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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.
Several characteristic craniofacial abnormalities are often visible in individuals with FAS. The presence of FAS facial features indicates brain damage, although brain damage may also exist in their absence. FAS facial features (and most other visible, but non-diagnostic, deformities) are believed to be caused mainly during the 10th and 20th week of gestation.
Refinements in diagnostic criteria since 1975 have yielded three distinctive and diagnostically significant facial features known to result from prenatal alcohol exposure and distinguishes FAS from other disorders with partially overlapping characteristics. The three FAS facial features are:
- A smooth philtrum: The divot or groove between the nose and upper lip flattens with increased prenatal alcohol exposure.
- Thin vermilion: The upper lip thins with increased prenatal alcohol exposure.
- Small palpebral fissures: Eye width decreases with increased prenatal alcohol exposure.
Measurement of FAS facial features uses criteria developed by the University of Washington. The lip and philtrum are measured by a trained physician with the Lip-Philtrum Guide, a five-point Likert Scale with representative photographs of lip and philtrum combinations ranging from normal (ranked 1) to severe (ranked 5). Palpebral fissure length (PFL) is measured in millimeters with either calipers or a clear ruler and then compared to a PFL growth chart, also developed by the University of Washington.
Ranking FAS facial features is complicated because the three separate facial features can be affected independently by prenatal alcohol. A summary of the criteria follows:
- Severe: All three facial features ranked independently as severe (lip ranked at 4 or 5, philtrum ranked at 4 or 5, and PFL two or more standard deviations below average).
- Moderate: Two facial features ranked as severe and one feature ranked as moderate (lip "or" philtrum ranked at 3, "or" PFL between one and two standard deviations below average).
- Mild: A mild ranking of FAS facial features covers a broad range of facial feature combinations:
- Two facial features ranked severe and one ranked within normal limits,
- One facial feature ranked severe and two ranked moderate, or
- One facial feature ranked severe, one ranked moderate and one ranked within normal limits.
- None: All three facial features ranked within normal limits.
Alcohol in pregnancy is the use of alcohol (also known formally as ethanol) during gestation. This also includes the time period between conception and awareness of the pregnancy. Alcohol use not only can result in Fetal Alcohol Spectrum Disorder (FASD), but it can result in one or many other disorders and conditions. Not all women who consume alcohol during pregnancy will have a baby with all of the features and characteristics of FASP. Alcohol use during pregnancy also can cause spontaneous abortion, stillbirth, low birthweight, and prematurity. Not all infants exposed to alcohol in utero will have defects related to the alcohol consumption. Alcohol use during pregnancy can also result in the inability to care for an infant after the birth if the drinking continues. The use of alcohol during pregnancy is associated with domestic violence and potential harm to the infant.
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.
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.
Different body systems in the infant grow, mature and develop at specific times during gestation. The consumption of alcohol during one or more of these developmental stages may only result in one or few conditions.
From conception and to the third week, the most susceptible systems and organs are the brain, spinal cord, and heart. Though these body systems complete their development later in the pregnancy, the effects of alcohol consumption early in the pregnancy can result in defects to these systems and organs.
During the fourth week of gestation, the limbs are being formed and it is at this point that alcohol can effect the development of arms, legs, fingers and toes. The eyes and ears also form during the fourth week and are more susceptible to the effects of alcohol.
By the sixth week of gestation, the teeth and palate are forming and alcohol consumption at this time will affect these structures.
By the 20th week of gestation the formation of organs and organ systems is well-developed. The infant is still susceptible to the damaging effects of alcohol.
The baby’s brain, body, and organs are developing throughout pregnancy and can be affected by exposure to alcohol at any time. Because every pregnancy is different, drinking alcohol may hurt one baby more than another. A child that has been affected by alcohol before birth may be appear 'normal' at birth. Intellectual disabilities may not appear until the child begins school.
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.
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).
Fetal trimethadione syndrome is characterized by the following major symptoms as a result of the teratogenic characteristics of trimethadione.
- Cranial and facial abnormalities which include; microcephaly, midfacial flattening, V-shaped eyebrows and a short nose
- Cardiovascular abnormalities
- Absent kidney and ureter
- Meningocele, a birth defect of the spine
- Omphalocele, a birth defect where portions of the abdominal contents project into the umbilical cord
- A in mental and physical development
Several terms are used to describe congenital abnormalities. (Some of these are also used to describe noncongenital conditions, and more than one term may apply in an individual condition.)
Much of the language used for describing congenital conditions predates genomic mapping, and structural conditions are often considered separately from other congenital conditions. It is now known that many metabolic conditions may have subtle structural expression, and structural conditions often have genetic links. Still, congenital conditions are often classified in a structural basis, organized when possible by primary organ system affected.
Fetal trimethadione syndrome (also known as paramethadione syndrome, German syndrome, tridione syndrome, among others) is a set of birth defects caused by the administration of the anticonvulsants trimethadione (also known as Tridione) or paramethadione to epileptic mothers during pregnancy.
Fetal trimethadione syndrome is classified as a rare disease by the National Institute of Health's Office of Rare Diseases, meaning it affects less than 200,000 individuals in the United States.
The fetal loss rate while using trimethadione has been reported to be as high as 87%.
Meronanencephaly is a rare form of anencephaly characterized by malformed cranial bones, a median cranial defect, and a cranial protrusion called area cerebrovasculosa. Area cerebrovasculosa is a section of abnormal, spongy, vascular tissue admixed with glial tissue ranging from simply a membrane to a large mass of connective tissue, hemorrhagic vascular channels, glial nodules, and disorganized choroid plexuses.
The most common type of anencephaly, where the brain has entirely failed to form, except for the brain stem. Infants rarely survive more than one day after birth with holoanencephaly.
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.
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.
Affected newborns generally have striking neurological defects and seizures. Severely impaired development is common, but disturbances in motor functions may not appear until later in life.
Infants with microcephaly are born with either a normal or reduced head size. Subsequently, the head fails to grow, while the face continues to develop at a normal rate, producing a child with a small head and a receding forehead, and a loose, often wrinkled scalp. As the child grows older, the smallness of the skull becomes more obvious, although the entire body also is often underweight and dwarfed. Development of motor functions and speech may be delayed. Hyperactivity and intellectual disability are common occurrences, although the degree of each varies. Convulsions may also occur. Motor ability varies, ranging from in some to spastic quadriplegia in others.
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.
Microlissencephaly is microcephaly combined with lissencephaly (smooth brain surface due to absent sulci and gyri). Most cases of microlissencephaly are described in consanguineous families suggesting an autosomal recessive inheritance.
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.
Common signs of Say–Meyer syndrome are trigonocephaly as well as head and neck symptoms. The head and neck symptoms come in the form of craniosynostosis affecting the metopic suture (the dense connective tissue structure that divides the two halves of the skull in children which usually fuse together by the age of six). Symptoms of Say–Meyer syndrome other than developmental delay and short stature include
- Intellectual disability.
- Low-set ears/posteriorly rotated ears
- Intellectual deficit as well as learning disability
- Intrauterine growth retardation (poor growth of a baby while it is in the mother's womb)
- Posterior fontanel
- Premature synostosis of the lambdoid suture (the fusion of the bones to the joint is premature)
- Narrow forehead
- Trigonocephaly (a frontal bone anomaly that is characterized by a premature fusion of the bones which gives the forehead a triangular shape)
- Hypotelorism or hypertelorism (reduced or increased width between the eyes)
- Craniosynostosis (when one or more seam-like junctions between two bones fuses by turning into bone. This changes the growth pattern of the skull)
- Low birth weight and height
The affected patients sometimes show a highly arched palate, clinodactyly (a defect in which toes or fingers are positioned abnormally) and ventricular septal defect (a heart defect that allows blood to pass directly from left to the right ventricle which is caused by an opening in the septum). Overall, Say–Meyer syndrome impairs growth, motor function, and mental state.
Some syndromes that frequently include ACC are Aicardi syndrome, Andermann syndrome, Shapiro syndrome, acrocallosal syndrome, septo-optic dysplasia (optic nerve hypoplasia), Mowat–Wilson syndrome, John Sayden syndrome, Menkes syndrome, and L1CAM Syndrome. Some conditions that are sometimes associated with ACC include maternal nutritional deficiencies or infections, metabolic disorders, fetal alcohol syndrome, craniofacial abnormalities, and other oral and maxillofacial pathologies.
Callosal disorders can be diagnosed through brain imaging studies or during autopsy. They may be diagnosed through an MRI, CT scan, Sonography, prenatal ultrasound, or prenatal MRI.
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