Drugs in pregnancy

Categorizations of drugs based on safety in pregnancy varies by country. Until 2014, the U.S. Code of Federal Regulations required that certain drugs and biological products be labelled specifically with respect to their effects on pregnant populations, including a definition of a "pregnancy category". These rules were enforced by the FDA, and medications that have been studied for their effects in pregnancy fell under the following Pregnancy Categories: A, B, C, D, or X depending on how they have been studied and what kind of results were found from the studies. In 2014, however, the FDA has developed a "Pregnancy and Lactation Labeling Rule (PLLR)" which requires product labels to include specific information related to the safety and effectiveness of medications to pregnant and lactating women. This ruling has removed the requirement of stating pregnancy categories in prescription drug labels. Australia's categorization system takes into account birth defects, the effects around birth or when the mother gives birth, and problems that will arise later in the child's life due to the drug taken. The system places them into a category based on the severity of the consequences that the drug can have on the infant when it crosses the placenta. == Medications ==

Medications during pregnancy must be carefully considered. Many drugs, medications, and nutritional supplements can affect fetal development or cause complications. For over-the-counter and prescription medications, healthcare professionals can help weigh the potential risks and benefits of taking medication while pregnant and if it is needed. Some medications may be necessary for the health and well being of both the mother and the unborn child, and some medications may come with a risk of harm to the unborn baby, but in some instances the benefits may outweigh the risks to the baby or mother. Medications for pain Short-term use of acetaminophen as directed is one of the only medications recommended for treating pain and fever in women who are pregnant. Ibuprofen and naproxen have not frequently been studied during pregnancy, but recent studies do not show increased risk of spontaneous abortion within the first six weeks of pregnancy. While aspirin should be avoided for use pain relief, low dose aspirin is used for prevention of preeclampsia and fetal growth restriction (FGR) in patients with previous risk factors (e.g. previous preeclampsia, multiple pregnancies, hypertension and diabetes). Pain medications containing opioids For more information, see the below section on Recreational drugs Pregnant women who use prescription medications containing opioids while pregnant may cause serious harm to the mother or unborn child. Women who have epilepsy often still require treatment to control or prevent seizures and therefore require very early advice (ideally before conceiving the child) from their doctor to determine the safest way to protect both the mother and unborn child. There is evidence that an increased dose or increased exposure in utero is associated with an increased risk of lower scores on neurodevelopmental tests. Valproic acid use during pregnancy increases the risk of neural tube defects by approximately 20-fold. Heartburn often indicates the development of gastro-esophageal reflux disease (GERD), where the lower esophageal sphincter relaxes due to elevated progesterone levels causing increased frequency and severity of gastric reflux or heartburn. If heartburn appears after 20 weeks of gestational age or is severe and persistent, this can indicate other conditions including HELLP syndrome and preeclampsia. Common antacids include aluminum hydroxide/magnesium hydroxide (Maalox) and calcium carbonate (Tums). Histamine H2 blockers and proton pump inhibitors, such as famotidine (Pepcid) and omeprazole (Prilosec), respectively, can also be used to help relieve heartburn, with no known teratogenic effects or congenital malformations. Ginger and acupressure are common non-pharmacological options used to treat nausea and vomiting as alternatives to antacids, histamine H2 blockers, and proton pump inhibitors. Lifestyle modifications are often recommended as well. Recommended modifications can include avoiding fatty food, reducing size and frequency of meals, and reducing caffeine intake. Antiacne Acne vulgaris (acne) can occur in pregnancy possibly due to the hormonal changes influencing sebum production. There are limited antiacne medications that are safe in pregnancy. External applications of azelaic acid, glycolic acid, or benzoyl peroxide (alone or combined with clindamycin or erythromycin) are the safest options to treat mild to moderate acne. Erythromycin is the antibiotic of choice for severe acne, barring the use of its estolate salt which risks maternal hepatotoxicity. Topical nicotinamide and topical zinc are safe, however, there are no FDA pregnancy category ratings. Topical salicylic acid and topical dapsone are classified as FDA pregnancy category C. As safety data is lacking, the use of topical retinoids, such as adapalene and tretinoin, is not recommended. Antiandrogenic drugs, including spironolactone and cyproterone acetate, should be avoided. Safety data supports the use of blue and red light therapy as non-drug treatments to consider. These medications are commonly used for both prevention and treatment in people who are at risk for or have experienced a heart attack, stroke, or venous thromboembolism. Anticoagulants must be prescribed with caution as these medications can have negative health consequences for the developing baby and need to consider dosing and medication management options. Warfarin (brand name Coumadin) is a commonly prescribed blood thinner both in the inpatient and outpatient hospital settings. In pregnant women, warfarin is contraindicated and should be avoided as it crosses the placental barrier. Additionally, warfarin is listed as Pregnancy Category D, which means it has a risk of harming the fetus. A common low molecular weight heparin drug is called enoxaparin (brand name Lovenox). Enoxaparin is listed as Pregnancy Category B, meaning animal studies have failed to show harmful effects to the fetus and therefore are safe to use in pregnant women. However, pregnant women taking LMWH may not experience the full anticoagulant effect due to the nature of the medication compared to other anticoagulants (i.e. warfarin) and may be less favorable for users as it is an injectable medication. Unfractionated heparin is another type of anticoagulant that has been widely used. UFH is classified as Pregnancy Category C, which means animal studies have shown potential for adverse effects to the fetus; however, there needs to be more studies done to confirm the presence of a risk to the fetus. UFH can be used in pregnant women as long as the benefits outweigh the risk. Antidepressants Antidiabetics Women who have diabetes mellitus may need intensive therapy with insulin to prevent complications to the mother and baby. Gestational diabetes is a form of diabetes that is first diagnosed during pregnancy and can accordingly cause high blood sugar that affects the woman and the baby. In 10-20% of women whose diet and exercise are not adequate enough to control blood sugar, insulin injections may be required to lower blood sugar levels. Antidiarrheal Diarrhea is not a common symptom of pregnancy; however, it can occur as a result of reduced gastric acidity and slowed intestinal motility. Bismuth subsalicylate (Pepto-Bismol), loperamide (Imodium), and atropine/diphenoxylate (Lomotil) are antidiarrheal agents that can be used to treat diarrhea. However, not all of them are safe to use during pregnancy. One of the components of bismuth subsalicylate is salicylate, which is a component that crosses the placenta. Due to this, there is an increased risk for intrauterine growth retardation, fetal hemorrhage, and maternal hemorrhage within organogenesis and in the second/third trimester. Second generation antihistamines include loratadine (Claritin), cetrizine (Zyrtec), and fexofenadine (Allegra). Antihistamines during pregnancy have not been linked to birth defects; however, further research is necessary for some antihistamine medications to determine safety during pregnancy. It is suggested that women speak to their healthcare professionals before taking any over-the-counter or prescription medication while pregnant to ensure that there are no adverse health outcomes. Anti-hypertensives Hypertensive issues are the most common cardiovascular disorders during pregnancy, occurring within 5 to 10% of all pregnant females. While the drug classes of Angiotensin Converting Enzyme inhibitors (ACEi), Angiotensin Receptor Blockers (ARB), and angiotensin receptor neprilysin inhibitors (ARNI) have been shown to be potent anti-hypertensive agents, their use is advised against during pregnancy. Signs and symptoms of ACEi and ARB use during pregnancy include kidney damage or failure, oligohydramnios, anuria, joint contractures, and hypoplasia of the skull. Common, alternative agents for high blood pressure in pregnant women include anti-adrenergic and beta-blocking medications, such as methyldopa or metoprolol, respectively. Decongestants Decongestants are often used in conjunction with cold medications or to combat pregnancy rhinitis in pregnant women. Common decongestants include pseudoephedrine and phenylephrine. Pseudoephedrine is an alpha-adrenergic receptor agonist that enacts a vasoconstrictive effect to reduce airflow resistance in the nasal cavity and allow easier breathing by relieving a stuffy or congested nose. When taken in early trimesters, there has been limited evidence to associate pseudoephedrine with birth defects. However, studies often found it difficult to isolate pseudoephedrine's involvement, due to the variety of combination products that contain pseudoephedrine in conjunction with other medications. Since pseudoephedrine activates alpha adrenergic receptors, it has the ability to elevate blood pressure and cause vasoconstriction within the uterine arteries. This can negatively affect blood flow to the fetus. Due to the lack of studies, decongestants in combination drugs or isolated forms are suggested to be used sparingly during pregnancy. Saline nasal sprays, among other non-pharmacological treatments, are considered to be safe alternatives for decongestants. == Dietary supplements ==

Dietary supplements such as folic acid and iron are important for a healthy pregnancy. Some dietary supplements can cause side effects and harm to the mother or unborn child. Folic Acid Many countries such as the USA, Canada, Chile, and Costa Rica have fortified foods with folic acid and have seen a reduced incidence of neural tube defect (NTD). The Center for Disease Control and Prevention (CDC) recommends that all women of child-barring age receive 400 μg of folic acid supplement (even if they are not planning on getting pregnant). Women who have already had an NTD-affected pregnancy and are planning to become pregnant again should receive 4000 μg each day for a month before and for the first three months of pregnancy. The recommendation came from a study conducted by the British Medical Research Council (MRC) Vitamin Study Group from July 1983 to April 1991 involving 33 centers (17 of which in the UK and the remaining 16 in 6 different countries) that compared pregnancy outcomes of folic acid and other vitamins interventions with placebo. That study found a risk reduction of 71% of NTD-affected pregnancies in groups receiving folic acid when compared to groups receiving placebo. In the study, there were four intervention groups, Group A received 4 mg of folic acid; Group B received a multivitamin that contained folic acid; Group C placebo and Group D received a multivitamin without folic acid. In the groups that received folic acid, 6 out of 593 (1%) infants and fetuses had NTD reoccurrence compared to the groups that received no folic acid, which had 21 infants and fetuses with NTD out of 602 (3.5%). There were no significant benefit found in the vitamin intervention groups. The Recommended Dietary Allowance (RDA) suggests 27 mg of iron a day which would account for normal iron losses, iron used by the fetus and related tissues during gestation and increased maternal hemoglobin mass changes. Dietary sources of iron include meat, poultry, fish, eggs, legumes, vegetables, fruits, grains, nuts and iron-fortified grain products. Eating at least one source of vitamin C with each meal is also recommended, as it can help increase iron absorption. Examples of vitamin C sources include broccoli, cantaloupe, citrus fruits and their juices, kiwis, mangos, potatoes, strawberries, sweet peppers, tomatoes, and tomato sauce. On the contrary, caffeine, calcium supplements and antacids should be separated from meals and iron supplements by 1–2 hours as they can decrease iron absorption. == Illicit and recreational drugs ==

According to the World Health Organization, substance abuse refers to the damaging or risky consumption of psychoactive substances, which includes alcohol and illegal drugs. When pregnant women use psychotropic substances, whether they are prescribed or not, it can have adverse effects on the developing fetus. These effects may include causing birth defects, delayed development, and intrauterine growth restriction. Even a small amount of alcohol is not known to be safe for the unborn baby. Alcohol passes easily from the mother's bloodstream through the placenta and into the bloodstream of the fetus. Since the fetus is smaller and does not have a fully developed liver, the concentration of alcohol in its bloodstream lasts longer, increasing the chances of detrimental side effects. The severity of effects alcohol may have on a developing fetus depends upon the amount and frequency of alcohol consumed; maternal weight, age, and alcohol metabolism; and the stage of pregnancy. Fetal alcohol spectrum disorder Heavy drinking and binge drinking are closely associated with a higher risk of fetal alcohol spectrum disorders (FASDs). The most severe form of FASD is fetal alcohol syndrome (FAS). This used to be the only diagnosis for fetal disorders due to alcohol consumption, but the term was broadened to a "spectrum" due to the variety of abnormalities observed in newborns. This was most likely because of the different amounts of alcohol ingested during pregnancy indicating that there is not a clear, specific dose that determines if a fetus will be affected by alcohol or not. FAS is characterized by slower physical growth, distinct facial abnormalities including smooth philtrum, thin vermilion, and short palpebral fissures, neurological deficits, or smaller head circumference.Other problems associated with FASD include delayed or uncoordinated motor skills, hearing or vision problems, learning disabilities, behavior problems, and inappropriate social skills compared to same-age peers. Those affected are more likely to have trouble in school, legal problems, participate in high-risk behaviors, and develop substance use disorders themselves. Miscarriage Alcohol consumption is a risk factor for miscarriage. Neonatal withdrawal Babies exposed to alcohol, benzodiazepines, barbiturates, and some antidepressants (SSRIs) during pregnancy may experience neonatal withdrawal. The onset of clinical presentation typically appears within 48 to 72 hours of birth but may take up to 8 days. Sudden infant death syndrome Drinking of alcohol by parents is linked to sudden infant death syndrome (SIDS). One study found a positive correlation between the two during New Years celebrations and weekends. Another found that alcohol use disorder was linked to a more than doubling of risk. Caffeine Caffeine is a widespread drug consumed by adults due to its behavioral and stimulating effects. According to the American College of Obstetricians and Gynecologists, an acceptable intake of caffeine for pregnant women is less than or equal to 200 mg per day. Consumption of caffeine is not associated with adverse reproductive and developmental effects. The half-life of caffeine is longer in pregnancy by 8 to 16 more hours, which means that caffeine stays in the person longer, increases fetal exposure to caffeine, and is eliminated slower in the body. Cannabis Cannabis use during pregnancy should be avoided. There is no known safe dose of cannabis while pregnant and use of cannabis may lead to birth defects, pre-term birth, or low birth weight. Cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. Cannabis is the most frequently used illicit drug amongst pregnant women. There are significant limitations to the current research available. One limitation is because most studies done are dated in the 1980s. Additionally, many studies done on cannabis that evaluate its safety often fail to account for confounding factors, a variable that could also be having an effect on an outcome that is not the test variable. For example, tobacco use and sociodemographic differences are often not adjusted for accordingly in many studies. Cocaine Use of cocaine in pregnant women is dangerous and can lead to cardiovascular complications like hypertension, myocardial infarction and ischemia, kidney failure, liver rupture, cerebral ischemia, cerebral infarction, and maternal death. Cardiac muscles become more sensitive to cocaine in pregnancy, in the presence of increasing progesterone concentrations. Prenatal cocaine exposure (PCE) is associated with premature birth, birth defects, attention deficit hyperactivity disorder (ADHD), and other conditions. Methamphetamine Use of methamphetamine is dangerous for pregnant women and to the fetus. Methamphetamines are a class of drugs that provide stimulant-like effects, including euphoria and alertness. The drug crosses the placenta and affects the fetus during the gestational stage of pregnancy. Women who use opioids during pregnancy in a non-medical fashion are at a higher risk for premature birth, lower birth weight, still birth, specific birth defects, and withdrawal (neonatal abstinence syndrome). Opioid use is the main cause of neonatal abstinence syndrome, which is where the baby experiences withdrawals from the opioid they were exposed to during the pregnancy. Typical symptoms may include tremors, convulsions, twitching, excessive crying, poor feeding or sucking, slow weight gain, breathing problems, fever, diarrhea, and vomiting. There is no consensus on the effects on cognitive abilities. Further research is required to determine the long-term effects of in utero exposure to opioid medications on children. Nicotine crosses the placenta and accumulates within fetal tissues. Children born to women who smoked heavily were more susceptible to behavioral problems such as ADHD, poor impulse control, and aggressive behaviors. == References ==