Maternal complications during pregnancy

Nausea and vomiting are common conditions of pregnancy and are typically treated with hydration and nonpharmacological management. If nausea is refractory to nonpharmacological management, antiemetics should be initiated in a step-wise manner. Hyperemesis gravidarum is a severe form of nausea and vomiting of pregnancy characterized by ketonuria and weight loss and typically requires inpatient admission, IV fluid hydration, and antiemetic therapy. Pregnancy-associated liver diseases most frequently occur in the second and third trimesters and are associated with significant maternal and fetal mortality and morbidity if not managed promptly. Cervical insufficiency refers to the inability of the cervix to retain a pregnancy in the second trimester in the absence of labor, contractions, or other pathologies; cervical cerclage may be required. Other maternal complications of pregnancy include peripheral edema, gestational thrombocytopenia, hypertensive pregnancy disorders, and gestational diabetes.

Metabolic complications

• Hypertensive pregnancy disorders
  • Gestational hypertension
  • Preeclampsia
  • Eclampsia
• Gestational diabetes
• Pregnancy-associated liver diseases
  • HELLP syndrome
  • AFLP
  • Cholestasis of pregnancy

Hemorrhagic complications

• First trimester: See “Vaginal bleeding.”
  • Spontaneous abortion
  • Ectopic pregnancy
• Second and third trimester: See “Antepartum hemorrhage.”
  • Placenta previa
  • Abruptio placentae
  • Uterine rupture
• Other: Fetomaternal hemorrhage

Infectious complications

• Chorioamnionitis
• UTI in pregnancy
• Sexually transmitted infections
• Pelvic inflammatory disease in pregnancy

Other complications

• Epidemiology
  • Occurs in up to 90% of pregnancies
  • Onset at 5–6 weeks' gestation
  • Peaks at 9 weeks' gestation
  • Usually abates by 16–20 weeks' gestation
• Risk factors
  • Multiple gestation
  • Hydatidiform mole
  • Nulliparity
  • Migraine headaches
  • GERD
• Clinical features
  • Nausea and/or vomiting
  • Normal vital signs, laboratory findings, and normal physical examination
• Differential diagnosis: See the differential diagnosis of nausea and vomiting.
• Treatment ^[2][3][4][5]
  • Rehydration (oral hydration is usually sufficient)
  • Nonpharmacologic options
    • Adapt diet and avoid triggers.
    • Ginger tea and/or ginger capsules
    • Acupressure , hypnosis
    • Replace iron-containing supplements with folate-containing prenatal vitamins.
  • Antiemetic therapy for nausea and vomiting of pregnancy: If the response to an antiemetic from one class is inadequate, add an antiemetic from another class in a stepwise manner, as shown below. ^[3][6]
    1. Pyridoxine (vitamin B₆) and/or doxylamine
       • Oral pyridoxine (Vitamin B₆)
       • Oral doxylamine
       • Oral pyridoxine/doxylamine combination
    2. For refractory symptoms, add one of the following:
       • Diphenhydramine
       • Dimenhydrinate
       • Prochlorperazine
       • Promethazine
    3. For refractory symptoms despite combination therapy above, add one of the following:
       • Metoclopramide
       • Ondansetron
       • Promethazine
       • Consider also:
         • Change oral dimenhydrinate to IV.
         • Trimethobenzamide
    4. Last resort; : Add chlorpromazine or methylprednisolone.
       • Chlorpromazine
       • Methylprednisolone
  • Thiamine repletion (in patients with severe recurrent vomiting)
• Acute management checklist for uncomplicated nausea and vomiting of pregnancy
  • Rule out alternate etiologies (see differential diagnosis of nausea and vomiting).
  • Identify and treat dehydration (see IV fluids).
  • If dehydration is present, check urine ketones and serum electrolytes to rule out hyperemesis gravidarum.
  • Electrolyte and thiamine repletion (in patients with severe recurrent vomiting)
  • Trial nonpharmacologic options (e.g., dietary changes, ginger tea/capsules)
  • Replace iron-containing supplements with folate-containing prenatal vitamins.
  • Start pyridoxine and/or doxylamine.
  • For refractory emesis, add antiemetic therapy in a stepwise manner (see above).
  • Consider OB/GYN consult.

In pregnant women, a thorough history, examination, and, if necessary, diagnostics are essential to rule out potential causes of nausea and vomiting that are not pregnancy-related.

Because antiemetics are potentially teratogenic, their use should be considered only if nausea and vomiting are refractory to dietary changes and supportive therapy.

• Definition: severe, persistent nausea and vomiting associated with a > 5% loss of prepregnancy weight and ketonuria with no other identifiable cause ^[3]
• Risk factors
  • Multiple gestation
  • Hydatidiform mole
  • Nulliparity
  • Migraine headaches
  • GERD
• Clinical features
  • Nausea, vomiting
  • Physical signs of dehydration
  • Hypersalivation,
  • Orthostatic hypotension
  • Malnourishment
• Diagnostics
  • Clinical diagnosis
  • Laboratory analysis
    • Electrolyte disturbances: hypokalemia and hypochloremic metabolic alkalosis or metabolic acidosis ^[7]
    • Signs of dehydration (e.g., ↑ hematocrit)
    • Ketonuria
• Treatment
  • Antiemetic therapy: See “Antiemetic therapy for nausea and vomiting of pregnancy.” ^[3]
    • May require glucocorticoid therapy (see stepwise approach above)
  • IV fluid resuscitation/replacement (see IV fluid therapy)
  • Electrolyte and thiamine repletion
  • Enteral feeding or TPN is recommended in patients with persistent symptoms and weight loss despite antiemetic therapy. ^[3]
• Complications ^[8][9]
  • Maternal
    • Hypokalemia
    • Wernicke encephalopathy
  • Fetal
    • Intrauterine growth restriction
    • Low birth weight
    • Preterm birth
• Acute management checklist for hyperemesis gravidarum ^[2][3][4][5]
  • Rule out alternate etiologies (see differential diagnosis of nausea and vomiting).
  • Identify and treat dehydration (see IV fluids).
  • Thiamine repletion
  • Electrolyte repletion
  • IV antiemetic therapy (see antiemetic therapy for nausea and vomiting of pregnancy)
  • Consider enteral tube feeding (nasogastric/nasoduodenal) or TPN.
  • Closely monitor vitals and urine output.
  • Monitor urine ketones, BMP, and body weight daily.
  • Inpatient admission
  • Consult OB/GYN.

Overview ^[10][11][12]

• Causes of abnormal liver chemistries unique to pregnancy include:
  • Hyperemesis gravidarum ^[13]
  • Intrahepatic cholestasis of pregnancy
  • Acute fatty liver of pregnancy (AFLP)
  • HELLP syndrome (detailed separately)
• These conditions typically manifest in the second and third trimesters; hyperemesis gravidarum manifests in the first trimester. ^[14]
• Early diagnosis and multidisciplinary management are imperative in order to minimize maternal and fetal morbidity and mortality.
• Consult specialists (e.g., gastroenterology, hepatology) to rule out liver diseases that are not specific to pregnancy. ^[10][12]
  • Elevated transaminases: Test for viral hepatitis , autoimmune liver diseases , and acetaminophen levels as clinically indicated. ^[10]
  • Consider abdominal imaging to rule out portal vein thrombosis, biliary disease, and hepatic masses.

Mildly elevated ALP is normal in pregnancy. Pregnant patients with elevated transaminase and/or bilirubin levels should be evaluated for hepatocellular and biliary disease. ^[10][12]

Acute fatty liver of pregnancy ^[10][12][15]

• Definition: idiopathic, rare, life-threatening obstetric emergency most commonly arising in the third trimester, characterized by extensive fatty infiltration of the liver, which can result in acute liver failure
• Epidemiology: 1–3 cases per 10,000 pregnancies ^[15]
• Risk factors: low BMI, multiple pregnancy ^[12]
• Pathophysiology: dysfunction of fatty acid β-oxidation
• Clinical features ^[12]
  • Sudden onset of jaundice
  • RUQ pain, nausea, and vomiting
  • Coagulopathy with an increased risk of DIC
  • Hypoalbuminemia → ascites ^[16]
  • Encephalopathy
  • Polyuria and polydipsia
  • ∼ 50% of patients have concurrent preeclampsia ^[12]
• Diagnostics ^[10][12]
  • Laboratory findings
    • CBC: ↑ WBC; platelet count variable
    • Liver chemistries: ↑ AST, ↑ ALT , hyperbilirubinemia
    • Hyperuricemia
    • Hypoglycemia
    • Coagulopathy (prolonged PT/aPTT)
    • Renal function test: may show acute renal failure
  • Imaging: used to help confirm the diagnosis and rule out differentials (e.g., liver hematoma)
    • Modality of choice: ultrasound
    • Findings: The liver appears bright white; ascites may also be present.
  • Liver biopsy
    • Consider in diagnostic uncertainty (e.g., atypical presentation) and in patients with persistent liver dysfunction postpartum. ^[10]
    • Findings: microvesicular steatosis
• Differential diagnosis: HELLP syndrome, preeclampsia with severe features, other causes of acute liver failure
• Management ^[10][15]
  • Consult the critical care team urgently.
  • Optimize maternal parameters before delivery (see "Management of acute liver failure" for details).
  • Deliver immediately regardless of gestational age. ^[12]
• Complications ^[10][15]
  • Acute liver failure ^[17]
  • Acute renal failure
  • Encephalopathy, pulmonary edema, pancreatitis
  • Maternal death (∼ 2%)
  • Fetal demise (∼ 10–20%)
  • Infection
• Prognosis ^[10]
  • Clinical improvement is typically seen within 4 days of delivery.
  • Laboratory abnormalities may persist for > 1 week.

Rule out causes of acute liver injury that are unrelated to pregnancy (e.g., acute viral hepatitis, autoimmune hepatitis, drug-induced liver injury, Wilson disease). ^[10]

It is often difficult to differentiate between AFLP, HELLP, and preeclampsia with severe features, and these conditions can also coexist. Renal failure, hyperuricemia, and hypoglycemia are more common and severe in AFLP than in HELLP and severe preeclampsia. ^[10]

Supportive care and immediate delivery are the main aspects of AFLP management. There is no role for expectant management. ^[10]

Intrahepatic cholestasis of pregnancy ^{[10][11][12][14]}

• Definition: common pregnancy-associated liver disease, most commonly manifesting in the second and third trimesters with pruritus and elevated serum bile acid levels ^[14]
• Epidemiology: occurs in ∼ 0.4–10% of pregnancies ^[11]
• Etiology: multifactorial ^[18]
• Clinical features ^[10][11]
  • Pruritus
  • Jaundice ^[12]
  • Steatorrhea (uncommon)
• Diagnostics
  • ↑ Total serum bile acid levels (> 10 mcmol/L): confirmatory ^[10][11][19]
  • ↑ ALT, ↑ AST
  • Normal or mildly elevated bilirubin
  • GGT is typically normal. ^[20]
• Treatment ^[10][11]
  • Medical management
    • First line: ursodeoxycholic acid (reduces bile acid levels and pruritus) ^[11][12][14]
    • Consider first-generation antihistamines, e.g., hydroxyzine for severe pruritus.
    • Administer corticosteroids for fetal lung maturity if preterm delivery is anticipated.
  • Obstetric management
    • Antenatal surveillance 1–2 times per week
    • Monitor serum bile acid levels regularly. ^[10]
    • Deliver at 36–39 weeks' gestation depending on severity (or at diagnosis if diagnosed at ≥ 37 weeks). ^[14]
      • Bile acid levels ≥ 100 mcmol/L
        • Deliver at 36 weeks' gestation.
        • Consider delivery between 34 and 36 weeks' gestation for severe disease.
      • Bile acid levels between 10 and 100 mcmol/L: Deliver between 36 and 39 weeks' gestation.
    • Continuous fetal monitoring is recommended during labor because of the increased risk of stillbirth.
• Prognosis: The condition is fully reversible postpartum.
• Complications ^[10][11]
  • Intrauterine fetal demise (1.2% after 37 weeks) ^[14]
  • Fetal growth restriction
  • Premature labor; and increased preterm birth rates
  • Meconium-stained amniotic fluid
  • Neonatal respiratory depression
  • Recurrence in subsequent pregnancies (60%–90%) ^[14][21]

Elevated total serum bile acid level (> 10 mcmol/L) in a patient with pruritus in the second or third trimester (without other causes of pruritus) is diagnostic for intrahepatic cholestasis of pregnancy. Elevated transaminases are not required for diagnostic confirmation. ^[11]

Early initiation of therapy with ursodeoxycholic acid may reduce the risk of preterm birth and stillbirth. ^[14]

Definition

Cervical insufficiency is the inability of the cervix to retain a pregnancy in the second trimester in the absence of contractions, labor, or other underlying pathologies (e.g., infection, bleeding, premature rupture of membranes).

Etiology

Most cases of cervical insufficiency are idiopathic.

Risk factors ^[22]

• Previous midtrimester pregnancy loss or preterm birth
• Previous obstetric or gynecological trauma (e.g., termination of pregnancy, precipitous labor, multiple gestations, conization)
• Short cervical length: transvaginal cervical length < 25 mm on ultrasound before 24 weeks' gestation
• Cervical connective tissue weakness (e.g., Ehler-Danlos syndrome)
• Diethylstilbestrol exposure

Clinical features

• Painless cervical dilation with or without prolapsed membranes
• Nonspecific findings
  • Pelvic cramps, back pain
  • Vaginal discharge: ↑ volume, yellow or blood-stained, and/or thinner consistency

Diagnosis

• Clinical diagnosis in individuals with painless cervical dilation before 24 weeks' (may be up to 28 weeks') gestation or a history of second-trimester preterm birth or pregnancy loss related to painless cervical dilation
• A short cervical length is not diagnostic of cervical insufficiency.
• Some experts make a diagnosis of cervical insufficiency in patients with a short cervical length before 24 weeks' gestation in the current pregnancy if they have a history of ≥ 1 preterm birth or pregnancy loss related to cervical dilation between 16 and 36 weeks' gestation. ^[22][23]

Management of cervical insufficiency and short cervical length ^[24]

• In women with risk factors (e.g., previous preterm birth): serial cervical ultrasound monitoring between 16 and 24 weeks' gestation
• Intravaginal progesterone should be considered if the patient has a short cervical length.
• Cervical cerclage ; ^[23][25][26]
  • Definition: placement of a supportive suture in the cervicovaginal junction to prevent early pregnancy loss and preterm birth
  • Methods
    • McDonald cerclage: a surgical procedure performed to prevent preterm birth in women with cervical insufficiency that involves placing a suture in the cervix, typically using a transvaginal approach, to reinforce cervical closure; usually removed between 36 and 37 weeks' gestation or at the onset of preterm labor.
    • Shirodkar cerclage: a surgical procedure during which a suture is placed in the cervical submucosal tissue to treat cervical insufficiency; usually removed between 36 and 37 weeks' gestation or at the onset of preterm labor (can be left in place if cesarean delivery is planned).
  • Timing: < 24 weeks' gestation; most commonly performed at 13–16 weeks' gestation
  • Indications
    • Cervical dilation at < 24 weeks' gestation
    • Singleton pregnancy with a short cervical length before 24 weeks' gestation and a history of preterm birth or pregnancy loss
    • Prior cerclage due to cervical insufficiency at < 24 weeks' gestation
    • Can be considered in a singleton pregnancy without a history of preterm birth if cervical length is < 10 mm before 24 weeks' gestation
  • Contraindications
    • Preterm labor
    • Premature rupture of membranes
    • Chorioamnionitis or vaginal infection
    • ≥ 24 weeks' gestation
    • Unexplained vaginal bleeding
• Strict bed rest, intramuscular progesterone injections, and cervical pessaries are not recommended.

A shortened cervical length is not sufficient to diagnose cervical insufficiency.

Etiology

• Infection of the amniotic fluid, fetal membranes, and placenta
• Most commonly due to ascending cervicovaginal bacteria
• Common bacteria: Ureaplasma urealyticum; (up to 50% of cases), Mycoplasma hominis; (up to 30% of cases), Gardnerella vaginalis, bacteroides; , group B Streptococcus; , E. coli
• Risk factors
  • Prolonged labor or premature rupture of membranes (PROM)
  • Pathological bacterial colonization of vaginal tract (e.g., STDs, frequent UTIs)
  • Iatrogenic: multiple digital vaginal exams, invasive procedures (e.g., amniocentesis)

Clinical features

• Maternal
  • Fever (> 38 °C or > 100°F)
  • Tachycardia > 120/min
  • Uterine tenderness, pelvic pain
  • Malodorous and purulent amniotic fluid, vaginal discharge
  • Premature contractions, PROM
• Fetal tachycardia > 160/min in cardiotocography

Diagnosis

Chorioamnionitis is a clinical diagnosis (fever plus ≥ 1 additional symptom). Tests support or confirm diagnosis if the clinical presentation is ambiguous (e.g., in subclinical chorioamnionitis).

• Maternal blood tests
  • Leukocytosis > 15,000 cells/μL (∼ 70–90% of cases)
  • ↑ CRP
• Bacterial cultures
  • Urogenital secretions
  • Amniotic fluid (most reliable, but rarely conducted)
• Group B Streptococcus screening: cervicovaginal and rectal swabs

Management

• Maternal antibiotic therapy
  • Vaginal delivery: IV ampicillin plus gentamicin (broad coverage) ^[27]
  • Cesarean delivery: IV ampicillin and gentamicin, plus clindamycin (anaerobe coverage to minimize postcesarean complications, e.g., endometritis)
• Delivery
  • Swift delivery is generally indicated to minimize both maternal and fetal complications.
  • Cesarean delivery is not generally indicated, but is often necessary because of obstetrical complications (e.g., insufficient contractions).
• For treatment of newborns, see “Neonatal infection” below.

Complications

• Maternal
  • Uterine atony, postpartum hemorrhage, endometritis
  • Septic shock, DIC, venous thrombosis, pulmonary embolism, death
• Fetal/neonatal
  • Fetal death, premature birth
  • Asphyxia, intraventricular hemorrhage, cerebral palsy
  • Neonatal infection

References:^{[27][28][29][30]}

Supine hypotensive syndrome

• Compression of the vena cava and pelvic veins by the uterus may occur during the third trimester of pregnancy (typically >20 weeks) as a result of the mother lying in a supine position.
  • Gravid uterus → compression of the abdominal aorta and IVC → impaired venous return and decrease in cardiac output → placental hypoperfusion → fetal hypoxia → deceleration (CTG)
  • After repositioning the mother in the left lateral position, the fetal heart rate recovers.
  • In the mother, supine hypotensive syndrome is characterized by tachycardia, dizziness, and nausea, and occasionally causes syncope.

Peripheral edema

• Very common, benign finding
• Management
  • Rule out DVT and preeclampsia
  • Monitoring; usually no treatment necessary

Pelvic girdle pain ^[31]

• Etiology: increased pressure from the uterus, lumbar lordosis, and relaxation of the ligaments supporting the joints of the pelvic girdle
• Epidemiology: common, occurring in 15–25 % of pregnant patients.
• Clinical features: lower back pain
  • Particularly between the posterior iliac crest and the gluteal fold and in the area of the sacroiliac joint
  • May radiate to the thighs and hips
  • Worsens with weight-bearing
• Diagnosis: positive pelvic pain provocation tests (e.g., posterior pelvic pain provocation test, FABER test, active straight leg raise)
• Management
  • Nonpharmacological: heat therapy, manual therapy (e.g., massage, spinal manipulation), braces, physical therapy
  • Pharmacological: acetaminophen

Round ligament pain

• Etiology: stretching of the round ligament of the uterus as the uterus expands
• Epidemiology: one of the most common conditions during pregnancy
• Clinical features
  • Typically manifests in the second and third trimester
  • Sharp pain in the lower abdomen and groin area (most often right-sided)
  • Triggered by sudden and/or rapid movements (e.g., rolling over in bed, sneezing, vigorous physical activity)
• Diagnosis: based on clinical history
• Management: usually no treatment required; resolves after delivery

Carpal tunnel syndrome

• Caused by peripheral edema
• Usually resolves after delivery

Meralgia paresthetica

• Compression at the level of the inguinal ligament (lateral femoral cutaneous nerve), caused by increased intraabdominal pressure during pregnancy → pain and paresthesias on the lateral surface of the anterior thigh
• Pain may worsen as pregnancy progresses but typically resolves after delivery as compression is relieved.

Polymorphic eruption of pregnancy (PEP)

• Description: A benign, inflammatory condition that most commonly affects primiparous women in the third trimester of pregnancy or immediately postpartum.
• Epidemiology: relatively common, occurring in ∼ 1:160 pregnant patients ^[32]
• Clinical features
  • Very pruritic, erythematous papules within abdominal striae
  • Lesions can spread to the chest, back, and extremities, and coalesce into urticarial plaques, sparing the face, palms, and soles
  • Lesions last 4–6 weeks and resolve spontaneously ^[33]
• Differential diagnosis: gestational pemphigoid
  • The early stages of PEP are similar to gestational pemphigoid.
  • However, PEP typically begins in the striae (with periumbilical sparing), while the lesions in gestational pemphigoid are located periumbilical.
• Management: : topical corticosteroids

Gestational thrombocytopenia ^[34][35]

• Description
  • A benign condition characterized by mild thrombocytopenia
  • Most common during the second half of pregnancy
• Pathophysiology: likely due to increased circulatory volume during pregnancy (i.e., dilutional thrombocytopenia) and consumption and pooling of platelets in the placenta
• Diagnostics
  • CBC: ↓ platelet count (100,000–150,000/mm³)
  • Diagnosis of exclusion; additional evaluation is not necessary.
  • Further workup to assess for more serious causes (e.g., immune thrombocytopenia, HELLP) is indicated in symptomatic patients or those with more severe thrombocytopenia (< 100,000/mm³).
• Management: does not require treatment or change in prenatal care and delivery

Cephalopelvic disproportion

• The fetal size is disproportionately large for the maternal pelvis.
• Can result in a prolonged second stage of labor

Others

• Gastrointestinal reflux
• Pregnancy luteoma