Richard A. Walsh, MD

• John H. Hord Professor of Medicine
• Professor and Chairman, Department of Medicine
• Physician-in-Chief, University Hospitals Health System
• Case Western Reserve University and University Hospitals
• Case Medical Center
• Cleveland, Ohio

Reports link heavy intake of approximately five cups of coffee per day-about 500 mg of caffeine-with a slightly greater abortion risk (Cnattingius antibiotics over the counter buy 250mg erythromycin overnight delivery, 2000; Klebanoff antimicrobial silver order erythromycin in united states online, 1999) antibiotic xan purchase erythromycin in india. Studies of "moderate" intake-less than 200 mg daily-did not indicate increased risk (Savitz natural antibiotics for sinus infection discount 500mg erythromycin, 2008; Weng bacteria reproduce asexually order erythromycin with mastercard, 2008) antibiotics for acne success buy 250 mg erythromycin with mastercard. In contrast, in one prospective cohort of more than 5100 gravidas, caffeine was linked to miscarriage but not in a dose-response relationship (Hahn, 2015). Currently, the American College of Obstetricians and Gynecologists (2016e) has concluded that moderate consumption likely is not a major abortion risk and that any associated risk with higher intake is unsettled. Also, a higher miscarriage risk was found for dental assistants exposed to more than 3 hours of nitrous oxide daily if there was no gas-scavenging equipment (Boivin, 1997). Paternal Factors Increasing paternal age is significantly associated with an greater risk for abortion (de La Rochebrochard, 2003). In the Jerusalem Perinatal Study, this risk was lowest before age 25 years, after which it progressively increased at 5-year intervals (Kleinhaus, 2006). The etiology of this association is not well studied, but chromosomal abnormalities in spermatozoa likely play a role (Sartorius, 2010). Spontaneous Abortion Clinical Classification Threatened Abortion this diagnosis is presumed when bloody vaginal discharge or bleeding appears through a closed cervical os during the first 20 weeks. This bleeding in early pregnancy must be differentiated from that with implantation, which some women have at the time of their expected menses. Aside from this, almost one fourth of women develop bleeding during early gestation that may persist for days or weeks. It may be accompanied by suprapubic discomfort, mild cramps, pelvic pressure, or persistent low backache. Of symptoms, bleeding is by far the most predictive risk factor for pregnancy loss. Even if miscarriage does not follow threatened abortion, rates of later adverse pregnancy outcomes are increased as shown in Table 18-1. Weiss and coworkers (2004) noted greater risks for adverse outcomes in later pregnancy if early bleeding was heavy rather than light. Compared with those without bleeding, women with first-trimester bleeding in an initial pregnancy have higher recurrence rates in their second (Lykke, 2010). Adverse Outcomes That Are Increased in Women with Threatened Abortion Every woman with an early pregnancy, vaginal bleeding, and pain should be evaluated. Because these are not 100-percent accurate to confirm early embryo death or location, repeat evaluations are often necessary. Although a less-used marker, serum progesterone concentrations <5 ng/mL suggest a dying pregnancy. The gestational sac-an anechoic fluid collection that represents the exocoelomic cavity-may be seen by 4. Another caveat is that a gestational sac may appear similar to other intrauterine fluid accumulations-the so-called pseudogestational sac. This pseudosac may be blood derived from a bleeding ectopic pregnancy and is easier to exclude once a yolk sac is seen. If anemia or hypovolemia is significant, then pregnancy evacuation is generally indicated. In cases in which there is a live fetus, some instead may choose transfusion and further observation. Incomplete Abortion During abortion, bleeding follows partial or complete placental separation and dilation of the cervical os. Thus, tissue may remain entirely within the uterus or partially extrude through the cervix. Products lying loosely within the cervical canal can be easily extracted with ring forceps. The last two are deferred in clinically unstable women or those with uterine infection. However, misoprostol and expectant care are associated with unpredictable bleeding, and some women will undergo unscheduled curettage. Expectant management of spontaneous incomplete abortion has failure rates that approximate 25 percent in randomized trials (Nadarajah, 2014; Nielsen, 1999; Trinder, 2006). Some observational studies have shown failure rates of 10 to 15 percent (Blohm, 2003; Casikar, 2012; Luise, 2002). Medical therapy carries failure rates of 5 to 30 percent (Dao, 2007; Shochet, 2012; Trinder, 2006). In many studies for this, an oral misoprostol dose of 600 g has been used (American College of Obstetricians and Gynecologists, 2009). Alternatively, an 800-g vaginal or a 400-g oral or sublingual misoprostol dose is suitable. Last, curettage usually results in a quick resolution that is 95- to 100percent successful. Complete Abortion At times, complete expulsion of the entire pregnancy may ensue, and the cervical os subsequently closes. Patients are encouraged to bring in passed tissue, in which a complete gestation should be discerned from blood clots or a decidual cast. The latter is a layer of endometrium in the shape of the uterine cavity that when sloughed can appear as a collapsed sac. If an expelled complete gestational sac is not identified, transvaginal sonography is performed to differentiate a complete abortion from threatened abortion or ectopic pregnancy. Characteristic findings of a complete abortion include a minimally thickened endometrium without a gestational sac. Condous and associates (2005) described 152 women with heavy bleeding, an empty uterus with endometrial thickness <15 mm, and a diagnosis of completed miscarriage. Thus, a complete abortion cannot be surely diagnosed unless: (1) true products of conception are seen grossly or (2) unless sonography confidently documents first an intrauterine pregnancy and then later an empty cavity. Calipers measure uterine length and anteroposterior thickness in a sagittal plane. During scanning, because of theoretical temperature elevation in tissues exposed to pulsed Doppler beam, this modality is applied only when needed for additional diagnostic purposes. M-mode should be used to document cardiac activity and measure the rate (Lane, 2013). In addition to the diagnostic parameters of Table 18-3, other softer sonographic markers may portend early pregnancy failure. Values for yolk sac diameters (measured inner-to-inner ring) for each gestational week in normal pregnancy have been established. A slower heart rate is unfavorable, especially those <85 bpm (Laboda, 1989; Stefos, 1998). Last, subchorionic hematoma, that is, blood collected between the chorion and uterine wall, often accompanies threatened miscarriage. Studies are contradictory as to its association with ultimate pregnancy loss (Pedersen, 1990; Stabile, 1989; Tuuli, 2011). Bennett and associates (1996) noted that miscarriage risk correlated with larger hematoma size, older maternal age, and bleeding at a gestational age 8 weeks. With rapid confirmation of embryonic or fetal death, surgical or medical evacuation or expectant observation is an option. As with induced abortion, nonsurgical options balance their noninvasiveness against heavier procedural bleeding, longer completion times, and lower success rates. Of options, expectant care underperforms medical or surgical options, and failure rates range from 15 to 50 percent (Luise, 2002; Trinder, 2006; Zhang, 2005). Also, weeks may pass between pregnancy failure diagnosis and actual spontaneous miscarriage. A single 800-g dose vaginally is a common standard (American College of Obstetricians and Gynecologists, 2016c). It may be repeated in 1 to 2 days, and one large trial reported that 22 percent of women required a second dose (Zhang, 2005). Overall, failure rates range from 15 to 40 percent (Petersen, 2014; Trinder, 2006). Unlike induced abortion, adding mifepristone does not add value (Stockheim, 2006). Contraindications mirror those listed in the section describing induced abortion (p. That said, there is no consensus on an endometrial thickness threshold that mandates additional intervention. Rupture may be spontaneous or may follow an invasive procedure such as amniocentesis or fetal surgery. A gush of vaginal fluid that is seen pooling during sterile speculum examination confirms the diagnosis. In suspect cases, amnionic fluid will fern on a microscope slide or will have a pH >7, or oligohydramnios will be seen on sonography (Sugibayashi, 2013). Also, amnionic fluid proteins placental alpha microglobulin-1 and insulin growth factor binding protein-1, described in Chapter 22 (p. In iatrogenic cases, defects are typically higher in the uterus and tend to self seal. Also, an occlusive plug-termed an amniopatch-can be created by intraamnionic instillation of autologous platelets and cryoprecipitate. Considered investigational, it is used to seal some surgical leaks (Richter, 2013). Spontaneous rupture in the first trimester is nearly always followed by either uterine contractions or infection, and termination is typical. In some secondtrimester cases not associated with pain, fever, or bleeding, fluid may have collected previously between the amnion and chorion. After 48 hours, if no additional amnionic fluid has escaped and if there is no bleeding, cramping, or fever, then a woman may resume ambulation and pelvic rest at home. With bleeding, cramping, or fever, abortion is considered inevitable, and the uterus is evacuated. Without these complications, expectant management is an option in the wellcounseled patient (American College of Obstetricians and Gynecologists, 2017f). Many will choose termination due to the just-described maternal risks and tenuous neonatal outcomes. Of surviving infants, 50 to 80 percent suffer long-term sequelae (Miyazaki, 2012; Pristauz, 2008). Further stratification of outcomes by gestational age is described in Chapter 42 (p. Neonatal mortality predominantly stems from pulmonary dysfunction, which has higher rates when oligohydramnios persists (Winn, 2000). Amnioinfusion has been investigated but is currently investigational (Roberts, 2014). Other topics include lung-maturing corticosteroids, magnesium sulfate neuroprophylaxis, group B streptococcus antibiotic prophylaxis, tocolytics, and neonatal resuscitation efforts. After initial hospitalization, the patient may be discharged home, with instruction for careful surveillance for complications until viability, at which time readmission is usual (American College of Obstetricians and Gynecologists, 2016f). In subsequent pregnancies, the risk for recurrent preterm birth is great, and in one cohort study, the rate neared 50 percent (Monson, 2016). Septic Abortion With abortion legalization, horrific infections and maternal deaths associated previously with criminal septic abortions are now rare. Still, with spontaneous or induced abortion, organisms may invade myometrial tissues and extend to cause parametritis, peritonitis, and septicemia. Particularly worrisome are severe necrotizing infections and toxic shock syndrome caused by group A streptococcus-S pyogenes (Daif, 2009). Rare but severe infections with otherwise low-virulence organisms can complicate medical or spontaneous abortions. Deaths have been reported from toxic shock syndrome due to Clostridium perfringens (Centers for Disease Control and Prevention, 2005). Similar infections are caused by Clostridium sordellii and have clinical manifestations that begin within a few days after an abortion. Women may be afebrile when first seen with severe endothelial injury, capillary leakage, hemoconcentration, hypotension, and a profound leukocytosis. Management of clinical infection includes prompt administration of broadspectrum antibiotics as discussed in Chapter 37 (p. Most women respond to this treatment within 1 to 2 days and are discharged when afebrile. In a very few women, severe sepsis syndrome develops, and intensive supportive care is essential. Although rare, clinical decline in the patient and widespread peritonitis despite curettage should raise concerns. Imaging that shows free air or air within the uterine wall typically prompts laparotomy (Eschenbach, 2015). Anti-D Immunoglobulin With spontaneous miscarriage, 2 percent of Rh D-negative women will become alloimmunized if not provided passive isoimmunization. For planned medical or expectant management, the injection is given within 72 hours of pregnancy failure diagnosis. With threatened abortion, immunoglobulin prophylaxis is controversial because of sparse evidence-based data (Hannafin, 2006). That said, it is reasonable to administer anti-D immunoglobulin for a threatened abortion and a live fetus, and this is our practice. Mindful of this threshold, data from two large studies showed the risk for a subsequent miscarriage to be similar whether following two or three prior pregnancy losses (Bhattacharya, 2010; Brigham, 1999).

Am J Obstet Gynecol 116:1097 antibiotic resistance in the environment erythromycin 250 mg cheap, 1973 Duff P: Diagnosis and management of face presentation bacteria ua purchase 500mg erythromycin visa. Am J Obstet Gynecol 63:392 infection 4 months after c section 500mg erythromycin for sale, 1952 Korhonen U antibiotics that cover mrsa trusted 250mg erythromycin, Taipale P virus protection for mac discount erythromycin 500 mg mastercard, Heinonen S: Fetal pelvic index to predict cephalopelvic disproportion-a retrospective clinical cohort study antibiotic vancomycin purchase generic erythromycin from india. Obstet Gynecol 124(1):57, 2014 Le Ray C, Audibert F, Goffinet F, et al: When to stop pushing: effects of duration of second-stage expulsion efforts on maternal and neonatal outcomes in nulliparous women with epidural analgesia. Acta Obstet Gynecol Scand 69:291, 1990 Marte K, Voutsos L: Reduction in the cesarean delivery rate after obstetric care consensus guideline implementation. Natl Vital Stat Rep 64(1):1, 2015 McCarthy S: Magnetic resonance imaging in obstetrics and gynecology. Radiology 171:265, 1989 Mozurkewich E, Chilimigras J, Koepke E, et al: Indications for induction of labour: a best-evidence review. Anesthesiology 100(1):142, 2004 Sheiner E, Levy A, Mazor M: Precipitate labor: higher rates of maternal complications. Eur J Obstet Gynecol Reprod Biol 116(1):43, 2004 Sporri S, Hanggi W, Brahetti A, et al: Pelvimetry by magnetic resonance imaging as a diagnostic tool to evaluate dystocia. J Matern Fetal Med 8:281, 1999 Thoms H: the obstetrical significance of pelvic variations: a study of 450 primiparous women. Obstet Gynecol 101:279, 2003 World Health Organization: Partographic management of labour. In this way it was found that the intra-uterine pressure, in the intervals between the contractions, was represented by a column of mercury 20 millimeters high, 5 of which were due to the tonicity of the walls and 15 to its contents. During the pains, however, the mercury rose considerably, reaching a height of from 80 to 250 millimeters. Whitridge Williams (1903) Little is written in the first edition of this textbook concerning monitoring of the fetus during labor. Much later, periodic auscultation of the fetal heartbeat with a fetoscope was adopted. These practices were eclipsed in the late 1960s and early 1970s by the development of electronic fetal monitoring (Hon, 1958). It was hoped that the continuous graph-paper portrayal of the fetal heart rate was potentially diagnostic in assessing pathophysiological events affecting the fetus. When first introduced, electronic fetal heart rate monitoring was used primarily in complicated pregnancies but gradually became used in most pregnancies. Now, more than 85 percent of all live births in the United States undergo electronic fetal monitoring (Ananth, 2013). The wire electrode penetrates the fetal scalp, and the second pole is a metal wing on the electrode. Also shown is the maternal heart and corresponding electrical complex (M) that is detected. Time (t) in milliseconds between fetal R waves is fed into a cardiotachometer, where a new fetal heart rate is set with the arrival of each new R wave. The phenomenon of continuous R-to-R wave fetal heart rate computation is known as beat-to-beat variability. Time intervals (t1, t2, t3) in milliseconds between successive fetal R waves are used by a cardiotachometer to compute instantaneous fetal heart rate. Electrical cardiac complexes detected by the electrode include those generated by the mother. This fetus is experiencing premature atrial contractions, which cause the cardiotachometer to rapidly and erratically seek new heart rates, resulting in the "spiking" shown in the standard fetal monitor tracing. Importantly, when the fetus is dead, the maternal R waves are still detected by the scalp electrode as the next best signal and are counted by the cardiotachometer. Spiking of the fetal rate in the monitor tracing is due to premature atrial contractions. The bottom two tracings represent cardiac electrical complexes detected from fetal scalp and maternal chest wall electrodes. In the upper panel, the fetal scalp electrode first detected the heart rate of the dying fetus. After fetal death, the maternal electrocardiogram complex is detected and recorded. External (Indirect) Electronic Monitoring Although membrane rupture may be avoided, external monitoring does not provide the precision of fetal heart rate measurement afforded by internal monitoring (Nunes, 2014). In some women-for example, those who are obese-external monitoring may be difficult (Brocato, 2017). With external monitoring, the fetal heart rate is detected through the maternal abdominal wall using the ultrasound Doppler principle. Ultrasound waves undergo a shift in frequency as they are reflected from moving fetal heart valves and from pulsatile blood ejected during systole (Chap. The unit consists of a transducer that emits ultrasound and a sensor to detect a shift in frequency of the reflected sound. The transducer is placed on the maternal abdomen at a site where fetal heart action is best detected. Correct positioning enhances differentiation of fetal cardiac motion from maternal arterial pulsations (Neilson, 2008). Ultrasound Doppler signals are edited electronically before fetal heart rate data are printed onto monitor paper. Reflected ultrasound signals from moving fetal heart valves are analyzed through a microprocessor that compares incoming signals with the most recent previous signal. This process, called autocorrelation, is based on the premise that the fetal heart rate has regularity, whereas "noise" is random and without regularity. Several fetal heart motions must be deemed electronically acceptable by the microprocessor before the fetal heart rate is printed. Such electronic editing has greatly improved the tracing quality of the externally recorded fetal heart rate. Many fetal monitors are capable of interfacing with archival storage systems, which obviates maintaining actual paper tracings. Technological advances now allow fetal heart rate monitoring from a remote, centralized location. Theoretically, the ability to monitor several patients simultaneously was hoped to improve neonatal outcomes. Anderson and colleagues (2011) measured the ability of 12 individuals to detect critical signals in fetal heart rate tracings on one, two, or four monitors. The results showed that detection accuracy declined as the number of displays increased. Fetal Heart Rate Patterns the interpretation of fetal heart rate patterns can be problematic without definitions and nomenclature. In one example, Blackwell and colleagues (2011) asked three Maternal-Fetal Medicine specialists to independently interpret 154 fetal heart rate tracings. Interobserver agreement was poor for the most ominous tracings and moderate for less severe patterns. The definitions proposed as a result of this second workshop are used in this chapter and have been adopted by the American College of Obstetricians and Gynecologists (2017a) (Table 24-1). Importantly, interpretation of electronic fetal heart rate data is based on the visual pattern of the heart rate as portrayed on chart recorder graph paper. Thus, the choice of vertical and horizontal scaling greatly affects the appearance of the fetal heart rate. Fetal heart rate variation is falsely displayed at the slower 1 cm/min paper speed compared with that of the smoother baseline recorded at 3 cm/min. Thus, pattern recognition can be considerably distorted depending on the scaling factors used. Electronic Fetal Monitoring Definitions Baseline Fetal Heart Activity this refers to the modal characteristics that prevail apart from periodic accelerations or decelerations associated with uterine contractions. Descriptive characteristics of baseline fetal heart activity include rate, beat-to-beat variability, fetal arrhythmia, and distinct patterns such as sinusoidal or saltatory fetal heart rates. This continues postnatally such that the average rate is 85 bpm by age 8 years (Tintinalli, 2016). This normal gradual slowing of the fetal heart rate is thought to correspond to maturation of parasympathetic (vagal) heart control (Renou, 1969). The baseline fetal heart rate is the approximate mean rate rounded to increments of 5 bpm during a 10-minute tracing segment. In any 10-minute window, the minimum interpretable baseline duration must be at least 2 minutes. The average fetal heart rate is considered the result of tonic balance between accelerator and decelerator influences on pacemaker cells. In this concept, the sympathetic system is the accelerator influence, and the parasympathetic system is the decelerator factor mediated by vagal slowing of heart rate (Dawes, 1985). Heart rate also is under the control of arterial chemoreceptors such that both hypoxia and hypercapnia can modulate rate. More severe and prolonged hypoxia, with a rising blood lactate level and severe metabolic acidemia, induces a prolonged fall in heart rate (Thakor, 2009). In the third trimester, the normal mean baseline fetal heart rate has generally been accepted to range between 120 and 160 bpm. But, pragmatically, a rate between 100 and 119 bpm, in the absence of other changes, usually is not considered to represent fetal compromise. Such low but potentially normal baseline heart rates also have been attributed to head compression from occiput posterior or transverse positions, particularly during second-stage labor (Young, 1976). Such mild bradycardias were observed in 2 percent of monitored pregnancies and averaged approximately 50 minutes in duration. Freeman and associates (2003) have concluded that bradycardia within the range of 80 to 120 bpm and with good variability is reassuring. Interpretation of rates less than 80 bpm is problematic, and such rates generally are considered nonreassuring. Some causes of fetal bradycardia include congenital heart block and serious fetal compromise (Jaeggi, 2008; Larma, 2007). Maternal hypothermia under general anesthesia for repair of a cerebral aneurysm or during maternal cardiopulmonary bypass for open-heart surgery can also cause fetal bradycardia. Sustained fetal bradycardia in the setting of severe pyelonephritis and maternal hypothermia also has been reported (Hankins, 1997). The most common explanation for fetal tachycardia is maternal fever from chorioamnionitis, although fever from any source can produce this. In some cases, fetal tachycardia may precede overt maternal fever (Gilstrap, 1987). Fetal tachycardia caused by maternal infection typically is not associated with fetal compromise unless there are associated periodic heart rate changes or fetal sepsis. Other causes of fetal tachycardia include fetal compromise, cardiac arrhythmias, and maternal administration of parasympathetic inhibiting (atropine) or sympathomimetic (terbutaline) drugs. Prompt relief of the compromising event, such as correction of maternal hypotension caused by epidural analgesia, can result in fetal recovery. The key feature to distinguish fetal compromise in association with tachycardia seems to be concomitant heart rate decelerations. This baseline rate is unsteady and "wanders" between 120 and 160 bpm (Freeman, 2003). This rare finding is suggestive of a neurologically abnormal fetus and may occur as a preterminal event. In contrast, changes of the normal baseline are common in labor and do not predict morbidity (Yang, 2017). Beat-to-Beat Variability Baseline variability is an important index of cardiovascular function and appears to be regulated largely by the autonomic nervous system (Kozuma, 1997). That is, a sympathetic and parasympathetic "push and pull" mediated via the sinoatrial node produces moment-to-moment or beat-to-beat oscillation of the baseline heart rate. Variability can be further analyzed over the short term and long term, although these terms have fallen out of use. Short-term variability reflects the instantaneous change in fetal heart rate from one beat-or R wave-to the next. Short-term variability can most reliably be determined to be normally present only when electrocardiac cycles are measured directly with a scalp electrode. Long-term variability is used to describe the oscillatory changes during 1 minute and result in the waviness of the baseline. The normal frequency of such waves is three to five cycles per minute (Freeman, 2003). Thus, most clinical interpretation is based on visual analysis with subjective judgment of the smoothness or flatness of the baseline. According to Freeman and associates (2003), no evidence suggests that the distinction between short- and long-term variability has clinical relevance. The workshop panel defined baseline variability as those baseline fluctuations of two cycles per minute or greater. This differs from variability in that it has a smooth, sinelike pattern of regular fluctuation and is excluded in the definition of fetal heart rate variability. Several physiological and pathological processes can affect beat-to-beat variability. Greater variability accompanies fetal breathing and body movements (Dawes, 1981; Van Geijn, 1980). Pillai and James (1990) reported increased baseline variability with advancing gestation.

Cesarean delivery was performed antibiotics for uti yahoo purchase erythromycin online pills, and the severely acidemic fetus could not be resuscitated antibiotics for acne pregnancy buy cheap erythromycin 500 mg on-line. Visser and associates (1980) described a terminal cardiotocogram virus 10 discount erythromycin 500mg, which included: (1) baseline oscillation of less than 5 bpm yeast infection 1 day treatment erythromycin 500mg low cost, (2) absent accelerations virus 68 sintomas order 250 mg erythromycin visa, and (3) late decelerations with spontaneous uterine contractions virus 89 erythromycin 500mg without prescription. These results were similar to experiences from Parkland Hospital in which absence of accelerations during an 80-minute recording period in 27 fetuses was associated consistently with evidence of uteroplacental pathology (Leveno, 1983). The latter included fetal-growth restriction in 75 percent, oligohydramnios in 80 percent, fetal acidemia in 40 percent, meconium in 30 percent, and placental infarction in 93 percent. Interval between Testing Set originally rather arbitrarily at 7 days, the interval between tests appears to have been shortened as experience evolved with nonstress testing. According to the American College of Obstetricians and Gynecologists (2016), more frequent testing is advocated by some investigators for women with postterm pregnancy, multifetal gestation, pregestational diabetes, fetal-growth restriction, or pregnancy hypertension. In these circumstances, some investigators perform twice-weekly tests, with additional testing completed for maternal or fetal deterioration regardless of the time elapsed since the last test. Others perform nonstress tests daily or even more frequently, such as with severe preeclampsia remote from term. Decelerations During Nonstress Testing Fetal movements commonly produce heart rate decelerations. Timor-Tritsch and associates (1978) reported this during nonstress testing in half to two thirds of tracings, depending on the vigor of the fetal motion. This high incidence of decelerations inevitably makes interpretation of their significance problematic. Indeed, Meis and coworkers (1986) reported that variable fetal heart rate decelerations during nonstress tests were not a sign of fetal compromise. The American College of Obstetricians and Gynecologists (2016) has concluded that variable decelerations, if nonrepetitive and brief-less than 30 seconds-do not indicate fetal compromise or the need for obstetrical intervention. In contrast, repetitive variable decelerations-at least three in 20 minutes-even if mild, have been associated with a greater risk of cesarean delivery for fetal distress. Decelerations lasting 1 minute or longer have been reported to have an even worse prognosis (Bourgeois, 1984; Druzin, 1981; Pazos, 1982). Hoskins and associates (1991) attempted to refine interpretation of testing that shows variable decelerations by adding sonographic estimation of amnionic fluid volume. The incidence of cesarean delivery for intrapartum fetal distress progressively rose concurrently with the severity of variable decelerations and decline of amnionic fluid volume. Fetal distress in labor, however, also frequently developed in those pregnancies with variable decelerations but with normal amounts of amnionic fluid. False-Normal Nonstress Tests Smith and associates (1987) performed a detailed analysis of the causes of fetal death within 7 days of normal nonstress tests. The mean interval between testing and death was 4 days, with a range of 1 to 7 days. The single most common autopsy finding was meconium aspiration, often associated with some type of umbilical cord abnormality. They also concluded that nonstress testing was inadequate to preclude such an acute asphyxial event and that other biophysical characteristics might be beneficial. Other ascribed frequent causes of fetal death included intrauterine infection, abnormal cord position, malformations, and placental abruption. A commercially available acoustic stimulator is positioned on the maternal abdomen, and a stimulus of 1 to 2 seconds is applied (Eller, 1995). This may be repeated up to three times for up to 3 seconds (American College of Obstetricians and Gynecologists, 2016). A positive response is defined as the rapid appearance of a qualifying acceleration following stimulation (Devoe, 2008). In a randomized trial of 113 women undergoing nonstress testing, vibroacoustic stimulation shortened the average time of testing from 24 to 15 minutes (Perez-Delboy, 2002). Laventhal and colleagues (2003) reported that fetal tachyarrhythmia could be provoked with vibroacoustic stimulation. Shown in Table 17-2 are the five fetal biophysical components assessed: (1) heart rate acceleration, (2) breathing, (3) movements, (4) tone, and (5) amnionic fluid volume. Normal variables were assigned a score of 2 each, and abnormal variables were given a score of 0. Maternal medications such as narcotics and sedatives can significantly lower the score (Kopecky, 2000). Ozkaya and associates (2012) found that biophysical test scores were higher if a test was performed in late evening-20:00 to 22:00 hours- compared with 08:00 to 10:00 hours. Components and Scores for the Biophysical Profile Manning and colleagues (1987) tested more than 19,000 pregnancies using the biophysical profile interpretation and management shown in Table 17-3. They reported a false-normal test rate-defined by an antepartum death of a structurally normal fetus-of approximately 1 per 1000. The most common identifiable causes of fetal death after a normal biophysical profile include fetomaternal hemorrhage, umbilical cord accidents, and placental abruption (Dayal, 1999). Interpretation of Biophysical Profile Score Manning and coworkers (1993) published a remarkable description of 493 fetuses in which biophysical scores were performed immediately before measurement of umbilical venous blood pH values obtained via antepartum cordocentesis. Approximately 20 percent of tested fetuses had growth restriction, and the remainder had alloimmune hemolytic anemia. As the abnormal score dropped from 2 or 4 down to 0, this decline was a more accurate predictor of abnormal fetal outcome. Salvesen and associates (1993) concluded that the biophysical profile was of limited value in the prediction of fetal pH. Weiner and coworkers (1996) assessed 135 overtly growth-restricted fetuses and came to a similar conclusion. Kaur and colleagues (2008) performed daily biophysical profiles to ascertain the optimal delivery time in 48 growthrestricted preterm fetuses that weighed less than 1000 g. Despite scores of 8 in 27 fetuses and 6 in 13, there were six deaths and 21 acidemic fetuses. Lalor and associates (2008) performed a Cochrane review and concluded that there is insufficient evidence to support the use of the biophysical profile as a fetal wellbeing test in high-risk pregnancies. Modified Biophysical Profile Because the biophysical profile is labor intensive and requires a person trained in sonography, Clark and coworkers (1989) used an abbreviated biophysical profile as a first-line screening test in 2628 singleton pregnancies. This abbreviated biophysical profile required approximately 10 minutes to perform, and they concluded that it was a superb antepartum surveillance method because there were no unexpected fetal deaths. They performed 17,429 modified biophysical profiles in 2774 women and concluded that such testing was an excellent fetal surveillance tool. Miller and associates (1996a) reported results with more than 54,000 modified biophysical profiles performed in 15,400 high-risk pregnancies. The American College of Obstetricians and Gynecologists (2016) has concluded that the modified biophysical profile test is as predictive of fetal well-being as other approaches to biophysical fetal surveillance. This is based on the rationale that diminished uteroplacental perfusion may lead to lower fetal renal blood flow, decreased urine production, and ultimately, oligohydramnios (Chap. For growth-restricted fetuses, several fetal vascular circuits including the umbilical artery, middle cerebral artery, and ductus venosus have been evaluated as diagnostic tools for fetal well-being (Chap. Maternal uterine artery Doppler velocimetry has also been assessed as a modality to predict placental dysfunction, with the goal to balance stillbirth against the risks of preterm delivery (Ghidini, 2007). Even the effects of sildenafil in pregnant sheep have been evaluated using Doppler velocimetry (Alanne, 2017). The rationale is that sildenafil would improve placental blood flow in the presence of placental insufficiency. This proved untrue, as sildenafil was associated with detrimental effects on fetal cardiovascular dynamics. Doppler Blood Flow Velocity Waveforms were first studied in the umbilical arteries late in pregnancy, and abnormal waveforms correlated with placental villous hypovascularity. Of the small placental arterial channels, 60 to 70 percent need to be obliterated before the umbilical artery Doppler waveform becomes abnormal. Such extensive placental vascular pathology has a major effect on fetal circulation. According to Trudinger (2007), because more than 40 percent of the combined fetal ventricular output is directed to the placenta, obliteration of placental vascular channel increases afterload and leads to fetal hypoxemia. This in turn leads to ventricular dilation and redistribution of middle cerebral artery blood flow. Ultimately, pressure rises in the ductus venosus due to afterload in the right side of the fetal heart (Baschat, 2004). Clinically, abnormal Doppler waveforms in the ductus venosus are a late finding in the progression of fetal deterioration due to chronic hypoxemia. Umbilical Artery Velocimetry the umbilical artery systolic-diastolic (S/D) ratio is considered abnormal if it is >95th percentile for gestational age or if diastolic flow is either absent or reversed (Chap. Absent or reversed end-diastolic flow signifies greater impedance to umbilical artery blood flow. It is reported to result from poorly vascularized placental villi and is seen in extreme cases of fetalgrowth restriction (Todros, 1999). According to Zelop and colleagues (1996), the perinatal mortality rate for absent end-diastolic flow was about 10 percent, and for reversed end-diastolic flow, it approximated 33 percent. Of infants who had shown absent or reversed umbilical artery flow, 8 percent had evidence of cerebral palsy compared with 1 percent of those in whom Doppler flow had been normal. Doppler ultrasound of the umbilical artery has been subjected to more extensive assessment with randomized controlled trials than has any previous test of fetal health. Williams and colleagues (2003) randomized 1360 high-risk women to either nonstress testing or Doppler velocimetry. They found a significantly higher incidence of cesarean delivery for fetal distress in the nonstress test group compared with that for those tested with Doppler velocimetry-8. One interpretation of this finding is that the nonstress test more frequently identified fetuses in jeopardy. Conversely, Gonzalez and associates (2007) found that abnormal umbilical artery Doppler findings in a cohort of growth-restricted fetuses were the best predictors of perinatal outcomes. The utility of umbilical artery Doppler velocimetry was reviewed by the American College of Obstetricians and Gynecologists (2016). They concluded that no benefit has been demonstrated other than in pregnancies with suspected fetalgrowth restriction. Similarly, velocimetry has not proved valuable as a screening test for fetal compromise in the general obstetrical population. Various other fetal-maternal Doppler indices have been studied, including the fetal middle cerebral artery and ductus venosus and the uterine arteries. The American College of Obstetricians and Gynecologists (2016) concluded that Doppler investigations of other blood vessels besides the umbilical artery have not been shown to improve perinatal outcome. Still, the technology has received particular attention because of observations that the hypoxic fetus attempts brain sparing by reducing cerebrovascular impedance and thus increasing blood flow. Such brain sparing in growth-restricted fetuses has been documented to undergo reversal (Konje, 2001). Ott and coworkers (1998) randomized 665 women undergoing modified biophysical profile evaluation to either the profile alone or combined with middle cerebral and umbilical artery velocity flow assessment. Middle cerebral artery Doppler velocimetry has proven valuable to detect severe fetal anemia in 165 fetuses with D-antigen alloimmunization. Oepkes and colleagues (2006) prospectively compared serial amniocentesis for measurement of bilirubin levels with Doppler measurement of peak systolic velocity in the middle cerebral artery. These investigators concluded that Doppler could safely replace amniocentesis in the management of alloimmunized pregnancies. Ductus Venosus Doppler ultrasound has also been used to assess the fetal venous circulation. They concluded that ductus venosus velocimetry was the best predictor of perinatal outcome. Importantly, negative or reversed flow in the ductus venosus was a late finding because these fetuses had already sustained irreversible multiorgan damage due to hypoxemia. Also, gestational age at delivery was a major determinant of perinatal outcome independent of ductus venosus flow. Baschat and coworkers (2007) studied 604 growth-restricted fetuses using umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry and reached similar conclusions. Specifically, absent or reversed flow in the ductus venosus was associated with profound generalized fetal metabolic collapse. They too reported that gestational age was a powerful cofactor in ultimate perinatal outcome for growth-restricted fetuses delivered before 30 weeks. Put another way, by the time severely abnormal flow is seen in the ductus venosus, it is too late because the fetus is already near death. Conversely, earlier delivery puts the fetus at risk for death due to preterm delivery. Ghidini (2007) concluded that these reports do not support routine use of ductus venosus Doppler in the monitoring of growth-restricted fetuses and recommended further study. Uterine Artery Vascular resistance in the uterine circulation normally decreases in the first half of pregnancy due to invasion of maternal uterine vessels by trophoblastic tissue (Chap. This process can be detected using Doppler flow velocimetry, and uterine artery Doppler may be most helpful in assessing pregnancies at high risk of uteroplacental insufficiency (Abramowicz, 2008). Persistence or development of high-resistance patterns has been linked to various pregnancy complications (Lees, 2001; Yu, 2005). The risk of fetal death before 32 weeks, when associated with abruption, preeclampsia, or fetal-growth restriction, was significantly linked to highresistance flow. This has led to suggestions for continued research of uterine artery Doppler velocimetry as a screening tool to detect pregnancies at risk for stillbirth (Reddy, 2008). Sciscione and Hayes (2009) reviewed the use of uterine artery Doppler flow studies in obstetrical practice.

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Vox Sang 107(1): 90 antibiotics for uti azithromycin generic 250mg erythromycin amex, 2014 Suwanrath-Kengpol C antibiotic vaginal infection purchase erythromycin 250mg otc, Kor-anantakul O antibiotics on the pill proven 500mg erythromycin, Suntharasaj T bacterial plasmid purchase erythromycin with mastercard, et al: Etiology and outcome of nonimmune hydrops fetalis in southern Thailand best antibiotics for acne reviews cheap erythromycin 500 mg on-line. Am J Obstet Gynecol 161:1498 antibiotic resistant bacteria kpc discount 500 mg erythromycin mastercard, 1989 Weinstein L: Irregular antibodies causing hemolytic disease of the newborn: a continuing problem. Am J Clin Pathol 145:744, 2016 Woelfer B, Schuchter K, Janisiw M, et al: Postdelivery levels of anti-D IgG prophylaxis in mothers depend on maternal body weight. On the other hand, when the abdomen is immensely distended and respiration is seriously hampered, the termination of pregnancy is urgently indicated. In such cases, the symptoms can be promptly relieved by perforating the membranes through the cervix, after which the amniotic fluid drains off and labour pains set in. Whitridge Williams (1903) the concept of fetal therapy-even amniocentesis-was not considered by Williams in his first edition. Aside from a few destructive procedures to aid vaginal delivery, any type of fetal treatment is not mentioned as even a remote possibility. Again, fast forward to this 25th edition, when interventions developed during the past three decades have dramatically altered the course of selected fetal anomalies and conditions. Reviewed in this chapter are fetal disorders amenable to treatment with either maternal medication or surgical procedures. The management of fetal anemia and thrombocytopenia is reviewed in Chapter 15, and treatment of some fetal infections is discussed in Chapters 64 and 65. Arrhythmias Fetal cardiac rhythm disturbances may be broadly categorized as tachyarrhythmias, heart rates >180 beats per minute (bpm); bradyarrhythmia, heart rate <110 bpm; and ectopy, typically premature atrial contractions. If these are identified, fetal M-mode sonography is performed to measure the atrial and ventricular rates and to clarify the relationship between atrial and ventricular beats, thereby diagnosing the type of rhythm disturbance. Premature Atrial Contractions this is by far the most common arrhythmia and is identified in 1 to 2 percent of pregnancies (Hahurij, 2011; Strasburger, 2010). Generally a benign finding, premature atrial contractions represent immaturity of the cardiac conduction system, and they typically resolve later in gestation or in the neonatal period. If the premature atrial contraction is conducted, it sounds like an extra beat when auscultated with handheld Doppler or fetoscope. However, premature atrial contractions are more commonly blocked and sound like dropped beats. In general, premature atrial contractions are not associated with major structural cardiac abnormalities, although they sometimes occur with an atrial septal aneurysm. They may occur as frequently as every other beat, known as blocked atrial bigeminy. Unlike other causes of bradycardia, atrial bigeminy is benign and does not require treatment (Strasburger, 2010). Approximately 2 percent of fetuses with premature atrial contractions are later found to have a supraventricular tachycardia (Copel, 2000; Srinivasan, 2008). Given the importance of identifying and treating supraventricular tachyarrhythmias, a fetus with premature atrial contractions is often monitored with heart rate assessment every 1 to 2 weeks until the ectopy resolves. This requires neither sonography nor fetal echocardiography, as the rate and rhythm may be easily ascertained with handheld Doppler. Atrial flutter is characterized by a much higher atrial rate, generally 300 to 500 bpm, with varying degrees of atrioventricular block. As a result, the ventricular rate in a fetus with atrial flutter may range from below normal to approximately 250 bpm. In contrast, fetal sinus tachycardia typically presents with a gradual heart rate rise to a rate that is only slightly above normal. With this, readily discernible causes may be maternal fever or hyperthyroidism, or rarely, fetal anemia or infection. There are two atrial beats (A) for each ventricular beat (V), such that the atrial rate is approximately 450 bpm with 2:1 atrioventricular block. If a fetal tachyarrhythmia is identified, it is important to determine whether it is sustained-defined as present for at least 50 percent of the time. It may be necessary to monitor the fetal heart rate for 12 to 24 hours upon initial detection, and then periodically to reassess (Srinivasan, 2008). Unsustained or intermittent tachyarrhythmias generally do not require treatment, provided that fetal surveillance is reassuring. Sustained fetal tachyarrhythmia with ventricular rates exceeding 200 bpm impairs ventricular filling to a degree that the risk for hydrops is significant. With atrial flutter, lack of coordinated atrioventricular contractions may further compound this risk. Maternal administration of antiarrhythmic agents that cross the placenta may convert the rhythm to normal or lower the baseline heart rate to forestall heart failure. Antiarrhythmic medications most commonly used include digoxin, sotalol (Betapace), flecainide (Tambocor), and procainamide (Pronestyl). Their selection depends on the type of tachyarrhythmia as well as provider familiarity and experience with the drug. Traditionally, digoxin has been the initial preferred treatment, although it may poorly transfer to the fetus after hydrops has developed. Many centers now use flecainide or sotalol as first-line therapy (Jaeggi, 2011; Shah, 2012). In many cases, additional agents are needed, particularly if hydrops has developed. With either arrhythmia, however, the overall neonatal survival rate now exceeds 90 percent (Ekman-Joelsson, 2015; Jaeggi, 2011; van der Heijden, 2013). Bradyarrhythmia the most common etiology of pronounced fetal bradycardia is congenital heart block. Approximately 50 percent of cases occur in the setting of a structural cardiac abnormality involving the conduction system. These include heterotaxy, in particular left-atrial isomerism; endocardial cushion defect; and less commonly corrected transposition of the great vessels (Srinivasan, 2008). The prognosis of heart block secondary to a structural cardiac anomaly is extremely poor, and fetal loss rates exceed 80 percent (Glatz, 2008; Strasburger, 2010). Many of these women have, or subsequently develop, systemic lupus erythematosus or other connective tissue disease (Chap. The risk of third-degree heart block with these antibodies is small-only about 2 percent. Immune-mediated congenital heart block confers a mortality rate of 20 to 30 percent, requires permanent pacing in two thirds of surviving children, and also poses a risk for cardiomyopathy (Buyon, 2009). If associated with effusions, bradyarrhythmias, or endocardial fibroelastosis, neonatal status may progressively worsen after birth (Cuneo, 2007). Initial research efforts focused on maternal corticosteroid therapy to potentially reverse fetal heart block or forestall it. Weekly sonographic surveillance was performed, and heart block was treated with maternal oral dexamethasone 4 mg daily. Unfortunately, progression from second- to thirddegree block was not prevented with maternal dexamethasone therapy, and thirddegree atrioventricular block was irreversible. In rare cases, there was a potential benefit in reversing first-degree atrioventricular block. In a subsequent review of 156 pregnancies with isolated second- or third-degree fetal heart block, dexamethasone therapy similarly did not affect disease progression, need for pacemaker in the neonatal period, or overall survival rates (Izmirly, 2016). More recent efforts have turned to potential therapy with hydroxychloroquine (Plaquenil), a mainstay of treatment for systemic lupus erythematosus (Chap. In a multicenter review of more than 250 pregnancies in women whose prior pregnancies had been complicated by neonatal lupus, recurrence of congenital heart block was significantly lower if the woman had been treated with hydroxychloroquine during pregnancy (Izmirly, 2012). Maternal terbutaline has also been given to increase the fetal heart rate in cases with sustained bradycardia of any cause in which the fetal heart rate is below 55 bpm. Congenital Adrenal Hyperplasia Several autosomal recessive enzyme deficiencies cause impaired fetal synthesis of cortisol from cholesterol by the adrenal cortex. Sequelae may include formation of labioscrotal folds, persistence of a urogenital sinus, or even creation of a penile urethra and scrotal sac. For example, it has been reported in approximately 1:300 Yupik Eskimos (Nimkarn, 2010). The efficacy of maternal dexamethasone treatment to suppress fetal androgen overproduction and either obviate or ameliorate virilization of female fetuses has been recognized for more than 30 years (David, 1984; New, 2012). Prenatal corticosteroid therapy is considered successful in 80 to 85 percent of cases (Miller, 2013; Speiser, 2010). The alternative is consideration of postnatal genitoplasty, a complex and somewhat controversial surgical procedure (Braga, 2009). The typical preventive regimen is oral dexamethasone given to the mother at a dosage of 20 g/kg/d-up to 1. Because this is an autosomal recessive condition, affected females make up only 1 in 8 at-risk conceptions. If this is uninformative, gene-targeted deletion/duplication analysis is performed, and additional testing such as whole exome sequencing may be considered (Chap. A goal of prenatal diagnosis is to limit dexamethasone exposure in males and in unaffected females. Maternal treatment with dexamethasone has become a topic of significant controversy. The Endocrine Society recommends that treatment be given only in the context of research protocols (Miller, 2013; Speiser, 2010). It should be noted that if therapy is initiated shortly before 9 weeks, the dose of dexamethasone used is not considered to have significant teratogenic potential because organogenesis of major organs has already taken place (McCullough, 2010). Ongoing concerns, however, focus on the potential effects of either excess endogenous androgens or excess exogenous dexamethasone on the developing brain. Congenital Cystic Adenomatoid Malformation Sonographically, this malformation is a well-circumscribed lung mass that may appear solid and echogenic or may have one or multiple variably sized cysts. Lesions with cysts 5 mm are termed macrocystic, whereas microcystic lesions have smaller cysts or appear solid (Adzick, 1985). The mass may become so large that it causes mediastinal shift, which may compromise cardiac output and venous return, resulting in hydrops (Cavoretto, 2008). Following a single course of corticosteroids, hydrops resolved in approximately 80 percent of cases, and 90 percent of treated fetuses survived (Loh, 2012; Peranteau, 2016). Thyroid Disease Identification of fetal thyroid disease is rare and usually prompted by sonographic detection of a fetal goiter. If a goiter is found, determination of fetal hyper- or hypothyroidism is essential, and thyroid hormone levels may be measured in amnionic fluid or fetal blood. Goals of therapy are correction of the physiological abnormality and diminished goiter size. The goiter may compress the trachea and esophagus to such a degree that severe hydramnios or neonatal airway compromise may develop. Fetal Thyrotoxicosis Untreated fetal thyrotoxicosis may present with goiter, tachycardia, growth restriction, hydramnios, accelerated bone maturation, and even heart failure and hydrops (Huel, 2009; Peleg, 2002). The cause is usually maternal Graves disease with transplacental passage of IgG thyroid-stimulating immunoglobulins. Fetal blood sampling may confirm the diagnosis (Duncombe, 2001; Heckel, 1997; Srisupundit, 2008). During this, if the mother develops hypothyroidism, she is given supplemental levothyroxine (Hui, 2011). Fetal Hypothyroidism In a woman receiving medication for Graves disease, transplacental passage of methimazole or propylthiouracil may cause fetal hypothyroidism (Bliddal, 2011a). Other potential causes of fetal hypothyroidism resulting in goiter include transplacental passage of thyroid peroxidase antibodies, fetal thyroid dyshormonogenesis, and maternal overconsumption of iodine supplements (Agrawal, 2002; Overcash, 2016). Goitrous hypothyroidism may lead to hydramnios, neck hyperextension, and delayed bone maturation. If the mother is receiving antithyroid medication, discontinuation is generally recommended, along with intraamnionic levothyroxine injection. However, optimal dosage and frequency have not been established, and reported dosages range from 50 to 800 g every 1 to 4 weeks (Abuhamad, 1995; Bliddal, 2011b; Ribault, 2009). Open fetal surgery is a highly specialized intervention performed at relatively few centers in the United States and for only a few fetal conditions. In many cases, data regarding the safety and efficacy of these procedures are limited. The Agency for Healthcare Research and Quality stresses that when considering fetal surgery, the overriding concern must be maternal and fetal safety. Guiding Principles for Fetal Surgical Procedures Accurate prenatal diagnosis for the defect is available, with staging if applicable the defect appears isolated, with no evidence of other abnormality or underlying genetic syndrome that would significantly worsen survival or quality of life the defect results in a high likelihood of death or irreversible organ destruction, and postnatal therapy is inadequate the procedure is technically feasible, and a multidisciplinary team is in agreement regarding the treatment plan Maternal risks from the procedure are well documented and considered acceptable There is comprehensive parental counseling It is recommended that there be an animal model for the defect and procedure Data from Deprest, 2010; Harrison, 1982; Vrecenak, 2013; Walsh, 2011. Some abnormalities amenable to fetal surgical treatment, antepartum or intrapartum, are shown in Table 16-2. An overview of these procedures, their indications, and complications is provided here to assist with initial patient evaluation and counseling. The mother must undergo general endotracheal anesthesia to suppress both uterine contractions and fetal responses. Using intraoperative sonographic guidance to avoid the placental edge, a low-transverse hysterotomy incision is made with a stapling device that seals the edges for hemostasis. To replace amnionic fluid losses, warmed fluid is continuously infused into the uterus thorough a rapid infusion device. The fetus is gently manipulated to permit pulse oximetry monitoring and to establish venous access, in case fluids or blood are emergently needed. Tocolysis typically includes intravenous magnesium sulfate for 24 hours, oral indomethacin for 48 hours, and, at some centers, oral nifedipine until delivery (Wu, 2009). Prophylactic antibiotics are also administered and generally continued for 24 hours following the procedure. In a review of 87 open procedures, Golombeck and coworkers (2006) reported the following morbidities: pulmonary edema-28 percent, placental abruption-9 percent, blood transfusion-13 percent, premature rupture of membranes-52 percent, and preterm delivery-33 percent. Wilson and associates (2010) reviewed subsequent pregnancy outcomes following open fetal surgery and reported that 14 percent of women experienced uterine rupture and 14 percent had uterine dehiscence.