Risk Factors for Pregnancy Complications

Preexisting diabetes mellitus is present in approximately 1% of pregnancies (1, 2), and gestational diabetes occurs in approximately 8% of pregnancies (3). Incidence is increasing as the incidence of obesity increases.

Preexisting insulin-dependent diabetes increases the risk of the following:

• Pyelonephritis

• Ketoacidosis

• Preeclampsia

• Fetal death

• Major fetal malformations

• Fetal macrosomia (fetal weight > 4.5 kg)

• If vasculopathy is present, fetal growth restriction

• The need for preterm, cesarean, or operative delivery

The incidence of fetal macrosomia is approximately 50% higher in pregnant women with preexisting diabetes than in pregnant women in the general population. The incidence of perinatal fetal or neonatal mortality is also higher.

Women with preexisting diabetes are more likely to require preterm delivery for obstetric or medical indications. Exercise during pregnancy (with judicious changes in diet) reduces the need for cesarean and operative deliveries in these women (4, 5).

Tight glucose control before conception and during early pregnancy is essential to prevent fetal malformations.

Insulin requirements usually increase during pregnancy.

Gestational diabetes increases the risk of the following:

• Hypertensive disorders of pregnancy

• Fetal macrosomia

• The need for cesarean delivery

Gestational diabetes is routinely screened for at 24 to 28 weeks and, if women have risk factors, during the first trimester. Risk factors include the following:

• Previous gestational diabetes

• A macrosomic infant in a previous pregnancy

• Unexplained fetal losses

• Prepregnancy body mass index (BMI) > 30 kg/m2

• Maternal age > 40 years

• Family history of diabetes

• Non-Hispanic Asian/Pacific Islander and Hispanic/Latina ethnicity

Screening and confirmation of the diagnosis of gestational diabetes can be done in 1 or 2 steps (6, 7):

• 1-step test: A fasting, 75-g glucose, 2-hour oral glucose tolerance test (GTT). Abnormal results are any of the following: fasting (≥ 92 mg/dL [5.1 mmol/L]); 1 hour (≥ 180 mg/dL [10 mmol/L]); or 2 hour (≥ 153 mg/dL [8.5 mmol/L).

• 2-step test: A non-fasting, 50-g glucose, 1-hour GTT; if abnormal (≥ 130 mg/dL [7.5 mmol/L] to 140 mg/dL [7.8 mmol/L]), then a fasting, 100-g, 3-hour GTT. For interpretation of results , see table Glucose Thresholds for Gestational Diabetes Mellitus Using a 3-hour Oral Glucose Tolerance Test.

The American College of Obstetricians and Gynecologists (ACOG) recommends the 2-step test to diagnosis gestational diabetes. The 1-step approach has been used and promoted by other organizations, including the International Association of Diabetes and Pregnancy Study Group (IADPSG) (6).

Optimal treatment of gestational diabetes (with dietary modification, exercise, and close monitoring of blood glucose levels and insulin when necessary) reduces risk of adverse maternal, fetal, and neonatal outcomes. Women with gestational diabetes are at a higher lifetime risk of cardiovascular events and, after delivery, should be referred for appropriate cardiovascular risk assessment and follow-up.

Women with gestational diabetes mellitus may have had undiagnosed diabetes mellitus before pregnancy. Thus, they should be screened for diabetes mellitus 6 to 12 weeks postpartum, using the same testing and criteria used for patients who are not pregnant.

See Diabetes Mellitus in Pregnancy for details regarding management of diabetes in pregnancy.

Hypertensive disorders of pregnancy are classified as (1)

• Chronic hypertension: Present before the pregnancy or developing before 20 weeks of pregnancy

• Gestational hypertension: New onset of systolic and/or diastolic blood pressure (BP) ≥ 140/≥ 90 mm Hg on 2 occasions at least 4 hours apart after 20 weeks of gestation

• Preeclampsia: New onset after 20 weeks of gestation of persistent (2 episodes within 4 hours) systolic and/or diastolic BP ≥ 140/≥ 90 mm Hg OR at least 1 measurement of systolic and/or diastolic BP ≥ 160/≥ 110 mm Hg PLUS new unexplained proteinuria (> 300 mg/24 hours or urine protein/creatinine ratio ≥ 0.3 or dipstick reading of 2+; in the absence of proteinuria, new-onset hypertension with new onset of other signs of end-organ damage (eg, thrombocytopenia [platelets < 100,000/mcL], impaired liver function, renal insufficiency, pulmonary edema, new-onset headache [unresponsive to medication and not accounted for by alternative diagnoses], visual symptoms).

• Preeclampsia with severe features: Preeclampsia with persistent (2 episodes within 4 hours) systolic and/or diastolic BP ≥ 160/≥ 110 mm Hg and/or other signs of end-organ damage

• HELLP syndrome: A form of severe preeclampsia with hemolysis, elevated liver enzymes, and low platelet count

• Chronic hypertension plus superimposed preeclampsia: Worsening hypertension and new or worsening proteinuria or other signs of end-organ damage after 20 weeks in a woman with preexisting hypertension

• Eclampsia: New-onset tonic-clonic, focal, or multifocal seizures not accounted for by other causes

Chronic hypertension increases risk of the following:

• Fetal growth restriction (by decreasing uteroplacental blood flow)

• Preeclampsia and eclampsia

• Adverse fetal and maternal outcomes

Before attempting to become pregnant, women with hypertension should be counseled about risks. Prenatal care should begin as early in pregnancy as possible. Pregnant women with chronic hypertension who require antihypertensive therapy should be started or continued on appropriate medications and referred to a maternal-fetal medicine specialist (2).

Management of chronic hypertension during pregnancy includes measurements of baseline renal function (eg, serum creatinine, blood urea nitrogen [BUN]), funduscopic examination, and directed cardiovascular evaluation (auscultation and sometimes ECG, echocardiography, or both). Each trimester, 24-hour urine protein, serum uric acid, serum creatinine, and hematocrit are measured.

Ultrasonography to monitor fetal growth is done at 28 weeks and every 4 weeks thereafter. Delayed growth is evaluated with multivessel Doppler testing by a maternal-fetal medicine specialist.

If women are at high risk of preeclampsia, clinicians may prescribe low-dose aspirin (81 to 162 mg orally once a day) to be taken daily starting at 12 to 28 weeks of gestation and taken until delivery (3, 4).

Women with a history of preeclampsia or gestational hypertension are at a higher lifetime risk of cardiovascular events and, after delivery, should be referred for appropriate cardiovascular risk assessment and follow-up.

Thyroid disorders may predate or develop during pregnancy. Pregnancy does not change the symptoms of hypothyroidism and hyperthyroidism.

Fetal effects vary with the disorder and the medications used for treatment. But generally, untreated or inadequately treated hyperthyroidism can result in

• Fetal growth restriction

• Preeclampsia

• Stillbirth

Untreated hypothyroidism can cause

• Intellectual deficits in children

• Spontaneous abortion

The most common causes of maternal hypothyroidism are Hashimoto thyroiditis and treatment of Graves disease.

If women have or have had a thyroid disorder, thyroid status should be closely monitored during and after pregnancy in the women and after delivery in infants. Goiters and thyroid nodules discovered during pregnancy should be evaluated as they are in nonpregnant patients (see Approach to the Patient With a Thyroid Nodule and Diagnosis of Simple Nontoxic Goiter).

(See also Sexually Transmitted Infections and Infectious Disease in Pregnancy.)

Screening for sexually transmitted infections should be done during pregnancy to make treatment possible and to prevent adverse effects of intrauterine or perinatal transmitted infections to the fetus or neonate. The rate of congenital syphilis in the United States consistently rises (see CDC: National Overview of STDs, 2021).

Routine prenatal care includes screening tests for HIV infection, hepatitis B, hepatitis C (1), and syphilis and, if < 25 years, for chlamydial infection and gonorrhea at the first prenatal visit. Syphilis testing is repeated during pregnancy and at delivery if risk continues or if the patient resides in an endemic area (2). Pregnant women who have any of these infections are treated with antimicrobials.

Fetal syphilis in utero can cause fetal death, congenital malformations, and severe disability.

Without treatment, risk of transmission of HIV from mother to child is approximately 30% prepartum and approximately 25% intrapartum. Antiretroviral treatment of the pregnant woman before and during pregnancy and of the neonate within 6 to 12 hours of birth reduces risk of HIV transmission to the fetus by two thirds; risk is lower (< 2%) with a combination of 2 or 3 highly active antiretrovirals. Highly active antiretrovirals are given to the mother during pregnancy and intrapartum to prevent mother-to-child transmission.

During pregnancy, hepatitis, bacterial vaginosis, gonorrhea, and genital chlamydial infection increase risk of preterm labor and prelabor rupture of the membranes.

Treatment of bacterial vaginosis, gonorrhea, or chlamydial infection may prolong the interval from rupture of the membranes to delivery and may improve fetal outcome by decreasing fetal inflammation.

Structural abnormalities of the uterus and cervix (eg, uterine septum, bicornuate uterus) make the following more likely:

• Spontaneous abortion during the second trimester

• Fetal malpresentation

• Preterm labor or delivery

• Dysfunctional labor

• The need for cesarean delivery

Uterine fibroids uncommonly cause placental abnormalities (eg, placenta previa), preterm labor, and recurrent spontaneous abortion. Fibroids may grow rapidly or degenerate during pregnancy; degeneration often causes severe pain and peritoneal signs and may also cause preterm labor.

Cervical insufficiency (incompetence) makes preterm delivery more likely. The risk of cervical insufficiency is higher in women who have had lacerations or injury of the cervix during a previous procedure (eg, therapeutic abortion, instrumental vaginal deliveries). Cervical insufficiency is treated with surgical intervention (cerclage).

If, before pregnancy, women have had a myomectomy in which the uterine cavity was entered, cesarean delivery is required because uterine rupture is a risk during subsequent vaginal delivery.

Uterine abnormalities that lead to poor obstetric outcomes often require surgical correction, which is done after delivery.

Substance use during pregnancy, including caffeine, alcohol, tobacco, and illicit drug use, is associated with adverse outcomes. Depending on the particular substance, misuse in pregnancy may lead to a range of complications, including preterm labor, low birth weight, congenital anomalies, developmental delays, and long-term behavioral and cognitive problems in the child.

Maternal substance use, especially with opioids, can also result in neonatal withdrawal symptoms requiring specialized care.

Alcohol is the most commonly used teratogen. Risk is probably related to amount of alcohol consumed, but no amount is known to be risk-free. Binge drinking in particular, possibly as little as 45 mL of pure alcohol (equivalent to about 3 drinks) a day, can cause fetal alcohol syndrome, which may result in fetal growth restriction, facial and cardiovascular defects, and neurologic dysfunction.

Clinicians should ask pregnant patients about substance misuse, utilize validated screening tools, and refer to addiction specialists when necessary.

Common teratogens (agents that cause fetal malformation) include infections, drugs, and physical agents. Malformations are most likely to result if exposure occurs between the second and eighth week after conception (the fourth to tenth week after the last menstrual period), when organs are forming. Other adverse pregnancy outcomes are also more likely. Pregnant women exposed to teratogens are counseled about increased risks and referred for detailed ultrasound evaluation to detect malformations.

Pregnancy Myths

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Common infections that may be teratogenic include

• Herpes simplex

• Rubella

• Varicella

• Syphilis

• Toxoplasmosis

• Cytomegalovirus infection

• Coxsackievirus infection

• Zika virus infection

Commonly used drugs that may be teratogenic include

• Alcohol

• Tobacco

• Cocaine

• Bath salts (cathinones)

• Some prescription drugs (see table Drugs With Adverse Effects During Pregnancy)

Hyperthermia or exposure to temperatures > 39° C (eg, in a sauna) during the first trimester has been associated with spina bifida.

Mercury in seafood can be toxic to the fetus. The FDA (see Advice about Eating Fish For Those Who Might Become or Are Pregnant or Breastfeeding and Children Ages 1–11 Years) recommends the following:

• Avoiding tilefish from the Gulf of Mexico, shark, swordfish, big-eye tuna, marlin, orange roughy, and king mackerel

• Limiting albacore tuna to 4 ounces (one average meal)/week

• Before eating fish caught in local lakes, rivers, and coastal areas, checking local advisories about the safety of such fish and, if levels of mercury are not known to be low, limiting consumption to 4 ounces/week while avoiding other seafood that week

Tilefish from the Gulf of Mexico have the highest levels of mercury of all fish (as tested by the U.S. Food and Drug Administration (FDA); tilefish from the Atlantic Ocean can be safely eaten.

Advice About Eating Fish

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Image from the U.S. Food and Drug Administration (FDA) and the United States Environmental Protection Agency (EPA).

Experts recommend that women who are pregnant or breastfeeding eat 8 to 12 ounces (2 or 3 average meals) per week of a variety of seafood that is lower in mercury. Such seafood includes flounder, shrimp, canned light tuna, salmon, pollock, tilapia, cod, and catfish. Fish has nutrients that are important for fetal growth and development.

Adolescents, who account for 13% of all pregnancies, have an increased incidence of preeclampsia, preterm labor, and anemia, which often leads to fetal growth restriction. The cause, at least in part, is that adolescents tend to neglect prenatal care, frequently smoke cigarettes or use other substances, and have higher rates of sexually transmitted infections.

In women ≥ 35 years, the incidence of preeclampsia is increased, as is that of gestational diabetes, dysfunctional labor, abruptio placentae, stillbirth, and placenta previa. These women are also more likely to have preexisting disorders (eg, chronic hypertension, diabetes). Because risk of fetal chromosomal abnormalities increases as maternal age increases, genetic screening and testing and detailed ultrasound screening for fetal malformations should be offered.

The most common chromosomal abnormality is autosomal trisomy. The United States National Birth Defects Prevention Study (NBDPS) found that children of women > 40 years are at increased risk of cardiac abnormalities, esophageal atresia, hypospadias, and craniosynostosis (1).

Pregnant women whose body mass index (BMI) was < 18.5 kg/m2 before pregnancy are considered underweight, which predisposes to low birth weight (< 2.5 kg) in neonates. Such women are encouraged to gain at least 12.5 kg during pregnancy.

Pregnant women whose BMI was 25 to 29.9 kg/m2 (overweight) or ≥ 30 kg/m2 (obese) before pregnancy are at risk of maternal hypertension and diabetes, postterm pregnancy, pregnancy loss, fetal macrosomia, congenital malformations, intrauterine growth restriction, preeclampsia, and the need for cesarean delivery. Ideally, weight loss should begin before pregnancy, first by trying lifestyle modifications (eg, increased physical activity, dietary changes). Women with overweight or obesity are encouraged to limit weight gain during pregnancy, ideally by modifying their lifestyle. The Institute of Medicine (IOM) uses the following guidelines:

• Overweight: Weight gain limited to 6.8 to 11.3 kg (15 to 25 lb)

• Obese: Weight gain limited to < 5 to 9 kg (11 to 20 lb)

However, not all experts agree with IOM recommendations. Many experts recommend an individualized approach that can include more limited weight gain plus lifestyle modifications (eg, increased physical activity, dietary changes), particularly for women with obesity (1). During pregnancy, most women should be encouraged to exercise at least 3 times a week for a total of 150 minutes each week (2).

For pregnant women with overweight or obesity, lifestyle modifications during pregnancy reduce the risk of gestational diabetes and preeclampsia.

Discussing appropriate weight gain, diet, and exercise at the initial visit and periodically throughout the pregnancy is important.

Clinical Calculators

Body Mass Index (Quetelet's index)

Multiple gestation increases risk of the following:

• Fetal growth restriction

• Preterm labor

• Placental abruption

• Chromosomal abnormalities

• Congenital malformations

• Perinatal morbidity and mortality

• After delivery, uterine atony and hemorrhage

Multiple gestation is usually detected with ultrasonography in the first trimester. Incidence of multiple gestations has been increasing; use of assisted reproductive technologies have contributed substantially to this increase (1).

Risk of having a fetus with a chromosomal disorder is increased for most couples who have had a fetus or neonate with a chromosomal disorder (recognized or missed). Recurrence risk for most genetic disorders is unknown. Most congenital malformations are multifactorial; risk of having a subsequent fetus with malformations varies based on the defect itself.

If couples have had a neonate with a genetic or chromosomal disorder, genetic consultation and screening is recommended. If couples have had a neonate with a congenital malformation, genetic screening, high-resolution ultrasonography, and evaluation by a maternal-fetal medicine specialist is recommended.

Stillbirth is death of a fetus at ≥ 20 weeks gestation before or during delivery, as defined by the Centers for Disease Control and Prevention (CDC [1]), or at > 28 weeks, as defined by the World Health Organization (2). Fetal death during late pregnancy may have maternal, placental, or fetal anatomic or genetic causes (see table Common Causes of Stillbirth). Having had a stillbirth or late abortion (ie, at 16 to 20 weeks) increases risk of fetal death in subsequent pregnancies. Degree of risk varies depending on the cause of a previous stillbirth. Fetal surveillance using antepartum testing (eg, nonstress testing, biophysical profile) is recommended.

Treatment of maternal disorders (eg, chronic hypertension, diabetes, infections) may lower risk of stillbirth in a current pregnancy.

Preterm delivery is delivery before 37 weeks. Previous preterm delivery due to preterm labor is associated with an increased risk of future preterm deliveries. Preterm delivery is also sometimes medically indicated due to certain pregnancy complications (eg, severe preeclampsia or symptomatic placenta previa). These diseases are not independent risk factors for preterm delivery, but they may recur, and appropriate monitoring or preventive measures should be done.

Women with prior preterm delivery due to unexplained preterm labor should be closely monitored at 2-week intervals beginning at 15 to 16 weeks gestation, up to 23 to 24 weeks. Evaluation may include (1)

• Ultrasound evaluation, including measurement of cervical length, beginning at 15 to 16 weeks

• Testing for bacterial vaginosis, if there are symptoms

• Measurement of fetal fibronectin for women with symptoms concerning for preterm labor

Most cerebral palsy and neurodevelopmental disorders are caused by factors unrelated to a birth injury. Injuries such as brachial plexus damage can result from procedures such as forceps or vacuum extractor delivery but often result from intrauterine forces during labor or malposition during the last weeks of pregnancy.

Previous shoulder dystocia is a risk factor for future dystocia, and the delivery records should be reviewed for potentially modifiable risk factors (eg, fetal macrosomia, operative vaginal delivery) that may have predisposed to the injury.