- Email: [email protected]
Spontaneous Preterm Labor and Premature Rupture of Membranes at Late Preterm Gestations: To Deliver or Not to Deliver
Spontaneous Preterm Labor and Premature Rupture of Membranes at Late Preterm Gestations: To Deliver or Not to Deliver John C. Hauth, MD Nationwide the American College of Obstetricians and Gynecologists noted in 1995 that the survival rate for newborns at 34 weeks is within 1% of those born at or beyond 37 weeks. Newborn major morbidity is slightly but significantly increased from 340 to 366 compared with 37 or greater weeks. These data form the basis for and reflect the perinatal outcomes associated with the standardized obstetric practices of effecting delivery for women with amnion rupture and also of not attempting tocolysis for preterm labor at or beyond 340 weeks gestation. Pragmatically, a prospective randomized management trial of women at late preterm gestation (340 to 366) and with spontaneous preterm labor or amnion rupture would require multi-institutional support to achieve a required study population. Semin Perinatol 30:98-102 © 2006 Elsevier Inc. All rights reserved. KEYWORDS preterm labor, prolonged rupture of membrane, stillbirth, infant newborn, infant mortality, perinatal epidemiology
I
n a recent NICHD workshop on near-term pregnancy and infant care, the panel opined that the phrase near-term be replaced, and instead “late preterm” be used as the latter will convey that the infant is still preterm, not “almost term.” Arbitrary suggestion was made that late preterm be defined as those births between 34 0/7 through 36 6/7 weeks (239th to 259th day). In this manuscript, the phrase “late preterm” is used. In the United States in 2002, almost 28,000 infants died in their first year of life (Table 1).1 Preterm birth, which is defined as delivery before 37 completed weeks, occurred in approximately two-thirds of these deaths. Overall, infant mortality has continued to decline from 1990 to 2000, and the causes of infant mortality have also declined, except for those associated with preterm birth or low birth weight (Fig. 1).2 From 1990 to 2000, singleton preterm births in this country have increased (Fig. 2),3 which has primarily occurred in white non-Hispanic women (not shown). Preterm births have also increased in Canada from 1990 to 2000 (Fig. 3).4 Preterm births in this country remain highest in black women (Fig. 4).5 Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL. Address reprint requests to John C. Hauth, MD, University of Alabama at Birmingham, Department of Obstetrics and Gynecology, 619 19th Street South, 246 OHB, Birmingham, AL. E-mail: [email protected]
98
0146-0005/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.semperi.2006.02.008
Management of Late Preterm (340 to 366 Weeks Gestation) Spontaneous Labor or Amnion Rupture In 1995, the American College of Obstetricians and Gynecologists6 noted that the survival rate for newborns at 34 weeks is within 1% of those born at or beyond 37 weeks. In a secondary analysis of 5700 patients from three Maternal Fetal Medicine Units Network trials, the outcomes of death (0/416 versus 4/5284) or newborn hospital days (mean 3.75 versus 2.8 days) were similar at 35 to 36 weeks compared with 37 weeks or beyond (personal communications, Elizabeth Thom, PhD, Data Center Director for the Maternal-Fetal Medicine Units Network, NICHD, Bethesda, MD). The issue of late preterm newborn outcomes raises the question: Is there a birth weight or gestational age threshold after which attempts to delay delivery are unwarranted? DePalma and coworkers7 found that the threshold for neonatal mortality at Parkland Hospital was 1600 g, and it was 1900 g for neonatal morbidity. They concluded that aggressive attempts to prevent births for fetuses whose weight estimates exceeded 1900 g offered few apparent benefits. At Parkland Hospital, 1900 g is at the 10th percentile for 34 weeks and the 50th percentile for 32 weeks gestation.2 In general, obstetric management of spontaneous preterm
Late spontaneous preterm labor
99
Table 1 Infant Mortality in the United States in 2002
Total infants Gestational age at birth Less than 32 weeks 32–36 weeks 37–41 weeks 42 weeks or more Unknown
Live Births (%)
Infant Deaths (%)
4,021,825 (100)
27,970 (100)
77,877 (1.9) 402,972 (10) 3,231,562 (80) 268,096 (7) 41,318 (1)
14,515 (52) 3,692 (13) 8,001 (29) 824 (2.9) 937 (3.3)
Adapted from Mathews and colleagues, 2004.
labor includes maternal treatment with glucocorticoids at ⱕ33 weeks gestation tocolysis at ⬍34 weeks and group B streptococcus prophylaxis at ⬍37 weeks gestation.2 Management of preterm amnion rupture at or beyond 340 weeks gestation is usually delivery and expectant management with maternal antimicrobial therapy at ⬍34 weeks gestation.2 Inherent risks with expectant management of amnion rupture include chorioamnionitis.
Tocolytic Use for Preterm Labor In many women, tocolytics may arrest contractions temporarily, but do not prevent preterm birth. In a meta-analysis of tocolytic therapy, Gyetvai and colleagues8 concluded that, although delivery may be delayed long enough for administration of corticosteroids (48 hours), treatment does not result in any improved perinatal outcomes. Berkman and col-
leagues9 reviewed 60 reports and concluded that tocolytic therapy can prolong gestation but that -mimetics were not better than other drugs and pose increased maternal danger. The infusion of -adrenergic agonists and less so other tocolytic agents has resulted in frequent and, at times, serious and fatal side effects (Table 2). Pulmonary edema is of special concern. Tocolysis was the third most common cause of acute respiratory distress and death in pregnant women during a 14-year period in Mississippi.10 The cause of pulmonary edema is multifactorial, and risk factors include tocolytic therapy, multifetal gestation, concurrent glucocorticoid therapy, tocolysis for more than 24 hours, and large intravenous crystalloid volume infusion. Data are not sufficient regarding maternal risks and or fetal/newborn benefits with the use of tocolysis with or without maternal glucocorticoid therapy in women with late preterm suspected spontaneous preterm labor.
Clinical Chorioamnionitis and Amnion Rupture Chorioamnionitis is increased in women with preterm amnion rupture.11 Among others, Ho and colleagues12 found prolonged membrane rupture associated with increased infectious morbidity. Before 34 weeks gestation and during expectant management of preterm amnion rupture, monitoring for sustained maternal or fetal tachycardia, for uterine tenderness, and for a malodorous vaginal discharge is warranted. If chorioamnionitis is diagnosed, prompt efforts to effect delivery, preferably vaginally, are initiated.
2000 Rank
1
198
Birth defects
142 97
2 Preterm/LBW 3
SIDS
6
RDS
108 130 62 69 25
0
1990 2000
50 100 150 200 Infant mortality per 100,000 live births
Figure 1 Selected leading causes of infant mortality and their rank orders for the United States, 1990 and 2000. (LBW, low birthweight; SIDS, sudden infant death syndrome; RDS, respiratory disease syndrome.) (Adapted from the National Center for Health Statistics, 2000; prepared by the March of Dimes Birth Defects Foundation, 2003.) (Color version of figure is available online.)
250
J.C. Hauth
100
14 12
11.6
11
10.6
Percent
10
7.6
8 6 4 2 0 1990
1995
2000
Very Preterm
Preterm
2010 Objective
Figure 2 Preterm and very preterm births, United States, 1990 to 2000. (Adapted from the National Center for Health Statistics, 2000; prepared by the March of Dimes Birth Defects Foundation, 2003.) (Color version of figure is available online.)
Preterm births per 100 live births* 8
7.6 7.4 7 7 6.6
6.7
7.1
7.1
1996
1997
7.2
6.8 6.6
6 1991
1992
1993
1994
1995
1997
1999
2000
Calendar year Figure 3 Rate of preterm birth, Canada (excluding Ontario), 1991 to 2000. (Data for Ontario were excluded because of data quality concerns.) ⴱExcludes live births with unknown gestational age. (Color version of figure is available online.)
Late spontaneous preterm labor
Percent of live births
20
101
17.6
15
12.9 10.7
11.4
10.2
11.9
10
5
0 White
Black
Native Asian or American Pacific Islander
Hispanic All races
Figure 4 Preterm births, defined as before 37 weeks, by maternal race/ethnicity for the United States in 2000 to 2002 average. (Adapted from National Center for Health Statistics, 2002; prepared by the March of Dimes Birth Defects Foundation, 2004.) (Color version of figure is available online.)
With chorioamnionitis, fetal and neonatal morbidity are substantively increased. Alexander and colleagues13 studied 1367 very-low-birth weight neonates delivered at Parkland Hospital. Approximately 7% were born to women with overt chorioamnionitis, and their outcomes were compared with newborns without clinical infection. Newborns in the infected group had a higher incidence of sepsis, respiratory distress syndrome, early-onset seizures, intraventricular hemorrhage, and periventricular leukomalacia. The investigators concluded that these very-low-birth weight neonates were vulnerable to neurological injury attributable to chorioamnionitis. There is other evidence that very small newborns exposed to intrauterine infection are at increased risk. Grether and Nelson14 reported that intrapartum maternal fever (⬎38°C) or the diagnosis of clinical or histologic chorioamnionitis were markedly increased in the mother’s of 48 children whose birthweight was ⬎2500 as compared with 367 controls. Yoon and colleagues15 found that intraamnionic infection in preterm neonates was related to increased rates of cerebral palsy at 3 years. Petrova and colleagues16 studied more than 11 million singleton live births from 1995 to 1997 who were in the database of the National Center for Health Statistics linked birth-infant death cohort. During labor, 1.6% of all women had fever, and this was a strong predictor of infection-related death in both term and preterm neonates. Bullard and associates,17 reported similar results. Ramsey and coworkers18 reported significantly increased neonatal major
morbidities in women with preterm amnion rupture and clinical chorioamnionitis at 27 to 29 weeks, at 30 to 34 weeks, and at 35 to 36 weeks gestation. Naef and colleagues19 randomized 120 women with amnion rupture at 34 to 37 weeks gestation to either delivery or expectant management. Outcomes were similar except for increased amnionitis (16% versus 2%) and neonatal sepsis (5% versus 0%) in women randomized to expectant management. Mercer and colleagues20 randomized the management Table 2 Potential Complications of Tocolytic Agents Beta-adrenergic Agents Pulmonary edema Hyperglycemia Hypokalemia Hypotension Arrhythmias Myocardial ischemia Magnesium Sulfate Respiratory depression Weakness diplopia Muscular paralysis Cardiac arrest Indomethacin Hepatitis Renal failure Nifedipine Transient hypotension
J.C. Hauth
102
Summary Points ●
● ●
●
Neonatal morbidity is significantly increased in infants born at late preterm gestations compared with term births. However, data are not sufficient to conclude that aggressive attempts to postpone preterm birth after 34 weeks of gestation would improve perinatal outcomes. There are no effective and safe tocolytic agents for women in labor at gestations after 34 weeks. In women with chorioamnionitis, premature amnion rupture, and in those with spontaneous labor after 34 weeks, timely delivery appears to most prudent at the present state of knowledge. Research is needed to develop best strategies to prevent preterm births at all gestations, especially at latepreterm gestations.
of women with amnion rupture and mature fetal pulmonary testing. They found no benefit and significantly increased amnionitis in women randomized to expectant management as compared with immediate delivery at 32 to 36 weeks gestation.
Summary Published data indicate that from 340 to 366 weeks gestation, neonatal mortality is similar to that at or beyond 37 weeks gestation, and that major and minor morbidity rates are slightly, but significantly increased. It is likely that most of the increased late preterm newborn morbidities are related to the reason for delivery, especially in women with late preterm amnion rupture and subclinical or overt chorioamnionitis. At present, we have no data to support that interventions to delay delivery of the late preterm fetus would lessen these morbidities. Thus, we have no basis on which to recommend a modification of the current obstetric management of spontaneous preterm labor or amnion rupture at 340 to 366 weeks gestation. Pragmatically, a prospective randomized management trial of women at late preterm gestation (340 to 366) and with spontaneous preterm labor or amnion rupture would require multi-institutional support to achieve the required study population. However, it is likely that a trial of obstetric management of preterm amnion rupture with expectant management or delivery or spontaneous preterm labor with tocolysis or no tocolysis at 300 or 320 to 336 weeks gestation can be accomplished and that either of these trials are medically justified. Indeed, the Maternal Fetal Medicine Units Network
has approved a tocolysis protocol from 240 to 316 weeks gestation that includes randomization to no tocolysis. Data from randomized trials similar to the above would also likely be of importance in consideration of obstetric management at 340 to 366 weeks gestation.
References 1. Mathews TJ, Menacker F, MacDorman MF: Infant mortality statistics from the 2002 period linked birth/infant death data set. National Vital Statistics Reports, Vol. 53, No. 10. Hyattsville, MD, National Center for Health Statistics, 2004 2. Cunningham GC, Leveno KJ, Bloom SL (eds): Williams Obstetrics (ed 22, chapter 36). New York, NY, McGraw-Hill, 2005, pp 855-880 3. National Center for Health Statistics, 2000; prepared by the March of Dimes Birth Defects Foundation, 2003 4. Health Canada: Canadian Perinatal Health Report, 2003. Ottawa, Minister of Public Works and Government Services Canada, 2003 5. National Center for Health Statistics. Final natality data. Available at: http://www.marchofdimes/com/peristats. Accessed July 8, 2005. 6. American College of Obstetricians and Gynecologists. Preterm Labor. Technical Bulletin No. 206, June 1995 7. DePalma RT, Leveno KJ, Kelly MA, et al: Birth weight threshold for postponing preterm birth. Am J Obstet Gynecol 167:1145, 1992 8. Gyetvai K, Hannah ME, Hodnett ED, et al: Tocolytics for preterm labor: a systematic review. Obstet Gynecol 94:869, 1999 9. Berkman ND, Thorp JM, Lohr KN, et al: Tocolytic treatment for the management of preterm labor: a review of the evidence. Am J Obstet Gynecol 188:1648, 2003 10. Perry KG, Martin RW, Blake PC, et al: Maternal outcome associated with adult respiratory distress syndrome. Am J Obstet Gynecol 174: 391, 1996 11. Lieman JM, Brumfield CG, Carlo W, et al: Preterm premature rupture of membranes: is there an optimal gestational age for delivery? Obstet Gynecol 105:12, 2005 12. Ho M, Ramsey P, Brumfield C, et al: Changes in maternal and neonatal infectious morbidity as latency increase after preterm premature rupture of membranes [abstract] Obstet Gynecol 101:41S, 2003 13. Alexander JM, Gilstrap LC, Cox SM, et al: Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol 91:725, 1998 14. Grether JK, Nelson KB: Maternal infection and cerebral palsy in fants of normal birth weight. JAMA 278:207, 1997 15. Yoon BH, Romero R, Park JS, et al: Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 182:675, 2000 16. Petrova A, Demissie K, Rhoads GG, et al: Association of maternal fever during labor with neonatal and infant morbidity and mortality. Obstet Gynecol 98:20, 2001 17. Bullard I, Vermillion S, Soper D: Clinical intraamniotic infection and the outcome for very low birth weight neonates. Am J Obstet Gynecol [abstract 48] 187:S73, 2002 18. Ramsey PS, Lieman JM, Brumfield CG, et al: Chorioamnionitis increases neonatal morbidity in pregnancies complicated by preterm premature rupture of membranes. Am J Obstet Gynecol 192:1162, 2005 19. Naef RW, Allbert JR, Ross EL, et al: Premature rupture of membranes at 34 to 37 weeks’ gestation: aggressive versus conservative management. Am J Obstet Gynecol 178:126, 1998 20. Mercer BM, Crocker LG, Boe NM, et al: Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: a randomized trial. Am J Obstet Gynecol 169:775, 1993
I
n a recent NICHD workshop on near-term pregnancy and infant care, the panel opined that the phrase near-term be replaced, and instead “late preterm” be used as the latter will convey that the infant is still preterm, not “almost term.” Arbitrary suggestion was made that late preterm be defined as those births between 34 0/7 through 36 6/7 weeks (239th to 259th day). In this manuscript, the phrase “late preterm” is used. In the United States in 2002, almost 28,000 infants died in their first year of life (Table 1).1 Preterm birth, which is defined as delivery before 37 completed weeks, occurred in approximately two-thirds of these deaths. Overall, infant mortality has continued to decline from 1990 to 2000, and the causes of infant mortality have also declined, except for those associated with preterm birth or low birth weight (Fig. 1).2 From 1990 to 2000, singleton preterm births in this country have increased (Fig. 2),3 which has primarily occurred in white non-Hispanic women (not shown). Preterm births have also increased in Canada from 1990 to 2000 (Fig. 3).4 Preterm births in this country remain highest in black women (Fig. 4).5 Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL. Address reprint requests to John C. Hauth, MD, University of Alabama at Birmingham, Department of Obstetrics and Gynecology, 619 19th Street South, 246 OHB, Birmingham, AL. E-mail: [email protected]
98
0146-0005/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.semperi.2006.02.008
Management of Late Preterm (340 to 366 Weeks Gestation) Spontaneous Labor or Amnion Rupture In 1995, the American College of Obstetricians and Gynecologists6 noted that the survival rate for newborns at 34 weeks is within 1% of those born at or beyond 37 weeks. In a secondary analysis of 5700 patients from three Maternal Fetal Medicine Units Network trials, the outcomes of death (0/416 versus 4/5284) or newborn hospital days (mean 3.75 versus 2.8 days) were similar at 35 to 36 weeks compared with 37 weeks or beyond (personal communications, Elizabeth Thom, PhD, Data Center Director for the Maternal-Fetal Medicine Units Network, NICHD, Bethesda, MD). The issue of late preterm newborn outcomes raises the question: Is there a birth weight or gestational age threshold after which attempts to delay delivery are unwarranted? DePalma and coworkers7 found that the threshold for neonatal mortality at Parkland Hospital was 1600 g, and it was 1900 g for neonatal morbidity. They concluded that aggressive attempts to prevent births for fetuses whose weight estimates exceeded 1900 g offered few apparent benefits. At Parkland Hospital, 1900 g is at the 10th percentile for 34 weeks and the 50th percentile for 32 weeks gestation.2 In general, obstetric management of spontaneous preterm
Late spontaneous preterm labor
99
Table 1 Infant Mortality in the United States in 2002
Total infants Gestational age at birth Less than 32 weeks 32–36 weeks 37–41 weeks 42 weeks or more Unknown
Live Births (%)
Infant Deaths (%)
4,021,825 (100)
27,970 (100)
77,877 (1.9) 402,972 (10) 3,231,562 (80) 268,096 (7) 41,318 (1)
14,515 (52) 3,692 (13) 8,001 (29) 824 (2.9) 937 (3.3)
Adapted from Mathews and colleagues, 2004.
labor includes maternal treatment with glucocorticoids at ⱕ33 weeks gestation tocolysis at ⬍34 weeks and group B streptococcus prophylaxis at ⬍37 weeks gestation.2 Management of preterm amnion rupture at or beyond 340 weeks gestation is usually delivery and expectant management with maternal antimicrobial therapy at ⬍34 weeks gestation.2 Inherent risks with expectant management of amnion rupture include chorioamnionitis.
Tocolytic Use for Preterm Labor In many women, tocolytics may arrest contractions temporarily, but do not prevent preterm birth. In a meta-analysis of tocolytic therapy, Gyetvai and colleagues8 concluded that, although delivery may be delayed long enough for administration of corticosteroids (48 hours), treatment does not result in any improved perinatal outcomes. Berkman and col-
leagues9 reviewed 60 reports and concluded that tocolytic therapy can prolong gestation but that -mimetics were not better than other drugs and pose increased maternal danger. The infusion of -adrenergic agonists and less so other tocolytic agents has resulted in frequent and, at times, serious and fatal side effects (Table 2). Pulmonary edema is of special concern. Tocolysis was the third most common cause of acute respiratory distress and death in pregnant women during a 14-year period in Mississippi.10 The cause of pulmonary edema is multifactorial, and risk factors include tocolytic therapy, multifetal gestation, concurrent glucocorticoid therapy, tocolysis for more than 24 hours, and large intravenous crystalloid volume infusion. Data are not sufficient regarding maternal risks and or fetal/newborn benefits with the use of tocolysis with or without maternal glucocorticoid therapy in women with late preterm suspected spontaneous preterm labor.
Clinical Chorioamnionitis and Amnion Rupture Chorioamnionitis is increased in women with preterm amnion rupture.11 Among others, Ho and colleagues12 found prolonged membrane rupture associated with increased infectious morbidity. Before 34 weeks gestation and during expectant management of preterm amnion rupture, monitoring for sustained maternal or fetal tachycardia, for uterine tenderness, and for a malodorous vaginal discharge is warranted. If chorioamnionitis is diagnosed, prompt efforts to effect delivery, preferably vaginally, are initiated.
2000 Rank
1
198
Birth defects
142 97
2 Preterm/LBW 3
SIDS
6
RDS
108 130 62 69 25
0
1990 2000
50 100 150 200 Infant mortality per 100,000 live births
Figure 1 Selected leading causes of infant mortality and their rank orders for the United States, 1990 and 2000. (LBW, low birthweight; SIDS, sudden infant death syndrome; RDS, respiratory disease syndrome.) (Adapted from the National Center for Health Statistics, 2000; prepared by the March of Dimes Birth Defects Foundation, 2003.) (Color version of figure is available online.)
250
J.C. Hauth
100
14 12
11.6
11
10.6
Percent
10
7.6
8 6 4 2 0 1990
1995
2000
Very Preterm
Preterm
2010 Objective
Figure 2 Preterm and very preterm births, United States, 1990 to 2000. (Adapted from the National Center for Health Statistics, 2000; prepared by the March of Dimes Birth Defects Foundation, 2003.) (Color version of figure is available online.)
Preterm births per 100 live births* 8
7.6 7.4 7 7 6.6
6.7
7.1
7.1
1996
1997
7.2
6.8 6.6
6 1991
1992
1993
1994
1995
1997
1999
2000
Calendar year Figure 3 Rate of preterm birth, Canada (excluding Ontario), 1991 to 2000. (Data for Ontario were excluded because of data quality concerns.) ⴱExcludes live births with unknown gestational age. (Color version of figure is available online.)
Late spontaneous preterm labor
Percent of live births
20
101
17.6
15
12.9 10.7
11.4
10.2
11.9
10
5
0 White
Black
Native Asian or American Pacific Islander
Hispanic All races
Figure 4 Preterm births, defined as before 37 weeks, by maternal race/ethnicity for the United States in 2000 to 2002 average. (Adapted from National Center for Health Statistics, 2002; prepared by the March of Dimes Birth Defects Foundation, 2004.) (Color version of figure is available online.)
With chorioamnionitis, fetal and neonatal morbidity are substantively increased. Alexander and colleagues13 studied 1367 very-low-birth weight neonates delivered at Parkland Hospital. Approximately 7% were born to women with overt chorioamnionitis, and their outcomes were compared with newborns without clinical infection. Newborns in the infected group had a higher incidence of sepsis, respiratory distress syndrome, early-onset seizures, intraventricular hemorrhage, and periventricular leukomalacia. The investigators concluded that these very-low-birth weight neonates were vulnerable to neurological injury attributable to chorioamnionitis. There is other evidence that very small newborns exposed to intrauterine infection are at increased risk. Grether and Nelson14 reported that intrapartum maternal fever (⬎38°C) or the diagnosis of clinical or histologic chorioamnionitis were markedly increased in the mother’s of 48 children whose birthweight was ⬎2500 as compared with 367 controls. Yoon and colleagues15 found that intraamnionic infection in preterm neonates was related to increased rates of cerebral palsy at 3 years. Petrova and colleagues16 studied more than 11 million singleton live births from 1995 to 1997 who were in the database of the National Center for Health Statistics linked birth-infant death cohort. During labor, 1.6% of all women had fever, and this was a strong predictor of infection-related death in both term and preterm neonates. Bullard and associates,17 reported similar results. Ramsey and coworkers18 reported significantly increased neonatal major
morbidities in women with preterm amnion rupture and clinical chorioamnionitis at 27 to 29 weeks, at 30 to 34 weeks, and at 35 to 36 weeks gestation. Naef and colleagues19 randomized 120 women with amnion rupture at 34 to 37 weeks gestation to either delivery or expectant management. Outcomes were similar except for increased amnionitis (16% versus 2%) and neonatal sepsis (5% versus 0%) in women randomized to expectant management. Mercer and colleagues20 randomized the management Table 2 Potential Complications of Tocolytic Agents Beta-adrenergic Agents Pulmonary edema Hyperglycemia Hypokalemia Hypotension Arrhythmias Myocardial ischemia Magnesium Sulfate Respiratory depression Weakness diplopia Muscular paralysis Cardiac arrest Indomethacin Hepatitis Renal failure Nifedipine Transient hypotension
J.C. Hauth
102
Summary Points ●
● ●
●
Neonatal morbidity is significantly increased in infants born at late preterm gestations compared with term births. However, data are not sufficient to conclude that aggressive attempts to postpone preterm birth after 34 weeks of gestation would improve perinatal outcomes. There are no effective and safe tocolytic agents for women in labor at gestations after 34 weeks. In women with chorioamnionitis, premature amnion rupture, and in those with spontaneous labor after 34 weeks, timely delivery appears to most prudent at the present state of knowledge. Research is needed to develop best strategies to prevent preterm births at all gestations, especially at latepreterm gestations.
of women with amnion rupture and mature fetal pulmonary testing. They found no benefit and significantly increased amnionitis in women randomized to expectant management as compared with immediate delivery at 32 to 36 weeks gestation.
Summary Published data indicate that from 340 to 366 weeks gestation, neonatal mortality is similar to that at or beyond 37 weeks gestation, and that major and minor morbidity rates are slightly, but significantly increased. It is likely that most of the increased late preterm newborn morbidities are related to the reason for delivery, especially in women with late preterm amnion rupture and subclinical or overt chorioamnionitis. At present, we have no data to support that interventions to delay delivery of the late preterm fetus would lessen these morbidities. Thus, we have no basis on which to recommend a modification of the current obstetric management of spontaneous preterm labor or amnion rupture at 340 to 366 weeks gestation. Pragmatically, a prospective randomized management trial of women at late preterm gestation (340 to 366) and with spontaneous preterm labor or amnion rupture would require multi-institutional support to achieve the required study population. However, it is likely that a trial of obstetric management of preterm amnion rupture with expectant management or delivery or spontaneous preterm labor with tocolysis or no tocolysis at 300 or 320 to 336 weeks gestation can be accomplished and that either of these trials are medically justified. Indeed, the Maternal Fetal Medicine Units Network
has approved a tocolysis protocol from 240 to 316 weeks gestation that includes randomization to no tocolysis. Data from randomized trials similar to the above would also likely be of importance in consideration of obstetric management at 340 to 366 weeks gestation.
References 1. Mathews TJ, Menacker F, MacDorman MF: Infant mortality statistics from the 2002 period linked birth/infant death data set. National Vital Statistics Reports, Vol. 53, No. 10. Hyattsville, MD, National Center for Health Statistics, 2004 2. Cunningham GC, Leveno KJ, Bloom SL (eds): Williams Obstetrics (ed 22, chapter 36). New York, NY, McGraw-Hill, 2005, pp 855-880 3. National Center for Health Statistics, 2000; prepared by the March of Dimes Birth Defects Foundation, 2003 4. Health Canada: Canadian Perinatal Health Report, 2003. Ottawa, Minister of Public Works and Government Services Canada, 2003 5. National Center for Health Statistics. Final natality data. Available at: http://www.marchofdimes/com/peristats. Accessed July 8, 2005. 6. American College of Obstetricians and Gynecologists. Preterm Labor. Technical Bulletin No. 206, June 1995 7. DePalma RT, Leveno KJ, Kelly MA, et al: Birth weight threshold for postponing preterm birth. Am J Obstet Gynecol 167:1145, 1992 8. Gyetvai K, Hannah ME, Hodnett ED, et al: Tocolytics for preterm labor: a systematic review. Obstet Gynecol 94:869, 1999 9. Berkman ND, Thorp JM, Lohr KN, et al: Tocolytic treatment for the management of preterm labor: a review of the evidence. Am J Obstet Gynecol 188:1648, 2003 10. Perry KG, Martin RW, Blake PC, et al: Maternal outcome associated with adult respiratory distress syndrome. Am J Obstet Gynecol 174: 391, 1996 11. Lieman JM, Brumfield CG, Carlo W, et al: Preterm premature rupture of membranes: is there an optimal gestational age for delivery? Obstet Gynecol 105:12, 2005 12. Ho M, Ramsey P, Brumfield C, et al: Changes in maternal and neonatal infectious morbidity as latency increase after preterm premature rupture of membranes [abstract] Obstet Gynecol 101:41S, 2003 13. Alexander JM, Gilstrap LC, Cox SM, et al: Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol 91:725, 1998 14. Grether JK, Nelson KB: Maternal infection and cerebral palsy in fants of normal birth weight. JAMA 278:207, 1997 15. Yoon BH, Romero R, Park JS, et al: Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol 182:675, 2000 16. Petrova A, Demissie K, Rhoads GG, et al: Association of maternal fever during labor with neonatal and infant morbidity and mortality. Obstet Gynecol 98:20, 2001 17. Bullard I, Vermillion S, Soper D: Clinical intraamniotic infection and the outcome for very low birth weight neonates. Am J Obstet Gynecol [abstract 48] 187:S73, 2002 18. Ramsey PS, Lieman JM, Brumfield CG, et al: Chorioamnionitis increases neonatal morbidity in pregnancies complicated by preterm premature rupture of membranes. Am J Obstet Gynecol 192:1162, 2005 19. Naef RW, Allbert JR, Ross EL, et al: Premature rupture of membranes at 34 to 37 weeks’ gestation: aggressive versus conservative management. Am J Obstet Gynecol 178:126, 1998 20. Mercer BM, Crocker LG, Boe NM, et al: Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: a randomized trial. Am J Obstet Gynecol 169:775, 1993