Volume 166 :-.Iumher I , Part I
aggravate impaired vascular endothelium, cau~ing va so~pasms. It is interesting to note that the first child had seizures after platelet transfusion and now has a lea rning disability. Of note, an uitrasonographic exammation of the current fetus had shown a - 1.9 SD in the head circumference at 29 weeks, but follow-up scan showed a les~ significant lag. Although unproved , it is also possible that some earlier in utem event, i.e ., hemorrhage, had taken place be fore therapy was initiated. There is still much unknown regarding the pathophysiology of this disease and the effects of therapy, ~uch as exogenous immunoglobulins and platelet transfusions, on the long-term outcome of these infant~. Platelet transfusiom would be the most reliable way to elevate the platelet count. However, they need to be performed with caution. Immunoglobulin treatment
Allolmmune thrombocytopenia and systemic disease
may be a better alternative, as our patient's platelet count was 90,OOO/mm-' with weekly intravenous doses of immune globulin. Although studies of long-term immune globulin therapy in patients with immunodeficiency syndrome have failed to reveal any significant risks to date, the long-term consequences of maternalfetal intravenous immune globulin therapy have yet to be defined. REFERENCES I. Bussel J p, Berkowitz RL, McFarland JG, Lynch L, Chitkara U. Antenatal treatment of neonatal alloimmune thrombocvtopema. N EnglJ Med 1988;3 19: 1374-8. 2. Glltay JC, Brinkman HM, Von Dem Borne A, Van Movrik JA. Expres;ion of the alloantigen Zw' (or PI''') on human vascu lar smooth muscle cells and foreskin fibroblasts: a study on normal mdividuals and a patient with Glanzmann'; thrombasthenia. Blood 1989; 74: 965-70.
Spontaneous abortion and subsequent adverse birth outcomes David H. Thorn, MD, PhD, Lorene M. Nelson, PhD, and Thomas L. Vaughan, MD, MPH Seattle, Wa.lhlllgtOIl OBJECTIVE: Our purpose was to evaluate the association between spontaneous abortion and subsequent adverse birth outcomes. STUDY DESIGN: Washington State birth certificate records for 1984 to 1987 were used to examine the association between spontaneous abortion and adverse outcomes in the subsequent live birth. Adverse birth outcomes were examined for women with one spontaneous abortion before the Index pregnancy (n = 2146) and for women with three or more prior spontaneous abortions and no other prior pregnancies (n = 638); compared with women with no prior spontaneous abortions (n = 3099) . Logistic regression was used to estimate the relative risk associated with prior spontaneous abortion of each adverse outcome. RESULTS: Women with three or more prior spontaneous abortions were at higher risk for delivery at < 37 weeks' gestation (relative risk 1.5, 95% confidence interval 1.1 to 2 .1), placenta previa (relative risk 6.0, 95% confidence interval 1.6 to 22.2), haVing membranes ruptured > 24 hours (relative risk 1.8, 95% confidence interval 1.2 to 2.9), breech presentation (relative risk 2.4, 95% confidence Interval 1.6 to 3.6), and having an infant With a congel1ltal malformation (relative risk 1.8, 95% confidence Interval 1.1 to 3.0) . CONCLUSION: These findings suggest that common causes may underlie recurrent spontaneous abortion and certain adverse birth outcomes. They may also help guide clinical management of pregnancies in women with a history of recurrent spontaneous abortions. (AM J OSSTET GVNECOL 1992;166:111-6.)
Key words: Spontaneous abortion, preterm delivery, congenital malformation
F,om the Department of Epldemwlogy, SC-36, School of Public H ealth and Cummumt)' MediCine, UntverSllyoj Ww/unglon. Supported !II part by Untted State I Publlc H ealth SennCf grant AI21885 alld National Institutes uf H ealth trallllng grant 1 F32 HL-
08194-01.
Received fur pubhcatlOll January 9, 199 1, revl;ed Apnl 25, 1991; a(repted Ma.v 28,1991. Reprmt requests: DaVid H. Thom, MD, PhD, Depaltment of EpldemlOiog)', SC-36, UllIverslly o!Wmlllltgton, Seattle, WA 98195.
611/31301
Spontaneous abortion before the 20th week of gestational age is reported to occur in 15% to 20% of recognized pregnancies." " Approximately 1 % of women experience three or more spontaneous abortions before the first live birth.' In spite of the frequency of this problem, the subsequent birth outcomes of women with prior spontaneous abortions have not been extensively studied. Previous studies have suggested 111
112 Thorn, Nelson, and Vaughan
that women with a history of spontaneous abortion are at increased risk for preterm delivery,'-' placenta previa,6 and having an infant with intrauterine growth retardation (IUGRf· 8 or congenital malformation .g • 10 These studies have been limited by small sample sizesS-9 and a lack of consideration of possible confounding variables.' -10 The current study sought to examine the incidence of adverse birth outcomes among women with one prior spontaneous abortion and women with three or more prior spontaneous abortions, compared with the incidence among women with no prior spontaneous abortions. We used a large data base that includes information on maternal age, parity, gravidity, smoking status during pregnancy, race, and prenatal care. Material and methods
Data were taken from Washington State birth certificate records for the years 1984 through 1987. Obstetric ward clerks are generally responsible for abstracting information from the medical chart into the birth certificate form. Handbooks describing procedures for birth certificate completion are provided by the State of Washington. Additional instruction is provided by each hospital. A state field representative makes periodic visits to review completion procedures. Most adverse birth outcomes are represented by a checklist format. The completeness of reporting birth com plications on the Washington State birth certificate was the subject of a recent stud y. II With the checklist format, reporting was 80% or better for most birth complications (e.g., preeclampsia, breech presentation, and cesarean section). Congenital malformations were reported less frequently, as judged by hospital discharge diagnoses. Reporting rates for congenital malformations ranged from 32% for polydactyly to 57% for cleft lip and palate. The birth certificate defines spontaneous abortion as fetal loss occurring before 20 weeks' gestation; firstand second-trimester spontaneous abortions are not differentiated . Two "exposure" groups were constructed. The group of women with one prior spontaneous abortion consisted of all women having a live singleton birth in 1987 who had one prior spontaneous abortion and no other prior pregnancies. A second group of women with recurrent spontaneous abortions consisted of all women having a live singleton birth in 1984 to 1987, who had three or more prior spontaenous abortions and no other prior pregnancies. Births ending in fetal death were not included because of their small numbers «0.7 % of all pregnancies >20 weeks' gestation). The unexposed comparison group consisted of 3099 randomly selected women having a live singleton birth in 1987 with no pregnancies prior to the index pregnancy. Use of this primigravid group thus controlled for the potential confounding effects of parity.
January 1992 Am J Obstet Gynecol
The adverse birth outcomes of interest were: low birth weight «2500 gm), IUGR, preterm birth «37 weeks' gestational age, calculated from the first day of the last menstrual period), congenital malformations, prolonged rupture of membranes (>24 hours), breech presentation, low I-minute «6) and 5-minute «7) Apgar scores, abruptio placentae, placenta previa, and preeclampsia. The definition of a low Apgar score was chosen to allow comparison of the results with those of a previous study. 10 Intrauterine growth retardation was defined as birth weight < 10th percentile for gestational age as determined by last menstrual period. The 10th percentile of birth weight by menstrual weeks' gestation was taken from a widely cited nomogram and table of birth weights. 12 Maximum likelihood logistic regression l3 was used to estimate the relative risk associated with prior spontaneous abortion for each adverse birth outcome while controlling for confounding variables. Results
The characteristics of women with one prior spontaneous abortion, three or more prior spontaneous abortions, and the primagravid comparison group are shown in Table I. Women with three or more spontaneous abortions were older and more likely to smoke, compared with the primigravid group. Women with one prior spontaneous abortion were intermediate for these characteristics. The differences in the proportion of smokers among women with one prior spontaneous abortion and women with three or more prior spontaneous abortions, compared with the proportion among women with no prior spontaneous abortions, were highly significant (p < 0.001) after controlling for age. The differences by maternal race, marital status, urban residence (living in an incorporated area), and prenatal care were relatively small. Information was missing on < 3% of the outcome variables examined, except for gestational age, congenital malformations, and preeclampsia. Gestational age was missing for 7% of the group with one prior spontaneous abortion, 9% of the group with the three or more prior spontaneous abortions, and 9% of the primigravid group. The totals missing for those with malformations were 14%, 13%, and 16%, respectively. All three groups had 10% of the preeclampsia data mlssmg. The frequencies of adverse outcomes by group are prese nted in Table II. Differences were found for low birth weight, IUGR, preterm delivery, congenital malformation, placenta previa, prolonged rupture of membranes, breech presentation, I-minute and 5-minute Apgar scores, and preeclampsia, but not for abruptio placentae. Table III displays the relative risk estimates with 95% confidence intervals for the adverse outcomes in Table
\'"llIllle
Spontaneous abortion and adverse birth outcomes
166
:'>lumber I. Pan 1
113
Table I. Characteristics of women during their index pregnancy by number of prior spontaneous abortions \romen 11'1/11 Ollt'
pI/or prepwllC/es (II )099)
.IPUIl/fllll'OIlI abl!l//(II/ (II 2J.16)
!'foll/ell WI/I! till 1'1' or mUIt' pru!l ;pull/a II t'o II I abor/w//I (II 638)
2:1.9 2Vl :H.H 2(i.:1 lti.O 19.7 H7.fi 72,4 51.6 77.fi
25.0 15.5 :HJi 2H !J 20.9 2H.I H9.5 76.2 50.2 HI.:I
26.3 10. 3 30.6 30.6 2H.5 36.5 91.2 75.9 54.2 79.7
H'0111f'1I wi/h CI!alllc/n u/lc
I!I WI
110
=
Maternal age Mean (yr) < 20 yr ('ic) 20-24 yr (o/c) 25-29 vr (o/c) > 30 IT ('iO Smoker ('1
aggravate impaired vascular endothelium, cau~ing va so~pasms. It is interesting to note that the first child had seizures after platelet transfusion and now has a lea rning disability. Of note, an uitrasonographic exammation of the current fetus had shown a - 1.9 SD in the head circumference at 29 weeks, but follow-up scan showed a les~ significant lag. Although unproved , it is also possible that some earlier in utem event, i.e ., hemorrhage, had taken place be fore therapy was initiated. There is still much unknown regarding the pathophysiology of this disease and the effects of therapy, ~uch as exogenous immunoglobulins and platelet transfusions, on the long-term outcome of these infant~. Platelet transfusiom would be the most reliable way to elevate the platelet count. However, they need to be performed with caution. Immunoglobulin treatment
Allolmmune thrombocytopenia and systemic disease
may be a better alternative, as our patient's platelet count was 90,OOO/mm-' with weekly intravenous doses of immune globulin. Although studies of long-term immune globulin therapy in patients with immunodeficiency syndrome have failed to reveal any significant risks to date, the long-term consequences of maternalfetal intravenous immune globulin therapy have yet to be defined. REFERENCES I. Bussel J p, Berkowitz RL, McFarland JG, Lynch L, Chitkara U. Antenatal treatment of neonatal alloimmune thrombocvtopema. N EnglJ Med 1988;3 19: 1374-8. 2. Glltay JC, Brinkman HM, Von Dem Borne A, Van Movrik JA. Expres;ion of the alloantigen Zw' (or PI''') on human vascu lar smooth muscle cells and foreskin fibroblasts: a study on normal mdividuals and a patient with Glanzmann'; thrombasthenia. Blood 1989; 74: 965-70.
Spontaneous abortion and subsequent adverse birth outcomes David H. Thorn, MD, PhD, Lorene M. Nelson, PhD, and Thomas L. Vaughan, MD, MPH Seattle, Wa.lhlllgtOIl OBJECTIVE: Our purpose was to evaluate the association between spontaneous abortion and subsequent adverse birth outcomes. STUDY DESIGN: Washington State birth certificate records for 1984 to 1987 were used to examine the association between spontaneous abortion and adverse outcomes in the subsequent live birth. Adverse birth outcomes were examined for women with one spontaneous abortion before the Index pregnancy (n = 2146) and for women with three or more prior spontaneous abortions and no other prior pregnancies (n = 638); compared with women with no prior spontaneous abortions (n = 3099) . Logistic regression was used to estimate the relative risk associated with prior spontaneous abortion of each adverse outcome. RESULTS: Women with three or more prior spontaneous abortions were at higher risk for delivery at < 37 weeks' gestation (relative risk 1.5, 95% confidence interval 1.1 to 2 .1), placenta previa (relative risk 6.0, 95% confidence interval 1.6 to 22.2), haVing membranes ruptured > 24 hours (relative risk 1.8, 95% confidence interval 1.2 to 2.9), breech presentation (relative risk 2.4, 95% confidence Interval 1.6 to 3.6), and having an infant With a congel1ltal malformation (relative risk 1.8, 95% confidence Interval 1.1 to 3.0) . CONCLUSION: These findings suggest that common causes may underlie recurrent spontaneous abortion and certain adverse birth outcomes. They may also help guide clinical management of pregnancies in women with a history of recurrent spontaneous abortions. (AM J OSSTET GVNECOL 1992;166:111-6.)
Key words: Spontaneous abortion, preterm delivery, congenital malformation
F,om the Department of Epldemwlogy, SC-36, School of Public H ealth and Cummumt)' MediCine, UntverSllyoj Ww/unglon. Supported !II part by Untted State I Publlc H ealth SennCf grant AI21885 alld National Institutes uf H ealth trallllng grant 1 F32 HL-
08194-01.
Received fur pubhcatlOll January 9, 199 1, revl;ed Apnl 25, 1991; a(repted Ma.v 28,1991. Reprmt requests: DaVid H. Thom, MD, PhD, Depaltment of EpldemlOiog)', SC-36, UllIverslly o!Wmlllltgton, Seattle, WA 98195.
611/31301
Spontaneous abortion before the 20th week of gestational age is reported to occur in 15% to 20% of recognized pregnancies." " Approximately 1 % of women experience three or more spontaneous abortions before the first live birth.' In spite of the frequency of this problem, the subsequent birth outcomes of women with prior spontaneous abortions have not been extensively studied. Previous studies have suggested 111
112 Thorn, Nelson, and Vaughan
that women with a history of spontaneous abortion are at increased risk for preterm delivery,'-' placenta previa,6 and having an infant with intrauterine growth retardation (IUGRf· 8 or congenital malformation .g • 10 These studies have been limited by small sample sizesS-9 and a lack of consideration of possible confounding variables.' -10 The current study sought to examine the incidence of adverse birth outcomes among women with one prior spontaneous abortion and women with three or more prior spontaneous abortions, compared with the incidence among women with no prior spontaneous abortions. We used a large data base that includes information on maternal age, parity, gravidity, smoking status during pregnancy, race, and prenatal care. Material and methods
Data were taken from Washington State birth certificate records for the years 1984 through 1987. Obstetric ward clerks are generally responsible for abstracting information from the medical chart into the birth certificate form. Handbooks describing procedures for birth certificate completion are provided by the State of Washington. Additional instruction is provided by each hospital. A state field representative makes periodic visits to review completion procedures. Most adverse birth outcomes are represented by a checklist format. The completeness of reporting birth com plications on the Washington State birth certificate was the subject of a recent stud y. II With the checklist format, reporting was 80% or better for most birth complications (e.g., preeclampsia, breech presentation, and cesarean section). Congenital malformations were reported less frequently, as judged by hospital discharge diagnoses. Reporting rates for congenital malformations ranged from 32% for polydactyly to 57% for cleft lip and palate. The birth certificate defines spontaneous abortion as fetal loss occurring before 20 weeks' gestation; firstand second-trimester spontaneous abortions are not differentiated . Two "exposure" groups were constructed. The group of women with one prior spontaneous abortion consisted of all women having a live singleton birth in 1987 who had one prior spontaneous abortion and no other prior pregnancies. A second group of women with recurrent spontaneous abortions consisted of all women having a live singleton birth in 1984 to 1987, who had three or more prior spontaenous abortions and no other prior pregnancies. Births ending in fetal death were not included because of their small numbers «0.7 % of all pregnancies >20 weeks' gestation). The unexposed comparison group consisted of 3099 randomly selected women having a live singleton birth in 1987 with no pregnancies prior to the index pregnancy. Use of this primigravid group thus controlled for the potential confounding effects of parity.
January 1992 Am J Obstet Gynecol
The adverse birth outcomes of interest were: low birth weight «2500 gm), IUGR, preterm birth «37 weeks' gestational age, calculated from the first day of the last menstrual period), congenital malformations, prolonged rupture of membranes (>24 hours), breech presentation, low I-minute «6) and 5-minute «7) Apgar scores, abruptio placentae, placenta previa, and preeclampsia. The definition of a low Apgar score was chosen to allow comparison of the results with those of a previous study. 10 Intrauterine growth retardation was defined as birth weight < 10th percentile for gestational age as determined by last menstrual period. The 10th percentile of birth weight by menstrual weeks' gestation was taken from a widely cited nomogram and table of birth weights. 12 Maximum likelihood logistic regression l3 was used to estimate the relative risk associated with prior spontaneous abortion for each adverse birth outcome while controlling for confounding variables. Results
The characteristics of women with one prior spontaneous abortion, three or more prior spontaneous abortions, and the primagravid comparison group are shown in Table I. Women with three or more spontaneous abortions were older and more likely to smoke, compared with the primigravid group. Women with one prior spontaneous abortion were intermediate for these characteristics. The differences in the proportion of smokers among women with one prior spontaneous abortion and women with three or more prior spontaneous abortions, compared with the proportion among women with no prior spontaneous abortions, were highly significant (p < 0.001) after controlling for age. The differences by maternal race, marital status, urban residence (living in an incorporated area), and prenatal care were relatively small. Information was missing on < 3% of the outcome variables examined, except for gestational age, congenital malformations, and preeclampsia. Gestational age was missing for 7% of the group with one prior spontaneous abortion, 9% of the group with the three or more prior spontaneous abortions, and 9% of the primigravid group. The totals missing for those with malformations were 14%, 13%, and 16%, respectively. All three groups had 10% of the preeclampsia data mlssmg. The frequencies of adverse outcomes by group are prese nted in Table II. Differences were found for low birth weight, IUGR, preterm delivery, congenital malformation, placenta previa, prolonged rupture of membranes, breech presentation, I-minute and 5-minute Apgar scores, and preeclampsia, but not for abruptio placentae. Table III displays the relative risk estimates with 95% confidence intervals for the adverse outcomes in Table
\'"llIllle
Spontaneous abortion and adverse birth outcomes
166
:'>lumber I. Pan 1
113
Table I. Characteristics of women during their index pregnancy by number of prior spontaneous abortions \romen 11'1/11 Ollt'
pI/or prepwllC/es (II )099)
.IPUIl/fllll'OIlI abl!l//(II/ (II 2J.16)
!'foll/ell WI/I! till 1'1' or mUIt' pru!l ;pull/a II t'o II I abor/w//I (II 638)
2:1.9 2Vl :H.H 2(i.:1 lti.O 19.7 H7.fi 72,4 51.6 77.fi
25.0 15.5 :HJi 2H !J 20.9 2H.I H9.5 76.2 50.2 HI.:I
26.3 10. 3 30.6 30.6 2H.5 36.5 91.2 75.9 54.2 79.7
H'0111f'1I wi/h CI!alllc/n u/lc
I!I WI
110
=
Maternal age Mean (yr) < 20 yr ('ic) 20-24 yr (o/c) 25-29 vr (o/c) > 30 IT ('iO Smoker ('1
