Medical care and pregnancy - Relevance to antepartum care

Normal changes in glucose metabolism in pregnancy Glucose, amino acids, and ketones pass through the placenta to the fetus. Maternal free insulin and glucagon do not traverse the placenta; fetal insulin secretion and glucagon secretion respond to levels of substrate presented to the fetus. Ketones may be associated with adverse effects upon neurophysiological development of the fetus. The “starvation” state is accelerated with pregnancy, and fasting hypoglycemia occurs after 12 hours in the fasting state, with fasting ketosis occurring as well. The “fed” state in pregnancy is characterized by hyperinsulinemia, hyperglycemia, and diminished sensitivity to insulin by multiple tissues (insulin resistance). Insulin resistance is greatest in the third trimester. Multiple hormones in pregnancy, human placental lactogen, prolactin, and progesterone, all contribute to alterations in glucose metabolism and insulin resistance. Risk of diabetes should be assessed in all pregnant women, with women at high risk, receiving glucose challenge testing (50 g of glucola with one hour blood glucose level) as soon as possible in early pregnancy to screen for undiagnosed type II diabetes. Patients who have a prior history of gestational diabetes but are documented with normal glucose testing in early pregnancy may benefit from a prudent diet during pregnancy to avoid excessive weight gain and concentrated fats or simple sugars. These patients should be screened again at 28 weeks as in routine prenatal care. Women with positive screening tests are confirmed or ruled out for the presence of diabetes during pregnancy using a 100 g glucose load and a three-glucose tolerance test.

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Medical care and pregnancy - Diabetes Preconception

Patients with preexisting diabetes should be euglycemic during the critical period of organogenesis. Congenital abnormalities are increased if first trimester control is poor. Preconception and early pregnancy control of diabetes reduces the incidence of congenital abnormalities to the same rate seen in the general population.39 Patient education includes discussion of contraception, general issues of care during pregnancy, and the need for ongoing follow-up. Therapeutic alliances with diabetic women of childbearing age must start before conception. Preconception care of type I diabetic women results in earlier prenatal care, lower glycosylated hemoglobin levels, fewer antepartum hospitalizations and fewer hospital days, and decreased intensity and length of stay for newborns. A multicenter prospective study of women who received preconception care versus women who received only antepartum care showed cost savings of more than $(US)30,000 per patient.40 A study in the UK found that women attending a preconception clinic were more likely to be in a stable relationship and to be non-smokers. Preconception care improved outcomes and a 50% decrease in neonatal intensive care unit admission rate.41 For adolescent diabetics, developmental changes and parental control issues may clash; unprepared pregnancy is an increased risk for these young women. Physicians must educate both parents and patients about the risks of pregnancy. In this situation, one therapeutic goal may be the establishment of a negotiated agreement between adolescent and parents where graduated autonomy and responsibility for self-care are emphasized. Type II diabetic patients may not be identified in the medical care system before or during early pregnancy. Patients with gestational diabetes should demonstrate normalized glucose status at the six-week postpartum check-up. The identification of unrecognized type II diabetes is enhanced by careful followup of all women with a history of gestational diabetes. Screening for diabetes should be considered prior to conception in women with increased risk factors of obesity, unexplained fetal death, strong family history, and a history of macrosomic babies, especially in ethnic groups with a high prevalence of diabetes. This identification allows improved preconception and antepartum management critical to avoid increases in perinatal morality (4.1–6.6%) and congenital malformations (3.4–6.7%) over the general population.

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Medical care and pregnancy - Medical care of chronic illness in pregnancy General approach

Preconception care of women with chronic illness falls into two categories: the assessment by physician and patient of special risk and the tailoring of care to enhance the safety and optimal outcome of pregnancy. Women should be given the opportunity to understand the extent of risk they may encounter, both to themselves and their babies, during pregnancies complicated by certain chronic conditions, especially chronic cardiovascular, renal, autoimmune, and hemoglobin disorders. See Table 9.2 for a list of disorders with a high risk of maternal complications. Most women will benefit from an understanding that their medical condition should not significantly lessen the chance of successful pregnancy outcome. A number of conditions, including rheumatoid arthritis and multiple sclerosis, demonstrate a tendency to improve during pregnancy. Other conditions, such as inflammatory bowel disease, migraine headaches, and asthma are variable in their clinical course during pregnancy. Women with severe preexisting lifethreatening disorders may be managed with good success during pregnancy, including women who have been treated for malignancy and renal transplantation. Perinatal consultation may be helpful as a preconception event in a number of high risk medical conditions and in women with an unexplained history of poor reproductive outcomes. A growing list of metabolic problems and hematological disorders are associated with preeclampsia, growth retardation, abruption, and other complications in late pregnancy. These include hyperhomocysteinemia, Factor V Leiden deficiency, Protein C and Protein S deficiency, and the antiphospholipid antibody syndrome. This includes patients with and without preexisting diagnoses of systemic lupus with anticardiolipin antibody or lupus anticoagulant. Treatment of several common disorders should be modified before conception. Asthma generally does not require preconception attention, but patients will frequently have questions about their medications. Heart disease in women of childbearing age encompasses a wide range of conditions, congenital and acquired, with variable risks and prognoses in pregnancy. Women with other neurological disorders, such as paraplegia and mysathenia gravis, may require changes in management, for the most part, during the intrapartum period. Specific preconception issues regarding common chronic disorders are addressed along with antepartum medical care in the latter part of this chapter. Common conditions that benefit from preconception evaluation and manipulation of treatment include hypertension, seizure disorders, and diabetes.

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Medical care and pregnancy - Medical care of common acute conditions

Self-limited acute illnesses can often be treated with non-pharmacological measures and/or common symptomatic medications. Table 9.6 lists some symptoms and medications that may be used for a variety of common problems. Systemic corticosteroids should be used, as indicated, for treatment of severe asthma attacks and when indicated in autoimmune disorders. Many antiarrhythmic and cardiac medications have been used in pregnancy with good outcome. Vaginitis Pregnant women commonly present with vaginal infection. Although a number of medications may be designated as category C, topical use of these medications has not been associated with significant absorption, and the risk of use seems minimal. Examples include antifungal preparations for candida vulvovaginitis. Diflucan has been associated with fetal defects in high doses (continuous administration at 400 mg/day) but is probably safe used in brief courses at standard doses.26 Treatment of symptomatic vaginal trichomoniasis with metronidazole continues to be a concern to some clinicians because of theoretical concerns of teratogenicity, despite meta-analysis and large population-based studies demonstrating no increased risk of defects,27,28 and long-term population-based studies showing no increase in childhood cancers.29 Viral infections Acute viral infections are often viewed as benign, selflimited conditions outside of pregnancy. During pregnancy, viral illness (such as rubella) may represent a threat to the fetus or a potentially serious threat to the mother’s health. Influenza The 1918 Spanish influenza pandemic and other severe influenza epidemics during the twentieth century manifested disproportionate mortality in pregnant women.30 In the USA, influenza vaccination has been recommended during pregnancy by the Center for Disease Control for more than a decade. Despite the agreement that vaccination should be given during pregnancy by more than 90% of obstetricians, vaccination rates remain low in this population, ranging from 1.5–40%.31,32 One population-based study determined the number needed to treat to prevent one influenza-like illness was between 20 and 43 pregnant women.33 Limited outcome data are available, with one study finding no difference in hospitalizations for women or their infants with viral respiratory illnesses during the flu season based on vaccination status.34 Herpes Genital herpes is a common recurrent problem in young women. It is associated with potential neonatal morbidity and mortality, and an increased rate of cesarean delivery. Two adequately powered randomized controlled trials now demonstrate a decrease in positive herpes cultures and cesarean deliveries with no increase in newborn infection when women with genital herpes simplex infection are treated with 500 mg of valcyclovir given twice daily starting at 36 weeks gestation.35,36 A cost-effectiveness study found acyclovir prophylaxis to be cost-effective and costsaving using a wide range of assumptions.37 Strength of recommendation A. Hepatitis Hepatitis A infection does not pose a threat to the newborn via perinatal transmission. Hepatitis B infection may be transmitted perinatally, as well as hepatitis C, D, and E. Immunization against hepatitis B and administration of hepatitis B immunoglobulin immediately at birth is protective against perinatal transmission of hepatitis B and D.38 The risks of neonatal transmission are increased with HBeAg-positive status and up to 90% if acute infection takes place during the third trimester.38 Chronic infection occurs in more than 90% of infected infants. Hepatitis C infection is rarely transmitted perinatally. Transmission usually occurs in mothers with concomitant HIV infection or with very high levels of hepatitis C virus RNA. Routine screening is not recommended, since no treatment is available to prevent infection, but women at high risk may warrant evaluation, and pediatric follow-up is warranted if hepatitis C is detected because of the risk of chronic liver disease in the infant. Common acute bacterial infections are usually treated as they would be in non-pregnant women. There are several antibiotics that should not be used in pregnancy unless an effective alternative is not available (e.g. quinolones, tetracycline). However, any therapeutic decision must weigh the risks to the pregnancy of possible medication ill effects versus the potential risk to the mother and the fetus of failure to adequately treat significant infections. Table 9.7 contains commonly used medications for infection.

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Medical care and pregnancy - Diagnostic testing

Diagnostic measures that would normally be employed
to evaluate the acute complaint can almost
always be used in pregnancy. Ultrasound modalities
(abdominal, renal, breast, and vascular) are considered
safe, although there may be some decrease in
accuracy of venous studies caused by the enlarged
uterus and inferior vena cava compression. If a renal
ultrasound is insufficient for evaluation of suspected
nephrolithiasis, a stone-protocol CT or single-shot
intravenous pyelogram may be utilized to assist in
management.
Diagnostic peritoneal lavage and/or computed
tomography (CT) scan of the abdomen may be indicated
in the evaluation of trauma; this modality
should not be neglected if clinically indicated, since
the single greatest cause of mortality for pregnant
women is motor vehicle accidents.
Physicians should not hesitate to utilize chest
X-rays when evaluating patients with symptoms suggestive
of serious acute illness, such as pneumonia.24
Flexible sigmoidscopy has been studied in all trimesters,
with efficacious diagnosis of gastrointestinal
bleeding and without negative outcomes.25
Nuclear medicine studies should be avoided. Multiple surgical series at this time support the
safety and utility of laparoscopic surgery during pregnancy.
Although timing of surgical procedures in
pregnancy is best during the second trimester to
decrease the risk of abortion and premature labor,
surgical treatment of trauma, appendicitis, and biliary
tract disease may not be able to be delayed.
The best time to perform surgical procedures in pregnancy
is during the second trimester to decrease the
risk of abortion and premature labor.

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Medical care and pregnancy - Physiological changes

Physiological changes of pregnancy are listed in
Table 9.5, along with possible implications for medical
care in pregnancy. Most changes are somewhat
dependent on gestational age. While the most sensitive
period with respect to congenital malformations
occurs during the first trimester in organogenesis, the
increase in plasma volume, cardiac output, and glomerular
filtration does not begin to manifest significantly
until the second trimester, with peak effect
noted by 30 weeks gestation. In general, the fetus poorly tolerates maternal
hypotension, hypoxemia, hypovolemia, and acidosis.
Thus, while a non-pregnant patient may tolerate
greater physiological stress, for example mild hypoxemia
during an acute asthmatic attack, the pregnant
woman should be treated vigorously for the acute
attack with medication and more liberal use of supplemental
oxygen. More importantly, preventive
measures should be undertaken, whenever possible,
to avoid acute exacerbations of chronic disease, such
as diabetes and asthma.

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Common medical issues in the antepartum period Medication use in pregnancy

Throughout the world, medical practitioners became alerted to the potential dangers of medication use in pregnancy with the occurrence of congenital limb defects associated with thalidomide use. Following these events, physicians became much more cautious in using any medication in pregnancy. Several largescale studies were conducted in the USA by the Collaborative Perinatal Project and the CDC that collected information on drug exposures and outcomes for a large number of medications in many thousands of women. More recently, a number of drug registries have been established to study anti-epileptic drugs (AEDs), asthma medications, and antidepressants in pregnancy. Ongoing medication surveillance and information services provide both public educational service and data collection, such as the Motherisk program in Toronto. Studies of medication use during pregnancy demonstrate that between 20 and 50% of women receive medication other than vitamins and minerals in pregnancy. 20 The most frequently used medications include antibiotics and anti-nausea medications. The appropriate use of medication in pregnancy hinges on several important clinical principles.
Firstly, practitioners must determine that treatment of an illness or symptoms of an illness is beneficial to the mother and beneficial to the fetus, or that the risk to the fetus is justified by the potential benefits of treating the mother.
Secondly, accurate information must be available to assess the risk of congenital malformation or other negative impact upon the fetus or pregnancy. Experts vary in recommendations about medication. Some conservative viewpoints express concern, not only about teratogenesis, but also about the risk of long-term subtle effects on neurodevelopment.21 Caution must be balanced, however, with the risk of untreated disease or the intolerability of untreated symptoms. Some medications do not appear to cause malformations, but may be associated with other poor outcome, such as restricted fetal growth, presumably caused by their effects on the uteroplacental circulation. Some medications are risky only at certain periods of time within the pregnancy, such as the effect of non-steroidal anti-inflammatory medications on fetal renal function or the risk of kernicterus caused by bilirubin displacement from albumin-binding sites by sulfonamides. Specific knowledge of the mechanism and timing of risk may enhance the clinician’s effective utilization of medications in pregnancy. Two systems of classification currently exist for medication use during pregnancy.
Table 9.3 depicts the Food and Drug Administration’s (FDA) classification system. This system has been criticized for providing insufficient information about the risks of medications in pregnancy. The requirements to achieve a category A rating are stringent, difficult to achieve, and extremely costly to pharmaceutical industries;22 many medications undergoing FDA approval are not submitted for consideration of category A status because of financial issues. A number of medications that are currently classified as “B” are poorly studied in human pregnancy (e.g. leukotriene receptor antagonists) and should be used only if treatment benefits are clear. Other medications currently classified as category C are frequently used in pregnancy and have good safety records.
The Swedish catalogue of registered pharmaceutical specialties (FASS) uses a different system to categorize medication, included in Table 9.4.
The TERIS protocol for cataloguing teratological information utilizes all available sources of information and assigns ratings of teratogenic risk of “none,” “minimal,” “small,” “moderate,” “high,” and “undetermined.” A 1990 overview of this resource demonstrated that approximately half of the commonly prescribed medications had insufficient information to assess teratogenic risk. Of the drugs that could be rated, over 90% were rated as minimal risk or less.23
Important initiatives underway include drug registries regarding medication for common chronic illness, such as epilepsy and asthma. It is to be hoped that these projects will provide better information for clinicians about the treatment of medical illness in pregnancy. Between 20 and 50% of women receive medication other than vitamins and minerals during pregnancy.

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Medical care and pregnancy - Assessment of poor pregnancy outcome

Consultation with a maternal-fetal specialist should be
considered in women with a history of recurrent spontaneous
abortion and mid-trimester abortion/delivery.Recurrent abortion and very preterm birth may be
related to uterine structural defects such as Müllerian
tube defects (uterine septum and variants), uterine
leiomyomata, or cervical incompetence. A specific history
of preterm premature rupture of membranes may
be caused by infection, a modifiable factor, whereas a
history of premature labor may be attributable to a
number of factors.
Patients with recurrent first trimester loss should
be offered genetic evaluation. Genetic consultation is
applicable for a growing list of preconception concerns,
including couples with a previous child with a
congenital defect, families with inherited metabolic
defects, and couples wherein one partner manifests a
genetically transmitted illness.

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Medical care and pregnancy: common preconception and antepartum issues

Introduction A general approach to women of reproductive age should include consideration of the possibility of pregnancy. The preconception approach to medical care includes optimization of chronic health problems and risks that may impact negatively on pregnancy. Medical care of women in pregnancy requires understanding of changes in maternal physiology and special risks to the fetus or mother. The preconception approach to medical care Preconception counseling Most women do not need special diagnostic testing or therapeutic interventions before the initiation of pregnancy. In general, women without chronic illness may undertake pregnancy with general preventive counseling for a healthy diet, avoidance of substance abuse, regular exercise, and common occupational precautions. This should be a part of preventive care in all young women. Most women without chronic disease should be able to undertake pregnancy healthily with advice about a healthy diet, avoiding abuse of substances, taking regular exercise, and common occupational precautions. Dietary precautions Low levels of serum and red blood cell folic acid have been demonstrated to increase the risk of neural tube defects. In randomized clinical trials, 0.8 mg of folic acid per day decreased the occurrence of neural tube defects and 4 mg of folic acid per day decreased the recurrence of neural tube defects.1 Lower effective doses were found in non-randomized trials; current recommendations from the Institute of Medicine and the US Public Health Service recommend 0.4 mg/day in women of childbearing potential.2 A populationbased study of birth registries in Europe, NorthAmerica, and Australia demonstrated significant reduction of neural tube defects occurring with fortification of food products but not with recommendation of supplementation alone.3 Fortification of flour is mandatory in Canada, the USA, and Chile, but not in most European countries. A study of low-income women found that significant numbers of women still had diets deficient in folic acid, and most had no knowledge of the foods that they should be eating to achieve a healthy level in their diet.4 At the same time, women with higher educational levels may be taking supplementation that is not recommended or needed, such as vitamin A, but still have diets deficient in folic acid.5 Thus supplementation with a multivitamin or folic acid seems warranted at this time in all women of childbearing potential, and higher levels of supplementation (4 mg/day) in high risk women.6 These include women with a history of a previous delivery of a child with a neural tube defect, women with a strong family history of neural tube defects, and women on antiepileptic drugs (AEDs). Fortification of grain products is ideal to achieve the greatest certainty of attaining optimal serum folate levels and prevention of neural tube defects. In countries that do not use fortification, all women of childbearing potential should be supplemented with folic acid 0.4 mg daily and 4–5 mg/day in high risk women. Strength of recommendation A. Occupational concerns Women with occupational exposures often seek specific information regarding the safety of pregnancy. This complex issue may be viewed from a number of perspectives, including the very personal concerns of the patient for her baby’s well-being and her family’s economic viability. Although much attention has been focused on maternal occupational exposures, a number of substances appear to cause subfecundity (reduced fertility) or other adverse pregnancy outcomes as a result of paternal exposures. Policies in US industries that exclude women from certain types of job may, therefore, be viewed as discriminatory. From a more general perspective, these exclusionary practices may be shortsighted if they preclude a goal of occupational safety for all workers. Legislative issues have been approached differently in a number of European countries compared with the USA, with special maternity leave status granted to 1% and 0.1% of women in Denmark and Finland respectively, whose occupation is judged to be sufficiently hazardous to exclude participation during pregnancy.7 Table 9.1 provides a brief overview of occupational exposures that are known to be associated with adverse pregnancy outcome. A number of possible exposures have been studied in pregnancy in an effort to decrease associated risk by protective practices. In health care positions, measurements of radiation with exposure to nuclear medicine patients receiving technetium-99m or iodine-131 have led to recommendations on limits for technologists and nursing staff.8 Changes in the practice of an occupation may affect risk. A study of hairdressers examined the high rate of adverse pregnancy outcomes in two time periods, 1986–88 and 1991–93 in hairdressers as compared to sales clerks. However, this study also demonstrated a decline in the higher incidence of spontaneous abortions and low birth weight infants in hairdressers between the two periods.9 This may be the result of changes in products used by the hairdressers. Exposure to anesthetic gases appears to have diminished among operating room personnel, but exposures may still remain at an unacceptable level for recovery room and surgical intensive care unit personnel caring for recovering post-anesthetic patients unless scavenging devices are in operation in these work zones.10 Radiation
The issue of occupational exposure to radiation includes workers from several industries.
Lower limits of exposure apply to pregnant women working in fluoroscopy suites than to non-pregnant individuals.
In the USA, these limits apply with voluntary declaration of pregnancy. Appropriate use of protective clothing can limit radiation exposure to recommended levels.11
The theoretical risk of cosmic radiation at high altitudes has been included in considering risks encountered by pregnant flight attendants and frequent business travelers. However, actual measurements of airline crews have failed to demonstrate doses of radiation exceeding the recommended limits to exposure.12 Adverse pregnancy outcomes and childhood malignancy have been studied in workers at nuclear plants with adverse pregnancy outcomes (stillbirth) noted in paternal exposures to external ionizing radiation,13 and possible increase in childhood cancers seen in children whose mothers experienced radiation work exposures.14 Stress
Occupational stress, especially physical stress, has been widely suspected by physicians and patients of causing adverse pregnancy outcomes, but most women are able to work safely throughout their pregnancies without difficulties. Physical stresses that have been associated with increased rates of prematurity and low birth weight include prolonged standing, long hours, protracted ambulation, and heavy lifting.15
Studies that examine these issues vary considerably in design and may include confounding factors, thus creating methodological concerns.
One study found greater risk of preterm birth, low birth weight, and small-for-gestational age birth in textile workers, food service workers, electrical equipment operators, and janitors when compared with women employed as clerks, teachers, and librarians.16 Another study found higher rates of preterm deliveries and low birth weight in nurses than in bank workers.17,18 A self-report survey of female physicians found higher rates of stillbirth and premature delivery than in the general population.18 However, a large cohort study of more than 7000 women found only a modest increase in risk of preterm delivery (OR ¼ 1.31) for women whose occupation entailed more than eight hours standing per day. In addition, this study found no increase in low birth weight or preterm delivery with heavy work or exercise after controlling for confounding variables, suggesting that other socioeconomic factors might account for differences in pregnancy outcome.19

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