The apprehension is not necessarily data driven and is a cautionary response to the lack of clinical studies in pregnant women. The indication is a trade-off between the adverse effects of the drug, the risks associated with intercurrent diseases and pregnancy complications, and the efficiency of the drug to prevent or ameliorate such risks. In some cases, the use of drugs in pregnancy carries benefits that outweigh the risks. For example, high fever is harmful for the fetus in the early months, thus the use of paracetamol (acetaminophen) is generally associated with lower risk than the fever itself. Similarly, diabetes mellitus during pregnancy may need intensive therapy with insulin to prevent complications to mother and baby. Pain management for the mother is another important area where an evaluation of the benefits and risks is needed. NSAIDs such as Ibuprofen and Naproxen are probably safe for use for a short period of time, 48–72 hours, once the mother has reached the second trimester. If taking aspirin for pain management the mother should never take a dose higher than 100 mg.

DES (diethylstilbestrol) is a drug that mimics estrogen, a female hormone. From 1938 until 1971 doctors prescribed this drug to help some pregnant women who had had miscarriages or premature deliveries on the theory that miscarriages and premature births occurred because some pregnant women did not produce enough estrogen naturally to sustain the pregnancy for full term . An estimated 5-10 million pregnant women and the children born during this period were exposed to DES. Currently, DES is known to increase the risk of breast cancer, and cause a variety of birth-related adverse outcomes exposed female offsprings such as spontaneous abortion, second-trimester pregnancy loss, preterm delivery, stillbirth, neonatal death, sub/infertility and cancer of reproductive tissues . DES is an important developmental toxicant which links the fetal basis of adult disease.

U.S. Code of Federal Regulations requires that certain drugs and biological products must be labelled very specifically with respect to their effects on pregnant populations, including a definition of a "pregnancy category." These rules are enforced by the Food and Drug Administration (FDA). The FDA does not regulate labelling for all hazardous and non-hazardous substances and some potentially hazardous substances are not assigned a pregnancy category.

Australia’s categorisations system takes into account the birth defects, the effects around the birth or when the mother gives birth, and problems that will arise later in the child's life caused from the drug taken. The system places them into a category of their severity that the drug could cause to the infant when it crosses the placenta(Australian Government, 2014).

Methylmercury and inorganic mercury is excreted in human breast milk and infants are particularly susceptible to toxicity due to this compound. The fetus and infant are especially vulnerable to mercury exposures with special interest in the development of the CNS since it can easily cross across the placental barrier, accumulate within the placenta and fetus as the fetus cannot eliminate mercury and have a negative effect on the fetus even if the mother does not show symptoms. Mercury causes damage to the nervous system resulting from prenatal or early postnatal exposure and is very likely to be permanent.

Studies have returned widely varying reports of the effects of PCE: some claim the physical disabilities are severe and generalized, others find specific effects, others none all.

The timing of the dose of the drug is an important determinant of outcome, in addition to how much is used, for how long, and what kind of care is rendered after birth. Drug use in the first trimester is the most harmful to the fetus in terms of neurological and developmental outcome. The effects of PCE later in a child's life are poorly understood; there is little information about the effects of "in utero" cocaine exposure on children over age five. Some studies have found PCE-related differences in height and weight while others have not; these differences are generally gone or small by the time children are school age. Much is still not known about what factors may exist to aid children who were exposed to cocaine "in utero". It is unknown if the effects of PCE are increased once children reach adolescence, or whether the neural rewiring that occurs during this developmental period attenuates the effects. A review of 27 studies performed between 2006 and 2012 found that cognitive development was mildly to moderately affected in PCE adolescents, but it was not clear how important these effects were in practical terms.

Unlike fetal alcohol syndrome, no set of characteristics has been discovered that results uniquely from cocaine exposure "in utero". Cocaine exposure "in utero" may affect the structure and function of the brain, predisposing children to developmental problems later, or these effects may be explained by children of crack-using mothers being at higher risk for domestic violence, deadbeat parenting, and maternal depression. When researchers are able to identify effects of PCE, these effects are typically small.

Studies have found after controlling for other factors that some effects are present in pregnancies involving cocaine: abruptio placenta, prematurity, low birth weight, and small size compared to babies of the same gestational time. PCE newborns have smaller heads and shorter bodies. PCE effects are more severe when the amounts of cocaine are greater. As many as 17–27% of cocaine-using pregnant women deliver prematurely. In association with prematurity, growth in the womb is reduced, and low birth weight is connected to PCE. There are also data showing that spontaneous abortion is associated with cocaine use. Cocaine reduces the appetite and has been linked with reduced maternal weight gain during pregnancy; in addition, constriction of the blood vessels may further limit supply of nutrients to the fetus. Using cocaine while pregnant also heightens the chances of maternal and fetal vitamin deficiencies,

respiratory distress syndrome for the baby, and infarction of the bowels. Early reports found that cocaine-exposed babies were at high risk for sudden infant death syndrome; however, by itself, cocaine exposure during fetal development has not subsequently been identified as a risk factor for the syndrome. Some, but not all, PCE children experience hypertonia (excessive muscle tone), and reduced reflexes and motor function have been found in babies four to six weeks old.

While newborns who were exposed prenatally to drugs such as barbiturates or heroin frequently have symptoms of drug withdrawal (neonatal abstinence syndrome), this does not happen with babies exposed to crack "in utero"; at least, such symptoms are difficult to separate in the context of other factors such as prematurity or prenatal exposure to other drugs.

Neonatal withdrawal is prevented by the mother abstaining from substance abuse. In some cases, a prescribed medication may have to be discontinued during the pregnancy to prevent addiction by the baby. Early pre-natal care can identify addictive behaviors in the mother and family system. Referrals to treatment centers is appropriate. Some prescribed medicines should not be stopped without medical supervision, or harm may result. Women can discuss all medicines, and alcohol and tobacco use with their health care provider and get assistance to help stop drug use as soon as possible. Indications that a woman needs help if she is:

- Using drugs non-medically

- Using drugs not prescribed to you

- Using alcohol or tobacco

If she is already pregnant and takes medicines or drugs not prescribed to her, she can talk to a health care provider about the best way to keep to keep the baby safe. Some medicines should not be stopped without medical supervision, or harm may result. Your health care provider will know how best to manage the risks.

The use of recreational drugs in pregnancy can cause various pregnancy complications.

- Ethanol during pregnancy can cause fetal alcohol syndrome and fetal alcohol spectrum disorder. Studies have shown that light to moderate drinking during pregnancy might not pose a risk to the fetus, although no amount of alcohol during pregnancy can be guaranteed to be absolutely safe.

- Tobacco smoking during pregnancy can cause a wide range of behavioral, neurological, and physical difficulties. Smoking during pregnancy causes twice the risk of premature rupture of membranes, placental abruption and placenta previa. Smoking is associated with 30% higher odds of preterm birth.

- Prenatal cocaine exposure is associated with premature birth, birth defects and attention deficit disorder.

- Prenatal methamphetamine exposure can cause premature birth and congenital abnormalities. Short-term neonatal outcomes show small deficits in infant neurobehavioral function and growth restriction. Long-term effects in terms of impaired brain development may also be caused by methamphetamine use.

- Cannabis in pregnancy has been shown to be teratogenic in large doses in animals, but has not shown any teratogenic effects in humans.

Drug and alcohol use during pregnancy can lead to many health problems in the baby besides NAS. These may include:

- Birth defects

- Low birth weight

- Premature birth

- Small head circumference

- Sudden infant death syndrome (SIDS)

- Problems with development and behavior

Neonatal abstinence syndrome treatment can last from 1 week to 6 months. Even after medical treatment for NAS is over and babies leave the hospital, they may need continued treatment for weeks or months.

Drugs used during pregnancy can have temporary or permanent effects on the fetus. Anything (including drugs) that can cause permanent deformities in the fetus are labeled as teratogens. In the U.S., drugs were classified into categories A, B, C, D and X based on the Food and Drug Administration (FDA) rating system to provide therapeutic guidance based on potential benefits and fetal risks. Drugs, including some multivitamins, that have demonstrated no fetal risks after controlled studies in humans are classified as Category A. On the other hand, drugs like thalidomide with proven fetal risks that outweigh all benefits are classified as Category X.

The only certain way to prevent FAS is to avoid drinking alcohol during pregnancy. In the United States, the Surgeon General recommended in 1981, and again in 2005, that women abstain from alcohol use while pregnant or while planning a pregnancy, the latter to avoid damage even in the earliest stages (even weeks) of a pregnancy, as the woman may not be aware that she has conceived. In the United States, federal legislation has required that warning labels be placed on all alcoholic beverage containers since 1988 under the Alcoholic Beverage Labeling Act.

There is some controversy surrounding the "zero-tolerance" approach taken by many countries when it comes to alcohol consumption during pregnancy. The assertion that moderate drinking causes FAS is said to lack strong evidence and, in fact, the practice of equating a responsible level of drinking with potential harm to the fetus may have negative social, legal, and health impacts. In addition, special care should be taken when considering statistics on this disease, as prevalence and causation is often linked with FASD, which is more common and causes less harm, as opposed to FAS.

Ionizing radiation levels given to a woman during cancer treatment cause miscarriage. Exposure can also impact fertility. The use of chemotherapeutic drugs used to treat childhood cancer increases the risk of miscarriage.

Immunizations have not been found to cause miscarriage. There is no significant association between antidepressant medication exposure and spontaneous abortion. The risk of miscarriage is not likely decrease by discontinuing SSRI prior to pregnancy. Some available data suggest that there is a small increased risk of miscarriage for women taking any antidepressant, though this risk becomes less statistically significant when excluding studies of poor quality.

Medicines that increase the risk of miscarriage include:

- retinoids

- nonsteroidal anti-inflammatory drugs (NSAIDs) , such as ibuprofen

- misoprostol

- methotrexate

There is no cure for FASD, but treatment is possible. Because CNS damage, symptoms, secondary disabilities, and needs vary widely by individual, there is no one treatment type that works for everyone.

While active maternal tobacco smoking has well established adverse perinatal outcomes such as LBW, that mothers who smoke during pregnancy are twice as likely to give birth to low-birth weight infants. Review on the effects of passive maternal smoking, also called environmental tobacco exposure (ETS), demonstrated that increased risks of infants with LBW were more likely to be expected in ETS-exposed mothers.

Regarding environmental toxins in pregnancy, elevated blood lead levels in pregnant women, even those well below 10 ug/dL can cause miscarriage, premature birth, and LBW in the offspring. With 10 ug/dL as the Centers for Disease Control and Prevention's “level of concern”, this cut-off value really needs to arise more attentions and implementations in the future.

The combustion products of solid fuel in developing countries can cause many adverse health issues in people. Because a majority of pregnant women in developing countries, where rate of LBW is high, are heavily exposed to indoor air pollution, increased relative risk translates into substantial population attributable risk of 21% of LBW.

One environmental exposure which has been found to increase the risk of low birth weight is particulate matter, a component of ambient air pollution. Because particulate matter is composed of extremely small particles, even nonvisible levels can be inhaled and present harm to the fetus. Particulate matter exposure can cause inflammation, oxidative stress, endocrine disruption, and impaired oxygen transport access to the placenta, all of which are mechanisms for heightening the risk of low birth weight. To reduce exposure to particulate matter, pregnant women can monitor the EPA’s Air Quality Index and take personal precautionary measures such as reducing outdoor activity on low quality days, avoiding high-traffic roads/intersections, and/or wearing personal protective equipment (i.e., facial mask of industrial design). Indoor exposure to particulate matter can also be reduced through adequate ventilation, as well as use of clean heating and cooking methods.

A correlation between maternal exposure to CO and low birth weight has been reported that the effect on birth weight of increased ambient CO was as large as the effect of the mother smoking a pack of cigarettes per day during pregnancy.

It has been revealed that adverse reproductive effects (e.g., risk for LBW) were correlated with maternal exposure to air pollution combustion emissions in Eastern Europe and North America.

Mercury is a known toxic heavy metal that can harm fetal growth and health, and there has been evidence showing that exposure to mercury (via consumption of large oily fish) during pregnancy may be related to higher risks of LBW in the offspring.

It was revealed that, exposure of pregnant women to airplane noise was found to be associated with low birth weight. Aircraft noise exposure caused adverse effects on fetal growth leading to low birth weight and preterm infants.

Low birthweight, pre-term birth and pre-eclampsia have been associated with maternal periodontitis exposure. But the strength of the observed associations is inconsistent and vary according to the population studied, the means of periodontal assessment and the periodontal disease classification employed. However the best is that the risk of low birth weight can be reduced with very simple therapy. Treatment of periodontal disease during gestation period is safe and reduction in inflammatory burden reduces the risk of preterm birth as well as low birth weight.

Cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. The American Congress of Obstetricians and Gynecologists recommended that cannabis use be stopped before and during pregnancy, Cannabis is the most commonly used illicit substance

among pregnant women.

Although it is difficult to draw firm conclusions, there is some evidence that prenatal exposure to marijuana may be associated with deficits in language, attention, cognitive performance, and delinquent behaviors. THC exposure in rats during the prenatal developmental phase may cause epigenetic changes in gene expression, but there is limited knowledge about the risk for psychiatric disorders because of ethical barriers to studying the developing human brain. While animal studies cannot take into account factors that could influence the effects of cannabis on human maternal exposure, such as environmental and social factors, a 2011 review of rodent studies by Campolongo "et al." said there was "... increasing evidence from animal studies showing that cannabinoid drugs ... induce enduring neurobehavioral abnormalities in the exposed offspring ..." Campolongo "et al." added that "clinical studies report hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis". Martin "et al." investigated recent trends in substance abuse treatment admissions for cannabis use in pregnancy in the US, based on Treatment Episodes Data Set (TEDS) from 1992 to 2012, and discovered that, while the proportion of treatment admissions for pregnant women was stable (about 4%), the admissions for women who were pregnant and reported any marijuana use grew from 29% to 43%. A 2015 review found that cannabis use by pregnant mothers impaired brain maturation in their children, and that it also predisposed their children to neurodevelopmental disorders.

Some disorders and conditions can mean that pregnancy is considered high-risk (about 6-8% of pregnancies in the USA) and in extreme cases may be contraindicated. High-risk pregnancies are the main focus of doctors specialising in maternal-fetal medicine.

Serious pre-existing disorders which can reduce a woman's physical ability to survive pregnancy include a range of congenital defects (that is, conditions with which the woman herself was born, for example, those of the heart or , some of which are listed above) and diseases acquired at any time during the woman's life.

A Dutch 2010 research showed that "low-risk" pregnancy in the Netherlands may actually carry a higher risk of perinatal death than a "high-risk" pregnancy.

Evidence links pesticide exposure to worsened neurological outcomes.

The United States Environmental Protection Agency finished a 10-year review of the organophosphate pesticides following the 1996 Food Quality Protection Act, but did little to account for developmental neurotoxic effects, drawing strong criticism from within the agency and from outside researchers. Comparable studies have not been done with newer pesticides that are replacing organophosphates.

Many studies have examined the effects of pesticide exposure on the risk of cancer. Associations have been found with: leukemia, lymphoma, brain, kidney, breast, prostate, pancreas, liver, lung, and skin cancers. This increased risk occurs with both residential and occupational exposures. Increased rates of cancer have been found among farm workers who apply these chemicals. A mother's occupational exposure to pesticides during pregnancy is associated with an increases in her child's risk of leukemia, Wilms' tumor, and brain cancer. Exposure to insecticides within the home and herbicides outside is associated with blood cancers in children.

Prenatal stress (or prenatal maternal stress) is exposure of an expectant mother to stress, which can be caused by stressful life events or by environmental hardships. The resulting changes to the mother's hormonal and immune system may harm the fetus's (and after birth, the infant's) immune function and brain development.

Prenatal stress is shown to have several affects in fetal brain development. In the hippocampus of adult male rats, prenatal stress has shown to decrease the rate of proliferation and cell death in the hypothalamus-pituitary axis. Prenatal stressed animals have prolonged corticosterone response. Removing the adrenal glands of the mother eliminates the effect of the pup's corticosterone response. Supplementing the adrenalectamized mother with corticosterone, rescued the hypothalamic-pituitary-axis response to maternal stress for prenatally stressed offspring. Prenatal stress caused high glucocorticoids, which in turn affects the hypothalamic-pituitary-axis negative feedback.

A study by García-Cáceres et al. showed that prenatal stress decreases cell turnover and proliferation in the hypothalamus of adult rats, which reduces structural plasticity and reduces the response to stress in adulthood. This study also showed that when prenatally stressed rats were stressed in adulthood the females showed an increase in corticotropin-releasing hormone suggesting it to be an up-regulation in the hypothalamic-pituitary adrenal axis. Males showed no elevation of corticosterone levels. Increase in adrenocorticotropic hormone with no effect of adult stress and a decrease in the corticotropin-releasing hormone mRNA in the hypothalamus showed a down-regulation. The author concludes that this makes prenatally stressed females less reactive to later life stressors than males.

The role of the endocannabinoid system (ECS) in female fertility has long been suspected and studied. Most studies through 2013 linking development of the fetus and cannabis show effects of consumption during the gestational period, but abnormalities in the endocannabinoid system during the phase of placental development are also linked with problems in pregnancy. According to Sun and Dey (2012), endocannabinoid signaling plays a role in "female reproductive events, including preimplantation embryo development, oviductal embryo transport, embryo implantation, placentation, and parturition". Karusu "et al" (2011) said that a "clear correlation ... in the actual reproductive tissues of miscarrying versus healthy women has yet to be established. However, the adverse effects of marijuana smoke and THC on reproductive functions point to processes that are modulated by ECS."

Keimpema and colleagues (2011) said, "Prenatal cannabis exposure can lead to growth defects during formation of the nervous system"; "[c]annabis impacts the formation and functions of neuronal circuitries by targeting cannabinoid receptors ... By indiscriminately prolonging the "switched-on" period of cannabinoid receptors, cannabis can hijack endocannabinoid signals to evoke molecular rearrangements, leading to the erroneous wiring of neuronal networks". A report prepared for the Australian National Council on Drugs concluded cannabis and other cannabinoids are contraindicated in pregnancy as they may interact with the endocannabinoid system.

Current antidotes for OP poisoning consist of a pretreatment with carbamates to protect AChE from inhibition by OP compounds and post-exposure treatments with anti-cholinergic drugs. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of "-oximes" has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally. These antidotes are effective at preventing lethality from OP poisoning, but current treatment lack the ability to prevent post-exposure incapacitation, performance deficits, or permanent brain damage. While the efficacy of atropine has been well-established, clinical experience with pralidoxime has led to widespread doubt about its efficacy in treatment of OP poisoning.

Enzyme bioscavengers are being developed as a pretreatment to sequester highly toxic OPs before they can reach their physiological targets and prevent the toxic effects from occurring. Significant advances with cholinesterases (ChEs), specifically human serum BChE (HuBChE) have been made. HuBChe can offer a broad range of protection for nerve agents including soman, sarin, tabun, and VX. HuBChE also possess a very long retention time in the human circulation system and because it is from a human source it will not produce any antagonistic immunological responses. HuBChE is currently being assessed for inclusion into the protective regimen against OP nerve agent poisoning. Currently there is potential for PON1 to be used to treat sarin exposure, but recombinant PON1 variants would need to first be generated to increase its catalytic efficiency.

One other agent that is being researched is the Class III anti-arrhythmic agents. Hyperkalemia of the tissue is one of the symptoms associated with OP poisoning. While the cellular processes leading to cardiac toxicity are not well understood, the potassium current channels are believed to be involved. Class III anti-arrhythmic agents block the potassium membrane currents in cardiac cells, which makes them a candidate for become a therapeutic of OP poisoning.

Prenatal stress and negative mood during pregnancy has been shown to increase the risk for poor childbirth outcomes and postnatal maternal mood problems. Additionally, prenatal distress can interfere with the mother-infant attachment and child development outcomes. Despite the clear association between prenatal stress and child outcomes, frequently women do not receive screening, prevention, or treatment for mood or stress concerns.

Given the relationship between prenatal stress and child outcomes, it is essential to examine interventions that aim to reduce anxiety, depression, and stress during pregnancy. Mindfulness based stress reduction has been demonstrated to reduce anxiety and depression for people with stress-related and chronic medical conditions.

One pilot study shows promise for the potential of a mindfulness-based intervention to reduce negative affect and anxiety of women during pregnancy. Based out of the California Pacific Medical Center Research Institute, investigators Dr. Cassandra Vieten and Dr. John Astin conducted a wait-list control pilot study that tested a group-based mindfulness intervention. There were 31 women enrolled in the study: 13 women were assigned to the intervention and 18 women were assigned to the control group. Measures of anxiety, negative affect, positive affect, depression, mindfulness, perceived stress, and affect regulation were taken before intervention or control was assigned and after the intervention or control was completed. Measures were repeated at a follow-up visit 3 months after the intervention or control was completed. The investigators found a significant decrease in anxiety (p<.05) and negative affect (p <.04) in women who completed the mindfulness based intervention, but not a significant decrease in depression, positive affect, mindfulness, affect regulation, and perceived stress. These results suggest that mindfulness intervention during pregnancy reduce anxiety and negative affect of mothers. This study is a promising start to the potential impact that mindfulness based interventions could have on reducing prenatal stress, and thereby improving child outcomes.