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Obstentrics_Williams. Modanlou H, Hutson 5, Merritt AT: Early blood transfusion and resolution of disseminated intravascular coagulation associated with massive subgaleal hemorrhage. Neonatal Netw 35(1):37,t2016 Moster D, Lie RT, Irgens LM: The association of the Apgar score with subsequent death and cerebral palsy: a population-based study in term infants. J Pediatr 138(6):798, 2001 Moster D, Lie RT, Markestad T: Long-term medical and social consequences of preterm birth. N Engl J Med 359:262, 2008 Natarajan CK, Sankar MJ, Jain K, et al: Surfactant therapy and antibiotics in neonates with meconium aspiration syndrome: a systematic review and meta-analysis. J Perinatol 36(Suppl 1):549 2016a Natarajan G, Pappas A, Shankaran 5: Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). Semin Perinatol 40(8):549, 2016b


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Obstentrics_Williams. Rossi AC, Vanderbilt 0, Chmait RH: Neurodevelopmental outcomes after laser therapy for twin-twin transfusion syndrome: a systematic review and meta-analysis. Obstet Gynecol 118(5):1145,t2011 Rutherford vlA, Ramenghi A, Cowan FM: Neonatal stroke. 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. ] Clin Pathol 54:796, 2001 Sankar M], Chandrasekaran A, Kumar P, et al: Vitamin K prophylaxis for prevenrion of vitamin K deficiency bleeding: a systematic review. ] Perinatol 36 (Suppl 1):S29, 2016 Saroha M, Batra P, Dewan P, et al: Genital injuries in neonates following breech presentation.] Neonatal Perinatal Med 8(4):421, 2015 Scheibl A, Calderon EM, Borau M], et al: Epidural hematoma.t] Pediatr Surg 47(2):el9,t2012


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Obstentrics_Williams. Simonson C, Barlow P, Dehennin N, et al: Neonatal complications of vacuumassisted delivery. Obstet Gynecol 110: 189, 2007 Singh BS, Clark RH, Powers RJ, et al: Meconium aspiration syndrome remains a significant problem in the NICU: outcomes and treatment patterns in term neonates admitted for intensive care during a ten-year period. ] Perinatol 29(7):497, 2009 Slusher TM, Olusanya BO, Vreman H], et al: A randomized trial of phototherapy with filtered sunlight in Mrican neonates. N Engl] Med 373(12): 1115, 2015 Smith C, Weinberg A, Forster ]E, et al: Maternallopinavir-ritonavir is associated with fewer adverse events in infants than nelfinavir or atazanavir. Infect Dis Obstet Gynecol 2016:9848041, 2016 Smithers-Sheedy H, McInryre S, Gibson C, et al: A special supplement: indings 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


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Obstentrics_Williams. 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. Obstet Gynecol 120(1):15, 2012 Stanley F], Blair E: Why have we failed to reduce the frequency of cerebral palsy? Med ] Aust 154:623, 1991 Stoknes M, Andersen GL, Dahlseng MO, et al: Cerebral palsy and neonatal death in term singletons born small for gestational age. Pediatrics 130(6):el629,t2012 Strijbis EM, Oudman I, van Essen P, et al: Cerebral palsy and the application of the inrernational criteria for acute intrapartum hypoxia. Obstet Gynecol 107:t1t357,t2006 Stuart A, Olausson PO, Kallen K: Apgar scores at 5 minutes after birth in relation to school performance at 16 years of age. Obstet Gynecol 11t8 (2 Pt 1):201, 2011 Swanson AE, Veldman A, Wallace EM, et al: Subgaleal hemorrhage: risk factors and outcomes. Acta Obstet Gynecol Scand 91 (2):260, 2012


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Obstentrics_Williams. Tagin A, Woolcott CG, Vincer M], et al: Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc vIed 166(6):558,t2012 Takenouchi T, KasdorfE, Engel M, et al: Changing pattern of perinatal brain injury in term infants in recent years. Pediatr Neurol 46(2): 106, 2012 hacker SB, Stroup OF, Peterson HB: Eicacy and safety of intrapartum electronic fetal monitoring: an update. Obstet Gynecol 86:613, 1995 harakan S], Lee R], White M, et al: Distal humeral epiphyseal separation in a newborn. Orthopedics 39(4):e764, 2016 horngren-]erneck K, Herbst A: Perinatal factors associated with cerebral palsy in children born in Sweden. Obstet Gynecolt108:1499, 2006 Tolia VN, Patrick SW, Bennett MM, et al: Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl] Med 372(22):2118, 2015


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Obstentrics_Williams. Tolia VN, Patrick SW, Bennett MM, et al: Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl] Med 372(22):2118, 2015 Torfs CP, van den Berg B, Oechsli FW, et al: Prenatal and perinatal factors in the etiology of cerebral palsy. ] Pediatr 116:615, 1990 Torki M, Barton L, Miller 0, et al: Severe brachial plexus palsy in women without shoulder dystocia. Obstet Gynecol 120(3):539,t2012 Turpenny PO, Nimmo A: Fractured clavicle of the newborn in a population with a high prevalence of grand-multiparity: analysis of78 consecutive cases. B]OG 100:338, 1993 Ubachs ]M, Sloof AC, Peeters LL: Obstetric antecedents of surgically treated obstetric brachial plexus injuries. B]OG 102:813, 1995 Vain NE, Szyld EG, Prudent LM, et al: Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomized controlled trial. Lancet 364:597, 2004


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Obstentrics_Williams. Walsh B, Boylan G, Dempsey E, et al: Association of nucleated red blood cells and severity of encephalopathy in normothermic and hypothermic infants. Acta Paediatr 102(2):e64, 2013 Walsh BH, Bovian GB, Murray OM: Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome. Early Hum Dev 87(5):335, 201t1 Walsh BH, Neil], Morey], et al: he frequency and severity of magnetic resonance imaging abnormalities in infants with mild neonatal encephalopathy. ] Pediatr 187:26, 2017 Wambach ]A, Wegner 0], Depass K, et al: Single ABCA3 mutations increase risk for neonatal respiratory distress syndrome. Pediatrics 130(6):e 15 75, 2012 Watchko ]F, Tiribelli C: Bilirubin-induced neurologic damage-mechanisms and management approaches. N Englt] Med 369:21,t2013 Wayock CP, Meserole RL, Saria S, et al: Perinatal risk factors for severe injury in neonates treated with whole-body hypothermia for encephalopathy. Am ] Obstet GynecoIt21t1(1):41.el, 2014


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Obstentrics_Williams. Wayock CP, Meserole RL, Saria S, et al: Perinatal risk factors for severe injury in neonates treated with whole-body hypothermia for encephalopathy. Am ] Obstet GynecoIt21t1(1):41.el, 2014 Wenstrom KD, Andrews W, Maher ]E: Amnioinfusion survey: prevalence, protocols, and complications. Obstet Gynecol 86:572, 1995 Wener EF, ]anevic TM, Illuzzi], et al: Mode of delivery in nulliparous women and neonatal intracranial injury. Obstet Gynecol 118(6): 1239,t201t1 Whitby EH, Griiths PO, Rutter S, et al: Frequency and natural history of subdural haemorrhages in babies and relation to obstetrical factors. Lancet 363:846, 2004 Wiberg N, Kallen K, Herbst A, et al: Relation between umbilical cord blood pH, base deicit, lactate, 5-minute Apgar score and development of hypoxic ischemic encephalopathy. Acta Obstet Gynecol Scand 89: 1263, 2010


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Obstentrics_Williams. Wiklund LM, Uvebrant P, Flodmark 0: Computed tomography as an adjunct in etiological analysis of hemiplegic cerebral palsy, 1. Children born preterm. Neuropediatrics 22:50, 1991 a Wiklund LM, Uvebrant P, Flodmark 0: Computed tomography as an adjunct in etiological analysis of hemiplegic cerebral palsy, 2. Children born at term. Neuropediatrics 22: 121) 1991 b Williams ]W: Obstetrics: a Text-book for the Use of Students and Practitioners. New York, Appleton, 1903 Winkelhorst 0, Murphy MF, Greinacher A, et al: Antenatal managemet in fetal and neonatal alloimmune thrombocytopenia: a systematic review. Blood 129(11):1538,t2017 Wiswell TE, Tuggle JM, Turner BS: Meconium aspiration syndrome: have we made a diference? Pediatrics 85:715, 1990 World Health Organization: Guidelines on Basic Newborn Resuscitation. Geneva, World Health Organization, 2012


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Obstentrics_Williams. World Health Organization: Guidelines on Basic Newborn Resuscitation. Geneva, World Health Organization, 2012 Wu YW, Bauer A, Ballard A, et al: Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics 130(4):683,t2012 Wu W, Croen A, Shah SJ, et al: Cerebral palsy in a term population: risk factors and neuroimaging findings. Pediatrics 1t18:691,t2006 Wu W, Plum TN, Danielsen B, et al: Nighttime delivery and risk of neonatal encephalopathy. Am J Obstet GynecoI204(l):37.e1, 2011 Diseases and Injuries of the Term Newborn 635 Wyckof MH, Aziz K, Escobedo MB, et al: Part 13: Neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics 136 (Suppl 2): SI96,t2015 Yaish HM, Christensen RD, Lemmons RS: Neonatal nonimmune hemolytic anemia. Curr Opin Pediatr 29(1): 12,t2017


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Obstentrics_Williams. SI96,t2015 Yaish HM, Christensen RD, Lemmons RS: Neonatal nonimmune hemolytic anemia. Curr Opin Pediatr 29(1): 12,t2017 Yeh P, Emary K, Impey L: The relationship between umbilical cord arterial pH and serious adverse neonatal ourcome: analysis of 51,519 consecurive validated samples. BlOG 119(7):824,t2012 Zipursky A: Prevention of vitamin K deficiency bleeding in newborns. Br J Haematol 104:430, 1999 CHAPTER 34 . The Preterm Newborn RESPIRATORY DISTRESS SYNDROME. .. .. ... 636 NECROTIZING ENTEROCOLITIS . .... ... 638 RETINOPATHY OF PREMATURITY ..639 BRAIN DISORDERS .. ........ . 639 INTRACRANIAL .......... 639 CEREBRAL PALSY . .... ............. 640 !he prognosis or the child depends, of course, upon the degree of development, as wel as the pathological condition or which premature delivery is undertaken. Generaly speaking, in the case of children born bore the thiry-second week, the chances of surviving are vey small. -]. Whitridge Williams (1903)


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Obstentrics_Williams. -]. Whitridge Williams (1903) At the time of this textbook's irst edition, preterm delivery of a living newborn was frequently followed by neonatal death. Contrast this with today's technological advances that have advanced the threshold of viability to 22 to 24 weeks' gestation. 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. These complications of prematurity can be placed in perspective in terms of overall neonatal outcomes. 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 is in part due to a decline in births to teen mothers (Ferre, 2016).


Obstentrics_Williams

Obstentrics_Williams. The seminal complication of the preterm newborn is respiratory distress syndrome (DS). 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. In addition, hyperoxia, a side efect of DS treatmentacontributes to morbidities such as bronchopulmonary dysplasia, pulmonary hypertension, necrotizing enterocolitis, periventricular leukomalacia, and retinopathy of prematurity. To provide blood gas exchange immediately following delivery, the lungs must rapidly fill with air while being cleared of fluid. Concurrently, pulmonary arterial blood low must rise remarkably. Although some of the luid is expressed as the chest is compressed during vaginal delivery, most is absorbed through the TABLE 34-1. Complications of Prematurity Retinopathy of prematurity (ROP) The Preterm Newborn 637


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Obstentrics_Williams. TABLE 34-1. Complications of Prematurity Retinopathy of prematurity (ROP) The Preterm Newborn 637 Chapter 32 (p. 606). Suicient surfactant, synthesized by type II pneumocytes, is essential to stabilize the air-expanded alveoli. It expiration (Chap. 7, p. 133). If surfactant is inadequate, hyaline membranes form in the distal bronchioles and alveoli, and RDS develops. 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, of meconium (Chap. 33, p. 619).


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Obstentrics_Williams. With inadequate surfactant, alveoli are unstable, and low pressures cause collapse at end expiration. Pneumocyte nutrition is compromised by hypoxia and systemic hypotension. Partial persistence of the fetal circulation may lead to pulmonary hypertension and a relative right-to-Ieft shunt. Eventually, alveolar cells undergo ischemic necrosis. 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 ibrin-rich protein and cellular debris line the dilated alveoli and terminal bronchioles. he epithelium underlying the membrane becomes necrotic. 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.


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Obstentrics_Williams. In typical RDS, tachypnea develops, the chest wall retracts, and expiration is accompanied by nostril flaring and by gruntingin an attempt to provide a positive end-expiratory pressure to prevent lung collapse. Shunting of blood through nonventilated lung contributes to hypoxemia and to metabolic and respiratory acidosis. Poor peripheral circulation and systemic hypotension may be evident. The chest radiograph shows a difuse reticulogranular infiltrate and an air-illed tracheobronchial tree-air bronchogram. As discussed further in Chapter 33 (p. 619), respiratory insuiciency can also be caused by sepsis, pneumonia, meconium aspiration, pneumothorax, persistent fetal circulation, heart failure, and malformations involving thoracic structures, such as diaphragmatic hernia. Common mutations in surfactant protein production and the phospholipid transporter (ABCA3) contribute to RDS (Beers, 2017; Tredano, 2003; Wert, 2009).


Obstentrics_Williams

Obstentrics_Williams. An important factor inluencing survival is neonatal intensive care. 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. For example, continuous positive airway pressure (CPAP) prevents the collapse of unstable alveoli. This allows high inspired-oxygen concentrations to be reduced, thereby minimizing its toxicity. In an attempt to minimize the need for tracheal intubation and intermittent positive-pressure ventilation, CPAP has been studied in well-designed multicenter trials (Morley, 2008; SUPPORT Study Group, 2010b). An initial CPAP strategy with subsequent selective surfactant use is a beneficial alternative to immediate intubation and surfactant for many neonates of extremely early gestational age (American Academy of Pediatrics, 2014).


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Obstentrics_Williams. Academy of Pediatrics, 2014). rates but is an important factor in the genesis of chronic lung dis ease of prematurity-bronchopulmonary dypasia (BPD). Namely, and volutrauma. Moreover, hyperoxia can create reactive oxy gen species that trigger inflammation. Infection can also be con tributory. In afected newborns, alveolar and pulmonary vascular development is disrupted and leads to hypoxia, hypercarbia, and chronic oxygen dependence (Davidson, 2017; Kair, 2012). As prevention, hightequency oscilatory ventilation has been evaluated. However, beneits and risks varied considerably between studies (Cools, 2015). Treatment of the ventilator-dependent neonate with gluco corticoids was also used previously to prevent BPD. he Ameri can Academy of Pediatrics now recommends against routine steroid use because of limited beneits and greater rates of in exposed neonates (Doyle, 20a14a,b; Watterberg, 2010).


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Obstentrics_Williams. In other eforts for BPD prevention, early animal studies demonstrated significant improvements in lung function with weeks of inhaled nitric oxide (McCurnin, 2005). Despite initial enthusiasm, clinical trials failed to demonstrate a consistent benefit. A National Institutes of Health (NIH) consensus statement and the American Academy of Pediatrics (2014) concluded that the available data do not support its use to prevent or treat BPD (Cole, 2011). Caeine has been used widely to treat apnea of prematurity, but it also has bronchodilatory efects. One large randomized trial of cafeine versus placebo showed lower BPD rates, improved neurodevelopmental outcomes during early childhood, and good evidence of safety up to 11 years (Schmidt, 2006, 2012, 2017). This therapy is now widely used for newborns weighing ; 1250 g.


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Obstentrics_Williams. The antioxidant vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm newborns have low vitamin A levels at birth, and this has been associated with a greater risk of developing BPD. Randomized trials support the use of vitamin A to achieve a modest reduction in BPD rates for very-Iow-birthweight neonates weighing <1500 g (Darlow, 2016) . Exogenous surfactant products are delivered via endotracheal tube to help prevent RDS. They contain biological or animal surfactants such as bovine-Survanta, calf-Inasu,or porcine-Curosuf Synthetic surfactants such as irst-generation Exosuf and second-generation Suaxin 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. here are currently no synthetic surfactants available.


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Obstentrics_Williams. Surfactant replacement was established decades ago as an efective and safe therapy for RDS. Treatment reduces rates of mortality and pneumothorax and improves survival without BPD (Polin, 2014). It has been used for prophyxis 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. However, randomized trials indicate that in populations with high use of antenatal steroids and routine use of CP P in the delivery room, prophylactant surfactant is no longer beneficial and is associated with more risk of death or BPD (Rojas-Reyes, 2012; Sardesai, 2017). Exploration of diferent, 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


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Obstentrics_Williams. 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).


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Obstentrics_Williams. The NIH (1994, 2000) has concluded that a single course of antenatal corticosteroid therapy reduces RDS and intraventricular hemorrhage rates in preterm neonates born between 24 and 34 weeks' gestation (p. 640). he 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. It also may be considered for pregnant women starting at 23 weeks' gestation who are at risk of preterm delivery within 7 days. his is discussed further is Chapter 42 (p. 823). More recently, administration of antenatal corticosteroids to women at risk for late-preterm delivery (34 to 36 weeks' gestation) was found to significantly reduce the rate of neonatal respiratory complications (Gyami-Bannerman, 2016). Amniocentesis to Assess Fetal Lung Maturity


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Obstentrics_Williams. Amniocentesis to Assess Fetal Lung Maturity In some instances, when gestational age is uncertain, knowledge of fetal lung maturity may inluence 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 (2017 a, b) counsels against its use in most of these cases. Instead the College recommends late-term delivery at "41 weeks' gestation" using the best clinical estimate of gestational age (Chap. 10, p. 183).


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Obstentrics_Williams. If amniocentesis is elected, luid acquisition is similar to that described for second-trimester amniocentesis (Chap. 14, p. 292). Complications requiring urgent delivery are rare (Zalud, 2008). Following analysis, the probability of RDS developing in a given newborn depends on the test used and fetal gestational age. Importantly, administration of corticosteroids to induce pulmonary maturation has variable efects on some of these tests. Varner and colleagues (2013) have provided a review of testing options. Of biochemical tests, the labor-intensive lecithin-sphingomyelin (LIS) ratio for many years was the gold-standard test. 2•..J• .-E c.o .-8 8c .0ll,� 2 FIGURE 34-1 Changes in mean concentrations of lecithin and sphingomyelin in amnionic fluid during gestation in normal pregnancy. (Modified with permission from Gluck L, Kulovich MV: Lecithin-sphingomyelin ratios in amniotic fluid in normal and abnormal pregnancy, Am J Obstet Gynecol. 1973 Feb 15;115(4):539-546.)


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Obstentrics_Williams. Lecithin-sphingomyelin ratios in amniotic fluid in normal and abnormal pregnancy, Am J Obstet Gynecol. 1973 Feb 15;115(4):539-546.) Dipalmitoylphosphatidylcholine (DPPC), that is, lecithin, and phingomyelin are surfactant components. Before 34 weeks, both are present in amnionic fluid in similar concentrations. At 32 to 34 weeks, the concentration of lecithin relative to sphingomyelin begins to rise (Fig. 34-1). The risk of neonatal RDS is slight whenever the concentration of lecithin is at least twice that of sphingomyelin-LIS ratio >2 (Gluck, 1971). Previously, RDS was thought to develop despite an LIS ratio > 2 in newborns of women with diabetes. Some recommend that phosphatidygycerol, 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).


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Obstentrics_Williams. Of biophysical tests, the luorescence poariation test is an automated assay that measures the surfactant-to-albumin ratio in uncentriuged amnionic luid and gives results in less than an hour. Investigators found the TDx-FLM to be equal or superior to the LIS ratio, foam stability index, or phosphatidylglycerol assessment. his included testing in diabetic pregnancies (Karcher, 2005; Varner, 2013). he modified TDx-FLM Ilis used by many hospitals as their primary test of pulmonary maturity. Thresholds vary by gestational age (Bennasar, 2009). he oam stabiliy or shake test relies on the ability of surfactant in amnionic luid, when mixed appropriately with ethanol, to generate stable foam at the air-liquid interface (Clements, 1972). Problems include errors caused by slight contamination and frequent false-negative test results. Of other tests, the Lumadex-FSI test, luorescent poariation (microviscomery), and amnionic luid absorbance at 650-nm waveength have all been used with variable


Obstentrics_Williams

Obstentrics_Williams. frequent false-negative test results. Of other tests, the Lumadex-FSI test, luorescent poariation (microviscomery), and amnionic luid absorbance at 650-nm waveength have all been used with variable success.


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Obstentrics_Williams. The lamelar body count is a rapid, simple, and accurate method of assessing fetal lung maturity and is comparable to TDx-FLM and LIS ratio accuracy (Karcher, 2005; Varner, 2013). This newborn bowel disorder has clinical findings that include abdominal distention, emesis, ileus, bilious gastric aspirates,


Obstentrics_Williams

Obstentrics_Williams. This newborn bowel disorder has clinical findings that include abdominal distention, emesis, ileus, bilious gastric aspirates, The Preterm Newborn 639 and bloody stools. here is often radiological evidence of bacteria. Other classic imaging findings include hepatobiliary gas and pneumoperitoneum. Bowel perforation may prompt resection. Necrotizing enterocolitis (NEC) is seen primarily in low-birthweight newborns but occasionally is encountered in mature neonates. Various hypothesized causes include peri natal hypotension, hypoxia, sepsis, umbilical catheterization, exchange transfusions, blood transfusions, and the feeding of cow milk and hypertonic solutions (Neu, 2010). he patho physiology is thought to be multifactorial, and genetic disposi tion, 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).


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Obstentrics_Williams. Medical treatment includes abdominal decompression, bowel rest, broad-spectrum 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). By 1950, this condition, formerly known as retrolental ibroplasia, became the largest single cause of blindness in this country. Mter the discovery that the disease resulted from hyperoxemia, its frequency declined but began to rise again with the increasing survival rates of extremely pre term newborns.


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Obstentrics_Williams. 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. his is followed by subsequent aberrant neovascularization, in which the new vessels penetrate the retina and extend into the vitreous. Here, they are prone to leak proteins or burst with subsequent hemorrhage. Adhesions can form to detach the retina. Vascular endothelial growth factor (VEGF) plays an important role in normal angiogenesis and is up regulated during retinopathy of prematurity (ROP) development (Sharma, 2017). his understanding has opened new avenues of treatment with anti-VEGF therapies.


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Obstentrics_Williams. Precise levels of hyperoxemia that can be sustained without causing ROP are unknown. Mter birth, there is a "relative" hyperoxia compared with in utero oxygen content, even in newborns not exposed to higher inspired oxygen concentrations. To better understand the oxygen saturation threshold necessary to minimize ROP without raising rates of other adverse outcomes, the Neonatal Research Network performed a randomized trial of oxygenation in 1316 neonates born between 24 and 27 weeks' gestation (SUPPORT Study Group, 2010a). he two target ranges of oxygen saturation were 85 to 89 percent in one arm and 91 to 95 percent in the other arm. hese targets were both commonly employed in neonatal intensive care units. Death before discharge occurred signiicantly more frequently in the lower-oxygen saturation group-20 versus 16 percent. However, severe ROP among survivors developed signiicantly less often in the lower-oxygen saturation group 8.6 versus 17.9 percent.


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Obstentrics_Williams. roanatomical sequelae in preterm newborns compared with those at term (Chap. 33, p. 621). In preterm neonates, cerebral orrhage, cerebellar hemorrhage, periventricular hemorrhagic infarction, cystic periventricular leukomalacia, and difuse white matter injury. All of these are strongly associated with adverse neurodevelopmental outcomes (Kwon, 2014).


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Obstentrics_Williams. Cranial sonography remains the preferred approach for events. It is readily available and reliable for detecting common abnormalities and monitoring brain growth. Because cystic inju ries may take 2 to 5 weeks to evolve, serial scans are obtained dur ing 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. At the same time, how ever, between 4 and 10 percent of prematurely born children may develop cerebral palsy (CP) in the absence of lesions. Put another way, 90 to 96 percent of preterm newborns with CP have cerebral lesions that are detectable using cranial sonography.


Obstentrics_Williams

Obstentrics_Williams. here are ive major categories of intracranial hemorrhage in the neonate (Volpe, 2008). Primay subarachnoid hemorrhage is more common in those born preterm and is frequently benign. Cerebelar hemorrhage is also more frequent in preterm neonates and is increasingly recognized as a cause of serious sequelae. Intraventricular hemorrhage IVH) is almost exclusively seen in preterm newborns, is relatively common, and can have serious efects. Subdural hemorrhages are more frequent in term newborns and can be serious. Miscelaneous intraparenchymal hemorrhage is also more frequent in those born at term and is of variable concern.


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Obstentrics_Williams. In preterm infants, the germinal matrix capillary network is fragile for several reasons. First, the subependymal germinal matrix provides poor support for the vessels coursing through it. Second, venous anatomy in this region causes stasis and congestion, which makes vessels susceptible to bursting if intravascular pressure rises. Third, vascular autoregulation is impaired in the preterm neonate (Matsuda, 2006; Verhagen, 2014).


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Obstentrics_Williams. If fragile capillaries in the germinal matrix rupture, blood escapes into surrounding tissues and may extend into the ventricular system and brain parenchyma. This type of hemorrhage is common in preterm neonates, especially those born before 32 weeks. However, it can also develop at later gestational ages and even in term neonates. Most hemorrhages develop within 72 hours of birth, but they have been observed as late as 24 days (Whitelaw, 20ll). Because IVH usually is recognized within 3 days of delivery, its genesis is often erroneously attributed to birth events. It is important to realize that prelabor IVH can also occur (Achiron, 1993; Nores, 1996).


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Obstentrics_Williams. The pathogenesis of IVH is multifactorial and includes hypoxic-ischemic events, carbon dioxide elevations, anatomical factors, blood pressure instability, coagulopathy, genetic factors, and many others (McCrea, 2008; Ment, 2016). Moreover, preterm birth is frequently associated with infection, which further predisposes to endothelial activation, platelet adherence, and thrombi (Redline, 2008). Respiratory distress and mechanical ventilation are commonly associated factors (Sarkar, 2009).


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Obstentrics_Williams. lmost half of hemorrhages are clinically silent. Most small germinal matrix hemorrhages and those confined to the cerebral ventricles resolve without impairment. But, nearly half do show some sign of neurological impairment (Patra, 2006). Survivors of extensive periventricularlintraventricular hemorrhage can have major neurodevelopmental handicaps (Mukerji, 2015). Large lesions can result in hydrocephalus or in degenerated cystic areas termed periventricular leukomalacia (PVL), discussed below. Importantly, the extent ofPVL correlates with CP risk (Bassan, 2006).


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Obstentrics_Williams. Ventricular hemorrhage incidences depends on gestational age at birth. From the Neonatal Research Network, approximately 65 percent of all neonates born before 28 weeks' gestation demonstrated some evidence of hemorrhage or PVL (Stoll, 2010). he incidence ranged from 60 percent in those born at 23 weeks to only 23 percent in those at 28 weeks. Importantly, grade IV intraventricular hemorrhage was documented in 21 percent of 23-week-old neonates but in only 3 percent of those at 28 weeks. The severity of IVH can be assessed by neuroimaging studies. Papile and coworkers (1978) devised the mostwidelyused grading scheme to quantiY the extent ofa lesion and estimate prognosis: Grade I-hemorrhage limited to the germinal matrix Grade Ill-hemorrhage with ventricular dilation Grade IV-parenchymal extension of hemorrhage.


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Obstentrics_Williams. Grade I-hemorrhage limited to the germinal matrix Grade Ill-hemorrhage with ventricular dilation Grade IV-parenchymal extension of hemorrhage. If given at least 24 hours before delivery, corticosteroids prevent or reduce the incidence and severity ofIVH (Wei, 2016). A Consensus Development Conference of the NIH (1994) concluded that such therapy reduced rates of mortality, RDS, and IVH in preterm neonates born between 24 and 32 weeks' gestation. A second consensus statement by the NIH (2000) recommended that repeated courses of corticosteroids not be given (Chap. 42, p. 823).


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Obstentrics_Williams. Subsequently, the Maternal-Fetal Medicine Units Network reported that repeated corticosteroid courses were associated with some improved preterm neonatal outcomes, but also with reduced birthweight and increased risk for fetal-growth restriction (Wapner, 2006). Surveillance of this cohort through age 2 to 3 years found that children exposed to repeated versus singledose steroid courses did not difer signiicantly in physical or neurocognitive measures (Wapner, 2007). It was worrisome, however, that there was a nonsignificant 5.7-fold relative risk of CP in infants exposed to multiple steroid courses.


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Obstentrics_Williams. At the same time, the 2-year follow-up ofthe Australian CollaborativeTrialwas reported byCrowtherand coworkers (2007). In more than 1100 newborns, the incidence of CP was almost identical4.2 versus 4.8 percent-in those given repeated versus single-course steroids, respectively. More recently, it was reported that for those born before 28 weeks' gestation, if 10 days or more had passed since betamethasone administration, the incidence of severe IVH was higher (Liebowitz, 2016).


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Obstentrics_Williams. he most recent recommendations from the American College of0bstetricians and Gynecologists (2016a) are for a single course of corticosteroids for pregnant women between 24°/ weeks and 336/ weeks' gestation who are at risk for preterm delivery. They further note that those given their initial course more than 14 days prior and who have imminent risk of preterm delivery may receive a second "rescue" course. Antenatal corticosteroids are "considered" for 23°/ to 236/7 weeks and not recommended for pregnancies <23 weeks (American College of Obstetricians and Gynecologists, 2017c).


Obstentrics_Williams

Obstentrics_Williams. Although antenatal magnesium suate for those at risk for preterm delivery does not reduce the incidence ofIVH, it does ofer protection from neurodevelopmental impairment (Crowther, 2007; Doyle, 2009). The American College of Obstetricians and Gynecologists (2016b) recommends its use for this indication, as discussed further in Chapter 42 (p. 824). he eicacy of antenatal vitamin K and phenobarbital, as well as postnatal phenobarbital, have not been shown to consistently reduce the incidence ofIVH (Crowther, 2010a,b; Smit, 2013). Although vitamin E reduced IVH rates, the associated risk for sepsis was increased (Brion, 2003). One metaanalysis of the many randomized trials ofpostnatal indomethacin showed a reduction in IVH rates, but no improvement in rates of death or neurodevelopmental impairment (Fowlie, 2010).


Obstentrics_Williams

Obstentrics_Williams. he beneits of cesarean delivery compared with vaginal birth to lower IVH rates remains controversial. One metaanalysis reported that cesarean delivery for very-Iow-birthweight neonates had no efect on rates of severe IVH but did reduce overall IVH rates (Barzilay, 2016). Delayed cord clamping compared with immediate cord clamping has been reported to reduce the risk for IVH in preterm newborns (Rabe, 2012). This pathological description refers to cystic areas deep in brain white matter that develop after hemorrhagic or ischemic infarction. Tissue ischemia leads to regional necrosis. Because brain tissue does not regenerate and the preterm neonate has minimal gliosis, these irreversibly damaged areas appear as echolucent cysts in neuroimaging studies. Generally, they require at least 2 weeks to form but may develop as long as 4 months after the initial insult. hus, their presence at birth may help to determine the timing of an inciting event.


Obstentrics_Williams

Obstentrics_Williams. This term refers to a group of conditions that are characterized by chronic movement or posture abnormalities that are cerebral in onglll, arise early in life, and are nonprogressive (Nelson, 2003). Epilepsy and mental retardation frequently accom pany CP. Its cause(s) are diferent in preterm and term infants (Chap. 33, p. 622). CP is commonly classified by the type of neurological dys function-spastic, dyskinetic, or ataxic-as well as the num ber and distribution of limbs involved-quadriplegia, diplegia, hemiplegia, or monoplegia. The major types and their frequen their associates: Spastic quadrplegia, which has a strong association with developmental retardation and seizure disorders-20 percent Diplegia, which is common in preterm or low-birthweight Mixed varieties.


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Obstentrics_Williams. Spastic quadrplegia, which has a strong association with developmental retardation and seizure disorders-20 percent Diplegia, which is common in preterm or low-birthweight Mixed varieties. According to the Centers for Disease Control and Prevention (2016), the prevalence of CP in the United States approximates 3 in 1000 children. In some countries, the incidence has risen because advances in care of very preterm newborns have improved their survival but not their neurological prognosis (O'Callaghan, 2011). For example, Moster and coworkers (2008) presented long-term follow-up of more than 900,000 births in Norway. he CP rate was 0.1 percent in nonanomalous term newborns but was 9.1 percent in those born at 23 to 27 weeks.


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Obstentrics_Williams. Various clinical and pathological data link CP with associated severe IVH (grade III or IV) and resulting PVL. In one study of nearly 1500 neonates born before ;28 weeks, the rate of CP was fivefold greater in those who had grade III or IV hemorrhage compared with those who sufered no IVH (Bolisetty, 2014).


Obstentrics_Williams

Obstentrics_Williams. Preterm newborns are most susceptible to brain ischemia and PVL. Before 32 weeks' gestation, the vascular anatomy of the brain is composed of two systems. One penetrates into the cortex-the ventrieulopedal system. The other reaches down to the ventricles, but then curves to flow outward-the ventrieulofugal system (Weindling, 1995). There are no vascular anastomoses connecting these two systems. As a result, the area between these systems, through which the pyramidal tracts pass near the lateral cerebral ventricles, is a watershed area vulnerable to ischemia. Vascular insuiciency before 32 weeks leading to ischemia would afect this watershed area first. Resulting damage of the pyramidal tracts may cause spastic diplegia. After 32 weeks, vascular flow shifts toward the cortex, and hypoxic injury after this time primarily damages the cortical region. The Preterm Newborn 641


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Obstentrics_Williams. The Preterm Newborn 641 PL is associated with infection and inflammation. Zupan and colleagues (1996) studied 753 infants born between 24 and 32 weeks, 9 percent of whom developed PVL. Those born before 28 weeks, those who had inflammatory events during the last days to weeks before delivery, and those who had both were at highest risk. In another study, PVL was strongly associated with prolonged membrane rupture, chorioamnionitis, and neonatal hypotension (Perlman, 1996). Bailis and coworkers (2008) reported that chronic-and not acute-placental inlammation was associated with PVL.


Obstentrics_Williams

Obstentrics_Williams. Fetal infection may be a key element in the pathway between preterm birth and CP (Burd, 2012; Leviton, 2010). As discussed in Chapter 42 (p. 810), chorioamnionitis is a major cause of spontaneous preterm delivery. In the pathway proposed in Figure 34-2, antenatal reproductive tract infection evokes the production of cytokines such as tumor necrosis factor and interleukins-1, -6, and -8. hese in turn stimulate prostaglandin production and preterm labor. Preterm fetal intracranial blood vessels are susceptible to rupture and damage, and the cytokines that stimulate preterm labor also have direct toxic efects on oligodendrocytes and myelin. Vessel rupture, tissue hypoxia, and cytokine-mediated damage result in massive neuronal cell death. Glutamate is released, stimulating membrane receptors to allow excess calcium to enter the neurons. High intracellular calcium levels are toxic to white matter, and glutamate may be directly toxic to oligodendrocytes (hwaja, 2008).


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Obstentrics_Williams. Many studies have shown that infection and cytokines can directly damage the immature brain (Chau, 2014; Yoon, 1997a). Tumor necrosis factor and interleukin-6 were more frequently found in the brains of infants who died with PVL (Yoon, 1997b). Cytokines are strongly linked to white matter lesions even when organisms cannot be demonstrated (Y oon, 2000). FIGURE 34-2 Schematic representation of the hypothesized pathway between maternal or intrauterine infection and preterm birth or periventricular leukomalacia. Both potentially lead to cerebral palsy. LPS = lipopolysaccharide; PG = prostaglandin.


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Obstentrics_Williams. Andrews and colleagues (2008) provided data that raise questions regarding a higher incidence of adverse neurodevelopmental outcomes related to exposure to chorioamnionitis. In a cohort born between 23 and 32 weeks, they studied several surrogate indicators and direct markers of in utero inflammation. These included clinical findings, cytokine levels, histological findings, and microbial culture results. Infants undergoing comprehensive psychoneurological testing had similar incidences of CP, intelligence quotient (IQ) scores <70, or both, regardless of these markers. The researchers interpreted their findings to support current practices that employ eforts to delay delivery with preterm pregnancies in the absence of overt intrauterine infection. Importantly, this does not apply to preterm pregnancy in which clinical chorioamnionitis is diagnosed. Of 3094 singletons born before 33 weeks' gestation, 15 percent had evidence of clinical chorioamnionitis (Soraisham, 2009). Compared with


Obstentrics_Williams

Obstentrics_Williams. pregnancy in which clinical chorioamnionitis is diagnosed. Of 3094 singletons born before 33 weeks' gestation, 15 percent had evidence of clinical chorioamnionitis (Soraisham, 2009). Compared with noninfected infants, cases complicated by infection had significantly higher rates of early-onset sepsis-4.8 versus 0.9 percent-and ofaIH-22 versus 12 percent.


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Obstentrics_Williams. The beneits of antenatal magnesium sulfate and corticosteroids have already been described. Few specific treatments have been identified to reduce or prevent brain injury in the vulnerable preterm newborn. One potential neuroprotective therapy is with erythropoiesis stimulating agents (ESAs) such as erythropoietin and darbepoetin. In addition to stimulating erythropoiesis, ESAs are protective in the developing brain in animal models (Wassink, 2017). Preliminary clinical studies are encouraging, and large trials are now underway (Beirer, 2014). Achiron R, Pinchas OH, Reichman B, et al: Fetal intracranial haemorrhage: clinical significance of in-utero ultrasonic diagnosis. BJOG 100:995, 1993 American Academy of Pediatrics: Respiratory support in preterm infants at birth. Pediatrics 133:171,t2014 American College of Obstetricians and Gynecologists, Society for MaternalFetal Medicine: Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. 677, October 2016a


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Obstentrics_Williams. American College of Obstetricians and Gynecologists, Society for MaternalFetal Medicine: Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. 677, October 2016a American College of Obstetricians and Gynecologists, Society for MaternalFetal Medicine: Magnesium sulfate before anticipated preterm birth for neuroprotection. Committee Opinion No. 455, March 2010, Reairmed 2016b American College of Obstetricians and Gynecologists: Medically indicated late-preterm and early-term deliveries. Committee Opinion No. 560, April 2013, Reairmed 2017a American College of Obstetricians and Gynecologists, Society for MaternalFetal Medicine: Management of suboptimally dated pregnancies. Committee Opinion No. 688, March 2017b American College of Obstetricians and Gynecologists: With the Society for Maternal-Fetal Medicine: Peri viable birth. Obstetric Care Consensus No. 6, October 2017 c


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Obstentrics_Williams. American College of Obstetricians and Gynecologists: With the Society for Maternal-Fetal Medicine: Peri viable birth. Obstetric Care Consensus No. 6, October 2017 c Andrews W, Cliver SP, Biasini F, et al: Early preterm birth: association between in utero exposure to acute inlammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol 198:466, 2008 Ardell S, Pister RH, Soli R: Animal derived surfactant extract versus protein free synthetic surfactant for the prevention and treatment of respiratory distress syndrome. Cochrane Database Syst Rev (5):CD000144, 2015 Bailis A, Maleki Z, Askin F, et al: Histopathological placental features associated with development of periventricular leukomalacia in preterm infants. Am J Obstet Gynecol 199(6):S43, 2008 Barzilay E, Gadot Y, Koren G. Safety of vaginal delivery in very low birthweight vertex singletons: a meta-analysis. J Matern Fetal Neonatal Med 29(22):3724,t2016


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Obstentrics_Williams. Barzilay E, Gadot Y, Koren G. Safety of vaginal delivery in very low birthweight vertex singletons: a meta-analysis. J Matern Fetal Neonatal Med 29(22):3724,t2016 Bassan H, Venson CB, Limperopoulos C, et al: Ultrasonographic features and severity scoring of periventricular hemorrhagic infarction in relation to risk factors and outcome. Pediatrics 117:2111, 2006 Beers MF, Mulugeta S: he biology of the ABCA3 lipid transporter in lung health and disease. Cell Tissue Res 367(3):481, 2017 Beirer R, Peceny MC, Hartenberger CH, et al: Erythropoietin concentrations and neurodevelopmental outcome in preterm infants. Pediatrics 118:635, 2006 Bennasar M, Figueras F, Palacio M et al: Gestational age-specific cutof levels ofTDx-FLM II for the prediction of neonatal respiratory distress syndrome. Fetal Diagn Ther 25:392, 2009 Bolisetty S, Dhawan A, Abdel-Latif M, et al: Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 133(1):55,t2014


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Obstentrics_Williams. Bolisetty S, Dhawan A, Abdel-Latif M, et al: Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 133(1):55,t2014 Brion LP, Bell EF, Raghuveer TS: Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev 4:CD003665, 2003 Burd I, Balakrishnan B, Kannan S: Models of fetal brain injury, intrauterine inlammation, and preterm birth. Am J Reprod Immunol 67(4):287, 2012 Caplan MS, Fanarof A. Necrotizing enterocolitis: a historical perspective. Semin PerinatoIt41(lt):2, 201 Centers for Disease Control and Prevention: Data and statistics for cerebral palsy. 2016. Available at: https:llwww.cdc.gov/ncbddd/cp/data.html. October 23, 2017 Chau V, McFadden DE, Poskitt KJ, et al: Chorioamnionitis in the pathogenesis of brain injury in preterm infants. Clin PerinatoIt41(1):83, 2014


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Obstentrics_Williams. Chau V, McFadden DE, Poskitt KJ, et al: Chorioamnionitis in the pathogenesis of brain injury in preterm infants. Clin PerinatoIt41(1):83, 2014 Clements JA, Platzker ACG, Tierney OF, et al: Assessment of the risk of respiratory distress syndrome by a rapid test for surfactant in amniotic fluid. N Engl J Med 286: 1 07 , 1972 Cole FS, Alleyne C, Barks JD et al: NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants. Pediatrics 127:363,t201t1 Cools F, Ofringa M, Askie LM: Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants. Cochrane Database Syst Rev 3:CDOOO 1 04, 2015 Crowther CA, Crosby DO, Henderson-Smart OJ: Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database Syst Rev 1 :CDOOO 164, 201 Oa


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Obstentrics_Williams. Crowther CA, Crosby DO, Henderson-Smart OJ: Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database Syst Rev 1 :CDOOO 164, 201 Oa Crowther CA, Crosby DO, Henderson-Smart OJ: Vitamin K prior to preteI'm birth for preventing neonatal peri ventricular haemorrhage. Cochrane Database Syst Rev 1:CD000229, 2010b Crowther CA, Doyle L W, Haslam RR, et al: Outcomes at 2 years of age after repeat doses of antenatal corticosteroids. N Engl J Med 357: 9, 2007 Darlow BA, Graham PJ, Rojas-Reyes MX: Vitamin A supplementation to prevent mortality and short-and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev 8:CD00050 1, 2016 Davidson LM, Berkelhamer SK: Bronchopulmonary dysplasia: chronic lung disease of infancy and long-term pulmonary outcomes. J Clin Med 6(1), 2017


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Obstentrics_Williams. Davidson LM, Berkelhamer SK: Bronchopulmonary dysplasia: chronic lung disease of infancy and long-term pulmonary outcomes. J Clin Med 6(1), 2017 De Luca AK, Nakazawa CY, Azevedo BC, et al: Influence of glycemic control on fetal lung maturity in gestations afected by diabetes or mild hyperglycemia. Acta Obstet Gynecol Scand 88(9):1036, 2009 Doyle LW, Crowther CA, Middleton P, et al: Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstet Gynecol 113: 1327, 2009


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Obstentrics_Williams. Doyle LW, Crowther CA, Middleton P, et al: Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstet Gynecol 113: 1327, 2009 Doyle L W, Ehrenkranz A, Halliday HL: Early « 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 5:CDOOI146, 2014a Doyle L W, Ehrenkranz A, Halliday HL: Late (> days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 5:CDOOI145, 2014b Ferre C, Callaghan W, Olson C et al: Efects of maternal age and age-speciic preterm birth rates on overall preterm birth rates-United States, 2007 and 2014. MMWR 65:1t181,t2016 Fowlie PW, Davis PG, McGuire W: Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 7:CD000174, 2010 Freeman JM, Nelson KB: Intrapartum asphyxia and cerebral palsy. Pediatrics 82:240, 1988


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Obstentrics_Williams. Freeman JM, Nelson KB: Intrapartum asphyxia and cerebral palsy. Pediatrics 82:240, 1988 Gluck L, Kulovich MV: Lecithin-sphingomyelin ratios in amniotic fluid in normal and abnormal pregnancy. Am J Obstet Gynecol 115:539, 1973 Gluck L, Kulovich MV, Borer RC J r, et al: Diagnosis of the respiratory distress syndrome by amniocentesis. Am J Obstet Gynecol 109:440, 1971 The Preterm Newborn 643 Gyami-Bannerman C, Thon EA, Blackwell Sc, et al: Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med 3 4(14):1311, 2016 Kair LR, Leonard DT, Anderson JM: Bronchopulmonary dysplasia. Pediatr Rev 33(6):255,t2012 Karcher R, Sykes E, Batton D, et al: Gestational age-speciic predicted risk of neonatal respiratory distress syndrome using lamellar body count and surfactant-to-albumin ratio in amniotic fluid. Am J Obstet Gynecol 193:1680, 2005


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Obstentrics_Williams. Khwaja 0, Volpe JJ: Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 93(2):F153, 2008 Kribs A: Minimally invasive surfactant therapy and noninvasive respiratory support. Clin Perinatol 55,t2016 Kwon SH, Vasung L, Ment LR et al: The role of neuroimaging in predicting neurodevelopmental outcomes of preterm neonates. Clin Perinatol 41(1):257,t2014 Leviton A, Allred EN, Kuban KC, et al: Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. The ELGAN study. Pediatr Res 67:95, 2010 Liebowitz M, Clyman R: Antenatal betamethasone: a prolonged time interval from administration to delivery is associated with an increased incidence of intraventricular hemorrhage before 28 weeks gestation. J Pediatr 177: 114,2016 Mathews TJ, MacDorman MF: Infant mortality statistics from the 2009 period linked birth/infant death data set. Natl Vital Stat Rep 61(8):1, 2013


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Obstentrics_Williams. Mathews TJ, MacDorman MF: Infant mortality statistics from the 2009 period linked birth/infant death data set. Natl Vital Stat Rep 61(8):1, 2013 Matsuda T, Okuyama K, Cho K, et al: Cerebral hemodynamics during the induction of antenatal periventricular leukomalacia by hemorrhagic hypotension in chronically instrumented fetal sheep. Am J Obstet Gynecol 194:1057,t2006 McCrea HJ, Ment LR: he diagnosis, management, and postnatal preven tion of intravetricular hemorrhage in the preterm neonate. Clin Perinatol 7,t2008 McCurnin DC, Pierce A, Chang LY, et al: Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease. Am J Physiol Lung Cell Mol Physiol 288:L540, 2005 Ment LR, Aden U, Bauer CR, et al: Genes and environment in neonatal intraventricular hemorrhage. Semin PerinatoI39(8):592, 2016


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Obstentrics_Williams. Ment LR, Aden U, Bauer CR, et al: Genes and environment in neonatal intraventricular hemorrhage. Semin PerinatoI39(8):592, 2016 Morley J, Davis PG, Doyle LW et al: Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 358:700, 2008 Moster D, Lie RT, Markestad T: Long-term medical and social consequences of preterm birth. N Engl J Med 359:262, 2008 Moya F, Sinha S, Gadzinowski j, et al: One year follow-up of very preterm infants who received lucinactat for prevention of respiratory distress syndrome: results from 2 multicenter randomized controlled trials. Pediatrics 119(6):e1361,t2007


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Obstentrics_Williams. Mukerji A, Shah V, Shah PS: Periventricularlintraventricular hemorrhage and neurodevelopmental ourcomes: a meta-analysis. Pediatrics 136(6):1132,t2015 National Institutes of Health: Antenatal corticosteroids revisited: repeat courses. NIH Consensus Statement 17(2):1, 2000 National Institutes of Health: The efects of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Statement 12(2): 1, 1994 Nelson KB: Can we prevent cerebral palsy? N Engl J Med 349: 1765, 2003 Neu j, Walker WA: Necrotizing enterocolitis. N Engl j Med 364:255,t2010 Nores j, Roberts A, Carr S: Prenatal diagnosis and management of fetuses with intracranial hemorrhage. Am j Obstet Gynecol 174:424, 1996 O'Caliaghan ME, MacLennan AH, Gibson CS, et al: Epidemiologic associations with cerebral palsy. Obstet Gynecol 118:576,2011


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Obstentrics_Williams. Papile LA, Burstein J, Burstein R, et al: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 gm. J Pediatr 92:529, Patra K, Wilson-Costello D, Taylor HG, et al: Grades I-II intraventricular hemorrhage in extremely low birth weight infants: efects on neurodevelopment. J Pediatr 149: 169,t2006 Perlman ]M, Risser R, Broyles RS: Bilateral cystic leukomalacia in the premature infant: associated risk factors. Pediatrics 97:822, 1996 Polin A, Carlo WA, Committee on Fetus and Newborn of the American Academy of Pediatrics: Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics 133(1):156,t2014 Rabe H, Diaz-Rossello JL, Duley L, et al: Efect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev 8:CD003248,t2012


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Obstentrics_Williams. Redline RW: Placental pathology: a systematic approach with clinical correlations. Placenta 22:S86, 2008 Rojas-Reyes MX, Morley CJ, Soli R: Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preteI'm infants. Cochrane Database Syst Rev 3:CD00051 0, 2012 Rosen MG, Dickinson JC: he incidence of cerebral palsy. Am J Obstet Gynecol 167:417, 1992 Sardesai S, Biniwale M, Wertheimer F, et al: Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future. Pediatr Res 81(1-2):240,t2017 Sarkar S, Bhagat I, Dechert R, et al: Severe intraventricular hemorrhage in preterm infants: comparison of risk factors and short-term neonatal morbidities between grade 3 and grade 4 intraventricular hemorrhage. Am J Perinatol 26:419,t2009 Schmidt B, Anderson Pj, Doyle LW, et al: Survival without disability to age 5 years after neonatal cafeine therapy for apnea of prematurity. JAMA 307(3):275,t2012


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Obstentrics_Williams. Schmidt B, Anderson Pj, Doyle LW, et al: Survival without disability to age 5 years after neonatal cafeine therapy for apnea of prematurity. JAMA 307(3):275,t2012 Schmidt B, Roberts RS, Anderson PJ, et al: Academic performance, motor function, and behavior 11 years after neonatal cafeine citrate therapy for apnea of prematuri ty: an I I-year follow-up of the CAP Randomized Clinical Trial. JAMA Pediatr 1(6):564,t2017 Schmidt B, Roberts RS, Davis P, et al: Cafeine therapy for apnea of prematurity. N Engl J Med 354(20):21t12,t2006 Sharma M, VanderVeen D: Identiication and treatment of retinopathy of prematurity: update 2017. New Reviews 18(2):e85, 2017 Smit E, Odd D, Whitelaw A: Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preteI'm infants. Cochrane Database SYSt Rev 8:CDOOI691, 2013 Soraisham AS, Singhal Nalini, McMillan DD, et al: A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am j Obstet 2.e1,t2009


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Obstentrics_Williams. Soraisham AS, Singhal Nalini, McMillan DD, et al: A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am j Obstet 2.e1,t2009 Stoll Bj, Hansen NI, Bell EF et al: Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 126(3):443,t2010 SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, et al: Target ranges of oxygen saturation in extremely preterm infants. N Engl j Med 362(21):1959, 2010a SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Finer NN, Carlo WA, et al: Early CPAP versus surfactant in extremely preterm infants. N Engl j Med 362(21):1970, 2010b Tredano M, Griese M, De Blic J, et al: Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB. Am J Med Genet A 119:324, 2003


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Obstentrics_Williams. Varner S, Sherman C, Lewis D et al: Amniocentesis for fetal lung maturity: will it become obsolete? Rev Obstet Gynecol 6(3/4): 126, 2013 Verhagen EA, Hummel LA, Bos AF, et al: Near-infrared spectroscopy to detect absence of cerebrovascular autoregulation in preteI'm infants. Clin Neurophysiol 125(1):47,t2014 Volpe JJ: Neurology of the Newborn, 5th ed. Philadelphia, Saunders, 2008 Wapner Rj, Sorokin Y, Mele L, et al: Long-term outcomes after repeated doses of antenatal corticosteroids. N Engl J Med 357: 1190, 2007 Wapner RJ, Sorokin Y, Thom EA, et al: Single versus weekly courses of antenatal corticosteroids: evaluation of safety and eicacy. Am J Obstet Gynecol 195:633,t2006 Wassink G, Davidson jO, Dhillon SK, et al: Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep. J Cereb Blood Flow Metab 37(3):1080, 201


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Obstentrics_Williams. Watterberg KL, American Academy of Pediatrics Committee on Fetus and Newborn: Policy statement-postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics 126(4):800,t2010 Wei JC, Catalano R, Proit J, et al: Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants. j Perinatol 36(5):352, 2016 Weindling M: Periventricular haemorrhage and periventricular leukomalacia. BJOG 102(4):278, 1995 Wert SE, Whitsett JA, Nogee LM: Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol 12(4):253, 2009 Whitelaw A: Core concepts: intraventricular hemorrhage. NeoReviews 12(2):e94,t2011 Yoon BH, Kim Cj, Romero R, et al: Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits. Am j Obstet Gynecol 177:797, 1997a Yoon BH, Romero R, Kim CJ, et al: High expression of tumor necrosis factoralpha and interleukin-6 in periventricular leukomalacia. Am J Obstet Gynecol 177:406, 1997b


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Obstentrics_Williams. Yoon BH, Romero R, Kim CJ, et al: High expression of tumor necrosis factoralpha and interleukin-6 in periventricular leukomalacia. Am J Obstet Gynecol 177:406, 1997b Yoon BH, Romero R, Park JS, et al: Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 182:6 5,t2000 Zalud I, Janas S: Risks of third trimester amniocentesis. J Reptod Med 53(1):45, 2008 Zupan V, Gonzalez P, Lacaze-Masmonteil T, et al: Periventricular leukomalacia: risk factors revisited. Dev Med Child NeuroIt38:1061, 1996 DEFINITION OF FETAL MORTALITY ................. 645 CAUSES OF FETAL DEATH ......................... 645 RISK FACTORS ....................................... 646 EVALUATION OF THE STILLBORN FETUS .............. 646 PSYCHOLOGICAL ASPECTS. . . . . . . . . . . . . . . . . . . . . . . 648 PRIOR STILLBIRTH .............................. 648 CHANGES IN STILLBIRTH RATES ................... 649


Obstentrics_Williams

Obstentrics_Williams. PSYCHOLOGICAL ASPECTS. . . . . . . . . . . . . . . . . . . . . . . 648 PRIOR STILLBIRTH .............................. 648 CHANGES IN STILLBIRTH RATES ................... 649 In the latter months of pregnancy, the disappearance of oetal movements usualy directs the attention of the patient to the possibiliy of oetal death. The diagnosis of this condition, however, can be considered absolute ony after repeated examinations, when one has ailed to hear the oetal heart or perceive the movements of the child. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) In Williams' time, absolute documentation of fetal death was frustrating for both patient and obstetrician. Now, sonography provides prompt conirmation, which allows expedient induction of labor and delivery. However, epidemiologically, defining and reporting fetal deaths was-and continues to be-a challenge. In response, eforts to standardize the deinition of stillbirth and analyze varying reports for application into clinical practice and public health policy are now being emphasized. Moreover, stillbirth research and prevention within the United States and abroad has expanded. Global public health eforts were stimulated in part by a six-part series in The Lancet.


Obstentrics_Williams

Obstentrics_Williams. his compilation was considered a call to action after the recognition that an estimated 2.65 million stillbirths occur each year and that 98 percent of stillborn fetuses are from low-and middle-income countries (The Lancei s Stillbirth Series Steering Committee, 201 la-). Unfortunately, progress in improving these rates has been slow, as outlined in The Lancet's subsequent five-part progress report, which emphasized the need for dedicated leadership, measured efects of interventions, and investigation into knowledge gaps (The Lancets Ending Preventable Stillbirths Series Study Group, 20 l6a-e).


Obstentrics_Williams

Obstentrics_Williams. In the United States, an estimated 1 million fetal losses are reported each year, and most occur before 20 weeks' gestation. Fetal mortality data from the National Vital Statistics system are usually presented for fetal deaths after the 20-week threshold (MacDorman, 2015). Using this definition, numbers of fetal deaths in the United States in 2013 slightly surpassed numbers of infant deaths (Fig. 35-1). As shown in Figure 35-2, 24.9% Undereage 28days 33.8% 16.1% FIGURE 35-1 Percent distribution of fetal deaths at 20 weeks' gestation or more and of infant deaths: United States, 2013. (Data from MacDorman MF, Reddy UM, Silver RM: Trends in stillbirth by gestational age in the United States, 2006-201o2, Obstet Gynecol. 2015 Dec;126(6):1146-1150.) 0.7 0.6 0.5 ) 0.4�: 0.3 0.2 0.1 0.0 weeks of gestation: United States, 2013. (Redrawn from MacDorman


Obstentrics_Williams

Obstentrics_Williams. MF, Reddy UM, Silver RM: Trends in stillbirth by gestational age in the United States, 2006-2012, Obstet Gynecol. 2015 Dec;126(6): 1146-1o150.) fetal death rates are highest at the earliest and latest gestational ages, which suggests etiological diferences.


Obstentrics_Williams

Obstentrics_Williams. he current definition of fetal death adopted by the Centers for Disease Control and Prevention National Center for Health Statistics is based on a deinition recommended by the World Health Organization (MacDorman, 2015). It states that "Fetal death means death prior to complete expulsion or extraction .rom the mother of a product of human conception irrespective of the duration of pregnancy and which is not an induced termination of pregnancy. The death is indicated by the act that after such expulsion or extraction, the etus does not breathe or show any other evidence of lie such as beating of the heart, pulsation of the umbilical cor, or deinite movement of voluntary muscles. Heartbeats are to be distinguished rom transient cardiac contractions; respirations are to be distinguished .rom fleeting respiratory eorts or gasps."


Obstentrics_Williams

Obstentrics_Williams. Reporting requirements for fetal deaths in the United States are determined by each state, and thus, criteria difer signiicantly (Chap. 1, p. 3). Most states mandate reporting of deaths of fetuses that are 20 weeks' gestation or older or have a minimum birthweight of 350 g (roughly equivalent to 20 weeks) or some combination of these two. However, several states require reporting of fetal deaths at all periods of gestation, and one sets the threshold at 16 weeks. lternatively, two states require reporting of deaths for fetuses with birthweights of 500 g, which approximates that at 22 weeks. here is substantial evidence that not all fetal deaths for which reporting is required are actually recorded (MacDorman, 2015). This is most likely for those at earlier gestational ages.


Obstentrics_Williams

Obstentrics_Williams. Comparisons of rates among countries are limited by incomplete fetal death data. Namely, internationally, less than 5 percent of neonatal deaths have formalized documentation (The Lancet's Ending Preventable Stillbirths Series Study Group, 2016d). Further, comparative analyses using birthweight versus gestational age among countries do not provide equivalent results. For example, in the United States, if stillbirth would be deined by a birthweight �500 g, the stillbirth rate would be reduced by 40 percent compared with FIGURE 35-3 Fetal mortality rates by period of gestation: United States, 2000-2013. (Data from MacDorman MF, Reddy UM, Silver RM: Trends in stillbirth by gestational age in the United States, 2006-2012, Obstet Gynecol. 2015 Dec;126(6):1146-1150.) a 22-week-age deined cohort (Blencowe, 2016). To address nomenclature diferences, some have called for changes to the current deini tion a oseph, 2015).


Obstentrics_Williams

Obstentrics_Williams. Overall, fetal mortality rates in the United States have remained relatively unchanged since 2006. However, the infant mortality rate has declined 11 percent, and both rates are now essentially equal (MacDorman, 2015). Three fetal mortality epochs are generally described: early (less than 20 completed weeks' gestation); intermediate (20 to 27 weeks); and late (28 weeks or more). The fetal mortality rate at 20 to 27 weeks in 2013 declined 3 percent from the prior year. Between 2006 and 2012, rates were essentially unchanged in this age group. The late fetal mortality rate has been relatively unchanged since 2006 35-3).


Obstentrics_Williams

Obstentrics_Williams. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) created the Stillbirth Collaborative Research Network to ascertain stillbirth causes in racially and geographically diverse populations in the United States. From this, the Stillbirth Collaborative Research Network Writing Group (201a1b) examined reasons for death at 20 weeks' gestation or later between 2006 and 2008 in 59 tertiary care and community hospitals in ive states. Standardized evaluations included autopsy, placental histology, and testing of maternal or fetal bloodltissues, including fetal karyotyping. Evaluations were performed in 500 women with 512 stillbirths. Of these losses, 83 percent were before labor. Causes of stillbirth were divided into eight categories shown in Table hese categories were then classified as probable, possible, or unknown. As an example, diabetes was considered a probable cause if the fetus had diabetic embryopathy with lethal anomalies or the mother had


Obstentrics_Williams

Obstentrics_Williams. were then classified as probable, possible, or unknown. As an example, diabetes was considered a probable cause if the fetus had diabetic embryopathy with lethal anomalies or the mother had diabetic ketoacidosis. It was a possible cause if the mother had poor glycemic control and the fetus had abnormal growth. Overal, a probable or possible source was identiied in 76 percent of cases.


Obstentrics_Williams

Obstentrics_Williams. This Network study is unprecedented in the United States for several reasons. It was a population-based cohort of TABLE 35-1. Causes of 512 Stillbirths in the Stillbirth Collaborative Research Network Study Percentages are rounded and total more than 100 percent because some stillbirths had more than one cause. Overall, a cause was identified in 76 percent of stillbirths. Data from Stillbirth Research Network Writing Group, 201n1 b.


Obstentrics_Williams

Obstentrics_Williams. Data from Stillbirth Research Network Writing Group, 201n1 b. stillbirths, in which all underwent systematic and thorough evaluation. Each assigned cause of fetal death is reasonably straightforward and comprehensible except for "placental abnormalities." This category contains "uteroplacental insufficiency" and a few other less clearly defined placental entities. his aside, the leading reasons for fetal death were obstetrical and primarily included abruption, multifetal gestation complications, and spontaneous labor or ruptured membranes before viability. Importantly, this study illustrated that systematic evaluation may identiy a likely cause in approximately three fourths of stillbirths. his rate is considerably higher than those in most prior analyses and serves to emphasize the importance of careful examination.


Obstentrics_Williams

Obstentrics_Williams. Many factors are associated with an increased risk of stillbirth. Among others, these include advanced maternal age; AfricanAmerican race; smoking; illicit drug use; maternal medical diseases-such as overt. diabetes or chronic hypertension; assisted reproductive technology; nulliparity; obesity; and prior adverse pregnancy outcomes-such as prior preterm birth or growth-restricted newborn (Reddy, 2010; Varner, 2014).


Obstentrics_Williams

Obstentrics_Williams. Two major studies have assessed whether stillbirth risk factors could be identiied either before or shortly after pregnancy confirmation. In the first, Reddy and colleagues (2010) analyzed data from the NICHD Consortium on Safe Labor. Briely, the pregnancy outcomes of 206,969 women delivered between 2002 and 2008 at 19 hospitals in the United States were analyzed. When the distribution of stillbirths according to gestational age was studied, the tragedy of stillbirth occurred primarily in term pregnancies. hese investigators concluded that their results did not support routine antenatal surveillance for any demographic risk factors.


Obstentrics_Williams

Obstentrics_Williams. The second analysis of stillbirth risk factors was included in the Stillbirth Collaborative Research Network study described earlier. he validity of stillbirth prediction was assessed based on risks identified in early pregnancy. They found that pregnancy factors known at the start of pregnancy accounted for only a small proportion of stillbirth risk. Except for prior stillbirth or pregnancy loss from causes such as preterm birth or fetal-growth restriction, other risks had limited predictive value (Stillbirth Collaborative Research Network Writing Group, 2011a). he importance of prior stillbirth as a risk for recurrence has been emphasized by Sharma and associates (2006). Specifically, the stillbirth risk was ivefold higher in women with a prior stillbirth. From another report, prior preterm birth, fetal-growth restriction, preeclampsia, and placental abruption were strongly associated with subsequent stillbirth (Rasmussen, 2009). Table 35-2 lists estimates of stillbirth risk


Obstentrics_Williams

Obstentrics_Williams. preterm birth, fetal-growth restriction, preeclampsia, and placental abruption were strongly associated with subsequent stillbirth (Rasmussen, 2009). Table 35-2 lists estimates of stillbirth risk according to maternal factors.


Obstentrics_Williams

Obstentrics_Williams. Determining the cause of fetal death aids maternal coping, helps assuage any perceived guilt, permits more accurate counseling regarding recurrence risk, and may prompt therapy or intervention to prevent a similar outcome in subsequent pregnancies (American College of Obstetricians and Gynecologists, 20 16a). Identification of inherited syndromes also provides useful information for other family members. Important tests in stillbirth evaluation are neonatal autopsy, chromosomal analysis, and examination of the placenta, cord, and chorioamnionic membranes (Pinar, 2014). Page and coworkers (2017) found placental pathology and fetal autopsy to be the most useful. One algorithm from the American College of Obstetricians and Gynecologists (2016a) is shown in


Obstentrics_Williams

Obstentrics_Williams. Figure 35-4. Findings are documented in the medical record, and relevant prenatal events are delineated. Photographs are taken whenever possible, and a full radiograph of the fetusa etogram-may be performed. Postnatal magnetic resonance (MR) imaging or sonography may be especially important in providing anatomical information if parents decline a full autopsy (McPherson, 2017; Shruthi, 2017). If autopsy and chromosomal studies are performed, up to 35 percent of stillborn fetuses are discovered to have major TABLE 35-2. Estimated Maternal Risk Factors and Risk Inspect fetus and placenta: Weight, head circumference, and length of fetus Weight of placenta Photographs of fetus and placenta Frontal and profile photographs of whole body, face, extremities, palms, and any abnormalities Document finding and abnormalities Obtain consent from parents for cytologic specimens:


Obstentrics_Williams

Obstentrics_Williams. Frontal and profile photographs of whole body, face, extremities, palms, and any abnormalities Document finding and abnormalities Obtain consent from parents for cytologic specimens: Obtain cytologic specimens with sterile techniques and instruments -Amniotic fluid obtained by amniocentesis at time of prenatal diagnosis of demise: paticularly valuable if delivery is not expected imminently -Placental block (1 x 1) cm taken from below the cord insertion site on the unfixed placenta -Umbilical cord segment (1e.5 cm) -Internal fetal tissue specimen, such as costochondral junction or patella; skin is not recommended Place specimens in a sterile tissue culture medium of lactated Ringer's solution and keep at room temperature when transported to cytology laboratory


Obstentrics_Williams

Obstentrics_Williams. Place specimens in a sterile tissue culture medium of lactated Ringer's solution and keep at room temperature when transported to cytology laboratory Fetal autopsy and placental If no consent is given for pathology (may include autopsy, send placenta fetal whole-body X-ray) alone for pathology (Chap. 13, p. 271). CMA does not require dividing cells and is reported to be more useful in the evaluation of fetal death. his is especially true because the culturing of macerated fetal tissue is frequently unsuccessful (Reddy, 2012). Both the American College of Obstetricians and Gynecologists (2016c) and the Society for Maternal-Fetal Medicine (2016) now endorse the use of CMA for stillborn fetuses.


Obstentrics_Williams

Obstentrics_Williams. Appropriate consent must be obtained to take fetal samples, including tissue or luid obtained postmortem by needle aspiration. As recently outlined by the American College of Obstetricians and Gynecologists (2016c), any type of fetal or placental tissue or amnionic fluid can be submitted for genetic testing by CMA. Contamination with maternal tissue or blood is ideally avoided. If fetal blood cannot be obtained from the umbilical cord or by cardiac puncture, the American College of Obstetricians and Gynecologists (20a16a) recommends at least one of the following samples: (1) a placental block measuring about 1 X 1 cm taken below the cord insertion site in the unfixed specimen; (2) umbilical cord segment approximately 1.5 cm long; or (3) internal fetal tissue specimen such as costochondral junction or patella. Tissue is washed with sterile saline before Cholestasis of pregnancy


Obstentrics_Williams

Obstentrics_Williams. Cholestasis of pregnancy BMI 25-29.9 kg/m2 ::12 yr) ::40 yr 6.4 4.0-5.5 1n.0 0.86 1.5-2.7 1n.2-4.0 1n.8-4.4 1n.2-2.2 1.7-7.0 2.2-30 2.2-3.0 2.8-5.0 1n.8-4.4 1n.7-3.0 1n.9-2.7 2.1n-2.8 1.6-2.0 2-4.6 1.4-3.2 1.8-2.2 1n.8-3.3 2.0-2.2 Twins Triplets Maternal age 12 1n.0-2.8 34 2.8-3.7 FIGURE 35-4 Flow chart for fetal and placental evaluation. (Modified with permission from ACOG Practice Bulletin No.o1 02: management of stillbirth, Obstet Gynecol. 2009 Mar;1o13(3):748-761o.) aOdds ratio of the factor being present compared with the risk factor being absent. BMI = body mass index; IUGR = intrauterine growth restriction; PIH = pregnancy-induced hypertension; SLE = systemic lupus erythematosus. Adapted from Fretts, 2005.


Obstentrics_Williams

Obstentrics_Williams. structural anomalies (Faye-Petersen, 1999). Approximately 20 percent have dysmorphic features or skeletal anomalies, and 8 percent have chromosomal abnormalities (Pauli, 1994; Saller, 1995). In the absence of anatomic dysmorphology, up to 5 percent of stillborn fetuses will have a chromosomal abnormality (Korteweg, 2008). Although the American College of Obstetricians and Gynecologists (20a1a6a) previously recommended karyotyping all stillborn fetuses, technological advancements of high-resolution, whole-genome sequencing-such as with chromosomal microarray anaysis ()-are now replacing standard karyotyping for chromosomal analysis of stillborn fetuses being placed in lactated Ringer solution or sterile cytogenetic medium. Notably, placement in formalin or alcohol kills viable cells. If conventional karyotyping is the only test available and the timing of death is recent, amnionic luid can be obtained by amniocentesis, as those cells obtained in a sterile fashion provide a greater


Obstentrics_Williams

Obstentrics_Williams. conventional karyotyping is the only test available and the timing of death is recent, amnionic luid can be obtained by amniocentesis, as those cells obtained in a sterile fashion provide a greater likelihood of cell growth and eventual result compared with tissue obtained after delivery. Maternal blood is obtained for Kleihauer-Betke staining; for anti phospholipid antibody and lupus anticoagulant testing if indicated; and for serum glucose measutement to exclude overt diabetes (Silver, 20al3).


Obstentrics_Williams

Obstentrics_Williams. In cases with significant growth restriction, with a family or personal history of thrombosis, or with severe placental pathology, testing for factor V Leiden mutation, prothrombin mutation, antithrombin level, and protein C and S activity may provide some information that could afect future pregnancy management (American College of Obstetricians and Gynecologists, 2016a). Our interpretation of relevant placental pathology includes derangements that stem from maternal vessel obstruction, which are described in Chapter 6. Although some have recommended routine evaluation of heritable thrombophilias, no evidence supports the clinical or financial eiciency of screening in an unselected population. Silver and colleagues (2016), with data from the Stillbirth Collaborative Research Network, found that most maternal and fetal thrombophilias were not associated with stillbirth and recommended against routine testing.