*Important Notice : Guided tours to the Parliament Chamber are suspended until further notice as a preventative measure in response to Covid-19


Douglas P. Jutte MD, MPH

  • Associate Adjunct Professor, Community Health and Human Development

J Pediatr 167(1):58 diabetes thirst buy actos us, 2015 Garg N gestational diabetes test vancouver buy 30 mg actos with mastercard, Choudhary M blood sugar in the morning buy cheapest actos and actos, Sharma D diabetes medicine overdose purchase on line actos, et al: the role of early inhaled budesonide therapy in meconium aspiration in term newborns: a randomized control study diabetes symptoms after eating sugar discount 15 mg actos visa. J Matern Fetal Neonatal Med 29(1):36, 2016 Gazzin S, Tiribelli C: Bilirubin-induced neurological damage. Am J Obstet Gynecol 196:463, 2007 Harteman J, Groenendaal F, Benders M, et al: Role of thrombophilic factors in full-term infants with neonatal encephalopathy. Obstet Gynecol 127(3):426, 2016 Hirakawa E, Ibara S, Tokuhisa T, et al: Extracorporeal membrane oxygenation in 61 neonates: Single-center experience. Arch Pediatr Adolesc Med 165(8):692, 2011 Johnson C, Burd I, Northington F, et al: Clinical chorioamnionitis is associated with a more severe metabolic acidosis in neonates with suspected hypoxic-ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 100(3):F216, 2015 Kaplan M, Bromiker R, Hammerman C: Severe neonatal hyperbilirubinemia and kernicterus: are these still problems in the third millennium Am J Perinatol 23(1):41, 2006 Kirton A, Armstrong-Wells J, Chang T, et al: Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study. Neonatology 107(3):225, 2015 Linder I, Melamed N, Kogan A, et al: Gender and birth trauma in full-term infants. Pediatr Dermatol 34(1):e40, 2017 Maisonneuve E, Audibert F, Guilbaud L, et al: Risk factors for severe neonatal acidosis. J Perinatol 37(5):596, 2017 Martinez-Biarge M, Madero R, Gonzalez A, et al: Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associated with intrapartum sentinel events. Am J Obstet Gynecol 174:318, 1996 Plevani C, Pozzi I, Locatelli A, et al: Risk factors of neurological damage in infants with asphyxia. Expert Rev Hematol 10(7):607, 2017 Reuter S, Moser C, Baack M: Respiratory distress in the newborn. Arch Dis Child Fetal Neonatal Ed 97(5):F377, 2012 Saksenberg V, Bauch B, Reznik S: Massive acute thymic haemorrhage and cerebral haemorrhage in an intrauterine fetal death. J Perinatol 36 (Suppl 1):S29, 2016 Saroha M, Batra P, Dewan P, et al: Genital injuries in neonates following breech presentation. J Pediatr Surg 47(2):e19, 2012 Sgro M, Campbell D, Barozzino T, et al: Acute neurological findings in a national cohort of neonates with severe neonatal hyperbilirubinemia. J Perinatol 31(6):392, 2011 Sgro M, Kandasamy S, Shah V, et al: Severe neonatal hyperbilirubinemia decreased after the 2007 Canadian guidelines. Obstet Gynecol 107:550, 2006 Simonson C, Barlow P, Dehennin N, et al: Neonatal complications of vacuum-assisted delivery. Infect Dis Obstet Gynecol 2016:9848041, 2016 Smithers-Sheedy H, McIntyre S, Gibson C, et al: A special supplement: findings from the Australian Cerebral Palsy Register, birth years 1993 to 2006. Dev Med Child Neurol 58(Suppl 2):5, 2016 Spruijt M, Steggerda S, Rath M, et al: Cerebral injury in twin-twin transfusion syndrome treated with fetoscopic laser surgery. Arch Pediatr Adolesc Med 166(6):558, 2012 Takenouchi T, Kasdorf E, Engel M, et al: Changing pattern of perinatal brain injury in term infants in recent years. Orthopedics 39(4):e764, 2016 Thorngren-Jerneck K, Herbst A: Perinatal factors associated with cerebral palsy in children born in Sweden. J Pediatr 116:615, 1990 Torki M, Barton L, Miller D, et al: Severe brachial plexus palsy in women without shoulder dystocia. J Oral Maxillofac Surg 67(1):218, 2009 Villamor E, Tedroff K, Peterson M, et al: Association between maternal body mass index in early pregnancy and incidence of cerebral palsy. Obstet Gynecol 123(6):1288, 2014 Walsh B, Boylan G, Dempsey E, et al: Association of nucleated red blood cells and severity of encephalopathy in normothermic and hypothermic infants. Lancet 363:846, 2004 Wiberg N, Kallen K, Herbst A, et al: Relation between umbilical cord blood pH, base deficit, lactate, 5-minute Apgar score and development of hypoxic ischemic encephalopathy. Pediatrics 85:715, 1990 World Health Organization: Guidelines on Basic Newborn Resuscitation. Curr Opin Pediatr 29(1):12, 2017 Yeh P, Emary K, Impey L: the relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. Generally speaking, in the case of children born before the thirty-second week, the chances of surviving are very small. Even so, the preterm newborn is susceptible to various serious medical complications both early and later in life (Table 34-1). A less commonly cited cause of morbidity and mortality is congenital malformations, which are much more prevalent in preterm births. In 2009, two thirds of all infant deaths in the United States were in the 12 percent born before 37 weeks (Mathews, 2013). Fortunately, during the past decade, rates of preterm birth have declined from approximately 12 percent in 2007 to 10 percent in 2014. This results from immature lungs that are unable to sustain necessary oxygenation. Resulting hypoxia is an underlying associated cause of neurological damage such as cerebral palsy. Etiopathogenesis To provide blood gas exchange immediately following delivery, the lungs must rapidly fill with air while being cleared of fluid. Although some of the fluid is expressed as the chest is compressed during vaginal delivery, most is absorbed through the pulmonary lymphatics via complex mechanisms described in Chapter 32 (p. It lowers surface tension and thereby prevents lung collapse during expiration (Chap. Although respiratory distress syndrome is generally a disease of preterm neonates, it does develop in term newborns, especially with sepsis or meconium aspiration. In these cases, surfactant can be inactivated by inflammation and/or presence of meconium (Chap. With inadequate surfactant, alveoli are unstable, and low pressures cause collapse at end expiration. Partial persistence of the fetal circulation may lead to pulmonary hypertension and a relative right-to-left shunt. When oxygen therapy is initiated, the pulmonary vascular bed dilates, and the shunt reverses. Protein-filled fluid leaks into the alveolar ducts, and the cells lining the ducts slough. Hyaline membranes composed of fibrin-rich protein and cellular debris line the dilated alveoli and terminal bronchioles. At autopsy, with hematoxylin-eosin staining of lung tissue, these membranes appear amorphous and eosinophilic, like hyaline cartilage. Because of this, respiratory distress syndrome is also termed hyaline membrane disease. Shunting of blood through nonventilated lung contributes to hypoxemia and to metabolic and respiratory acidosis. The chest radiograph shows a diffuse reticulogranular infiltrate and an airfilled tracheobronchial tree-air bronchogram. Although hypoxemia prompts supplemental oxygen, excess oxygen can damage the pulmonary epithelium, retina, and other immature tissues. Despite this, advances in mechanical ventilation technology have improved neonatal survival rates. This allows high inspired-oxygen concentrations to be reduced, thereby minimizing its toxicity. Namely, mechanical ventilation places a newborn at risk for barotrauma and volutrauma. In affected newborns, alveolar and pulmonary vascular development is disrupted and leads to hypoxia, hypercarbia, and chronic oxygen dependence (Davidson, 2017; Kair, 2012). The American Academy of Pediatrics now recommends against routine steroid use because of limited benefits and greater rates of impaired motor and cognitive function and school performance in exposed neonates (Doyle, 2014a,b; Watterberg, 2010). Despite initial enthusiasm, clinical trials failed to demonstrate a consistent benefit. Caffeine has been used widely to treat apnea of prematurity, but it also has bronchodilatory effects. The antioxidant vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. They contain biological or animal surfactants such as bovine-Survanta, calf -Infasurf, or porcine-Curosurf. Synthetic surfactants such as first-generation Exosurf and second-generation Surfaxin R are equivalent but not superior to animal-derived surfactant (Moya, 2007). In a Cochrane review, Ardell and coworkers (2015) found that animal-derived surfactants led to better outcomes than synthetic surfactants, which do not contain important surfactant proteins. It has been used for prophylaxis of preterm, at-risk newborns and for rescue of those with established disease. Given together, antenatal corticosteroids and surfactant result in an even greater reduction in the overall death rate. Exploration of different, less invasive ways to deliver rescue surfactant to spontaneously breathing preterm neonates is currently underway. Potential routes include surfactant application into the pharynx, surfactant nebulization, or application via laryngeal mask or via a thin catheter placed in the trachea (Kribs, 2016). The American College of Obstetricians and Gynecologists (2016a) considers all women at risk for preterm birth in this gestational-age range to be potential candidates for therapy. Amniocentesis to Assess Fetal Lung Maturity In some instances, when gestational age is uncertain, knowledge of fetal lung maturity may influence plans for delivery. One example is the woman with a prior classical cesarean delivery in whom repeat operation is planned and gestational age cannot be confirmed. Several tests are used to ensure fetal pulmonary maturity by analysis of amnionic fluid obtained by sonographically guided amniocentesis. At Parkland Hospital, we still find an occasional indication for such testing, however, the American College of Obstetricians and Gynecologists (2017a,b) counsels against its use in most of these cases. If amniocentesis is elected, fluid acquisition is similar to that described for second-trimester amniocentesis (Chap. Importantly, administration of corticosteroids to induce pulmonary maturation has variable effects on some of these tests. Of biochemical tests, the labor-intensive lecithin-sphingomyelin (L/S) ratio for many years was the gold-standard test. At 32 to 34 weeks, the concentration of lecithin relative to sphingomyelin begins to rise. Some recommend that phosphatidylglycerol, another surfactant phospholipid, be documented in amnionic fluid of these women. Based on current evidence, it is unclear if either diabetes, per se, or its level of control causes false-positive phospholipid test results for fetal lung maturity (De Luca, 2009). Problems include errors caused by slight contamination and frequent false-negative test results. There is often radiological evidence of pneumatosis intestinalis-bowel wall gas derived from invading bacteria. Various hypothesized causes include perinatal hypotension, hypoxia, sepsis, umbilical catheterization, exchange transfusions, blood transfusions, and the feeding of cow milk and hypertonic solutions (Neu, 2010). The pathophysiology is thought to be multifactorial, and genetic disposition, intestinal immaturity, imbalance in microvascular tone, abnormal microbial colonization in the intestine, exposure to enteral feeds, and highly immunoreactive intestinal mucosa play potential roles (Caplan, 2017; Neu, 2010). Medical treatment includes abdominal decompression, bowel rest, broadspectrum antibiotics, and parenteral nutrition. Surgery is reserved for neonates with intestinal perforation or deteriorating clinical or biochemical status. Possible surgical procedures include drain placement, exploratory laparotomy with resection of diseased bowel, or enterostomy with creation of a stoma (Neu, 2010). After the discovery that the disease resulted from hyperoxemia, its frequency declined but began to rise again with the increasing survival rates of extremely preterm newborns. Normally, the fetal retina vascularizes centrifugally from the optic nerve starting at approximately the fourth month and continues until shortly after birth. During vascularization, excessive oxygen induces severe retinal vasoconstriction with endothelial damage and vessel obliteration. This is followed by subsequent aberrant neovascularization, in which the new vessels penetrate the retina and extend into the vitreous. After birth, there is a "relative" hyperoxia compared with in utero oxygen content, even in newborns not exposed to higher inspired oxygen concentrations. The two target ranges of oxygen saturation were 85 to 89 percent in one arm and 91 to 95 percent in the other arm. Death before discharge occurred significantly more frequently in the lower-oxygen saturation group-20 versus 16 percent. In preterm neonates, cerebral lesions detected by neuroimaging include intraventricular hemorrhage, cerebellar hemorrhage, periventricular hemorrhagic infarction, cystic periventricular leukomalacia, and diffuse white matter injury. All of these are strongly associated with adverse neurodevelopmental outcomes (Kwon, 2014). Cranial sonography remains the preferred approach for detecting frequently occurring brain abnormalities and acute events. It is readily available and reliable for detecting common abnormalities and monitoring brain growth. Because cystic injuries may take 2 to 5 weeks to evolve, serial scans are obtained during this time. In those whose findings are transient and resolve in the neonatal period, prognosis is improved compared with infants whose lesions remain and evolve. Intracranial Hemorrhage There are five major categories of intracranial hemorrhage in the neonate (Volpe, 2008). Primary subarachnoid hemorrhage is more common in those born preterm and is frequently benign. Cerebellar hemorrhage is also more frequent in preterm neonates and is increasingly recognized as a cause of serious sequelae.

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Investigators found no significant difference in immediate neonatal or maternal morbidity compared with that of 42 women delivered for similar indications by cesarean but without such a trial diabetes in dogs last stages purchase actos 30mg on-line. Conversely diabetes medications weight gain buy actos 15 mg without a prescription, in 61 women who had "unexpected" vacuum or forceps failure in which there was no prior preparation for immediate cesarean delivery diabetes mellitus 2 medications purchase 45mg actos overnight delivery, neonatal morbidity was higher diabetes mellitus quotes buy actos 45 mg low price. Some factors associated with operative delivery failure are persistent occiput posterior position and birthweight >4000 g (Ben-Haroush non sugar diabetes in dogs generic actos 15 mg with mastercard, 2007; Verhoeven, 2016). However, Palatnik and associates (2016) found that risk factors poorly predicted success. In general, to avert morbidity with failed forceps or vacuum delivery, the American College of Obstetricians and Gynecologists (2015) cautions that these trials should be attempted only if the clinical assessment suggests a successful outcome. Sequential instrumentation most often involves an attempt at vacuum extraction followed by one with forceps. This most likely stems from the higher completion rate with forceps compared with vacuum extraction noted earlier. This practice significantly increases risks for fetal trauma (Dupuis, 2005; Gardella, 2001; Murphy, 2011). Because of these adverse outcomes, the American College of Obstetricians and Gynecologists (2015) recommends against the sequential use of instruments unless there is a "compelling and justifiable reason. In many programs, training in even low and outlet forceps procedures has reached critically low levels. For residents completing training in 2015, the Accreditation Council for Graduate Medical Education reported a median of only five forceps deliveries, and that for vacuum deliveries was 16. Because traditional hands-on training has evolved, residency programs should have readily available skilled operators to teach these procedures by simulation as well as through actual cases (Skinner, 2017; Spong, 2012). And, the effectiveness of simulation training has been reported (Dupuis, 2006, 2009; Leslie, 2005). In one program, maternal and neonatal morbidity rates with operative delivery decreased after the implementation of a formal education program that included a manikin and pelvic model (Cheong, 2004). In another, a 59-percent increase in forceps deliveries over 2 years was related to a single experienced and proactive instructor assigned to teach forceps to residents in labor and delivery (Solt, 2011). Branches are designated left or right according to the side of the maternal pelvis to which they are applied. Of these, the outward cephalic curve conforms to the round fetal head, whereas the upward pelvic curve corresponds more or less to the curve of the birth canal. Some blades have an opening within or a depression along the blade surface and are termed fenestrated or pseudofenestrated, respectively. With pseudofenestration, the forceps blade is smooth on the outer maternal side but indented on the inner fetal surface. The goal is to reduce head slipping yet improve the ease and safety of application and removal of forceps compared with pure fenestrated blades. In general, fenestrated blades are used for a fetus with a molded head or for rotation. In most situations, however, despite these subtle differences any are appropriate. Locks are found on all forceps and help to connect the right and left branches and stabilize the instrument. They can be located at the end of the shank nearest to the handles (English lock), at the ends of the handles (pivot lock), or along the shank (sliding lock). Although varied in design, handles, when squeezed, raise compression forces against the fetal head. Blade Application and Delivery Forceps blades grasp the head and are applied according to fetal head position. The handle of the left branch is grasped between the thumb and two fingers of the left hand. The blade tip is then gently passed into the vagina between the fetal head and the palmar surface of the fingers of the right hand. For application of the right blade, two or more fingers of the left hand are introduced into the right posterior portion of the vagina to serve as a guide for the right blade. With each blade, the thumb is positioned behind the heel, and most of the insertion force comes from this thumb. The fetal head is perfectly grasped only when the long axis of the blades corresponds to the occipitomental diameter. Applied in this way, the forceps should not slip, and traction may be applied most advantageously. With most forceps, if one blade is applied over the brow and the other over the occiput, the instrument cannot be locked, or if locked, the blades will slip off when traction is applied. With both branches in place, it should be an easy matter to articulate the handles, engage the lock, and correct asynclitism if present. Asynclitism is resolved by pulling and/or pushing each branch along the long axis of the instrument until the finger guards align. When the head is at 0 to +2 of +5 station, the initial direction of traction is quite posterior, almost toward the floor. As a teaching tool for this, a Bill axis traction device can be attached over the finger guards of most forceps. When the arrow points directly to the line, traction is along the path of least resistance. With traction, as the vulva is distended by the occiput, an episiotomy may be performed if indicated. Additional horizontal traction is applied, and the handles are then gradually elevated. During the birth of the head, mechanisms of spontaneous delivery should be simulated as closely as possible. The force produced by the forceps on the fetal skull is a function of both traction and compression by the forceps, as well as friction produced by maternal tissues. It is impossible to ascertain the amount of force exerted by forceps for an individual patient. Traction should therefore be intermittent, and the head should be allowed to recede between contractions, as in spontaneous labor. Except when urgently indicated, as in severe fetal bradycardia, delivery should be sufficiently slow, deliberate, and gentle to prevent undue head compression. After the vulva has been well distended by the head, the delivery may be completed in several ways. If this is done, however, the blade volume adds to vulvar distention, thus increasing the likelihood of laceration or necessitating a large episiotomy. To prevent this, the forceps may be removed, and delivery is then completed by maternal pushing. Importantly, if blades are disarticulated and removed too early, the head may recede and lead to a prolonged delivery. The first is fetal head flexion to provide a smaller diameter for rotation and subsequent descent. Second, slight destationing of the fetal head moves the head to a level in the maternal pelvis with sufficient room to complete the rotation. Importantly, destationing should not be confused with disengaging the fetal head, which is proscribed. Concurrently, some prefer to also place the other hand externally on the corresponding side of the maternal abdomen to pull the fetal back up toward the midline in synchrony with the internal rotation. Le Ray and colleagues (2007, 2013) reported a success rate of greater than 90 percent with manual rotation. The handles are then slowly elevated until the occiput gradually emerges over the upper margin of the perineum. The forceps are directed downward again, and the nose, mouth, and chin successively emerge from the vulva. The characteristic features are minimal pelvic curvature (A), sliding lock (B), and light weight. With experienced operators, high success rates with minimal maternal morbidity can be achieved (Burke, 2012; Stock, 2013). Either standard forceps, such as Simpson, or specialized forceps, such as Kielland, are employed. With Kielland forceps, each handle has a small knob, and branches are placed so that this knob faces the occiput. The station of the fetal head must be accurately determined to be at, or preferably below, the level of the ischial spines, especially in the presence of extreme molding. With the wandering method, the anterior blade is first introduced into the posterior pelvis. To permit this sweep of the blade, the handle is held close to the maternal left buttock throughout the maneuver. Insertion of the left branch of the Kielland forceps directly posterior along the hollow of the sacrum. This branch is inserted to the maternal right of the anterior branch to aid in engaging the sliding lock. The first and second fingers of the left hand are placed over the finger guards with the palm against the handles. For rotation in a counterclockwise direction, the wrist of the left hand supinates, to direct this palm upward. Simultaneously, two fingers of the right hand press on the edge of the right parietal bone that borders the lambdoid suture. The second type of blade application introduces the anterior blade with its cephalic curve directed upward to curve under the symphysis. After it has been advanced far enough toward the upper vagina, it is turned on its long axis through 180 degrees to adapt the cephalic curvature to the head. With either application, after rotation completion, the operator may choose from two acceptable methods for delivery. In one, the operator applies traction on the Kielland forceps using a bimanual grip described previously for conventional forceps (p. When the posterior fontanel has passed under the subpubic arch, the handles can be elevated to the horizontal. Raising the handles above the horizontal may cause vaginal sulcus tears because of the reverse pelvic curve (Dennen, 1955). Alternatively, the Kielland forceps can be removed after rotation and replaced with conventional forceps. With this approach, moderate traction is first employed to seat the head before switching instruments. Face Presentations With a mentum anterior face presentation, forceps can be used to effect vaginal delivery. The blades are applied to the sides of the head along the occipitomental diameter, with the pelvic curve directed toward the neck. Then, by an upward movement, the face is slowly extracted, with the nose, eyes, brow, and occiput appearing in succession over the anterior margin of the perineum. Forceps should not be applied to the mentum posterior presentation because vaginal delivery is impossible except in very small fetuses. In the United States, vacuum extractor is the preferred term, whereas in Europe it is commonly called a ventouse. Theoretical benefits of this tool compared with forceps include simpler requirements for precise positioning on the fetal head and avoidance of space-occupying blades within the vagina, thereby mitigating maternal trauma. The Kiwi OmniCup contains a handheld vacuum-generating pump, which is attached via flexible tubing to a rigid plastic mushroom cup. Vacuum cups may be metal or hard or soft plastic, and they may also differ in their shape, size, and reusability. In the United States, nonmetal cups are generally preferred, and there are two main types. The soft cup is a pliable bell-shaped dome, whereas the rigid type has a firm flattened mushroom-shaped cup and circular ridge around the cup rim (Table 29-2). When compared, rigid mushroom cups generate significantly more traction force (Hofmeyr, 1990; Muise, 1993). Vacuum Cups for Operative Vaginal Delivery Several investigators have compared outcomes with various rigid and soft cups. In another study, Kuit and coworkers (1993) found that the only advantage of the soft cups was a lower incidence of scalp injury. They reported a 14-percent episiotomy extension rate with both rigid and pliable cups. In a review, Vacca (2002) concluded that there were fewer scalp lacerations with the soft cup, but that the rate of cephalohematomas and subgaleal hemorrhage was similar between soft and rigid cups. Importantly, high-pressure vacuum generates large amounts of force regardless of the cup used (Duchon, 1998). Aside from the cup, the shaft that connects the cup and handle may be flexible or semiflexible. Last, the vacuum generator may be handheld and actuated by the operator or may be held and operated by an assistant. Technique An important step in vacuum extraction is proper cup placement over the flexion point. This pivot point maximizes traction, minimizes cup detachment, flexes but averts twisting the fetal head, and delivers the smallest head diameter through the pelvic outlet. This improves success rates, lowers fetal scalp injury rates, and lessens perineal trauma because the smallest fetal head diameter distends the vulva (Baskett, 2008). The flexion point is found along the sagittal suture, approximately 3 cm in front of the posterior fontanel and approximately 6 cm from the anterior fontanel. Because cup diameters range from 5 to 6 cm, when properly placed, the cup rim lies 3 cm from the anterior fontanel.

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However diet diabetes kalori generic actos 45 mg overnight delivery, if an IgG red cell antibody is detected and there is any doubt as to its significance diabetic humor purchase actos paypal, the clinician should err on the side of caution diabetes signs on feet buy actos 30 mg overnight delivery, and the pregnancy should be evaluated for hemolytic disease diabetes mellitus statistics purchase actos 45mg free shipping. They are predominantly IgM and are not expressed on fetal red cells (American College of Obstetricians and Gynecologists blood glucose levels actos 45mg mastercard, 2016). Approximately 90 percent of non-Hispanic white Americans and up to 98 percent of African Americans are Kell negative. Transfusion history is important, as nearly 90 percent of Kell sensitization cases result from transfusion with Kell-positive blood. Kell sensitization may develop more rapidly and may be more severe than with sensitization to D and other blood group antigens. This is because Kell antibodies attach to erythrocyte precursors in the fetal bone marrow, thereby impairing the normal hemopoietic response to anemia. With fewer erythrocytes produced, there is less hemolysis, and severe anemia may not be predicted by the maternal Kell antibody titer. One option is to use a lower critical titer-1:8-for Kell sensitization (Moise, 2012). The American College of Obstetricians and Gynecologists (2016) has recommended that antibody titers not be used to monitor Kell-sensitized pregnancies. This is because most group O women have developed anti-A and anti-B isoagglutinins before pregnancy from exposure to bacteria displaying similar antigens. This is because most anti-A and anti-B antibodies are IgM and do not cross the placenta. Fetal red cells also have fewer A and B antigenic sites than adult cells and are thus less immunogenic. Careful neonatal observation is essential, however, because hyperbilirubinemia may require treatment with phototherapy or occasionally transfusion (Chap. Management of the Alloimmunized Pregnancy An estimated 25 to 30 percent of fetuses from D-alloimmunized pregnancies will have mild-to-moderate hemolytic anemia. And without treatment, up to 25 percent will develop hydrops (Tannirandorn, 1990). If alloimmunization is detected and the titer is below the critical value, the titer is generally repeated every 4 weeks for the duration of the pregnancy (American College of Obstetricians and Gynecologists, 2016). Importantly, if a prior pregnancy was complicated by alloimmunization, serial titer assessment is not indicated, and the pregnancy is assumed to be at risk regardless of titer. In any pregnancy in which an antibody titer has reached a critical value, there is no benefit to repeating it. The pregnancy is at risk even if the titer drops, and further evaluation is still required. Determining Fetal Risk Up to 40 percent of D-negative pregnant women carry a D-negative fetus. The presence of anti-D antibodies reflects maternal sensitization but does not indicate whether the fetus is D-positive. If a woman became sensitized in a prior pregnancy, her antibody titer might rise to high levels during the current pregnancy even if the current fetus is D-negative, due to an amnestic response. In a non-Hispanic white couple in which the woman is D-negative, there is an 85-percent chance that the man is D-positive. And, if he is heterozygous, then half of his children will be at risk for hemolytic disease. Alloimmunization to a red cell antigen other than D may have occurred following a blood transfusion in the past, and if that antigen is not present on paternal erythrocytes, the pregnancy is not at risk. Initial evaluation of alloimmunization begins with determining the paternal erythrocyte antigen status. Provided that paternity is certain, if the father is negative for the red cell antigen to which the mother is sensitized, the pregnancy is not at risk. If the father is heterozygous-or if paternity is not known-the woman should be offered assessment of fetal genotype. Fetal testing for other antigens-such as E/e, C/c, Duffy, Kell, Kidd, and M/N-is also available with this method. Chorionic villus sampling is not recommended because of greater risk for fetomaternal hemorrhage and subsequent worsening of alloimmunization. The reported sensitivity exceeds 99 percent, the specificity exceeds 95 percent, and positive- or negativepredictive values are similarly very high (de Haas, 2016; Johnson, 2017; Moise, 2016; Vivanti, 2016). There are two potential indications in D-negative pregnant women: (1) in women with D alloimmunization, testing can identify fetuses that are also Dnegative and do not require anemia surveillance, and (2) in women without D alloimmunization, anti-D immune globulin might be withheld if the fetus is D negative. The gestational age at which fetal anemia developed in prior pregnancies is important because anemia tends to occur earlier and be sequentially more severe. The anemic fetus shunts blood preferentially to the brain to maintain adequate oxygenation. The velocity rises because of increased cardiac output and decreased blood viscosity. This provided a sensitivity of 100 percent, with a false-positive rate of 12 percent. The blue line indicates the median peak systolic velocity in normal pregnancies, and the red line shows 1. More than 50 years ago, Liley (1961) demonstrated the utility of amnionic fluid spectral analysis to measure bilirubin concentration and to thereby estimate hemolysis severity. These zones roughly correlated with fetal hemoglobin concentration, and thus with anemia severity. However, the amnionic fluid bilirubin level is normally high in midpregnancy, limiting the reliability of this technique. Fetal blood sampling and intrauterine transfusion are generally performed prior to 34 to 35 weeks (Society for Maternal-Fetal Medicine, 2015a). Intravascular transfusion into the umbilical vein under sonographic guidance is the preferred method of fetal transfusion. Transfusion into the fetal peritoneal cavity may be necessary with severe, early-onset hemolytic disease in the early second trimester, a time when the umbilical vein is too narrow to readily permit needle entry. With hydrops, although peritoneal absorption is impaired, some prefer to transfuse into both the fetal peritoneal cavity and the umbilical vein. Transfusion is generally recommended only if the fetal hematocrit is <30 percent (Society for Maternal-Fetal Medicine, 2015a). The red cells transfused are type O, D-negative, cytomegalovirus-negative, packed to a hematocrit of approximately 80 percent to prevent volume overload, irradiated to prevent fetal graft-versus-host reaction, and leukocyte-poor. Before transfusion, a paralytic agent such as vecuronium may be given to the fetus to minimize movement. The volume transfused may be estimated by multiplying the estimated fetal weight in grams by 0. Subsequent transfusions usually take place every 2 to 4 weeks, depending on the hematocrit. It is hypothesized that the change in threshold compensates for the contribution of donor cells in the initial transfusion, because donor cells (from adults) have a smaller mean corpuscular volume. Alternately, the timing of subsequent transfusions is based on anemia severity and posttransfusion hematocrit. Following transfusion, the fetal hematocrit generally drops by approximately 1 percent per day. Procedure-related complications have declined significantly at experienced centers in recent years, with overall survival rates exceeding 95 percent (Zwiers, 2017). Complications include fetal death in approximately 2 percent, need for emergent cesarean delivery in 1 percent, and infection and preterm rupture of membranes in 0. The stillbirth rate exceeds 15 percent if transfusion is required before 20 weeks (Lindenberg, 2013; Zwiers, 2017). Considering that fetal transfusion is potentially lifesaving in severely compromised fetuses, these risks should not dissuade therapy. Van Kamp (2001) reported that if hydrops had developed, the survival rate approached 75 to 80 percent. However, of the nearly two thirds with resolution of hydrops following transfusion, more than 95 percent survived. Lindenberg (2012) reviewed long-term outcomes following intrauterine transfusion in a cohort of more than 450 alloimmunized pregnancies. Alloimmunization was secondary to anti-D in 80 percent, anti-Kell in 12 percent, and anti-c in 5 percent. Approximately a fourth of affected fetuses had hydrops, and more than half also required exchange transfusion in the neonatal period. Among nearly 300 children aged 2 to 17 years who participated in neurodevelopmental testing, fewer than 5 percent had severe impairments. These included severe developmental delay in 3 percent, cerebral palsy in 2 percent, and deafness in 1 percent. Prevention of Anti-D Alloimmunization Anti-D immune globulin is one of the success stories of modern obstetrics. In countries without access to anti-D immune globulin, up to 10 percent of D-negative pregnancies are complicated by hemolytic disease of the fetus and newborn (Zipursky, 2015). Despite long-standing and widespread use, its mechanism of action is not completely understood. As many as 90 percent of alloimmunization cases occur from fetomaternal hemorrhage at delivery. Routine postpartum administration of anti-D immune globulin to at-risk pregnancies within 72 hours of delivery lowers the alloimmunization rate by 90 percent (Bowman, 1985). If not needed, it will not cause harm, but failure to provide it when needed can have severe consequences. Current preparations of anti-D immune globulin are derived from human plasma donated by individuals with high-titer anti-D immunoglobulin D antibodies. Formulations prepared by cold ethanol fractionation and ultrafiltration must be administered intramuscularly because they contain plasma proteins that could result in anaphylaxis if given intravenously. However, formulations prepared using ion exchange chromatography may be administered either intramuscularly or intravenously. This is important for treatment of significant fetomaternal hemorrhage, which is discussed subsequently. Both preparation methods effectively remove viral particles, including hepatitis and human immunodeficiency viruses. Depending on the preparation, the half-life of anti-D immune globulin ranges from 16 to 24 days, which is why it is given both in the third trimester and following delivery. Before the 28-week dose of anti-D immune globulin, repeat antibody screening is recommended to identify individuals who have become alloimmunized (American Academy of Pediatrics, 2017). Recognizing that 40 percent of neonates born to D-negative women are also D negative, administration of immune globulin is recommended only after the newborn is confirmed to be D positive (American College of Obstetricians and Gynecologists, 2017). If immune globulin is inadvertently not administered following delivery, it should be given as soon as the omission is recognized, because there may be some protection up to 28 days postpartum (Bowman, 2006). Anti-D immune globulin is also administered after pregnancy-related events that could result in fetomaternal hemorrhage (see Table 15-2). Anti-D immune globulin may produce a weakly positive-1:1 to 1:4-indirect Coombs titer in the mother. Additionally, as the body mass index increases above 27 to 40 kg/m2, serum antibody levels decrease by 30 to 60 percent and may be less protective (MacKenzie, 2006; Woelfer, 2004). D-negative women who receive other types of blood products-including platelet transfusions and plasmapheresis-are also at risk of becoming sensitized, and this can be prevented with anti-D immune globulin. Rarely, a small amount of antibody crosses the placenta and results in a weakly positive direct Coombs test in cord and infant blood. Despite this, passive immunization does not cause significant fetal or neonatal hemolysis. It is estimated that in 2 to 3 per 1000 pregnancies, the volume of fetomaternal hemorrhage exceeds 30 mL of whole blood (American College of Obstetricians and Gynecologists, 2017). If additional anti-D immune globulin is considered only for women with risk factors such as those shown in Table 15-2, then half of those who require additional immune globulin may be missed. For this reason, all D-negative women should be screened at delivery, typically with a rosette test, followed by quantitative testing if indicated (American College of Obstetricians and Gynecologists, 2017). The rosette test is a qualitative test that identifies whether fetal D-positive cells are present in the circulation of a D-negative woman. A sample of maternal blood is mixed with anti-D antibodies that coat any D-positive fetal cells present in the sample. Indicator red cells bearing the D-antigen are then added, and rosettes form around the fetal cells as the indicator cells attach to them by the antibodies. Thus, if rosettes are visualized, there are fetal D-positive cells in that sample. In the setting of D incompatibility, or any time a large fetomaternal hemorrhage is suspected- regardless of antigen status, a Kleihauer-Betke test or flow cytometry test are used. The dosage of anti-D immune globulin is calculated from the estimated volume of the fetal-to-maternal hemorrhage, as described on page 307. One 300-g dose is given for each 15 mL of fetal red cells or 30 mL of fetal whole blood to be neutralized. If using an intramuscular preparation of anti-D immune globulin, no more than five doses may be given in a 24-hour period. If using an intravenous preparation, two ampules-totaling 600 g-may be given every 8 hours.

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Am J Obstet Gynecol 179(4):957 diabetic diet calories actos 45mg cheap, 1998 Bhattacharya S diabetes type 1 essay buy actos 15mg with amex, Townend J diabetes symptoms hypoglycemia purchase actos 30 mg overnight delivery, Bhattacharya S: Recurrent miscarriage: are three miscarriages one too many Occup Environ Med 54:541 diabetic diet without medication order actos with visa, 1997 Borgatta L diabetes diet tips in hindi buy actos in india, Roncari D, Sonalkar S, et al: Mifepristone vs. Radiology 178(2):375, 1991 Bukulmez O, Arici A: Luteal phase defect: myth or reality. Contraception 75(3):230, 2007 Caruso A, Trivellini C, De Carolis S, et al: Emergency cerclage in the presence of protruding membranes: is pregnancy outcome predictable Acta Obstet Gynecol Scand 79:265, 2000 Casikar I, Lu C, Oates J, et al: the use of power Doppler colour scoring to predict successful expectant management in women with an incomplete miscarriage. Fertil Steril 85(2): 508, 2006 Clark W, Bracken H, Tanenhaus J, et al: Alternatives to a routine follow-up visit for early medical abortion. Reprod Biomed Online 17:151, 2008 Condous G, Okaro E, Khalid A, et al: Do we need to follow up complete miscarriages with serum human chorionic gonadotrophin levels Am J Obstet Gynecol 171(2):380, 1994 Dao B, Blum J, Thieba B, et al: Is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care Am J Obstet Gynecol 168(3 Pt 1):903, 1993 Dean G, Colarossi L, Porsch L, et al: Manual compared with electric vacuum aspiration for abortion at less than 6 weeks of gestation: a randomized controlled trial. Obstet Gynecol 125(5):1121, 2015 de La Rochebrochard E, Thonneau P: Paternal age >or = 40 years: an important risk factor for infertility. Obstet Gynecol 123(6):1162, 2014 Diedrich J, Drey E, Society of Family Planning: Induction of fetal demise before abortion. Obstet Gynecol 126(1):125, 2015 Eiben B, Bartels I, Bahr-Prosch S, et al: Cytogenetic analysis of 750 spontaneous abortions with the direct-preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. N Engl J Med 374(9):843, 2016 Fjerstad M, Trussell J, Sivin I, et al: Rates of serious infection after changes in regimens for medical abortion. Contraception 89(2):75, 2014 Garber J, Cobin R, Gharib H, et al: Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. McGraw-Hill Education, New York, 2016 Hannafin B, Lovecchio F, Blackburn P: Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin J Obstet Gynaecol Can 35(2):138, 2013 Hawkins E, Nimaroff M: Vaginal erosion of an abdominal cerclage 7 years after laparoscopic placement. New York, McGraw-Hill Education, 2017 Heuser C, Dalton J, Macpherson C, et al: Idiopathic recurrent pregnancy loss recurs at similar gestational ages. Fertil Steril 37:542, 1982 Kajii T, Ferrier A, Niikawa N, et al: Anatomic and chromosomal anomalies in 639 spontaneous abortions. Am J Perinatol 33(14):1337, 2016 Kangatharan C, Labram S, Bhattacharya S: Interpregnancy interval following miscarriage and adverse pregnancy outcomes: systematic review and meta-analysis. Int J Gynaecol Obstet 116(3):244, 2012 Kibel M, Asztalos E, Barrett J, et al: Outcomes of pregnancies complicated by preterm premature rupture of membranes between 20 and 24 weeks of gestation. N Engl J Med 341:1639, 1999 Kleinhaus K, Perrin M, Friedlander Y, et al: Paternal age and spontaneous abortion. Hum Reprod 30(3):495, 2015 Korjamo R, Mentula M, Heikinheimo O: Immediate versus delayed initiation of the levonorgestrelreleasing intrauterine system following medical termination of pregnancy-1 year continuation rates: a randomised controlled trial. J Ultrasound Med 8(10):561, 1989 Lahteenmaki P, Luukkainen T: Return of ovarian function after abortion. Radiology 183(1):115, 1992 Locatelli A, Vergani P, Bellini P, et al: Amnioreduction in emergency cerclage with prolapsed membranes: comparison of two methods for reducing the membranes. Obstet Gynecol 115:935, 2010 MacIsaac L, Darney P: Early surgical abortion: an alternative to and backup for medical abortion. Am J Obstet Gynecol 183:S76, 2000 MacIsaac L, Grossman D, Balistreri E, et al: A randomized controlled trial of laminaria, oral misoprostol, and vaginal misoprostol before abortion. N Engl J Med 364(4):332, 2011 Muris C, Girard B, Creveuil C, et al: Management of premature rupture of membranes before 25 weeks. J Thromb Haemost 4(2):295, 2006 Miyazaki K, Furuhashi M, Yoshida K, et al: Aggressive intervention of previable preterm premature rupture of membranes. J Reprod Med 43(10):877, 1998 Nakayama D, Masuzaki H, Miura K, et al: Effect of placenta previa on blood loss in secondtrimester abortion by labor induction using gemeprost. Contraception 75(3):238, 2007 National Abortion Federation: 2016 Clinical policy guidelines. Obstet Gynecol 118(3):601, 2011 Nielsen S, Hahlin M, Platz-Christensen J: Randomised trial comparing expectant with medical management for first trimester miscarriages. Obstet Gynecol Surv 54:391, 1999 Olund A, Kindahl H, Oliw E, et al: Prostaglandins and thromboxanes in amniotic fluid during rivanol-induced abortion and labour. Prostaglandins 19(5):791, 1980 Owen J: First- and second-trimester pregnancy termination. 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Fertil Steril 37(5):593, 1982 Schneider D, Bukovsky I, Caspi E: Safety of midtrimester pregnancy termination by laminaria and evacuation in patients with previous cesarean section. Am J Obstet Gynecol 171(2):554, 1994 Schneider D, Golan A, Langer R, et al: Outcome of continued pregnancies after first and second trimester cervical dilatation by laminaria tents. J Ultrasound Med 33(2):337, 2014 Shannon C, Wiebe E, Jacot F: Regimens of misoprostol with mifepristone for early medical abortion: a randomized trial. Antiseptic 52:299, 1955 Shochet T, Diop A, Gaye A, et al: Sublingual misoprostol versus standard surgical care for treatment of incomplete abortion in five sub-Saharan African countries. J Obstet Gynecol Neonatal Nurs 37(4):395, 2008 Society for Assisted Reproductive Technology: Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril 90(5 Suppl):S136, 2008 Society for Maternal-Fetal Medicine: Cervical cerclage for the woman with prior adverse pregnancy outcome. J Clin Ultrasound 26(1):33, 1998 Stein Z, Kline J, Susser E, et al: Maternal age and spontaneous abortion. Hum Reprod 25(9):2203, 2010 Stockheim D, Machtinger R, Wiser A, et al: A randomized prospective study of misoprostol or mifepristone followed by misoprostol when needed for the treatment of women with early pregnancy failure. Am J Obstet Gynecol 143(4):481, 1982 Sugibayashi S, Aeby T, Kim D, et al: Amniotic fluid arborization in the diagnosis of previable preterm premature rupture of membranes. Obstet Gynecol 104:784, 2004 Sundtoft I, Langhoff-Roos J, Sandager P, et al: Cervical collagen is reduced in non-pregnant women with a history of cervical insufficiency and a short cervix. Int J Gynaecol Obstet 99 Suppl 2:S160, 2007 Templeton A, Grimes D: A request for abortion. Obstet Gynecol 101:565, 2003 Thangaratinam S, Tan A, Knox E, et al: Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. Lancet 363:1849, 2004 Trinder J, Brocklehurst P, Porter R, et al: Management of miscarriage: expectant, medical, or surgical Fetal Diagn Ther March 29, 2017 [Epub ahead of print] Virk J, Zhang J, Olsen J: Medical abortion and the risk of subsequent adverse pregnancy outcomes. Lancet 369:1938, 2007 von Hertzen H, Piaggio G, Wojdyla D, et al: Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomized factorial controlled equivalence trial. Obstet Gynecol 126(2):258, 2015 Zaveri V, Aghajafari F, Amankwah K, et al: Abdominal versus vaginal cerclage after a failed transvaginal cerclage: a systematic review. Whitridge Williams (1903) Following fertilization and fallopian tube transit, the blastocyst normally implants in the endometrial lining of the uterine cavity. This small proportion disparately accounts for 3 percent of all pregnancy-related deaths (Creanga, 2017). As a result, both maternal survival rates and conservation of reproductive capacity are improved. The ampulla (70 percent) is the most frequent site, followed by isthmic (12 percent), fimbrial (11 percent), and interstitial tubal pregnancies (2 percent) (Bouyer, 2002). The remaining 5 percent of nontubal ectopic pregnancies implant in the ovary, peritoneal cavity, cervix, or prior cesarean scar. Occasionally, a multifetal pregnancy contains one conceptus with normal uterine implantation that coexists with one implanted ectopically. The natural incidence of these heterotopic pregnancies approximates 1 per 30,000 pregnancies (Reece, 1983). Rarely, twin tubal pregnancy with both embryos in the same tube or with one in each tube has been reported (Eze, 2012; Goswami, 2015). Regardless of location, D-negative women with an ectopic pregnancy who are not sensitized to D-antigen are given IgG anti-D immunoglobulin (American College of Obstetricians and Gynecologists, 2017). In first-trimester pregnancies, a 50-g or 300-g dose is appropriate, whereas a standard 300-g dose is used for later gestations (Chap. Risks Abnormal fallopian tube anatomy underlies many cases of tubal ectopic pregnancy. Surgeries for a prior tubal pregnancy, for fertility restoration, or for sterilization confer the highest risk. After one previous ectopic pregnancy, the chance of another is increased fivefold (Bhattacharya, 2012). Prior sexually transmitted disease or other tubal infection, which can distort normal tubal anatomy, is another factor. Specifically, one episode of salpingitis can be followed by a subsequent ectopic pregnancy in up to 9 percent of women (Westrom, 1992). Peritubal adhesions subsequent to salpingitis, appendicitis, or endometriosis can also increase chances. Salpingitis isthmica nodosa, which is a condition in which epithelium-lined diverticula extend into a hypertrophied muscularis layer, is another (Bolaji, 2015). Finally, congenital fallopian tube anomalies, especially those secondary to in utero diethylstilbestrol exposure, can predispose (Hoover, 2011). And "atypical" implantations-cornual, abdominal, cervical, ovarian, and heterotopic pregnancy-are more frequent. Smoking is another known association, although the underlying mechanism is unclear (Hyland, 2015). Last, with any form of contraception, the absolute number of ectopic pregnancies is decreased because pregnancy occurs less often. However, with some contraceptive method failures, the relative number of ectopic pregnancies is increased. Evolution and Potential Outcomes With tubal pregnancy, because the fallopian tube lacks a submucosal layer, the fertilized ovum promptly burrows through the epithelium. The zygote comes to lie near or within the muscularis, which is invaded by rapidly proliferating trophoblast. Outcomes of ectopic pregnancy include tubal rupture, tubal abortion, or pregnancy failure with resolution. With rupture, the invading expanding conceptus and associated hemorrhage can tear rents in the fallopian tube. Tubal ectopic pregnancies usually burst spontaneously but may occasionally rupture following coitus or bimanual examination. Tubal abortion frequency depends in part on the initial implantation site, and distal implantations are favored. Blood slowly trickles from the tubal fimbria into the peritoneal cavity and typically pools in the rectouterine cul-de-sac. If the fimbriated extremity is occluded, the fallopian tube may gradually become distended by blood, forming a hematosalpinx. Uncommonly, an aborted fetus will implant on a peritoneal surface and become an abdominal pregnancy, which is discussed on page 383. Last, an unknown number of ectopic pregnancies spontaneously fail and are reabsorbed. Distinctions between "acute" ectopic pregnancy just described and "chronic" ectopic pregnancy can be drawn. Chronic ectopic pregnancies typically rupture late, if at all, but commonly form a complex pelvic mass, which often is the reason prompting diagnostic surgery (Cole, 1982; Uur, 1996). Clinical Manifestations Earlier patient presentation and more precise diagnostic technology typically allow identification before rupture. In these cases, symptoms and signs of ectopic pregnancy are often subtle or even absent. The woman does not suspect tubal pregnancy and assumes that she has a normal early pregnancy or is having a miscarriage. With later diagnosis, the classic triad is delayed menstruation, pain, and vaginal bleeding or spotting. With tubal rupture, lower abdominal and pelvic pain is usually severe and frequently described as sharp, stabbing, or tearing. The posterior vaginal fornix may bulge from blood in the rectouterine cul-de-sac, or a tender, boggy mass may be felt beside the uterus. Symptoms of diaphragmatic irritation, characterized by neck or shoulder pain, especially on inspiration, develop in perhaps half of women with sizable hemoperitoneum. Some degree of vaginal spotting or bleeding is reported by 60 to 80 percent of women with tubal pregnancy.

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