Small-for-Gestational-Age Infants and Risk of Fetal Death in Subsequent Pregnancies
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《新英格兰医药杂志》
One of the triumphs of modern obstetrics has been the dramatic reduction in late fetal mortality (defined as the rate of antepartum or intrapartum fetal death at 20 weeks of gestation or later) in the developed world during the second half of the 20th century. The reduction can be attributed to better access to vastly improved antepartum and intrapartum care; improved antepartum fetal surveillance; the virtual elimination of Rh isoimmunization; and the revolution in neonatal care that enabled obstetricians to deliver a fetus, particularly one remote from term, when its health was in jeopardy. The fetal mortality rate in the United States decreased from 18.4 per 1000 total births in 1950 to 6.7 per 1000 births in 2000. However, the pace of the decrease has slowed substantially during the past 20 years. The number of fetal deaths is now equal to the number of infant deaths in the United States. The psychological effects of a late fetal loss on a woman and her family can be as profound as those of the loss of a child.
In this issue of the Journal, Surkan et al. (pages 777–785) use data from the Swedish Medical Birth Register to demonstrate that women whose first infant was severely small for its gestational age had a significantly higher risk of late fetal death at 28 or more weeks of gestation in the subsequent pregnancy than women whose first infant was not small for gestational age. The increased risk was further amplified if the first delivery was also preterm. For example, as compared with women with a first delivery at term of an infant that was not small for gestational age, women who had a first delivery at term of an infant that was small for gestational age had twice the risk of subsequent fetal death. The odds ratio increased to 3.4 if the first delivery was also moderately preterm (occurring at 32 to 36 weeks of gestation) and to 5.0 if the first delivery occurred before 32 weeks of gestation. Surkan et al. defined an infant that was "small for gestational age" as one with a birth weight that was more than 2 SD below the mean at a given week of gestation (i.e., below the 2.5th percentile) — a cutoff that is considered to indicate a severely small-for-gestational-age infant by U.S. standards.
Women who have a small-for-gestational-age infant, a preterm delivery, or a fetal death tend to have these outcomes repeated in subsequent pregnancies. Surkan et al. further demonstrate that a history of delivering a small-for-gestational-age infant, particularly one delivered remote from term, is also associated with an increased risk of late fetal death in the succeeding pregnancy. This association presumably occurs because reduced fetal growth and fetal death often share underlying causes, such as congenital anomalies, placental defects, and maternal vascular disease. Abnormalities in placental implantation, vascularization, and function play a particularly important role. As the fetus grows larger with advancing gestation, the demands on the placenta increase. Poor growth in a fetus at less than 32 weeks' gestation suggests that, even remote from term, the maternal–placental unit has already exhausted its reserve. The data presented by Surkan et al. demonstrate that the conditions that cause this exhaustion tend to recur and can have manifold effects.
The broad categories of obstetrical conditions that are associated with fetal death are shown in the Figure. Fully one quarter of fetal deaths are unexplained even after careful pathological examination of the fetus and the placenta. When one considers that conditions such as placental abruption, hypertensive disorders, and idiopathic growth restriction themselves often have unknown causes, our lack of understanding of the underlying causes of late fetal death becomes even more apparent. In order to focus on this long-neglected area, the National Institute of Child Health and Human Development recently launched the Stillbirth Collaborative Research Network, a cooperative network of five sites in the United States that are using standardized protocols to investigate the scope and causes of stillbirth in a given population.
Figure. Causes of Fetal Death.
Data, for 61,957 pregnancies between 1978 and 1995, are from Fretts RC, Usher RH. Causes of fetal death in women of advanced maternal age. Obstet Gynecol 1997;89:40-5. Fetal death was considered to have been caused by abruption if there was antepartum bleeding or a retroplacental blood clot; by an anomaly if there was a potentially lethal anomaly; by infection if there was pathological evidence of infection in the fetus or the placenta; by diabetes if the mother was diabetic and the fetal death was otherwise unexplained; by hypertension if the mother was hypertensive and the fetal death was otherwise unexplained; by labor if there was unexplained intrapartum asphyxia; and by intrauterine growth restriction ("fetal malnutrition") if the death was asphyxial or unexplained and the weight of the fetus was below the third percentile; a fetal death was attributed to intrauterine growth restriction only if there was no other identified cause, except in the case of hypertension (if there was both intrauterine growth restriction and maternal hypertension, the death was attributed to the former condition). The "other" category included the following causes: a prolapsed cord, knots, placenta previa, hydrops, twin–twin transfusion, maternal disease, trauma, and Rh disease.
Unfortunately, many of the underlying causes of fetal death can neither be predicted accurately nor be prevented. Although recent literature suggests that Doppler velocimetry may help to prevent fetal death through the earlier detection and confirmation of fetal compromise in high-risk pregnancies, its low predictive value implies that many high-risk women would need to be monitored in order to prevent one fetal death. In addition, because abnormal findings on Doppler velocimetry are not specific for immediate fetal jeopardy, its use may lead to unnecessary early delivery, with its attendant risks. Once a compromised fetus is discovered and the compromise is deemed to be severe enough to place the fetus at high risk of imminent death, there are few specific therapeutic options other than delivery, which is undertaken after the administration of corticosteroids to the mother to promote fetal lung maturity if the fetus is remote from term.
Although being severely small for gestational age is generally considered to be pathologic, a weight above the cutoff point may not necessarily mean that the fetal growth is normal. Since fetuses have varying potential for growth, a given birth weight may be appropriate for one fetus but indicative of growth restriction for another. This variability may partially explain why, in the Swedish study, most of the women who had a fetal death (84 percent) had given birth at term to an infant that was not small for gestational age in the previous pregnancy. At the same time, pregnant women and their physicians should be reassured by the fact that even when the previous delivery occurred at less than 32 weeks of gestation and the infant was severely small for gestational age, the probability of a late fetal death in the current pregnancy was still less than 2 percent.
Source Information
From the Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Md.(Jun Zhang, Ph.D., M.D., a)
In this issue of the Journal, Surkan et al. (pages 777–785) use data from the Swedish Medical Birth Register to demonstrate that women whose first infant was severely small for its gestational age had a significantly higher risk of late fetal death at 28 or more weeks of gestation in the subsequent pregnancy than women whose first infant was not small for gestational age. The increased risk was further amplified if the first delivery was also preterm. For example, as compared with women with a first delivery at term of an infant that was not small for gestational age, women who had a first delivery at term of an infant that was small for gestational age had twice the risk of subsequent fetal death. The odds ratio increased to 3.4 if the first delivery was also moderately preterm (occurring at 32 to 36 weeks of gestation) and to 5.0 if the first delivery occurred before 32 weeks of gestation. Surkan et al. defined an infant that was "small for gestational age" as one with a birth weight that was more than 2 SD below the mean at a given week of gestation (i.e., below the 2.5th percentile) — a cutoff that is considered to indicate a severely small-for-gestational-age infant by U.S. standards.
Women who have a small-for-gestational-age infant, a preterm delivery, or a fetal death tend to have these outcomes repeated in subsequent pregnancies. Surkan et al. further demonstrate that a history of delivering a small-for-gestational-age infant, particularly one delivered remote from term, is also associated with an increased risk of late fetal death in the succeeding pregnancy. This association presumably occurs because reduced fetal growth and fetal death often share underlying causes, such as congenital anomalies, placental defects, and maternal vascular disease. Abnormalities in placental implantation, vascularization, and function play a particularly important role. As the fetus grows larger with advancing gestation, the demands on the placenta increase. Poor growth in a fetus at less than 32 weeks' gestation suggests that, even remote from term, the maternal–placental unit has already exhausted its reserve. The data presented by Surkan et al. demonstrate that the conditions that cause this exhaustion tend to recur and can have manifold effects.
The broad categories of obstetrical conditions that are associated with fetal death are shown in the Figure. Fully one quarter of fetal deaths are unexplained even after careful pathological examination of the fetus and the placenta. When one considers that conditions such as placental abruption, hypertensive disorders, and idiopathic growth restriction themselves often have unknown causes, our lack of understanding of the underlying causes of late fetal death becomes even more apparent. In order to focus on this long-neglected area, the National Institute of Child Health and Human Development recently launched the Stillbirth Collaborative Research Network, a cooperative network of five sites in the United States that are using standardized protocols to investigate the scope and causes of stillbirth in a given population.
Figure. Causes of Fetal Death.
Data, for 61,957 pregnancies between 1978 and 1995, are from Fretts RC, Usher RH. Causes of fetal death in women of advanced maternal age. Obstet Gynecol 1997;89:40-5. Fetal death was considered to have been caused by abruption if there was antepartum bleeding or a retroplacental blood clot; by an anomaly if there was a potentially lethal anomaly; by infection if there was pathological evidence of infection in the fetus or the placenta; by diabetes if the mother was diabetic and the fetal death was otherwise unexplained; by hypertension if the mother was hypertensive and the fetal death was otherwise unexplained; by labor if there was unexplained intrapartum asphyxia; and by intrauterine growth restriction ("fetal malnutrition") if the death was asphyxial or unexplained and the weight of the fetus was below the third percentile; a fetal death was attributed to intrauterine growth restriction only if there was no other identified cause, except in the case of hypertension (if there was both intrauterine growth restriction and maternal hypertension, the death was attributed to the former condition). The "other" category included the following causes: a prolapsed cord, knots, placenta previa, hydrops, twin–twin transfusion, maternal disease, trauma, and Rh disease.
Unfortunately, many of the underlying causes of fetal death can neither be predicted accurately nor be prevented. Although recent literature suggests that Doppler velocimetry may help to prevent fetal death through the earlier detection and confirmation of fetal compromise in high-risk pregnancies, its low predictive value implies that many high-risk women would need to be monitored in order to prevent one fetal death. In addition, because abnormal findings on Doppler velocimetry are not specific for immediate fetal jeopardy, its use may lead to unnecessary early delivery, with its attendant risks. Once a compromised fetus is discovered and the compromise is deemed to be severe enough to place the fetus at high risk of imminent death, there are few specific therapeutic options other than delivery, which is undertaken after the administration of corticosteroids to the mother to promote fetal lung maturity if the fetus is remote from term.
Although being severely small for gestational age is generally considered to be pathologic, a weight above the cutoff point may not necessarily mean that the fetal growth is normal. Since fetuses have varying potential for growth, a given birth weight may be appropriate for one fetus but indicative of growth restriction for another. This variability may partially explain why, in the Swedish study, most of the women who had a fetal death (84 percent) had given birth at term to an infant that was not small for gestational age in the previous pregnancy. At the same time, pregnant women and their physicians should be reassured by the fact that even when the previous delivery occurred at less than 32 weeks of gestation and the infant was severely small for gestational age, the probability of a late fetal death in the current pregnancy was still less than 2 percent.
Source Information
From the Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Md.(Jun Zhang, Ph.D., M.D., a)