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Maternal mortality
The Centers for Disease Control and Prevention (CDC) defines maternal mortality as the death of a woman while pregnant or within one year of termination of pregnancy, irrespective of the duration and sight of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.[1] It is reported as a ratio of deaths to 100,000 live births. The US maternal mortality rate in 1950 was reported as 83 deaths/100,000 live births. This rate fell to a low of 7.2 deaths/100,000 live births in 1997. Since 2007, the United States has seen an increase in maternal mortality, which last reported by the CDC in 2009 was 17.8 deaths/100,000 live births.[1, 2] When broken down by race, the maternal mortality ratio for white women, black women, and women of other races are 11.7, 35.6, and 17.6 deaths/100,000 live births, respectively.[1, 3]
Although peripartum hemorrhage remains a leading cause of maternal mortality in nondeveloped countries, cardiovascular diseases are the leading cause of maternal mortality in the United States. This is followed by infection, noncardiovascular disease, cardiomyopathy, hemorrhage, hypertensive disorders of pregnancy, venous thromboembolism, cerebrovascular accidents, amniotic fluid embolism, and anesthesia related complications.[1]
Comprehensive pregnancy care includes preconception, prenatal and postpartum care. Although the focus of prenatal care is to promote the health of the pregnant women and developing fetus, the health of the entire family can be affected during this time period.[4] The goal of prenatal care is to achieve a healthy outcome for the mother and her baby by ensuring availability of resources and delivering treatments that improve the outcome of the pregnancy.[5]
The success of prenatal care in ensuring a healthy outcome for both the mother and her baby is not solely dependent on the provider or mother but must be a cooperative approach. Improving access to care is considered an integral step in the goal of improving pregnancy outcomes. The US Department of Health and Human Services launched the program Healthy People 2020 with the goal of raising the proportion of pregnant women who receive early and adequate prenatal care from a baseline goal of 70% in 2012 to 77% by 2020.[6] Access to care in the United States continues to vary significantly among different racial, ethnic and socioeconomic groups.[7]
Although there have not been randomized controlled trials comparing prenatal care to no prenatal care, several trials have demonstrated the benefits of assessment of maternal and fetal conditions. Examples include the benefit of early ultrasound to detect multiple pregnancy, accurate dating and congenital anomalies, as well as HIV screening of women to improve maternal and neonatal outcomes.[8, 9]
Medical assessment
To achieve the best possible outcome for pregnancy, a thorough history should be obtained to identify conditions that may affect or be affected by pregnancy. Chronic medical disease may improve or be exacerbated by pregnancy, while some will remain unaffected. Chronic conditions may pose a threat to normal pregnancy while others will have no impact on the pregnancy. Many times, it is not the disease itself but the treatment that must be addressed in pregnancy; some medications such as angiotensin-converting enzyme inhibitors are considered contraindicated in pregnancy, whereas other medications pose no additional risk. It is imperative that any chronic conditions are addressed as early in pregnancy as possible.
First trimester
Establishing gestational age
Gestational age in modern obstetrics is first established by knowledge of the last menstrual period (LMP). Using the first day of the LMP through delivery, pregnancy has a duration of 280 days. Traditionally, Naegele’s rule has been used estimate a date of delivery (EDD) by subtracting three months and adding one week from the first day of the LMP.[4] Because of the possible variation of menstrual cycle days and to avoid reliance on maternal recall of the LMP, many clinicians use a combination of Naegele’s rule and fetal biometry measurements to establish as accurate an EDD as possible. When there is discrepancy between the EDDs of the LMP and fetal biometry, ultrasound dating should be used. The American College of Obstetricians and Gynecologists (ACOG), American Institute of Ultrasound in Medicine and the Society of Maternal-Fetal Medicine have recommended a protocol to follow when dating by LMP and ultrasound do not agree.[15] When there is discrepancy between ultrasound dating and LMP dating in the third trimester, caution should be used in reassigning EDD. Some centers use a three-week discrepancy to reassign dates. In these cases, a follow-up ultrasound to assess interval growth is often performed to detect cases of fetal growth restriction.[4]
Prior obstetric outcome
Prior fetal demise
Although stillbirth does not have a uniform definition among all jurisdictions, fetal deaths after 20 weeks’ gestation are reported by the CDC. The fetal mortality rate in 2006 was reported as 6.05 deaths at 20 weeks of gestation or more per 1,000 live births and fetal deaths.[16] In women with a prior unexplained stillbirth, the risk of recurrence has been cited to be between 7 and 10 per 1,000, if growth was present, the risk of recurrence is much greater, up to 21 per 1,000.[12] If not already completed, a workup for the etiology of the prior stillbirth is indicated; evaluation for conditions such as antiphospholipid antibody syndrome, tobacco use, and diabetes should be completed as these will impact the management of future pregnancies.
Antenatal testing with non-stress test or biophysical profile can be considered at 32–34 weeks’ gestation. Delivery timing of subsequent pregnancies should not take place before 39 weeks’ gestation in the absence of other indications. Delivery before 39 weeks’ gestation for the history of prior stillbirth should only be done after documenting fetal lung maturity by amniocentesis.[12]
History of spontaneous preterm delivery
All pregnant women are at risk of spontaneous preterm delivery (SPTD). Demographic factors such as African American or black race, low socioeconomic status, and less education increase a woman’s risk of SPTD. Pregnancy characteristics such as multiple gestation, assisted reproductive technology, shortened cervical length, and tobacco use are also associated with a higher rate of SPTD.[4, 17] One of the strongest risk factors for SPTD is a history of SPTD in a prior pregnancy. The earlier the gestational age of delivery in the prior affected pregnancy, the greater the risk of recurrence in future pregnancies. The risk also appears to increase according to the number of prior pregnancies complicated by SPTD. Using baseline population-specific risks for non-Hispanic white women and non-Hispanic black women, an estimated recurrence risk for SPTD can be calculated. Using the baseline risk for non-Hispanic white women of 11%, a factor of 1.5 for each prior SPTD can be used to calculate recurrence risk.[18] For a non-Hispanic white woman with one prior SPTD, her recurrence risk would be 17% (11% × 1.5).
Women with a history of SPTD can benefit from several interventions to reduce the risk of recurrence. Smoking cessation, progestational agents, and cerclage are all potential interventions depending on the obstetric history and current pregnancy risk factors. Use of 17-alpha-hydroxyprogesterone caproate in pregnancies complicated by prior SPTD between 20 and 36 weeks’ gestation has been shown to reduce the risk of recurrence PTD and should be offered to this population.[19] The weekly intramuscular injection of 17 alpha-hydroxyprogesterone caproate (250 mg) is started between 16 and 20 weeks’ gestation and continued through 36 weeks’ gestation.[19] Women with a history of SPTD between 17 and 34 weeks’ gestation who have a sonographically demonstrated shortened cervix in the current pregnancy (less than 25 mm between 16 and 23 weeks’ gestation) have been shown to benefit from placement of a cerclage to reduce the risk of recurrent preterm delivery.[20] Women with a history of SPTD benefit from preconception consultation and/or maternal-fetal medicine consultation early in pregnancy to evaluate for appropriate screening modalities and potential treatment with cerclage or progestational agents.
Prior congenital malformation
Women who have had prior pregnancies complicated by fetal congenital anomaly are best served with preconception consultation as potential preventative efforts may need to begin prior to or very early in subsequent pregnancies. Two populations where prevention is possible is with pregnancies complicated by a fetal neural tube defect (NTD) and congenital anomalies in the setting of poorly controlled diabetes evident by an elevated glycosylated hemoglobin (HbA1 C). For all women capable of becoming pregnant, 0.4 mg/day of folic acid supplementation is recommended. In women with a prior pregnancy complicated by a NTD, the recommended folic acid supplementation is 4 mg beginning 1 month prior to conception carried throughout the first trimester.[17]
Women whose pregnancies are complicated by pregestational diabetes are at risk for fetal congenital anomalies greater than the general population. Approximately 6%–12% of infants of diabetic women will have a congenital anomaly.[10] Women should attempt to bring the HbA1 C below 6.1% as a HbA1 C greater than 10% is associated with a significant increase in the risk for congenital anomalies.[21]
History of severe preeclampsia
In women with a history of preeclampsia/ecclampsia in a prior pregnancy are indeed at risk for developing preeclampsia/ecclampsia in future pregnancies. Recurrence rates have been reported between 11%–70% for recurrence of preeclampsia. Recurrence of eclampsia has been reported at 5%.[17] In women with a history of early onset severe preeclampsia with subsequent delivery less than 34 weeks’ gestation, low-dose aspirin beginning in the late first trimester is recommended to reduce the risk of recurrence.[22] Women with multiple pregnancies complicated by preeclampsia may benefit from low-dose aspirin therapy as well.[22]
Initial visit
History and physical
Once pregnancy has been documented, prenatal care is begun with a history and physical examination. This is accompanied by laboratory testing to screen for various comorbidities that will affect the care of the pregnant women.
A medical, surgical, and family history including genetic history is obtained. Medications, allergies, drug use, and substance abuse screening should be carried out as well.
It is important to review prior pregnancies regardless if the pregnancy resulted in a live birth. The circumstances surrounding prior pregnancies should be documented, including if the onset of labor was spontaneous, the mode of delivery, the weight of the newborn(s), location of delivery and any complications that occurred in the antepartum, during the time of delivery or postpartum periods. It is important to note details of the delivery such as the need for assisted-vaginal delivery, the presence of shoulder dystocia or the occurrence of postpartum hemorrhage.
The gynecologic history including menstrual details, prior results of Pap smears and any history of sexually transmitted infections should be obtained. Gynecologic surgeries or procedures should be noted such as colposcopies, loop electrosurgical excision procedure (LEEP), tubal ligations, or surgery for adnexal pathologies.
A good social history is important. The family dynamics such as occupation or schooling, partner status, contact with animals, living conditions and relationships with others that may live or spend time in the home should be elicited. This is an appropriate time to screen for intimate partner violence (IPV). IPV affects more than 300,000 pregnant women annually; screening of women at the initial prenatal visit and each trimester including postpartum visits is recommended.[23]
Laboratory evolution
Infection screening
Sexually transmitted infections can cause significant morbidity and at times mortality in women. Infections in pregnancy may result in fetal or neonatal infections, maternal infection, and may contribute to pregnancy morbidity including preterm delivery.
It is important to screen all pregnant women for sexually transmitted infections; positive results must be promptly treated. The CDC recommends that all pregnant women undergo screening for Chlamydia trachomatis at the first prenatal visit. Treatment should prompt rescreening three to six months later or during the third trimester. High-risk populations should undergo rescreening in the third trimester regardless of negative results during initial screening. High-risk populations should be screened for N. gonorrheae. Treatment, if positive, is followed by retesting at three to six months.[24]
HIV
HIV testing in pregnancy should follow a provider-initiated approach and be done as early in the pregnancy as possible. Women should be informed that an HIV test is considered routine for all pregnant women and should be given the option to opt out of testing.[25] Populations that are considered high risk should be retested in the third trimester.[24]
Hepatitis B
Hepatitis B screening should be carried out in all pregnant women as early as possible in the pregnancy regardless of vaccination history. Initial screening should test for hepatitis B surface antigen (HbSAg).[24] Susceptible women should be offered vaccination as pregnancy is not a contraindication.[26]
In the event that HbSAg is detected, further testing is necessary to identify evidence of an acute or chronic infection and active viral replication via hepatitis B core antibodies (IgG and IgM) and hepatitis “e” antigen. Immunity is evident if hepatitis surface antibody (IgG) is present.
Syphilis
All pregnant women should be screened with serologic testing for syphilis; tests include rapid plasma reagin (RPR) or Venereal Disease Research Laboratories (VDRL) studies.[24] False positive results are seen in other health conditions, so reactive tests should be confirmed with Treponema pallidum (MHA-TP) or fluorescent terponemal antibody absorbed (FTA-ABS) testing.[4] In high-risk populations, rescreening at 28–32 weeks’ gestation is appropriate. Some states may require testing at the time of delivery. Infants should not be sent home from the hospital without evidence of maternal testing for syphilis.[5]
Cervical cancer screening
Women should undergo cervical cancer screening beginning at age 21 and pregnancy does not alter this recommendation. An exception to screening initiation is women with HIV under the age of 21; screening of this population should begin when HIV is diagnosed.[27] The goal of cervical cancer screening in pregnancy is to identify invasive disease. Colposcopy and biopsy is appropriate if indicated, although endocervical curettage or endometrial biopsy should not be done. Once invasive cancer is ruled out, it is appropriate to reevaluate postpartum. Cervical intraepithelial neoplasm 2 or 3 are unlikely to progress to invasive disease during pregnancy.[28] Management of abnormal cervical cytology should follow guidelines published by ACOG.[28]
Complete blood count
A complete blood count (CBC) should be obtained early in pregnancy. Not only are baseline values established, but many diseases are screened for via the CBC. The CBC screens for anemia and thrombocytopenia and provides clues to hemogloblinopathies. Pregnancy is associated with a dilutional anemia secondary to increased plasma volume; this effect is greatest after 30 weeks’ gestation.[4] Microcytic anemia is often the result of iron deficiency anemia. If treatment with iron supplementation does not improve the red cell indices, further studies should take place to investigate the cause of the anemia. In African-American, Asian, and Mediterranean women, screening for hemoglobinopathies with a hemoglobin electrophoresis should accompany a baseline CBC.
Screening for asymptomatic bacteruria
Urinalysis may give clues to underlying urinary system pathologies including urolithiasis and infection. Pregnancy is associated with an increased risk for asymptomatic bacteruria that may result in pyelonephritis. To prevent pyelonephritis and the associated comorbidities, urinalysis and culture is recommended in early pregnancy for all women.[29]
Physical examination
A full examination should be completed at the first prenatal visit. The purpose of the examination is to screen for any pathology such as poor dentition, breast masses, cardiac/respiratory abnormalities, adnexal masses, and uterine or cervical pathologies. Normal physiologic changes of pregnancy can be appreciated as well and should not be considered pathologic. Examples of these changes in the cardiovascular system include lateral displacement of the left ventricular apex, mild tachycardia, exaggerated splitting of the first and second heart sounds and a mid-systolic ejection murmur.[4] Although a clinically enlarged goiter should be evaluated further, the thyroid is normally mildly enlarged in pregnancy.[4] The gravid uterine fundus can be palpated easily after 12–13 weeks’ gestation as it grows above the pelvic brim. The cervix may appear bluish in pregnancy due to the increased vascularization; this is known as “Chadwick’s sign.” Although normal changes to the maternal anatomy are often appreciated, any suspected pathology must be addressed. Diagnosis must not be delayed due to pregnancy.
Second trimester
Visits during the second trimester will increase as the pregnancy approaches term. Many important tests should be performed during this period. These include aneuploidy screening, ultrasound for fetal abnormalities, evaluation for the development of gestational diabetes, and immunoprophylaxis for prevention of Rh isoimmunization in Rh negative mothers.
Aneuploidy screening
This topic has become very complicated over the last 30 years since a low MSAFP was found to predict fetuses with trisomy 21.[30] Currently several tests and screening protocols are available. This topic has even become more complicated with the introduction of free cell fetal DNA detection from maternal plasma of pregnant women.
Second trimester quad screening became the primary test used for many years in the United States.[31] This is usually performed between 15 and 21 weeks of gestational age. This test includes the analysis of MSAFP, HCG, inhibin A, unconjugated estriol. The identification rate for Down’s syndrome using a 5% positive rate is 81%.[32] Some companies have added other analytes such as free beta sub unit of HCG but this only increases the detection rate slightly.[33] Recently, a first trimester test has been added.[34] This has the advantage of earlier detection and therefore the potential for earlier intervention for confirmed cases of aneuploidy. The test includes the measurement of the nuchal translucency, plus PAPP-A along with free or total beta HCG. This test has an identification rate of 82%–87%.[35] First and second trimester testing can be combined in a variety of ways to further increase the detection rate. Use of the test in a step wise sequential manner may offer a detection rate as high as 95% using a 5% positive screening rate.[36]
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