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The outlook for future pregnancies in women immunized to Rh
Obstetrics THE OUTLOOK FOR FUTURE PREGNANCIES IN WOMEN IMMUNIZED TO Rh*f EDITH L. POTTER, (From Chicago
the Department Lying-in Hospital)
of
Obstetrics
rmd
Gynecology,
The
M.D.,
Urtiversity
of
ILL.
CHICAGO,
Chicago,
and
the
B
ETWEEN Jan. 1, 1935, and Jan. 3, 1955, 241 women who have been immunized to D (238) or c (3) have given birth at this hospital to 302 erythroblastotic infants or fetuses. These same women have had 18 spontaneous abortions and 9 Rh-negative infants, making a total of 329 pregnancies in which we have observed them. Not included in the figures are women known IO be immunized but who in this hospital have had only Rh-negative infants, sponta,neous or therapeut,ic abortions. We have been anxious to find out what to expect in future pregnancies and what effect the outcome of earlier pregnancies might have on a current pregnancy in order to know what counsel to give our patients concerning future childbearing. We initially analyzed these patients only in relation to the outcome of the first aflected pregnancy. It became apparent early in the analysis that the place of the affected child in the t.otal pregnancies of any patient did not alter the conclusions that could be drawn. Consequently, it seemed desirable to divide these patients into three principal groups and to include in one group all the women who have given birth at our hospital to at least one surviving child, in another all women who have had at least one child who died, and in the third all who have had at least one stillbirt,h. Because of this, 17 women are included in 2 groups and I is considered in all 3 groups. *The data on which this paper is based were obtained Health Service Grant for Medical Research No. 3166. TPresented at the Symposium on Maternal Immunization the Chicago Gynecological Society, May 17, 1957.
Public of
348
with to Rh
the and
aid
of
Other
United Blood
StzXteS Groups
Volume 75 Number 2
FUTURE
PREGNANCIES
IN WOMES
rimmw?m
To Rh
There were 119 who were delivered in this hospita.1 on’ly of infants who WY’vived, 59 who were delivered only of infants who died, and 49 who were dt.livered only of stillborn’ fetuses weighing over 400 grams.” In addit,ion 6 had at, least one child who lived and one who died, 7 had at least one who lirctl and one who was stillborn, 4 had both deaths and stillbirths, and om hacl ;)I least one pregnancy in each category.
Mothers With Surviving Erythroblastotic Infants Of the 302 pregnancies in immunized women in which a reportable i’etus or infant was delivered, 149 terminated in the birth of a surviving chilr I. These pregnancies were found among 133 patients, 3 having had twins both of whom survived, 11 having had 2 surviving erythrohlastotir infants in tlifftw ent pregnancies, and one having had 3 such infants. Pregnancies Preceding Evidence of Imm?inization.-There were 20 Wolllt~JJ who had no living children at the time their first surviving erythroblast.ot-ic infant was born. Six of these had had no pregnancies but had received trausfusions which were believed to have been the cause of t,he immunization. Ten women had had a total of 21 unsuccessful pregnancies terminating in 9 neonatal deaths, one stillbirth, and 11 abortions. Only 4 women denied a previous prtgnancy or transfusion. The 113 who had at least one surviving child had had a t,otal of 789 WVcessful pregnancies. These women also had had 3 transfusions and 27 unsuecessful pregnancies, including 4 neonatal deaths, 2 stillbirths, and 21 abortions. These latter pregnancies and t,ransfusions were followed by the delivery of normal living children prior to the birth of one with ervthroblast,oais, so it may be assumed they had no relation to the production of ‘immunizat#ion. The proportion of successful to unsuccessful pregnancies is approximately what ~0ulc1 be expected in any group of normal women. Dlnszcccessful Pregnancies Prior to h-nouw Irnmcnization but Not F7011r~ud by D&very of a Normal ChiZd.-It is impossible to know for certain whether these pregnancies belong to the period prior to immunization and arc t’hc pregnancies responsible for immunization or whether they may have hccn unsuccessful because of the action of antibodies, For this reason they have been kept separate. Most of these pregnancies were not observed in this hospital and there are very few records of antibody determinations; the t’ew that were done showed no evidence that. immunization was present. Tn this group are included 20 women who had 10 neonatal deaths or stillbirths and l:! abortions. Twelve women had transfusions either associated with the termination of the last pregnancy or unassociated with a pregnancy. P,regnanci’es After Immzrnization but Pre8cerling the Birth of u, l.,i&nq Erythroblastotic Infant at the Chicago Lying-in Aos~,ital.--Twent,?l-fo~~l. women had 35 such pregnancies. Delivered in ot,her hospitals were 11 infants who survived, 7 who died, 4 that were stillborn, and 3 that, were aborted. &l+red at the Chicago Lying-in Hospital were 2 who appeared normal in spite of being Rh positive, 3 who died, and 5 who were stillborn. All patients who had more than one living erythroblastotic infant at the Chicago Lying-in Eospital are considered as being in the first of these pregnancies so there arc IIO ]iving children listed among those who were delivered previously in this hospit;ri. *The word fetus as used in this paper refers to a product of conception dca,i at the time of delivery that weighs over 400 grams. Twenty-two weeks’ gestation is the period beyond which the delivery of a dead fetus must be reported in Chica o. Since we believe weight is more accurate than the history of the last nkenstrual perio % we have useit 400 grams as the dividing line between reportable and nonreportable fetuies: whert, 8. fetus weighing less than 400 grams is meant. it is so designated or is palled an abortion.
S’irst Pregnancy at the Chica,go f&y-in Hospital Ilesulting Ida the Girth a Living ErythroDlastotic infant.-One hundred thirty-three womctl gave birth to 136 surviving infants. This includes 6 sets of twins. In 3 sets both twins were Rh positive and both survived. In one set, one infant survived and one died, and in 2 sets one survived and one was stillborn. of
Pwgnancies
Following
the F”irst Delkery
of n Swviving
Erythroblasto
tic
Infant to a Patielzt in the Chicago LyCng-in, Hospital.-Twenty-nine women had 41 subsequent pregnancies. These terminated in the delivery of 14 surviving erythroblastotic infants, 10 who were stillborn, 5 who died neonatally, 5 Of the latter, 3 were known to that were aborted, and 7 who were unaffected. be Rh negative, one Rh positive and unaffected, and 3 of unknown Rh were delivered in other hospitals. Of the total of 41 pregnancies, there were 21, or Of the 30 pregnancries which went 50 per cent, in which the infant survived. beyond the period of abortion in which the fetus was known to be Rh positive there were 15 survivors, also 50 per cent. Total Pregnancies.Before 2Ymmunization: One hundred thirty-three women had 259 pregnancies prior to known immunization, or 1.9 per patient. Of these, 189, or 73 per cent, were successful, ma,king 1.4 successful and 0.5 unsuccessful per patient. The 70 unsuccessful pregnancies (17 deaths, 9 stillbirths, and 44 abortions) were in 49 patients; 16 additional women had transfusions that contributed t,o immunization. In the entire group 65 women had unsuccessful pregnancies or transfusions, 64 had only normal pregnancies, and 4 had no history of transfusion or pregnancy. It was believed that in 21, or 15 per cent, of these women transfusion played an important role in the production of immunization. After immunization: The 133 women had 212 pregnancies after imOf these, munization was known to have been established, or 1.80 per patient. 170, or 85.0 per cent, resulted in the birth of surviving infants. This figure includes 9 unaffected children; 3 known to be Rh positive, 3 Rh negative, and 3 of unknown Rh. The 42 unsuccessful pregnancies included 34 stillbirths or neonatal deaths and 8 abortions. Twenty-two occurred before the birth in this hospital of the living infant. The number of living infants per patient is 1.3, of unsuccessful pregnancies, 0.5. All pregnancies per patient: These 133 women have had a total of 471 pregnancies, or 3.7 per patient. This includes 2.7 per patient that yielded a surviving infant and 1.0 per patient that were unsuccessful. Pregnancy immediately preceding birth of a surviving erythroblastotic infant : Among 123 women whose first, affected erythroblastotic infant sur-
vived, regardless of where it was born, the last preceding pregnancy terminated normally in 92 instances with a normal living infant and with no need for a maternal transfusion then or in the intervening period. The remaining 31 cases included 5 deaths, one stillbirth, 8 abortions, 15 transfusions (following a stillbirth in one! abortion in one, a normal child 2, and without pregnancy, 11) and 2 with no pregnancy, This is a frequency of 74.5 per cent who had neither a transfusion nor an unsuccessful pregnancy immediately preceding the birth of the erythrohlastotic infant. Considering all the pregnancies of our entire group of women, there were 155 in which an erythroblastotic infant survived. In t,hese, 21, or 13.5 per cent, were immediately preceded by a death or stillbirth and 14, or 9 per cent, by an abortion. This leaves 77.5 per cent, with a surviving child in the preceding pregnancy. Pregnan&s
If WC investigate
following
th,e birth. of n swviving
the entire group
of mothers
[email protected]
i-rtfant:
for the outcome of the next
Volume 7.5
lu‘umber 2
FUTURE
PREGNANCIES
IN
WOMEN
IMMUNlZED
TO
Rh
351
after a surviving erythroblastotic infant, regardless of wflethel: these children were born at the Chicago Lying-in Hospital or elsewhere, we find the following : When the surviving child was the first erythroblastotic child to be delivered, 38 women had subsequent pregnancies terminating in 9 deaths, 9 stillbirths, 4 spontaneous abortions, 12 living affected infants, 2 Rh negative, and 2 normal infants of unknown Rh. There were only 8 additional eases in which there had been a pregnancy following the birth of a surviving erythroblastotic child who had not been the first chi.ld of that mother to be affected. The next pregnancy of these 8 terminated in one death, 2 stillbirths, 2 living erythroblastotic infants, one Rh-negative infant, and 2 of unknown Rh. If all pregnancies are considered, there is a 45.6 per cent survival of infants born after a surviving erythroblastotic infant has been previously dalivered. If onlv the pregnancies progressing beyond the stage of abortion are This includes the I&-negative and included, there* is a 50 per cent survival. unaffected infants. pregnancy
Hothers With Infants Who Died After Birth Among the total pregnancies in our immunized women, 76 have terminated in the delivery of a living infant who succumbed after birth. In at least 3 instances erythroblastosis was believed in no way responsible for the death, but since the infants did have erythroblastosis, they are included here. Six of the mothers considered here are also included in the group with surviving infants, 5 of the infant~s who died having been preceded by a living infant delivered in this hospital and one being survived by a twin. There are only 65 mothers in the group with infants who died since 9 women had a second child who died and one had 2 subsequent children who did not survive. Pregnancies Preceding Evidence of Immunization.-There were only 7 women who had no living children at the time a nonsurviving erythroblast,ot,ic child was born. Two had had no previous pregnancies and had been immunized by transfusions and 5 had had 10 unsuccessful pregnancies, including 5 infants who died in the neonatal period and 5 abortions. There was none without an earlier pregnancy or transfusion. The other 58 patients had had 83 normal living children. Preceding the birth of the last living child, 5 of these women had had one death, 2 stillbirths, and 5 abortions. Two had been transfused in association with 2 of the abortions and 2 had been transfused following the birth of a normal infant, but in all cases a normal birth had followed subsequent,ly. Unsuccessful Pregnancies Prior to Known Immunization but Not FobEowed by Delivery of a Norm.aZ ChiZd.- In the interval between the last normal
pregnancy and the birth of the first infant recognized as being erythroblastotic, 13 women had 2 stillbirths, 14 abortions, and 5 transfusions. Pregnancies Erythroblastotic
After Infant
Immunied.on but Preceding the Birtk of -2he First to Die at the Chicago Lying-in Hog@‘tal,.-Twenty-six
women had 46 such pregnancies, 19 having been del.ivered elsewhere, and 7 having been delivered at our hospital. The outcome of these 46 pregnancies was 17 deaths, 17 stillbirths, 2 abortions, 10 living affected Rh-positive infants, and 2 living unaffected Rh-negative infants, Twelve, or 26.0 per cent, were successful. Neonatal Deaths Among Erythroblastotic Inffznts.-There were 76 infants who died after birth: the length of survival was: less than 3 hours 25 (all except one lived less than l$$ hours), 3 to 24 hours 10, 25 to 48 hours 12, 49 to 72 hours 17, 73 to 96 hours 7, 4 to 13 days 5. Almost half the infants who failed to survive died during the first day of life. Among the 191 erythroblastotic infants born in this hospital in the past 20 years who survived the first 24 hours the mortality has been only 21 per cent. For the 261 who
Volume 15 Number 2
FUTURE
PREGNANCIES
IN
WOMEN
IMMUNIZED
TO
Rh
35:;
child to be delivered survived in 9 instances (6 erythroblast,otic, 3 Rh-negative j , died in 14, was stillborn in 12, and was aborted in 8. This is a total survival of 9 in 43 pregnancies, or 20.9 per cent. If abortions a.re omitted from the calculations, it is a survival of 25.7 per cent. In 24 instances where the chihl who died was not the first affected offspring, the outcome in the next folknv-. ing pregnancy was the same as when the child who died was the first afkte~l infant. There were 5 living infants (3 affected, 1 Rh-negative, I Rh-positive but normal) in a total of 24 such pregnancies, giving a survival of 20.X or. if abol*tions are excluded, of 25 per cent.
Mothers With Stillborn Fetuses Seventy-seven stillborn fetuses with erythroblastosis have been deliverrtl by 62 women. In 2 instances both of the twins were stillborn, 9 women were delivered of a second stillborn erythroblastotic infant, and 2 women wvvc~~ delivered of 2 subsequently stillborn erythroblast,otic fetuses. Pregnancies Preceding Evidence of Immzcnization.-There were 11 women who had no living children at the time of the delivery of the first stillborzn erythroblastotic fetus. Four had had no pregnancies and had been immuniztld by transfusions. Seven others had had 5 stillbirths (presumably not erythroblastotic), 2 neonatal deaths, and 8 abortions, 3 of which were followed by transfusions. Seven of the 11 were believed to have been immunized b! transfusions. The remaining 51 women had 81 living nonerythroblastotic infants and, preceding the birth of the last normal child, 8 women had had 2 stillbirths, one neonatal death, and 5 abortions, one of which was followeil bs 2 transfusions. Unsuccessful Pregnancies Preceding Knom. Immunization but IYot .1’01lowed by a Normal Infant.-During this time 18 women had 26 unsuccessful
pregnancies; these included 5 stillbirths, 4 neonatal deaths, 17 abortions? -1,of which were followed by transfusions. There were 3 additional women who had had a transfusion after the birth of a normal child or unarsociatcd with pregnancy. Pregmncies After Immunization but Preceding the Birth of a StillhmwPrtus at the Chicago Lyingin Hospit&.-Thirty-two women had had 66 crythreblastotic infants previously. Delivered at other hospitals were 19 women tvbose pregnancies ended in 2 surviving infank, 12 neonatal deaths, 14 stillbirths, and 16 abortions; at, the Chicago Lying-in Wospit’al there were 15 women with 12 living erythroblastotic infants, 2 R.h-negative infants, 2 infants who died neonatally, and 6 abortions. Two women are included in both groups. Pregnancies Following the First Stillborn Erythroblastoic Delivered at the Chicago Lying-in Hospital.-Nineteen women
Fctm
to lje
have had 28 subsequent pregnancies (plus 2 terminating in therapeutic abortions not ineluded). These terminated in the delivery of 2 normal Rh-negative infants, 2 Rh-positive severely erythroblastotic infants who survived, 5 who died, 1.5 who were stillborn, 4 spontaneously aborted. This is a survival of 4 in a total of 28 pregnancies (14.3 per cent) or 2 in 22 Rh-positive fetuses that wcnf: bcyon(l t,he stage of abortion (9.0 per cent). Total Pregnancies.Before immunization:
The total number of pregnancies in this group of 62 women is 130, or 2.1 pregnancies per patient. Of these, 81, or 62.3 per cent, were successful, giving an average of 1.3 living children per patient, and 0.8 unsuccessful pregnancies. The 49 unsuccessful pregnancies (7 deaths, 12 stillbirths, 30 abortions) occurred among 33 women; 7 additional women had transfusions but no unsuccessful pregnancies. In the entire group, 40 women
354
had an unsuccessful pregnancy or a tratlsfusion preceding evidence of immunization; only 22, or 35.5 per cent, had had only normal pregnancies. It was believed that in 15, or 24.2 per rent, transfusion was an important factor contributing to immunization. After immzcnisation : The 62 women who had stillborn erythroblastotic infants in this hospital had a total of 156 pregnancies during which evidence of immunization was present. This is an average of 2.5 per patient. Of these 20 terminated in living infants (16 surviving afFected infants and 4 Rh-negative infants). The remaining 136 terminated in 19 deaths, 93 stillbirths, and 26 abortions. Only 12 per cent of the pregnancies were successful in produring a living infant. The frequency per patient of unsuccessful pregnancies is 2.2, of living infants 0.4. All pregnancies per patient: These 62 women have had a total of 286 pregnancies, or 4.7 per patient. This includes 1.7 successful and 3.0 unsuccessful. Preg%%cy immediately preceding the birth of a surviving erythoblmtotic Infant: Among 51 women in our entire group of 241 whose first pregnancy after immunization terminated in an erythroblastotic stillborn fetus, the preceding pregnancy terminated in 34 normal infants, one death, and 13 abortions. Three had had only transfusions, and in 4 more a transfusion had accompanied an abortion. There were 72 additional ergthroblastotic stillborn infants not from the first pregnancy after immunization was present. The pregnancy immediately preceding these stillbirths terminated in 11 living erythroblastotiv infants, one normal Rh-positive and 2 normal Rh-nega.tivc infants, 14 deaths and 33 stillbirths from erythroblastosis and 11 abortions. Of t,he total of 12:) stillbirths, only 37, or 30 per cent, followed the hirt,h of a normal nonerythroblast&c infant. Pregnancies folLowGag the birth of a stillborn erythroblastotic fetus: If we look at the pregnancies that have followed the birth of the first, erythroblastotic infant when that child was stillborn (regardless of whether or not that particular child was born at the Chicago Lying-in Hospital), we find 34 women with subsequent pregnancies. Those immediately following the first stillborn erythroblastotic fetus terminated in the birth of 3 surviving erythroblast.otic infants, one normal R,h-negative infant, 7 who died, 16 who were stillborn from erythroblastosis, and 7 abortions. This is a survival of 11.7 per cent (4 in 34) in all pregnancies, or 11.4 per cent (3 in 26) of the Rh-positive fetuses who passed the stage of abortion. In a total of 82 subsequent pregnancies in these women, the result was 8 surviving affected infants and 3 Rh-negative infants, 17 deaths, 40 stillbirths, and 14 abortions. This is a total survival of 13.4 per cent, or 12.3 per cent of 65 pregnancies which went beyond the sta.pe of abortion and in which the fetus was Rh positive. If in all women the pregnancy that followed immediately after the delivery of a stillborn erythroblasto& infant is considered, regardless of the posi&on of the stillbirth in relation to other erythroblastotic infants, we have a total of 103. The next pregnancy terminated in a stillbirth in 48 instances, a death in 29, a spontaneous abortion in 17, a living erythroblastotic child in 6, an unaffected Rh-positive child in one, and an Rh-negative child in 2. This is a frequency of survival of 9 in 103, or 9.1 per cent; or of 8 in 85 Rh-positive fetuses who passed the &age of abortion, making 9.4 per cent. There is very little difference in the outcome of a pregnancy that follows the delivery of a stillborn fetus in which that fetus is the first affected erythroblastotic infant to be delivered and one in which the erythroblastotic stillborn infant has been preceded by other erythroblastotic infants. In either case the total survival rat,e is approximately 10 per cent.
Volume 75 Number 2
FUTURE
PREGNANCIES
IN
WOMEN
IMMUNIZED
TO
Rh
355
comment The case histories analyzed in this report extend back 20 years, all of OUI cases having been used in order to follow our patients as many years as possible. It means, consequently, that we have a total of fewer living children than if it had been possible to use only current pregnancies, since the diagnosis was rarely made in a living child until 10 years ago, and it means also that some of the deaths and stillbirths that were regarded as occurring in the first erythroblastotic child were doubtless preceded by some affected but living infants whose cases were not diagnosed. The subsequent pregnancies, however-thosr in which we are especially interested-show practically no difference today from those observed many years ago. Among currently observed infants there are fewer deaths and more survivors than in the entire group, but the proportion of stillbirths among affected infants remains the same. Of the total of 302 erythroblastotic infants observed in this hospital, 49.3 per cent survived, 25.2 per cent died, and 25.5 per cent were stillborn. For the past 10 years the survival rate has increased to 58 per cent (132 of 230 cases), the deaths ha.ve decreased to 19 per cent (44 of 230 cases), and the stillbirths to 23 per cent (54 in 230 cases). In the last 4 years the survival has been 64 per cent (72 of 113 cases), deaths 14 per cent (16 of 113 cases), and stillbirths 22 per cent (25 in 113 cases). Of all 241 women observed during 20 years, half have given birth to living children in their first pregnancy with erythroblastosis. There were 171 who had had only normal living children and had had no transfusions before the birth of their first erythroblastotic child. The first affected infant survived in 92 (53.8 per cent) of these cases, died in 45 (26.2 per cent, and was stillborn in 34 (20 per cent). Of the 123 women whose first affected child lived, 74.5 per cent had had neither an unsuccessful pregnancy nor a transfusion; of the 67 whose first affected child died, 67.1 per cent had had neither an unsuccessful pregnancy nor a transfusion; and of the 51 whose first affected child was stillborn, 66.7 per cent had had only normal children. These figures are at variance with the often repeated statement that the disease can always be expected to be more severe in. succeeding pregnancies. Although more first affected children live than die or are stillborn, the siblings of these surviving children will also have a greater chance of surviving. In this series the child following the birth of any surviving erythroblastotic infant also survived in 50 per cent of the cases. Following a stillbirth from ervthroblastosis, the next child survived only 10 per cent of the time. From this and from inspection of individual case histories, it seems as if in some instances maternal immunization affected all offspring only mildly while in others t,he majority were severely affected. Everyone is familiar with the woman who has had repeated stillbirths and, on the other hand, with women who, although they ‘have antibodies, have had several infants in whom the disease was so mild that there was some question as to whether the diagnosis should actually be made. Our mothers whose first affected child survived have had fewer succeeding pregnancies than those who have had stillbirths and few of those who have had a second living child have had subsequent pregnancies. There were only 14 who did have more than one pregnancy subsequentIy and all but 2 of these had a later death or stillbirth. Two women have had 3 pregnancies, in each of which erythroblastotic infants survived, and a third had 2 surviving erythroblastot,ic and one R&negative infants.
the Department Lying-in Hospital)
of
Obstetrics
rmd
Gynecology,
The
M.D.,
Urtiversity
of
ILL.
CHICAGO,
Chicago,
and
the
B
ETWEEN Jan. 1, 1935, and Jan. 3, 1955, 241 women who have been immunized to D (238) or c (3) have given birth at this hospital to 302 erythroblastotic infants or fetuses. These same women have had 18 spontaneous abortions and 9 Rh-negative infants, making a total of 329 pregnancies in which we have observed them. Not included in the figures are women known IO be immunized but who in this hospital have had only Rh-negative infants, sponta,neous or therapeut,ic abortions. We have been anxious to find out what to expect in future pregnancies and what effect the outcome of earlier pregnancies might have on a current pregnancy in order to know what counsel to give our patients concerning future childbearing. We initially analyzed these patients only in relation to the outcome of the first aflected pregnancy. It became apparent early in the analysis that the place of the affected child in the t.otal pregnancies of any patient did not alter the conclusions that could be drawn. Consequently, it seemed desirable to divide these patients into three principal groups and to include in one group all the women who have given birth at our hospital to at least one surviving child, in another all women who have had at least one child who died, and in the third all who have had at least one stillbirt,h. Because of this, 17 women are included in 2 groups and I is considered in all 3 groups. *The data on which this paper is based were obtained Health Service Grant for Medical Research No. 3166. TPresented at the Symposium on Maternal Immunization the Chicago Gynecological Society, May 17, 1957.
Public of
348
with to Rh
the and
aid
of
Other
United Blood
StzXteS Groups
Volume 75 Number 2
FUTURE
PREGNANCIES
IN WOMES
rimmw?m
To Rh
There were 119 who were delivered in this hospita.1 on’ly of infants who WY’vived, 59 who were delivered only of infants who died, and 49 who were dt.livered only of stillborn’ fetuses weighing over 400 grams.” In addit,ion 6 had at, least one child who lived and one who died, 7 had at least one who lirctl and one who was stillborn, 4 had both deaths and stillbirths, and om hacl ;)I least one pregnancy in each category.
Mothers With Surviving Erythroblastotic Infants Of the 302 pregnancies in immunized women in which a reportable i’etus or infant was delivered, 149 terminated in the birth of a surviving chilr I. These pregnancies were found among 133 patients, 3 having had twins both of whom survived, 11 having had 2 surviving erythrohlastotir infants in tlifftw ent pregnancies, and one having had 3 such infants. Pregnancies Preceding Evidence of Imm?inization.-There were 20 Wolllt~JJ who had no living children at the time their first surviving erythroblast.ot-ic infant was born. Six of these had had no pregnancies but had received trausfusions which were believed to have been the cause of t,he immunization. Ten women had had a total of 21 unsuccessful pregnancies terminating in 9 neonatal deaths, one stillbirth, and 11 abortions. Only 4 women denied a previous prtgnancy or transfusion. The 113 who had at least one surviving child had had a t,otal of 789 WVcessful pregnancies. These women also had had 3 transfusions and 27 unsuecessful pregnancies, including 4 neonatal deaths, 2 stillbirths, and 21 abortions. These latter pregnancies and t,ransfusions were followed by the delivery of normal living children prior to the birth of one with ervthroblast,oais, so it may be assumed they had no relation to the production of ‘immunizat#ion. The proportion of successful to unsuccessful pregnancies is approximately what ~0ulc1 be expected in any group of normal women. Dlnszcccessful Pregnancies Prior to h-nouw Irnmcnization but Not F7011r~ud by D&very of a Normal ChiZd.-It is impossible to know for certain whether these pregnancies belong to the period prior to immunization and arc t’hc pregnancies responsible for immunization or whether they may have hccn unsuccessful because of the action of antibodies, For this reason they have been kept separate. Most of these pregnancies were not observed in this hospital and there are very few records of antibody determinations; the t’ew that were done showed no evidence that. immunization was present. Tn this group are included 20 women who had 10 neonatal deaths or stillbirths and l:! abortions. Twelve women had transfusions either associated with the termination of the last pregnancy or unassociated with a pregnancy. P,regnanci’es After Immzrnization but Pre8cerling the Birth of u, l.,i&nq Erythroblastotic Infant at the Chicago Lying-in Aos~,ital.--Twent,?l-fo~~l. women had 35 such pregnancies. Delivered in ot,her hospitals were 11 infants who survived, 7 who died, 4 that were stillborn, and 3 that, were aborted. &l+red at the Chicago Lying-in Hospital were 2 who appeared normal in spite of being Rh positive, 3 who died, and 5 who were stillborn. All patients who had more than one living erythroblastotic infant at the Chicago Lying-in Eospital are considered as being in the first of these pregnancies so there arc IIO ]iving children listed among those who were delivered previously in this hospit;ri. *The word fetus as used in this paper refers to a product of conception dca,i at the time of delivery that weighs over 400 grams. Twenty-two weeks’ gestation is the period beyond which the delivery of a dead fetus must be reported in Chica o. Since we believe weight is more accurate than the history of the last nkenstrual perio % we have useit 400 grams as the dividing line between reportable and nonreportable fetuies: whert, 8. fetus weighing less than 400 grams is meant. it is so designated or is palled an abortion.
S’irst Pregnancy at the Chica,go f&y-in Hospital Ilesulting Ida the Girth a Living ErythroDlastotic infant.-One hundred thirty-three womctl gave birth to 136 surviving infants. This includes 6 sets of twins. In 3 sets both twins were Rh positive and both survived. In one set, one infant survived and one died, and in 2 sets one survived and one was stillborn. of
Pwgnancies
Following
the F”irst Delkery
of n Swviving
Erythroblasto
tic
Infant to a Patielzt in the Chicago LyCng-in, Hospital.-Twenty-nine women had 41 subsequent pregnancies. These terminated in the delivery of 14 surviving erythroblastotic infants, 10 who were stillborn, 5 who died neonatally, 5 Of the latter, 3 were known to that were aborted, and 7 who were unaffected. be Rh negative, one Rh positive and unaffected, and 3 of unknown Rh were delivered in other hospitals. Of the total of 41 pregnancies, there were 21, or Of the 30 pregnancries which went 50 per cent, in which the infant survived. beyond the period of abortion in which the fetus was known to be Rh positive there were 15 survivors, also 50 per cent. Total Pregnancies.Before 2Ymmunization: One hundred thirty-three women had 259 pregnancies prior to known immunization, or 1.9 per patient. Of these, 189, or 73 per cent, were successful, ma,king 1.4 successful and 0.5 unsuccessful per patient. The 70 unsuccessful pregnancies (17 deaths, 9 stillbirths, and 44 abortions) were in 49 patients; 16 additional women had transfusions that contributed t,o immunization. In the entire group 65 women had unsuccessful pregnancies or transfusions, 64 had only normal pregnancies, and 4 had no history of transfusion or pregnancy. It was believed that in 21, or 15 per cent, of these women transfusion played an important role in the production of immunization. After immunization: The 133 women had 212 pregnancies after imOf these, munization was known to have been established, or 1.80 per patient. 170, or 85.0 per cent, resulted in the birth of surviving infants. This figure includes 9 unaffected children; 3 known to be Rh positive, 3 Rh negative, and 3 of unknown Rh. The 42 unsuccessful pregnancies included 34 stillbirths or neonatal deaths and 8 abortions. Twenty-two occurred before the birth in this hospital of the living infant. The number of living infants per patient is 1.3, of unsuccessful pregnancies, 0.5. All pregnancies per patient: These 133 women have had a total of 471 pregnancies, or 3.7 per patient. This includes 2.7 per patient that yielded a surviving infant and 1.0 per patient that were unsuccessful. Pregnancy immediately preceding birth of a surviving erythroblastotic infant : Among 123 women whose first, affected erythroblastotic infant sur-
vived, regardless of where it was born, the last preceding pregnancy terminated normally in 92 instances with a normal living infant and with no need for a maternal transfusion then or in the intervening period. The remaining 31 cases included 5 deaths, one stillbirth, 8 abortions, 15 transfusions (following a stillbirth in one! abortion in one, a normal child 2, and without pregnancy, 11) and 2 with no pregnancy, This is a frequency of 74.5 per cent who had neither a transfusion nor an unsuccessful pregnancy immediately preceding the birth of the erythrohlastotic infant. Considering all the pregnancies of our entire group of women, there were 155 in which an erythroblastotic infant survived. In t,hese, 21, or 13.5 per cent, were immediately preceded by a death or stillbirth and 14, or 9 per cent, by an abortion. This leaves 77.5 per cent, with a surviving child in the preceding pregnancy. Pregnan&s
If WC investigate
following
th,e birth. of n swviving
the entire group
of mothers
[email protected]
i-rtfant:
for the outcome of the next
Volume 7.5
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after a surviving erythroblastotic infant, regardless of wflethel: these children were born at the Chicago Lying-in Hospital or elsewhere, we find the following : When the surviving child was the first erythroblastotic child to be delivered, 38 women had subsequent pregnancies terminating in 9 deaths, 9 stillbirths, 4 spontaneous abortions, 12 living affected infants, 2 Rh negative, and 2 normal infants of unknown Rh. There were only 8 additional eases in which there had been a pregnancy following the birth of a surviving erythroblastotic child who had not been the first chi.ld of that mother to be affected. The next pregnancy of these 8 terminated in one death, 2 stillbirths, 2 living erythroblastotic infants, one Rh-negative infant, and 2 of unknown Rh. If all pregnancies are considered, there is a 45.6 per cent survival of infants born after a surviving erythroblastotic infant has been previously dalivered. If onlv the pregnancies progressing beyond the stage of abortion are This includes the I&-negative and included, there* is a 50 per cent survival. unaffected infants. pregnancy
Hothers With Infants Who Died After Birth Among the total pregnancies in our immunized women, 76 have terminated in the delivery of a living infant who succumbed after birth. In at least 3 instances erythroblastosis was believed in no way responsible for the death, but since the infants did have erythroblastosis, they are included here. Six of the mothers considered here are also included in the group with surviving infants, 5 of the infant~s who died having been preceded by a living infant delivered in this hospital and one being survived by a twin. There are only 65 mothers in the group with infants who died since 9 women had a second child who died and one had 2 subsequent children who did not survive. Pregnancies Preceding Evidence of Immunization.-There were only 7 women who had no living children at the time a nonsurviving erythroblast,ot,ic child was born. Two had had no previous pregnancies and had been immunized by transfusions and 5 had had 10 unsuccessful pregnancies, including 5 infants who died in the neonatal period and 5 abortions. There was none without an earlier pregnancy or transfusion. The other 58 patients had had 83 normal living children. Preceding the birth of the last living child, 5 of these women had had one death, 2 stillbirths, and 5 abortions. Two had been transfused in association with 2 of the abortions and 2 had been transfused following the birth of a normal infant, but in all cases a normal birth had followed subsequent,ly. Unsuccessful Pregnancies Prior to Known Immunization but Not FobEowed by Delivery of a Norm.aZ ChiZd.- In the interval between the last normal
pregnancy and the birth of the first infant recognized as being erythroblastotic, 13 women had 2 stillbirths, 14 abortions, and 5 transfusions. Pregnancies Erythroblastotic
After Infant
Immunied.on but Preceding the Birtk of -2he First to Die at the Chicago Lying-in Hog@‘tal,.-Twenty-six
women had 46 such pregnancies, 19 having been del.ivered elsewhere, and 7 having been delivered at our hospital. The outcome of these 46 pregnancies was 17 deaths, 17 stillbirths, 2 abortions, 10 living affected Rh-positive infants, and 2 living unaffected Rh-negative infants, Twelve, or 26.0 per cent, were successful. Neonatal Deaths Among Erythroblastotic Inffznts.-There were 76 infants who died after birth: the length of survival was: less than 3 hours 25 (all except one lived less than l$$ hours), 3 to 24 hours 10, 25 to 48 hours 12, 49 to 72 hours 17, 73 to 96 hours 7, 4 to 13 days 5. Almost half the infants who failed to survive died during the first day of life. Among the 191 erythroblastotic infants born in this hospital in the past 20 years who survived the first 24 hours the mortality has been only 21 per cent. For the 261 who
Volume 15 Number 2
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child to be delivered survived in 9 instances (6 erythroblast,otic, 3 Rh-negative j , died in 14, was stillborn in 12, and was aborted in 8. This is a total survival of 9 in 43 pregnancies, or 20.9 per cent. If abortions a.re omitted from the calculations, it is a survival of 25.7 per cent. In 24 instances where the chihl who died was not the first affected offspring, the outcome in the next folknv-. ing pregnancy was the same as when the child who died was the first afkte~l infant. There were 5 living infants (3 affected, 1 Rh-negative, I Rh-positive but normal) in a total of 24 such pregnancies, giving a survival of 20.X or. if abol*tions are excluded, of 25 per cent.
Mothers With Stillborn Fetuses Seventy-seven stillborn fetuses with erythroblastosis have been deliverrtl by 62 women. In 2 instances both of the twins were stillborn, 9 women were delivered of a second stillborn erythroblastotic infant, and 2 women wvvc~~ delivered of 2 subsequently stillborn erythroblast,otic fetuses. Pregnancies Preceding Evidence of Immzcnization.-There were 11 women who had no living children at the time of the delivery of the first stillborzn erythroblastotic fetus. Four had had no pregnancies and had been immuniztld by transfusions. Seven others had had 5 stillbirths (presumably not erythroblastotic), 2 neonatal deaths, and 8 abortions, 3 of which were followed by transfusions. Seven of the 11 were believed to have been immunized b! transfusions. The remaining 51 women had 81 living nonerythroblastotic infants and, preceding the birth of the last normal child, 8 women had had 2 stillbirths, one neonatal death, and 5 abortions, one of which was followeil bs 2 transfusions. Unsuccessful Pregnancies Preceding Knom. Immunization but IYot .1’01lowed by a Normal Infant.-During this time 18 women had 26 unsuccessful
pregnancies; these included 5 stillbirths, 4 neonatal deaths, 17 abortions? -1,of which were followed by transfusions. There were 3 additional women who had had a transfusion after the birth of a normal child or unarsociatcd with pregnancy. Pregmncies After Immunization but Preceding the Birth of a StillhmwPrtus at the Chicago Lyingin Hospit&.-Thirty-two women had had 66 crythreblastotic infants previously. Delivered at other hospitals were 19 women tvbose pregnancies ended in 2 surviving infank, 12 neonatal deaths, 14 stillbirths, and 16 abortions; at, the Chicago Lying-in Wospit’al there were 15 women with 12 living erythroblastotic infants, 2 R.h-negative infants, 2 infants who died neonatally, and 6 abortions. Two women are included in both groups. Pregnancies Following the First Stillborn Erythroblastoic Delivered at the Chicago Lying-in Hospital.-Nineteen women
Fctm
to lje
have had 28 subsequent pregnancies (plus 2 terminating in therapeutic abortions not ineluded). These terminated in the delivery of 2 normal Rh-negative infants, 2 Rh-positive severely erythroblastotic infants who survived, 5 who died, 1.5 who were stillborn, 4 spontaneously aborted. This is a survival of 4 in a total of 28 pregnancies (14.3 per cent) or 2 in 22 Rh-positive fetuses that wcnf: bcyon(l t,he stage of abortion (9.0 per cent). Total Pregnancies.Before immunization:
The total number of pregnancies in this group of 62 women is 130, or 2.1 pregnancies per patient. Of these, 81, or 62.3 per cent, were successful, giving an average of 1.3 living children per patient, and 0.8 unsuccessful pregnancies. The 49 unsuccessful pregnancies (7 deaths, 12 stillbirths, 30 abortions) occurred among 33 women; 7 additional women had transfusions but no unsuccessful pregnancies. In the entire group, 40 women
354
had an unsuccessful pregnancy or a tratlsfusion preceding evidence of immunization; only 22, or 35.5 per cent, had had only normal pregnancies. It was believed that in 15, or 24.2 per rent, transfusion was an important factor contributing to immunization. After immzcnisation : The 62 women who had stillborn erythroblastotic infants in this hospital had a total of 156 pregnancies during which evidence of immunization was present. This is an average of 2.5 per patient. Of these 20 terminated in living infants (16 surviving afFected infants and 4 Rh-negative infants). The remaining 136 terminated in 19 deaths, 93 stillbirths, and 26 abortions. Only 12 per cent of the pregnancies were successful in produring a living infant. The frequency per patient of unsuccessful pregnancies is 2.2, of living infants 0.4. All pregnancies per patient: These 62 women have had a total of 286 pregnancies, or 4.7 per patient. This includes 1.7 successful and 3.0 unsuccessful. Preg%%cy immediately preceding the birth of a surviving erythoblmtotic Infant: Among 51 women in our entire group of 241 whose first pregnancy after immunization terminated in an erythroblastotic stillborn fetus, the preceding pregnancy terminated in 34 normal infants, one death, and 13 abortions. Three had had only transfusions, and in 4 more a transfusion had accompanied an abortion. There were 72 additional ergthroblastotic stillborn infants not from the first pregnancy after immunization was present. The pregnancy immediately preceding these stillbirths terminated in 11 living erythroblastotiv infants, one normal Rh-positive and 2 normal Rh-nega.tivc infants, 14 deaths and 33 stillbirths from erythroblastosis and 11 abortions. Of t,he total of 12:) stillbirths, only 37, or 30 per cent, followed the hirt,h of a normal nonerythroblast&c infant. Pregnancies folLowGag the birth of a stillborn erythroblastotic fetus: If we look at the pregnancies that have followed the birth of the first, erythroblastotic infant when that child was stillborn (regardless of whether or not that particular child was born at the Chicago Lying-in Hospital), we find 34 women with subsequent pregnancies. Those immediately following the first stillborn erythroblastotic fetus terminated in the birth of 3 surviving erythroblast.otic infants, one normal R,h-negative infant, 7 who died, 16 who were stillborn from erythroblastosis, and 7 abortions. This is a survival of 11.7 per cent (4 in 34) in all pregnancies, or 11.4 per cent (3 in 26) of the Rh-positive fetuses who passed the stage of abortion. In a total of 82 subsequent pregnancies in these women, the result was 8 surviving affected infants and 3 Rh-negative infants, 17 deaths, 40 stillbirths, and 14 abortions. This is a total survival of 13.4 per cent, or 12.3 per cent of 65 pregnancies which went beyond the sta.pe of abortion and in which the fetus was Rh positive. If in all women the pregnancy that followed immediately after the delivery of a stillborn erythroblasto& infant is considered, regardless of the posi&on of the stillbirth in relation to other erythroblastotic infants, we have a total of 103. The next pregnancy terminated in a stillbirth in 48 instances, a death in 29, a spontaneous abortion in 17, a living erythroblastotic child in 6, an unaffected Rh-positive child in one, and an Rh-negative child in 2. This is a frequency of survival of 9 in 103, or 9.1 per cent; or of 8 in 85 Rh-positive fetuses who passed the &age of abortion, making 9.4 per cent. There is very little difference in the outcome of a pregnancy that follows the delivery of a stillborn fetus in which that fetus is the first affected erythroblastotic infant to be delivered and one in which the erythroblastotic stillborn infant has been preceded by other erythroblastotic infants. In either case the total survival rat,e is approximately 10 per cent.
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comment The case histories analyzed in this report extend back 20 years, all of OUI cases having been used in order to follow our patients as many years as possible. It means, consequently, that we have a total of fewer living children than if it had been possible to use only current pregnancies, since the diagnosis was rarely made in a living child until 10 years ago, and it means also that some of the deaths and stillbirths that were regarded as occurring in the first erythroblastotic child were doubtless preceded by some affected but living infants whose cases were not diagnosed. The subsequent pregnancies, however-thosr in which we are especially interested-show practically no difference today from those observed many years ago. Among currently observed infants there are fewer deaths and more survivors than in the entire group, but the proportion of stillbirths among affected infants remains the same. Of the total of 302 erythroblastotic infants observed in this hospital, 49.3 per cent survived, 25.2 per cent died, and 25.5 per cent were stillborn. For the past 10 years the survival rate has increased to 58 per cent (132 of 230 cases), the deaths ha.ve decreased to 19 per cent (44 of 230 cases), and the stillbirths to 23 per cent (54 in 230 cases). In the last 4 years the survival has been 64 per cent (72 of 113 cases), deaths 14 per cent (16 of 113 cases), and stillbirths 22 per cent (25 in 113 cases). Of all 241 women observed during 20 years, half have given birth to living children in their first pregnancy with erythroblastosis. There were 171 who had had only normal living children and had had no transfusions before the birth of their first erythroblastotic child. The first affected infant survived in 92 (53.8 per cent) of these cases, died in 45 (26.2 per cent, and was stillborn in 34 (20 per cent). Of the 123 women whose first affected child lived, 74.5 per cent had had neither an unsuccessful pregnancy nor a transfusion; of the 67 whose first affected child died, 67.1 per cent had had neither an unsuccessful pregnancy nor a transfusion; and of the 51 whose first affected child was stillborn, 66.7 per cent had had only normal children. These figures are at variance with the often repeated statement that the disease can always be expected to be more severe in. succeeding pregnancies. Although more first affected children live than die or are stillborn, the siblings of these surviving children will also have a greater chance of surviving. In this series the child following the birth of any surviving erythroblastotic infant also survived in 50 per cent of the cases. Following a stillbirth from ervthroblastosis, the next child survived only 10 per cent of the time. From this and from inspection of individual case histories, it seems as if in some instances maternal immunization affected all offspring only mildly while in others t,he majority were severely affected. Everyone is familiar with the woman who has had repeated stillbirths and, on the other hand, with women who, although they ‘have antibodies, have had several infants in whom the disease was so mild that there was some question as to whether the diagnosis should actually be made. Our mothers whose first affected child survived have had fewer succeeding pregnancies than those who have had stillbirths and few of those who have had a second living child have had subsequent pregnancies. There were only 14 who did have more than one pregnancy subsequentIy and all but 2 of these had a later death or stillbirth. Two women have had 3 pregnancies, in each of which erythroblastotic infants survived, and a third had 2 surviving erythroblastot,ic and one R&negative infants.