Diseases, Disorders information

Alcohol
Maternal alcohol ingestion during pregnancy may result in a recognizable pattern of congenital anomalies known as fetal alcohol syndrome. Fetal alcohol syndrome features include prenatal and postnatal growth restriction, characteristic facial anomalies (ie, short palpebral fissures, microphthalmia, indistinct or absent philtrum, thin upper lip, midfacial hypoplasia), microcephaly, joint contractures, and cardiac defects. Fetal alcohol syndrome is associated postnatally with mental retardation, hyperactivity, and developmental delays. Alcohol abuse during pregnancy is a leading cause of mental retardation. Maternal alcohol abuse is also associated with an increased risk of spontaneous abortion.

It is difficult to correlate the amount of alcohol consumed to the risk of fetal alcohol syndrome. Among pregnant women who consume four or more drinks per day during pregnancy, the risk for fetal alcohol syndrome may be as high as 20%, with risks increasing to perhaps 40% with six drinks per day. Women who have eight or more drinks per day are at significant risk (perhaps 60% or higher) for giving birth to an infant with fetal alcohol syndrome. The American Medical Association has stated that any woman who consumes four or more alcoholic drinks per day during pregnancy is significantly endangering the health of her unborn child. One beer, one shot of liquor, one mixed drink, and one glass of wine all contain the same amount of alcohol, approximately 0.5 oz of absolute alcohol. Thus, all forms of alcohol are equally hazardous. Risks associated with binge drinking are unknown but are likely to be substantial. No quantifiable risk has been associated with an occasional alcoholic beverage during pregnancy, but prudent medical advice is for pregnant women to avoid alcohol consumption completely.
Drugs and Chemicals Associated with Birth Defects
Tobacco

Smoking tobacco poses a threat to reproductive function and pregnancy outcome in women. The prevalence of smoking among adults has decreased from approximately 40% in 1965 to approximately 25% in the 1990s, with a similar decrease among women of reproductive age.
Stop smoking
The pregnant smoker may be at increased risk for the spontaneous abortion of an otherwise normal fetus, fetal death associated with placental abruption or placenta previa, preterm delivery, and PROM. A dose-response relationship has been shown between the amount of maternal smoking and reduced birth weight. The offspring of women who smoke approximately 20 cigarettes (one pack) per day during pregnancy have birth weights that are approximately 200 g less than those of infants born to women who do not smoke. If a woman stops smoking during the last 4 months of pregnancy, the risk of delivering a baby with lowered birth weight is similar to that of a nonsmoker. The use of smokeless tobacco also increases blood nicotine levels to levels comparable to those associated with cigarette smoking and, based on limited data, may result in similarly decreased birth weight. The possible clinical effects of passive smoking during pregnancy have not been clearly established.

Occupational and Environmental Agents

Pregnant women may be occupationally or environmentally exposed to a variety of chemicals that are associated with poor reproductive outcomes, including spontaneous abortion, low birth weight, neurologic abnormalities, and congenital anomalies. These chemicals include methyl mercury, lead, polychlorinated biphenyls, polybrominated biphenyls, and organic solvents. Verified human teratogens in this class of agents include methyl mercury and organic solvents. Lead is associated with growth restriction and myelination defects but not gross congenital anomalies. Polychlorinated biphenyls and polybrominated biphenyls are associated with skin discoloration and stillbirth.

Ionizing Radiation

Embryonic or fetal radiation exposure usually results from diagnostic radiologic studies. Diagnostic radiation usually exposes the conceptus to less than 5 cGy (5 rads), depending on the number of radiographs taken and the maternal site examined (Table 6). Any woman who is considering pregnancy and who is exposed to ionizing radiation on the job may wish to have her film badge evaluated more frequently to monitor radiation exposure. She should also wear a badge over the pelvic area for a more precise estimate of potential fetal exposure.

Thyrotoxic (therapeutic) radioisotope (131I) exposure is considerably more hazardous to the fetus than diagnostic studies that use iodine I 121. The fetal thyroid is not susceptible to radioisotope damage before 9-11 weeks of gestation. Dosimetry calculations should be made by experienced professionals, and risks may then be estimated based on isotope and biologic half-lives of the specific agents used and gestational timing of the exposure. Generally, the use of radioisotopes should be avoided during pregnancy. Risks associated with radioisotope iodine exposure during pregnancy include microcephaly, fetal growth restriction, goiter, and hypothyroidism. Risks to the infant include mental retardation and stunted physical growth.

Lithium

Lithium may produce malformations in 1% of offspring exposed prenatally. The anomalies frequently involve the heart and great vessels, with Ebstein’s anomaly of the tricuspid valve being observed most frequently. The concern regarding lithium exposure is the potentially lethal cardiac defect that occurs at a rate of 1 per 20,000. Exposure late in pregnancy may produce transplacental lithium intoxication with neonatal cyanosis, hypotonia, bradycardia, goiter with hypothyroidism, diabetes insipidus, and polyhydramnios. Additionally, maternal diuresis warrants perinatal dose adjustment to avoid lithium toxicity to neonate and mother.

Diethylstilbestrol

The synthetic estrogen diethylstilbestrol produces structural defects of the genital tract, as well as reproductive problems in prenatally exposed females. Vaginal adenosis has been detected in more than 50% of women whose mothers took this drug before the ninth week of pregnancy. A small percentage of women exposed in utero may develop clear-cell adenocarcinoma of the vagina. A variety of abnormalities of the genitourinary tract have also been observed in as many as 25% of males exposed in utero.

Vitamin A and Its Congeners

Isotretinoin. The vitamin A isomer isotretinoin is a potent teratogen, with serious congenital anomalies reported among approximately 35% of exposed fetuses. The specific congenital anomalies observed after oral administration of isotretinoin during early pregnancy include heart disease, thymic agenesis, microphthalmia, hydrocephalus, microtia, cleft palate, deafness and blindness, and an increased risk of spontaneous abortion.

Tretinoin. Topical tretinoin does not result in an increased risk of congenital anomalies because skin metabolizes the drug and no detectable systemic concentrations result.

Etretinate. Etretinate is an oral agent used to treat psoriasis. Case reports link the use of this agent to birth defects similar to those observed after the use of isotretinoin during pregnancy. Unlike vitamin A and its congeners, etretinate has been detected in serum of patients at therapeutic levels for as long as 7 years after cessation of use. Infants with congenital anomalies similar to those observed with isotretinoin use have been seen when the mothers had ceased use of etretinate up to 18 months before conception.
Drugs and Chemicals Associated with Birth Defects
High-Dose Vitamin A. The Centers for Disease Control and Prevention recently evaluated the use of vitamin A during pregnancy. Daily supplementation with 5,000 IU of vitamin A should be considered the maximum intake before and during pregnancy. A recent report associated maternal use of 15,000 IU or more of this nutrient during pregnancy with a significant risk (about triple the background) of congenital anomalies (eg, renal, craniofacial). This is of particular concern because some nutritional supplements contain 25,000 IU or more in a single dose.

Hormonal Agents

Danazol and other androgenic hormone agents may produce clitoral enlargement or labioscrotal fusion in the female fetus when they are given before 13 weeks of gestation. Recent studies, however, have failed to demonstrate a significant relationship between congenital anomalies and first-trimester use of oral contraceptive agents or medroxyprogesterone acetate.

Anticoagulants

Warfarin and other coumarin-derived anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors, and use during gestation can produce major and minor congenital anomalies in as many as 25% of fetuses exposed during the first trimester. Abnormalities characteristic of warfarin include hypoplastic nose, epiphyseal stippling, optic atrophy, microcephaly, IUGR, and other central nervous system anomalies. Heparin and low-molecular-weight heparin are not associated with an increased frequency of congenital anomalies.

Antithyroid Drugs

Thyroid medications such as propylthiouracil, methimazole, and iodide cross the placenta and may occasionally produce transient fetal hypothyroidism and goiter. Infants exposed to methimazole in utero also may develop scalp defects, but this association is rare. Thyroid replacement therapy (ie, thyroxine) does not cross the placenta and is not associated with congenital anomalies, fetal abnormalities, or neonatal abnormalities.

Anticonvulsants

Each of the commonly used anticonvulsant medications has been implicated as teratogenic, but there is no clear consensus concerning which one has the most teratogenic potential. Diphenylhydantoin may produce a syndrome characterized by abnormal facies, microcephaly, growth deficiency, mental retardation, and hypoplastic nails and distal phalanges in as many as 10% of exposed offspring. However, as many as 30% of exposed newborns may demonstrate some aspects of the syndrome. Intrauterine exposure to diphenylhydantoin is also associated with a three- to fourfold increase in the incidence of cleft lip or cleft palate and congenital heart disease. Mild to moderate mental retardation is observed in two thirds of children who have the most severe malformations associated with the syndrome. The syndrome was recently linked to lowered maternal epoxide hydrolase activity, an enzyme involved in the metabolism of hydantoin.
Drugs and Chemicals Associated with Birth Defects
Both valproic acid and carbamazepine have been associated with NTDs. Exposure during embryogenesis poses approximately a 1% risk of spina bifida to exposed fetuses. Specific syndromes have been described.

Trimethadione and paramethadione have been associated with abnormalities similar to those observed with the hydantoins. The risk for congenital anomalies or spontaneous abortion is 60-80% with first-trimester exposure. A syndrome including V-shaped eyebrows, low-set ears, high arched palate, and irregular dentition was identified.

Major congenital anomalies are observed in about 3% of all births. Maternal exposure to drugs or environmental chemicals may be responsible for 4-6% of these anomalies, or approximately 1 in 400 liveborn infants.

Whether birth defects occur in a conceptus exposed to a potentially teratogenic agent depends in large part on two factors: 1) gestational timing of the exposure and 2) the genetic makeup of the conceptus and the mother. Morphogenetic stage of the organism’s development is a key factor in susceptibility to a potential teratogen. Exposure to a teratogenic agent during organogenesis may result in a gross defect involving the organ undergoing formation at that time. Conversely, exposure to such an agent during histogenesis may produce finer structural defects within the target organ system. Substantial evidence suggests that, second only to the gestational timing of exposure, the most important variable is difference in the genetically determined activity of the enzymes involved in the metabolism of drugs and chemicals. This difference is termed pharmacogenetic variation. An important determinant of teratogenic potential is mode of exposure. The teratogenic agent may reach the developing embryo or fetus either by direct passage through maternal tissues (eg, ionizing radiation) or by placental transfer (eg, drugs or chemicals).

Drugs and Chemicals

Epidemiologic studies have determined that most drugs commonly used during pregnancy (eg, aspirin, acetaminophen, metronidazole, caffeine, phenothiazines) are not associated with an increased risk of congenital anomalies. However, based on anecdotal evidence, maternal hyper-thermia seems to be associated with congenital anomalies when the fever persists for a protracted period of time (>24 hours) and is high (at least 101 o F). Numerous other agents have been implicated as teratogens, including chemotherapeutic agents. However, approximately 95% of the 200 most frequently prescribed drugs appear safe for use during pregnancy.

This shows fecal incontinence over a ten-year period of time, and importantly, in the same 300 patients. In other words, patients surveyed – same group – at 1,5 and 10 years. Not different patients at different years. So daytime perfect fecal incontinence is shown here at about 75%. Imperfect, meaning once or twice a week – or perhaps slightly more frequently – shown here at about 5%. Frequent fecal incontinence is very low. The night time success rate is lower than the daytime, for obvious reasons. This reaches about a 55%-60% chance of having perfect fecal control at night.

The mortality – for this usually, completely elective procedure – is very low. Morbidity is also not bad. Pelvic sepsis being a particularly difficult problem in 5% of patients. Wound infections are good at Mayo in general, but in this group it’s about 3%. Small bowel obstructions occur with a frequency no higher than the literature frequency of Brooke ileostomy.

The problem of pouchitis. About 40%-50% of our patients will experience an episode of pouchitis in the postoperative period. What does that mean? Well, let’s take a flow diagram of pouchitis in our patients. So of 100 patients after ileoanal anastomosis, 50 will never have the problem. So let’s go to the 50 that do. Twenty-five of the 50 will have one episode leaving 25 with more than one episode. Of that 25 patients, only four will have something called chronic, unremitting, long term problems with pouchitis, of whom three of the four will be managed. We can talk about the management perhaps later. And one will fail. So about half will have one episode. Among all the others with a rate of 15% have chronic pouchitis or 4% of all patients after ileoanal anastomosis, and most of those are managed medically. Among the patients that failed this operation, only 4% – if you have 100 patients who failed the operation – only four will fail because of pouchitis. They mainly fail for septic problems, mechanical problems with the operation. Perhaps something akin to Crohn’s disease occurring in the pouch or in the anal canal. But again, here’s that four patients with pouchitis as a cause of failure. So there’s no doubt that there are implications for patients with pouchitis, if there is increased incontinence, there are systemic manifestations of the disease at times, there is a need to take canadian medications and a whole host of different things have come along, and there are some workplace and social inconveniences. But there is no permanent increase in stool frequency in these patients and there is little chance of outright failure.