Preconception care (Table 4-1) should include a thorough assessment of an individual’s medical problems. This is becoming increasingly important as the incidence of obesity-related comorbidities, such as diabetes mellitus and hypertension, increases. These conditions should be as well-controlled as possible prior to conception because they can have significant adverse effects on the developing fetus and adverse effects in the mother. For example, the risk of birth defects increases with hemoglobin A1C level in diabetic patients, with an A1C greater than 10.6% conferring eight times the risk of having a birth defect compared to women with an A1C of less than 8%.
With maternal medical issues, it is important to discuss the impact on the fetus and the potential for the pregnancy to exacerbate the underlying medical condition.
With any complex medical condition, expertise from a maternal-fetal medicine specialist is advised and ongoing collaboration with other specialists may be indicated.
The gynecologic and obstetric history may reveal potential factors contributing to infertility or complications in a future pregnancy.
Discussion of menstrual and contraceptive history provides an educational opportunity for conception counseling and to discuss optimal timing of a pregnancy in a medically complex patient.
Past history of sexually transmitted infections is important to note because these women may be at increased risk of these infections in a future pregnancy. These infections include Neisseria gonorrhea, Chlamydia trachomatis, Treponema pallidum, genital herpes simplex virus (HSV), and HIV.
TABLE 4-1 Preconception Risk Assessment: Laboratory Testing
Recommended for All Women
Recommended for Some Women
Hemoglobin level or hematocrit
Rh factor
Urine dipstick testing (protein and sugar)
Pap smear test (for cervical cancer)
Gonococcal/chlamydial screen
Syphilis test
Hepatitis B surface antigen
Rubella IgG
HIV screen
Illicit drug screen (offer)
Tuberculosis screen
Hepatitis C
Lead level
Varicella IgG screen
Toxoplasmosis IgG screen
CMV IgG screen
Parvovirus B19 IgG screen
Genetic carrier screening for hemoglobinopathies, Tay-Sachs disease, Canavan disease, cystic fibrosis, or other genetic diseases
Screening for parental karyotype for habitual spontaneous abortion
IgG, immunoglobulin G; CMV, cytomegalovirus. Adapted from U.S. Department of Health and Human Services. Caring for our Future: The Content of Prenatal Care. A Report of the PHS Export Panel. Washington, DC: U.S. Department of Health and Human Services, 1989, with permission.
With prior poor pregnancy outcomes, the recurrence risk of an adverse outcome should be discussed. In some cases, there are interventions to reduce these risks in a future pregnancy.
Known congenital uterine malformations are important to identify because these conditions can be associated with recurrent pregnancy loss, malpresentation, or preterm birth.
Advanced maternal age (older than 35 years at time of delivery) is associated with increased risks that include infertility, fetal aneuploidy, gestational diabetes, preeclampsia, and stillbirth.
Prior to pregnancy, it is important to educate women about these risks and discuss aneuploidy screening and diagnostic tests that are available, as well as management options, if available.
A patient’s family history can identify genetic risks to a future pregnancy.
A preconception history includes evaluation for family history of congenital anomalies; chromosomal abnormalities (e.g., Down syndrome); mental retardation/developmental delay; inherited diseases such as hemoglobinopathies, cystic fibrosis, and hemophilia; recurrent pregnancy loss/stillbirth/early infant death in the family; ethnicity; and consanguinity.
Carrier screening for hereditary disease is traditionally based on ethnic background of the couple and allows counseling before the first potentially affected pregnancy. Early recognition of carrier status informs patients of their risks outside of the emotional context of pregnancy and facilitates educated decisions about reproductive goals and testing during or after pregnancy. Expanded carrier screening is an option for patients, in which over 100 diseases are screened in a single test. Family history can identify those at increased risks for specific diseases, such as muscular dystrophy, fragile X syndrome, or Down syndrome, for which genetic counseling should be offered. Information about diagnostic tests, such as chorionic villus sampling (CVS) or amniocentesis, can be explained. In some instances, genetic counseling may result in a decision to forgo pregnancy or to use assisted reproductive technologies that can decrease this risk.
Isotretinoin (Accutane): An oral treatment for severe cystic acne, it is highly teratogenic, causing craniofacial defects (microtia, anotia). It should be discontinued prior to pregnancy.
Warfarin (Coumadin) and vitamin K antagonists: Such anticoagulants have been associated with warfarin embryopathy. Because heparins (both unfractionated and low-molecular-weight) do not cross the placenta, women requiring anticoagulation should be encouraged to switch to heparin therapy prior to conception, except in rare cases.
Antiepileptic drugs (AED): Children born to mothers treated with certain AEDs are at increased risk for congenital malformations, particularly when these drugs are used in the first trimester. Valproic acid is associated with neural tube defects (NTDs); adverse neurocognitive effects; and craniofacial, limb, and cardiac abnormalities. Carbamazepine exposure has been associated with facial dysmorphism and fingernail hypoplasia. Data on newer AEDs are still limited. For women with seizure disorders, it is important to have them on AED regimens with less teratogenicity. Notably, a patient with an unintended pregnancy using an AED should not abruptly discontinue her medication but rather be switched to another medication where possible, due to risk of seizure recurrence. A detailed fetal anatomy sonogram, maternal serum alpha-fetoprotein (MSAFP), and fetal echocardiogram may provide useful information for these patients.
Lithium has been associated with increased incidence of heart defects and should only be continued based on the severity and frequency of illness. Fetal echocardiogram is recommended for women taking lithium in the first trimester. Lamotrigine is a mood stabilizer with a significantly better reproductive safety profile than lithium. It should be considered as an alternative in women with bipolar disorder.
Selective serotonin reuptake inhibitors (SSRIs) are considered safe; however, paroxetine early in pregnancy has been associated with increased risk of heart defects, and an FDA advisory notes an association between late-term SSRI use and persistent pulmonary hypertension in the newborn. SSRI use in pregnancy should be individualized, balancing the risks of maternal depression and potential fetal effects.
Folic acid supplementation reduces the risk of NTDs. The U.S. Public Health Service recommends daily supplementation with 0.4 mg of folic acid for all women capable of becoming pregnant. Unless contraindicated by the presence of pernicious anemia, women who have previously had a fetus with an NTD should take 4.0 mg of folic acid daily.
The body mass index (BMI), defined as (weight in kilograms/[height in meters]2), is the preferred indicator of nutritional status. Very overweight (BMI above 30) and very underweight women (BMI <20) are at risk for poor pregnancy outcomes.
Eating habits (fasting, pica, eating disorders, and the use of megavitamin supplementation) should be discussed.
Excess use of multivitamin supplements containing vitamin A should be avoided because the estimated dietary intake of vitamin A for most women in the United States is sufficient. Vitamin A is teratogenic in humans at dosages of more than 20,000 to 50,000 IU daily, producing fetal malformations like those seen with isotretinoin.
Women with a history of anorexia or bulimia may benefit from both nutritional and psychological counseling before conception.
Women with history of gastric bypass must see a nutritional specialist in addition to their obstetrician to ensure they are getting adequate caloric and nutritional needs in a pregnancy.
Smoking: Approximately 11% of pregnant women in the United States smoke. Carbon monoxide and nicotine are believed to be the main ingredients in cigarette smoke that are responsible for adverse fetal effects. Smoking is associated with increases in the following:
Spontaneous abortion (1.2 to 1.8 times greater in smokers than in nonsmokers)
Abortion of a chromosomally normal fetus (39% more likely in smokers than in nonsmokers)
Abruptio placentae, placenta previa, and premature rupture of membranes
Preterm birth (1.2 to 1.5 times greater in smokers than in nonsmokers)
Low infant birth weight
Sudden infant death syndrome
Smoking cessation should be encouraged prior to conception. However, cessation during pregnancy still improves the birth weight of the infant, especially if use stops before 16 weeks’ gestation. Prospective randomized controlled clinical trials have shown that intensive smoking reduction programs, with frequent patient contact and close supervision, aid in smoking cessation and result in increased infant birth weights.
Successful interventions emphasize ways to stop smoking rather than merely providing mandates to stop smoking.
Nicotine replacement therapy (chewing gum or transdermal patch) carry warnings about the adverse effects of nicotine on mother and fetus. However, nicotine is only one of the toxins in tobacco smoke. Smoking cessation with nicotine replacement reduces fetal exposure to carbon monoxide and other toxins and may improve outcomes. For women who are otherwise unable to reduce their smoking, it may be reasonable to advise nicotine replacement as an adjunct to counseling even during pregnancy. Use of nicotine replacement in a patient who is unable to reduce her smoking may impose greater fetal risk.
Alcohol: Ethanol freely crosses the placenta and the fetal blood-brain barrier and is a known teratogen. Fetal ethanol toxicity is dose-related but without a defined lower threshold of exposure.
The exposure time of greatest risk is the first trimester. Nevertheless, fetal brain development may be affected throughout gestation.
Although an occasional drink during pregnancy has not been shown to be harmful, patients should be counseled that the threshold for adverse effects is unknown.
Fetal alcohol syndrome is characterized by growth retardation, facial abnormalities, and central nervous system (CNS) dysfunction. Facial abnormalities include shortened palpebral fissures, low-set ears, midfacial hypoplasia, a smooth philtrum, and a thin upper lip. CNS abnormalities of fetal alcohol syndrome include microcephaly, mental retardation, and behavioral disorders, such as attention
deficit disorder. Skeletal abnormalities and structural cardiac defects are also seen with greater frequency in the children of women who abuse alcohol during pregnancy than in those who do not. The most common cardiac structural anomaly is ventricular septal defect, but several others occur.
Illicit drug use: Recent data show approximately 4% of pregnant women use some illicit substance in pregnancy.
Marijuana: Marijuana has been shown to alter brain neurotransmitters as well as brain chemistry. Marijuana can remain in the body for up to 30 days, thus prolonging fetal exposure. Smoking marijuana produces as much as five times the amount of carbon monoxide as does cigarette smoking, perhaps altering fetal oxygenation. Marijuana has been associated with deficits in problem-solving skills that require sustained attention and visual memory, analysis, and integration and with subtle deficits in learning and memory.
Cocaine: Adverse maternal effects include profound vasoconstriction, leading to malignant hypertension, cardiac ischemia, and cerebral infarction. Cocaine may have a direct cardiotoxic effect, leading to sudden death. Complications of cocaine use in pregnancy include spontaneous abortion, fetal death in utero, premature rupture of membranes, preterm labor and delivery, IUGR, meconium staining of amniotic fluid, and abruptio placentae. Cocaine is teratogenic, and its use has been associated with cases of in utero fetal cerebral infarction, microcephaly, and limb reduction defects. Genitourinary malformations have been reported with first-trimester cocaine use. Infants born to women who use cocaine are at risk for neurobehavioral abnormalities and impairment in orientation and motor function.
Opiates: Opiate use is associated with increased rates of stillbirth, fetal growth restriction, prematurity, and neonatal mortality, perhaps due to risky behaviors in opiate substance abusers. Methadone treatment is associated with improved pregnancy outcomes. Neonates born to narcotic addicts are at risk for a severe, potentially fatal, narcotic withdrawal syndrome. Although the incidence of clinically significant withdrawal is slightly lower among methadone-treated addicts, its course can be just as severe. Neonatal withdrawal is characterized by a high-pitched cry, poor feeding, hypertonicity, tremors, irritability, sneezing, sweating, vomiting, diarrhea, and, occasionally, seizures. Frequent sharing of needles has resulted in high rates of HIV infection (>50%) and hepatitis among intravenous narcotic addicts.
Amphetamines: Crystal methamphetamine, a potent stimulant that is inhaled, injected, or snorted, has been associated with decreased fetal head circumference and increased risk of abruptio placentae, IUGR, and fetal death in utero. However, no proven teratogenicity exists.
Hallucinogens: No evidence proves that lysergic acid diethylamide (LSD) or other hallucinogens cause chromosomal damage, as was once reported. Few studies exist on the possible deleterious effects of maternal hallucinogen use during pregnancy. No proven teratogenicity to LSD exists.
Domestic violence: Women are more likely to be abused during pregnancy than at other times. Approximately 37% of abused women are assaulted during their pregnancy, resulting in possible abruptio placentae, antepartum hemorrhage, fetal
fractures, rupture of the internal organs, and preterm labor. Information about community, social, and legal resources should be made available to women who are abused and a plan devised for dealing with the abusive partner. See Chapter 33.
Insurance coverage and financial difficulties: Many women and couples do not know the eligibility requirements or amount of maternity coverage provided by their insurance carriers or may lack medical insurance coverage altogether. Referral for medical assistance programs should be part of preconception planning as needed.
Assisted reproductive technologies, such as donor egg and sperm, sperm sorting, and preimplantation genetic diagnosis (PGD), may obviate the risk in specific cases. Adoption and avoidance of pregnancy represent other choices. CVS and amniocentesis permit early diagnosis, facilitate preparation for the care of an affected child, and give the option for pregnancy termination.
TABLE 4-2 Recommendations for Ethnicity-Based Carrier Screening
Disease
Carrier Frequency
Ashkenazi Jewish
Tay-Sachs
1/30
Canavan
1/40
Cystic fibrosis
1/29
Familial dysautonomia
1/30
Mediterranean
Thalassemia
1/20-1/50
Sickle cell anemia
1/30-1/50
European Caucasian
Cystic fibrosis
1/25-1/29
African American
Sickle cell anemia
1/10
Thalassemia
1/30-1/75
Cystic fibrosis
1/65
Asian
Thalassemia
1/20-1/50
Cystic fibrosis
1/90
Hispanic
Cystic fibrosis
1/46
Sickle cell anemia
1/30-1/200
Thalassemia
1/30-1/75
French Canadian
Tay-Sachs
1/15
Cystic fibrosis
1/29
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