the fda advises for the risk of birth defects with the use of paroxetine and the maoi should be avoided. a 2013 systematic review and meta-analysis found that antidepressant use during pregnancy was statistically significantly associated with some pregnancy outcomes, such as gestational age and preterm birth, but not with other outcomes. the same review cautioned that because differences between the exposed and unexposed groups were small, it was doubtful whether they were clinically significant. a neonate (infant less than 28 days old) may experience a withdrawal syndrome from abrupt discontinuation of the antidepressant at birth. antidepressants can be present in varying amounts in breast milk, but their effects on infants are currently unknown. moreover, ssris inhibit nitric oxide synthesis, which plays an important role in setting the vascular tone. several studies have pointed to an increased risk of prematurity associated with ssri use, and this association may be due to an increased risk of pre-eclampsia during pregnancy. 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. loperamide has limited data on the impact it has on pregnancy, but there is an association with cardiovascular malformation in the first trimester. atropine/diphenoxylate currently has insufficient evidence of teratogenicity in humans, but trials with animals showed evidence of teratogenic effects. antihistamines antihistamines may be prescribed in early pregnancy for the treatment of nausea and vomiting along with symptoms of asthma and allergies. first generation antihistamines include diphenhydramine (benadryl), chlorpheniramine (diabetic tussin), hydroxizine (atarax), and doxepin (sinequan). second generation antihistamines include loratadine (claritin), cetrizine (zyrtec), and fexofenadine (allegra). first generation antihistamines have the ability to cross the blood-brain barrier which can result in sedative and anticholinergic effects while effectively treating allergic reactions and nausea and vomiting related to pregnancy. on the other hand, second generation antihistamines do not cross the blood-brain barrier, thus eliminating sedating effects. currently, there is a lack of association between prenatal antihistamine exposure and birth defects. 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. anti-hypertensives are blood pressure medications used to treat high blood pressure in pregnant women. this class of medication is commonly used to treat problems such as heart failure, heart attack, and kidney failure. caution must be exercised with the use of various hypertensive agents for the treatment of blood pressure. 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. acei and arb have known fetotoxicities when used during the second or third trimester or both. 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. pregnant women should discuss all dietary supplements with their health care professional to determine the appropriate dosage and which supplements are safe during pregnancy. caution should be taken before consuming dietary supplements while pregnant as dietary supplements are considered "foods" rather than medications and are not regulated for safety and efficacy by the fda. folic acid example of a neural tube defect: spina bifida 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. iron main articles: iron deficiency and iron-deficiency anemia iron deficiency is common in pregnancy, with the highest occurrence rate during the third trimester as iron demand increases to support the placenta, fetal development and the iron stores for the first six months after birth. low iron levels can cause fatigue, reduced work capacity, cardiovascular stress, lower resistance to infection and iron deficiency anemia. iron deficiency anemia in pregnancy can lead to an increased risk of premature delivery, low birth weight and increased risk of perinatal mortality. 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. who recommends taking supplements of 30-60 mg of elemental iron a day throughout pregnancy for all pregnant individuals. iron demand depends on individual specific factors and risk of deficiency; for specific dose recommendations, individuals should discuss with their doctors. dietary sources of iron include meat, paltry, 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 alcohol main articles: alcohol and pregnancy and fetal alcohol spectrum disorders alcohol should not be consumed while pregnant. 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 as well as the stage of pregnancy. rates of alcohol consumption can generally be categorized in one of three ways: heavy drinking (more than 48-60 grams of ethanol/day), moderately high drinking (24-48 grams of ethanol/day), and binge drinking (4-5 drinks/90 grams of ethanol at a time). 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. 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. other comprehensive reviews reported that caffeine intake of more than 300 mg per day have been associated with spontaneous abortions and low birth weight, but further research is needed to establish this causal relationship. cannabis main article: cannabis in pregnancy 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. tetrahydrocannabinol (thc), an active ingredient in cannabis, can both cross the placenta and accumulates in high concentrations in breast milk. cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. infants exposed to prenatal cannabis may show signs of increased tremors and altered sleep patterns. 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 main article: prenatal cocaine exposure 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. cocaine