Placental Abruption and Perinatal Mortality in the United States

Cande V. Ananth1 and Allen J. Wilcox2

1 Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ.
2 Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Placental abruption is an uncommon obstetric complication associated with high perinatal mortality rates. The authors explored the associations of abruption with fetal growth restriction, preterm delivery, and perinatal survival. The study was based on 7,508,655 singleton births delivered in 1995 and 1996 in the United States. Abruption was recorded in 6.5 per 1,000 births. Perinatal mortality was 119 per 1,000 births with abruption compared with 8.2 per 1,000 among all other births. The high mortality with abruption was due, in part, to its strong association with preterm delivery; 55% of the excess perinatal deaths with abruption were due to early delivery. Furthermore, babies in the lowest centile of weight (<1% adjusted for gestational age) were almost nine times as likely to be born with abruption than those in the heaviest (>=90%) birth weight centiles. This relative risk progressively declined with higher birth weight centiles. After controlling for fetal growth restriction and early delivery, the high risk of perinatal death associated with abruption persisted. Even babies born at 40 weeks of gestation and birth weight of 3,500–3,999 g (where mortality was lowest) had a 25-fold higher mortality with abruption. The link between fetal growth restriction and abruption suggests that the origins of abruption lie at least in midpregnancy and perhaps even earlier.

abruptio placentae; birth weight; fetal growth retardation; infant mortality


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In normal pregnancies, placental separation occurs immediately after birth, while in pregnancies complicated by abruption, the placenta begins to detach before birth (1Go). This premature detachment commonly produces pain and vaginal bleeding, the clinical hallmarks of placental abruption, and occurs in about 0.6–1.0 percent of pregnancies (2Go). Maternal risks associated with abruption include massive blood loss, disseminated intravascular coagulopathy, renal failure, and, less commonly, maternal death (1Go, 3Go). Abruption is potentially disastrous to the fetus as well, with perinatal mortality as high as 60 percent (4GoGoGo–7Go). Surprisingly little is known about the underlying etiology of abruption. We present recent data from the United States to explore the associations of abruption with fetal growth restriction, preterm delivery, and perinatal survival.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Analysis was based on 7,508,655 singleton US births for 1995 and 1996 assembled by the National Center for Health Statistics and derived from the linked birth/infant death data sets. Perinatal mortality was defined to include stillbirths (occurring after 20 weeks of gestation) and neonatal deaths (occurring up to 28 days after birth). Abruption was defined as the complete or partial separation of the placenta prior to the delivery of the fetus. The diagnosis of abruption is based on clinical presentation and examination of the delivered placenta by the attendant at delivery. It is recorded on current US birth certificates using a check-box (yes or no) (8Go), but grades and severity of abruption are not documented. The diagnosis of abruption on vital statistics is subject to potential underascertainment (9Go), and information on some important risk factors and confounders of abruption is poorly recorded or unavailable on vital statistics data.

For 95 percent of births, the gestational age assignment on vital records was based on the date of the last menstrual period. A clinical estimate was used when the date of the last menstrual period was missing or when the reported birth weight was inconsistent with last menstrual period-based gestational age (10Go). Missing data on the month of the last menstrual period were imputed (11Go). Growth restriction was assessed in centiles of weight (<1, 1–2, 3–4, 5–9, and thereafter in 10-centile increments derived from the complete US data set) within strata of gestational age. Babies at or above the 90th centile (who had the lowest risk of abruption) served as the comparison group.

One reason that babies born with abruption are at higher risk of mortality is that they are delivered prematurely. In order to estimate the portion of abruption mortality that might be explained by early delivery, we performed direct standardization by gestational age. Specifically, we applied the gestational age-specific mortality rates of nonabruption births to the gestational age distribution of abruption births. This provided an estimate of total mortality for nonabruption births had they had the same gestational age distribution of abruption births. The increase in mortality due to the change in the gestational age distribution was divided by the total excess mortality observed among abruption births to estimate the fraction of deaths attributable to the excess of preterm births among women with abruption. In the same fashion, we assessed the contribution of growth restriction to abruption mortality by applying weight-specific mortality rates to the birth weight distributions of abruption and nonabruption births. In the case of birth weight, the analysis was further stratified by gestational age to remove the effects of early delivery from the effects of growth restriction.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Placental abruption was recorded in 46,731 pregnancies, an incidence of 6.2 per 1,000 pregnancies (table 1). Pregnancies diagnosed with abruption were far more likely to end in preterm delivery; 51 percent ended before 37 completed weeks compared with 10.1 percent of all other births (figure 1). This substantial increase in early delivery resulted in more small babies. Among babies born with abruption, 46 percent weighed less than 2,500 g compared with 6.4 percent among all other pregnancies.


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TABLE 1. Weight-specific perinatal mortality rates in relation to placental abruption, United States, 1995 and 1996

 


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FIGURE 1. Distribution of gestational age at delivery for pregnancies with and without placental abruption, United States, 1995 and 1996.

 
The smaller size of babies born with abruption, however, was not due simply to preterm delivery. Babies born with abruption were also smaller at most gestational ages (figure 2). Since fetal growth restriction precedes delivery, the risk of abruption at delivery can be expressed as a function of fetal size. The relative risk for abruption was highest among babies in the lowest 1 percent of weight at each gestational age and progressively declined with increasing weight centiles (table 2).



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FIGURE 2. Distributions of mean birth weight for pregnancies with and without placental abruption, United States, 1995 and 1996.

 

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TABLE 2. Relative risk for placental abruption in relation to centiles* of birth weight, United States, 1995 and 1996

 
The perinatal mortality rate associated with abruption was 119.2 per 1,000 births or nearly 12 percent. This rate was nearly 15 times the mortality among other pregnancies (8.2 deaths per 1,000 births) (table 1). At the optimal gestational age of 40 weeks (when overall mortality was lowest), perinatal mortality was 19-fold greater for abruption than for nonabruption births (34.6 vs. 1.8 per 1,000 births, respectively) (figure 3). Mortality with abruption was more likely to occur before delivery than after (relative risk for stillbirth was 18 compared with 10 for neonatal death).



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FIGURE 3. Gestational age-specific perinatal mortality rates (plotted on a logarithmic scale) for pregnancies with and without placental abruption, United States, 1995 and 1996.

 
In order to separate fetal growth restriction from early delivery, we examined term babies alone (>=37 weeks). Both weight distributions were strikingly Gaussian (figure 4) but with a downward shift of the abruption births by about 250 g. (This shift was also seen at preterm gestational ages down to 28 weeks.) Given this generalized growth restriction with abruption, there was nonetheless a high risk of mortality among babies of normal fetal size (figure 5). The best survival (with or without abruption) was among babies weighing 3,500–3,999 g. Even among term babies with this optimal weight, abruption was associated with a 25-fold mortality risk.



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FIGURE 4. Distribution of birth weight for term pregnancies (>=37 weeks) with and without placental abruption, United States, 1995 and 1996.

 


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FIGURE 5. Birth weight-specific perinatal mortality rates (plotted on a logarithmic scale) in term pregnancies (>=37 weeks) with and without placental abruption, United States, 1995 and 1996.

 
The strong association of abruption with preterm delivery implies that some of the mortality associated with abruption may simply be due to the delivery of an immature fetus. Fifty-five percent of the excess perinatal deaths linked with an abruption delivery were due to early gestational age alone. In contrast, the small fetal size at birth contributed only 9 percent to the perinatal mortality associated with abruption (despite the strong predictive value of poor fetal growth as a risk factor for abruption).


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Placental abruption is an obstetric complication that poses severe hazards to the pregnant woman and her fetus. Although uncommon, abruption accounts for 12 percent of all perinatal deaths. Several studies have reported increased frequency of this condition among older women, multiparous women, smokers, illicit substance users, and those with hypertensive disorders. However, most cases of abruption occur with no known cause.

The incidence of abruption may be increasing with time. Recorded abruptions in the United States increased 29 percent between 1979 and 1987 (8.2–11.5 per 1,000 births) (12Go). Similar data from Norway (13Go) indicated a 31 percent increase in the incidence between 1967–1971 and 1987–1991 (5.7–8.3 per 1,000 births). At least some of this increase may reflect improvements in ultrasound techniques to detect mild or partial abruption. The prevalence of some risk factors for abruption including cocaine and drug use (7Go, 14Go) increased between 1980 and 1987 (15Go), which may also have contributed to an increased incidence. Multiple births due to assisted reproductive methods have been increasing over time, with multiple fetuses raising the risk for abruption (1Go, 5Go).

In searching for the causes of abruption, clinical studies have sometimes focused on events near the time of delivery, such as trauma (1Go). While abruption often appears to be an acute event, its association with poor fetal growth suggests that the origins of abruption may lie at least in midpregnancy, perhaps extending back to the earliest stages of pregnancy. The association with fetal growth restriction is so strong that growth restriction in itself can serve as a marker for abruption risk (table 2). The chronic processes underlying abruption may also contribute to the risk of preterm delivery, which accounts for the majority of excess mortality that accompanies abruption.

The diagnosis of abruption on vital statistics data is subject to misclassification (9Go) and is recorded with knowledge of the outcome of pregnancy. A pregnancy with severe hemorrhage may be more likely to be recorded as an abruption if the baby dies. The present analysis also does not take into account some known or suspected risk factors for abruption including smoking, crack use, chronic hypertension, preeclampsia, chorioamnionitis, and prolonged rupture of membranes. These factors are reported poorly or not at all on vital statistics. Some of these factors might contribute to the results noted here, but it is unlikely that these factors could explain more than a small portion of the powerful associations with fetal growth and preterm delivery.

Pathologic studies suggest that abruption is associated with abnormal placental vasculature, thrombosis, and reduced placental perfusion. Genetic variations may predispose to these problems. A high prevalence of mutations in the genes that encode or regulate factor V Leiden, prothrombin, methylenetetrahydrofolate reductase, and homocysteine has been seen among women with abruption compared with other uncomplicated pregnancies (16Go, 17Go). These genetic factors may also be contributing to the fetal growth restriction and preterm delivery associated with abruption, perhaps through compromise of placental function.

Since abruption is apparently a disease of the placenta, aspects of placental development (even preconception factors) merit attention. Placental growth is primarily under the control of fetal genes inherited from the father (18Go). Imprinted paternal alleles regulate the formation of the placenta and membranes surrounding the embryo, whereas the development of the embryo itself requires contribution from the maternally derived alleles. A search for genetic susceptibility to abruption should include a consideration for paternally imprinted genes.


    ACKNOWLEDGMENTS
 
At the time of this study, Dr. Ananth was supported, in part, through grant 029553 from the Robert Wood Johnson Foundation, New Jersey, awarded to the Center for Perinatal Health Initiatives.

The authors are indebted to Drs. Kitaw Demissie, Lorentz Irgens, Robert Knuppel, Dawn Misra, George Rhoads, Andrew Rowland, Amy Sayle, John Smulian, John Thorp, Anthony Vintzileos, and Jun Zhang for their comments, criticisms, and insightful discussions. They are also grateful to Susan Fosbre for secretarial assistance.

This paper was presented at the Society for Pediatric and Perinatal Epidemiologic Research meeting in Baltimore, Maryland, June 1999.


    NOTES
 
Correspondence to Dr. Cande V. Ananth, Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901-1977 (e-mail: ananthcv{at}EPI.UMDNJ.EDU).


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication January 18, 2000. Accepted for publication June 12, 2000.