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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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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.
No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options: watchful waiting, medical management, and surgical treatment. With no treatment (watchful waiting), most miscarriages (65–80%) will pass naturally within two to six weeks. This treatment avoids the possible side effects and complications of medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage. Medical treatment usually consists of using misoprostol (a prostaglandin) to contract the uterus, expelling remaining tissue out of the cervix. This works within a few days in 95% of cases. Vacuum aspiration or sharp curettage can be used, though vacuum aspiration is lower-risk and more common.
In delayed or incomplete miscarriage, treatment depends on the amount of tissue remaining in the uterus. Treatment can include surgical removal of the tissue with vacuum aspiration or misoprostol. Some organizations recommend delaying sexual relations immediately after a miscarriage to prevent infection.
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.
If the likely cause of recurrent pregnancy loss can be determined treatment is to be directed accordingly. In pregnant women with a history of recurrent miscarriage, anticoagulants seem to increase the live birth rate among those with antiphospholipid syndrome and perhaps those with congenital thrombophilia but not in those with unexplained recurrent miscarriage. One study found that in many women with chronic endometritis, "fertility was restored after appropriate antibiotic treatment."
There are currently no treatments for women with unexplained recurrent pregnancy loss. The majority of patients are counseled to try to conceive again, and chances are about 60% that the next pregnancy is successful without treatment. However, each additional loss worsens the prognostic for a successful pregnancy and increases the psychological and physical risks to the mother. Aspirin has no effect in preventing recurrent miscarriage in women with unexplained recurrent pregnancy loss. Immunotherapy has not been found to help. There is currently one drug in development, NT100, which is in clinical trials for the treatment of unexplained recurrent miscarriage. The study investigates the role of NT100 in improving maternal-fetal tolerance for women with unexplained recurrent miscarriage
In certain chromosomal situations, while treatment may not be available, in vitro fertilization with preimplantation genetic diagnosis may be able to identify embryos with a reduced risk of another pregnancy loss which then would be transferred. However, in vitro fertilization does not improve maternal-fetal tolerance imbalances.
Close surveillance during pregnancy is generally recommended for pregnant patients with a history of recurrent pregnancy loss. Even with appropriate and correct treatment another pregnancy loss may occur as each pregnancy develops its own risks and problems.
Treatment may be delivery by caesarean section and abdominal hysterectomy if placenta accreta is diagnosed before birth. Oxytocin and antibiotics are used for post-surgical management. When there is partially separated placenta with focal accreta, best option is removal of placenta. If it is important to save the woman's uterus (for future pregnancies) then resection around the placenta may be successful. Conservative treatment can also be uterus sparing but may not be as successful and has a higher risk of complications.
Techniques include:
- Leaving the placenta in the uterus and curettage of uterus. Methotrexate has been used in this case.
- Intrauterine balloon catheterisation to compress blood vessels
- Embolisation of pelvic vessels
- Internal iliac artery ligation
- Bilateral uterine artery ligation
In cases where there is invasion of placental tissue and blood vessels into the bladder, it is treated in similar manner to abdominal pregnancy and manual placental removal is avoided. However, this may eventually need hysterectomy and/or partial cystectomy.
If the patient decides to proceed with a vaginal delivery, blood products for transfusion and an anesthesiologist are kept ready at delivery.
There is significant, and often unrecognized, psychological and psychiatric trauma for the mother – for many, miscarriage represents the loss of a future child, of motherhood, and engenders doubts regarding her ability to procreate.
"There is tremendous psychological impact of recurrent miscarriage. Psychological support in the form of frequent discussions and sympathetic counseling are crucial to the successful evaluation and treatment of the anxious couple. When no etiologic factor is identified, no treatment started at 60% to 80% fetal salvage rate still may be expected. Therefore, couples with unexplained recurrent miscarriage should be offered appropriate emotional support and reassurance."
Treatment depends on diagnosis and may include hormonal therapy, iv fluids, blood transfusion, and/or a dilation and curettage. Internal bleeding requires laparoscopy or abdominal surgery, in rare and extreme cases a hysterectomy is performed.
Miscarriage is the loss of a pregnancy prior to 20 weeks. In the UK miscarriage is defined as the loss of a pregnancy during the first 23 weeks.
True cervical pregnancies tend to abort; if, however, the pregnancy is located higher in the canal and the placenta finds support in the uterine cavity it can go past the first trimester. With the placenta being implanted abnormally extensive vaginal bleeding can be expected at time of delivery and placental removal. While early cervical pregnancies may abort spontaneously or can be managed with excision, D&C, suturing, electrocautery, and tamponading, by medication such as methotrexate, and/or by uterine artery embolization, a more advanced pregnancy may require a hysterectomy to control bleeding. The more advanced the pregnancy the higher the risk for a major bleeding necessitating a hysterectomy.
On a very rare occasion, a cervical pregnancy results in the birth of a live baby, typically the pregnancy is in the upper part of the cervical canal and manages to extend into the lower part of the uterine cavity.
A cervical pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as to not to endanger the intrauterine pregnancy.
Warfarin, heparin and LMWH do not seem to pass into breast milk, so these are not contraindicated in breastfeeding.
Severe acute bleeding, such as caused by ectopic pregnancy and post-partum hemorrhage, leads to hypovolemia (the depletion of blood from the circulation), progressing to shock. This is a medical emergency and requires hospital attendance and intravenous fluids, usually followed by blood transfusion. Once the circulating volume has been restored, investigations are performed to identify the source of bleeding and address it. Uncontrolled life-threatening bleeding may require uterine artery embolization (occlusion of the blood vessels supplying the uterus), laparotomy (surgical opening of the abdomen), occasionally leading to hysterectomy (removal of the uterus) as a last resort.
A possible complication from protracted vaginal blood loss is iron deficiency anemia, which can develop insidiously. Eliminating the cause will resolve the anemia, although some women require iron supplements or blood transfusions to improve the anemia.
Levels of hemoglobin are lower in the third trimesters. According to the United Nations (UN) estimates, approximately half of pregnant women suffer from anemia worldwide. Anemia prevalences during pregnancy differed from 18% in developed countries to 75% in South Asia.
Treatment varies due to the severity of the anaemia, and can be used by increasing iron containing foods, oral iron tablets or by the use of parenteral iron.
Protamine reverses the effect of unfractionated heparin, but only partially binds to and reverses LMWH. A dose of 1 mg protamine / 100 IU LMWH reverses 90% of its anti-IIa and 60% of anti-Xa activity, but the clinical effect of the residual anti-Xa activity is not known. Both anti-IIa and anti-Xa activity may return up to three hours after protamine reversal, possibly due to release of additional LMWH from depot tissues.
Gynecologic hemorrhage needs to be evaluated as soon as possible by a physician. The amount and duration of bleeding will dictate whether a bleeding event is an emergency event.
Continuing glucocorticoids at the lowest effective dose and/or cautious use of azathioprine may be preferred in some patients, but needs to be weighed against potential adverse effects of such medications.
Fertility may sometimes be restored by removal of adhesions, depending on the severity of the initial trauma and other individual patient factors. Operative hysteroscopy is used for visual inspection of the uterine cavity during adhesion dissection (adhesiolysis). However, hysteroscopy is yet to become a routine gynaecological procedure and only 15% of US gynecologists perform office hysteroscopy {Isaacson, 2002}. Adhesion dissection can be technically difficult and must be performed with care in order to not create new scars and further exacerbate the condition. In more severe cases, adjunctive measures such as laparoscopy are used in conjunction with hysteroscopy as a protective measure against uterine perforation. Microscissors are usually used to cut adhesions. Electrocauterization is not recommended.
As IUA frequently reform after surgery, techniques have been developed to prevent recurrence of adhesions. Methods to prevent adhesion reformation include the use of mechanical barriers (Foley catheter, saline-filled Cook Medical Balloon Uterine Stent, IUCD) and gel barriers (Seprafilm, Spraygel, autocrosslinked hyaluronic acid gel Hyalobarrier) to maintain opposing walls apart during healing {Tsapanos, 2002}; {Guida, 2004};{Abbott, 2004}, thereby preventing the reformation of adhesions. Antibiotic prophylaxis is necessary in the presence of mechanical barriers to reduce the risk of possible infections. A common pharmacological method for preventing reformation of adhesions is sequential hormonal therapy with estrogen followed by a progestin to stimulate endometrial growth and prevent opposing walls from fusing together {Roge, 1996}. However, there have been no randomized controlled trials (RCTs) comparing post-surgical adhesion reformation with and without hormonal treatment and the ideal dosing regimen or length of estrogen therapy is not known. The absence of prospective RCTs comparing treatment methods makes it difficult to recommend optimal treatment protocols. Furthermore, diagnostic severity and outcomes are assessed according to different criteria (e.g. menstrual pattern, adhesion reformation rate, conception rate, live birth rate). Clearly, more comparable studies are needed in which reproductive outcome can be analysed systematically.
Follow-up tests (HSG, hysteroscopy or SHG) are necessary to ensure that adhesions have not reformed. Further surgery may be necessary to restore a normal uterine cavity.
According to a recent study among 61 patients, the overall rate of adhesion recurrence was 27.9% and in severe cases this was 41.9%. Another study found that postoperative adhesions reoccur in close to 50% of severe AS and in 21.6% of moederate cases. Mild IUA, unlike moderate to severe synechiae, do not appear to reform.
In places lacking the necessary medical skill for dilation and extraction, or where preferred by practitioners, an abortion can be induced by first inducing labor and then inducing fetal demise if necessary. This is sometimes called "induced miscarriage". This procedure may be performed from 13 weeks gestation to the third trimester. Although it is very uncommon in the United States, more than 80% of induced abortions throughout the second trimester are labor induced abortions in Sweden and other nearby countries.
Only limited data are available comparing this method with dilation and extraction. Unlike D&E, labor induced abortions after 18 weeks may be complicated by the occurrence of brief fetal survival, which may be legally characterized as live birth. For this reason, labor induced abortion is legally risky in the U.S.
In pregnancy, changes in the levels of female sex hormones, such as estrogen, make a woman more likely to develop candidal vulvovaginitis. During pregnancy, the "Candida" fungus is more prevalent (common), and recurrent infection is also more likely. There is no clear evidence that treatment of asymptomatic candidal vulvovaginitis in pregnancy reduces the risk of preterm birth. Candidal vulvovaginitis in pregnancy should be treated with intravaginal clotrimazole or nystatin for at least 7 days.
Pregnancy does not have an adverse effect on the course of Behçet's disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçet's disease confers an increased risk of pregnancy complications, miscarriage and Cesarean section.
Medical abortions are those induced by abortifacient pharmaceuticals. Medical abortion became an alternative method of abortion with the availability of prostaglandin analogs in the 1970s and the antiprogestogen mifepristone (also known as RU-486) in the 1980s.
The most common early first-trimester medical abortion regimens use mifepristone in combination with a prostaglandin analog (misoprostol or gemeprost) up to 9 weeks gestational age, methotrexate in combination with a prostaglandin analog up to 7 weeks gestation, or a prostaglandin analog alone. Mifepristone–misoprostol combination regimens work faster and are more effective at later gestational ages than methotrexate–misoprostol combination regimens, and combination regimens are more effective than misoprostol alone. This regime is effective in the second trimester. Medical abortion regiments involving mifepristone followed by misoprostol in the cheek between 24 and 48 hours later are effective when performed before 63 days' gestation.
In very early abortions, up to 7 weeks gestation, medical abortion using a mifepristone–misoprostol combination regimen is considered to be more effective than surgical abortion (vacuum aspiration), especially when clinical practice does not include detailed inspection of aspirated tissue. Early medical abortion regimens using mifepristone, followed 24–48 hours later by buccal or vaginal misoprostol are 98% effective up to 9 weeks gestational age. If medical abortion fails, surgical abortion must be used to complete the procedure.
Early medical abortions account for the majority of abortions before 9 weeks gestation in Britain, France, Switzerland, and the Nordic countries. In the United States, the percentage of early medical abortions is far lower.
Medical abortion regimens using mifepristone in combination with a prostaglandin analog are the most common methods used for second-trimester abortions in Canada, most of Europe, China and India, in contrast to the United States where 96% of second-trimester abortions are performed surgically by dilation and evacuation.
In postmenopausal bleeding, guidelines from the United States consider transvaginal ultrasonography to be an appropriate first-line procedure to identify which women are at higher risk of endometrial cancer. A cut-off threshold of 3 mm or less of endometrial thickness should be used for in women with postmenopausal bleeding in the following cases:
- Not having used hormone replacement therapy for a year or more
- Usage of continuous hormone replacement therapy consisting of both an estrogen and a progestagen
A cut-off threshold of 5 mm or less should be used for women on sequential hormone replacement therapy consisting both of an estrogen and a progestagen.
It the endometrial thickness equals the cut-off threshold or is thinner, and the ultrasonography is otherwise reassuring, no further action need be taken. Further investigations should be carried out if symptoms recur.
If the ultrasonography is not reassuring, hysteroscopy and endometrial biopsy should be performed. The biopsy may be obtained either by curettage at the same time as inpatient or outpatient hysteroscopy, or by using an endometrium sampling device such as a pipelle which can practically be done directly after the ultrasonography.
Treatment is often started without confirmation of infection because of the serious complications that may result from delayed treatment. Treatment depends on the infectious agent and generally involves the use of antibiotic therapy. If there is no improvement within two to three days, the patient is typically advised to seek further medical attention. Hospitalization sometimes becomes necessary if there are other complications. Treating sexual partners for possible STIs can help in treatment and prevention.
For women with PID of mild to moderate severity, parenteral and oral therapies appear to be effective. It does not matter to their short- or long-term outcome whether antibiotics are administered to them as inpatients or outpatients. Typical regimens include cefoxitin or cefotetan plus doxycycline, and clindamycin plus gentamicin. An alternative parenteral regimen is ampicillin/sulbactam plus doxycycline. Erythromycin-based medications can also be used. Another alternative is to use a parenteral regimen with ceftriaxone or cefoxitin plus doxycycline. Clinical experience guides decisions regarding transition from parenteral to oral therapy, which usually can be initiated within 24–48 hours of clinical improvement.
A 2013 review concluded that there were no studies reporting on the link between intrauterine adhesions and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to surgical management (e.g. D&C), medical management or conservative management (that is, watchful waiting). There is an association between surgical intervention in the uterus and the development of intrauterine adhesions, and between intrauterine adhesions and pregnancy outcomes, but there is still no clear evidence of any method of prevention of adverse pregnancy outcomes.
In theory, the recently pregnant uterus is particularly soft under the influence of hormones and hence, easily injured. D&C (including dilation and curettage, dilation and evacuation/suction curettage and manual vacuum aspiration) is a blind, invasive procedure, making it difficult to avoid endometrial trauma. Medical alternatives to D&C for evacuation of retained placenta/products of conception exist including misoprostol and mifepristone. Studies show this less invasive and cheaper method to be an efficacious, safe and an acceptable alternative to surgical management for most women. It was suggested as early as in 1993 that the incidence of IUA might be lower following medical evacuation (e.g. Misoprostol) of the uterus, thus avoiding any intrauterine instrumentation. So far, one study supports this proposal, showing that women who were treated for missed miscarriage with misoprostol did not develop IUA, while 7.7% of those undergoing D&C did. The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging.
Alternatively, D&C could be performed under ultrasound guidance rather than as a blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury.
Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the recurrence of AS, as the longer the period after fetal death following D&C, the more likely adhesions may be to occur. Therefore, immediate evacuation following fetal death may prevent IUA.
The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative that could theoretically improve future pregnancy outcomes, although it could be less effective if tissue is abundant. Also, hysteroscopy is not a widely or routinely used technique and requires expertise.
There is no data to indicate that suction D&C is less likely than sharp curette to result in Asherman's. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration.
Patients with a unicornuate uterus may need special attention during pregnancy as pregnancy loss, fetal demise, premature birth, and malpresentation are more common. It is unproven that cerclage procedures are helpful.
A pregnancy in a rudimentary horn cannot be saved and needs to be removed with the horn to prevent a potentially fatal rupture of the horn and uterus.
Although it is unclear whether interventions before conception or early in pregnancy such as resection of the rudimentary horn and prophylactic cervical cerclage decidedly improve obstetrical outcomes, current practice suggests that such interventions may be helpful.