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Obstetric ultrasonography can detect fetal abnormalities, detect multiple pregnancies, and improve gestational dating at 24 weeks. The resultant estimated gestational age and due date of the fetus are slightly more accurate than methods based on last menstrual period. Ultrasound is used to measure the nuchal fold in order to screen for Downs syndrome.
Pregnancy detection can be accomplished using one or more various pregnancy tests, which detect hormones generated by the newly formed placenta, serving as biomarkers of pregnancy. Blood and urine tests can detect pregnancy 12 days after implantation. Blood pregnancy tests are more sensitive than urine tests (giving fewer false negatives). Home pregnancy tests are urine tests, and normally detect a pregnancy 12 to 15 days after fertilization. A quantitative blood test can determine approximately the date the embryo was conceived because HCG doubles every 36 to 48 hours. A single test of progesterone levels can also help determine how likely a fetus will survive in those with a threatened miscarriage (bleeding in early pregnancy).
Amniocentesis and chorionic villus sampling are procedures conducted to assess the fetus. A sample of amniotic fluid is obtained by the insertion of a needle through the abdomen and into the uterus. Chorionic villus sampling is a similar procedure with a sample of tissue removed rather than fluid. These procedures are not associated with pregnancy loss during the second trimester but they are associated with miscarriages and birth defects in the first trimester. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%).
A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization:
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.
Prenatal cocaine exposure is associated with, for example, premature birth, birth defects and attention deficit disorder.
A recent study on cocaine in Prenatal Drug Exposure(2008) explores how the differences between children who were exposed to drugs prenatal and those with non-drug prenatal exposure differ at the age of five.
Many of the side effects from the children who were exposed to the recreational drug being cocaine had side effects including the following; lack in school readiness, slower impulse control and lack in visual attention.
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.
Fetal alcohol spectrum disorders (FASD) is a term that constitutes the set of conditions that can occur in a person whose mother drank alcohol during the course of pregnancy. These effects can include physical and cognitive problems. FASD patient usually has a combination of these problems. Extent of effect depends on exposure frequency, dose and rate of ethanol elimination from amniotic fluid. FAS disrupts normal development of the fetus, which may cause certain developmental stages to be delayed, skipped, or immaturely developed. Since alcohol elimination is slow in a fetus than in an adult and the fact that they do not have a developed liver to metabolize the alcohol, alcohol levels tend to remain high and stay in the fetus longer. Birth defects associated with prenatal exposure to alcohol can occur in the first three to eight weeks of pregnancy before a woman even knows that she is pregnant.
The data presented is for comparative and illustrative purposes only, and may have been superseded by updated data.
For many adopted or adults and children in foster care, records or other reliable sources may not be available for review. Reporting alcohol use during pregnancy can also be stigmatizing to birth mothers, especially if alcohol use is ongoing. In these cases, all diagnostic systems use an unknown prenatal alcohol exposure designation. A diagnosis of FAS is still possible with an unknown exposure level if other key features of FASD are present at clinical levels.
While most pregnant women experience some itch from time to time, itching on the palms and soles without a visible rash, or persisting severe or extensive itch symptoms should be reported to the midwife or obstetrican.
To obtain a diagnosis of ICP, there are two LFT (liver function tests) and Serum bile acid test. The liver function tests (LFTs) is a simple blood test, the results of which should be available by the next day. If the ALT level is elevated, this, plus pruritus of palms and soles, could be considered as potentially diagnostic of ICP but only with elevated bile acid levels (however LFTs are not always elevated in ICP patients). The serum bile acid blood test for ICP is a quantitative measurement of bile salts. The results of this test often take longer to return, but the test is more specific for ICP.
Other problems with the liver that occur in pregnancy should be considered by the treating clinician. These include preeclampsia, the HELLP syndrome, and acute fatty liver of pregnancy. Furthermore, other causes of hepatitis, like hepatitis viruses, cancer and certain medications, should also be considered.
Confirmed absence of exposure would apply to planned pregnancies in which no alcohol was used or pregnancies of women who do not use alcohol or report no use during the pregnancy. This designation is relatively rare, as most people presenting for an FASD evaluation are at least "suspected" to have had a prenatal alcohol exposure due to presence of other key features of FASD.
The Centers for Disease Control and Prevention (CDC) recommends HIV testing for all pregnant women as a part of routine prenatal care. The test is usually performed in the first trimester of pregnancy with other routine laboratory tests. HIV testing is recommended because HIV-infected women who do not receive testing are more likely to transmit the infection to their children.
HIV testing may be offered to pregnant women on an "opt-in" or an "opt-out" basis. In the "opt-in" model, women are counseled on HIV testing and elect to receive the test by signing a consent form. In the "opt-out" model, the HIV test is automatically performed with other routine prenatal tests. If a woman does not want to be tested for HIV, she must specifically refuse the test and sign a form declining testing. The CDC recommends "opt-out" testing for all pregnant women because it improves disease detection and treatment and helps reduce transmission to children.
If a woman chooses to decline testing, she will not receive the test. However, she will continue to receive HIV counseling throughout the pregnancy so that she may be as informed as possible about the disease and its impact. She will be offered HIV testing at all stages of her pregnancy in case she changes her mind.
HIV testing begins with a screening test. The most common screening test is the rapid HIV antibody test which tests for HIV antibodies in blood, urine, or oral fluid. HIV antibodies are only produced if an individual is infected with the disease. Therefore, presence of the antibodies is indicative of an HIV infection. Sometimes, however, a person may be infected with HIV but the body has not produced enough antibodies to be detected by the test. If a woman has risk factors for HIV infection but tests negative on the initial screening test, she should be retested in 3 months to confirm that she does not have HIV. Another screening test that is more specific is the HIV antigen/antibody test. This is a newer blood test that can detect HIV infection quicker than the antibody test because it detects both virus particles and antibodies in the blood.
Any woman who has a positive HIV screening test must receive follow-up testing to confirm the diagnosis. The follow-up test can differentiate HIV-1 from HIV-2 and is a more specific antibody test. It may also detect the virus directly in the bloodstream.
There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling. Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.
- Free Cell DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.
- Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.
- CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.
Upon diagnosis, many providers will prescribe Ursodeoxycholic Acid. While there is no cure for ICP, and no way to guarantee a successful outcome, studies have shown a slightly better fetal and maternal outcome from administration of Ursodeoxycholic Acid, whereas Cholestyramine appears to only relieve itching.
If additional blood tests to check clotting function identify a problem, giving Vitamin K may help avoid the risk of hemorrhage at delivery.
Delivery by 35–37 completed weeks may be important to fetal outcome as a recent study demonstrated that in severe ICP (defined as bile acids greater than 40 umol/L) the risk of stillbirth was 1.5% compared to 0.5% of uncomplicated pregnancies. This risk rose further if bile acids doubled,
During any pregnancy a small amount of the baby's blood can enter the mother's circulation. If the mother is Rh negative and the baby is Rh positive, the mother produces antibodies (including IgG) against the rhesus D antigen on her baby's red blood cells. During this and subsequent pregnancies the IgG is able to pass through the placenta into the fetus and if the level of it is sufficient, it will cause destruction of rhesus D positive fetal red blood cells leading to the development of Rh disease. It may thus be regarded as insufficient immune tolerance in pregnancy. Generally rhesus disease becomes worse with each additional rhesus incompatible pregnancy.
The main and most frequent sensitizing event is child birth (about 86% of sensitized cases), but fetal blood may pass into the maternal circulation earlier during the pregnancy (about 14% of sensitized cases). Sensitizing events during pregnancy include c-section, miscarriage, therapeutic abortion, amniocentesis, ectopic pregnancy, abdominal trauma and external cephalic version. However, in many cases there was no apparent sensitizing event.
The incidence of Rh disease in a population depends on the proportion that are rhesus negative. Many non-Caucasian people have a very low proportion who are rhesus negative, so the incidence of Rh disease is very low in these populations. In Caucasian populations about 1 in 10 of all pregnancies are of a rhesus negative woman with a rhesus positive baby. It is very rare for the first rhesus positive baby of a rhesus negative woman to be affected by Rh disease. The first pregnancy with a rhesus positive baby is significant for a rhesus negative woman because she can be sensitized to the Rh positive antigen. In Caucasian populations about 13% of rhesus negative mothers are sensitized by their first pregnancy with a rhesus positive baby. Without modern prevention and treatment, about 5% of the second rhesus positive infants of rhesus negative women would result in stillbirths or extremely sick babies. Many babies who managed to survive would be severely ill. Even higher disease rates would occur in the third and subsequent rhesus positive infants of rhesus negative women. By using anti-RhD immunoglobulin (Rho(D) immune globulin) the incidence is massively reduced.
Rh disease sensitization is about 10 times more likely to occur if the fetus is ABO compatible with the mother than if the mother and fetus are ABO incompatible.
Blood testing for the mother is called an Indirect Coombs Test (ICT) or an Indirect Agglutination Test (IAT). This test tells whether there are antibodies in the maternal plasma. If positive, the antibody is identified and given a titer. Critical titers are associated with significant risk of fetal anemia and hydrops. Titers of 1:8 or higher is considered critical for Kell. Titers of 1:16 or higher are considered critical for all other antibodies. After critical titer is reached, care is based on MCA scans. If antibodies are low and have a sudden jump later in pregnancy, an MCA scan is warranted. If the titer undergoes a 4 fold increase, it should be considered significant regardless of if the critical value has been reached. It should be noted that maternal titers are not useful in predicting fetal anemia after the first affected gestation and should not be used for the basis of care. Titers are tested monthly until 24 weeks, after which they are done every 2 weeks.
"In only 2 situations are patients not monitored identically to patients who are Rh sensitized. The first is that of alloimmunization to the c, E, or, C antigens. Some concern exists that hemolysis may occur in these patients with a lower than 1:16 titer. Thus, if the initial titer is 1:4 and stable but increases at 26 weeks' gestation to 1:8, assessment with MCA Doppler velocity at that point is reasonable. However, if the patient presents in the first trimester with a 1:8 titer that remains stable at 1:8 throughout the second trimester, continued serial antibody titers are appropriate.
The second situation in which patients should not be treated identically to patients who are Rh D sensitized is that of Kell isoimmunization because several cases of severe fetal hemolysis with anti-Kell antibodies have occurred in the setting of low titers."
In the case of a positive ICT, the woman must carry a medical alert card or bracelet for life because of the risk of a transfusion reaction.
Most Rh disease can be prevented by treating the mother during pregnancy or promptly (within 72 hours) after childbirth. The mother has an intramuscular injection of anti-Rh antibodies (Rho(D) immune globulin). This is done so that the fetal rhesus D positive erythrocytes are destroyed before the immune system of the mother can discover them and become sensitized. This is passive immunity and the effect of the immunity will wear off after about 4 to 6 weeks (or longer depending on injected dose) as the anti-Rh antibodies gradually decline to zero in the maternal blood.
It is part of modern antenatal care to give all rhesus D negative pregnant women an anti-RhD IgG immunoglobulin injection at about 28 weeks gestation (with or without a booster at 34 weeks gestation). This reduces the effect of the vast majority of sensitizing events which mostly occur after 28 weeks gestation. Giving Anti-D to all Rhesus negative pregnant women can mean giving it to mothers who do not need it (because her baby is Rhesus negative or their blood did not mix). Many countries routinely give Anti-D to Rhesus D negative women in pregnancy. In other countries, stocks of Anti-D can run short or even run out. Before Anti-D is made routine in these countries, stocks should be readily available so that it is available for women who need Anti-D in an emergency situation.
A recent review found research into giving Anti-D to all Rhesus D negative pregnant women is of low quality. However the research did suggest that the risk of the mother producing antibodies to attack Rhesus D positive fetal cells was lower in mothers who had the Anti-D in pregnancy. There were also fewer mothers with a positive kleihauer test (which shows if the mother’s and unborn baby’s blood has mixed).
Anti-RhD immunoglobulin is also given to non-sensitized rhesus negative women immediately (within 72 hours—the sooner the better) after potentially sensitizing events that occur earlier in pregnancy.
The discovery of cell-free DNA in the maternal plasma has allowed for the non-invasive determination of the fetal RHD genotype. In May 2017, the Society for Obstetrics and Gynecology of Canada is now recommending that the optimal management of the D-negative pregnant woman is based on the prediction of the fetal D-blood group by cell-free DNA in maternal plasma with targeted antenatal anti-D prophylaxis. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. It is no longer considered appropriate to treat all D-negative pregnant women with human plasma derivatives when there are no benefits to her or to the fetus in a substantial percentage of cases.
Where no intrauterine pregnancy is seen on ultrasound, measuring β-human chorionic gonadotropin (β-hCG) levels may aid in the diagnosis. The rationale is that a low β-hCG level may indicate that the pregnancy is intrauterine but yet too small to be visible on ultrasonography. While some physicians consider that the threshold where an intrauterine pregnancy should be visible on transvaginal ultrasound is around 1500 IU/ml of β-hCG, a review in the JAMA Rational Clinical Examination Series showed that there is no single threshold for the β-human chorionic gonadotropin that confirms an ectopic pregnancy. Instead, the best test in a pregnant woman is a high resolution transvaginal ultrasound. The presence of an adnexal mass in the absence of an intrauterine pregnancy on transvaginal sonography increases the likelihood of an ectopic pregnancy 100-fold (LR+ 111). When there are no adnexal abnormalities on transvaginal sonography, the likelihood of an ectopic pregnancy decreases (LR- 0.12). An empty uterus with levels higher than 1500 IU/ml may be evidence of an ectopic pregnancy, but may also be consistent with an intrauterine pregnancy which is simply too small to be seen on ultrasound. If the diagnosis is uncertain, it may be necessary to wait a few days and repeat the blood work. This can be done by measuring the β-hCG level approximately 48 hours later and repeating the ultrasound. The serum hCG ratios and logistic regression models appear to be better than absolute single serum hCG level. If the β-hCG falls on repeat examination, this strongly suggests a spontaneous abortion or rupture. The fall in serum hCG over 48 hours may be measured as the hCG ratio, which is calculated as:
formula_1
An hCG ratio of 0.87, that is, a decrease in hCG of 13% over 48 hours, has a sensitivity of 93% and specificity of 97% for predicting a failing PUL. The majority of cases of ectopic pregnancy will have serial serum hCG levels that increase more slowly than would be expected with an IUP (that is, a "suboptimal rise"), or decrease more slowly than would be expected with a failing PUL. However, up to 20% of cases of ectopic pregnancy have serum hCG doubling times similar to that of an IUP, and around 10% of EP cases have hCG patterns similar to a failing PUL.
Most women with a PUL are followed up with serum hCG measurements and repeat TVS examinations until a final diagnosis is confirmed. Low-risk cases of PUL that appear to be failing pregnancies may be followed up with a urinary pregnancy test after 2 weeks and get subsequent telephone advice. Low-risk cases of PUL that are likely intrauterine pregnancies may have another TVS in 2 weeks to access viability. High-risk cases of PUL require further assessment, either with a TVS within 48 h or additional hCG measurement.
According to current recommendations by the WHO, US CDC and U.S. Department of Health and Human Services (DHHS), all individuals with HIV should begin ART. The recommendation is stronger under the following conditions:
- CD4 count below 350 cells/mm
- High viral load (>100,000 copies/ml)
- Progression of HIV to AIDS
- Development of HIV-related infections and illnesses
- Pregnancy
Women are encouraged to begin treatment as soon as they are diagnosed with HIV. If they are diagnosed prior to pregnancy, they should continue with ART during the pregnancy. If the diagnosis of HIV is made during the pregnancy, ART should be initiated immediately.
There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling. Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.
- Free Cell DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.
- Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.
- CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.
MCA scans Middle cerebral artery - peak systolic velocity is changing the way sensitized pregnancies are managed. This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with IUT.
Pre-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or thrombotic thrombocytopenic purpura, antiphospholipid syndrome and hemolytic-uremic syndrome. It must be considered a possibility in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when preexisting disease such as hypertension is present. Women with acute fatty liver of pregnancy may also present with elevated blood pressure and protein in the urine, but differ by the extent of liver damage. Other disorders that can cause high blood pressure include thyrotoxicosis, pheochromocytoma, and drug misuse.
Blood is generally drawn from the father to help determine fetal antigen status. If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDN. If he is heterozygous, there is a 50% chance of offspring to be positive for the antigen. This test can help with knowledge for the current baby, as well as aid in the decision about future pregnancies. With RhD, the test is called the RhD genotype. With RhCE, and Kell antigen it is called an antigen phenotype.
There have been many assessments of tests aimed at predicting pre-eclampsia, though no single biomarker is likely to be sufficiently predictive of the disorder. Predictive tests that have been assessed include those related to placental perfusion, vascular resistance, kidney dysfunction, endothelial dysfunction, and oxidative stress. Examples of notable tests include:
- Doppler ultrasonography of the uterine arteries to investigate for signs of inadequate placental perfusion. This test has a high negative predictive value among those individuals with a history of prior pre-eclampsia.
- Elevations in serum uric acid (hyperuricemia) is used by some to "define" pre-eclampsia, though it has been found to be a poor predictor of the disorder. Elevated levels in the blood (hyperuricemia) are likely due to reduced uric acid clearance secondary to impaired kidney function.
- Angiogenic proteins such as vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) and anti-angiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt-1) have shown promise for potential clinical use in diagnosing pre-eclampsia, though evidence is sufficient to recommend a clinical use for these markers.
- Recent studies have shown that looking for podocytes (specialized cells of the kidney) in the urine has the potential to aid in the prediction of preeclampsia. Studies have demonstrated that finding podocytes in the urine may serve as an early marker of and diagnostic test for preeclampsia.