasting effects, but in this module you will only explore two of the more common complications. You will explore the impact of both intrauterine growth restriction (IUGR) and preterm birth. 5.5.1 INTRAUTERINE GROWTH RESTRICTION Intrauterine growth restriction (IUGR) refers to the significant reduction in fetal growth during gestation. IUGR is typically a result of placental insufficiency. IUGR infants have a birth weight below the 10th percentile for their gestational age. This is an important distinction when classifying infants as suffering from IUGR, or as simply small for their gestational age. IUGR is estimated to affect 3-7% of all pregnancies, and has been linked to poorer health outcomes later in adult life. The health consequences of IUGR depend on the cause and extent of growth restriction. As shown in the figure, there are many potential factors that can lead to IUGR. Preeclampsia is a condition associated with impaired placentation, and results in I U G R about 30% of the time. Impaired fetal growth is associated with a higher risk of fetal morbidities, such as preterm birth and mortality in rare cases. 5.5.2 PRETERM BIRTH As previously mentioned in the module, preterm birth occurs before 37 weeks of gestation. This condition affects 5-18% of all pregnancies. Preterm births are the leading cause of neonatal death, and the second leading cause of infant deaths below the age of 5 years. Two-thirds of preterm births occur after a spontaneous onset of premature labor, while the remaining one-third of preterm births are medically induced because of maternal or fetal complications. Although numerous factors can lead to a premature delivery, the exact causes of preterm birth are not well understood. 5.6 EFFECT OF PRETERM BIRTH ON DEVELOPMENT AND ADULT HEALTH Preterm infants are exposed to various stressors and environmental conditions, both in utero and after birth, during critical stages in the development of their organ systems. These stressors can lead to permanent changes in the organ system development, which may be harmful to the long-term health of the newborn, and increase the risk of specific disorders. Long term studies have demonstrated that preterm babies and those who suffered I U G R are more likely to develop chronic disorders in adult life. These disorders include but are not limited to hypertension, coronary artery disease, and diabetes, demonstrating how the fetal environment can even impact the development of diseases later in life. 5.7 ACTIVITY: WORLWIDE TRENDS IN PRETERM BIRTHS From this table we see that the rate of preterm births increased worldwide from 1990 to 2010. This rising trend may seem counterintuitive given the advancements in medical technology and perinatal care. Interestingly, developed countries also had one of the most drastic increases in the proportion of preterm births. **Changing Pregnancy Demographics** The widespread availability of effective contraception, and other social changes, have led to women in developed countries having children later in life. Additionally, now more than ever, even women whoexperience fertility issues are able to conceive by using assistive reproductive technologies such as IVF. Both older maternal age and the use of these technologies are associated with higher rates of preterm births. **Induced Preterm Births Improve Fetal Mortality Rates** The induction of a preterm birth ultimately leads to a lower rate of stillbirths and neonatal morbidity. For example, there have been studies that have noted an association between the rising rate of Cesarean (C) sections (done both preterm and full term), with falling perinatal morbidity rates. It is likely that these preterm births are being induced via C-sections when the baby is in more distress by remaining in-utero, preventing intrauterine fetal deaths. **Reporting of Medically Induced Preterm Births** The rise in preterm births can also be attributed to the increased registration and documentation of preterm births. Rather than a genuine change in preterm births, this simply reflects improved reporting of such cases. **The Case of a Complex Relationship** Taken together, you can appreciate that not one of these factors alone accounts for why we have seen an increasing trend in preterm births. Rather, it is important to understand that there is a complex relationship between the changes seen in perinatal care and changing pregnancy demographics. To get an even deeper understanding of these intricacies, you may choose to read 5.11 MATERNAL AND FETAL SCREENING Advances in diagnostics and treatment procedures have decreased maternal and neonatal morbidity and mortality by increasing the early detection of maternal and fetal problems. The information obtained from such tests allow both medical practitioners and parents to make informed decisions about any potential interventions or the necessary preparations for a negative outcome or for the arrival of a baby with special medical needs. This figure shows the most common screening tests performed and the time of gestation when they are usually performed. Note that you do not need to memorize all of the tests or when they occur, but appreciate that the bulk of tests are concentrated in the first trimester, in accordance with the fact that this is the most sensitive developmental time for both mother and fetus. 5.11.1 MATERNAL AND FETAL OPTIMAL SCREENING TIMELINE **First Trimester** *First trimester Ultrasound (week 5-8):* Confirmation of viable pregnancy, check heartbeat and determine gestational age *First trimester Screening (week 11-14):* Determine early risk of trisomy 18 and down syndrome (trisomy 21) *Prenatal blood work (week 8):* Check iron, hemoglobin and antibody levels. Blood is also tested for hepatitis, syphilis, H I V and other infectious disease. **Second Trimester** *Second trimester screening (week 15-20):* Assess potential neural tube defects and other genetic abnormalities *Second trimester ultrasound (week 18-20):* determines structural abnormalities, amniotic fluid levels *Glucose Screening (week 24-28):* Determines mother's risk of gestational diabetes **Third Trimester** *Third trimester (week 28):* Repeat hemoglobin and antibody tests *Third trimester:* Give and discuss newborn screening information