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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.
Nutrition during pregnancy is important to ensure healthy growth of the fetus. Nutrition during pregnancy is different from the non-pregnant state. There are increased energy requirements and specific micronutrient requirements. Women benefit from education to encourage a balanced energy and protein intake during pregnancy. Some women may need professional medical advice if their diet is affected by medical conditions, food allergies, or specific religious/ ethical beliefs.
Adequate periconceptional (time before and right after conception) folic acid (also called folate or Vitamin B) intake has been shown to decrease the risk of fetal neural tube defects, such as spina bifida. The neural tube develops during the first 28 days of pregnancy, a urine pregnancy test is not usually positive until 14 days post-conception, explaining the necessity to guarantee adequate folate intake before conception. Folate is abundant in green leafy vegetables, legumes, and citrus. In the United States and Canada, most wheat products (flour, noodles) are fortified with folic acid.
DHA omega-3 is a major structural fatty acid in the brain and retina, and is naturally found in breast milk. It is important for the woman to consume adequate amounts of DHA during pregnancy and while nursing to support her well-being and the health of her infant. Developing infants cannot produce DHA efficiently, and must receive this vital nutrient from the woman through the placenta during pregnancy and in breast milk after birth.
Several micronutrients are important for the health of the developing fetus, especially in areas of the world where insufficient nutrition is common. Women living in low and middle income countries are suggested to take multiple micronutrient supplements containing iron and folic acid. These supplements have been shown to improve birth outcomes in developing countries, but do not have an effect on perinatal mortality. Adequate intake of folic acid, and iron is often recommended. In developed areas, such as Western Europe and the United States, certain nutrients such as Vitamin D and calcium, required for bone development, may also require supplementation. Vitamin E supplementation has not been shown to improve birth outcomes. Zinc supplementation has been associated with a decrease in preterm birth, but it is unclear whether it is causative. Daily iron supplementation reduces the risk of maternal anemia. Studies of routine daily iron supplementation for pregnant women found improvement in blood iron levels, without a clear clinical benefit. The nutritional needs for women carrying twins or triplets. are higher than those of women carrying one baby.
Women are counseled to avoid certain foods, because of the possibility of contamination with bacteria or parasites that can cause illness. Careful washing of fruits and raw vegetables may remove these pathogens, as may thoroughly cooking leftovers, meat, or processed meat. Unpasteurized dairy and deli meats may contain "Listeria," which can cause neonatal meningitis, stillbirth and miscarriage. Pregnant women are also more prone to "Salmonella" infections, can be in eggs and poultry, which should be thoroughly cooked. Cat feces and undercooked meats may contain the parasite Toxoplasma gondii and can cause toxoplasmosis. Practicing good hygiene in the kitchen can reduce these risks.
Women are also counseled to eat seafood in moderation and to eliminate seafood known to be high in mercury because of the risk of birth defects. Pregnant women are counseled to consume caffeine in moderation, because large amounts of caffeine are associated with miscarriage. However, the relationship between caffeine, birthweight, and preterm birth is unclear.
Early treatment of an ectopic pregnancy with methotrexate is a viable alternative to surgical treatment which was developed in the 1980s. If administered early in the pregnancy, methotrexate terminates the growth of the developing embryo; this may cause an abortion, or the developing embryo may then be either resorbed by the woman's body or pass with a menstrual period. Contraindications include liver, kidney, or blood disease, as well as an ectopic embryonic mass > 3.5 cm.
Also, it may lead to the inadvertent termination of an undetected intrauterine pregnancy, or severe abnormality in any surviving pregnancy. Therefore, it is recommended that methotrexate should only be administered when hCG has been serially monitored with a rise less than 35% over 48 hours, which practically excludes a viable intrauterine pregnancy.
If bleeding has already occurred, surgical intervention may be necessary. However, whether to pursue surgical intervention is an often difficult decision in a stable patient with minimal evidence of blood clot on ultrasound.
Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected Fallopian and remove only the pregnancy (salpingostomy) or remove the affected tube with the pregnancy (salpingectomy). The first successful surgery for an ectopic pregnancy was performed by Robert Lawson Tait in 1883. It is estimated that an acceptable rate of PULs that eventually undergo surgery is between 0.5 and 11%.
Autotransfusion of a woman's own blood as drained during surgery may be useful in those who have a lot of bleeding into their abdomen.
Published reports that a re-implanted embryo survived to birth were debunked as false.
Ideally the management of abdominal pregnancy should be done by a team that has medical personnel from multiple specialties. Potential treatments consist of surgery with termination of the pregnancy (removal of the fetus) via laparoscopy or laparotomy, use of methotrexate, embolization, and combinations of these. Sapuri and Klufio indicate that conservative treatment is also possible if the following criteria are met: 1. there are no major congenital malformations; 2. the fetus is alive; 3. there is continuous hospitalization in a well-equipped and well-staffed maternity unit which has immediate blood transfusion facilities; 4. there is careful monitoring of maternal and fetal well being; and 5. placental implantation is in the lower abdomen away from the liver and spleen. The choice is largely dictated by the clinical situation. Generally, treatment is indicated when the diagnosis is made; however, the situation of the advanced abdominal pregnancy is more complicated.
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.
This procedure involves the tearing of the dividing membrane between fetuses such that the amniotic fluid of both twins mixes under the assumption that pressure is different in either amniotic sac and that its equilibration will ameliorate progression of the disease. It has not been proven that pressures are different in either amniotic sac. Use of this procedure can preclude use of other procedures as well as make difficult the monitoring of disease progression. In addition, tearing the dividing membrane has contributed to cord entanglement and demise of fetuses through physical complications.
This procedure involves removal of amniotic fluid periodically throughout the pregnancy under the assumption that the extra fluid in the recipient twin can cause preterm labor, perinatal mortality, or tissue damage. In the case that the fluid does not reaccumulate, the reduction of amniotic fluid stabilizes the pregnancy. Otherwise the treatment is repeated as necessary. There is no standard procedure for how much fluid is removed each time. There is a danger that if too much fluid is removed, the recipient twin could die. This procedure is associated with a 66% survival rate of at least one fetus, with a 15% risk of cerebral palsy and average delivery occurring at 29 weeks gestation.
Advanced abdominal pregnancy refers to situations where the pregnancy continues past 20 weeks of gestation (versus early abdominal pregnancy < 20 weeks). In those situations, live births have been reported in academic journals and also in the lay press where the babies are not uncommonly referred to as 'Miracle babies'. A patient may carry a dead fetus but will not go into labor. Over time, the fetus calcifies and becomes a lithopedion.
It is generally recommended to perform a laparotomy when the diagnosis of an abdominal pregnancy is made. However, if the baby is alive and medical support systems are in place, careful watching could be considered to bring the baby to viability. Women with an abdominal pregnancy will not go into labor. Delivery in a case of an advanced abdominal pregnancy will have to be via laparotomy. The survival of the baby is reduced and high perinatal mortality rates between 40–95% have been reported.
Babies of abdominal pregnancies are prone to birth defects due to compression in the absence of the uterine wall and the often reduced amount of amniotic fluid surrounding the unborn baby. The rate of malformations and deformations is estimated to be about 21%; typical deformations are facial and cranial asymmetries and joint abnormalities and the most common malformations are limb defects and central nervous malformations.
Once the baby has been delivered placental management becomes an issue. In normal deliveries the contraction of uterus provides a powerful mechanism to control blood loss, however, in an abdominal pregnancy the placenta is located over tissue that cannot contract and attempts of its removal may lead to life-threatening blood loss. Thus blood transfusion is frequent in the management of patients with this kind of pregnancy, with others even using tranexamic acid and recombinant factor VIIa, which both minimize blood loss.
Generally, unless the placenta can be easily tied off or removed, it may be preferable to leave it in place and allow for a natural regression. This process may take several months and can be monitored by clinical examination, checking human chorionic gonadotropin levels and by ultrasound scanning (in particular using doppler ultrasonography. Use of methotrexate to accelerate placental regression is controversial as the large amount of necrotic tissue is a potential site for infection, mifepristone has also be used to promote placental regression. Placental vessels have also been blocked by angiographic embolization. Complications of leaving the placenta can include residual bleeding, infection, bowel obstruction, pre-eclampsia (which may all necessitate further surgery) and failure to breast feed due to placental hormones.
Outcome with abdominal pregnancy can be good for the baby and mother, Lampe described an abdominal pregnancy baby and her mother who were well more than 22 years after surgery.
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).
A septum can be resected with surgery. Hysteroscopic removal of a uterine septum is generally the preferred method, as the intervention is relatively minor and safe in experienced hands. A follow-up imaging study should demonstrate the removal of the septum.
Tactile cold scissor metroplasty was described as a back technique for hysteroscopic challenges that interfere with proper visualization or uterine distention
It is not considered necessary to remove a septum that has not caused problems, especially in women who are not considering pregnancy. There is controversy over whether a septum should be removed prophylactically to reduce the risk of pregnancy loss prior to a pregnancy or infertility treatment.
A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), metoclopramide, and phenothiazines (such as promethazine). With respect to effectiveness it is unknown if one is superior to another. In the United States and Canada, the doxylamine-pyridoxine combination (as Diclegis in US and Diclectin in Canada) is the only approved pregnancy category "A" prescription treatment for nausea and vomiting of pregnancy.
Ondansetron may be beneficial, but there are some concerns regarding an association with cleft palate, and there is little high quality data. Metoclopramide is also used and relatively well tolerated. Evidence for the use of corticosteroids is weak.
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.
Psychoactive drugs are frequently tried on those with FASD as many FASD symptoms are mistaken for or overlap with other disorders, most notably ADHD.
The data presented is for comparative and illustrative purposes only, and may have been superseded by updated data.
Some studies support the use of ginger, but overall the evidence is limited and inconsistent. Safety concerns have been raised regarding its anticoagulant properties.
The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does "not" include any risks conferred by pharmaceutical agents or their metabolites in breast milk.
Every drug has specific information listed in its product literature. The British National Formulary used to provide a table of drugs to be avoided or used with caution in pregnancy, and did so using a limited number of key phrases, but now Appendix 4 (which was the Pregnancy table) has been removed. Appendix 4 is now titled "Intravenous Additives". However, information that was previously available in the former Appendix 4 (pregnancy) and Appendix 5 (breast feeding) is now available in the individual drug monographs.
As a chromosomal condition, there is no cure for Turner syndrome. However, much can be done to minimize the symptoms. For example:
- Growth hormone, either alone or with a low dose of androgen, will increase growth and probably final adult height. Growth hormone is approved by the U.S. Food and Drug Administration for treatment of Turner syndrome and is covered by many insurance plans. There is evidence that this is effective, even in toddlers.
- Estrogen replacement therapy such as the birth control pill, has been used since the condition was described in 1938 to promote development of secondary sexual characteristics. Estrogens are crucial for maintaining good bone integrity, cardiovascular health and tissue health. Women with Turner Syndrome who do not have spontaneous puberty and who are not treated with estrogen are at high risk for osteoporosis and heart conditions.
- Modern reproductive technologies have also been used to help women with Turner syndrome become pregnant if they desire. For example, a donor egg can be used to create an embryo, which is carried by the Turner syndrome woman.
- Uterine maturity is positively associated with years of estrogen use, history of spontaneous menarche, and negatively associated with the lack of current hormone replacement therapy.
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.
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.
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.
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
There is no ‘standard treatment’ for people with CFND due to the large variations in phenotypic expression. Each patient needs to be assessed and treated based on their specific presentation in order to restore the aesthetic and functional balance.
Surgical corrections for the main symptoms;
- Craniosynostosis correction: The preferred age for this procedure is between 6–9 months of age. Performing this surgery at such an early age can limit the further development of facial asymmetry, if the asymmetry is caused by the craniosynostosis, and prevents prolonged elevated intracranial pressure (ICP). However, the data for the exact risk of an elevated intracranial pressure for patients with CFND is lacking in the published literature. The surgery involves a frontal bone advancement in combination with remodellation of the supraorbital rim.
- Orbital hypertelorism: It is preferred to wait with this treatment until the age of 5–8 years old, after permanent dentition. The procedures that can be performed are the facial bipartition and the box osteotomy. Facial bipartition is the more preferable choice as there are less additional corrections needed, as well as providing a more stable long-term result after treatment. After the correction of the orbitas, the medial corners of the eyes are put more into a horizontal line.
- Nasal deformity correction: The correction of the broad nasal base is simultaneously done with the orbital hypertelorism repair. This is for good alignment of the eyes with the nose for the best aesthetic result. A bifid nose tip will only be treated at the age of 18, when the patient's skeleton has fully matured.
The genetic variation is irreversible, however, individuals who want to look more masculine can take testosterone. Treating adolescents with implants of controlled release testosterone has shown good results when appropriately monitored. Hormone therapy is also useful in preventing the onset of osteoporosis.
Often individuals that have noticeable breast tissue or hypogonadism experience depression and/or social anxiety because they are outside of social norms. An academic term for this is psychosocial morbidity. At least one study indicates that planned and timed support should be provided for young men with Klinefelter syndrome to ameliorate current poor psychosocial outcomes. The surgical removal of the breasts may be considered for both the psychological reasons and to reduce the risk of breast cancer.
The use of behavioral therapy can mitigate any language disorders, difficulties at school and socialization. An approach by occupational therapy is useful in children, especially those who have dyspraxia.
Because XLI is caused by a gene mutation or deletion, there is no "cure." One of the aims of treatment is to reduce scaling by removing the excess, flaky scales, and keep the skin hydrated. This can be achieved using a variety of topical creams.
- Keratolytic agents such as Ammonium lactate (Lac-Hydrin) are used to facilitate the release of retained corneocytes.
- Topical isotretinoin
- The topical receptor-selective retinoid tazarotene
Research is ongoing with regard to the use of gene therapy to treat XLI.