7.1: Normal Pregnancy

7.1.1 Introduction

Pregnancy is a complex and dynamic physiological process that encompasses conception, development, and birth. Spanning approximately forty weeks from the last menstrual period, it represents a period of remarkable anatomical, hormonal, and metabolic adaptations within the maternal body that support fetal growth and prepare for parturition. Understanding these changes is essential for recognizing normal progression, identifying potential complications, and providing comprehensive, evidence-based care. This chapter provides an overview of the fundamental biological mechanisms underpinning pregnancy, highlighting key clinical considerations relevant to medical students as they develop foundational knowledge in obstetrics and reproductive health.

7.1.2 Early Pregnancy

7.1.2.1 Diagnosis

In normal implantation, the blastocyst adheres to the uterine endometrium approximately 6 to 7 days after fertilization. Trophoblast cells at the periphery of the blastocyst begin to invade the decidualized endometrium, a process that establishes early maternal–fetal interface and ultimately gives rise to the placenta. The syncytiotrophoblast lineage synthesizes human chorionic gonadotropin (hCG), a glycoprotein hormone essential for the maintenance of early pregnancy. hCG supports the corpus luteum, enabling continued progesterone production, which is required to sustain the early gestational environment.  By roughly 10 days after fertilization, circulating hCG concentrations are sufficient for detection in maternal serum, and by approximately 2 weeks, commercial home pregnancy tests can identify hCG in the urine. hCG consists of two subunits, alpha and beta. The alpha subunit is shared with other anterior pituitary hormones including thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Therefore, clinical pregnancy testing relies on assays that specifically detect the unique beta subunit of hCG.

As the pregnancy progresses, characteristic embryonic and extraembryonic structures become visible on transvaginal ultrasound. Between 4 and 5 weeks of gestation, a gestational sac containing a yolk sac can typically be visualized. By 5 to 6 weeks, the fetal pole becomes detectable, and by 6 to 7 weeks, cardiac electrical activity is generally apparent. (Figure 7.1) Because modern commercial pregnancy tests are highly sensitive, beta-hCG may be detectable in the urine before the embryo can be visualized sonographically. In such cases, serial quantitative beta-hCG measurements in conjunction with repeat ultrasound examinations may be required to confirm an intrauterine pregnancy and to distinguish it from an ectopic pregnancy or early pregnancy loss.

Figure 7.1 Fetal development from the 9th week to the 20th week.
Image Source: Thapaliya, Arbin, Alec Sithole, Michael Welsh and Gaston Dana. Ultrasound Physics and its Application in Medicine. This work is distributed under a CC BY 4.0. Availalbe from https://pressbooks.palni.org/ultraso...ioninmedicine/.

7.1.2.2 Gestational Age

Gestational age is defined as the time elapsed since the first day of the last menstrual period (LMP). In individuals with a typical 28-day menstrual cycle, the LMP precedes ovulation by approximately 14 days and implantation by roughly 3 weeks. Because pregnancy duration averages 40 weeks, or 280 days, from the LMP, an estimated due date can be calculated when the patient is able to recall the first day of her last menstrual period. 

Because variation in menstrual cycle length can result in ovulation occurring earlier or later than the standard 14-day interval, reliance on LMP alone may lead to inaccurate estimation of gestational age. In early pregnancy, gestational age can instead be estimated using measurements of early embryonic and extraembryonic structures, such as the gestational sac and fetal pole. The crown rump length (CRL) of the fetal pole represents the most precise ultrasound parameter for dating a first-trimester pregnancy. (Figure 7.2) If the CRL-based gestational age differs substantially from that predicted by the LMP, the estimated due date should be recalculated using the CRL measurement. 

Figure 7.2. Embryo at 7 weeks. An embryo at the end of 7 weeks of development is only 10mm in length, but its developing eyes, limb buds, and tail are already visible. (This embryo was derived from an ectopic pregnancy. Credit: Ed Uthman)
Source:  Markell, Dawn. Women's Health.  2021. This work is distributed under a CC BY 4.0 license. Availalbe from https://mhcc.pressbooks.pub/he265/fr...ion-statement/. 

Some patients may not present for evaluation during the first trimester and therefore may not receive an early dating ultrasound. At and beyond 14 weeks of gestation, the CRL is no longer an accurate metric. Instead, gestational age estimation relies on a combination of biometric parameters, including biparietal diameter, head circumference, abdominal circumference, and femur length. (Figure 7.3)  As pregnancy advances, biological variation in fetal size increases, leading to a gradual decline in the precision of ultrasound-based gestational age calculations.

Figure 7.3 Fetal biparietal diameter and a head circumference in the second trimester with an estimated gestational age of 21 weeks 1 day.
Source: Skinner C, Mount CA. Sonography Assessment of Gestational Age. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Figure, This ultrasound image demonstrates a...] . This book is distributed under the terms of CC BY-NC-ND 4.0.  Available from: https://www.ncbi.nlm.nih.gov/books/NBK570610/figure/article-128641.image.f1/. 

Once the estimated due date is established, gestational age is tracked in weeks and days, expressed as a decimal fraction (for example, 32+3/7 weeks indicates 32 weeks and 3 days). Pregnancy is typically divided into trimesters based on gestational age. The first trimester spans from the LMP to 13+6/7 weeks. The second trimester extends from 14 weeks to 27+6/7 weeks. The third trimester includes 28 weeks through 41+6/7 weeks. Key gestational milestones include the designation of full-term pregnancy at 37 weeks, the estimated due date at 40 weeks, and the classification of post-term pregnancy at 42 weeks and beyond.

7.1.3 Placental and Umbilical Cord Anatomy

7.1.3.1 Placenta

The placenta is fundamental to normal fetal growth and development, and it plays a critical role in maintaining maternal physiological stability throughout pregnancy. Placental formation begins when trophoblast cells attach to the decidua at the blastocyst stage. As the embryo develops, cytotrophoblasts proliferate and fuse to form syncytiotrophoblasts that further invade the decidua, expand, and generate chorionic villi. These villous structures remodel the maternal spiral arteries within the endometrium, creating intervillous spaces that allow for efficient transfer of oxygen and nutrients from the mother to the fetus, as well as removal of fetal metabolic waste. (Figure 7.4) Abnormalities in the development of the maternal–fetal interface are implicated in several major pregnancy complications, including PRE ECLAMPSIA, STILLBIRTH, and FETAL GROWTH RESTRICTION.¹ 

 

Figure 7.4: Architecture of different villous and vessel branches of a cotyledon. A: types of placental villi in human placenta. B: A villous tree connects to the fetal surface (chorionic plate) and the maternal surface (basal plate). The villous trees are so named because they resemble trees and their basic structure is established early in gestation. A “trunk” dives down into the placenta from the fetal surface vessels, as the stem villous, which divides into large branches, the intermediate villi, with nutrient gathering structures at their ends, followed by the terminal villi. However, during the second and third trimesters, the terminal villi continue to mature in such a way as to increase the quantity and quality of oxygen and nutrient exchange across the terminal villi between the maternal and fetal blood, in response to the demands of the growing fetus. (A is adapted from Benirschke et al. Fifth Edition of Pathology of the Human Placenta (page 123). Used with permission from Springer, and B is from http://showcase.netins.net/web/placenta/placentaltriage101.htm.). A: Reproduced from Pathology of the Human Placenta, Benirschke et al. with permission of Springer. B: Used with permission of DSM Pathworks Inc. 
Source: Wang Y, Zhao S. Vascular Biology of the Placenta. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Figure 3.1, [Architecture of different villous and...]. Available from: https://www.ncbi.nlm.nih.gov/books/N...figure/fig3.1/.

The mature placenta consists of two distinct surfaces. The maternal surface, known as the basal plate, is divided into lobulated units called cotyledons. The fetal surface, known as the chorionic plate, contains the site of umbilical cord insertion.² (Figure 7.5)

Figure 7.5: Maternal and Fetal Sides of Placenta. 
Source: Smith, Deborah H. and Judith Rogers Fruiterman. Maternal-Infant Nursing Review. 2024. This work is distributed under a  CC BY SA 3.0. Available from https://sites.google.com/view/maternitynursingreview/home. 

7.1.3.2 Umbilical Cord

The umbilical cord serves as the essential anatomical connection between the fetus and the placenta, functioning as a bidirectional conduit for blood flow. It contains two umbilical arteries, one umbilical vein, and the obliterated allantois, also known as the urachus. These structures are embedded within Wharton jelly, a gelatinous protective matrix that cushions the vessels against compression.3 (Figure 7.6 and Figure 7.7)

Figure 7.6:  Velamentous Cord Insertion. The umbilical cord attaches to the membranes instead of the placental surface. Umbilical vessels travel unprotected between the amnion and chorion, without the surrounding Wharton jelly.
Source: Brahmandam G, Lipsett BJ. Anatomy, Abdomen and Pelvis: Umbilical Cord. [Updated 2025 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) Available from: https://www.ncbi.nlm.nih.gov/books/NBK557389/.

Figure 7.7 Umbilical cord cross section. 
Source: Smith, Deborah H. and Judith Rogers Fruiterman. Maternal-Infant Nursing Review. 2024. This work is distributed under a  CC BY SA 3.0. Available from https://sites.google.com/view/maternitynursingreview/home.

Oxygenated blood is transported from the placenta to the fetus through the umbilical vein, which subsequently enters the fetal circulation. A portion of this blood perfuses the developing hepatic system, while a substantial amount is diverted to the inferior vena cava via the ductus venosus. De oxygenated blood returns to the placenta through the umbilical arteries.⁴ 

Clinical Correlation

The obliterated umbilical arteries can be visualized on the deep surface of the anterior abdominal wall within the medial umbilical folds.

Umbilical cord blood flow is closely tied to placental function. In cases of fetal growth restriction caused by uteroplacental insufficiency, Doppler evaluation of umbilical artery resistance can help assess disease severity and guide clinical management. Any occlusion of the umbilical vessels can compromise fetal perfusion. Acute interruptions in flow may result in fetal hypoxia or demise. As will be discussed in ANTENATAL FETAL SURVEILLANCE, intermittent cord compression can produce variable decelerations on fetal heart rate monitoring.⁵  

7.1.4 Maternal Anatomy and Physiology

Sources used for this topic section:

Pascual ZN and MD Langakar. 2023⁶

Soma-Pillay P, C Nelson-Piercy, H Tolppanen and A. Mebazaa. 2016.⁷

7.1.4.1 Cardiovascular

Increased blood volume

Maternal blood volume increases by approximately 45% to 55% during pregnancy, driven largely by an expansion of plasma volume. This volume increase supports adequate uteroplacental perfusion and prepares the maternal circulation for the expected blood loss that accompanies delivery. 

  Decreased vascular resistance  

Tp accommodate the expanded intravascular volume, systemic vascular resistance decreases, with the most pronounced decline occurring in the second trimester due to rising progesterone levels.

Clinical Correlation

The reduction in systemic vascular resistance predisposes patients to venous stasis. This stasis can contribute to lower extremity edema and increases the risk of venous thrombosis. (Figure 7.8 forthcoming) Any new elevation in blood pressure warrants evaluation for hypertensive disorders of pregnancy, including pre-eclampsia.

Blood pressure changes

 Beginning in the second trimester,  decreased systemic vascular resistance results in a reduction in systolic blood pressure by approximately 5 to 10 mmHg and in diastolic pressure by 10 to 15 mmHg. As plasma volume continues to expand in the late second trimester, blood pressure generally returns to pre-pregnancy levels. (Figure 7.9 forthcoming)

Clinical Correlation

The physiologic decline in blood pressure can lead to pre-syncopal symptoms. Patients may report lightheadedness when rising from a seated position or may experience syncope with prolonged standing.

Increased stroke volume and cardiac output 

The increase in blood volume produces enhanced preload, resulting in increased stroke volume and a 30% to 60% rise in cardiac output. Mild maternal tachycardia later in pregnancy is considered physiologic as stroke volume plateaus.

Clinical Correlation

Due to the augmented stroke volume, benign systolic ejection murmurs are frequently auscultated in pregnant patients.

7.1.4.2 Hematologic

Increased plasma volume

As noted in the cardiovascular section, plasma volume expands significantly during pregnancy.

Clinical Correlation

Adequate maternal hydration is essential to support this physiologic expansion. 

Increased red blood cell volume with dilutional anemia 

Red blood cell mass increases by 15% to 25%, though this expansion is proportionally smaller than that of plasma volume, resulting in dilutional anemia. Anemia in pregnancy is defined by hemoglobin levels less than 11 g/dL (hematocrit levels less than 33%) in the first and third trimesters, and less than 10.5 g/dL (hematocrit level less than 32%) in the second trimester.⁸  (Figure 7.10 forthcoming)

Clinical Correlation

All pregnant individuals undergo anemia screening in the first trimester and again between 24 and 28 weeks. Those with values below diagnostic thresholds should receive further evaluation. Iron deficiency anemia, the most common form of anemia in pregnancy, is treated with iron supplementation^.9

Increased white blood cell volume

A mild leukocytosis is common in pregnancy, with white blood cell counts up to 15,000 per L considered within normal physiologic range.¹⁰

 

Increased coagulation factors

Concentrations of clotting factors and fibrinogen increase during pregnancy due to estrogen-induced hepatic stimulation. Although these changes promote hemostasis during delivery, they also heighten the risk of thromboembolic events during pregnancy and the postpartum period.¹¹

7.1.4.3 Pulmonary

Physiologic changes in the pulmonary system accommodate increased oxygen demands and reduced intrathoracic space resulting from uterine enlargement. 

Decreased Functional Residual Capacity (FRC)

Upward displacement of the diaphragm by up to 5cm occurs as the gravid uterus elevates abdominal contents, leading to mechanical lateral expansion of the chest wall. Despite this compensatory change, total functional capacity decreases by roughly 5%.

Increased tidal volume

Rising  fetal CO2 production increases maternal ventilatory demands, resulting in a 30% to 40% increase in tidal volume.

Respiratory rate

Maternal respiratory rate remains similar to that of the non-pregnant state. (Figure 7.11)

Figure 7.11. Tidal volume increases by 30-50%. Increased diaphragmatic excursion changes the tidal volume from (for example) 500ml in the first trimester to over 700ml in the third trimester. Respiratory rate increases from 15-17 on average. FEV₁/FVC remains essentially the same. 
Source: Yartsev, Alex. Influence of pregnancy on respiratory function. In Deranged Physciology. 2023. Freely available resource: https://derantedphysiology.com/main/home.

Respiratory alkalosis

Increased minute ventilation lowers maternal CO2 levels, producing a slight respiratory alkalosis. Normal maternal pH ranges from 7.40 to 7.45, slightly higher than the non-pregnant range of 7.35 to 7.45. 

Clinical Correlation

Lower CO2 levels, increased tidal volume, and reduced total lung capacity may contribute to dyspnea of pregnancy. This sensation is most prominent in the third trimester, though oxygen saturation should remain normal. 

 7.1.4.4. Gastrointestinal

Nausea and vomiting

Elevated levels of hCG, progesterone, and estrogen in early pregnancy contribute to nausea and vomiting. 

Clinical Correlation

Symptoms usually improve in the second trimester and may be managed with over-the-counter therapies. Severe vomiting with dehydration or electrolyte abnormalities may warrant hospitalization.

Slower gut motility

Progesterone reduces gastrointestinal smooth muscle activity, resulting in slowed gastric emptying and increased risk of constipation.

Esophageal sphincter relaxation

Progesterone also relaxes the lower esophageal sphincter. Combined with upward displacement of the stomach, this contributes to increased gastroesophageal reflux.

Hemorrhoids

Constipation, decreased systemic vascular resistance, and mechanical compression from the gravid uterus increase the incidence of hemorrhoids.

Gallstones

Elevated estrogen promotes cholesterol production and decreases bile salt synthesis, leading to bile supersaturation. Progesterone-induced gallbladder hypomotility promotes bile stasis, increasing gallstone formation. 

Clinical Correlation

Cholelithiasis may be managed conservatively with dietary modification, although cholecystitis or choledocholithiasis may necessitate surgical intervention. 

 

7.1.4.5 Renal and Urinary

Increased GFR

Increased plasma volume and decreased renal vascular resistance enhance renal perfusion, leading to up to a 50% rise in glomerular filtration rate (GFR). This increase contributes to lower maternal BUN and creatinine levels. Mild physiologic proteinuria may occur, but new onset proteinuria with elevation in blood pressure requires evaluation for pre-eclampsia.  

Increased urination

Higher urine production and compression of the bladder by the gravid uterus contribute to urinary frequency. 

Clinical Correlation

Nocturia is a common concern in pregnancy. 

Increased risk of complicated urinary tract infection

Progesterone reduces ureteral motility, causing ureteral dilation and increasing the risk of reflux. Compression from the gravid uterus further enhances this risk, predisposing patients to pyelonephritis. 

Clinical Correlation

Screening urine cultures are obtained early in pregnancy, and asymptomatic bacteriuria is treated to reduce risk of complications.

7.1.4.6 Endocrine

Thyroid

TSH shares an alpha subunit with hCG, so the peak of hCG in early pregnancy may weakly stimulate the thyroid to produce additional T3 and T4. This will transiently reduce TSH levels, while free T3 and T4 typically remain within normal range due to the simultaneous increase in thyroid-binding globulin. 

Prolactin and Oxytocin

Rising estrogen levels stimulate prolactin production and increase uterine oxytocin receptor density. Oxytocin levels rise progressively during pregnancy and play an essential role in labor contractions, while prolactin promotes milk production.  

Clinical Correlation

Synthetic oxytocin, known as Pitocin, is used to induce labor by augmenting uterine contractions.

7.1.4.7 Breast

Areolar enlargement

Most pregnancies involve enlargement and darkening of the areolae. 

Breast tenderness and enlargement

Estrogen promotes ductal proliferation beginning in the first trimester, resulting in breast enlargement and tenderness. Although prolactin increases during pregnancy, elevated estrogen and progesterone inhibit milk production until after delivery.1

7.1.4.8 Uterus

Uterine growth

High maternal estrogen levels and fetal growth stimulate uterine enlargement and elongation. By the third trimester, uterine growth slows as musculature stretches to accommodate fetal size. Several weeks after delivery, the uterus returns to its pre-pregnancy dimensions.

Uterine quiescence

Progesterone maintains uterine relaxation throughout pregnancy by suppressing myometrial contractility. 

7.1.5 Routine Prenatal Care

Prenatal care scheduling is designed to support the management of pre-existing medical conditions and to facilitate early detection of pregnancy related complications. As gestation advances, the incidence and complexity of potential complications increase, necessitating more frequent clinical encounters. Historically, prenatal care was conducted entirely through in-person visits, occurring every 4 weeks during the first and second trimesters, every 2 weeks from 28 to 36 weeks, and weekly from 36 weeks until delivery. The COVID-19 pandemic accelerated the adoption of alternative care strategies, including telehealth appointments, home blood pressure and fetal monitoring, and individualized adjustments in visit frequency based on risk stratification. Contemporary models of prenatal care increasingly incorporate these flexible approaches and may be tailored to the needs of each clinical practice and patient population.13

7.1.5.1 Components of Prenatal Visit

Blood pressure assessment

Blood pressure is measured at every prenatal visit. Elevated readings prior to 20 weeks gestation may suggest previously undiagnosed chronic hypertension. New onset elevations after 20 weeks require evaluation for pregnancy related hypertensive disorders, including pre-eclampsia.

Fundal height measurement

For low-risk pregnancies, fundal height measurement is initiated at 24 weeks. Using a tape measure, the clinician assesses the distance from the pubic symphysis to the uterine fundus, which in centimeters generally correlates with gestational age in weeks. Discrepancies greater than 3 centimeters warrant further evaluation with ultrasound to assess for abnormalities in AMNIOTIC FLUID or FETAL GROWTH. Certain conditions, such as HYPERTENSIVE DISORDERS (increasing risk for growth restriction) and GESTATIONAL DIABETES (increasing risk for macrosomia) place a patient at high risk for growth disorders.  Other disorders, such as, the presence of fibroids, MULTIFETAL GESTATION, or elevated maternal BMI, may render fundal height less reliable. In such individuals, serial growth ultrasounds at 3 to 4 week intervals are preferred.

Maternal weight

Expected weight gain in pregnancy is 25 to 35 pounds, with the majority occurring in the third trimester. Individuals with elevated pre-pregnancy BMI have lower recommended weight gain thresholds. Excessive weight gain is associated with increased risk of fetal macrosomia and cesarean delivery, while inadequate weight gain may indicate or contribute to fetal growth restriction.14 

Fetal heart rate

Fetal heart rate is evaluated at each prenatal visit using a handheld doppler device. Patients at increased risk of stillbirth may require additional surveillance through non-stress tests, discussed further in ANTENATAL TESTING.

 

Assessment of fetal movement

Beginning when the patient can reliably perceive fetal movement, clinicians routinely inquire whether fetal activity feels normal for the individual. Evidence regarding the utility of formal kick count instruction is mixed, but any report of subjectively decreased fetal movement after viability warrants prompt evaluation.15 

 

Assessment for miscarriage or preterm labor

At each visit, patients should be screened for vaginal bleeding, leakage of fluid, or uterine contractions, which may suggest miscarriage or preterm labor.

Assessment for pre-eclampsia  

In addition to blood pressure monitoring, clinicians assess for symptoms suggestive of pre-eclampsia beginning in the second half of pregnancy. Symptoms include persistent headache, visual disturbance, right upper quadrant pain, dyspnea, and chest pain. 

7.1.5.2 Ultrasounds

Source for this section topic:

ACOG. Ultrasound in Pregnancy. Practice Bulleting, No. 175. (December 2016). Restricted access, https://www.acog.org/clinical/clinic...d-in-pregnancy.¹⁶

First trimester ultrasound

As discussed in the EARLY PREGNANCY section, ultrasound evaluation in the first trimester is used to confirm intrauterine pregnancy, assess for multifetal gestation, and establish accurate gestational dating. Ideally, this scan is performed prior to 14 weeks gestation.

Anatomy ultrasound

A detailed fetal anatomy ultrasound is recommended between 18 and 22 weeks gestation. A standard examination includes evaluation of the fetal head, face, neck, chest, abdomen, spine, extremities, and genitalia. Placental location is recorded, and cervical length is often measured to assess risk for preterm birth. In pregnancies at increased risk for fetal anomalies, a more comprehensive targeted examination may be performed. 

Growth ultrasounds

Serial growth ultrasounds may be obtained at 3 to 4 week intervals when there is concern for fetal growth abnormalities or when maternal body habitus or other factors limit the accuracy of fundal height measurements.

Additional ultrasound assessments

Specialized measurements such as biophysical profile, amniotic fluid index, umbilical artery dopplers, and middle cerebral artery dopplers may be performed when clinically indicated. 

7.1.5.3 Immunizations

Source for this section topic:

ACOG. Maternal Immunization. Practice Advisory (October 2022). Availabe from: https://www.acog.org/clinical/clinic...l-immunization.¹⁷

Immunizations play a critical role in pregnancy by reducing the risk of maternal morbidity from infectious diseases and by providing passive immunity to the fetus and newborn. Pregnant patients should not receive live attenuated vaccines, including measles-mumps-rubella, varicella, and live attenuated influenza formulations. These vaccines carry theoretical risks of transplacental infection and are therefore contraindicated during pregnancy. 

Tetanus toxoid, reduced diphtheria toxoid, and acelluar pertussis (Tdap)

All pregnant individuals should receive the Tdap vaccine between 27 and 36 weeks gestation in each pregnancy, regardless of prior vaccination history. Maternal vaccination during this window optimizes transplacental transfer of pertussis antibodies, providing passive immunity to the newborn for the first several months of life, when morbidity from pertussis infection is highest.

Hepatitis B

The American College of Obstetrics and Gynecology advises screening for hepatitis B surface antibody to assess immunity. Pregnant patients who are not immune may safely receive the hepatitis B vaccine series during pregnancy.

Influenza

Pregnancy increases the risk of severe complications from influenza infection, including pneumonia and preterm labor. Vaccination with an inactivated or recombinant influenza vaccine is recommended for all pregnant patients during influenza season.

COVID-19

 

Pregnant individuals experience higher risks of morbidity, mortality, and obstetric complications from COVID 19 infection. Vaccination is recommended for those who remain unvaccinated, and booster vaccination is advised for those who have previously completed a primary series. 

Respiratory Syncytial Virus (RSV)

 

The American College of Obstetrics and Gynecology recommends administration of the bivalent RSV vaccine between 32 and 37 weeks gestation during respiratory virus season for individuals who have not yet received it. If the vaccine is not given during pregnancy, the newborn should receive the recommended monoclonal antibody for RSV prophylaxis if born during RSV season.   

7.1.5.4 Laboratory

Complete blood count (CBC)  

A CBC should be obtained during the first trimester and repeated between 24 and 28 weeks gestation. As noted in HEMATOLOGIC CHANGES OF PREGNANCY, physiologic hemodilution may result in mild anemia. Hemoglobin levels less than 11 g/dL in the first or third trimesters warrant evaluation for underlying causes, with iron deficiency representing the most common etiology.18
 

Platelet counts typically decrease slightly during pregnancy. Thrombocytopenia is conventionally defined as a platelet count less than 150 × 10⁹ per L. The most frequent cause is gestational thrombocytopenia, a benign condition accounting for approximately 80% of cases and not requiring intervention. Platelet counts less than 100 × 10⁹ per L are less likely to be gestational and warrant additional evaluation.19 

Blood type

 

Maternal blood type should be determined in the first trimester. Red blood cell antigens are classified into the ABO and Rh systems. ABO incompatibility between mother and fetus may lead to neonatal jaundice and anemia. Rh D antigen incompatibility carries the risk of maternal alloimmunization, which can cause hydrops fetalis and stillbirth. 

• If the patient is Rh D positive, repeat blood typing is generally unnecessary until delivery. 

• If the patient is Rh D negative, preventative management is required to avoid alloimmunization, as detailed in ALLOIMMUNIZATION PREVENTION. 

Antibody screen

 

An antibody screen is performed early in pregnancy to assess for maternal red blood cell antibodies. Although many antibodies do not result in clinically significant hemolytic disease, others such as anti-D, anti-Kell, and anti-Duffy can cause severe fetal anemia. Pregnancies complicated by high-risk antibodies require serial fetal assessment throughout gestation.20 

1-Hour oral glucose text

Source for this section topic:

ACOG. Gestational Diabetes Mellitus. Practice Bulletin, No. 190 (Febrary 2019). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/02/gestational-diabetes-mellitus.²¹ 

Gestational diabetes is one of the most common medical complications of pregnancy and is discussed in detail in PREGNANCY COMPLICATIONS. Screening is recommended for all pregnant patients without a preexisting diabetes diagnosis between 24 and 28 weeks gestation.  

All pregnant patients meeting these criteria should undergo an oral glucose tolerance screening with a 50 mg glucose load, followed by a venous blood glucose measurement 1 hour later. Institutional thresholds for abnormal values vary but are most commonly between 130 and 140 mg/dL. 

Patients who fail the screening test undergo a diagnostic 3-hour glucose tolerance test. After an overnight fast, a fasting glucose level is obtained, followed by ingestion of a 100 mg glucose load. Venous glucose measurements are repeated at 1, 2, and 3 hours. Diagnostic cutoffs vary, and no universal consensus exists. A diagnosis of gestational diabetes is made when at least 2 of the 4 values exceed institutional thresholds. Emerging evidence suggests that even one abnormal value may confer increased risk, though current guidelines do not recommend treatment solely on this basis. 

Hemoglobin A1c is not a reliable screening tool for gestational diabetes. Because gestational diabetes develops due to placental hormone mediated insulin resistance, which becomes more pronounced in the late second and early third trimesters, A1c may not reflect current glycemic status. 

 

Select individuals at high risk for undiagnosed type 2 diabetes should undergo first trimester glucose screening. Risk factors include obesity, prior gestational diabetes, hypertension, dyslipidemia, family history of diabetes, high risk race or ethnicity, and history of a macrosomic infant. 

7.1.5.5 Infection Screening

Rubella IgG

Rubella immunity is assessed during the first trimester of each pregnancy. Non-immune individuals should receive the measles-mumps-rubella vaccine in the postpartum period, as it is contraindicated during pregnancy.

Hepatitis B

Prenatal hepatitis B infection is a significant cause of chronic liver disease worldwide. Prophylaxis and antiviral therapy can markedly reduce neonatal transmission. All pregnant individuals should undergo hepatitis B surface antigen (HBsAg) testing in the first trimester, regardless of prior vaccination or testing. Those who test positive should receive further testing, including hepatitis B virus DNA levels and hepatitis B core and surface antigens, to differentiate acute from chronic infection and determine the need for antiviral therapy. As mentioned previously, COG also recommends hepatitis B surface antibody (anti-HBs) and core antibody (anti-HBc) testing for pregnant patients over age 18 without documented prior screening. Individuals lacking surface antibodies are considered non-immune and may safely receive the hepatitis B vaccine series during pregnancy.  Historically, hepatitis B vaccination has been administered to the infant immediately after delivery to reduce the risk of chronic hepatitis B infection acquired in infancy from household or caregiver exposure. This practice has significantly decreased the burden of childhood and lifelong liver disease. Although the CDC has recently modified its recommendations regarding routine neonatal vaccination, many medical institutions continue to endorse this approach based on longstanding evidence of its protective benefit.22 

Hepatitis C

Universal screening for hepatitis C antibodies is recommended in each pregnancy. No current interventions have been demonstrated to reduce perinatal hepatitis C transmission.23 

Human Immunodeficiency Virus (HIV)

All pregnant patients should be screened for HIV early in pregnancy. Repeat testing in the third trimester is recommended for high-risk individuals or in regions with high HIV incidence.24

Without treatment, perinatal HIV transmission rates range from 25% to 30%, but modern antiretroviral therapies can reduce transmission to less than 1%.25 

For more information...

For more details about preventing perinatal HIV transmission, see Kalapila, Aly G. and David H. Spach. Preventing Perinatal HIV Transmission. National HIV Curriculum, Module 5, Lession 1.  Available from: https://www.hiv.uw.edu/go/prevention/preventing-perinatal-transmission/core-concept/all. 

Syphilis

Rates of congenital syphilis have risen substantially in the United States, with notable racial and ethnic disparities. Because early detection and treatment prevent most cases, universal screening is recommended in the first trimester. Many states also recommend repeat testing in the third trimester and again at delivery for high-risk populations.26  

Gonorrhea and Chlamydia

Chlamydia (Chlamydia trachomatis) and Gonorrhea (Neisseria gonorrhoeae) are the most common sexually transmitted infections in the United States. In pregnancy, these infections can result in preterm rupture of membranes, preterm birth, and chorioamnionitis. During delivery, these bacteria can cause neonatal conjunctivitis, resulting in permanent blindness, as well as neonatal sepsis. To prevent these complications, individuals considered high risk for sexually transmitted infections or patients with symptoms should be screened for gonorrhea and chlamydia in the first trimester with cervical swabs and treated if necessary. Universal erythromycin ointment is also recommended for neonates at the time of birth to prevent conjunctivitis in the case of undiagnosed infection.  

Group B Streptococcus (GBS)

Source for this section topic:

ACOG. Prevention of Group B Streptococcal Early-Onset Disease in Newborns, Committee Opinion, Nov. 797 (February 2020). Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns.27 

Streptococcus agalactiae colonizes the vaginal and rectal flora of 10% to 30% of pregnant individuals and is the leading cause of neonatal early-onset sepsis. Vertical transmission most commonly occurs during labor. All pregnant patients should undergo GBS screening with vaginal and anorectal swabs between 36 and 37 weeks gestation. Positive individuals should receive intrapartum antibiotic prophylaxis with penicillin or ampicillin, unless allergic, ideally at least 4 hours before delivery. Patients with a history of neonatal GBS sepsis do not require rescreening and should receive intrapartum antibiotics in all future pregnancies. Patients documented GBS bacteriuria at any point during the current pregnancy are considered positive and require intrapartum prophylaxis.

7.1.5.6 Alloimmunization Prevention

Source for this section content:

 ACOG. Prevention of RhD Alloimmunization. Practice Bulletin, No. 181 (August 2017). Restricted access, https://www.acog.org/clinical/clinic...loimmunization.²⁸

Alloimmunization occurs when an Rh-negative mother, who lacks the Rh D antigen on her red blood cells, is exposed to Rh positive fetal red blood cells and subsequently forms antibodies against the Rh D antigen. This immune response typically does not affect the current pregnancy. However, in subsequent pregnancies with an Rh-positive fetus, maternal anti-D antibodies can cross the placenta and destroy fetal erythrocytes, potentially resulting in hemolytic disease of the fetus and newborn. 

To prevent alloimmunization in Rh negative patients, several approaches can be used to determine fetal Rh D status. 

• Cell-free DNA testing:  Advances in technology now allow noninvasive determination of fetal blood type through analysis of cell free fetal DNA in maternal blood.²⁹ 
• Paternal blood type testing:  If cell free DNA is unavailable and the father of the fetus is known, paternal Rh status may be assessed. Because the Rh D antigen is inherited in an autosomal dominant manner, an Rh-negative father will have only Rh-negative offspring.³⁰ (Figure 7.12)

Figure 7.12. Simple Punnett Square
Source: Stanford Blood Center. Can two Rh-positive parents have an Rh negative child? (October 2018). Available from: https://stanfordbloodcenter.org/can-...egative-child/. 

If fetal blood type cannot be definitively established, or if the fetus is determined to be Rh-positive, Rh-negative mothers should receive anti-D immune globulin at 28 weeks gestation and within 72 hours of any event associated with possible fetomaternal hemorrhage, such as abdominal trauma, vaginal bleeding, or invasive procedures like amniocentesis. Anti-D immune globulin binds fetal Rh positive red blood cells in maternal circulation, preventing maternal immune recognition and antibody formation.30 

• Early pregnancy events:  Recent evidence indicates that the volume of fetomaternal hemorrhage prior to 12 weeks gestation is insufficient to cause alloimmunization. As a result, anti-D immune globulin is no longer routinely recommended for miscarriages or pregnancy terminations before 12 weeks.32

After delivery, newborn blood type should be assessed. If the infant is Rh positive, the mother should receive an additional postpartum dose of anti-D immune globulin. 

Patients who are already alloimmunized, indicated by the presence of maternal anti-D antibodies, require close surveillance throughout pregnancy to assess for fetal anemia.33  

7.1.5.7 Antenatal Testing

Source for this section topic:

ACOG. Indications for outpatient antenatal fetal surveillance. Committee Opinion, No. 828 (June 2021). Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/06/indications-for-outpatient-antenatal-fetal-surveillance.³⁴ 

Certain pregnancies carry an elevated risk of stillbirth compared with the general obstetric population. These risks may arise from maternal factors (such as advanced maternal age, chronic hypertension, diabetes), fetal factors (such as multifetal gestation, fetal growth restriction, or congenital anomalies), or pregnancy-related conditions (such as chronic abruption or a history of prior stillbirth). Pregnancies associated with an estimated stillbirth risk greater than 0.8 per 1,000, corresponding to a relative risk of at least 2.0, warrant closer fetal surveillance to identify early signs of hypoxia or compromise. Antenatal testing may begin at 32 weeks, 36 weeks, or after 39 weeks, depending on the magnitude and timing of risk. 

The physiologic rationale behind antenatal testing is based on the sensitivity of fetal heart rate patterns, activity level, muscular tone, and amniotic fluid volume to hypoxia and acidemia. A fetus demonstrating normal activity, tone, and heart rate reactivity is unlikely to be acidemic at that point in time. 

Nonstress Test (NST)

A reassuring fetal heart rate tracing at or beyond 32 weeks gestation includes temporary accelerations in heart rate that rise at least 15 beats per minute above baseline and persist for at least 15 seconds. An NST is performed by placing an external doppler transducer on the maternal abdomen to record fetal heart rate over a 20-to-40-minute period.

A normal (reactive) NST includes the following features:

• Baseline fetal heart rate between 110 and 160 beats per minute
• Baseline variability of 5 to 20 beats per minute
• At least two accelerations meeting the 15 beat per minute by 15 second criteria
• No decelerations in the fetal heart rate

Failure to meet these criteria may reflect fetal sleep cycles, but persistent abnormalities can signal hypoxia and warrant further evaluation. 

Contraction Stress Test (CST)

Uterine contractions temporarily decrease blood flow to the placenta. A healthy fetus with normal placental reserve tolerates this reduction without evidence of compromise. However, when baseline placental perfusion is diminished or when cord compression is present, contractions may reveal fetal intolerance. A CST evaluates fetal heart rate patterns during contractions. Contractions may be stimulated through nipple stimulation or by administering intravenous oxytocin to achieve at least three contractions in a 10 minute interval. 

Interpretation is as follows:

• Negative CST:  No late decelerations are observed
• Positive CST: Late decelerations occur following at least 50 percent of contractions 
• Equivocal CST: Variable decelerations or late decelerations occurring with less than 50 percent of contractions 

A positive CST is concerning for uteroplacental insufficiency and generally requires prompt clinical assessment. 

 

Biophysical Profile (BPP) 

The biophysical profile combines ultrasound-based assessments of fetal well-being with the results of the NST. A non-hypoxic fetus should demonstrate adequate amniotic fluid, normal tone, and ongoing gross movement. Each component of the BPP is assigned 2 points, for a maximum score of 10. Scores of 8 out of 10 or 10 out of 10 are considered reassuring. 

The components are:

• NST:  A reactive nonstress test
• Fetal breathing movements: At least one episode of rhythmic diaphragmatic movement lasting 30 seconds or longer within a 30-minute observation period
• Fetal body movements: At least three discrete movements of the body or limbs within 30 minutes
• Fetal tone: At least one episode of extension-flexion of a limb or opening-closing of a hand one episode of extension-flexion of a limb or opening-closing of a hand    
• Amniotic fluid volume: A single deepest vertical pocket greater than 2 cm. A low BPP score may reflect fetal hypoxia and requires timely evaluation and possible intervention depending on gestational age and clinical context. 

Footnotes

1. Cindrova-Davies, Tereza and Amanda N. Sferruzzi-Perri. Human placental development and function. Seminars in Cell & Developmental Biology, (November 2022) Vol 131; 66-77. CC BY 4.0 Available from: https://doi.org/10.1016/j.semcdb.2022.03.039
2. Cindrova-Davies, 2022.
3. Brahmandam G, Lipsett BJ. Anatomy, Abdomen and Pelvis: Umbilical Cord. [Updated 2025 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. This book is distributed under the terms of the CC BY-NC-ND 4.0 license. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557389/
4. Brahmandam, 2025
5. Brahmandam, 2025
6. Pascual, Zoey, Michelle D. Langaker. Physiology, Pregnancy. [Updated 2023 May 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. This book is distributed under the terms of the CC BY-NC-ND 4.0 license. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559304/.
7. Soma-Pillay, Priya, Michelle D. Langaker. Physiology, Pregnancy. [Updated 2023 May 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. This book is distributed under the terms of the CC BY-NC-ND 4.0 license. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559304/.
8. ACOG. Anemia in Pregnancy. Practice Bulletin, Number 233, August 2021. Restricted Access. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2021/08/anemia-in-pregnancy. 
9. ACOG, 2021.
10. Dockree S, Shine B, Pavord S, Impey L, Vatish M. White blood cells in pregnancy: reference intervals for before and after delivery. EBioMedicine. (2021 Dec) Vol. 74:103715. This is an open access article under the CC BY-NC-ND license. doi: 10.1016/j.ebiom.2021.103715. Epub 2021 Nov 23. PMID: 34826802; PMCID: PMC8626574. 
11. Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol, (2003 Jun) Vol. 16, No. 2:153-68. doi: 10.1016/s1521-6926(03)00021-5. PMID: 12763484. Restricted access.
12. Alex, Ashley, Eva Ghandary and Kandace P. McGuire. Anatomy and Physiology of the Breast during Pregnancy and Lactation. In: Alipour, S., Omranipour, R. (eds) Advances in Experimental Medicine and Biology, vol 1252. (August 2020).  https://doi.org/10.1007/978-3-030-41596-9_1
13. ACOG. Tailored prenatal care delivery for pregnant individuals. Clinical Consensus, No. 8 (May 2025). https://www.acog.org/clinical/clinic...nt-individuals. 
14. ACOG, 2025.
15. Hayes, Dexter J.L., Jo C. Dumville, Tanya Walsh, Lucy E. Higgins, Margaret Fisher, Anna Akselsson, Melissa Whitworth and Alexander E.P. Heazell. Effect of encouraging awareness of reduced fetal movement and subsequent clinical management on pregnancy outcome: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. Vol 5, No 3 (Mar 2023):100821. This is an open access article distributed under the terms of the Creative Commons CC-BY license Available from:  https://www.ajogmfm.org/article/S258...251-8/fulltext. 
16. ACOG. Ultrasound in Pregnancy. Practice Bulleting, No. 175. (December 2016). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2016/12/ultrasound-in-pregnancy. 
17. ACOG. Maternal Immunization. Practice Advisory (October 2022). Availabe from: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/10/maternal-immunization.
18. ACOG. Anemai in Pregnancy. Practice Bulletin, No. 233 (August 2021). Restricted Access. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2021/08/anemia-in-pregnancy. 
19. ACOG. Thrombocytopenia in Pregnancy. Practice Bulletin, No. 207. (March 2019). Restricted access, https://www.acog.org/clinical/clinic...a-in-pregnancy. 
20. ACOG. Management of Alloimmunization During Pregnancy. Practice Bulletin, No. 192 (March 2018). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/03/management-of-alloimmunization-during-pregnancy. 
21. ACOG. Gestational Diabetes Mellitus. Practice Bulletin, No. 190 (Febrary 2019). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/02/gestational-diabetes-mellitus.
22. AOCG. Viral Hepatitis in Pregnancy. Clinical Practice Guideline, No. 6 (Septebmer 2023). Available from https://www.acog.org/clinical/clinical-guidance/clinical-practice-guideline/articles/2023/09/viral-hepatitis-in-pregnancy. 
23. ACOG, No. 6, 2023.
24. ACOG.  Prenatal and Perinatal Human Immunodeficincy Virus Testing. Committee Opinion, No. 752 (Septebmer 2018). Available from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2018/09/prenatal-and-perinatal-human-immunodeficiency-virus-testing.
25. Kalapila, Aley G. and David H. Spach. Preventing Perinatal HIV Transmission. National HIV Curriculum, Module 5, Lession 1.  Available from: https://www.hiv.uw.edu/go/prevention/preventing-perinatal-transmission/core-concept/all. 
26. ACOG. Screening for Syphilis in Pregnancy. Practice Advisory (Aril 2024). Available from https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2024/04/screening-for-syphilis-in-pregnancy. 
27. ACOG. Prevention of Group B Streptococcal Early-Onset Disease in Newborns, Committee Opinion, Nov. 797 (February 2020). Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns.
28.  ACOG. Prevention of RhD Alloimmunization. Practice Bulletin, No. 181 (August 2017). Restricted access, https://www.acog.org/clinical/clinic...loimmunization.   
29. Moise, Kenneth J. The use of free DNA for fetal RHD genotyping in the Rh negative pregnant patient – the time has come. American Journal of Obstetrics & Gynecology, 232, No. 2 (February 2025): 188-193. Available from: https://www.ajog.org/article/S0002-9...840-8/fulltext.
30. ACOG. Prevention of Rh D Alloimmunization. Practice Bulleting, No. 181 (August 2017). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2017/08/prevention-of-rh-d-alloimmunization.
31. ACOG, No. 181, 2017.
32. Society for Maternal-Fetal Medicine Statement. RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation. American Journal of Obstetrics & Gynecology, 230, No. 5, (May 2024); B2-BS.
33. ACOG. Management of Alloimmunization druing Pregnancy. Practice Bulletin, No. 102 (March 2018). Restricted access, https://www.acog.org/clinical/clinic...ring-pregnancy.  
34. ACOG. Indications for outpatient antenatal fetal surveillance. Committee Opinion, No. 828 (June 2021). Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/06/indications-for-outpatient-antenatal-fetal-surveillance.

Image Acknowledgements

Brahmandam G, Lipsett BJ. Anatomy, Abdomen and Pelvis: Umbilical Cord. [Updated 2025 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) Available from: https://www.ncbi.nlm.nih.gov/books/NBK557389/

Markell, Dawn. Women's Health.  2021. This work is distributed under a CC BY 4.0 license. Availalbe from https://mhcc.pressbooks.pub/he265/fr...ion-statement/ 

Skinner C, Mount CA. Sonography Assessment of Gestational Age. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Figure, This ultrasound image demonstrates a...] . This book is distributed under the terms of CC BY-NC-ND 4.0.  Available from: https://www.ncbi.nlm.nih.gov/books/NBK570610/figure/article-128641.image.f1/

Smith, Deborah H. and Judith Rogers Fruiterman. Maternal-Infant Nursing Review. 2024. This work is distributed under a  CC BY SA 3.0. Available from https://sites.google.com/view/maternitynursingreview/home

Stanford Blood Center. Can two Rh-positive parents have an Rh negative child? (October 2018). Available from: https://stanfordbloodcenter.org/can-...egative-child/

Thapaliya, Arbin, Alec Sithole, Michael Welsh and Gaston Dana. Ultrasound Physics and its Application in Medicine. This work is distributed under a CC BY 4.0. Availalbe from https://pressbooks.palni.org/ultraso...ioninmedicine/

Wang Y, Zhao S. Vascular Biology of the Placenta. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Figure 3.1, [Architecture of different villous and...]. Available from: https://www.ncbi.nlm.nih.gov/books/N...figure/fig3.1/

Yartsev, Alex. Influence of pregnancy on respiratory function. In Deranged Physciology. 2023. Freely available resource: https://derantedphysiology.com/main/home