7.2: Pregnancy Complications

7.2.1 Early Pregnancy Complications   

7.2.1.1 Hydatidiform Mole

Molar pregnancies are a form of gestational trophoblastic disease arising from abnormal fertilization. Although considered benign, hydatidiform moles are premalignant lesions with potential for malignant transformation and tissue invasion.³⁵

Types

Source for this section content: 

Cue, Lauren, Fabiola Farci, Sassan Ghassemzadeh, Michael Kang. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/ Available from: https://www.ncbi.nlm.nih.gov/books/NBK45915. ³⁶

Complete hydatidiform mole:

A complete mole results from fertilization of an “empty” ovum that lacks maternal genetic material. This may occur when two sperm fertilize an empty egg, producing a 46 XX or 46 XY karyotype, though the more common mechanism is fertilization by a single 23X sperm followed by duplication of the paternal genome, producing a 46XX karyotype of entirely paternal origin. (Figure 7.13)

Figure. 7.13 Hydatiform Mole. Chorionic villi with hydropic change, formation of cystic spaces and exuberant villous trophoblastic hyperplasia. Contributed by F Farci, MD. 
Source: Cue, Lauren, Fabiola Farci, Sassan Ghassemzadeh, Michael Kang. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/ Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/.

Partial hydatidiform mole:

A partial mole occurs when a normal 23X ovum is fertilized by either two sperm or one sperm that subsequently duplicates. This produces a triploid zygote with a 69XXX, 69XXY, or 69XYY karyotype. Because maternal DNA is present, partial moles may contain fetal tissue or fetal parts. Partial moles are less common than complete moles.(Figure 7.14)

Figure 7.14. Partial Hydatiform Mole. Histologic image demonstrating irregular, indented villi with lace-like trophoblast proliferation, H/E 4×. Contributed by F Farci, MD
Source: Cue, Lauren, Fabiola Farci, Sassan Ghassemzadeh, Michael Kang. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/ Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/.

Diagnosis

Molar pregnancies are nonviable and characterized by trophoblastic hyperplasia. Rapid proliferation of abnormal villi produces markedly elevated hCG levels, often leading to severe nausea and vomiting and a uterine size larger than expected for gestational age. Vaginal bleeding is common due to separation of molar tissue from the decidua. Late clinical features may include symptoms of thyrotoxicosis, as hCG and TSH share an alpha subunit. Ultrasound classically demonstrates a “snowstorm” appearance composed of numerous cystic spaces resembling “grape clusters.” Partial moles may show fetal tissue. (Figure 7.15)

Figure 7.15. Ultrasound image of a molar pregnancy displaying a "snowstorm-like" appearance. Contributed by S Dulebohn, MD. 
Source: Cue, Lauren, Fabiola Farci, Sassan Ghassemzadeh, Michael Kang. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/ Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/. 

Treatment  

Management consists of evacuation via suction dilation and curettage. Hysterectomy is an option for individuals who have completed childbearing. Following evacuation, quantitative hCG levels should be monitored weekly until undetectable, then monthly for 1 to 3 months.³⁷ 

Histopathology 

Gross specimens show enlarged, cystic, “grape-like” villi. Microscopically, hydatidiform moles demonstrate hydropic villi with trophoblastic hyperplasia. Complete moles show diffuse villous enlargement, while partial moles show focal changes. (Figure 7.16)

Figure 7.16. Hydropic Villi and Trophoblastic Proliferation. Microscopic examination of complete moles reveals poorly vascularized chorionic villi with hydropic swelling and myxomatous, edematous stroma, creating a florid cistern filled with stromal fluid, H/E 4×. Contributed by F Farci, MD. 
Source: Cue, Lauren, Fabiola Farci, Sassan Ghassemzadeh, Michael Kang. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/ Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/.

7.2.1.2 Ectopic Pregnancy

An ectopic pregnancy results from implantation of the blastocyst outside the uterine cavity. The ampulla of the fallopian tube is the most common site, but implantation may also occur in the ovary, cervical canal, cesarean scar, cornua/interstitium, infundibulum, abdominal cavity, or peritoneum.(Figure 7.18) 

Figure 7.18 An ectopic pregnancy adjacent to the left ovary.  
Source: Heilman, James. Ectopic left mass. Licensed under CC BY-SA 3.0. Available from: https://commons.wikimedia.org/wiki/File:Ectopicleftmass.PNG.

Ruptured Ruptured ectopic pregnancy is a life-threatening emergency and accounts for over 2% of pregnancy-related mortality.³⁸ 

Risk Factors

Any condition associated with tubal damage or impaired ovum transport increases ectopic risk.

Examples include:

• Prior pelvic inflammatory disease
• Endometriosis
• Tubal occlusion or sterilization procedures
• Assisted reproductive technology
• Reproductive
• Congenital or acquired tubal abnormalities
• Smoking
• Advanced maternal age

Individuals with a prior ectopic pregnancy remain at elevated risk in subsequent pregnancies.39 

Although the overall risk of pregnancy is low with intrauterine device (IUD) use, any pregnancy that occurs with an IUD in place carries approximately a 50% chance of being ectopic. 40

Diagnosis 

Symptoms typically include unilateral lower abdominal pain and vaginal bleeding. Pain may become diffuse with tubal rupture. Transvaginal ultrasound may demonstrate an adnexal yolk sac or fetal pole, although diagnosis often relies on the combination of imaging, beta-hCG levels, and clinical suspicion.41 Signs of rupture include free intraperitoneal fluid and hemodynamic instability.

Pregnancy of unknown location 

  Sensitive pregnancy tests may reveal early pregnancy before an intrauterine gestation is detectable. Serial hCG measurements and ultrasound should be performed until a pregnancy location is confirmed. Inappropriately rising hCG levels without visualization of an intrauterine pregnancy raise concern for ectopic pregnancy or early pregnancy loss. Management may involve uterine aspiration or methotrexate.42 

Treatment

Methotrexate

Methotrexate is a folate antagonist that inhibits DNA synthesis in rapidly dividing cells. It is administered intramuscularly for hemodynamically stable patients. Close follow-up with serial hCG measurements is required. Contraindications include renal or hepatic dysfunction, bone marrow suppression, and active gastrointestinal disease. Higher initial hCG levels, fetal cardiac activity, or large ectopic size are associated with lower methotrexate success rates.43 

Surgical Management

Patients who prefer definitive therapy or have contraindications to methotrexate may undergo surgical management.

• Salpingectomy removes the affected fallopian tube and eliminates future ectopic risk in the tube.
• Salpingostomy excises the ectopic pregnancy while preserving the tube but requires postoperative hCG monitoring and carries recurrent ectopic risk.  

Treatment choice should incorporate patient preference, fertility considerations, and clinical stability.44 

7.2.1.3 Miscarriage

Early pregnancy loss, also known as miscarriage or spontaneous abortion, is defined as pregnancy loss before 13 weeks gestation. It is common, occurring in 15% to 25% of clinically recognized pregnancies and up to 30% to 60% of all conceptions.45 

Risk Factors

Approximately half of early pregnancy losses are due to chromosomal abnormalities. The most common risk factors are advanced maternal age and prior miscarriage. Additional contributors include uterine anomalies, antiphospholipid syndrome, diabetes, and certain infections, although the differential is broad.46 

Diagnosis

Some patients are asymptomatic, with pregnancy failure detected on ultrasound. Others present with bleeding and cramping.

Diagnostic criteria include:

• Crown-rump length greater than 7 mm without cardiac activity
• Mean gestational sac diameter greater than 25 mm without an embryo
• Loss of previously documented embryo or cardiac activity

A significant drop in hCG may indicate pregnancy loss, but ectopic pregnancy must be excluded, especially in pregnancies of unknown location.47

Treatment

Management options include expectant, medical, and surgical approaches.

Expectant management

Appropriate for stable patients with counseling on what to expect. Up to 80% will spontaneously complete expulsion within 8 weeks. Signs of infection or hemorrhage require prompt intervention. Follow-up is necessary to confirm passage of all tissue.48 

Medical management

Highly effective for most patients. The preferred regimen is oral mifepristone (anti-progesterone) followed by buccal, vaginal, or oral misoprostol (prostaglandin). Success rates approximate 95% When mifepristone is unavailable, misoprostol alone is approximately 83 percent effective.49  Risks include heavy bleeding, incomplete expulsion, infection, and treatment failure. Follow-up is required.

Surgical management

Suction dilation and curettage is appropriate for patients who decline other options or have contraindications to medical or expectant management. The procedure may be performed in an outpatient or operating room setting. Risks include bleeding, infection, and uterine perforation. 

 

7.2.2 Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, are among the leading causes of maternal and perinatal morbidity and mortality worldwide. Their prevalence continues to rise in the United States, largely attributable to increasing maternal age, higher rates of obesity, and a growing burden of chronic health conditions.

7.2.2.1 Classification

Source for this section topic:

ACOG. Gestational Hypertension and Preeclampsia. Practice Bulletin, No. 222 (June 2020). Restricted access, https://www.acog.org/clinical/clinic...d-preeclampsia.⁵⁰

Chronic Hypertension 

Chronic hypertension is defined as the presence of elevated blood pressures before pregnancy. In individuals without prior medical care, blood pressure elevation diagnosed before 20 weeks gestation should be considered chronic hypertension.

Gestational Hypertension

Gestational hypertension is defined as new onset systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg after 20 weeks gestation. Diagnosis requires two elevated measurements at least 4 hours apart.

Pre-eclampsia

Pre-eclampsia without severe features

This condition is diagnosed when gestational hypertension is accompanied by proteinuria.

Proteinuria criteria:

• Greater than 300 mg per 24 hours, or
• Protein/creatinine ratio greater than 0.3

Patients must not have severe range blood pressures or evidence of end organ dysfunction.

Pre-eclampsia with severe features

This diagnosis is made when any of the following are present:

• Severe range blood pressure (systolic greater than 160 mmHg or diastolic greater than 110 mmHg), or
• Signs of end organ damage:
  • Elevated liver transaminases at least twice normal
  • Persistent right upper quadrant or epigastric pain unresponsive to medication
  • Serum creatinine greater than 1.1 mg per dL or doubling of baseline 
  • Platelet count less than 100 × 10⁹ per L
  • Pulmonary edema
  • New onset headache unresponsive to medication 
  • Visual disturbances

Proteinuria is no longer required for diagnosis if severe features are present.

HELLP Syndrome

HELLP syndrome is considered a variant of pre-eclampsia with severe features.

It is defined by:

• Hemolysis (elevated LDH, elevated bilirubin, or schistocytes on smear)  
• Elevated Liver enzymes (LFTs twice normal)
• LP: Low platelets (less than 100 × 10⁹ per L)

 Although HELLP may occur in the absence of elevated blood pressure, it should be managed similarly to pre-eclampsia with severe features.

Eclampsia

Eclampsia is the most severe manifestation of hypertensive disease in pregnancy and is characterized by tonic clonic seizures without another identifiable cause. Prodromal symptoms may include blurred vision, severe headache, or altered mental status. Seizures may lead to trauma, hypoxia, and aspiration. Although eclampsia is typically considered a progression of pre-eclampsia, seizures may occur even in the absence of classic pre-eclampsia symptoms.

Causes

The precise etiology of pre-eclampsia is not fully understood. Current evidence suggests a multifactorial process beginning with abnormal placentation, which leads to systemic endothelial dysfunction, increased vascular permeability, and vasoconstriction.

Risk Factors

Risk factors for the development of pre-eclampsia include chronic hypertension, pregestational diabetes, kidney disease, systemic lupus erythematosus, and antiphospholipid syndrome. Additional factors include nulliparity, multifetal gestation, advanced maternal age, obesity, and conception via assisted reproductive technology. 

Prevention

Although no definitive method exists to prevent pre-eclampsia, daily low dose aspirin has been shown to reduce the risk in individuals with elevated baseline risk. Proposed mechanisms involve imbalance between prostacyclin, a vasodilator and inhibitor of platelet aggregation, and thromboxane A2, a vasoconstrictor and platelet activator. Low dose aspirin selectively inhibits COX 1, reducing thromboxane A2 production. Current recommendations advise initiation of 81 mg aspirin daily for individuals with one high risk factor or two moderate risk factors. Aspirin should be started between 12 and 28 weeks gestation, optimally before 16 weeks, and continued until delivery.51 

 

7.2.2.2 Management

 

Gestational Hypertension and Pre-eclampsia without severe features

These conditions can be managed in an outpatient setting with close monitoring. Planned delivery at 37 weeks gestation is recommended. 

Pre-eclampsia with Severe Features and HELLP Syndrome

Management should occur in an inpatient setting.

Key components include:

• Blood pressure control: Patients with severe range blood pressures should receive intravenous antihypertensives to maintain systolic blood pressure below 160 mmHg and diastolic blood pressure below 110 mmHg. Labetalol, nifedipine, and hydralazine are considered safe and effective.
• Seizure prophylaxis: Intravenous magnesium sulfate is recommended, as it prevents eclamptic seizures more effectively than other antiepileptics.
• Delivery: Delivery is indicated at 34 weeks gestation or earlier depending on maternal or fetal status. Betamethasone should be administered for fetal lung maturity when delivery is anticipated before 34 weeks. After 34 weeks, delivery should not be delayed for steroid administration.

Eclampsia

Acute management includes supportive measures during active seizure, including lateral positioning to prevent aspiration and oxygen supplementation as needed. Magnesium sulfate should be administered promptly, and blood pressure should be controlled with intravenous antihypertensives if indicated. Delivery should occur once the patient is stabilized.

7.2.2.3 Postpartum Considerations

Pre-eclampsia, HELLP, and eclampsia may occur in the postpartum period. Individuals who present postpartum with new onset hypertension, laboratory abnormalities, or seizures should be evaluated for pre-eclampsia spectrum disorders.

7.2.2.4 Future Implications

Individuals with hypertensive disorders of pregnancy have an increased likelihood of recurrence in subsequent pregnancies. Counseling regarding optimal pregnancy spacing and early initiation of aspirin prophylaxis should occur at the postpartum visit. Long term, these individuals carry an elevated risk for chronic hypertension and cardiovascular disease. Annual follow up with a primary care clinician is recommended for cardiovascular monitoring and risk reduction through lifestyle modification.

7.2.3 Gestational Diabetes

Source for this section content:

ACOG. Gestational Diabetes Mellitus. Practice Bulletin, No. 190 (February 2018). Restricted access, https://www.acog.org/clinical/clinic...betes-mellitus.⁵² 

Causes and Risk Factors

During pregnancy, the placenta produces several hormones, including human placental lactogen, that induce significant insulin resistance. In response, maternal pancreatic beta cell mass ordinarily increases to augment insulin production and maintain euglycemia. Individuals who develop gestational diabetes are unable to compensate adequately, often due to underlying genetic susceptibility. Risk factors include a prior history of gestational diabetes, obesity, a family history of diabetes, hypertension, hyperlipidemia, and polycystic ovary syndrome.53

Diagnosis

As discussed in the ROUTINE PRENATAL CARE: LABORATORY section, all pregnant individuals without pre-existing diabetes undergo a 1 hour oral glucose screening test between 24 and 28 weeks gestation. Details of this diagnostic process are outlined in that section.

Complications

Maternal

Although gestational diabetes rarely leads to diabetic ketoacidosis, hyperosmolar hyperglycemic syndrome, or vascular complications during the pregnancy, it is associated with increased risk of pre-eclampsia.

Fetal

Because hyperglycemia in gestational diabetes typically develops after organogenesis, the risk of congenital anomalies is significantly lower compared with pregestational diabetes. However, poor glycemic control can result in multiple fetal complications. Chronic maternal hyperglycemia stimulates fetal hyperinsulinemia, which promotes excessive fetal growth. Macrosomia increases the risk of shoulder dystocia, cesarean birth, and birth trauma. Uncontrolled hyperglycemia also increases the risk of stillbirth.

Neonatal

Neonates of diabetic mothers experience a sudden drop in glucose levels after delivery when maternal glucose supply ceases. Persistently elevated fetal insulin levels can lead to neonatal hypoglycemia. Long term, these neonates have increased risk of childhood obesity and type 2 diabetes.

Management

Treatment of gestational diabetes has been shown to reduce the rates of maternal pre-eclampsia, macrosomia, shoulder dystocia, birth trauma, and perinatal death.⁵⁴

Blood Glucose Control

Diet and Lifestyle

Nutritional counseling emphasizing controlled carbohydrate intake and regular exercise forms the cornerstone of treatment. Individuals whose glucose levels remain within target range with diet and exercise alone are classified as having A1GDM.

Medications

If lifestyle modifications are insufficient, pharmacologic therapy is required. Individuals who require medication are classified as having A2GDM.

• Insulin: Insulin is the first line therapy because of its efficacy and inability to cross the placenta.
• Metformin: Metformin is an option for individuals who cannot use or prefer to avoid insulin. It is effective but does cross the placenta, and long-term outcomes for exposed offspring are not fully characterized.

Delivery

Timing of delivery depends on degree of glycemic control and presence of complications. 

• Poorly controlled gestational diabetes may warrant earlier delivery, individualized to the clinical picture.
• Well controlled gestational diabetes requiring medication should be delivered between 39 and 40 weeks.
• Well controlled gestational diabetes managed with diet alone may be delivered at 39 weeks but can be expectantly managed to 41 weeks.
• If the estimated fetal weight exceeds 4500 grams, the risk of shoulder dystocia increases. In such cases clinicians should offer counseling regarding elective cesarean birth.

Postpartum

All individuals should undergo postpartum screening with a 75 gram 2 hour oral glucose tolerance test to evaluate for persistent glucose intolerance. Individuals diagnosed with impaired glucose metabolism or diabetes should be referred for appropriate long term management. 

Future Implications

Approximately half of individuals with gestational diabetes will develop type 2 diabetes later in life. For this reason, even those with normal postpartum testing should undergo repeat assessment of glycemic status every 1 to 3 years.

7.2.4 Preterm Birth and Preterm Prelabor Rupture of Membranes

Sources for this section content:

ACOG. Prelabor Rupture of Membranes. Practice Bulletin, No. 217 (March 2020). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/03/prelabor-rupture-of-membranes.⁵⁵

ACOG. Prediction and Prevention of Spontaneous Preterm Birth. Practice Bulletin, No. 234 (August 2021). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2021/08/prediction-and-prevention-of-spontaneous-preterm-birth.⁵⁶ 

ACOG. Management of Preterm Labor. Practice Bulletin, No. 171 (October 2016). Restricted access, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2016/10/management-of-preterm-labor.^₅₇ 

Preterm birth is defined as delivery occurring after 20 weeks gestation and before 37 weeks gestation. Etiologies are varied and often multifactorial. In some cases, medically indicated preterm delivery is required for maternal or fetal benefit, such as in severe hypertensive disorders or fetal growth restriction. The focus of this section is spontaneous preterm birth, which encompasses spontaneous preterm labor and preterm prelabor rupture of membranes. 

Causes and Risk Factors

Preterm Labor

Approximately half of spontaneous preterm births are the result of preterm labor. Risk factors are numerous and reflect broader social, environmental, and structural inequities. A prior spontaneous preterm birth is one of the strongest predictors of recurrence. Other associations include urinary tract infection, genital tract infection, and multifetal gestation. Most pregnancies undergo transvaginal ultrasound assessment of cervical length during the anatomy scan. Significant cervical shortening increases the risk for spontaneous preterm birth and warrants further evaluation and management when appropriate. 

Preterm Prelabor Rupture of Membranes (PPROM)

PPROM refers to spontaneous rupture of the membranes before the onset of labor and prior to 37 weeks gestation. Risk factors largely overlap with those for spontaneous preterm labor.  

Diagnosis and Clinical Presentation

Preterm Labor

Individuals presenting before 37 weeks with abdominal cramping or vaginal spotting should be evaluated for possible preterm labor. Uterine activity should be assessed with a tocodynamometer, and a sterile digital cervical examination should be performed by a trained clinician. Preterm labor is diagnosed when cervical dilation progresses or when dilation of more than 2 cm is noted at presentation.

Preterm Prelabor Rupture of Membranes

Patients typically report leakage of fluid. A sterile speculum examination may reveal pooling of amniotic fluid in the vaginal vault.

Diagnostic adjuncts include:

• pH testing: Amniotic fluid has a pH of 7.1 to 7.3, whereas normal vaginal secretions range from 3.8 to 4.5. False positives can occur with blood, semen, or infections such as bacterial vaginosis or trichomonas. 
• Commercial biochemical tests: These tests are more specific than pH testing but still carry a substantial false positive rate.
• Ferning: The gold standard involves evaluation for characteristic ferning patterns after drying the fluid on a slide.  (Figure 7.19) 

Management

   Preterm Labor

All patients should undergo evaluation for potential infectious precipitants, including urinary tract and genital tract infections. 

If Group B Streptococcus (GBS) status is unknown, a GBS swab should be obtained and empiric intrapartum prophylaxis initiated with penicillin or ampicillin. 

• After 34 weeks gestation: No interventions to inhibit labor are recommended, as neonatal benefit from prolongation is outweighed by risks.   
• Before 34 weeks gestation:
  • Antenatal corticosteroids: Intramuscular betamethasone should be administered to enhance fetal lung maturity. Optimal benefit occurs when both doses are administered 24 hours apart.  
  • Tocolysis: Medications can be used to delay delivery for 48 hours to allow completion of steroid therapy. Common agents include indomethacin (avoided after 32 weeks due to risk of premature ductal constriction) and nifedipine. Tocolysis should not be used in the setting of maternal instability or fetal compromise
  • Magnesium sulfate: Prior to 32 weeks, magnesium sulfate should be administered for fetal neuroprotection to reduce the risk and severity of cerebral palsy. 

 Preterm Prelabor Rupture of Membranes 

• After 34 weeks gestation: Historically induction of labor has been recommended because risks of prematurity are lower than risks associated with expectant management. Emerging evidence suggests that expectant management up to 37 weeks may be safe in select individuals, although this remains beyond the scope of this discussion. 
• Before 34 weeks gestation: 
  • Expectant management: If both mother and fetus are stable, expectant management is recommended.
  • Antenatal corticosteroids: Given to promote fetal lung maturity
  • Latency antibiotics: A 7 day course of antibiotics prolongs latency and reduces risks of intrauterine infection and neonatal morbidity.  
  • Inpatient monitoring: Patients are admitted due to increased risk of placental abruption, intraamniotic infection, and umbilical cord prolapse.
• Before 32 weeks gestation: Magnesium sulfate should also be administered for fetal neuroprotection. 

Prevention

Individuals with a history of spontaneous preterm birth may benefit from tailored preventive strategies. These include prophylactic cerclage, vaginal progesterone, or serial cervical length assessments.58 

7.2.5 Multifetal Gestation

Multifetal gestation includes twin, triplet, and higher order pregnancies. This section focuses primarily on twin gestations, which represent the majority of multifetal pregnancies. 

7.2.5.1 Zygosity

Twin gestations may arise from division of a single fertilized ovum (monozygosity) or from fertilization of two separate ova (dizygosity). Monozygotic twins share identical genetic material and are commonly referred to as identical twins. Dizygotic twins have genetic similarity comparable to that of ordinary siblings and are referred to as fraternal twins. If separation of a monozygotic embryo occurs very early, determining zygocity through ultrasound alone becomes challenging, and DNA testing may be required. (Figure 7.20 forthcoming) 

7.2.5.2 Chorionicity and Amnionicity 

Chorionicity refers to the number of placentas present, while amnionicity refers to the number of amniotic sacs. Determining these features early in pregnancy is essential because risks and management vary significantly by chorionicity and amnionicity. (Figure 7.21) 

Figure 7.21 Relationship between zygosity and chorionicity Zygosity and placentation in twins.  

Source: International Society for Twin Studies. Zygosity and Chorionicity of Twins. Available from: https://twinstudies.org/zygosity-and...city-of-twins/. 

Dichorionic-Diamniotic Twins 

These twins have two separate placentas and two separate amniotic sacs. This configuration can result from dizygotic fertilization or from monozygotic division occurring 1 to 4 days after fertilization, leading to two distinct blastocysts. (Figure 7.22 forthcoming) 

Monochorionic-Diamniotic Twins

These twins arise from monozygotic division occurring 4 to 8 days after fertilization, just before implantation. They share one placenta but each fetus is enclosed within an individual amniotic sac. (Figure 7.23 forthcoming) 

Monochorionic-Monamniotic Twins

Division occurring between 8 and 13 days after fertilization results in twins that share both a single placenta and a single amniotic sac. (Figure 7.24 forthcoming) 

Conjoined Twins

When division occurs after day 13 post-fertilization, separation is incomplete because the embryonic disc has already begun to form. These twins remain physically connected and represent a rare outcome of late monozygotic division. (Figure 7.25 forthcoming) 

7.2.5.3 Complications of Multifetal Gestation

Multifetal gestations face higher risks of placental-associated complications, including hypertensive disorders and gestational diabetes. Increased fetal crowding also contributes to elevated risk of fetal growth restriction and preterm labor.

Additional complications include:

• Twin-to-twin transfusion syndrome (TTTS): Seen in monochorionic twins when abnormal placental vascular connections lead to unbalanced blood flow between fetuses. Classic findings include discordant fetal sizes and amniotic fluid levels. Screening with ultrasound every 2 weeks is recommended. (Figure 7.26 forthcoming)
• Umbilical cord entanglement Particularly common in monoamniotic twins who share a single amniotic sac. Cord entanglement can result in sudden occlusion with fetal demise, necessitating intensive monitoring, often with prolonged inpatient fetal heart rate surveillance. (Figure 2.27 forthcoming)

7.2.6 Fetal Growth Disorders

7.2.6.1 Macrosomia

Macrosomia is defined as an estimated fetal weight greater than 4000 g or 4500 g.

Causes and Risk Factors

Risk factors include maternal diabetes, obesity, excessive gestational weight gain, a prior macrosomic infant, and post-term pregnancy.

Screening and Diagnosis

Fundal height should be measured at each prenatal visit as described in the Routine Prenatal Care section. A fundal height measurement more than 3 cm above gestational age warrants ultrasound evaluation for possible macrosomia. Ultrasound estimates become less accurate as gestation advances and may differ by up to 1 pound near term. An ultrasound-estimated fetal weight above 4000 to 4500 g is consistent with macrosomia.

Complications

Maternal risks include increased likelihood of cesarean delivery, postpartum hemorrhage, intrapartum infection, significant perineal lacerations, and shoulder dystocia. Fetal risks include shoulder dystocia, meconium aspiration, neonatal hypoglycemia, and NICU admission. Macrosomic infants also have increased long term risk of obesity

Management

Elective cesarean delivery should be offered for estimated fetal weights greater than 5000 g in non-diabetic individuals and greater than 4500 g in diabetic individuals to reduce risk of shoulder dystocia and maternal trauma. Current evidence does not support early induction of labor solely for macrosomia.59 

7.2.6.2 Fetal Growth Restriction

Source for this section content: 

ACOG. Fetal Growth Restriction. Practice Bulletin, No. 227 (February 2021).Restriced access, https://www.acog.org/clinical/clinic...th-restriction.⁶⁰

Fetal growth restriction (FGR) is defined as an estimated fetal weight less than the 10th percentile or an abdominal circumference less than the 10th percentile for gestational age.  

Causes

FGR may result from uteroplacental insufficiency, teratogenic exposures, maternal infections, or fetal genetic or structural abnormalities. Hypertensive disorders, tobacco or cocaine use, and primary placental dysfunction are common contributors. Some fetuses are constitutionally small, yet evaluation and management proceed under the assumption of potential pathology.

Screening and Diagnosis

Fundal height is used as the primary screening tool. A discrepancy exceeding 3 cm below gestational age warrants ultrasound assessment. Individuals at higher risk, such as those with hypertensive disorders, often undergo serial growth ultrasounds every 3 to 4 weeks. An ultrasound-estimated fetal weight or abdominal circumference below the 10th percentile confirms FGR.

Complications

FGR increases the risk of stillbirth, neonatal death, developmental delay, preterm birth, and NICU admission.

Management

Management includes serial growth assessment and evaluation of umbilical artery Doppler velocimetry to determine severity. Delivery timing is individualized based on Doppler results and degree of growth restriction, with earlier delivery recommended for evidence of significant placental insufficiency.

7.2.7 Amniotic Fluid Disorders

Amniotic fluid protects the fetus, facilitates movement, regulates temperature, and is essential for pulmonary development. Early in gestation, amniotic fluid composition resembles fetal plasma. By the third trimester, it consists largely of fetal urine. Ultrasound estimation of the amniotic fluid index (AFI) measures the deepest pocket in each quadrant.

7.2.7.1 Polyhydramnios

Polyhydramnios may result from excess fetal urine production (as in maternal diabetes) or impaired fetal swallowing (as in congenital anomalies). Many cases, however, are idiopathic.

7.2.7.2 Oligohydramnios

Oligohydramnios may arise from ruptured membranes, uteroplacental insufficiency, or fetal renal dysfunction. It may both reflect and contribute to impaired fetal perfusion. Complications include cord compression, pulmonary hypoplasia, and congenital anomalies. Evaluation includes assessment for membrane rupture, fetal renal pathology (such as Potter sequence in bilateral renal agenesis), and placental insufficiency.

7.2.8 Fetal Demise

Despite advancements in obstetrics and antenatal surveillance, fetal demise after 20 weeks remains a significant adverse pregnancy outcome. Stillbirth affects approximately 1 in 150 to 1 in 175 pregnancies, with persistent racial and socioeconomic disparities.61 

Causes and Risk Factors

Risk factors inlcude advanced maternal age, chronic conditions such as diabetes or hypertension, obesity, and substance use (including alcohol, tobacco, and illicit drugs). Fetal factors include growth restriction, multifetal gestation, and post-term pregnancy. Non-Hispanic black individuals experience nearly twice the rate of stillbirth as other racial groups.

Prevention

As outlined in the Antenatal Testing section, individuals with increased stillbirth risk should receive antenatal fetal surveillance to detect early signs of hypoxia or acidosis.

Clinical Presentation

Patients may present with decreased fetal movement, acute complications such as placental abruption, infection, or preterm labor, or may be asymptomatic with demise identified incidentally. Diagnosis is confirmed by ultrasound demonstrating absent fetal cardiac activity.

Management

Delivery is recommended once fetal demise is diagnosed, with vaginal delivery preferred when feasible. Dilation and evacuation is an option up to approximately 24 weeks but may limit the ability to conduct a complete fetal autopsy. Evaluation for underlying etiologies includes maternal laboratory testing, fetal genetic analysis, and placental and fetal autopsy. Unfortunately, many cases remain unexplained. Bereavement support is essential as part of comprehensive care.62 

7.2.9 Placental Disorders

7.2.9.1 Abruption

Placental abruption occurs when the placenta prematurely separates from the uterine wall. (Figure 7.28)

Figure 7.28. Marginal and Concealed Placental Abruption.
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.  

Causes and Risk Factors

Risk factors include prior abruption, preterm prelabor rupture of membranes, cigarette smoking, cocaine use, hypertensive disorders, and abdominal trauma.

Clinical Presentation

Abruption most commonly presents with sudden, constant abdominal pain accompanied by vaginal bleeding. Bleeding may be scant or absent in cases of concealed abruption. Depending on the severity of placental separation, there may be significant fetal anemia, fetal distress, or both. A high index of suspicion should be maintained for individuals with risk factors who present with painful vaginal bleeding.

Management

Management depends on gestational age and degree of separation. Significant abruption leading to maternal or fetal instability requires delivery. The route and timing of delivery are based upon the clinical scenario.

7.2.9.2 Placenta Accreta Spectrum

Under normal conditions , the placenta attaches to the endometrium, allowing spontaneous separation after delivery. When the placenta abnormally adheres to or invades the myometrium, it is classified within the placenta accreta spectrum.

Types of Morbidly Adherent Placenta

• Placenta accreta: The placenta attaches directly to the myometrium without intervening decidua.(Figure 7.29 forthcoming)
• Placenta increta: The placenta invades into the myometrium.
• Placenta percreta: The placenta penetrates through the myometrium to the serosal surface. Percreta may invade surrounding structures and confers the highest morbidity.

Causes and Risk Factors

Placenta accreta spectrum typically results from a defect in the endometrium, exposing underlying myometrium. The most common risk factor is prior uterine surgery, including myomectomy, dilation and curettage, and especially prior cesarean delivery. The risk increases with each successive cesarean birth, particularly when paired with a low-lying placenta or placenta previa.

Clinical Presentation

Many cases are asymptomatic during pregnancy and are identified on routine obstetric ultrasound. Postnatally, the classic presentation is failure of placental separation after delivery, followed by significant hemorrhage. Prenatal diagnosis greatly improves maternal outcomes.

Management

When diagnosed antenatally, planned preterm cesarean hysterectomy is recommended. Delivery should ideally occur before the onset of labor to reduce complications. When placenta accreta spectrum is discovered intrapartum, maternal morbidity increases due to uncontrolled hemorrhage and emergent operative intervention.

7.2.9.3 Placenta Previa and Vasa Previa

A placenta that implants low in the uterus may lie near or cover the cervical os. A placenta within 2 cm of the internal cervical os is considered low lying, while complete or partial coverage of the internal os is termed placenta previa. (Figure 7.30 forthcoming)  In some pregnancies, the placenta may have two lobes connected by fetal vessels, or the umbilical cord may insert into the membranes rather than the placental disk (velamentous insertion). If fetal vessels traverse the membranes overlying or near the cervical os, the condition is vasa previa. (Figure 7.31 forthcoming)

Causes and Risk Factors

Risk factors for placenta previa include advanced maternal age, multiparity, cigarette smoking, multifetal gestation, and assisted reproductive technologies. Accessory placental lobes and velamentous cord insertion increase the risk of vasa previa.

Clinical Presentation

Most cases of placenta previa or vasa previa are diagnosed incidentally through routine prenatal ultrasound. However, any patient presenting with painless vaginal bleeding should be evaluated for placenta previa or vasa previa.

• Placenta previa: Commonly identified on ultrasound.
• Vasa previa: May be overlooked unless specifically evaluated. Patients with a velamentous cord insertion or accessory lobe require targeted transvaginal ultrasound evaluation.   

Management

General Measures

• Patients with placenta previa or vasa previa should maintain pelvic rest and avoid high impact activities.
• Those diagnosed early in pregnancy should undergo repeat transvaginal ultrasound around 32 weeks to assess for resolution.

Placenta Previa

• Stable placenta previas without bleeding are managed expectantly with planned cesarean delivery at 36 to 37 weeks to avoid labor onset.63 
• Management of active bleeding depends on gestational age and degree of hemorrhage. Patients should undergo fetal monitoring and speculum examination. Significant bleeding with maternal or fetal instability requires delivery.
• Even in stable scheduled cases, increased risk of postpartum hemorrhage exists because the lower uterine segment contains less contractile myometrium. Preparations for hemorrhage management should be in place.

Vases Previa

• Management is more aggressive due to the risk of rapid fetal exsanguination with membrane rupture.
• Stable cases are typically delivered between 34 and 37 weeks.
• Many individuals are admitted between 30 and 34 weeks for inpatient monitoring until delivery.  

Footnotes

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Image Acknowledgements

Cue, Lauren, Fabiola Farci, Sassan Ghassemzadeh, Michael Kang. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155/ Available from: https://www.ncbi.nlm.nih.gov/books/NBK459155

Heilman, James. Ectopic left mass. Licensed under CC BY-SA 3.0. Available from: https://commons.wikimedia.org/wiki/File:Ectopicleftmass.PNG

International Society for Twin Studies. Zygosity and Chorionicity of Twins. Available from: https://twinstudies.org/zygosity-and...city-of-twins/

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