Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and which is caused by environmental insult (including drugs, lifestyle factors such as alcohol, diet, and environmental toxic chemicals or physical factors). It is the study of adverse effects on the development of the organism resulting from exposure to toxic agents before conception (either parent), during prenatal development, or post-natally until puberty. The substance that causes developmental toxicity from embryonic stage to birth is called teratogens. The effect of the developmental toxicants depends on the type of substance, dose and duration and time of exposure.

Certain Pathogens are also included since the toxins they secrete are known to cause adverse effects on the development of the organism when the mother or fetus is infected. Developmental toxicology is a science studying adverse developmental outcomes. This term has widely replaced the early term for the study of primarily structural congenital abnormalities, teratology, to enable inclusion of a more diverse spectrum of congenital disorders. Typical factors causing developmental toxicity are radiation, infections (e.g. rubella), maternal metabolic imbalances (e.g. alcoholism, diabetes, folic acid deficiency), drugs (e.g. anticancer drugs, tetracyclines, many hormones, thalidomide), and environmental chemicals (e.g. mercury, lead, dioxins, PBDEs, HBCD, tobacco smoke). The first-trimester exposure is considered the most potential for developmental toxicity.

Once fertilization has taken place, the toxicants in the environment can pass through the mother to the developing embryo or fetus across the placental barrier. The fetus is at greatest risk during the first 14th to 60th day of the pregnancy when the major organs are being formed. However, depending on the type of toxicant and amount of exposure, a fetus can be exposed toxicant at any time during pregnancy. For example, exposure to a particular toxicant at one time in the pregnancy may result in organ damage and at another time in the pregnancy could cause death of the fetus and miscarriage. There are a number of chemicals, biological agents (such as bacteria and viruses), and physical agents (such as radiation) used in a variety of workplaces that are known to cause developmental disorders. Developmental disorders can include a wide range of physical abnormalities, such as bone or organ deformities, or behavioral and learning problems, such as a mental retardation. Exposures to some chemicals during pregnancy can lead to the development of cancer later in the life of the child and are called transgenerational carcinogens. Exposure to toxicants during the second and the third trimester of a pregnancy can lead to slow fetal grown and result in low birth weight.

Drug use during pregnancy can have temporary or permanent effects on the fetus. Any drug that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen. Drugs may refer to both pharmaceutical drug and recreational drugs.

Developmental toxicity is the alterations of the developmental processes (organogenesis, morphogenesis) rather than functional alterations of already developed organs. The effects of the toxicants depends on the dose, threshold and duration. The effects of toxicity are:

1. Minor structural deformities - e.g. Anticonvulsant drugs, Warfarin, Retinoic Acid derivatives

2. Major structural deformities - e.g. DES (diethylstilbestrol), cigarette smoking

3. Growth Retardation - e.g. Alcohol, Polychlorinated Biphenyls

4. Functional alterations - e.g. Retinoic Acid derivatives, Polychlorinated Biphenyls, Phenobarbitol, Lead

5. Death- e.g. Rubella, ACE inhibitors

Withdrawal from marijuana can initiate a preterm birth and meconium staining.

Symptoms often begin within 1 to 3 days after birth, but may take up to a week to appear. Because of this, the baby will most often need to stay in the hospital for observation and monitoring for up to a week. Withdrawing from different drugs, including prescribed medications, and nicotine from smoking produces its own signs and symptoms in the infant. Neonatal abstinence syndrome may occur when a pregnant woman takes drugs such as heroin, codeine, oxycodone (Oxycontin), methadone or buprenorphine. Benzodiazepines, barbiturates, and certain antidepressants (SSRIs) can cause dependence in the infant while in the womb. The severity of the withdrawal symptoms in the neonate is dependent upon the route of administration used by the mother (injection vs inhalation). The metabolism and elimination of the drug from the mother's system, and the length of time that the drug was taken will also impact the development of withdrawal symptoms in the newborn. More severe findings may include acting irritable or jittery, feeding problems, and diarrhea. Symptoms vary depending on which substances were used. A history of substance of abuse in the mother before the birth increases the likelihood that the infant will develop symptoms of withdrawal.

Generally, an infant going through withdrawal has a distinctive cry. It can be described as being high-pitched, non-stop and shrill. A newborn withdrawing from drugs or alcohol may be hypertonic and have convulsions. Seizures, increased Moro reflex, tremors, irritability, and disturbed sleep patterns can be observed.

Respiratory symptoms of withdrawal include a temperature greater than normal, tachypnea, apnea, nasal congestion, nasal flaring, blotchy skin, and yawning.

Withdrawal can produce gastro-intestinal symptoms such as poor appetite, regurgitation, projectile vomiting and diarrhea. The sucking reflex can be incessant and uncoordinated. Babies of mothers who use other addictive drugs (e.g. nicotine, amphetamines, cocaine, marijuana) may have long-term problems. While there is no clear evidence of a neonatal abstinence syndrome for other drugs, they may contribute to the severity of a baby's NAS symptoms.

Prenatal cocaine exposure (PCE), theorized in the 1970s, occurs when a pregnant woman uses cocaine and thereby exposes her fetus to the drug. "Crack baby" was a term coined to describe children who were exposed to crack (freebase cocaine in smokable form) as fetuses; the concept of the crack baby emerged in the US during the 1980s and 1990s in the midst of a crack epidemic. Other terms are "cocaine baby" and "crack kid". Early studies reported that people who had been exposed to crack in utero would be severely emotionally, mentally, and physically disabled; this belief became common in the scientific and lay communities. Fears were widespread that a generation of crack babies were going to put severe strain on society and social services as they grew up. Later studies failed to substantiate the findings of earlier ones that PCE has severe disabling consequences; these earlier studies had been methodologically flawed (e.g. with small sample sizes and confounding factors). Scientists have come to understand that the findings of the early studies were vastly overstated and that most people who were exposed to cocaine "in utero" do not have disabilities.

No specific disorders or conditions have been found to result for people whose mothers used cocaine while pregnant. Studies focusing on children of six years and younger have not shown any direct, long-term effects of PCE on language, growth, or development as measured by test scores. PCE also appears to have little effect on infant growth.

However, PCE is associated with premature birth, birth defects, attention deficit hyperactivity disorder, and other conditions. The effects of cocaine on a fetus are thought to be similar to those of tobacco and less severe than those of alcohol. No scientific evidence has shown a difference in harm to a fetus between crack and powder cocaine.

PCE is very difficult to study because it very rarely occurs in isolation: usually it coexists with a variety of other factors, which may confound a study's results. Thus, studies have failed to clearly show that PCE has negative cognitive effects, partly because such effects may be due to concurrent factors. Pregnant mothers who use cocaine often use other drugs in addition, or they may be malnourished and lacking in medical care. Children in households where cocaine is abused are at risk of violence and neglect, and those in foster care may experience problems due to unstable family situations. Factors such as poverty that are frequently associated with PCE have a much stronger influence on children's intellectual and academic abilities than does exposure to cocaine in isolation. Thus researchers have had difficulty in determining which effects result from PCE and which result from other factors in the children's histories.

Slowed growth is well documented in fetuses, but it is not as clear whether older children remain smaller or catch up to their peers. Some studies show that growth remains slowed for as many as ten years. PCE may also interfere with the way the motor system matures. Motor effects that have been documented include poorer reflexes and quality of movement in infants. PCE may have an effect on the neuroendocrine system, but more study is needed to determine whether it does and what the effects are.

A review of the literature reported that cocaine use causes congenital defects between 15 and 20% of the time; however another large-scale study found no difference in rates of birth anomalies in PCE and non-PCE infants. It has been suggested that some birth defects could be due to cocaine's disruption of blood vessel growth.

Most PCE-related congenital defects are found in the brain, heart, genitourinary tract, arms and legs.

Cocaine use by pregnant mothers may directly or indirectly contribute to defects in the formation of the circulatory system and is associated with abnormalities in development of the aorta. Heart malformations can include a missing ventricle and defects with the septum of the heart, and can result in potentially deadly congestive heart failure. Genital malformations occur at a higher-than-normal rate with PCE.

The liver and lungs are also at higher risk for abnormalities. Cloverleaf skull, a congenital malformation in which the skull has three lobes, the brain is deformed, and hydrocephalus occurs, is also associated with PCE. Like birth defects, small head size, and stroke are risks in PCE.

The CDC reviewed nine syndromes that have overlapping features with FAS; however, none of these syndromes include all three FAS facial features, and none are the result of prenatal alcohol exposure:

- Aarskog syndrome

- Williams syndrome

- Noonan syndrome

- Brachman-DeLange syndrome

- Toluene syndrome

- Fetal hydantoin syndrome

- Fetal valproate syndrome

- Maternal PKU fetal effects

Other conditions may commonly co-occur with FAS, stemming from prenatal alcohol exposure. However, these conditions are considered alcohol-related birth defects and not diagnostic criteria for FAS.

- Heart: A heart murmur that frequently disappears by one year of age. Ventricular septal defect most commonly seen, followed by an atrial septal defect.

- Bones: Joint anomalies including abnormal position and function, altered palmar crease patterns, small distal phalanges, and small fifth fingernails.

- Kidneys: Horseshoe, aplastic, dysplastic, or hypoplastic kidneys.

- Eyes: Strabismus, optic nerve hypoplasia (which may cause light sensitivity, decreased visual acuity, or involuntary eye movements).

- Occasional problems: ptosis of the eyelid, microophthalmia, cleft lip with or without a cleft palate, webbed neck, short neck, tetralogy of Fallot, coarctation of the aorta, spina bifida, and hydrocephalus.

Low birth weight (LBW) is defined by the World Health Organization as a birth weight of a

infant of 2,499 g or less, regardless of gestational age. Subcategories include very low birth weight (VLBW), which is less than 1500 g (3 pounds 5 ounces), and extremely low birth weight (ELBW), which is less than 1000 g (2 pounds 3 ounces). Normal weight at term delivery is 2500–4200 g (5 pounds 8 ounces – 9 pounds 4 ounces).

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.

Each year, ill health as a result of pregnancy is experienced (sometimes permanently) by more than 20 million women around the world. In 2013 complications of pregnancy resulted in 293,000 deaths down from 377,000 deaths in 1990. Common causes include maternal bleeding (44,000), complications of abortion (44,000), high blood pressure of pregnancy (29,000), maternal sepsis (24,000), and obstructed labor (19,000).

The following are some examples of pregnancy complications:

- Pregnancy induced hypertension

- Anemia

- Postpartum depression

- Postpartum psychosis

- Thromboembolic disorders. These are the leading cause of death in pregnant women in the US.

- PUPPP (Pruritic Urticarial Papules and Plaques of Pregnancy), a skin disease that develops around the 32nd week. Signs are red plaques, papules, and itchiness around the belly button that then spreads all over the body except for the inside of hands and face.

- Ectopic pregnancy, implantation of the embryo outside the uterus.

- Hyperemesis gravidarum, excessive nausea and vomiting that is more severe than normal morning sickness.

- Pulmonary embolism, blood clots that form in the legs that can migrate to the lungs.

There is also an increased susceptibility and severity of certain infections in pregnancy.

Hyperemesis gravidarum is the presence of severe and persistent vomiting, causing dehydration and weight loss. It is more severe than the more common morning sickness and is estimated to affect 0.5–2.0% of pregnant women.

Signs of a miscarriage include vaginal spotting, abdominal pain or cramping, and fluid or tissue passing from the vagina. Bleeding can be a symptom of miscarriage, but many women also have bleeding in early pregnancy and don't miscarry. Bleeding during pregnancy may be referred to as a threatened miscarriage. Of those who seek clinical treatment for bleeding during pregnancy, about half will miscarry. Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing.

Gestational diabetes is when a woman without diabetes develops high blood sugar levels during pregnancy.

The beginning of pregnancy may be detected either based on symptoms by the woman herself, or by using pregnancy tests. However, an important condition with serious health implications that is quite common is the denial of pregnancy by the pregnant woman. About one in 475 denials will last until around the 20th week of pregnancy. The proportion of cases of denial, persisting until delivery is about 1 in 2500. Conversely, some non-pregnant women have a very strong belief that they are pregnant along with some of the physical changes. This condition is known as a false pregnancy.

Miscarriage, also known as spontaneous abortion and pregnancy loss, is the natural death of an embryo or fetus before it is able to survive independently. Some use the cutoff of 20 weeks of gestation, after which fetal death is known as a stillbirth. The most common symptom of a miscarriage is vaginal bleeding with or without pain. Sadness, anxiety and guilt often occur afterwards. Tissue and clot-like material may leave the uterus and pass through and out of the vagina. When a woman keeps having miscarriages, infertility is present.

Risk factors for miscarriage include an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, thyroid problems, and drug or alcohol use. About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.

Prevention is occasionally possible with good prenatal care. Avoiding drugs, alcohol, infectious diseases, and radiation may prevent miscarriage. No specific treatment is usually needed during the first 7 to 14 days. Most miscarriages will complete without additional interventions. Occasionally the medication misoprostol or a procedure such as vacuum aspiration is used to remove the remaining tissue. Women who have a blood type of rhesus negative (Rh negative) may require Rho(D) immune globulin. Pain medication may be beneficial. Emotional support may help with negative emotions.

Miscarriage is the most common complication of early pregnancy. Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilisation is around 30% to 50%. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. About 5% of women have two miscarriages in a row. Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress.

Health effects of pesticides may be acute or delayed in those who are exposed. A 2007 systematic review found that "most studies on non-Hodgkin lymphoma and leukemia showed positive associations with pesticide exposure" and thus concluded that cosmetic use of pesticides should be decreased. Strong evidence also exists for other negative outcomes from pesticide exposure including neurological problems, birth defects, fetal death, and neurodevelopmental disorder.

According to The Stockholm Convention on Persistent Organic Pollutants, 9 of the 12 most dangerous and persistent chemicals are pesticides.

Confined placental mosaicism (CPM) represents a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the baby. CPM was first described by Kalousek and Dill in 1983. CPM is diagnosed when some trisomic cells are detected on chorionic villus sampling and only normal cells are found on a subsequent prenatal test, such as amniocentesis or fetal blood sampling. In theory, CPM is when the trisomic cells are found only in the placenta. CPM is detected in approximately 1-2% of ongoing pregnancies that are studied by chorionic villus sampling (CVS) at 10 to 12 weeks of pregnancy. Chorionic villus sampling is a prenatal procedure which involves a placental biopsy. Most commonly when CPM is found it represents a trisomic cell line in the placenta and a normal diploid chromosome complement in the baby. However, the fetus is involved in about 10% of cases.

LBW is either caused by preterm birth (that is, a low gestational age at birth, commonly defined as younger than 37 weeks of gestation) or the infant being small for gestational age (that is, a slow prenatal growth rate), or a combination of both.

In general, risk factors in the mother that may contribute to low birth weight include young ages, multiple pregnancies, previous LBW infants, poor nutrition, heart disease or hypertension, untreated coeliac disease, drug addiction, alcohol abuse, and insufficient prenatal care. Environmental risk factors include smoking, lead exposure, and other types of air pollutions.

The symptoms of organophosphate poisoning include muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis. Other symptoms include hypertension, and hypoglycemia.

Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur.

The effects of organophosphate poisoning on muscarinic receptors are recalled using the mnemonic SLUDGEM (salivation, lacrimation, urination, defecation, gastrointestinal motility, emesis, miosis) An additional mnemonic is MUDDLES: miosis, urination, diarrhea, diaphoresis, lacrimation, excitation, and salivation.

The onset and severity of symptoms, whether acute or chronic, depends upon the specific chemical, the route of exposure (skin, lungs, or GI tract), the dose, and the individuals ability to degrade the compound, which the PON1 enzyme level will affect.

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.

Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

Cholinergic syndrome occurs in acute poisonings with OP pesticides and is directly related to levels of AChE activity. Symptoms include miosis, sweating, lacrimation, gastrointestinal symptoms, respiratory difficulties, shortness of breath, slowed heart rate, cyanosis, vomiting, diarrhea, trouble sleeping, as well as other symptoms. Along with these central effects can be seen and finally seizures, convulsions, coma, respiratory failure. If the person survives the first day of poisoning personality changes can occur, aggressive events, psychotic episodes, disturbances and deficits in memory and attention, as well as other delayed effects. When death occurs, it is most commonly due to respiratory failure from the combination of central and peripheral effects, paralysis of respiratory muscles and depression of the brain respiratory center. For people afflicted with cholinergic syndrome, atropine sulfate combined with an oxime is used to combat the effects of the acute OP poisoning. Diazepam is sometimes also administered in combination with the atropine and oximes.

The intermediate syndrome (IMS) appears in the interval between the end of the cholinergic crisis and the onset of OPIDP. Symptoms associated with IMS manifest within 24–96 hours after exposure. The exact etiology, incidence, and risk factors associated with IMS are not clearly understood, but IMS is recognized as a disorder of neuromuscular junctions. IMS occurs when a person has a prolonged and severe inhibition of AChE and has been linked to specific OP pesticides such as methylparathion, dichlorvos, and parathion. Patients present with increasing weakness of facial, neck flexor and respiratory muscles.

OPIDP occurs in a small percentage of cases, roughly two weeks after exposure, where temporary paralysis occurs. This loss of function and ataxia of peripheral nerves and spinal cord is the phenomenon of OPIDP. Once the symptoms begin with shooting pains in both legs, the symptoms continue to worsen for 3–6 months. In the most severe cases quadriplegia has been observed. Treatment only affects sensory nerves, not motor neurons which may permanently lose function. The aging and phosphorylation of more than 70% of functional NTE in peripheral nerves is one of the processes involved in OPIDP. Standard treatments for OP poisoning are ineffective for OPIDP.

COPIND occurs without cholinergic symptoms and is not dependent on AChE inhibition. COPIND appears with a delay and is long lasting. Symptoms associated with COPIND include cognitive deficit, mood change, autonomic dysfunction, peripheral neuropathy, and extrapyramidal symptoms. The underlying mechanisms of COPIND have not been determined, but it is hypothesized that withdrawal of OP pesticides after chronic exposure or acute exposure could be a factor.

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.

Chronic poisoning usually presents with symptoms affecting multiple systems, but is associated with three main types of symptoms: gastrointestinal, neuromuscular, and neurological. Central nervous system and neuromuscular symptoms usually result from intense exposure, while gastrointestinal symptoms usually result from exposure over longer periods. Signs of chronic exposure include loss of short-term memory or concentration, depression, nausea, abdominal pain, loss of coordination, and numbness and tingling in the extremities. Fatigue, problems with sleep, headaches, stupor, slurred speech, and anemia are also found in chronic lead poisoning. A "lead hue" of the skin with pallor and/or lividity is another feature. A blue line along the gum with bluish black edging to the teeth, known as a Burton line, is another indication of chronic lead poisoning. Children with chronic poisoning may refuse to play or may have hyperkinetic or aggressive behavior disorders. Visual disturbance may present with gradually progressing blurred vision as a result of central scotoma, caused by toxic optic neuritis.