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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.
The data presented is for comparative and illustrative purposes only, and may have been superseded by updated data.
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).
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.
According to American Congress of Obstetricians and Gynecologists, the main methods to calculate gestational age are:
- Directly calculating the days since the beginning of the last menstrual period.
- Early obstetric ultrasound, comparing the size of an embryo or fetus to that of a reference group of pregnancies of known gestational age (such as calculated from last menstrual periods), and using the mean gestational age of other embryos or fetuses of the same size. If the gestational age as calculated from an early ultrasound is contradictory to the one calculated directly from the last menstrual period, it is still the one from the early ultrasound that is used for the rest of the pregnancy.
- In case of in vitro fertilization, calculating days since oocyte retrieval or co-incubation and adding 14 days.
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.
In some cases, the direct coombs will be negative but severe, even fatal HDN can occur. An indirect coombs needs to be run in cases of anti-C, anti-c, and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN.
- Hgb - the infant’s hemoglobin should be tested from cord blood.
- Reticulocyte count - Reticulocytes are elevated when the infant is producing more blood to combat anemia. A rise in the retic count can mean that an infant may not need additional transfusions. Low retic is observed in infants treated with IUT and in those with HDN from anti-Kell
- Neutrophils - as Neutropenia is one of the complications of HDN, the neutrophil count should be checked.
- Thrombocytes - as thrombocytopenia is one of the complications of HDN, the thrombocyte count should be checked.
- Bilirubin should be tested from cord blood.
- Ferritin - because most infants affected by HDN have iron overload, a ferritin must be run before giving the infant any additional iron.
- Newborn Screening Tests - Transfusion with donor blood during pregnancy or shortly after birth can affect the results of the Newborn Screening Tests. It is recommended to wait and retest 10–12 months after last transfusion. In some cases, DNA testing from saliva can be used to rule out certain conditions.
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.
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.
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.
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.
In terms of ovarian reserve, a typical woman has 12% of her reserve at age 30 and has only 3% at age 40. 81% of variation in ovarian reserve is due to age alone, making age the most important factor in female infertility.
The most common methods of checking the status of the ovarian reserve is to perform a blood test on day 3 of the menstrual cycle to measure serum FSH level, alternatively a blood test to measure the serum AMH level can give similar information. Transvaginal ultrasound can also be used to “count the number of follicles” and this procedure is called Antral Follicle Count.
The American College of Obstetricians and Gynecologists recommends ovarian reserve testing should be performed for women older than 35 years who have not conceived after 6 months of attempting pregnancy and women at higher risk of diminished ovarian reserve, such as those with a history of cancer treated with gonadotoxic therapy, pelvic irradiation, or both; those with medical conditions who were treated with gonadotoxic therapies; or those who had ovarian surgery for endometriomas.
It is important to recognize that a poor result from ovarian reserve testing does not signify an absolute inability to conceive and should not be the sole criterion considered to limit or deny access to infertility treatment.
Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.
In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening.
Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated.
Hormonal and other changes in pregnancy affect physical performance. In the first three months it is known that a woman’s body produces a natural surplus of red blood cells, which are well supplied with oxygen-carrying hemoglobin, in order to support the growing fetus. A study of athletes before and after pregnancy by Professor James Pivarnik at the Human Energy Research laboratory in Michigan State University has found there is a 60 per cent increase in blood volume and that this could improve the body’s ability to carry oxygen to muscles by up to 30 percent. This would have obvious positive effects on aerobic capacity. Other potential advantages are obtained from the surge in hormones that pregnancy induces, predominantly progesterone and estrogen, but also testosterone, which could increase muscle strength. Increases in hormones like relaxin, which loosens the hip joints to prepare for childbirth, may have a performance-enhancing effect on joint mobility.
Several world records have been set by female athletes shortly after giving birth to their first child. This is accepted as a natural and unintended event.
The effects of high blood pressure during pregnancy vary depending on the disorder and other factors. Preeclampsia does not in general increase a woman's risk for developing chronic hypertension or other heart-related problems. Women with normal blood pressure who develop preeclampsia after the 20th week of their first pregnancy, short-term complications--including increased blood pressure--usually go away within about 6 weeks after delivery.
Some women, however, may be more likely to develop high blood pressure or other heart disease later in life. More research is needed to determine the long-term health effects of hypertensive disorders in pregnancy and to develop better methods for identifying, diagnosing, and treating women at risk for these conditions.
Even though high blood pressure and related disorders during pregnancy can be serious, most women with high blood pressure and those who develop preeclampsia have successful pregnancies. Obtaining early and regular prenatal care is the most important thing you can do for you and your baby.
Types of HDN are classified by the type of antigens involved. The main types are ABO HDN, Rhesus HDN, Kell HDN, and other antibodies. ABO hemolytic disease of the newborn can range from mild to severe, but generally it is a mild disease. It can be caused by anti-A and anti-B antibodies. Rhesus D hemolytic disease of the newborn (often called Rh disease) is the most common form of severe HDN. Rhesus c hemolytic disease of the newborn can range from a mild to severe disease - is the third most common form of severe HDN. Rhesus e and rhesus C hemolytic disease of the newborn are rare. Combinations of antibodies, for example, anti-Rhc and anti-RhE occurring together can be especially severe.
Anti-Kell hemolytic disease of the newborn is most commonly caused by anti-K antibodies, the second most common form of severe HDN. Over half of the cases of anti-K related HDN are caused by multiple blood transfusions. Antibodies to the other Kell antigens are rare.
In some cases, the direct coombs will be negative but severe, even fatal HDN can occur. An indirect coombs needs to be run in cases of anti-C, anti-c, and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN.
Blood pressure control can be accomplished before pregnancy. Medications can control blood pressure. Certain medications may not be ideal for blood pressure control during pregnancy such as angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (AII) receptor antagonists. Controlling weight gain during pregnancy can help reduce the risk of hypertension during pregnancy.
Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first 2 trimesters is only around 10% and the positive predictive value is around 20%.
Prenatal stress and negative mood during pregnancy has been shown to increase the risk for poor childbirth outcomes and postnatal maternal mood problems. Additionally, prenatal distress can interfere with the mother-infant attachment and child development outcomes. Despite the clear association between prenatal stress and child outcomes, frequently women do not receive screening, prevention, or treatment for mood or stress concerns.
Given the relationship between prenatal stress and child outcomes, it is essential to examine interventions that aim to reduce anxiety, depression, and stress during pregnancy. Mindfulness based stress reduction has been demonstrated to reduce anxiety and depression for people with stress-related and chronic medical conditions.
One pilot study shows promise for the potential of a mindfulness-based intervention to reduce negative affect and anxiety of women during pregnancy. Based out of the California Pacific Medical Center Research Institute, investigators Dr. Cassandra Vieten and Dr. John Astin conducted a wait-list control pilot study that tested a group-based mindfulness intervention. There were 31 women enrolled in the study: 13 women were assigned to the intervention and 18 women were assigned to the control group. Measures of anxiety, negative affect, positive affect, depression, mindfulness, perceived stress, and affect regulation were taken before intervention or control was assigned and after the intervention or control was completed. Measures were repeated at a follow-up visit 3 months after the intervention or control was completed. The investigators found a significant decrease in anxiety (p<.05) and negative affect (p <.04) in women who completed the mindfulness based intervention, but not a significant decrease in depression, positive affect, mindfulness, affect regulation, and perceived stress. These results suggest that mindfulness intervention during pregnancy reduce anxiety and negative affect of mothers. This study is a promising start to the potential impact that mindfulness based interventions could have on reducing prenatal stress, and thereby improving child outcomes.
There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the hepatic vein in Budd-Chiari syndrome), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis. In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventative treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent orthopedic surgery, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results.
When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patient's indicated treatment. In 2013, the American Society of Hematology, as part of recommendations in the Choosing Wisely campaign, cautioned against overuse of thrombophilia screening; false positive results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical need
In the United Kingdom, professional guidelines give specific indications for thrombophilia testing. It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In particular situations, such as retinal vein thrombosis, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as evidence-based. If cost-effectiveness (quality-adjusted life years in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.
Recurrent miscarriage is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as thromboelastography.
Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has suffered from thrombosis, the risk of developing thrombosis is increased. Screening this selected group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.
Thrombophilia screening in people with arterial thrombosis is generally regarded unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by smoking or use of estrogen-containing hormonal contraceptives) and those in whom revascularization, such as coronary arterial bypass, fails because of rapid occlusion of the graft.
Abortion doping refers to the rumoured practice of purposely inducing pregnancy for athletic performance-enhancing benefits, then aborting the pregnancy.
Prenatal stress (or prenatal maternal stress) is exposure of an expectant mother to stress, which can be caused by stressful life events or by environmental hardships. The resulting changes to the mother's hormonal and immune system may harm the fetus's (and after birth, the infant's) immune function and brain development.
Prenatal stress is shown to have several affects in fetal brain development. In the hippocampus of adult male rats, prenatal stress has shown to decrease the rate of proliferation and cell death in the hypothalamus-pituitary axis. Prenatal stressed animals have prolonged corticosterone response. Removing the adrenal glands of the mother eliminates the effect of the pup's corticosterone response. Supplementing the adrenalectamized mother with corticosterone, rescued the hypothalamic-pituitary-axis response to maternal stress for prenatally stressed offspring. Prenatal stress caused high glucocorticoids, which in turn affects the hypothalamic-pituitary-axis negative feedback.
A study by García-Cáceres et al. showed that prenatal stress decreases cell turnover and proliferation in the hypothalamus of adult rats, which reduces structural plasticity and reduces the response to stress in adulthood. This study also showed that when prenatally stressed rats were stressed in adulthood the females showed an increase in corticotropin-releasing hormone suggesting it to be an up-regulation in the hypothalamic-pituitary adrenal axis. Males showed no elevation of corticosterone levels. Increase in adrenocorticotropic hormone with no effect of adult stress and a decrease in the corticotropin-releasing hormone mRNA in the hypothalamus showed a down-regulation. The author concludes that this makes prenatally stressed females less reactive to later life stressors than males.
There is a lack of good evidence to support the use of any particular intervention for morning sickness.
A study of a population of French women from 1670 and 1789 shows that those who married at age 20–24 had 7.0 children on average and 3.7% remained childless. Women who married at age 25–29 years had a mean of 5.7 children and 5.0% remained childless. Women who married at 30–34 years had a mean of 4.0 children and 8.2% remained childless. The average age at last birth in natural fertility populations that have been studied is around 40.
In 1957, a study was done on a large population (American Hutterites) that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s.)
This 1957 study found that:
- By age 30, 7% of couples were infertile
- By age 35, 11% of couples were infertile
- By age 40, 33% of couples were infertile
- At age 45, 87% of couples were infertile
Thalidomide was originally developed and prescribed as a cure for morning sickness in West Germany, but its use was discontinued when it was found to cause birth defects. The United States Food and Drug Administration never approved thalidomide for use as a cure for morning sickness.