Obstentrics_Williams

Obstentrics_Williams. he timing of delivery is crucial, and the risks of fetal death versus the hazards of preterm birth must be considered. Several multicenter studies address these problems, but unfortunately, none have elucidated the optimal timing of delivery. For the preterm fetus, the only randomized trial of delivery timing is the Growth Restriction Intervention Trial (GRIT) (hornton, 2004). This trial involved 548 women between 24 and 36 weeks' gestation with clinical uncertainty regarding delivery timing. Women were randomly assigned to immediate delivery or to delayed delivery until the situation worsened. he primary outcome was perinatal death or disability after reaching age 2 years. Mortality rates did not difer through 2 years of age. Moreover, children aged 6 to 13 years did not show clinically signiicant diferences between the two groups (Walker, 2011).


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Obstentrics_Williams. In the Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE), ductus venosus Doppler evaluation was compared with fetal heart rate monitoring. There were 310 pregnancies between 26 and 32 weeks' gestation with fetuses displaying an abdominal circumference < 10th percentile and an umbilical artery pulsatility index >95th percentile (Lees, 2015). Delivery timing was determined by the results of three difering antenatal fetal assessment arms that were: short-term fetal heart rate variability, early ductus venosus Doppler velocimetry changes, or late ductus changes. he proportion of children with neuroimpairment at 2 years of age was not diferent among the groups. Of note, only 32 percent of the newborns overall were delivered according to this randomization. Safety net criteria and other maternal/fetal indications prompted these protocol deviations (Visser, 2016). In a post-hoc analysis, these authors concluded that before 32 weeks, delaying delivery until ductus venosus


Obstentrics_Williams

Obstentrics_Williams. and other maternal/fetal indications prompted these protocol deviations (Visser, 2016). In a post-hoc analysis, these authors concluded that before 32 weeks, delaying delivery until ductus venosus Doppler or fetal heat rate abnormalities occur is likely safe and possibly beneits long-term outcome (Ganzevoort, 2017).


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Obstentrics_Williams. he Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) study examined the delivery timing of growth-restricted fetuses who were 36 weeks' gestation or older. In these 321 women who were randomized to induction or to expectant management, composite neonatal morbidity did not difer, except that neonatal admissions were lower after 38 weeks in a secondary analysis (Boers, 2010, 2012). Another secondary analysis of DIGITAT did not identiy a clear subgroup that beneited from labor induction (T ajik, 2014). Other secondary analyses included assessment of neurodevelopmental and behavioral outcomes at age 2, and these also were similar between the randomized groups (Van Wyk, 2012). Management of the Near-Term Fetus


Obstentrics_Williams

Obstentrics_Williams. As shown in Figure 44-9, delivery of a suspected growthrestricted fetus with normal umbilical artery Doppler velocimetry, normal amnionic luid volume, and reassuring fetal heart rate testing can likely be deferred until 38 weeks' gestation. Said another way, uncertainty regarding the diagnosis should preclude intervention until fetal lung maturity is assured. Expectant management can be guided using antepartum fetal surveillance techniques described in Chapter 17. Most clinicians, however, recommend delivery at 34 weeks or beyond if there is clinically signiicant oligohydramnios. Consensus statements by the Society for Maternal-Fetal Medicine (Spong, 2011) and the American College of Obstetricians and Gynecologists (2017a) are similar. These recommend delivery between 34 and 37 weeks when there are comorbid conditions such as oligohydramnios. With a reassuring fetal heart rate pattern, vaginal delivery is planned. Notably, some of these fetuses do not tolerate labor.


Obstentrics_Williams

Obstentrics_Williams. Management of the Fetus Remote from Term If growth restriction is identiied in an anatomically normal fetus before 34 weeks, and amnionic luid volume and fetal surveillance indings are normal, observation is recommended. Screening for toxoplasmosis, cytomegalovirus infection, rubella, herpes, and other infections is recommended by some. However, we and others have not found this to be productive (Yamamoto, 2013).


Obstentrics_Williams

Obstentrics_Williams. As long as interval fetal growth and fetal surveillance test results are normal, pregnancy is allowed to continue until fetal lung maturity is reached (see Fig. 44-9). Reassessment of fetal growth is typically made no sooner than 3 to 4 weeks. Weekly assessment of umbilical artery Doppler velocimetry and amnionic fluid volume is combined with periodic nons tress testing, although the optimal frequency has not been determined. As mentioned, we hospitalize these women in our High-Risk Pregnancy Unit and monitor their fetuses daily. If interval growth, amnionic luid volume, and umbilical artery Doppler velocimetry are normal, then the mother is discharged home and seen intermittently for outpatient surveillance.


Obstentrics_Williams

Obstentrics_Williams. With growth restriction remote from term, no speciic treatment ameliorates the condition. For example, evidence does not support diminished activity or bed rest to accelerate growth or improve outcomes. Despite this, many clinicians intuitively advise a program of modiied rest. Nutrient supplementation, attempts at plasma volume expansion, oxygen therapy, antihypertensive drugs, heparin, and aspirin are all inefective (American College of Obstetricians and Gynecologists, 2015).


Obstentrics_Williams

Obstentrics_Williams. In most cases diagnosed before term, neither a precise etiology nor a specific therapy is apparent. Management decisions hinge on assessment of the relative risks of fetal death during expectant management versus the risks from preterm delivery. lthough reassuring fetal testing may allow observation with continued maturation, long-term neurological outcome is a concern (Baschat, 2014; Lees, 2015; Thornton, 2004). Baschat and associates (2009) showed that neurodevelopmental outcome at 2 years in growth-restricted fetuses was best predicted by birthweight and gestational age. Doppler abnormalities are generally not associated with poor childhood cognitive developmental scores among low-birthweight fetuses delivered in the third trimester (Llurba, 20l3). hese indings emphasize that adverse neurodevelopmental outcomes cannot always be predicted.


Obstentrics_Williams

Obstentrics_Williams. Fetal-growth restriction is commonly the result of placental insuiciency due to faulty maternal perfusion, reduction of functional placenta, or both. If present, these conditions are likely aggravated by labor. Equally important, diminished amnionic luid volume raises the likelihood of cord compression during labor. For these and other reasons, the frequency of cesarean delivery is increased. Accordingly, a woman with a suspected growth-restricted fetus should undergo "high-risk" intrapartum monitoring (Chap. 24, p. 478).


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Obstentrics_Williams. The risk of neonatal hypoxia or meconium aspiration is also greater. hus, care for the newborn should be provided immediately by an attendant who can skillfully clear the airway and ventilate a neonate as needed (Chap. 32, p. 608). he severely growth-restricted newborn is particularly susceptible to hypothermia and may also develop other metabolic derangements such as hypoglycemia, polycythemia, and hyperviscosity. In addition, low-birthweight newborns are at higher risk for motor and other neurological disabilities. Risk is greatest at the lowest extremes of birth weight (Baschat, 2009, 2014; Llurba, 2013).


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Obstentrics_Williams. The term macrosomia is used rather imprecisely to describe a very large fetus or newborn. Although there is general agreement among obstetricians that neonates weighing < 4000 g are not excessively large, a similar consensus has not been reached for the definition of macrosomia. Newborn weight rarely exceeds 11 pounds (5000 g), and excessively large infants are a curiosity. The largest newborn cited in the Guinness Book of World Records was a 23-lb 12-oz (10,800 g) infant boy born in 1879 to a Canadian woman (Barnes, 1957). In the United States in 2015, of more than 4 million births, 6.9 percent weighed 4000 to 4499 g; 1 percent weighed 4500 to 4999 g; and 0.1 percent were born weighing 5000 g or more 4500-4649 3221 (Martin, 2017) . To be sure, the incidence of excessively large 4750-4999 1146 0.3 134 12 infants grew during the 20th century. According to Williams 5000-5249 385 0.1 57 15 (1903), at the beginning of the 20th century, the incidence 5250-5499 127 0.04 31


Obstentrics_Williams

Obstentrics_Williams. TABLE 44-2. Birthweight Distribution of 354,509 Liveborn Infants at Parkland Hospital between 1988 and 2012 (g) No. % No. /0 500-3999 322,074 90.9 13,365 4 4000-4249 19,106 5.4 1043 5 4250-4499 8391 2.4 573 7 of birthweight > 5000 g was 1 to 2 per 10,000 births. his 5500 or more 0.02 14 24 compares with 16 per 10,000 births at Parland Hospital from 1988 through 2008 and with 11 per 10,000 in the United States in 2010. he influence of increasing maternal obesity rates is overwhelming, and its association with diabetes is well known. Of Parkland mothers with newborns weighing > 5000 g, more than 15 percent were diabetic. Several terms currently describe pathological fetal overgrowth. he most common ofthese-macrosomia-is defined by birthweights that exceed certain percentiles for a given population. Another commonly used scheme is to deine macrosomia by an empirical birthweight threshold.


Obstentrics_Williams

Obstentrics_Williams. Macrosomia is frequently deined based on mathematical distributions of birthweight. Those newborns exceeding the 90th percentile for a given gestational week are usually used as the threshold for macrosomia or large-for-gestational age (LGA) birthweight. For example, the 90th percentile at 39 weeks is 4000 g. If, however, birthweights that are 2 standard deviations above the mean are used, then thresholds lie at the 97th percentile. Thus, substantially larger newborns are considered macrosomic compared with those at the 90th percentile. Specifically, the birthweight threshold at 39 weeks to be macrosomic would be approximately 4500 g for the 97th percentile rather than 4000 g for the 90th percentile.


Obstentrics_Williams

Obstentrics_Williams. Newborn weight exceeding 4000 g (8 lb 13 oz) is also a frequently used threshold to deine macrosomia. Others use 4250 g or even 4500 g (10 lb). As shown in Table 44-2, birthweights ::4500 g are uncommon. During a 30-year period at Parkland Hospital, during which there were more than 350,000 singleton births, only 1.4 percent of newborns weighed 4500 g or more. We are of the view that the upper limit of fetal growth, above which growth can be deemed abnormal, is likely two standard deviations above the mean, representing perhaps 3 percent of births. At 40 weeks, such a threshold would correspond to approximately 4500 g. The American College of Obstetricians and Gynecologists (2016a) concludes that the term macrosomia was an appropriate appellation for newborns who weigh 4500 g or more at birth. Total 354,509 15,501 Some factors associated with fetal overgrowth are listed in Table 44-3. Many are interrelated and thus likely are additive.


Obstentrics_Williams

Obstentrics_Williams. Total 354,509 15,501 Some factors associated with fetal overgrowth are listed in Table 44-3. Many are interrelated and thus likely are additive. For example, advancing age is usually related to multiparity and diabetes, and obesity is related to diabetes. In one study, the incidence of macrosomia exceeded 24 percent in China among obese women, and macrosomia rates were also signiicantly higher (approximately 2.5-fold) for prolonged pregnancy and gestational diabetes (Wang, 2017). Of these, maternal diabetes is an important risk factor for fetal overgrowth (Chap. 57, p. 1100). s shown in Table 44-2, the incidence of maternal diabetes grows s birthweights >4000 g rise. It should be emphasized, however, that maternal diabetes is associated with only a small percentage of the total number of such large newborns.


Obstentrics_Williams

Obstentrics_Williams. The adverse consequences of excessive fetal growth are considerable. Neonates with a birthweight of at least 4000 g have cesarean delivery rates > 50 percent. This is particularly true with maternal obesity or diabetes or with birthweights >5000 g (Cordero, 2015; Crosby, 2017; Gaudet, 2014; Hehir, 2015). One study found a higher risk for traumatic neonatal morbidity in LGA neonates compared with normal-weight ones (Chauhan, 2017). Rates of shoulder dystocia vary greatly and can reach nearly 30 percent for macrosomic neonates when maternal diabetes is comorbid (Cordero, 2015). In general obstetrical populations that include diabetic mothers, dystocia rates are at least 5 percent for neonates with birthweights ::5000 g (Crosby, TABLE 44-3. Risk Factors for Fetal Overgrowth Large size of parents Advancing maternal age Previous macrosomic infant Racial and ethnic factors


Obstentrics_Williams

Obstentrics_Williams. TABLE 44-3. Risk Factors for Fetal Overgrowth Large size of parents Advancing maternal age Previous macrosomic infant Racial and ethnic factors TABLE 4-4. Maternal and Fetal Outcomes for 208,090 Pregnancies Delivered at Parkland Hospital from 1998 through 201e2 <4000 9 4000-4499 9 4500-4999 9 �5000 9 Outcomea n = 187,1 19 n = 17,750 n = 2849 n = 372 P value Cesa rea n totaI 46,577 (25) 5,362 (30) 1204 (42) 224 (60) <0.001 Scheduled 12,564 (7) 1,481 (8) 316 (11) 65 (17) <0.001 Dystocia 7589 (4) 1388 (8) 337 (1n2) 46 (1n2) <0.001 Shou Ider dystocia 437 (0) 366 (2) 192 (7) 56 (15) <0.001 3rd-or 4th-degree laceration 7296 (4) 932 (5) 190 (7) 37 (1n0) <0.001 Labor induction 26,118 (13) 2499 (14) 420 (15) 39 (10) 0.141 Prolonged second stage 6905 (4) 899 (5) 147 (5) 14 (4) <0.001 Chorioamnionitis 13,448 (7) 1778 (1n0) 295 (1n0) 35 (9) <0.001 pH <7.0 925 (0.5) 96 (0.6) 20 (0.7) 4 (1.1) 0.039 Apgar <7 @ 5 minutes 1898 (1n.0) 80 (0.5) 22 (0.8) 10 (2.7) <0.001


Obstentrics_Williams

Obstentrics_Williams. Apgar <7 @ 5 minutes 1898 (1n.0) 80 (0.5) 22 (0.8) 10 (2.7) <0.001 ICN admission 4266 (2.2) 123 (0.7) 36 (1n.3) 9 (2.4) <0.00'1 Fractured clavicle 1880 (1.0) 616 (3.5) 125 (4.4) 16 (4.3) <0.001 Mechanical ventilation 2305 (1n.2) 54 (0.3) 11 (0.4) 9 (2.4) <0.001 Hypoglycemia 480 (0.2) 89 (0.5) 31 (1.1) 12 (3.2) <0.001 Hyperbilirubinemia 5829 (3.0) 305 (1.7) 60 (2.1) 12 (3.2) <0.001 Erb palsy 470 (0.2) 224 (1n.3) 74 (2.6) 22 (5.9) <0.001 Neonatal death 402 (0.2) 3 (0) 2 (0.1) 1 (0.3) <0.001 aOutcome data presented as n (%). ICN = intensive care nursery. 2017; Hehir, 2015). Rates of postpartum hemorrhage, perineal laceration, and maternal infection, which are related complications, are also higher in mothers delivering overgrown newborns. Maternal and neonatal outcomes by birthweight for large babies >4000 g delivered at Parkland Hospital are shown in Table 44-4.


Obstentrics_Williams

Obstentrics_Williams. Because current methods fail to accurately estimate excessive fetal size, macrosomia cannot be deinitively diagnosed until delivery. Inaccuracy in clinical estimates of fetal weight by physical examination is often attributable, at least in part, to maternal obesity. Numerous attempts have been made to improve the accuracy of sonographic fetal-weight estimation. Several formulas have been proposed to calculate fetal weight using measurements of the head, femur, and abdomen. Estimates provided by these computations are reasonably accurate for predicting the weight of small, preterm fetuses but are less valid in predicting the weight of large fetuses. In one study of 248 LGA and 655 non-LGA newborns from pregnancies complicated by diabetes, only 23 percent of women diagnosed with an LGA fetus before delivery actually delivered an LGA infant (Scifres, 2015). his resulted in a more than threefold rise in the cesarean delivery rate for suspected LGA birthweights.


Obstentrics_Williams

Obstentrics_Williams. From the foregoing, it is apparent that sonographic estimation of fetal weight is unreliable, and its routine use to identiy macrosomia is not recommended. Indeed, the American College of Obstetricians and Gynecologists (2016a) concludes that clinical fetal weight estimates are just as accurate as sonographic ones.


Obstentrics_Williams

Obstentrics_Williams. Several interventions have been proposed to interdict fetal overgrowth. Some include prophylactic labor induction for poorly deined indications such as "impending macrosomia," or elective cesarean delivery to avoid diicult delivery and shoulder dystocia. For women with diabetes in pregnancy, insulin therapy and close attention to good glycemic control reduces birthweight. However, this has not consistently translated into reduced cesarean delivery rates. Furthermore, as noted above, erroneous diagnosis of fetal overgrowth among women with diabetes raises cesarean delivery rates (Scifres, 2015). Also previously mentioned, fetal overgrowth irrespective of the diagnosis of diabetes mellitus is strongly associated with maternal obesity and excessive gestational weight gain (Durie, 2011; Durst, 2016; Harper, 2015). Dietary intervention to limit fetal overgrowth by curbing gestational weight gain, for example, is an active area of research. Currently recommended weight gains for pregnancy


Obstentrics_Williams

Obstentrics_Williams. 2016; Harper, 2015). Dietary intervention to limit fetal overgrowth by curbing gestational weight gain, for example, is an active area of research. Currently recommended weight gains for pregnancy according to maternal BMI are described in Chapter 9 (p. 165).


Obstentrics_Williams

Obstentrics_Williams. Some clinicians induce labor when fetal macrosomia is suspected in nondiabetic women. his approach is suggested to obviate further fetal growth and thereby reduce potential delivery complications. Such prophylactic induction should theoretically reduce the risk of shoulder dystocia and cesarean delivery. In one systematic review of 11 studies of expectant management versus labor induction for suspected macrosomia, labor induction increased cesarean delivery rates without improving perinatal outcomes (Sanchez-Ramos, 2002). In contrast, Magro-Malosso and colleagues (2017) performed a metaanalysis of four randomized trials involving 1r190 women and concluded that labor induction at 38 or more weeks for suspected macrosomia significantly reduces the frequency of fetal overgrowth and fractures. In one of these studies, 822 women with suspected LGA fetuses were randomly assigned either to early term delivery (37°/7 to weeks) or to expectant management (Boulvain, 2015). here was a higher


Obstentrics_Williams

Obstentrics_Williams. In one of these studies, 822 women with suspected LGA fetuses were randomly assigned either to early term delivery (37°/7 to weeks) or to expectant management (Boulvain, 2015). here was a higher rate of vaginal delivery that was marginally significant and a lower composite measure of morbidity. These authors cautioned that any beneits should be balanced with the risks of earlyterm labor induction and delivery. Namely, a review of earlyterm births indicates that elective delivery before 39 weeks' gestation does not improve maternal outcomes and is associated with worse neonatal outcomes (Tita, 2016). We agree with the American College of Obstetricians and Gynecologists (2016a, 2017a,b) that current evidence does not support a policy for early labor induction or delivery before 39 weeks' gestation. It remains unclear whether delivery or induction for suspected macrosomia at term is better than expectan t management.


Obstentrics_Williams

Obstentrics_Williams. With the delivery of macrosomic infants, shoulder dystocia and its attendant risks described in Chapter 27 (p. 520) are major concerns. That said, the American College of Obstetricians and Gynecologists (20 17b) concluded that fewer than 10 percent of all shoulder dystocia cases result in a persistent brachial plexus injury, and 4 percent of these injuries still follow cesarean delivery. For prevention, planned cesarean delivery on the basis of suspected macrosomia to prevent brachial plexopathy is an unreasonable strategy in the general population (Chauhan, 2005). Ecker and coworkers (1997) analyzed 80 cases of brachial plexus injury in 77,616 consecutive infants born at Brigham and Women's Hospital. They concluded that an excessive number of otherwise unnecessary cesarean deliveries would be needed to prevent a single brachial plexus injury in neonates born to women without diabetes. Rouse and colleagues (1996) echoed these sentiments in their analysis of nondiabetic mothers.


Obstentrics_Williams

Obstentrics_Williams. Conversely, planned cesarean delivery may be a reasonable strategy for diabetic women with an estimated fetal weight >4250 or >4500 g. Conway and Langer (1998) described a protocol of routine cesarean delivery for sonographic estimates of �4250 g in diabetic women. This management significantly lowered the shoulder dystocia rate from 2.4 to 1.1 percent. In summaly, we agree with the College that elective delivery for the fetus that is suspected to be overgrown is inadvisable, particularly before 39 weeks' gestation. Finally, we also conclude that elective cesarean delivery is not indicated when estimated fetal weight is <5000 g among women without diabetes and < 4500 g among women with diabetes (American College of Obstetricians and Gynecologists, 2016a, 2017b).


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Obstentrics_Williams. Alexander GR, Himes ]H, Kaufman RB, et al: A United States national refer ence for fetal growth. Obstet Gynecol 87: 163, 1996 Aman ], Hansson U, Osrlund I, et al: Increased fat mass and cardiac septal hypertrophy in newborn infants of mothers with well-controlled diabetes during pregnancy. Neonatology 100(2): 14 ,201t1 American College of Obstetricians and Gynecologists: Fetal growth restriction. Practice Bulletin No. 134, May 2013, Reairmed 2015 American College of Obstetricians and Gynecologists: Fetal macrosomia. Practice Bulletin No. 173, November 2016a American College of Obstetricians and Gynecologists: Moderate cafeine consumption during pregnancy. Committee Opinion No. 462, August 2010, Reairmed 2016b American College of Obstetricians and Gynecologists: Nonmedically indicated earlyterm deliveries. Committee Opinion No. 561, AprU 2013, Reairmed 2017a American College of Obstetricians and Gynecologists: Shoulder dystocia. Prac tice Bulletin No. 178, May 2017b


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Obstentrics_Williams. Bahado-Singh RO, Lynch L, Deren 0, et al: First-trimester growth restriction and fetal aneuploidy: the efect of type of aneuploidy and gestational age. Amt] Obstet GynecoIt176(5):976, 1997 Barker 0] (ed): Fetal and Infant Origins of Adult Disease. London, BM] Publishing, 1992 Barnes AC: An obstetric record from the medical record. Obstet Gynecol 9(2):237, 1957 Baschat A: Neurodevelopment after fetal growth restriction. Fetal Diagn her 36:136,t2014 Baschat A, Cosmi E, Bilardo CM, et al: Predictors of neonatal outcome in early-onset placental dysfunction. Obstet Gynecol 109(2, pt 1):253, 2007 Baschat A, Viscardi RM, Hussey-Gardner B, et al: Infant neurodevelopment following fetal growth restriction: relationship with antepartum surveillance parameters. Ultrasound Obstet Gynecol 33(1):44, 2009 Battaglia FC, Lubchenco LO: A practical classiication of newborn infants by weight and gestational age.t] Pediatr 71(2):159, 1967


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Obstentrics_Williams. Battaglia FC, Lubchenco LO: A practical classiication of newborn infants by weight and gestational age.t] Pediatr 71(2):159, 1967 Begemann M, Zirn B, Santen G, et al: Paternally inherited IGF2 mutation and growth restriction. N Engl] Med 373:349, 2015 Blackwell SC, Landon MB, Mele L, et al: Relationship between excessive gestational weight gain and neonatal adiposity in women with mild gestational diabetes mellitus. Obstet GynecoIt128:1325, 2016 Boers KE, van Wyk L, van der Post ]A, et al: Neonatal morbidity after induction vs expectant monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT. Am] Obstet GynecoIt206:344.e1, 2012 Boers E, Vijgen SM, Bijlenga 0, et al: Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BM] 341:c7087, 2010


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Obstentrics_Williams. Bricker L, Medley N, Pratt]]: Routine ultrasound in late pregnancy (after 24 weeks' gestation). Cochrane Database Syst Rev 6:CDOO 1451, 2015 Brifa ]F, McAinch A], Romano T, et al: Leptin in pregnancy and development: a contributor to adulthood disease? Am ] Physiol Endocrinol Metab 308:E335,t20t15 Brosens I, Benagiano G, Brosenst]J: The potential perinatal origin of placentation disorders in the young primigravida. Amt] Obstet Gynecol 212:580, 2015 Burton G], Fowden AL, Thornburg KL: Placen tal origins of chronic disease. Physiol Rev 96:t1t509, 2016 Calabuig-Navarro Y, Puchowicz M, Glazebrook P, et al: Efect of w-3 supplementation on placental lipid metabolism in overweight and obese women. Am] Clin Nutr 103:1064,t2016 Campbell S, Thoms A: Ultrasound measurement of the fetal head to abdomen circumference ratio in the assessment of growth retardation. B]OG 84(3):165, 1977


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Obstentrics_Williams. Campbell S, Thoms A: Ultrasound measurement of the fetal head to abdomen circumference ratio in the assessment of growth retardation. B]OG 84(3):165, 1977 Capobiango ]0, Bregan6 M, Navarro IT, et al: Congenital toxoplasmosis in a reference center of Parana, Southern Brazil. Braz] Infect Dis 18:364, 2014 Catalano PM, Hauguel-De Mouzon S. Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am] Obstet GynecoIt204(6):479, 2011 Cervera R, Serrano R, Pons-Estel G], et al: Morbidity and mortality in the anti phospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 74:1011, 2015 Chauhan SP, Grobman WA, Gherman A, et al: Suspicion and treatment of the macrosomic fetus: a review. Am] Obstet Gynecol 193(2):332, 2005 Chauhan SP, Rice MM, Grobman WA, et al: Neonatal morbidity of small-and large-for-gestational-age neonates born at term in uncomplicated pregnancies. Obstet Gynecol 130(3):511, 2017


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Obstentrics_Williams. Chauhan SP, Rice MM, Grobman WA, et al: Neonatal morbidity of small-and large-for-gestational-age neonates born at term in uncomplicated pregnancies. Obstet Gynecol 130(3):511, 2017 Chen S, Cao P, Dong N, et al: PCSK6-mediated corin activation is essential for normal blood pressure. Nat Med 21:1048, 2015a Chen Z, He P, Ding X, et al: PPAR, stimulates expression of I-type amino acid and taurine transporters in human placentas: the evidence of PPAR, regulating fetal growth. Sci Rep 5:12650, 2015b Chiossi G, Pedroza C, Costantine MM, et al: Customized versus populationbased growth charts to identiy neonates at risk of adverse outcomes: a systematic review and Bayesian meta-analysis of observational studies. Ultrasound Obstet Gynecol 50(2): 156, 2017 Cohen E, Wong FY, Horne RS, Yiallourou SR: Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy. Pediatr Res 79:821, 2016


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Obstentrics_Williams. Crosby DA, Ahmed S, Razley A, et al: Obstetric and neonatal characteristics of pregnancy and delivery for infant birthweight �5.0 kg. J Matern Fetal Neonatal Med 30(24):2961, 201 Crovetto F, T riunfo S, Crispi F, et al: Diferential performance of first trimester screening in predicting small for gestational age neonates or fetal growth restriction. Ultrasound Obstet GynecoIt49(3):349, 2017 Crume TL, Shapiro AL, Brinton JT, et al: Maternal fuels and metabolic measures during pregnancy and neonatal body composition: the healthy start study. J Clin Endocrinol Metab 100:1672,t2015 Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, et al: Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine growth restriction. Ultrasound Obstet GynecoIt48:349, 2016


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Obstentrics_Williams. Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, et al: Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine growth restriction. Ultrasound Obstet GynecoIt48:349, 2016 Cui Y, Wang W, Dong N, et al: Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature 484(7393):246,t2012 Cunningham FG, Cox SM, Harstad W, et al: Chronic renal disease and pregnancy outcome. Am J Obstet Gynecol 163(2):453, 1990 Cyganek A, Pietrzak B, Kociszewska-Najman B, et al: Intrauterine growth restriction in pregnant renal and liver transplant recipients: risk factors assessment. Transplant Proc 46:2794,t20t14


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Obstentrics_Williams. Unterscheider J, Daly S, Geary MP, et al: Predictable progressive Doppler deterioration in IUGR: does it really exist? Am J Obstet Gynecol 209:539. e1, 2013b Unterscheider J, O'Donoghue K, Malone FD: Guidelines of fetal growth restriction: a comparison of recent national publications. Am J Perinatol 32:307,t2015 Usher R, McLean F: Intrauterine growth of live-born Caucasian infants at sea level: standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks' gestation. J Pediatr 4( 6) :90 1, 1969 van Wyk L, Boers E, van der Post JA, et al: Efects on (neuro)developmental and behavioral outcome at 2 years of age of induced labor compared with expectant management in intrauterine growth-restricted infants: long-term outcomes of the DIGITAT trial. Am J Obstet GynecoIt206(5):406.e1, 2012


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Obstentrics_Williams. Villar J, Papageorghiou AT, Pang R, et al: The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study. Lancet Diabetes Endocrinol 2: 781, 2014 Visser GH, Bilardo CM, Derks JB, et al: he TRUFFLE study; fetal monitoring indications for delivery in 310 IUGR infants with 2 year's outcome delivered before 32 weeks of gestation. Ultrasound Obstet Gynecol November 11t, 2016 [Epub ahead of print] Waldhoer T, K1ebermass-Schrehof K: he impact of altitude on birth weight depends on further mother-and infant-related factors: a population-based study in an altitude range up to 1600 m in Austria between 1984 and 2013. J Perinatol 35:689, 2015 Walker DM, Marlow N, Upstone L, et al: he Growth Restriction Intervention Trial: long-term outcomes in a randomized trial of timing of delivery in fetal growth restriction. Am J Obstet Gynecol 204(1):34.e1, 2011


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Obstentrics_Williams. Wang D, Hong Y, Zhu L, et al: Risk factors and outcomes of macrosomia in China: a multicentric survey based on birth data. J Matern Fetal Neonatal Med 30:623,t2017 Wiebe HW, Boule NG, Chari R, et al: he efect of supervised prenatal exercise on fetal growth: a meta-analysis. Obstet Gynecol 125: 1185, 2015 Wigby K, D'Epagnier C, Howell S, et al: Expanding the phenotype of Triple X syndrome: a comparison of prenatal versus postnatal diagnosis. Am J Med Genet A 170:2870, 2016 Williams JW: Williams Obstetrics, New York, D. Appleton and Co., 1903 Williams RL: Intrauterine growth curves. Intra-and international comparisons with diferent ethnic groups in California. Prev Med 4: 163, 1975 Williams RL, Creasy RK, Cunningham GC, et al: Fetal growth and perinatal viability in California. Obstet Gynecol 59:624, 1982


Obstentrics_Williams

Obstentrics_Williams. Williams RL, Creasy RK, Cunningham GC, et al: Fetal growth and perinatal viability in California. Obstet Gynecol 59:624, 1982 Yamamoto R, Ishii K, Shimada M, et al: Signiicance of maternal screening for toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus infection in cases offetal growth restriction. J Obstet Gynaecol Res 39(3):653, 2013 Yang X, Li M, Haghiac M, Catalano PM, et al: Causal relationship between obesity-related traits and TLR4-driven responses at the maternal-fetal interface. Oiabetologia 59:2459, 2016 Yelnik CM, Laskin CA, Porter TF, et al: Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med 3:e000131, 2016


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Obstentrics_Williams. Zhang J, Merialdi M, Platt LO, et al: Deining normal and abnormal fetal growth: promises and challenges. Am J Obstet Gynecol 202(6):522, 2010 Zhang J, Mikolajczyk R, Grewal J, et al: Prenatal application of the individual ized fetal growth reference. Am J Epidemiol 173(5):539,t2011 Zhu JL, Obel C, Hammer Bech B, et al: Infertility, infertility treatment, and fetal growth restriction. Obstet Gynecol 110(6):1326,200 Zhu MY, Milligan N, Keating S, et al: The hemodynamics of late-onset intrauterine growth restriction by MRI. Am J Obstet Gynecol 214:367.e1, 2016 MECHANISMS OF MULTIFETAL GESTATIONS ......... 864 DIAGNOSIS OF MULTIFETAL GESTATION ........... 869 MATERNAL PHYSIOLOGICAL ADAPTATIONS ........ 870 PREGNANCY COMPLICATIONS ....................i. 871 UNIQUE FETAL COMPLICATIONS ................... 873 DISCORDANT GROWTH OF TWIN FETUSES .......... 881


Obstentrics_Williams

Obstentrics_Williams. PREGNANCY COMPLICATIONS ....................i. 871 UNIQUE FETAL COMPLICATIONS ................... 873 DISCORDANT GROWTH OF TWIN FETUSES .......... 881 FETAL DEMISE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 882 PRENATAL CARE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884 PRETERM BIRTH ................................ 885 LABOR AND DELIVERY ......................... 887 SELECTIVE REDUCTION OR TERMINATION .......... 891 In single-ovum twins, there is always a certain area of the placenta in which there is anastomosis between vascular systems which is never present in the fused placenta of doubleovum twins. Thus, if at an eary period the heart of one embryo is consideraby stronger than that of the other, a gradualy increasing area of the communicating portion of the placenta is monopolized by the ormer, so that its heart increases rapidy in size, whilst that of the latter receives less blood and eventualy atrophies.


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) In Williams' time, a great deal concerning the embryological and morphological development of multifetal pregnancies was unknown. These pregnancies may result from two or more fer tilization events, from a single fertilization followed by a split ting of the zygote, or from a combination of both. Multifetal today for both the mother and her fetuses. For example, in this country, approximately a fourth of very-low-birthweight gestations (Martin, 2017).


Obstentrics_Williams

Obstentrics_Williams. Fueled largely by infertility therapy, both the rate and the number of twins and higher-order multi fetal births grew dramatically during the 1980s and 1990s in the United States. National data from Martin and coworkers (2017) presented here is informative. he twinning rate rose 76 percent from 18.9 per 1000 live births in 1980 to 33.2 in 2009. During the same time, the number of higher-order multifetal births peaked in 1998 at a rate of 1.9 per 1000 total births. Since then, however, evolving infertility management has lowered rates of higher-order multifetal births-especially among nonHispanic white women. For example, the rate of triplets or more declined by more than 50 percent from 1998 to 2015 in this demographic group. And, in 2015, the overall m ultifetal birth rate was 34.5 per 1000, with twins representing nearly 97 percent of these births.


Obstentrics_Williams

Obstentrics_Williams. These rates of multi fetal pregnancies have a direct efect on the rates of preterm birth and its comorbidities. In addition, the risks for congenital malformation and its consequences are greater with multifetal gestations. Importantly, this increased risk applies to each fetus and is not simply the result of more fetuses. In sum, in 2013 in the United States, multifetal births accounted for 3 percent of all live births but for 15 percent of all infant deaths. Moreover, the risk of infant death rose proportionally with the number of fetuses in the pregnancy (Matthews, 2015). Speciically, the infant mortality rate for twins was more than four times the rate for single births. In the same year, the infant mortality rate for triplets was nearly 12 times the rate for singletons, and for quadruplets, it was a staggering 26 times that TABLE 45-1. Selected Outcomes in Singleton and Twin Outcome Singletons (No.) Twins (No.) Pregnancies 202,306 241n2 Birthsa 202,306 4824


Obstentrics_Williams

Obstentrics_Williams. TABLE 45-1. Selected Outcomes in Singleton and Twin Outcome Singletons (No.) Twins (No.) Pregnancies 202,306 241n2 Birthsa 202,306 4824 Stillbirths 1 011 (5.0) 114 (23.6) Neonatal deaths 590 (2.9) 92 (1n9.5) Perinatal deaths 1601 (7.9) 206 (42.7) Very low birthweight 1927 (9.6) 507 (1n07.6) aBirth data are represented as number (per 1000). bDenominator for neonatal deaths and very low birthweight is liveborn infants. Data from Dr. Don Mcintire. for singletons! From Parkland Hospital, a comparison of singleton and twin outcomes is shown in Table These risks are magnified further with higher-order births.


Obstentrics_Williams

Obstentrics_Williams. for singletons! From Parkland Hospital, a comparison of singleton and twin outcomes is shown in Table These risks are magnified further with higher-order births. he mother may also experience higher obstetrical morbidity and mortality rates. hese rates lso rise with the number of fetuses (Mhyre, 2012; Young, 2012). In one study of more than 44,000 multifetal pregnancies, the risks for preeclampsia, postpartum hemorrhage, and maternal death were twofold higher than these rates in singleton gestations (Walker, 2004). The risk for peripartum hysterectomy is also greater. Francois and associates (2005) reported this to be threefold for twins and 24-fold for triplets or quadruplets. Last, compared with women with a singleton pregnancy, these mothers are at increased risk for depression as well as parental divorce (Choi, 2009; Jenna, 2011).


Obstentrics_Williams

Obstentrics_Williams. Twin fetuses usually result from fertilization of two separate ova, which yields dizygotic orratenal twins. Less often, twins arise from a single fertilized ovum that then divides to create monozygotic or identical twins. Either or both processes may be involved in the formation of higher numbers. Quadruplets, for example, may arise from as few as one to as many as four ova. These traditional models of twinning discussed in the next sections have been taught for more than 50 years and remain the widely accepted theory. More recently, Herranz (2015) ofered a provocative alternative hypothesis, which posits that monozygotic twinning occurs with splitting at the postzygotic twocell stage. Notably, data are not robust in support of either the traditional or the newly proposed model (Denker, 2015).


Obstentrics_Williams

Obstentrics_Williams. Dizygotic twins are not in a strict sense true twins because they result from the maturation and fertilization of two ova during a single ovulatory cycle. Moreover, from a genetic perspective, dizygotic twins are like any other pair of siblings.


Obstentrics_Williams

Obstentrics_Williams. On the other hand, monozygotic or identical twins, although they have virtually the same genetic heritage, are usually not identical. Namely, the division of one fertilized zygote into two does not necessarily result in equal sharing of protoplasmic material. Monozygotic twins may actually be discordant for genetic mutations because of a postzygotic mutation, or may have the same genetic disease but with marked variability in expression. In female fetuses, skewed lyonization can produce diferential expression of X-linked traits or diseases. Further, the process of monozygotic twinning is in a sense a teratogenic event, and monozygotic twins have a higher incidence of often discordant malformations (Glinianaia, 2008). For example, in one study of 926 monozygotic twins, the prevalence of congenital heart defects was 12-fold greater than the general population rate, but 68 percent of afected infants had a normal sibling (Pettit, 20l3). From any of these mechanisms, dizygotic twins of the


Obstentrics_Williams

Obstentrics_Williams. heart defects was 12-fold greater than the general population rate, but 68 percent of afected infants had a normal sibling (Pettit, 20l3). From any of these mechanisms, dizygotic twins of the same sex may appear more nearly identical at birth than monozygotic twins.


Obstentrics_Williams

Obstentrics_Williams. • Genesis of Monozygotic Twins The developmental mechanisms underlying monozygotic twinning are poorly understood. The incidence of monozygotic twins is increased two-to fivefold in pregnancies conceived using assisted reproductive technology (ART). he predisposition to splitting may stem from specimen handling, growth media, or sperm DNA microinjection or may arise from intrinsic abnormalities associated with infertility (McNamara, 2016).


Obstentrics_Williams

Obstentrics_Williams. The outcome of the monozygotic twinning process depends on when division oCCuts. If zygotes divide within the irst 72 hours after fertilization, two embryos, two amnions, and two chorions develop, and a diamnionic, dichorionic twin pregnancy evolves (Fig. 45-1). Two distinct placentas or a single, fused placenta may develop. If division occurs between the fourth and eighth day, a diamnionic, monochorionic twin pregnancy results. By approximately 8 days after fertilization, the chorion and the amnion have already diferentiated, and division results in two embryos within a common amnionic sac, that is, a monoamnionic, monochorionic twin pregnancy. Conjoined twins result if twinning is initiated later.


Obstentrics_Williams

Obstentrics_Williams. It has long been accepted that monochorionicity incontrovertibly indicated monozygosity. Rarely, however, monochorionic twins may in fact be dizygotic (Hackmon, 2009). Mechanisms for this are speculative, but in one review of 14 cases, nearly all had been conceived after ART procedures (Ekelund, 2008) . McNamara and colleagues (2016) ofer an excellent review of the mechanisms and evidence for both typical and atypical twinning.


Obstentrics_Williams

Obstentrics_Williams. In supeetation, an interval as long as or longer than a menstrual cycle intervenes between fertilizations. Superfetation requires ovulation and fertilization during the course of an established pregnancy, which is theoretically possible until the uterine cavity is obliterated by fusion of the decidua capsularis to the decidua parietalis. Although known to occur in mares, superfetation is not known to occur spontaneously in humans. Lantieri and associates (2010) reported a case ater ovarian hyperstimulation and intrauterine insemination in the presence of an undiagnosed tubal pregnancy. Most authorities believe that alleged cases of human superfetation result from markedly FIGURE 45-1 Mechanism of monozygotic twinning. Black boxing and blue arrows in columns A, B, and C indicates timing of division.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 45-1 Mechanism of monozygotic twinning. Black boxing and blue arrows in columns A, B, and C indicates timing of division. A. At 0 to 4 days postfertilization, an early conceptus may divide into two. Division at this early stage creates two chorions and two amnions (dichorionic, diamnionic). Placentas may be separate or fused. B. Division between 4 to 8 days leads to formation of a blastocyst with two separate embryoblasts (inner cell masses). Each embryoblast will form its own amnion within a shared chorion (monochorionic, diamnionic). C. Between 8 and 12 days, the amnion and amnionic cavity form above the germinal disc. Embryonic division leads to two embryos with a shared amnion and shared chorion (monochorionic, monoamnionic). D. Difering theories explain conjoined twin development. One describes an incomplete splitting of one embryo into two. The other describes fusion of a portion of one embryo from a monozygotic pair onto the other.


Obstentrics_Williams

Obstentrics_Williams. unequal growth and development of twin fetuses with the same setting of paternity lawsuits (Girela, 1997). Given that superfegestational age. cundation may also occur with ART, women should be advised Supeecundation refers to fertilization of two ova within the to consider avoiding intercourse after embryo transfer (McNasame menstrual cycle but not at the same coitus, nor necesmara, 2016; Peigne, 201r1). sarily by sperm from the same male. An instance of superfecundation or heteropaternity, documented by Harris (1982), is demonstrated in Figure 45-2. he mother was delivered of • Factors Afecting Twinning a black neonate whose blood type was A and a white neonate Dizygotic twinning is much more common than monozygotic whose blood type was O. The blood type of the mother and her splitting of a single oocyte, and its incidence is influenced by husband was O. More recent cases have been reported in the race, heredity, maternal age, parity, and, especially, fertility )c::0)�000 5.)�:


Obstentrics_Williams

Obstentrics_Williams. FIGURE 45-2 An example ofdizygotic twin boys as the consequence of superfecundation. treatment. By contrast, the frequency of monozygotic twin births is relatively constant worldwide-approximately 1 set per 250 births, and this incidence is generally independent of demographic factors. One exception is that rates of zygotic splitting are increased following ART (Aston, 2008). Among diferent races and ethnic groups, the frequency of multifetal births varies significantly. In one analysis of more than 8 million births in the United States between 2004 and 2008, the rate oftwinning was 3.5 percent in black women and 3 percent in whites (Abel, 2012). Hispanic, Asian, and Native merican women had comparatively lowerrates than white women. In one rural community in Nigeria, twinning occurred once in every 20 births (nox, 1960)! hese marked diferences in twinning frequency may be the consequence ofracial variations in levels of follicle-stimulating hormone-FSH (Nylander, 1973).


Obstentrics_Williams

Obstentrics_Williams. Maternal age is another important risk factor for multifetal pregnancies (Fig. 45-3). Dizygotic twinning frequency rises almost fourfold between the ages of 15 and 37 years (Painter, 2010). As such, there is a paradox of declining fertility but increasing twinning rates with advancing maternal age (Beemsterboer, 2006). Another explanation for the dramatic rise in twinning with advancing maternal age may be a higher use of ART in older women (Ananth, 2012). Paternal age has also been linked to twinning frequency, but its efect is felt to be small (Abel, 2012). Although twin pregnancy is associated with greater risks for most adverse perinatal outcomes, McLennan and associates (2017) did not find advanced maternal age to be an additional risk factor for fetal and infant death. From this population-based study of the United States, they concluded that women in their 30s may be counseled that their age is not a major additional risk factor for adverse obstetric outcomes in the setting


Obstentrics_Williams

Obstentrics_Williams. population-based study of the United States, they concluded that women in their 30s may be counseled that their age is not a major additional risk factor for adverse obstetric outcomes in the setting oftwin pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Increasing pariy independently raises the incidence of twinning in all populations studied. During a 30-year period, Antsaklis and coworkers (2013) noted a progressively increasing positive correlation between multiparity and twinning. However, they FIGURE 45-3 Multifetal birth rates in the United States according to maternal age and race, 2015. (Data from Martin, 201o7.) cautioned that greater use ofRT may be partially contributory. In a two-year study from Nigeria, where such technology is not commonly available, Olusanya (2012) calculated the efects of multiparity compared with primiparity. They found an eightfold rise in multifetal gestation rates when parity was ;4, and a 20-fold rise when parity was :5.


Obstentrics_Williams

Obstentrics_Williams. As a determinant of twinning, the family history ofthe mother supersedes that of the father. One study of 4000 genealogical records showed that women who themselves were a dizygotic twin gave birth to twins at a rate of 1 set per 58 births (White, 1964). Women who were not a twin, but whose husbands were a dizygotic twin, gave birth to twins at a rate of 1 set per 116 pregnancies. Painter and associates (2010) performed genomewide linkage analyses on more than 500 families of mothers of dizygotic twins and identified four potential linkage peaks. he highest peak was on the long arm ofchromosome 6, and other suggestive peaks were on chromosomes 7, 9, and 16. That said, the contribution of these variants to the overall incidence of twinning is likely small (Hoekstra, 2008).


Obstentrics_Williams

Obstentrics_Williams. In animals, the litter size number grows in proportion to nutritional suiciency. Evidence from various sources indicates that this occurs in humans as well. Nylander (1971) showed an increasing gradient in the twinning rate related to greater nutritional status as relected by maternal size. Taller, heavier women had a twinning rate 25 to 30 percent greater than short, nutritionally deprived women. Likewise, Reddy and associates (2005) found an association of maternal weight and dizygotic twinning in the United States, in the absence of fertility drugs. Indeed, the influ ence of maternal weight s a factor for twinning will continue to rise in importance s the percentage of obese women in the United States continues to grow.


Obstentrics_Williams

Obstentrics_Williams. States continues to grow. Evidence acquired during and after World War II suggested that twinning correlated more with nutrition than with body size. Widespread undernourishment in Europe during those years was associated with a marked fall in the dizygotic twinning rate (Bulmer, 1959). Several investigators have reported a greater prevalence of twinning among women who have taken supplementary folic acid (Ericson, 2001; Haggarty, 2006). Conversely, in a systematic review, Muggli and Halliday (2007) were unable to demonstrate a significant association. Analysis of twinning rate in Texas after folic acid fortiication of cerealgrain products also failed to demonstrate an independent increase in twinning rates (Waller, 2003).


Obstentrics_Williams

Obstentrics_Williams. he common factor linking race, age, weight, and fertility to multifetal gestation may be FSH levels (Benirschke, 1973). This theory is supported by the fact that greater fecundity and a higher rate of dizygotic twinning have been reported in women who conceive within 1 month after stopping oral contraceptives, but not during subsequent months (Rothman, 1977). This may be due to the sudden release of pituitary gonadotropin in amounts greater than usual during the irst spontaneous cycle after stopping hormonal contraception. Indeed, the paradox of declining fertility but increasing twinning with advancing maternal age can be explained by an exaggerated pituitary release of FSH in response to decreased negative feedback from impending ovarian failure (Beemsterboer, 2006).


Obstentrics_Williams

Obstentrics_Williams. Ovulation induction with FSH plus human chorionic gonadotropin (hCG) or clomiphene citrate remarkably enhances the likelihood of multiple concurrent ovulations. In their review of this practice, McClamrock and coworkers (2012) reported rates of twins and higher-order multifetal pregnancies as high as 28.6 percent and 9.3 percent, respectively. Rates this high remain a major concern. Two ongoing multicenter trialsAssessment of Multiple Gestations from Ovarian Stimulation (AMIGOS) and Pregnancy in Polycystic Ovary Syndrome II (PPCOSII)-are designed to provide guidance on achieving maximum pregnancy rates while minimizing multifetal gestation rates (Diamond, 2015; Legro, 2014).


Obstentrics_Williams

Obstentrics_Williams. In general with in vitro fertilization (IVF), the greater the number of embryos that are transferred, the greater the risk of twins and other multifetal gestations. In 2014, ART contributed to 1.6 percent of all newborns in the United States and to 18.3 percent of all neonates in multifetal gestations (Sunderam, 2017). The American Society for Reproductive Medicine (2017) recently revised their age-related guidelines regarding the number of cleavage-stage embryos or blastocysts to transfer during IVF. This efort aims to reduce the incidence of higher-order multifetal pregnancies. Based on these new recommendations, women younger than 35 years are encouraged to receive a single-embryo transfer, regardless of embryo stage. hese practices have efectively lowered multifetal rates, and the rate of triplet or higher-order multifetal pregnancy has declined every year since 2009 (Kulkarni, 2013; Martin, 2017).


Obstentrics_Williams

Obstentrics_Williams. In humans, as the number of fetuses per pregnancy rises, the percentage of male conceptuses declines. Strandskov and coworkers (1946) found the percentage of males in 31 million singleton births in the United States was 51.6 percent. For twins, it was 50.9 percent; for triplets, 49.5 percent; and for quadruplets, 46.5 percent. Swedish birth data spanning 135 years reveals the number of males per 100 female newborns was 106 among singletons, 103 among twins, and 99 among triplets (Fellman, 2010). Females predominate even more in twins from late twinning events. For example, 68 percent of thoracopagus conjoined twins are female (Mutchinick, 2011). Two explanations have been ofered. First, beginning in utero and extending throughout the life cycle, mortality rates are lower in females. Second, female zygotes have a greater tendency to divide.


Obstentrics_Williams

Obstentrics_Williams. Twins of opposite sex are almost always dizygotic. In rare instances, due to somatic mutations or chromosome aberrations, the karyotype or phenotype of a monozygotic twin gestation can be diferent (Turpin, 1961). Most reported cases describe postzygotic loss of the Y chromosome in one 46,XY twin resulting in a phenotypically female twin with Turner syndrome (45,X). Zech and coworkers (2008) found a rare case of a 47,Y zygote that underwent postzygotic loss of the X chromosome in some cells and loss of the Y chromosome in other cells. The phenotype of the resultant twins was one male and one female. Karyotype analyses revealed both to be 46,XXJ46,XY genetic mosaics.


Obstentrics_Williams

Obstentrics_Williams. he risk for twin-speciic complications varies in relation to both zygosity and chorionicity-the number of chorions. Shown in Table 45-2, the latter is the more important determinant. Speciically, perinatal mortality and neurological injury rates are greater in monochorionic diamnionic twins compared with dichorionic diamnionic pairs (Hack, 2008; Lee, 2008). In one retrospective analysis of more than 2000 twins, the risk of fetal demise in one or both monochorionic twin(s) was twice that in dichorionic multifetal gestations (McPherson, 2012). Moreover, the prospective risk of antepartum stillbirth is higher for monochorionic than for dichorionic twins at all preterm gestational ages. he highest risk is before 28 weeks' gestation (Glinianaia, 2011). In contrast, chorionicity diferences do not signiicantly afect maternal outcomes (Carter, 2015).


Obstentrics_Williams

Obstentrics_Williams. This has become an integral tool to assist in multifetal pregnancy management. Indeed, the diagnosis and evaluation of a multifetal gestation is now considered a recognized indication for irst-trimester sonography (Reddy, 2014). In addition, the North American Fetal Therapy Network (NAFTNet)-a TABLE 45-2. Overview of the Incidence of Twin Pregnancy Zygosity and Corresponding Twin-Specific Complications Rates of Twin-Specific Complications in Percent consortium of 30 medical institutions in the United States and Canada-have provided recommendations for determination of chorionicity using sonography (Emery, 2015).


Obstentrics_Williams

Obstentrics_Williams. Sonographic features used to evaluate chorionicity vary according to gestational age. Accuracy is greatest in the irst trimester and diminishes as gestational age advances. Namely, chorionicity can be determined sonographically with 98-percent accuracy in the irst trimester but may be incorrect in up to 10 percent of second-trimester examinations (Emery, 2015; Lee, 2006). Moreover, for sonographic evaluations between 15 and 20 weeks' gestation, the odds of chorionicity misclassiication rise by approximately 10 percent for each week of advancing gestational age in pregnancies compared with those completed before 14 weeks (Blumenfeld, 2014). Overall, chorionicity can be correctly determined with sonography before 24 weeks in approximately 95 percent of cases (Lee, 2006).


Obstentrics_Williams

Obstentrics_Williams. Early in the first trimester, the number of chorions equates to the number of gestational sacs. A thick band of chorion separating two gestational sacs signals a dichorionic pregnancy, whereas monochorionic twins have a single gestational sac. If the gestation is monochorionic diamnionic, it may be diicult to visualize the thin intervening amnion before 8 weeks' gestation (Emery, 2015). If the intervening membrane is diicult to visualize, the number of yolk sacs usualy correlates with the number of amnions. However, the number of yolk sacs as a predictor of amnionicity may not always be accurate (Shen, 2006). Although uncommonly seen early, cord entanglement identifies a monoamnionic gestation. When chorionicity is uncertain, additional later sonographic examinations are performed.


Obstentrics_Williams

Obstentrics_Williams. Ater 10 to 14 weeks' gestation, sonographic assessment of chorionicity may be determined using four features. These are the number of placental masses, thickness of the membrane dividing the sacs, presence of an intervening membrane, and fetal gender (Emery, 2015). First, two separate placentas suggest dichorionicity. The converse is not necessarily true, such as cases with a single fused placental mass. Second, identiication of a thick dividing membrane-generally �2 mm-supports a presumed diagnosis of dichorionicity. In a dichorionic pregnancy, this visualized membrane is composed of a total of four layers-two amnion and two chorion. Also, the twin peak sign-also called lambda or delta sign-is seen by examining the point of origin of the dividing membrane on the placental surface. he peak appears as a triangular projection of placental tissue extending a short distance between the layers of the dividing membrane (Fig. 45-4).


Obstentrics_Williams

Obstentrics_Williams. FIGURE 45-4 A. Sonographic image of the "twin-peak" sign, also termed the "lambda sign," in a 24-week gestation. At the top of this sonogram, tissue from the anterior placenta is seen extending downward between the amnion layers. This sign confirms dichorionic twinning. B. The "tWin-peak" sign is seen at the bottom of this schematic diagram. The triangular portion of placenta insinuates between the amniochorion layers. FIGURE 45-5 A. Sonographic image of the '" sign in a monochorionic diamnionic gestation at 30 weeks. B. Schematic diagram of the '" sign. Twins are separated only by a membrane created by the juxtaposed amnion of each twin. A '" is formed at the point at which amnions meet the placenta.


Obstentrics_Williams

Obstentrics_Williams. In contrast, monochorionic pregnancies have a dividing membrane that is so thin (generally <2 mm) that it may not be seen until the second trimester. The relationship between the membranes and placenta without apparent extension of placenta between the dividing membranes is called the T sign (Fig. 45-5). Evaluation of the dividing membrane can establish chorionicity in more than 99 percent of pregnancies in the first trimester (Miller, 2012). Lack of a dividing membrane signals a monochorionic monoamnionic gestation. Last, twins with difering gender indicates a dichorionic (and dizygotic) gestation (Emery, 2015). A rare exception to this scenario would be a heterokaryotypic monochorionic gestation, described earlier (p. 867). If both twins are the same gender, additional measures are necessary.


Obstentrics_Williams

Obstentrics_Williams. A carefully performed visual examination of the placenta and membranes ater delivery serves to establish zygosity and chorionicity promptly in approximately two thirds of cases. The following systematic examination is recommended. As the irst neonate is delivered, one damp is placed on a portion of its FIGURE 45-6 Dichorionic diamnionic twin placenta. The membrane partition that separated twin fetuses is elevated and consists of chorion (c) between two amnions (0).


Obstentrics_Williams

Obstentrics_Williams. FIGURE 45-6 Dichorionic diamnionic twin placenta. The membrane partition that separated twin fetuses is elevated and consists of chorion (c) between two amnions (0). cord. Cord blood is generally not collected until after deliv ery of the other twin. As the second neonate is delivered, two damps are placed on that cord, and so on as necessary. lter natively, in higher-order deliveries, color-tagged damps can be simpler. Until the delivery of the last fetus, each cord segment must remain damped to prevent fetal hypovolemia and anemia caused by blood leaving the placenta via anastomoses and then through an undamped cord. At this time, evidence is insuicient in multifetal gestations (American College of Obstetricians and Gynecologists, 2017a). At Parkland Hospital, we currently do not perform delayed cord damping in these pregnancies.


Obstentrics_Williams

Obstentrics_Williams. Gynecologists, 2017a). At Parkland Hospital, we currently do not perform delayed cord damping in these pregnancies. The placenta is carefully delivered to preserve the attachment of the amnion and chorion. With one common amnionic sac or with juxtaposed amnions not separated by chorion, the fetuses are monozygotic (see Fig. 45-1). If adjacent amnions are separated by chorion, the fetuses could be either dizygotic or monozygotic, but dizygosity is more common (Fig. 45-6). If the neonates are of the same sex, blood typing of cord blood samples may be helpful. Diferent blood types conirm dizygosity, although demonstrating the same blood type in each fetus does not conirm monozygosity. For deinitive diagnosis, more complicated techniques such as DNA ingerprinting can be used. However, these tests are generally not performed at birth unless medical indications dictate a need.


Obstentrics_Williams

Obstentrics_Williams. During physical examination, accurate fundal height measurement, described in Chapter 9 (p. 164), is essential. With multifetal pregnancies, uterine size is typically larger during the second trimester than expected for a singleton. Rouse and associates (1993) reported fundal heights in 336 well-dated twin pregnancies. Between 20 and 30 weeks' gestation, fundal heights averaged approximately 5 cm greater than expected for singletons of the same fetal age. FIGURE 45-7 Sonograms of first-trimester twins. A. Dichorionic diamnionic twin pregnancy at 6 weeks' gestation. Note the thick dividing chorion (yellow arrow). One of the yolk sacs is indicated (blue arrow). B. Monochorionic diamnionic twin pregnancy at 8 weeks' gestation. Note the thin amnion encircling each embryo, resulting in a thin dividing membrane (blue arrow).


Obstentrics_Williams

Obstentrics_Williams. Diagnosing twins by palpation of fetal parts before the third trimester is diicult. Even late in pregnancy, this may be challenging, especially if one twin overlies the other, if the woman is obese, or if there is hydramnios. Palpating two fetal heads, often in diferent uterine quadrants, strongly supports a twin diagnosis. Late in the first trimester, two fetal heartbeats may be diferentiated with Doppler ultrasonic equipment if their rates are clearly distinct from each other and from that of the mother.


Obstentrics_Williams

Obstentrics_Williams. Overall, however, using clinical criteria alone to diagnose multifetal gestations is unreliable. For example, in the Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial, for 37 percent of women who did not have a screening ultrasound examination, their twin pregnancies were not diagnosed until 26 weeks' gestation. And, in 13 percent of unscanned women, their multifetal gestations were only diagnosed during their admission for delivery (American College of Obstetricians and Gynecologists, 2016; LeFevre, 1993).


Obstentrics_Williams

Obstentrics_Williams. Sonographic examination should detect practically all sets of twins. And, given the increased frequency of sonographic examinations during the first trimester, early detection of a twin pregnancy is common. Sonography can also be used to determine fetal number, estimated gestational age, chorionicity, and amnionicity. With careful examination, separate gestational sacs, if present, can be identiied early in twin pregnancy (Fig. 45-7). Subsequently, each fetal head should be seen in two perpendicular planes so as not to mistake a cross section of the fetal trunk for a second fetal head. Ideally, two fetal heads or two abdomens should be seen in the same image plane to avoid scanning the same fetus twice and interpreting it as twins.


Obstentrics_Williams

Obstentrics_Williams. Higher-order multifetal gestations are more challenging to evaluate. Even in the irst trimester, it can be diicult to identiY the actual number of fetuses and their position. This determination is especially important if pregnancy reduction or selective termination is considered (p. 891). Abdominal radiography can be used if fetal number in a higherorder multifetal gestation is uncertain. However, radiographs generally have limited utility and may lead to an incorrect diagnosis if fetuses move during the exposure or if exposure time is inadequate. Additionally, fetal skeletons before 18 weeks' gestation are insuiciently radiopaque and may be poorly seen.


Obstentrics_Williams

Obstentrics_Williams. Although not typically used to diagnose multifetal pregnancy, magnetic resonance (MR) imaging may help delineate complications in monochorionic twins (Hu, 2006). In one review of 17 complicated twin gestations evaluated by both sonographic and MR imaging, the latter provided a more detailed assessment of twin pathology (Bekiesinska-Figatowska, 2013). This was particularly helpful in cases of conjoined twins. No biochemical test reliably identifies multifetal gestations. Serum and urine levels of 3-hCG and maternal serum levels of alpha-fetoprotein (MSAFP) are generally higher with twins compared with those in singletons. However, levels may vary considerably and overlap with those of singletons.


Obstentrics_Williams

Obstentrics_Williams. he various physiological burdens of pregnancy and the likelihood of serious maternal complications are typically greater with multifetal gestations than with a singleton pregnancy. his is considered, especially when counseling a woman whose health is compromised and in whom a multifetal gestation is recognized early. Similar consideration is given to the woman who is not pregnant but is considering infertility treatment.


Obstentrics_Williams

Obstentrics_Williams. Beginning in the first trimester, and temporarily associated with higher serum 3-hCG levels, women with a multifetal gestation oten have nausea and vomiting in excess of that with a singleton pregnancy. In women carrying more than one fetus, blood volume expansion is greater and averages 50 to 60 percent compared with 40 to 50 percent in those with a singleton (Pritchard, 1965). This augmented hypervolemia teleologically ofsets blood loss with vaginal delivery of twins, which is twice that with a single fetus. Although red cell mass also accrues, it does so proportionately less in twin pregnancies. Combined with greater iron and folate requirements, this predisposes to anemia.


Obstentrics_Williams

Obstentrics_Williams. Women carrying twins also have a typical pattern of arte rial blood pressure change. MacDonald-Wallis and coworkers (2012) analyzed serial blood pressures in more than 13,000 singleton and twin pregnancies. As early as 8 weeks' gestation, the diastolic blood pressure in women with twins was lower than that with singleton pregnancies but generally rose by a greater degree at term. An earlier study demonstrated that this rise was at least 15 mm Hg in 95 percent of women with twins compared with only 54 percent of women with a singleton (Campbell, 1986).