Obstentrics_Williams

Obstentrics_Williams. heart rate pattern, although not ominous by itself, was the saltatory baseline. As described in Chapter 24 (p. 468), these indings are consistent with cord occlusion as the proximate cause of the nonreassuring tracings. Other correlates included oligohydramnios and viscous meconium. Schafer and colleagues (2005) implicated a nuchal cord in abnormal intrapartum fetal heart rate patterns, meconium, and compromised newborn condition in prolonged pregnancies.


Obstentrics_Williams

Obstentrics_Williams. he volume of amnionic luid normally continues to decline ater 38 weeks and may become problematic. Moreover, meconium release into an already reduced amnionic luid volume results in thick, viscous meconium that may cause meconium aspiration syndrome (Chap. 33, p. 620). Trimmer and coworkers (1990) sonographically measured hourly fetal urine production using sequential bladder volume measurements in 38 postterm pregnancies. Diminished urine production was found to be associated with oligohydramnios. They hypothesized that decreased fetal urine flow was likely the result of preexisting oligohydramnios that limited fetal swallowing. Oz and associates (2002), using Doppler waveforms, concluded that fetal renal blood low is reduced in those postterm pregnancies complicated by oligohydramnios. s a possible cause, again, the study by Link and associates (2007) showed that umbilical blood flow did not increase past term.


Obstentrics_Williams

Obstentrics_Williams. In the late 19905, the clinical significance of fetal-growth restriction in the otherwise uncomplicated pregnancy became more fully appreciated. Divon (1998) and Clausson (1999) and their coworkers analyzed births between 1991 and 1995 in the National Swedish Medical Birth Registry. Stillbirths were more common among growth-restricted newborns who were delivered after 42 weeks. Indeed, a third of postterm stillborn neonates were growth restricted. During this time in Sweden, labor induction and antenatal fetal testing usually commenced at 42 weeks. In a study from Parkland Hospital, Alexander and colleagues (2000d) analyzed outcomes for 355 neonates from pregnancies ::42 weeks and whose birthweights were <3rd percentile. hey compared these with outcomes of 14,520 similarly aged newborns above the 3rd percentile and found that morbidity and mortality rates were significantly increased in the growth-restricted neonates. Notably, a fourth of all stillbirths associated with prolonged


Obstentrics_Williams

Obstentrics_Williams. above the 3rd percentile and found that morbidity and mortality rates were significantly increased in the growth-restricted neonates. Notably, a fourth of all stillbirths associated with prolonged pregnancy were in this comparatively small number of growth-restricted fetuses.


Obstentrics_Williams

Obstentrics_Williams. In the event of a medical or other obstetrical complication, it is generally not recommended that a pregnancy be allowed to continue past 42 weeks. Indeed, in many such instances, earlier delivery is indicated. Common examples include gestational hypertensive disorders, prior cesarean delivery, and diabetes. Other clinically important factors include amnionic luid volume and potential fetal macrosomia.


Obstentrics_Williams

Obstentrics_Williams. Most clinical studies support theview that diminished amnionic fluid determined by various sonographic methods identifies a postterm fetus with increased risks. Indeed, decreased amnionic luid in any pregnancy signiies increased fetal risk (Chap. 11r, p. 231). Unfortunately, lack of an exact method to define "decreased amnionic luid" has limited investigators, and many diferent criteria for sonographic diagnosis have been proposed. Fischer and colleagues (1993) attempted to determine which criteria were most predictive of normal versus abnormal outcomes in postterm pregnancies. As shown in Figure 43-5, the smaller the amnionic luid pocket, the greater the likelihood that there was clinically signiicant oligohydramnios. Importantly, normal amnionic luid volume did not preclude abnormal outcomes. lfirevic and coworkers (1997) randomly assigned 500 women with postterm pregnancies to assessment using either the amnionic luid index (AFI) or the deepest vertical pocket described in Chapter


Obstentrics_Williams

Obstentrics_Williams. lfirevic and coworkers (1997) randomly assigned 500 women with postterm pregnancies to assessment using either the amnionic luid index (AFI) or the deepest vertical pocket described in Chapter 11 (p. 226). They concluded that the AFI overestimated the number of abnormal outcomes in postterm pregnancies.


Obstentrics_Williams

Obstentrics_Williams. Regardless of the criteria used to diagnose oligohydramnios in postterm pregnancies, most investigators have found a higher incidence of some measure of "fetal distress" during labor. Thus, oligohydramnios by most definitions is a clinically meaningful finding. Conversely, reassurance of continued fetal well-being in the presence of "normal" amnionic luid volume is tenuous. This may be related to how quickly pathological oligohydramnios develops. Although such cases are unusual, Clement and coworkers (1987) described six postterm pregnancies in which amnionic luid volume diminished abruptly over 24 hours, and in one of these, the fetus died. : 80 00 20 : 6.7em< 5em< 2em< 1 em


Obstentrics_Williams

Obstentrics_Williams. FIGURE 43-5 Comparison of the prognostic value of various pregnancies. Abnormal outcomes include cesarean or operative vaginal delivery for fetal jeopardy, 5-minute Apgar score �6, umbili cal arterial blood pH <7.1, or admission to the neonatal intensive care unit. (Redrawn from Fischer RL, McDonnell M, Bianculli KW, et al: Amniotic fluid volume estimation in the postdate pregnancy: a comparison oftechniques. Obstet Gynecol 81 :698, 1993.) he velocity of fetal weight gain peaks at approximately 37 weeks (see Fig. 43-3). Although growth velocity slows at that time, most fetuses continue to gain weight. For example, the percentage of fetuses born in 2009 whose birthweight exceeded 4000 g was 8.2 percent at 37 to 41 weeks and increased to 11.0 percent at 42 weeks or more (Martin, 2011). According to Duryea and associates (2014), the 95th percentile at 42 weeks is 4475 g. Even so, in some studies, brachial plexus injurywas not related to postterm gestation (Walsh, 2011). Intuitively, it


Obstentrics_Williams

Obstentrics_Williams. to Duryea and associates (2014), the 95th percentile at 42 weeks is 4475 g. Even so, in some studies, brachial plexus injurywas not related to postterm gestation (Walsh, 2011). Intuitively, it seems that both maternal and fetal morbidity associated with macrosomia would be mitigated with timely induction to preempt urther growth. This, however, does not appear to be the case. The American College ofObstetricians and Gynecologists (2016c) has concluded that current evidence does not support such a practice in women at term with suspected fetal macrosomia. Moreover, the College concluded that in the absence of diabetes, vaginal delivery is not contraindicated for women with an estimated fetal weight up to 5000 g (Chap. 27, p. 520). Obvious problems with all such recommendations are substantive variations in fetal weight estimation.


Obstentrics_Williams

Obstentrics_Williams. Although some intervention is indicated for prolonged pregnancies, the method and timing of this are not unanimous. he decision focuses on whether labor induction is warranted or if expectant management with fetal surveillance is best. In a survey done more than 10 years ago, Cleary-Goldman and associates (2006) reported that 73 percent of members of the American College ofObstetricians and Gynecologists routinely induced women at 41 weeks. Most of the remainder performed twice weekly fetal testing until 42 weeks.


Obstentrics_Williams

Obstentrics_Williams. Although all obstetricians know what an "unfavorable cervix" is, the term unfortunately defies precise objective deinition. Thus, investigators have used difering criteria for studies of prolonged pregnancies. Harris and coworkers (1983) defin�d an unfavorable cervix by a Bishop score <7 and reported thiS m 92 percent of women at 42 weeks (Chap. 26, p. 505). Hannah and colleagues (1992) found that 40 percent of 3407 women with a 41-week pregnancy had an "undilated cervix." In a study of 800 women undergoing induction for postterm pregnancy at Parkland Hospital, Alexander and associates (2000b) reported that women in whom there was no cervical dilation had a twofold higher cesarean delivery rate fore" dystocia. " Yang and coworkers (2004) found that cervical length 53 em measured with transvaginal sonography was predictive of successful induction. In a similar study, Vankayalapati and associates (2008) found that cervical length 525 mm was predictive of spontaneous labor or successful


Obstentrics_Williams

Obstentrics_Williams. sonography was predictive of successful induction. In a similar study, Vankayalapati and associates (2008) found that cervical length 525 mm was predictive of spontaneous labor or successful induction.


Obstentrics_Williams

Obstentrics_Williams. Several investigators have evaluated prostaglandin E2 (PGE2) and E1 (PGE1) for induction in women with an unfavorable cervix and prolonged pregnancies. A study by the MaternalFetal Medicine Units Network (1994) found that PGE2 gel was not more efective than placebo. Alexander and associates (2000c) treated 393 women with a postterm pregnancy with PGE2, regardless of cervical "favorability," and reported that almost half of the 84 women with cervical dilatation of 2 to 4 em entered labor with PGE2 use alone. In another study, mifepristone was reported to increase uterine activity without uterotonic agents in women beyond 41 weeks (Fasset, 2008). Prostaglandins and other agents used for cervical ripening are discussed in Chapter 26 (p. 506).


Obstentrics_Williams

Obstentrics_Williams. Sweeping or stripping of the membranes to induce labor and thereby prevent postterm pregnancy was studied in 15 randomized trials during the 1990s. Boulvain and coworkers (2005) performed a metaanalysis of these and found that membrane stripping at 38 to 40 weeks lowered the frequency of postterm pregnancy. Although maternal and neonatal infection rates were not increased, this practice did not modiy the cesarean delivery rate. Since then, randomized trials by Wong (2002), Kashanian (2006), Hill (2008), and their coworkers found that sweeping membranes did notereduce the need to induce labor. Drawbacks of membrane stripping included pain, vaginal bleeding, and irregular contractions without labor.


Obstentrics_Williams

Obstentrics_Williams. Drawbacks of membrane stripping included pain, vaginal bleeding, and irregular contractions without labor. The station of the fetal head within the pelvis is another predictor of successful postterm pregnancy induction. Shin and colleagues (2004) studied 484 nulliparas who underwent induction after 41 weeks. The cesarean delivery rate was directly related to station. The rate was 6 percent if the vertex before induction was at -1 station; 20 percent at -2 station; 43 percent at -3 station; and 77 percent at -4 station.


Obstentrics_Williams

Obstentrics_Williams. Because of the marginal benefits from induction with an unfavorable cervix, as just discussed, some clinicians prefer instead to implement a strategy of fetal testing beginning at 41 completed weeks. For example, in a Canadian study, 3407 women were randomly assigned at 41 or more weeks to induction or to fetal testing (Hannah, 1992). In the surveillance group, evaluation included: (1) counting fetal movements during a 2-hour period each day, (2) nons tress testing three times weekly, and (3) amnionic fluid volume assessment two to three times weekly, with pockets <3 em considered abnormal. Labor induction resulted in a small but signiicant reduction in the cesarean delivery rate compared with fetal testing-2e1 versus 24 percent, respectively. This diference was due to fewer procedures for fetal distress. here were only two stillbirths in the fetal testing group.


Obstentrics_Williams

Obstentrics_Williams. The !v1aternal-Fetal Medicine Network performed a randomized trial of induction versus fetal testing beginning at 41 weeks (Gardner, 1996). Fetal surveillance included nonstress testing and sonographic estimation of amnionic fluid volume performed twice weekly in 175 women. Perinatal outcomes were compared with those of 265 women also at 41 weeks randomly assigned to induction with or without cervical ripening. There were no perinatal deaths, and the cesarean delivery rate was not diferent between management groups. he results of this study could be used to support the validity of either management scheme. In an analysis of 22 trials, Gulmezoglu and colleagues (2012) found that induction after 41 weeks rather than surveillance was associated with significantly fewer perinatal deaths and meconium aspiration syndrome cases and a lower cesarean delivery rate. In a review of two metaanalyses and a randomized study, similar conclusions were reached (Mozurkewich, 2009).


Obstentrics_Williams

Obstentrics_Williams. In most studies, labor induction at 42°/7 weeks has a higher cesarean delivery rate compared with spontaneous labor. From Parkland Hospital, Alexander and coworkers (2001) evaluated pregnancy outcomes in 638 such women in whom labor was induced and compared them with outcomes of 687 women with postterm pregnancies who had spontaneous labor. Cesarean delivery rates were signiicantly increased-19 versus 14 percent-in the induced group because of failure to progress. When these investigators corrected for risk factors, however, they concluded that intrinsic maternal factors, rather than the induction itself, led to the higher rate. These factors included nulliparity, an unfavorable cervix, and epidural analgesia.


Obstentrics_Williams

Obstentrics_Williams. A large study from Denmark by Zizzo and associates (20e17) is also instructive. In 2011e, the Danish national guidelines were changed from labor induction at 42°/7 weeks with no fetal sur veillance to labor induction at 41e/7 to 416/7 weeks with fetal surveillance beginning at 41°/7 weeks. They compared two 3-year epochs-one before and one ater 20 II-and the results are shown in Table 43-2. The rate of pregnancies that progressed past 42°/7 weeks decreased from 2.85 to 0.62 percent. Concu�rently, as expected, the induction rate rose signiicantly, and thiS was accompanied by a drop in the perinatal mortality rate-22 to 13 per 1000 births. The cesarean delivery rate was not changed. A similar before-and-ater observational study reported that induction at ::42 weeks was associated with a signiicantly lower cesarean delivery rate-15 versus 19.4 percent (Bleicher, 2017).


Obstentrics_Williams

Obstentrics_Williams. From the foregoing, evidence to substantiate interventionwhether induction or fetal testing-commencing at 41 versus 42 weeks is limited. Most evidence used to justiy intervention TABLE 43-2. National Death Cohort Study of 102,1e67 Pregnancies that Reached 41e°/7 Weeks' Gestation EGA >42°/7 2.85% 0.62% Stillbirths 9/1000 5/1000 0.018 Neonatal deaths 13/1000 811000 .033 Vacuum delivery 11.3% 10.2% <0.001 Induction 28% 43% <0.001 aNational guidelines changed between epochs as described in text. NS = not significant. Data from Zizzo, 201n7. at 41 weeks is from the randomized Canadian and American investigations cited earlier. No randomized studies have specifically assessed intervention at 41 weeks versus an identical intervention used at 42 weeks. A large Swedish multicenter randomized trial of more than 10,000 women at 41°1 weeks has been designed to address the question (Elden, 2016).


Obstentrics_Williams

Obstentrics_Williams. he American College of Obstetricians and Gynecologists (2016a) deines postterm pregnancies as having completed 42 weeks, namely, beyond 42°/7 weeks. There is insuicient evidence to mandate a management strategy between 40 and 42 completed weeks. hus, although not considered mandatory, initiation of fetal surveillance at 41 weeks is a reasonable option. After completing 42 weeks, recommendations are for labor induction as summarized in Figure 43-6. When gestational age is uncertain, the American College of Obstetricians and Gynecologists (2017b) recommends delivery at 41 weeks' gestation using the best clinical estimate of gestational age. he College also recommends against amniocentesis for fetal lung maturity. At Parkland Hospital, based on results from the trials just discussed, we consider 41-week pregnancies without other


Obstentrics_Williams

Obstentrics_Williams. FIGURE 43-6 Algorithm for management of postterm pregnancy. (Summarized from American College of Obstetricians and Gynecologists,o201o6d.) complications to be normal. hus, no interventions are practiced solely based on fetal age until 42 completed weeks. With complications such as hypertension, decreased fetal movement, or oligohydramnios, labor induction is carried out. It is our view that large, randomized trials should be performed before otherwise uncomplicated 41-week gestations are routinely considered pathologically prolonged. In women in whom a certain gestational age is known, labor is induced at the completion of 42 weeks. Almost 90 percent of such women are induced successfully or enter labor within 2 days of induction. For those who do not deliver with the first induction, a second induction is performed within 3 days. lmost all women are delivered using this management plan, but in the unusual few who are not delivered, management decisions involve a third-or even


Obstentrics_Williams

Obstentrics_Williams. a second induction is performed within 3 days. lmost all women are delivered using this management plan, but in the unusual few who are not delivered, management decisions involve a third-or even more-induction versus cesarean delivery. Women classiied as having uncertain postterm pregnancies are managed with weekly nonstress fetal testing and assessment ofamnionic luid volume. Women with an AFI ;5 cm or with reports ofdiminished fetal movement undergo labor induction.


Obstentrics_Williams

Obstentrics_Williams. Labor is a particularly dangerous time for the postterm fetus. Therefore, women whose pregnancies are known or suspected to be postterm ideally come to the hospital as soon as they suspect labor. While being evaluated for active labor, we monitored electronically for variations consistent with fetal compromise. During labor, the decision to perform amniotomy is problematic. Further reduction in luid volume following amniotomy can enhance the possibility of cord compression. Conversely, after membrane rupture, a scalp electrode and an intrauterine pressure catheter can be placed. These usually provide more precise data concerning fetal heart rate and uterine contractions. Amniotomy also aids identification of thick meconium.


Obstentrics_Williams

Obstentrics_Williams. Thick meconium in the amnionic luid is particularly worrisome. The viscosity probably signiies the lack of liquid and thus oligohydramnios. Aspiration of thick meconium may cause severe pulmonary dysfunction and neonatal death (Chap. 33, p. 620). Because of this, amnioinfusion during labor has been proposed as a way of diluting meconium to lower the incidence of aspiration s) ndrome (Wenstrom, 1989). As discussed in Chapter 24 (p. 475), the benefits of amnioinfusion remain controversial. In a large randomized trial by Fraser and colleagues (2005), amnioinfusion did not reduce the risk of meconium aspiration syndrome or perinatal death. According to the American College of Obstetricians and Gynecologists (2016a), amnioinfusion does not prevent meconium aspiration, however, it remains a reasonable treatment approach for repetitive variable decelerations.


Obstentrics_Williams

Obstentrics_Williams. he likelihood of a successful vaginal delivery is reduced appreciably for the nullipara who is in early labor with thick, meconium-stained amnionic fluid. Therefore, if the woman is remote from delivery, strong consideration should be given to prompt cesarean delivery, especially when cephalopelvic disproportion is suspected or either hypotonic or hypertonic dysfunctional labor is evident. Some practitioners choose to avoid oxytocin use in these cases. Until recently, it was taught-including at Parkland Hospital -that aspiration of meconium could be minimized but not eliminated by suctioning the pharynx as soon as the head was delivered. According to the American Heart Association guidelines, this in no longer recommended (Wyckof, 2015). The merican College of Obstetricians and Gynecologists (2017a) does not recommend routine intrapartum suctioning. Alternatively, if the depressed newborn has meconium-stained fluid, then intubation is carried out.


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Obstentrics_Williams. Alexander JM, McIntire DO, Leveno KJ: Forty weeks and beyond: pregnancy outcomes by week of gestation. Obstet Gynecol 96:291, 2000a lexander JM, McIntire DO, Leveno KJ: Postterm pregnancy: does induction increase cesarean rates? J Soc Gynecol Invest 7:79A, 2000b lexander JM, McIntire DO, Leveno KJ: Postterm pregnancy: is cervical "ripening" being used in the right patients? J Soc Gynecol Invest 7:247 A, 2000c Alexander JM, McIntire DO, Leveno KJ: Prolonged pregnancy: induction of labor and cesarean births. Obstet Gynecol 97:9t11t, 2001 Alexander JM, McIntire DO, Leveno KJ: he efect of fetal growth restriction on neonatal outcome in postterm pregnancy. Abstract No. 463. Am J Obstet Gynecol 182:S148, 2000d Alfirevic Z, Luckas M, Walkinshaw SA, et al: A randomized comparison between amniotic fluid index and maximum pool depth in the monitoring of postterm pregnancy. Br J Obstet Gynaecol 104:207, 1997


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Obstentrics_Williams. Alfirevic Z, Luckas M, Walkinshaw SA, et al: A randomized comparison between amniotic fluid index and maximum pool depth in the monitoring of postterm pregnancy. Br J Obstet Gynaecol 104:207, 1997 American College of Obstetricians and Gynecologists: Amnioinfusion does not prevent meconium aspiration syndrome. Committee Opinion No. 346, October 2006, Reairmed 2016a American College of Obstetricians and Gynecologists Qoint with the Society for Maternal-Fetal Medicine): Deinition of term pregnancy. Committee Opinion No. 579, November 20t13, Reairmed 20t16b American College of Obstetricians and Gynecologists: Fetal macrosomia. Practice Bulletin No. 173, November 20t16c American College of Obstetricians and Gynecologists: Management of lateterm and postterm pregnancies. Practice Bulletin No. 146, August 20t14, Reairmed 2016d


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Obstentrics_Williams. American College of Obstetricians and Gynecologists: Management of lateterm and postterm pregnancies. Practice Bulletin No. 146, August 20t14, Reairmed 2016d American College of Obstetrics and Gynecologists: Management of delivery of a newborn with meconium-stained amniotic fluid. Committee Opinion No. 689, March 20t17a American College of Obstetricians and Gynecologists: Management of suboptimally dated pregnancies. Committee Opinion No. 688, March 2017b Arrowsmith S, Wray S, Quenby S: Maternal obesity and labour complications following induction of labour in prolonged pregnancy. BJOG 118(5):578, 2011 Ayyavoo A, Derraik JG, Hofman PL, et al: Postterm births: are prolonged pregnancies roo long? J Pediatr 164(3):647,t2014 Bakketeig LS, Bergsj0 P: Post-term pregnancy: magnitude of the problem. In Chalmers I, Enkin M, Keirse M (eds): Efective Care in Pregnancy and Childbirth. Oxford, Oxford University Press, 1991, p 765


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Obstentrics_Williams. In Chalmers I, Enkin M, Keirse M (eds): Efective Care in Pregnancy and Childbirth. Oxford, Oxford University Press, 1991, p 765 Bennett A, Crane JM, O'Shea P, et al: First trimester ultrasound screening is efective in reducing postterm labor induction rates: a randomized controlled trial. Am J Obstet Gynecol 190: 107 , 2004 Bleicher I, Vinter 0, Iofe A, et al: When should pregnancies that extended beyond term be induced? J Matern Fetal Neonatal Med 30(2):219,t2017 Blondel B, Morin I, Platt RW, et al: Algorithms for combining menstrual and ultrasound estimates of gestational age: consequences for rates of preterm and postterm birth. Br J Obstet Gynaecol 109: 18, 2002 Boulvain M, Stan CM, Irion 0: Membrane sweeping for induction of labour. Cochrane Database Syst Rev 1 :CD00045t1, 2005 Cheng W, Nicholson JM, Nakagawa S, et al: Perinatal outcomes in low-risk term pregnancies: do they difer by week of gestation? Am J Obstet Gynecol 0.e1,t2008


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Obstentrics_Williams. Cheng W, Nicholson JM, Nakagawa S, et al: Perinatal outcomes in low-risk term pregnancies: do they difer by week of gestation? Am J Obstet Gynecol 0.e1,t2008 Clausson B, Cnattingus S, Axelsson 0: Outcomes of postterm births: the role of fetal growth restriction and malformations. Obstet Gynecol 94:758, 1999 Cleary-Goldman J, Bettes B, Robinon IN, et al: Postterm pregnancy: practice patterns of contemporary obstetricians and gynecologists. Am J Perinatol 23:15,t2006 Clement 0, Schifrin BS, Kates RB: Acute oligohydramnios in postdate pregnancy. Am J Obstet Gynecol 157:884, 1987 Cliford SH: Postmaturity with placental dysfunction. Clinical syndromes and pathologic indings. J Pediatr 44: 1, 1954 Divon MY, Haglund B, Nisell H, et al: Fetal and neonatal mortality in the postterm pregnancy: the impact of gestational age and fetal growth restriction. Am J Obstet Gynecol 178:726, 1998


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Obstentrics_Williams. Divon MY, Haglund B, Nisell H, et al: Fetal and neonatal mortality in the postterm pregnancy: the impact of gestational age and fetal growth restriction. Am J Obstet Gynecol 178:726, 1998 Duryea EL, Hawkins JS, McIntire DO, et al: A revised birth weight reference for the United States. Obstet GynecoIt124:16, 2014 Elden H, Hagberg H, Wessberg A, et al: Study protocol of SWEPIS a Swedish multicentre register based randomised controlled trial to compare induction of labour at 41 completed gestational weeks versus expectant management and induction at 42 completed gestational weeks. BMC Pregnancy Childbirth 16:49,t2016 Fasset MJ, Wing DA: Uterine activity after oral mifepristone administration in human pregnancies beyond 41 weeks' gestation. Gynecol Obstet Invest 65(2): ll2, 2008 Fischer RL, McDonnell M, Bianculli W, et al: Amniotic luid volume estimation in the postdate pregnancy: a comparison of techniques. Obstet Gynecol 81t:698, 1993


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Obstentrics_Williams. Fischer RL, McDonnell M, Bianculli W, et al: Amniotic luid volume estimation in the postdate pregnancy: a comparison of techniques. Obstet Gynecol 81t:698, 1993 Fraser WD, Hofmeyr J, Lede R, et al: Amnioinfusion for the prevention of the meconium aspiration syndrome. New Engl J Med 353:909, 2005 Gardener H, Spiegelman D, Buka SL: Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics 128:344,t2011 Gardner M, Rouse 0, Goldenberg R, et al: Cost comparison of induction of labor at 41 weeks versus expectant management in the postterm pregnancy. Am J Obstet 4:351, 1996 Gulmezoglu M, Crowther CA, Middleton P, et l: Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev 6:CD004945, 2012 Hannah ME, Hannah J, Hellman J, et al: Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. N Engl J vIed 326:1587, 1992


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Obstentrics_Williams. Hannah ME, Hannah J, Hellman J, et al: Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. N Engl J vIed 326:1587, 1992 Harris BA Jr, Huddleston JF, Sutlif G, et al: he unfavorable cervix in prolonged pregnancy. Obstet Gynecol 62: 1, 1983 Hendricks CH: Patterns of fetal and placental growth: the second half of pregnancy. Obstet Gynecol 24:357, 1964 Hill MJ, McWilliams GC, Garcia-Sur, et al: he efect of membrane sweeping on prelabor rupture of membranes: a randomized controlled trial. Obstet Gynecoltll1(6):1313,t2008 Jazayeri A, Tsibris JC, Spellacy N: Elevated umbilical cord plasma erythropoietin levels in prolonged pregnancies. Obstet Gynecol 92:6t1, 1998 Joseph KS, Huang L, Liu S, et l: Reconciling the high rates of preterm and postterm birth in the United States. Obstet Gynecol 109(4):798,t200


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Obstentrics_Williams. Kashanian M, Aktarian A, Baradaron H, et al: Efect of membrane sweeping at term pregnancy on duration of pregnancy and labor induction: a randomized trial. Gynecol Obstet Invest 62:41,t2006 Larsen LG, Clausen HV, Andersen B, et al: A stereologic study of postmature placentas fixed by dual perfusion. Am J Obstet Gynecol 2:500, 1995 Laursen M, Bille C, Olesen A W, et al: Genetic inluence on prolonged gestation: a population-based Danish twin study. Am J Obstet Gynecol 190:489, 2004 Leveno KJ, Quirk JG, Cunningham FG, et al: Prolonged pregnancy, 1. Observations concerning the causes of fetal distress. Am J Obstet Gynecol 150:465, 1984 Lindell A: Prolonged pregnancy. Acta Obstet Gynecol Scand 35: 136, 1956 Link G, Clark KE, Lang U: Umbilical blood low during pregnancy: evidence for decreasing placental perfusion. Am J Obstet Gynecol 196(5)489.e1, 2007 MacDonald PC, Siiteri PK: Origin of estrogen in women pregnant with an anencephalic fetus. J Clin Invest 44:465, 1965


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Obstentrics_Williams. MacDonald PC, Siiteri PK: Origin of estrogen in women pregnant with an anencephalic fetus. J Clin Invest 44:465, 1965 MacDorman MF, Kirmeyer S: Fetal and perinatal mortality, United States, 2005. Natl Vital Stat Rep 57(8):1, 2009 Martin JA, Hamilton BE, Osterman MJK, et al: Births: inal data for 2013. Natl Vital Stat Rep 64:t1,t2015 Martin JA, Hamilton BE, Sutton PO, et al: Births: inal data for 2015. Natl Vital Stat Rep 66(1):1,t2017 Maternal-Fetal Medicine Units Network: A clinical trial of induction of labor versus expectant management in postterm pregnancy. Am J Obstet Gynecol 170:716,t1994 Mission JF, Marshall NE, Caughey AB: Pregnancy risks associated with obesity. Obstet Gynecol Clin North Am 42:335,t2015 Moster 0, Wilcox AJ, Vollset SE, et al: Cerebral palsy among term and postterm births. JAMA 304(9):976,t2010 Mozurkewich E, Chilimigras J, Koepke E, et al: Indications for induction of labour: a best-evidence review. BJOG 116(5):626, 2009


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Obstentrics_Williams. Mozurkewich E, Chilimigras J, Koepke E, et al: Indications for induction of labour: a best-evidence review. BJOG 116(5):626, 2009 Nahum GG, Stanislaw H, Hufaker B]: Fetal weight gain at term: linear with minimal dependence on maternal obesity. Amt] Obstet Gynecol 172: 1387, 1995 Oberg AS, Frisell T, Svensson AC, et al: Matenal and fetal genetic contributions to postterm birth: familial clustering in a population-based sample of 475,429 Swedish births. Amt] Epidemiol 177(6):531,t2013 Olesen A W, Westergaard ]G, Olsen ]: Perinatal and maternal complications related to postterm delivery: a national register-based study, 1978-1993. Amt] Obstet Gynecol 189:227,t2003 Olesen AW, Westergaard ]G, Olsent]: Prenatal risk indicators of a prolonged pregnancy. The Danish Birth Cohort 1998-2001. Acta Obstet Gynecol Scand 85: 1338, 2006 Oz AU, Holub B, Mendilcioglu 1, et aI: Renal artery Doppler investigation of the etiology of oligohydramnios in postterm pregnancy. Obstet Gynecol 100:715,t2002


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Obstentrics_Williams. Oz AU, Holub B, Mendilcioglu 1, et aI: Renal artery Doppler investigation of the etiology of oligohydramnios in postterm pregnancy. Obstet Gynecol 100:715,t2002 Redman CW, Staf AC: Preeclamptic biomarkers, syncytiotrophoblast stress, and placental capacity. Amt] Obstet Gynecol 213 (4 Suppl):S9.e 1, 2015 Rushton DI: Pathology of placenta. In Wigglesworth ]5, Singer DB (eds): Textbook of Fetal and Perinatal Pathology. Boston, Blackwell, 1991, P 171 Schafer L, Burkhardt T, Zimmerman R, et al: Nuchal cords in term and postterm deliveries-do we need to know? Obstet Gynecol 106:23,t2005 Shin KS, Brubaker L, Ackerson LM: Risk of cesarean delivery in nulliparous women at greater than 41 weeks' gestational age with an unengaged vertex. Am] Obstet Gynecol 190:129,t2004 Smith GC: Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies. Amt] Obstet Gynecol 184:489,t2001


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Obstentrics_Williams. Smith GC: Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies. Amt] Obstet Gynecol 184:489,t2001 Smith Sc, Baker PN: Placental apoptosis is increased in postterm pregnancies. B]OG 106:861, 1999 Torricelli M, Novembri R, Conti N, et al: Correlation with kisspeptin in postterm pregnancy and apoptosis. Reprod Sci 19(10): 1133, 2012 Trimmer K], Leveno K], Peters MT, et al: Observation on the cause of oligohydramnios in prolonged pregnancy. Am] Obstet Gynecol 163: 1900, 1990 Van del' Ven Aj, van Os MA, Kleinrouweler CE, et al: Midpregnancy cervical length in nulliparous women and its association with postterm delivery and intrapartum cesarean delivery. Am ] Perinatol 33 (1) :40, 2016 Vankayalapati P, Sethna F, Roberts N, et al: Ultrasound assessment of cervical length in prolonged pregnancy: prediction of spontaneous onset of labor and successful vaginal delivery. Ultrasound Obstet Gynecol 31 (3):328, 2008


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Obstentrics_Williams. Walsh ]M, Kandamany N, Shuibhne NN, et al: Neonatal brachial plexus injury: comparison of incidence and antecedents between 2 decades. Amt] Obstet Gynecol 204:324, 201t1. Wenstrom KD, Parsons MT: The prevention of meconium aspiration in labor using amnioinfusion. Obstet Gynecol 73:647, 1989 Wong SF, Hui SK, Choi H, et al: Does sweeping of membranes beyond 40 weeks reduce the need for formal induction of labour? Br] Obstet Gynaecol 109:632, 2002 Wyckof MH, Aziz K, Escobedo MB, et al: Part 13: neonatal resuscitation. 2015 American Heart Association guidelines for cardiopulmonaty resuscitation and emergency cardiovascular care. Circulation 132:5543, 20t15 Yang 5, Platt RW, Kramer MS: Variation in child cognitive ability by week of gestation among healthy term births. Am] Epidemiol 171 :399, 2010 Yang SH, Roh CR, Kim ]H: Transvaginal ultrasonography for cervical assessment before induction of labor. Obstet Gynecol Surv 59:577, 2004


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Obstentrics_Williams. Yang SH, Roh CR, Kim ]H: Transvaginal ultrasonography for cervical assessment before induction of labor. Obstet Gynecol Surv 59:577, 2004 Zizzo AR, Kirkegaard I, Pin borg A, et al: Decline in stillbirths and perinatal mortality after implementation of a more aggressive induction policy in post-date pregnancies: a nationwide register study. Acta Obstet Gynecol Scand 96(7):862, 2017 FETAL GROWTH. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 844 FETAL-GROWTH RESTRICTION.................... 847 RISK FACTORS AND ETIOLOGIES.................. 849 FETAL-GROWTH RESTRICTION RECOGNITION....... 852 MANAGEMENT................................. 854 FETAL OVERGROWTH......................... 856 RISK FACTORS ................................. 857 MANAGEMENT. ............................... 858


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Obstentrics_Williams. MANAGEMENT................................. 854 FETAL OVERGROWTH......................... 856 RISK FACTORS ................................. 857 MANAGEMENT. ............................... 858 When inants are of large size and abundant, they may mechanicaly throw out of function so great a portion of the placenta as seriousy to inteere with the nutrition of the oetus, and sometimes cause its death. Excessive development of the oetus can usualy be traced to prolongation of pregnancy, large size of one or both parents, advancing age, or multipariy of the mother. -J. Whitridge Williams (1903) he concept of excessive or impaired fetal growth was not considered in detail by Williams in his irst edition. Abnormally diminished fetal growth was attributed to placental lesions and fetal infections. Conversely, a large fetus was of obvious concern because of associated dystocia. Currently, fetal-growth disorders at both ends of the spectrum are major problems in obstetrics.


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Obstentrics_Williams. Nearly 20 percent of the almost 4 million neonates born in the United States are at the low and high extremes of fetal growth.


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Obstentrics_Williams. In 2015, 8.1 percent of newborns weighed <2500 g at birth, whereas 8.0 percent weighed >4000 g. And, although almost 70 percent of low-birthweight neonates are born preterm, the balance of low-birthweight newborns accounted for approximately 3 percent of term births in 2015 (Martin, 2017). Between 1990 and 2006, the proportion of newborns with birthweights <2500 g grew by more than 20 percent when the rate peaked at 8.3 percent (Martin, 2012). his trend toward smaller babies has slowed since the mid-to late-2000s and might partly be explained by the concurrent movement toward fewer deliveries prior to 39 weeks' gestation (Richards, 2016). In contrast, between 1990 and 2006, the incidence of birth weights >4000 g declined approximately 30 percent to a nadir of 7.6 percent in 2010 (Martin, 2012). This trend away from the upper extreme is diicult to explain because it coincides with the epidemic prevalence of obesity, a known cause of macrosomia (Morisaki, 2013).


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Obstentrics_Williams. Human fetal growth is characterized by sequential patterns of tissue and organ growth, diferentiation, and maturation. However, the "obstetrical dilemma" postulates a conlict between the need to walk upright-requiring a narrow pelvis-and the need to think-requiring a large brain, and thus a large head. Some speculate that evolutionary pressures restrict growth late in pregnancy (Mitteroecker, 2016). Thus, the ability to growth restrict may be adaptive rather than pathological. Fetal growth has been divided into three phases. The initial phase of hyperplasia occurs in the irst 16 weeks and is characterized by a rapid increase in cell number. The second phase, which extends up to 32 weeks' gestation, includes both cellular hyperplasia and hypertrophy. After 32 weeks, fetal mass accrues by cellular hypertrophy, and it is during this phase that most fetal fat and glycogen are accumulated. The corresponding c 5..,


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Obstentrics_Williams. FIGURE 44-1 Increments in fetal weight gain in grams per day from 24 to 42 weeks' gestation. The black line represents the mean and the outer blue lines depict ±2 standard deviations. (Data from pregnancies managed at Parkland Hospital.) levels below the threshold for diabetes. Overgrowth does occur in the fetuses of euglycemic women. Its etiology is thus likely more complicated than merely dysregulated glucose metabolism (Catalano, 2011). Genetic factors, including genomic imprinting and epigenetic modifications via gene methylation, are also important and emphasize the potential role of inheritance (Begemann, 2015; Nawathe, 2016).


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Obstentrics_Williams. Excessive transfer of lipids may also lead to fetal overgrowth (Higa, 2013). Free or nonesteriied fatty acids in maternal plasma may be transferred to the fetus via facilitated diusion or ater liberation of fatty acids from triglycerides by trophoblastic lipases (Gil-SGnchez, 2012). Generally speaking, lipolytic activity is augmented in pregnancy, and fatty acid levels are increased in nonobese women during the third trimester (Diderholm, 2005). fetal-growth rates during these three phases are 5 g/d at 15 weeks' gestation, 15 to 20 g/d at 24 weeks', and 30 to 35 g/d at 34 weeks' (Williams, 1982). As shown in Figre 44-1, the velocity of fetal growth varies considerably.


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Obstentrics_Williams. Fetal development is determined by maternal provision of substrate and placental transfer of these, whereas fetal growth potentil is governed by the genome. The precise cellular and molecular mechanisms by which normal fetal growth ensues are incompletely understood. That said, considerable evidence support an important role for insulin and insulin-like growth factors (IGFs) in regulation offetal growth and weight gain (Luo, 2012). hese growth factors are produced by virtually all fetal organs and are potent stimulators of cell division and diferentiation.


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Obstentrics_Williams. Other hormones implicated in fetal growth have been identified, particularly hormones derived from adipose tissue. These hormones are known broadly as adipokines and include leptin, the protein product of the obesiy gene. Fetal leptin concentrations rise during gestation, and they correlate both with birthweight and with neonatal fat mass (Brifa, 2015; Logan, 2017; Simpson, 2017). Other adipokines possibly involved include adiponectin, ghrelin, follistatin, resistin, visfatin, vaspin, omentin-I, apelin, and chemerin.


Obstentrics_Williams

Obstentrics_Williams. Fetal growth is also dependent on an adequate supply of nutrients. As discussed in Chapter 7 (p. 138), both excessive and diminished maternal glucose availability afect fetal growth. Reduced maternal glucose levels may result in a lower birthweight. Still, growth-restricted neonates do not typically show pathologically low glucose concentrations in cord blood (Pardi, 2006). Fetal-growth restriction in response to glucose deprivation generally results only after long-term severe maternal caloric deprivation (Lechtig, 1975). Conversely, excessive glycemia produces macrosomia. Varying levels of glucose afect fetal growth via insulin and its associated IGFs. he Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study Cooperative Research Group (2008) found that elevated cord C-peptide levels, which relect fetal hyperinsulinemia, are associated with greater birthweight. his relationship was noted even in women with maternal glucose


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Obstentrics_Williams. Independent of prepregnancy body mass index (BMI), higher free fatty acid levels during the latter half of pregnancy correlate with birthweight (Crume, 2015). Other studies have correlated mater nal triglyceride levels with birthweight (Di Cianni, 2005; Vrijkotte, 2011). Greater intake of certain fatty acids, particularly omega-3, is also associated with greater birthweight (Calabuig-Navarro, 2016).


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Obstentrics_Williams. Placental fatty acid metabolism and transfer may be dysregulated in fetal-growth restriction and in maternal conditions associated with fetal overgrowth. For example, levels of endothelial lipase are reduced with deicient fetal growth, and this enzyme is overexpressed in placentas of women with diabetes (Gauster, 2007, 2011). Others have reported that diabetes and obesity are associated with altered placental lipid-transport gene expression (Radaelli, 2009). Obesity is also linked with greater expression of fatty acid binding/transport proteins within the trophoblast (Myatt, 2016; Scifres, 2011). he end result of these alterations is an abnormal accumulation of lipids that can result in pathological placental inlammation and dysfunction (Calabuig-Navarro, 2016; Myatt, 2016; Yang, 2016).


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Obstentrics_Williams. mino acids undergo active transport, which explains the normally higher fetal concentrations compared with maternal levels. In growth restriction, this pattern is reversed. One possible mechanism is altered transport of these amino acids. Remember, amino acids that reach the fetus must first cross the microvillus membrane at the maternal interface. Amino acids then traverse the trophoblastic cell, and inally cross the basal membrane into fetal blood (Chap. 5, p. 90). In human placentas, fetal growth correlates with peroxisome proliferator activator receptor gamma (PPAR-,) activity, which governs placental regulation of L-type amino acid (A T) receptors 1 and 2 (Chen, 2015b). Additional modulation is from rap amycin complex (mTORC) 1 and 2 receptors (Rosario, 2013). Placental mTORC activity is reduced in fetal-growth restriction. Others have shown that increasing birthweight and maternal BMI are linked to expression and activity of particular aminoacid transporters at the microvillus


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Obstentrics_Williams. is reduced in fetal-growth restriction. Others have shown that increasing birthweight and maternal BMI are linked to expression and activity of particular aminoacid transporters at the microvillus membrane (Jansson, 2013).


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Obstentrics_Williams. Normative data for fetal growth based on birthweight vary with ethnicity and geographic region. Accordingly, researchers have developed fetal-growth curves using various populations and geographic locations throughout the United States (Brenner, 1976; Ott, 1993; Overpeck, 1999; Williams, 1975). Because


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Obstentrics_Williams. TABLE 4-1. 2011 Gestational Age Birthweight (g) Percentiles for 3,252,01e1 Singleton Live Births in the United States (Duryea, 2014). hese current curves plot birthweight against a gestational age based on n obsteical estimate, formed in part by sonography. hese curves are thought to be more accurate and reflect more precise pregnancy dating. Older curves used gestational age derived rom a last menstrual period. Comparing birthweights rom 1991 to data from 2011, the more recent growth curves indicate that the earlier assessments overestimated birthweihts in the ase of preterm birth. In particular, the 50th percentile for fetal growth that previ ously corresponded to 31 to 32 weeks' gestation now corresponds to 33 to 34 weeks' when improved obstetrical dating is used.


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Obstentrics_Williams. The curves by Alexander (1996) and Duryea (2014) and their associates are most accurately termed a population rerence, rather than a standard. A population reference incorporates pregnancies of varying risks, along with the resulting outcomes, both normal and abnormal. In contrast, a stanard incorporates normal 1414 1573 2053 2579 2861 pregnancies with normal outcomes. Because population refer 34 1632 1793 2296 2846 3093 ences include preterm births, which are more likely to be growth 1871 2030 2549 3119 3345 restricted, it has been argued that the associated birthweight data 36 2117 2270 2797 3380 3594 overestimate deficient fetal growth (Mayer, 2013; Zhang, 2010). 37 2353 2500 3025 361n2 381n8 One recent project sought to define regional standards in health and socioeconomic conditions. Growth trajectories from the International Fetal and Newborn Growth Consortium for these curves are based on speciic ethnic or regional groups, they do not represent the entire population.


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Obstentrics_Williams. To address this, birthweights such as those shown in Table 4-1 are derived nationwide in the United States. Shown in Figure 4-2 are growth curves rom more thn 3.2 million mothers with singleton livebon neonates in the United States during 1991 and 2011 5,000 -By last menstrual period 4,000 impaired growth. hus, they cannot be used to identiy the fetus that fails to achieve an expected size but whose birthweight is above the 21st Century-INTERGROWTH 21 were similar in these eight: China, India, Kenya, Brazil, Oman, Italy, the United Kingdom, and the United States (Villar, 2014). However, an international standard based on the healthiest women is of questionable value (Hanson, 2015). Most of what is known regarding normal and abnormal human fetal growth is actually based on birthweights that are assembled as references for fetal growth at particular gestational ages. his is problematic, however, because birth weight does not deine the rate of fetal growth.


Obstentrics_Williams

Obstentrics_Williams. his is problematic, however, because birth weight does not deine the rate of fetal growth. Indeed, such birthweight curves reveal com- the of � the 10th percentile. For example, a fetus with 3,000 ) a birthweight in the 40th percentile may not have achieved its genomic growth potential for a birthweight in the 80th percentile. : 2,000 m The rate or velociy of fetal growth can be estimated by serial sonographic anthropometry. For example, Milovanovic (2012) 1,000 demonstrated that the growth rate of intrin borns (those below the 10th percentile) 22 24 26 28 30 32 34 36 38 40 42 44 approximates that of appropriate-for-gestaGestational age (weeks) tional-age neonates. However, diminished growth velocity may be linked to perinatal FIGURE 44-2 Fetal-growth curves for births in the United States in 2011. Curves vary depending on whether gestational age was calculated from the last menstrual changes that are independent of birthweight.


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Obstentrics_Williams. period or from an improved obstetrical estimate, derived in part using sonography. (Modified with permission from Duryea EL, Hawkins JS, Mcintire DO, et al: A revised Recently, Sovio and colleageus (2015) demonbirth weight reference for the United States. Obstet Gynecol. 2014 Jul;124(1 ):16-22.) strated that growth velocity of the abdominal circumference in the lowest decile distinguishes SGA newborns who sufer increased morbidity. Conversely, an excessive fetalgrowth velocity, particularly ofthe abdominal circumferencewhich may be correlated with increased hepatic blood low-is associated with an overgrown neonate (American College of Obstetricians and Gynecologists, 2016a). Several conditions or disorders can adversely afect the normal growth of a fetus. It is important clinically to distinguish between fetal-growth restriction and constitutional low birth weight. u


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Obstentrics_Williams. Fetal-Growth Disorders 100 -Morbidity 175 90 -Mortality) 150U) 80D �S s· C 70 > 0 100g0 60 30 0-E �� 75 50 -30 � u 0S 20 0E 259J) 10 >1010987654321<1 Birthweightpercentile FIGURE 44-3 Relationship between birthweight percentile and perinatal mortality and morbidity rates in 1560 small-for-gestationalage fetuses. A progressive increase in both mortality and morbidity rates is observed as birthweight percentile decreases.. (Data from Manning, 1995.) • Symmetrical versus Asymmetrical Growth Restriction Campbell and Thoms (1977) described the use of the sonographically determined head-to-abdomen circumerence ratio (HCIA) to diferentiate growth-restricted fetuses. Those who were symmetrical were proportionately small, and those who were asymmetrical had disproportionately lagging abdominal growth compared with head growth. The onset or etiology of a particular fetal insult is hypothetically linked to either type of growth restriction. In the instance ofsymmetricalgrowth restriction, an


Obstentrics_Williams

Obstentrics_Williams. growth compared with head growth. The onset or etiology of a particular fetal insult is hypothetically linked to either type of growth restriction. In the instance ofsymmetricalgrowth restriction, an early insult could result in a relative decrease in cell number and size. For example, early global insults such as those from chemical exposure, viral infection, or cellular maldevelopment with aneuploidy may cause a proportionate reduction of both head and body size. Asymmetricalgrowth restriction might follow a later pregnancy insult such as placental insuiciency from hypertension. In this variation, resultant diminished glucose transfer and hepatic storage would primarily afect cell size and not number. Thereby, fetal abdominal circumferencewhich relects liver size-would be reduced. Brain Sparing Such somatic growth restriction is proposed to result from preferential shunting of oxygen and nutrients to the brain. This allows normal brain and head growth, that is-brain sparing.


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Obstentrics_Williams. Brain Sparing Such somatic growth restriction is proposed to result from preferential shunting of oxygen and nutrients to the brain. This allows normal brain and head growth, that is-brain sparing. Accordingly, the ratio of brain weight to liver weight during the last 12 weeks-usually about 3 to I-may be increased to 5 to 1 or more in severely growth-restricted infants. Because of brainsparing efects, asymmetrical fetuses were thought to be preferentially protected from the full efects ofgrowth restriction. Considerable evidence has since accrued that fetal growth patterns are much more complex. For example, fetuses with 847 .�..,40


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Obstentrics_Williams. Lubchenco and coworkers (1963) published detailed comparisons of gestational ages with birthweights to derive norms for expected fetal size at a given gestational week. Battaglia and Lubchenco (1967) then classiied smalor-gestational-age neonates as those whose weights were below the 10th percentile for their gestational age. Low-birthweight newborns who are small for gestational age are often designated as having etalgrowth restriction. Such infants were shown to be at increased risk for neonatal death. For example, the mortality rate of SGA neonates born at 38 weeks was 1 percent compared with 0.2 percent in those with appropriate birthweights.


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Obstentrics_Williams. Importantly, manyneonates with birthweights < 10th percentile are not pathologically growth restricted, but instead are small simply because of normal biological factors. s many as 70 percent ofsuch SGA infants have normal outcomes and are thought to be appropriately grown when maternal ethnic group, parity, weight, and height are considered (Unterscheider, 2015). These small but normal infants also do not show evidence ofthe postnatal metabolic derangements commonly associated with deficient fetal growth. Moreover, intrinsically SGA newborns remain significantly smaller during surveillance to 2 years compared with appropriate-for-gestational age neonates, but they do not show diferences in measures ofmetabolic risk (Milovanovic, 2012).


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Obstentrics_Williams. Because of these disparities, other classifications have been developed. Usher and McLean (1969) suggested that fetal growth standards should be based on mean weights-for-age, with normal limits deined by ±2 standard deviations. This definition would limit SGA infants to 3 percent of births instead of 10 percent. In a population-based analysis of 122,754 births at Parkland Hospital, McIntire and colleagues (1999) showed this definition to be clinically meaningful. Also, as shown in Figure 44-3, most adverse outcomes are in newborns smaller than the 3rd percentile. The importance ofthis cut-ofhas been independently confirmed in a prospective study by Unterscheider and colleagues (2013a).


Obstentrics_Williams

Obstentrics_Williams. More recently, individual or customized fetal-growth potential is proposed to replace a population-based threshold. In this model, a fetus that deviates from its individual optimal size at a given gestational age is considered either overgrown or growth restricted (Chiossi, 2017). Such optimal projections are based on maternal race or ethnicity. But, the superiority of customized growth curves has not been established (Chiossi, 2017; Costantine, 2013; Grobman, 2013; Zhang, 2011). aneuploidy typically have disproportionately large head sizes and thus are asymmetricaLy growth restricted, which is contrary to contemporaneous thinking (Nicolaides, 1991). Moreover, most preterm neonates with growth restriction due to preeclampsia and associated utero placental insuiciency are found to have more symmetrical growth impairment-again, a departure from accepted principles (Salaia, 1995).


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Obstentrics_Williams. More evidence of the complexity of growth patterns was presented by Dashe and associates (2000). These investigators analyzed 8722 consecutive liveborn singletons who had undergone sonographic examination within 4 weeks of delivery. Although only 20 percent of growth-restricted fetuses demonstrated sonographic head-to-abdomen asymmetry, these fetuses were at greater risk for intrapartum and neonatal complications. Symmetrically growth-restricted fetuses were not at increased risk for adverse outcomes compared with those appropriately grown. These investigators concluded that asymmetrical fetalgrowth restriction represented signiicantly disordered growth, whereas symmetrical growth restriction more likely represented normal, genetically determined small stature. Other data further challenge the concept of brain sparing.


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Obstentrics_Williams. Roza and associates (2008) found that fetuses with circulatory redistribution-brain sparing-had a higher incidence of later behavioral problems. In another study, evidence of brain sparing was found in half of 62 growth-restricted fetuses with birthweights < 10th percentile and who showed abnormal middle cerebral artery Doppler low studies (Figueras, 2011). Compared with controls, these neonates had significantly lower neurobehavioral scores in multiple areas, suggesting profound brain injury. Zhu and coworkers (2016) prospectively compared late-onset growth restriction in 14 fetuses with that in 26 non-growth-restricted fetuses using magnetic resonance imaging to analyze hemodynamic flow. Despite the concept of brain sparing, growth-restricted infants had significantly smaller brains than controls. he complex efects of such insults-with respect to timing and severity-on brain structure, connectivity, and neurobehavioral outcomes have been recently reviewed by Miller and colleagues


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Obstentrics_Williams. controls. he complex efects of such insults-with respect to timing and severity-on brain structure, connectivity, and neurobehavioral outcomes have been recently reviewed by Miller and colleagues (2016).


Obstentrics_Williams

Obstentrics_Williams. Fetal-growth restriction is one of the "major obstetrical syndromes" associated with defects in early placentation (Brosens, 2015). Rogers and coworkers (1999) concluded that implantation-site disorders may be both a cause and consequence of hypoperfusion at the placental site. This comports with the association of certain placental angiogenic factors with pregnancy hypertensive disorders (Chap. 40, p. 716). Thus, it may be that placentas from pregnancies complicated by hypertension elaborate these angiogenic factors in response to placental-site hypoperfusion, whereas pregnancies complicated by fetal-growth restriction without hypertension do not Qeyabalan, 2008).


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Obstentrics_Williams. Mechanisms leading to abnormal trophoblastic invasion are likely multifactorial, and both vascular and immunological etiologies have been proposed. For example, atriaL natriuretic peptide converting enzyme, also known as corin, plays a critical role in trophoblastic invasion and remodeling of the uterine spiral arteries (Cui, 2012). hese processes are impaired in corin-deficient mice, which also develop evidence of preeclampsia. Moreover, mutations in the gene for corin have been reported in women with preeclampsia (Chen, 2015a).


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Obstentrics_Williams. Several immunological abnormalities are associated with fetalgrowth restriction. This raises the prospect of maternal rejection of ther" paternal semiallograft." Rudzinski and colleagues (2013) studied C4d, a component of complement that is associated with humoral rejection of transplanted tissues. They found this to be highly associated with chronic villitis-88 percent of cases versus only 5 percent of controls-and with reduced placental weight. In a study of 10,204 placentas, chronic villitis was associated with placental hypoperfusion, fetal acidemia, and fetal-growth restriction and its sequelae (Greer, 2012). im and coworkers (2015) extensively reviewed chronic inflammatory placental lesions and their association with fetal-growth restriction, preeclampsia, and preterm birth.


Obstentrics_Williams

Obstentrics_Williams. Several short-term and long-term adverse sequelae are linked with fetal-growth restriction. First, perinatal morbidity and mortality rates are substantive (see Fig. 44-3). Rates of stillbirth and adverse neonatal outcomes that include birth asphyxia, meconium aspiration, hypoglycemia, and hypothermia are all increased, as is the prevalence of abnormal neurological development. This is true for both term and preterm growth-restricted newborns. In one analysis of nearly 3000 newborns born before 27 weeks' gestation, those weighing < 10th percentile had a nearly fourfold higher risk of neonatal death or neurodevelopmental impairment and a 2.6-fold increased risk of cerebral palsy compared with non-SGA neonates (De Jesus, 2013). In another analysis of more than 91,000 uncomplicated pregnancies, newborns with weights < 5th percentile had a higher risk of low 5-minute Apgar score, respiratory distress, necrotizing enterocolitis, and neonatal sepsis than appropriate-weight neonates. The


Obstentrics_Williams

Obstentrics_Williams. newborns with weights < 5th percentile had a higher risk of low 5-minute Apgar score, respiratory distress, necrotizing enterocolitis, and neonatal sepsis than appropriate-weight neonates. The risks of stillbirth and neonatal death were sixfold and fourfold higher, respectively .\1endez-Figueroa, 2016).


Obstentrics_Williams

Obstentrics_Williams. The most severely growth-impaired newborns also have the worst outcomes. In one study of more that 44,561 neonates, only 14 percent of those weighing < 1st percentile at birth survived to discharge (Griin, 2015). For those infants who survive, the risks of adverse neurodevelopmental outcomes are substantial, especially for growth-impaired fetuses with either brain sparing or a major birth defect (Meher, 2015; Nelson, 2015b). Poor motor, cognitive, language and attention, and behavioral outcomes in growth-restricted newborns unfortunately persist into early childhood and adolescence (Baschat, 2014; Levine, 2015; Rogne, 2015).


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Obstentrics_Williams. Barker (1992) hypothesized that aduLt mortality and morbidity are related to fetal and infant health. This includes both under-and overgrowth. In the context of fetal-growth restriction, numerous reports describe a relationship between suboptimal fetal nutrition and an increased risk of subsequent adult hypertension, atherosclerosis, type 2 diabetes, and metabolic derangement (Burton, 2016; J ornayvaz, 2016). he degree to which low birthweight mediates adult disease is controversial, as weight gain in early life also appears important (Breij, 2014; Kerhof, 2012; McCloskey, 2016).


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Obstentrics_Williams. Kerhof, 2012; McCloskey, 2016). Mounting evidence suggests that fetal-growth restriction may afect organ development, particularly that of the heart. Individuals with low birthweight demonstrate cardiac structural changes and dysfunction persisting through childhood, adolescence, and adulthood. In one study, 80 infants who were born SGA before 34 weeks' gestation were compared at 6 months with 80 normally grown children (Cruz-Lemini, 2016). The heart in the SGA children had a more globular ventricle that resulted in systolic and diastolic dysfunction. In another study, echocardiography in 418 adolescents showed that low birthweight was associated with a thicker let ventricular posterior wall (Hietalampi, 2012). In their review, Cohen and colleagues (2016) concluded, however, that these findings have unclear long-term signiicance.


Obstentrics_Williams

Obstentrics_Williams. Deficient fetal growth is also associated with postnatal structural and functional renal changes. In a review by Luyckx and Brenner (2015), birthweight abnormalities were evaluated for linkage with disordered nephrogenesis, renal dysfunction, chronic kidney disease, and hypertension. Both low and high birthweight, as well as maternal obesity and gestational diabetes, afect in-utero development of the kidney and its health into adulthood. However, other variables that include childhood nutrition, acute kidney injury, excessive childhood weight gain, and obesity also worsen long-term renal function.


Obstentrics_Williams

Obstentrics_Williams. Particularly in women with diabetes and elevated cord blood levels of IGF-1, fetal overgrowth is associated with greater neonatal fat mass and morphological heart changes. Pedersen (1954) irst proposed that hyperglycemia leads to fetal hyperinsulinemia and fetal overgrowth. This has been extended to organ dysmorphia, for example, increased interventricular septal thickness in neonates of mothers with gestational diabetes (nan, 2011; Garcia-Flores, 2011). he cardiopulmonary vasculature is also adversely afected by diabetes in pregnancy. In 3277 cases of persistent pulmonary hypertension of the newborn (PPHN), maternal obesity, diabetes, and both deficient and excessive fetal growth were independent risk factors (Steurer, 2017). Longterm consequences of fetal overgrowth from obesity and diabetes are discussed in Chapters 48 (p. 941) and 57 (p. 1097).


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Obstentrics_Williams. Numerous reports have described accelerated fetal pulmonary maturation in complicated pregnancies associated with growth restriction (Perelman, 1985). One possible explanation is that the fetus responds to a stressed environment by augmenting adrenal glucocorticoid secretion, which leads to accelerated fetal lung maturation (Laatikainen, 1988). Although this concept pervades modern perinatal thining, evidence to support it is negligible.


Obstentrics_Williams

Obstentrics_Williams. To examine this hypothesis, Owen and associates (1990) analyzed perinatal outcomes in 178 women delivered because of hypertension. hey compared these with outcomes in newborns of 159 women delivered because of spontaneous preterm labor or ruptured membranes. They concluded that a "stressed" pregnancy did not confer an appreciable survival advantage. Similar findings were described by Friedman and colleagues (1995) in women with severe preeclampsia. Two studies from Parkland Hospital also substantiate that the preterm infant accrues no apparent advantages from fetal-growth restriction (McIntire, 1999; Tyson, 1995).


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Obstentrics_Williams. Risk factors for impaired fetal growth include potential abnormalities in the mother, fetus, and placenta. hese three "compartments" are depicted in Figure 44-4. Some of these factors are known causes of fetal-growth restriction and may afect more than one compartment. For instance, cytomegalovirus infections can afect the fetus directly. In contrast, bacterial infections such as tuberculosis may have signiicant maternal efects that lead to poor fetal growth. Similarly, malaria, a protozoal infection, is a recognized cause of fetal-growth restriction (Briand, 2016). Importantly, many causes of diminished fetal growth are prospectively considered risk factors, because impaired fetal growth is not consistent in all afected women.


Obstentrics_Williams

Obstentrics_Williams. It is axiomatic that small women typically have smaller newborns. As discussed subsequently, both prepregnancy weight and gestational weight gain modulate this risk. Durie and colleagues (2011) showed that the risk of delivering an SGA neonate was highest among underweight women who gained less weight than recommended by the Institute of Medicine (Chap. 9, p. 166). Also, both maternal and paternal size inluences birthweight. In a Swedish study of 137,538 term births, it was estimated that the maternal and paternal birthweights explained 6 and 3 percent of variance in birthweight, respectively (Mattsson, 2013). In the study by Durie (2011) cited above, gestational weight gain during the second and third trimesters that was less than FIGURE 44-4 Risk factors and causes of impaired fetal growth centering on the mother, her fetus, and the placenta.


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Obstentrics_Williams. FIGURE 44-4 Risk factors and causes of impaired fetal growth centering on the mother, her fetus, and the placenta. that recommended by the Institute of Medicine was associated with SGA neonates in women of all weight categories except class II or III obesity. Conversely, excessive gestational weight gain was associated with an overgrown newborn in all weight categories (Blackwell, 2016).


Obstentrics_Williams

Obstentrics_Williams. As perhaps expected, eating disorders are linked with significantly higher risks for low birthweight and preterm birth (Micali, 2016). Marked weight gain restriction ater midpregnancy should not be encouraged even in obese women (Chap. 48, p. 941). Even so, it appears that food restriction to < 1500 kcal/d adversely afects fetal growth minimally (Lechtig, 1975). The best documented efect of famine on fetal growth was in the Hunger Winter of 1944 in Holland. For 6 months, the German occupation army restricted dietary intake to 500 kcal/ d for civilians, including pregnant women. This resulted in an average birthweight decline of only 250 g (Stein, 1975).


Obstentrics_Williams

Obstentrics_Williams. It is unclear whether undernourished women may beneit from micronutrient supplementation. In one study, almost 32,000 Indonesian women were randomly assigned to receive micronutrient supplementation or only iron and folate tablets (Prado, 2012). Ofspring of those receiving the supplement had lower risks of early infant mortality and low birthweight and had improved childhood motor and cognitive abilities. Conversely, Liu and coworkers (2013) randomly assigned 18,775 nulliparas to folic acid alone; folic acid and iron; or folic acid, iron, and 13 other micronutrients. Folic acid and iron, with or without the additional micro nutrients, resulted in a 30-percent reduction in risk of third-trimester anemia. But, supplementation did not afect other maternal or neonatal outcomes. A Cochrane database review of 19 trials involving 138,538 women concluded that supplementation of iron and folic acid improved birth outcomes, including lower risks of low birthweight and SGA (Haider, 2017). he


Obstentrics_Williams

Obstentrics_Williams. database review of 19 trials involving 138,538 women concluded that supplementation of iron and folic acid improved birth outcomes, including lower risks of low birthweight and SGA (Haider, 2017). he importance of antenatal vitamins and trace metals is further discussed in Chapter 9 (p. 168).


Obstentrics_Williams

Obstentrics_Williams. Exercise in pregnancy may be beneficial for optimal fetal growth. One metaanalysis of28 studies involving 5322 women concluded that exercise reduces the risk of fetal overgrowth without raising the risk of poor growth (Wiebe, 2015). Another metaanalysis concluded that aerobic exercise did not result in low-birthweight neonates (Di Mascio, 2016). The efect of social deprivation on birthweight is interconnected with lifestyle factors such as smoking, alcohol or other substance abuse, and poor nutrition. With appropriate modiying interventions, women with psychosocial factors were signiicantly less likely to deliver a low-birthweight infant and also had fewer preterm births and other pregnancy complications (Coker, 2012).


Obstentrics_Williams

Obstentrics_Williams. Women who are immigrants may be at particular risk for poor fetal growth. In one study of 56,443 singleton pregnancies in Rotterdam, social deprivation was associated with adverse perinatal outcomes that included SGA newborns (Poeran, 2013). That said, a similar linkage was not found in socially deprived women of non-Western origin. The efect of immigration, however, is complex and dependent on the population studied (Howell, 2017; Sanchez-Vaznaugh, 2016).


Obstentrics_Williams

Obstentrics_Williams. Especially when complicated by superimposed preeclampsia, chronic vascular disease commonly causes growth restriction (Chap. 50, p. 980). In a study of more than 2000 women, vascular disease as evidenced by abnormal uterine artery Doppler velocimetry early in pregnancy was associated with higher rates of preeclampsia, SGA neonates, and delivery before 34 weeks (Groom, 2009). Using Washington state birth certiicate data, Leary and colleagues (2012) found that maternal ischemic heart disease was linked to SGA infants in 25 percent of 186 births. Roos-Hesselink and coworkers (2013) described similar pregnancy outcomes in 25 women with ischemic heart disease. Chronic renal insuiciency is frequently associated with underlying hypertension and vascular disease. Nephropathies are commonly accompanied by restricted fetal growth (Cunningham, 1990; Feng, 2015; Saliem, 2016). hese relationships are considered further in Chapter 53 (p. 1034).


Obstentrics_Williams

Obstentrics_Williams. Fetal-growth restriction in the newborns of women with diabetes may be related to congenital malformations or may follow substrate deprivation from advanced maternal vascular disease (Chap. 57, p. 1100). Also, the likelihood of restricted growth increases with worsening White classification, particularly nephropathy (Klemetti, 2016). hat said, the prevalence of serious vascular disease associated with diabetes in pregnancy is low, and the primary efect of overt diabetes, especially type 1, is fetal overrowth. For example, in a prospective study of 682 consecutive pregnancies complicated by diabetes, women with type 1 diabetes were significantly more likely than women with type 2 diabetes to have a neonate weighing above the 90th and 97.7th percentiles (Murphy, 2011). Additionally, women with type 1 diabetes were significantly less likely to deliver an SGA newborn. In a recent study of 375 term singleton pregnancies complicated by type 1 diabetes, the risk of fetal overgrowth


Obstentrics_Williams

Obstentrics_Williams. women with type 1 diabetes were significantly less likely to deliver an SGA newborn. In a recent study of 375 term singleton pregnancies complicated by type 1 diabetes, the risk of fetal overgrowth correlated with rising third-trimester glycemic values (C yganek, 2017) . Nearly a fourth of neonates were macrosomic. And, third-trimester hemoglobin Al c and fasting glucose values were independent predictors for the risk of macrosomia.


Obstentrics_Williams

Obstentrics_Williams. Conditions associated with chronic uteroplacental hypoxia include preeclampsia, chronic hypertension, asthma, maternal cyanotic heart disease, smoking, and high altitude. When exposed to a chronically hypoxic environment, some fetuses have signiicantly reduced birthweight. In more than 1.8 million births in Austria, the birthweight declined 150 g for each 1000meter rise in altitude (Waldhoer, 2015). In 63,620 Peruvian live births, the mean birthweight was significantly decreased at higher compared with lower altitudes-3065 g ± 475 g versus 3280 g ± 525 g (Gonzales, 2009). In this study, the rate of birth weights <2500 g was 6.2 percent at low altitudes, and it was 9.2 percent at high altitudes. In contrast, the rate of birthweights >4000 g was 6.3 percent at low altitudes and 1.6 percent at high altitudes.


Obstentrics_Williams

Obstentrics_Williams. In most cases, maternal anemia does not restrict fetal growth. Exceptions include sickle-cell disease and some other inherited anemias (Desai, 2017; Thame, 2016). Importantly, curtailed maternal blood-volume expansion is linked to fetal-growth restriction (de Haas, 2017; Stott, 2017). This is further discussed in Chapter 40 (p. 718).


Obstentrics_Williams

Obstentrics_Williams. Adverse obstetrical outcomes including fetal-growth restriction have been associated with three species of antiphospholipid antibodies: anticardiolipin antibodies, lupus anticoagulant, and anti-32 gycoprotein-I antibodies. Mechanistically, a "wohit" hypothesis suggests that initial endothelial damage is then followed by intervillous placental thrombosis. More specifically, oxidative damage to certain membrane proteins such as 32 glycoprotein-I is followed by antiphospholipid antibody binding, which leads to immune complex formation and ultimately to thrombosis (Giannakopoulos, 2013). his syndrome is considered in detail in Chapters 52 (p. 1008) and 59 (p. 1143). Pregnancy outcomes in women with these antibodies may be poor and include fetal-growth restriction and fetal demise (Cervera, 2015). he primary autoantibody that predicts obstetrical antiphospholipid syndrome appears to be lupus anticoagulant (Yelnik,r2016).


Obstentrics_Williams

Obstentrics_Williams. It is controversial whether pregnancies in women with prior infertility with or without treatment have an increased risk of SGA newborns (Zhu, 2007). Dickey and colleagues (2016) compared birthweight curves for singletons conceived by in vitro fertilization to the birthweight curves of Duryea (2014), described on page 846. hey found no reduction in fetal growth. Kondapalli and Perales-Puchalt (2013) reviewed possible links between low birthweight and infertility with its various interventions and concluded that any association remains unexplained for singletons. Placental, Cord, and Uterine Abnormalities


Obstentrics_Williams

Obstentrics_Williams. Placental, Cord, and Uterine Abnormalities Several placental abnormalities may cause poor fetal growth. These are discussed further throughout Chapter 6 and include chronic placental abruption, extensive chorioangioma, velamentous cord insertion, placenta previa, and umbilical artery thrombosis. Growth failure in these cases is presumed secondary to uteroplacental insuiciency. Abnormal placental implantation leading to endothelial dysfunction may also limit fetal growth (Brosens, 2015). This pathology is implicated in pregnancies complicated by preeclampsia (Chap. 40, p. 714). If the placenta is implanted outside the uterus, the fetus is usually growth restricted (Chap. 19, p. 383). Finally, some uterine malformations have been linked to impaired fetal growth (Chap. 3, p. 44).


Obstentrics_Williams

Obstentrics_Williams. Pregnancy with two or more fetuses is more likely to be complicated by diminished growth of one or more fetuses compared with that ofnormal singletons. This is illustrated in Figure 44-5 and discussed in Chapter 45 (p. 872). Drugs with Teratogenic and Fetal Effects Several drugs and chemicals are capable oflimiting fetal growth. Some are teratogenic and afect the fetus before organogenesis is ::,1500 FIGURE 44-5 Birthweight and gestational age relationships in multifetal gestations without malformations delivered at Parkland Hospital.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 44-5 Birthweight and gestational age relationships in multifetal gestations without malformations delivered at Parkland Hospital. complete. Some exert-or continue to exert-fetal efects after embryogenesis ends at 8 weeks. Many ofthese are considered in detail in Chapter 12, and examples include anticonvulsants and antineoplastic agents. Cigarette smoking, opiates and related drugs, alcohol, and cocaine may also cause growth restriction, either primarily or by decreasing maternal food intake. he link with cafeine use and fetal-growth restriction remains speculative (American College of Obstetricians and Gynecologists, 2016b). In contrast, Cyganek and colleagues (2014) studied growth restriction in pregnancies complicated by renal and liver transplants and concluded that common immunosuppressive drugs-prednisone, azathioprine, cyclosporine A, and tacrolimus-did not significantly afect fetal-growth rates.


Obstentrics_Williams

Obstentrics_Williams. Viral, bacterial, protozoan, and spirochetal infections have been implicated in up to 5 percent of fetal-growth restriction cases and are discussed throughout Chapters 64 and 65. The best known of these are rubela and cytomegalovirus inection. Both promote calcifications in the fetus that are associated with cell death, and infection earlier in pregnancy correlates with worse outcomes. Toda and colleagues (2015) described a Vietnamese epidemic in which 39 percent of 292 term newborns with congenital rubella syndrome were low birthweight. In one study of 238 primary cytomegalovirus infections, no severe cases were observed when infection occurred after 14 weeks' gestation (Picone, 2013). hese investigators later identified sonographic findings in 30 of 69 cases of congenital infection, and growth restriction was noted in 30 percent of these 30 cases (Picone, 2014).


Obstentrics_Williams

Obstentrics_Williams. Tuberculosis and syphilis have also both been associated with poor fetal growth. Both extrapulmonary and pulmonary tuberculosis are linked with low birthweight (Chap. 51, p. 995). Sobhy (2017) analyzed 13 studies that included a total of3384 women with active tuberculosis. The odds ratio was 1.7 for low birthweight. The etiology is uncertain, however, the adverse efects on maternal health, compounded by efects of poor nutrition and poverty, are important Gana, 2012). Congenital syphilis is more common, and paradoxically, the placenta is almost always larger and heavier due to edema and perivascular inflammation (Chap. 65, p. 1237). Congenital syphilis is strongly linked with preterm birth and thus low-birthweight newborns (Sheield, 2002).


Obstentrics_Williams

Obstentrics_Williams. Toxoplasma gondii can also cause congenital infection, and Paquet and Yudin (2013) describe its classic association with fetal-growth restriction. Capobiango (2014) described 31 Brazilian pregnancies complicated by congenital toxoplasmosis. Only 13 percent were treated antepartum for toxoplasmosis, and low birthweight complicated nearly 40 percent of all the pregnancies. Congenital maaria also causes low birthweight and poor fetal growth. Briand and colleagues (2016) emphasize the importance of prophylaxis early in pregnancy for women at risk.


Obstentrics_Williams

Obstentrics_Williams. In a study of more than 13,000 fetuses with major structural anomalies, 22 percent had accompanying growth restriction (Khoury, 1988). In one study of 111 pregnancies complicated by fetal gastroschisis, a third had birthweights < 10th percentile (Nelson, 20 15a). As a general rule, the more severe the malformation, the more likely it is that the fetus will be SGA. This is especially evident in fetuses with chromosomal abnormalities or those with serious cardiovascular malformations.


Obstentrics_Williams

Obstentrics_Williams. Depending on which chromosome is redundant, fetuses with autosomal trisomies may display poor fetal growth. For example, in trisomy 21, fetal-growth restriction is generally mild. By contrast, fetal growth in trisomy 18 is virtually always significantly limited. he crown-rump length in fetuses with trisomy 18 and 13, unlike that with trisomy 21, is typically shorter than expected (Bahado-Singh, 1997; Schemmer, 1997). By the second trimester, long-bone measurements usually are below the 3rd percentile. In one group of 174 children with trisomy 13, the mean birthweight with trisomy 13 was 2500 g, and in 254 children with trisomy 18, it was 1800 g (Nelson, 2016).


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Obstentrics_Williams. Poor fetal growth also complicates Turner syndrome, and the severity correlates with increasing haploinsuiciency of the short arm of the X chromosome (Fiot, 2016). In contrast, poor growth is not characteristic of an increased number of X chromosomes (Ottesen, 2010; Wigby, 2016). As discussed in Chapter 13 (p. 263), aneuploidic patches in the placentaconined placental mosaicism (CPM)-is a recognized cause of fetal-growth restriction. Evidence suggests that aneuploidy afecting both the cytotrophoblast and mesenchymal core of the placenta, which is type 3 CPM, is associated with fetalgrowth restriction (Toutain, 2010).


Obstentrics_Williams

Obstentrics_Williams. First-trimester prenatal programs that screen for fetal aneuploidy'may incidentally identiy pregnancies at risk for fetalgrowth restriction unrelated to karyotype. In their analysis of 8012 women, the risk for growth restriction was higher in eukaryotic fetuses with extremely low free 3-human chorionic gonadotropin (3-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels (Krantz, 2004). From her review, Dugof (2010) concluded that a low PAPP-A level is strongly associated with poor fetal growth, but studies of free 3-hCG are conflicting.


Obstentrics_Williams

Obstentrics_Williams. Second-trimester analytes, including elevated alpha-fetoprotein and inhibin A levels and low unconjugated serum estriol concentrations, are significantly associated with birthweight below the 5th percentile. An even greater risk of poor growth is linked with certain combinations of these analytes. Still, these markers are poor screening tools for complications such as fetalgrowth restriction due to low sensitivity and positive-predictive values (Dugof, 2010). Nuchal translucency is also not predictive of fetal-growth restriction. he role of all these markers in aneuploidy screening is discussed in Chapter 14 (p. 281).


Obstentrics_Williams

Obstentrics_Williams. Identification of the inappropriately growing fetus remains a challenge. Eary establishment of gestational age, ascertainment of maternal weight gain, and careful measurement of uterine fundal growth throughout pregnancy will identiy many cases of abnormal fetal growth in low-risk women. Risk factors, including aprior growth-restricted etus, raise the recurrence risk to nearly 20 percent (American College of Obstetricians and Gynecologists, 2015). In women with risk factors, serial sonographic evaluation is considered. Although examination frequency varies depending on indications, an initial early dating examination followed by an examination at 32 to 34 weeks, or when otherwise clinically indicated, will identiy many growthrestricted fetuses. Even so, deinitive diagnosis frequently cannot be made until delivery.


Obstentrics_Williams

Obstentrics_Williams. According to one systematic review, insuicient evidence supports the utility of fundal height measurement to detect fetalgrowth restriction (Robert Peter, 2015). Nonetheless, carefully performed serial fundal height measurements are recommended as a simple, safe, inexpensive, and reasonably accurate screening method to detect growth-restricted fetuses. As a screening tool, its principal drawback is imprecision. Haragan and coworkers (2015) reported sensitivities of 71 and 43 percent for detecting excessive or deficient fetal growth. Specificities were 85 and 66 percent, respectively. he method used by most for fundal height measurement is described in Chapter 9 (p. 164). Between 18 and 30 weeks' gestation, the uterine fundal height in centimeters coincides within 2 weeks of gestational age. Thus, if the measurement is more than 2 to 3 cm from the expected height, inappropriate fetal growth is suspected and sonography is considered.


Obstentrics_Williams

Obstentrics_Williams. One supporting point for routine sonographic evaluation of all pregnancies is the opportunity to diagnose growth restriction. Typically, such routine screening incorporates an early initial sonographic examination-usually at 16 to 20 weeks' gestation. Increasingly, a first-trimester examination is added to establish gestational age and identiy anomalies. Some then recommend repeat sonographic evaluation at 32 to 34 weeks to evaluate fetal growth. First-trimester sonography has limited accuracy to predict SGA newborns. For example, Croverro and associates (2017) reported detection rates of 35 and 42 percent with false-positive rates of 5 and 10 percent, respectively. From nearly 9000 screened pregnancies, Tuuli and colleagues (2011) concluded


Obstentrics_Williams

Obstentrics_Williams. FIGURE 44-6 Correlation of sonographic fetal weight estimation using abdominal circumference (A C) and actual birthweight. (Data from pregnancies managed at Parkland Hospital.) that second-trimester sonography is superior to first-trimester scans for predicting SGA neonates. At Parkland Hospital, we provide midpregnancy sonographic screening examination of all pregnancies. Additional sonographic evaluations of fetal growth are performed as clinically indicated.


Obstentrics_Williams

Obstentrics_Williams. With sonography, the most common method for identiying poor fetal growth is estimation of weight using multiple fetal biometrical measurements. Combining head, abdomen, and femur dimensions provides optimum accuracy, whereas little incremental improvement is gained by adding other biometrical measurements (Platz, 2008). Of the dimensions, femur length measurement is technically the easiest and the most reproducible. Biparietal diameter and head circumference measurements are dependent on the plane of section and may also be afected by deformative pressures on the skull. Last, abdominal circumference measurements are more variable. However, these are most frequently abnormal with fetal-growth restriction because soft tissue predominates in this dimension (Fig. 44-6). Shown in Figure 44-7 is an example of a severely growth-restricted newborn.


Obstentrics_Williams

Obstentrics_Williams. Some studies have reported a significant predictive value for small abdominal circumference with respect to lagging fetal growth. One study screened nearly 4000 pregnancies using either clinically indicated or universal sonography in the third trimester (Sovio, 2015) . Universal sonography raised the rate of detection of SGA from 20 percent to 57 percent. Importantly, however, the neonatal morbidity rate was increased only if the abdominal circumference growth velocity was in the lowest decile.


Obstentrics_Williams

Obstentrics_Williams. Sonographic estimates of fetal weight and actual weight may be discordant by 20 percent or more, leading to both false-positive and false-negative indings. Dashe and associates (2000) studied 8400 live births at Parkland Hospital in which fetal sonographic evaluation had been performed within 4 weeks of delivery. They reported that 30 percent of growth-restricted fetuses were not detected. In a study of 2586 women with low-risk pregnancies randomly assigned to sonography at 32 or 36 weeks' gestation, sensitivity to identiy grow restriction was improved at the later gestational age (Roma, 2015). Still, nearly 40 percent of cases of growth restriction deined as birthweight <3rd percentile were missed. A Cochrane database analysis of 13 trials with 34,980 women concluded that routine late pregnancy ultrasound for a low-risk or an unselected population is not associated with maternal or fetal benefit (Bricker, 2015).


Obstentrics_Williams

Obstentrics_Williams. FIGURE 44-7 A 36-week newborn with severe fetal-growth restriction. (Used with permission from Dr. Roxane Holt.) An association between pathological fetal-growth restriction and oligohydramnios has long been recognized. Petrozella and associates (201r1) reported that decreased amnionic fluid volume between 24 and 34 weeks' gestation was signiicantly associated with malformations. In the absence of malformations, a birthweight < 3rd percentile was seen in 37 percent of pregnancies with oligohydramnios, in 21 percent with borderline amnionic fluid volume, but in only 4 percent with normal volumes. Also, from a recent metaanalysis of 15 studies involving more than 35,000 pregnancies, high-risk pregnancies with oligohydramnios were more likely to be complicated by low birthweight compared with low-risk pregnancies with oligohydramnios (Rabie, 2017). Hypoxia and diminished renal blood low are proposed explanations for oligohydramnios.


Obstentrics_Williams

Obstentrics_Williams. With this technique, early changes in placenta-based growth restriction are detected in peripheral vessels such as the umbilical and middle cerebral arteries. Late changes are characterized by reversal of umbilical artery flow and by abnormal flow in the ductus venosus and fetal aortic and pulmonary outlow tracts.


Obstentrics_Williams

Obstentrics_Williams. Of these, abnormal umbilical artery Doppler velocimetry indings-characterized by absent or reversed end-diastolic low-are uniquely linked with fetal-growth restriction (Chap. 10, p. 213). hese abnormalities highlight early versus severe growth restriction and represent the transition from fetal adaptation to failure. Thus, persistently absent or reversed end-diastolic flow, such as that shown in Figure 44-8, has long been correlated with hypoxia, acidosis, and fetal death. In one prospective sonographic examination of 1116 fetuses with estimated fetal weights < 10th percentile, only 1.3 percent of fetuses with normal umbilical artery Doppler studies had adverse outcomes compared with 11.5 percent of those with Doppler abnormalities (O'Dwyer, 2014). Unterscheider and associates (2013a) reported that abnormal umbilical artery Doppler velocimetry combined with an estimated fetal weight <3rd percentile is most strongly associated with poor obstetrical outcome.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 44-8 Doppler velocity waveforms. A. Normal waveform with normal SID ratio. B. Increased impedance to flow with abnormally elevated SID ratio. C. Absent end-diastolic flow. D. Reversed end-diastolic flow. Because of these findings, umbilical artery Doppler velocimetry is considered standard in the evaluation and management of the growth-restricted fetus. he American College of Obstetricians and Gynecologists (2015) has concluded that umbilical-artery Doppler velocimetry improves clinical outcomes. It is recommended in the management of fetal-growth restriction as an adjunct to standard surveillance techniques such as nonstress testing and biophysical proile.


Obstentrics_Williams

Obstentrics_Williams. Other Doppler assessments are still investigational. Interrogation of the ductus venosus was evaluated in a series of 604 fetuses <33 weeks' gestation who had an abdominal circumference <5th percentile (Baschat, 2007). Ductus venosus Doppler parameters were the primary cardiovascular factor in predicting neonatal outcome. These late changes are felt to relect myocardial deterioration and acidemia, which are major contributors to adverse perinatal and neurological outcome. In another study of 46 growth-restricted fetuses, Doppler flow abnormalities of the aortic valve isthmus preceded those in the ductus venosus by 1 week (Figueras, 2009). In their evaluation of several fetal vessels, Turan and associates (2008) described the seq uence of changes characteristic of mild placental dysfunction, progressive placental dysfunction, and severe, early-onset placental dysfunction. However, Unterscheider and colleagues (2013b) questioned whether a predictable progression of Doppler indices


Obstentrics_Williams

Obstentrics_Williams. progressive placental dysfunction, and severe, early-onset placental dysfunction. However, Unterscheider and colleagues (2013b) questioned whether a predictable progression of Doppler indices actually exists in fetal-growth restriction.


Obstentrics_Williams

Obstentrics_Williams. Fetal-growth restriction prevention ideally begins before conception. Maternal medical conditions, medications, and nutrition are optimized, and smoking cessation is critical. Other risk factors are tailored to the maternal condition, such as antimalarial prophylaxis for women living in endemic areas and correction of nutritional deficiencies. Of note, treatment of mild-to-moderate hypertension does not reduce the incidence of growth-restricted newborns (Chap. 50, p. 981).


Obstentrics_Williams

Obstentrics_Williams. Accurate dating is essential during early pregnancy. Serial sonographic evaluations are typically used, but the best interval between assessments has not been clearly established. Given that a prior SGA newborn is associated with other adverse outcomes in a subsequent pregnancy, particularly stillbirth and preterm birth, surveillance during a subsequent pregnancy may be beneicial (Mendez-Figueroa, 2016; Spong, 2012). he American College of Obstetricians and Gynecologists (2015) notes that if growth is normal during a pregnancy following a prior pregnancy complicated by fetal-growth restriction, then Doppler velocimetry and fetal surveillance are not indicated. A recent metaanalysis of 45 trials involving 20,909 women reported that low-dose aspirin initiated prior to 16 weeks' gestation was associated with a significantly lower risk of fetal-growth restriction (Roberge, 2017). Moreover, they described a dose-response efect. he American College of Obstetricians and Gynecologists (2015)


Obstentrics_Williams

Obstentrics_Williams. associated with a significantly lower risk of fetal-growth restriction (Roberge, 2017). Moreover, they described a dose-response efect. he American College of Obstetricians and Gynecologists (2015) has not endorsed prophylaxis with low-dose aspirin for women with a prior growth-restricted fetus.


Obstentrics_Williams

Obstentrics_Williams. If fetal-growth restriction is suspected, then eforts are made to conirm the diagnosis, assess fetal condition, and search for possible causes. Early-onset growth restriction is especially problematic. In pregnancies in which fetal anomalies are suspected, patient counseling and prenatal diagnostic testing are indicated (American College of Obstetricians and Gynecologists, 2015). Ifnoindications for immediate delivery, Ifnoindications for immediate delivery: begin antepartum fetal surveillance: -Antepartum fetal surveillance-BPP, NST, etc. -Regular fetal testing -Umbilical artery Doppler velocimetry weekly -Weekly umbilical artery Doppler velocimetry -Amnionic fluid evaluation weekly -Weekly evaluation of amnionic fluid surveillance until delivery 38 weeks, then deliver delivery 34 weeks, then begin FIGURE 44-9 Algorithm for management of fetal-growth restriction at Parkland Hospital. BPP = biophysical profile; NST = nonstress test.


Obstentrics_Williams

Obstentrics_Williams. One management algorithm is shown in Figure 44-9. In pregnancies with suspected fetal-growth restriction, antepartum fetal surveillance includes periodic Doppler velocimetry of the umbilical arteries in addition to more frequent fetal testing. At Parkland Hospital, for women whose fetus measures ;3rd percentile and has reached a viable age, we encourage hospitalization on our High-Risk Pregnancy Unit. Daily fetal heart rate tracings, weekly Doppler velocimetry, and sonographic assessment of fetal growth every 3 to 4 weeks are initiated. Other modalities of Doppler velocimetry, such as middle cerebral arteries or ductus venosus assessment, are considered experimental. he American College of Obstetricians and Gynecologists (2015) recommends that antenatal corticosteroids for pulmonary maturation be given to pregnancies complicated by fetal-growth restriction and at risk for birth before 34 weeks' gestation.