Risk factors include preexisting maternal disorders (see Pregnancy Complicated by Disease), physical and social characteristics, age, problems in previous pregnancies (eg, spontaneous abortions), and problems that develop during pregnancy (see Abnormalities of Pregnancy) or during labor and delivery (see Abnormalities and Complications of Labor and Delivery).

Hypertension

Pregnant women are considered to have chronic hypertension (CHTN) if hypertension was present before the pregnancy or if it develops before 20 wk of pregnancy. CHTN is differentiated from gestational hypertension, which develops after 20 wk of pregnancy. In either case, hypertension is defined as systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg on 2 occasions > 24 h apart. Hypertension increases risk of fetal growth restriction by decreasing uteroplacental blood flow and risk of adverse fetal and maternal outcomes (see Pregnancy Complicated by Disease: Hypertension in Pregnancy).

Before attempting to conceive, women with hypertension should be counseled about the risks of pregnancy. If they become pregnant, prenatal care begins as early as possible and includes measurements of baseline renal function (eg, serum creatinine, BUN), funduscopic examination, and directed cardiovascular evaluation (auscultation and sometimes ECG, echocardiography, or both). Each trimester, 24-h urine protein, serum uric acid, serum creatinine, and Hct are measured. Ultrasonography to monitor fetal growth is done at 28 wk and every 4 wk thereafter. Delayed growth is evaluated with multivessel Doppler testing by a maternal-fetal medicine specialist (for management of hypertension during pregnancy, see Pregnancy Complicated by Disease: Treatment).

Diabetes

Diabetes mellitus occurs in 3 to 5% of pregnancies, but incidence is increasing as the incidence of obesity increases.

If pregnant women have preexisting insulin-dependent diabetes, risk is increased for pyelonephritis, ketoacidosis, preeclampsia, fetal death, major fetal malformations, fetal macrosomia (fetal weight > 4.5 kg), and, if vasculopathy is present, fetal growth restriction. Insulin requirements usually increase during pregnancy.

If women have gestational diabetes, risk of hypertensive disorders and fetal macrosomia is increased. Gestational diabetes is routinely screened for at 24 to 28 wk or, if women have risk factors, also during the 1st trimester. Risk factors include previous gestational diabetes, a macrosomic infant in a previous pregnancy, family history of non-insulin–dependent diabetes, unexplained fetal losses, and body mass index (BMI) > 30 kg/m². Some clinicians think the diagnosis can be based on a fasting plasma glucose of > 126 mg/dL or a random plasma glucose of > 200 mg/dL. However, most accurate results are obtained with a glucose tolerance test. A 50-g, 1-h glucose tolerance test is used. If the result is 140 to 200 mg/dL, a full glucose tolerance test is done (see Table 2: Diabetes Mellitus and Disorders of Carbohydrate Metabolism: Diagnostic Criteria for Diabetes Mellitus and Impaired Glucose Regulation); if glucose is > 200 mg/dL, insulin is begun. If ≥ 2 test results are abnormal, women are treated for the rest of the pregnancy with diet and, if necessary, insulin or oral hypoglycemic drugs.

Good control of plasma glucose during pregnancy almost eliminates the risk of adverse outcomes attributable to diabetes (for management of diabetes during pregnancy, see Pregnancy Complicated by Disease: During pregnancy).

Sexually transmitted diseases (STDs)

(see Sexually Transmitted Diseases (STD)) Fetal syphilis in utero can cause fetal death, congenital malformations, and severe disability. Risk of transmission of HIV from woman to offspring in utero or perinatally is 30 to 50% within 6 mo (see Human Immunodeficiency Virus (HIV): Transmission; see Infections in Infants and Children: Human Immunodeficiency Virus (HIV) Infection in Children). During pregnancy, bacterial vaginosis, gonorrhea, and genital chlamydial infection increase risk of preterm labor and premature rupture of the membranes. Routine prenatal care includes screening tests for these infections at the first prenatal visit. Syphilis testing is repeated during pregnancy if risk continues and at delivery for all women. Pregnant women who have any of these infections are treated with antimicrobials.

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. Treating HIV with zidovudine or nevirapine reduces risk of transmission by ²/₃; risk is probably lower (< 2%) with a combination of 2 or 3 antivirals (see Infections in Infants and Children: Prevention). These drugs are recommended despite potential toxic effects in the fetus and woman.

Pyelonephritis

Pyelonephritis increases risk of premature rupture of the membranes, preterm labor, and infant respiratory distress syndrome. Pregnant women with pyelonephritis are hospitalized for evaluation and treatment, primarily with urine culture plus sensitivities, IV antibiotics (eg, a 3rd-generation cephalosporin with or without an aminoglycoside), antipyretics, and hydration. Pyelonephritis is the most common nonobstetric cause of hospitalization during pregnancy. Oral antibiotics specific to the causative organism are begun 24 to 48 h after fever resolves and continued to complete the whole course of antibiotic therapy, usually 7 to 10 days. Prophylactic antibiotics (eg, nitrofurantoin, trimethoprim/sulfamethoxazole) with periodic urine cultures are continued for the rest of the pregnancy.

Acute surgical problems

Major surgery, particularly intra-abdominal, increases risk of preterm labor and fetal death. However, surgery is usually tolerated well by pregnant women and the fetus when appropriate supportive care and anesthesia (maintaining BP and oxygenation at normal levels) are provided, so physicians should not be reluctant to operate; delaying treatment of an abdominal emergency is far more dangerous.

After surgery, antibiotics and tocolytic drugs are given for 12 to 24 h. If nonemergency surgery is necessary during pregnancy, it is most safely done during the 2nd trimester.

Genital tract abnormalities

Structural abnormalities of the uterus and cervix (eg, uterine septum, bicornuate uterus) make fetal malpresentation, dysfunctional labor, and the need for cesarean delivery more likely. Although unlikely, uterine fibroids can 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. Cervical insufficiency (incompetence—see Abnormalities of Pregnancy: Cervical Incompetence) makes preterm delivery more likely. If women have had a myomectomy before pregnancy 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.

Maternal age

Teenagers, 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 teenagers tend to neglect prenatal care, frequently smoke, and have higher rates of sexually transmitted diseases.

In women > 35, 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, CHTN, diabetes). Because risk of fetal chromosomal abnormalities increases as maternal age increases, genetic testing should be offered (see Prenatal Genetic Counseling and Evaluation: Genetic Evaluation).

Maternal weight

Pregnant women whose BMI was < 19.8 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 > 29.0 kg/m² before pregnancy are considered overweight, making maternal hypertension and diabetes, postterm pregnancy, fetal macrosomia, and the need for cesarean delivery more likely. Such women are encouraged to limit weight gain during pregnancy to < 11.5 kg.

Maternal height

Short (about < 152 cm) women are more likely to have a small pelvis, which can lead to dystocia with fetopelvic disproportion or shoulder dystocia. For short women, preterm labor and intrauterine growth restriction are also more likely.

Exposure to teratogens

Common teratogens (agents that cause fetal malformation) include infections, drugs, and physical agents. Malformations are most likely to result if exposure occurs between the 2nd and 8th wk after conception (the 4th to 10th wk 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.

Common infections that may be teratogenic include herpes simplex, viral hepatitis, rubella, varicella, syphilis, toxoplasmosis, and cytomegalovirus and coxsackievirus infections.

Commonly used drugs that may be teratogenic include alcohol, tobacco, cocaine, and some prescription drugs (see Table 2: High-Risk Pregnancy: Drugs With Adverse Effects During Pregnancy).

Table 2
Drugs With Adverse Effects During Pregnancy Examples Adverse Effects Pregnancy Safety Category* Antibacterials Aminoglycosides Ototoxicity (eg, damage to fetal labyrinth), resulting in deafness D Chloramphenicol Gray baby syndrome In women or fetuses with G6PD deficiency, hemolysis C Fluoroquinolones Possibly arthralgia; theoretically, musculoskeletal defects (eg, impaired bone growth), but no proof of this effect C Primaquine In women or fetuses with G6PD deficiency, hemolysis C Sulfonamides (except sulfasalazine, which has minimal fetal risk) When the drugs are given after about 34 wk gestation, neonatal jaundice and, without treatment, kernicterus In women or fetuses with G6PD deficiency, hemolysis C Tetracycline Slowed bone growth, enamel hypoplasia, permanent yellowing of the teeth, and increased susceptibility to cavities in offspring Occasionally, liver failure in pregnant women D Trimethoprim Increased risk of neural tube defects due to folate antagonism C Anticoagulants Low mol wt heparin When heparin is taken a long time (eg, > 6 mo), maternal osteoporosis B Unfractionated heparin When heparin is taken a long time (eg, > 6 mo), maternal osteoporosis and thrombocytopenia C Warfarin When warfarin is given during the 1st trimester, often fetal warfarin syndrome (eg, nasal hypoplasia, bone stippling, bilateral optic atrophy, various degrees of mental retardation) When the drug is given during the 2nd or 3rd trimester, optic atrophy, cataracts, mental retardation, microcephaly, microphthalmia, and fetal and maternal hemorrhage X Anticonvulsants Carbamazepine Hemorrhagic disease of the newborn Some risk of congenital malformations D Phenobarbital Hemorrhagic disease of the newborn Some risk of congenital malformations D Phenytoin Congenital malformations (eg, cleft lip, GU defects such as a narrowed or an incompletely formed urethra, cardiovascular defects) Hemorrhagic disease of the newborn D Trimethadione High risk of congenital malformations (eg, cleft palate; cardiac, craniofacial, hand, and abdominal defects) and risk of spontaneous abortion Almost always contraindicated during pregnancy D Valproate Major congenital malformations (eg, meningomyelocele; cardiac, craniofacial, and limb defects) D Antivertigo drugs Meclizine Teratogenic in rodents, but no proof of this effect in humans B Antihypertensives ACE inhibitors (see Table 8: Arterial Hypertension: ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension) When the drugs are given during the 2nd or 3rd trimester, fetal hypocalvaria and hypoperfusion (which can cause renal defects), renal failure, and the oligohydramnios sequence (oligohydramnios, craniofacial deformities, limb contractures, and hypoplastic lung development) D β-Blockers Fetal bradycardia, hypoglycemia, and possibly fetal growth restriction C Thiazide diuretics Prevention of normal maternal volume expansion, reducing placental perfusion and contributing to fetal growth restriction Neonatal hyponatremia, hypokalemia, and thrombocytopenia D Antineoplastic drugs Actinomycin Teratogenic in animals, but no proof of this effect in humans D Busulfan Congenital malformations (eg, fetal growth restriction, mandibular hypoplasia, cleft palate, cranial dysostosis, spinal defects, ear defects, clubfoot) D Chlorambucil Same as those for busulfan D Colchicine Possibly congenital malformations and sperm abnormalities D Cyclophosphamide Same as those for busulfan D Mercaptopurine Same as those for busulfan D Methotrexate Same as those for busulfan X Vinblastine Teratogenic in animals, but no proof of this effect in humans D Vincristine Teratogenic in animals, but no proof of this effect in humans D Anxiolytics Diazepam When diazepam is given late in pregnancy, respiratory depression or a withdrawal syndrome that can cause neonatal irritability, tremors, and hyperreflexia D Hypoglycemic drugs (oral) Chlorpropamide Neonatal hypoglycemia C Glyburide Same as those for chlorpropamide C Tolbutamide Same as those for chlorpropamide D Lithium Lithium Teratogenic Neonatal lethargy, hypotonia, poor feeding, hypothyroidism, goiter, and nephrogenic diabetes insipidus D Opioids Codeine Meperidine Morphine In neonates of women addicted to opioids, withdrawal symptoms 6 h to 8 days after birth With large doses given in the hour before delivery, possibly neonatal CNS depression and bradycardia C Retinoids Isotretinoin Congenital malformations, spontaneous abortion, and mental retardation X Salicylates Aspirin Fetal kernicterus With large doses of the drugs, delayed onset of labor, premature closing of the fetal ductus arteriosus, jaundice, and occasionally maternal (intrapartum or postpartum) and neonatal hemorrhage When the drugs are taken late in pregnancy, oligohydramnios D Others Same as those for aspirin D Sex hormones Danazol When these drugs are given during the first 14 wk, masculinization of a female fetus's genitals (eg, pseudohermaphroditism), sometimes requiring surgery to correct X Synthetic progestins (but not the low doses used in oral contraceptives) Same as those for danazol X Thyroid drugs Methimazole Fetal goiter and neonatal scalp defects (aplasia cutis) D Propylthiouracil Fetal goiter D Radioactive iodine (131I) Destruction of the fetal thyroid gland or, when the drug is given near the end of the 1st trimester, severe fetal hyperthyroidism D Saturated solution of K iodide Large fetal goiter, which may obstruct breathing in neonates   Triiodothyronine Fetal goiter D Vaccines Live-virus vaccines such as those for measles, mumps, rubella, polio, chickenpox, and yellow fever With rubella vaccine, potential infection of the placenta and developing fetus With other vaccines, potential but unknown risks   Others Naphthalene In women or fetuses with G6PD deficiency, hemolysis C Vitamin K In women or fetuses with G6PD deficiency, hemolysis C *FDA pregnancy categories: A: Studies in pregnant women show no risk. B: Animal studies show no risk, but human data are insufficient; or animal studies show toxicity, but human studies show no risk. C: Animal studies show toxicity, human data are insufficient, but clinical benefit may exceed risk. D: There is evidence of human risk, but clinical benefits may outweigh risk. X: There is evidence of fetal abnormalities in humans, and risk exceeds benefits. G6PD = glucose-6-phosphate dehydrogenase.

Cigarette smoking is the most common addiction among pregnant women. Also, percentages of women who smoke and of those who smoke heavily appear to be increasing. Only 20% of smokers quit during pregnancy. Carbon monoxide and nicotine in cigarettes cause hypoxia and vasoconstriction, increasing risk of spontaneous abortion (fetal loss or delivery < 20 wk), fetal growth restriction, abruptio placentae, placenta previa, premature rupture of the membranes, preterm birth, chorioamnionitis, and stillbirth. Neonates whose mothers smoke are also more likely to have anencephaly, congenital heart defects, orofacial clefts, sudden infant death syndrome, deficiencies in physical growth and intelligence, and behavioral problems. Smoking cessation or limitation reduces risks.

Alcohol is the most commonly used teratogen. Drinking alcohol during pregnancy increases risk of spontaneous abortion. Risk is probably related to amount of alcohol consumed, but no amount is known to be risk-free. Regular drinking decreases birth weight by about 1 to 1.3 kg. 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. This syndrome occurs in 2.2/1000 live births; it includes fetal growth restriction, facial and cardiovascular defects, and neurologic dysfunction. It is a leading cause of mental retardation and can cause neonatal death due to failure to thrive.

Cocaine use has indirect fetal risks (eg, maternal stroke or death during pregnancy). It also directly causes fetal vasoconstriction and hypoxia. Repeated use increases risk of spontaneous abortion, fetal growth restriction, abruptio placentae, preterm birth, stillbirth, and congenital malformations (eg, CNS, GU, and skeletal malformations; isolated atresias).

Although marijuana's main metabolite can cross the placenta, recreational use of marijuana use does not consistently appear to increase risk of congenital malformations, fetal growth restriction, or postnatal neurobehavioral abnormalities.

Prior stillbirth

Causes of stillbirth (fetal death > 20 wk) may be maternal, placental, or fetal (see Abnormalities of Pregnancy: Stillbirth). Having had a stillbirth or late abortion (ie, at 16 to 20 wk) increases risk of fetal death in subsequent pregnancies. Fetal surveillance using antepartum testing (eg, nonstress testing, biophysical profile) is recommended. Treatment of maternal disorders (eg, CHTN, diabetes, infections) may lower risk of stillbirth in a current pregnancy.

Prior preterm delivery

Preterm delivery is delivery before 37 wk (see Abnormalities and Complications of Labor and Delivery: Preterm Labor). Previous preterm delivery due to preterm labor increases risk of future preterm deliveries; if the previous preterm neonate weighed < 1.5 kg, risk of preterm delivery in the next pregnancy is 50%. Women with prior preterm delivery due to preterm labor should be closely monitored at 2-wk intervals after 20 wk. Monitoring includes

• Ultrasound evaluation, including measurement of cervical length and shape, at 16 to 18 wk
• Uterine contraction monitoring
• Testing for bacterial vaginosis
• Measurement of fetal fibronectin

Women with prior preterm birth due to preterm labor or with shortening (< 25 mm) or funneling of the cervix should be given 17 α-OH-progesterone 250 mg IM once/wk.

Prior neonate with a genetic or congenital disorder

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—see Prenatal Genetic Counseling and Evaluation: Risk factors). Recurrence risk for most genetic disorders is unknown. Most congenital malformations are multifactorial; risk of having a subsequent fetus with malformations is ≤ 1%. If couples have had a neonate with a genetic or chromosomal disorder, genetic 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.

Polyhydramnios (hydramnios) and oligohydramnios

Polyhydramnios (excess amniotic fluid) can lead to severe maternal shortness of breath and preterm labor. Risk factors include uncontrolled maternal diabetes, multifetal pregnancy, isoimmunization, and fetal malformations (eg, esophageal atresia, anencephaly, spina bifida).

Oligohydramnios (deficient amniotic fluid) often accompanies congenital malformations of the fetal urinary tract and severe fetal growth restriction (< 3rd percentile). Also, Potter's syndrome with pulmonary hypoplasia or fetal surface compression abnormalities may result, usually in the 2nd trimester, and cause fetal death.

Polyhydramnios and oligohydramnios are suspected if uterine size does not correspond to gestational date or may be discovered incidentally via ultrasonography, which is diagnostic.

Multifetal (multiple) pregnancy

Multifetal pregnancy increases risk of fetal growth restriction, preterm labor, abruptio placentae, congenital malformations, perinatal morbidity and mortality, and, after delivery, uterine atony and hemorrhage (see Abnormalities and Complications of Labor and Delivery: Postpartum Hemorrhage). Multifetal pregnancy is detected during routine ultrasonography at 18 to 20 wk.

Prior birth injury

Most cerebral palsy and developmental delay is 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 (eg, causing shoulder dystocia). 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.

Last full review/revision January 2009 by Christian M. Briery, MD; John Morrison, MD