NEONATOLOGY
Congenital Cytomegalovirus Infection Outcome for the Subsequent Sibling Anne S.
HE
CHRONICITY of excretion of cytomegalovirus (CMV) has aroused concern over the possibility of a subsequent fetus being infected when a previous child has been severely damaged by an intrauterine infection due to CMV. Among 15 infants delivered to 12 mothers whose previous children had had symptomatic congenital CMV infections, Berenberg and I~ankervis~ found no clinical evidence of congenital CMV infection. Two subsequent siblings studied by Krech et al., and one studied by Medearis, were uninfected at birth despite excretion of CMV by two of the mothers for 4 to 5 months during the second pregnancy. 2,-3 In 3 other families, however, siblings from 2 sequential pregnancies were both excreting CMV at birth. 2,4,5 The scanty data available makes it difficult to estimate the risk in later pregnancies for a mother who has previously had an infected infant. We here describe the outcomes of 12 This paper was presented, in part, at the meeting of the Western Society for Pediatric Research in Carmel, California, February 6, 1975. * Department of Pediatrics, University of Colorado Medical Center, Denver, Colorado; and ** Perinatal Virology Branch, Center for Disease Control, Public Health Service, U.S. Department of Health, Education, and Welfare, Atlanta, Georgia 30333. Correspondence to Anne S. Yeager, Department of Pediatrics, Sanford University School of Medicine, Stanford. California 94305.
Yeager, Harold
P.
Martin,* John A. Stewart**
such pregnancies, with respect to evidences of infection and of intellectual prognosis. These 12 families are all the families known to us
in which
a
subsequent sibling
has been
delivered.
Population 1968 and March, 1974, 29 children were shown to be excreting CMV during the newborn period. Viral cultures had been obtained by the patients’ physicians or during the course of prospective research studies. The patients were primarily from the Denver metropolitan area and were representative of the population served by the three affiliated hospitals (University of Colorado Hospital, Denver General Hospital, and Children’s Hospital). The mothers of 7 of these 29 children have had a later child; 15 mothers have not had another child, and 7 have been lost to follow-up. In 5 additional instances, subsequent siblings were studied in which a child had had symptoms at birth compatible with a symptomatic congenital CMV infection but was first tested and shown to be excreting CMV after the newborn period. Between
July,
Viral Isolation and
Serology
The methods used for isolation o~‘ ~ ~~ V and for measurement of complement fixation and
455
Downloaded from cpj.sagepub.com at Monash University on June 17, 2015
TABLE l. Index Cases -Evidence for the
*
N,D.
=
not
done.
indirect
hemag~lutin~tion antibody titers are already on record.G.1 Antibody in the IgM fraction was measured after separation of the immunoglobulins by sucrose gradient density
centrifugation.8 Developmental Tests The developmental quotient (D.Q.) was ascertained by the Revised Gesell Test (revised Yale Developmental Schedules.)9 Observations
original siblings in Cases 1 to 7 (Table found to be excreting CMV between 0 and 9 days of age. Six of these 7 were symptomatic at birth. Clinical findings included low birth weight, microcephaly, hepatosplenomegaly, hyperbilirubinemia, elevated serum glutamic oxaloacetic transaminase, abnormal neurologic findings with elevated spinal fluid protein, and thrombocytopenia. The
1)
were
Congenital Nature of the Infection
Case 7 was clinically asymptomatic. Cases 8 to 12 all had clinical symptoms at birth compatible with classic symptomatic congenital
infection but, due to lack of earlier investigation, were not shown to be excreting CMV until after the newborn period. Serologic tests showed no persisting antibody to toxoplasma or rubella. The intervals between the birth of the first child and the onset of the next pregnancy varied from 4.5 to 43 months. All subsequent siblings were of normal birth weight. The total IgM in cord serum was normal in the seven instances in which it was tested. As shown in Table 2, the complement fixation titers to CMV at birth ranged from 1:32 to 1:256 but no antibody to CMV could be measured at the 1:8 level in the IgM fraction by the complement fixation or indirect hemagglutination techniques in the eight children in whom the IgM fraction was separated and tested.
456
Downloaded from cpj.sagepub.com at Monash University on June 17, 2015
v
TABLE.2,..Laboratory Findings in Subsequent Siblings of Children with Congenital Cytomegalovirxes Infections
* N.D.
=
not
done.
obtained from all subsequent siblings except one, and all with negative results. At the time of follow-up, all 10 children who were more than 6 months of age had CMV complement fixation titers as measured uf ~ 1: $. Titers were also
Congenital Cytomegalovirus Infection Outcome for the Subsequent Sibling Anne S.
HE
CHRONICITY of excretion of cytomegalovirus (CMV) has aroused concern over the possibility of a subsequent fetus being infected when a previous child has been severely damaged by an intrauterine infection due to CMV. Among 15 infants delivered to 12 mothers whose previous children had had symptomatic congenital CMV infections, Berenberg and I~ankervis~ found no clinical evidence of congenital CMV infection. Two subsequent siblings studied by Krech et al., and one studied by Medearis, were uninfected at birth despite excretion of CMV by two of the mothers for 4 to 5 months during the second pregnancy. 2,-3 In 3 other families, however, siblings from 2 sequential pregnancies were both excreting CMV at birth. 2,4,5 The scanty data available makes it difficult to estimate the risk in later pregnancies for a mother who has previously had an infected infant. We here describe the outcomes of 12 This paper was presented, in part, at the meeting of the Western Society for Pediatric Research in Carmel, California, February 6, 1975. * Department of Pediatrics, University of Colorado Medical Center, Denver, Colorado; and ** Perinatal Virology Branch, Center for Disease Control, Public Health Service, U.S. Department of Health, Education, and Welfare, Atlanta, Georgia 30333. Correspondence to Anne S. Yeager, Department of Pediatrics, Sanford University School of Medicine, Stanford. California 94305.
Yeager, Harold
P.
Martin,* John A. Stewart**
such pregnancies, with respect to evidences of infection and of intellectual prognosis. These 12 families are all the families known to us
in which
a
subsequent sibling
has been
delivered.
Population 1968 and March, 1974, 29 children were shown to be excreting CMV during the newborn period. Viral cultures had been obtained by the patients’ physicians or during the course of prospective research studies. The patients were primarily from the Denver metropolitan area and were representative of the population served by the three affiliated hospitals (University of Colorado Hospital, Denver General Hospital, and Children’s Hospital). The mothers of 7 of these 29 children have had a later child; 15 mothers have not had another child, and 7 have been lost to follow-up. In 5 additional instances, subsequent siblings were studied in which a child had had symptoms at birth compatible with a symptomatic congenital CMV infection but was first tested and shown to be excreting CMV after the newborn period. Between
July,
Viral Isolation and
Serology
The methods used for isolation o~‘ ~ ~~ V and for measurement of complement fixation and
455
Downloaded from cpj.sagepub.com at Monash University on June 17, 2015
TABLE l. Index Cases -Evidence for the
*
N,D.
=
not
done.
indirect
hemag~lutin~tion antibody titers are already on record.G.1 Antibody in the IgM fraction was measured after separation of the immunoglobulins by sucrose gradient density
centrifugation.8 Developmental Tests The developmental quotient (D.Q.) was ascertained by the Revised Gesell Test (revised Yale Developmental Schedules.)9 Observations
original siblings in Cases 1 to 7 (Table found to be excreting CMV between 0 and 9 days of age. Six of these 7 were symptomatic at birth. Clinical findings included low birth weight, microcephaly, hepatosplenomegaly, hyperbilirubinemia, elevated serum glutamic oxaloacetic transaminase, abnormal neurologic findings with elevated spinal fluid protein, and thrombocytopenia. The
1)
were
Congenital Nature of the Infection
Case 7 was clinically asymptomatic. Cases 8 to 12 all had clinical symptoms at birth compatible with classic symptomatic congenital
infection but, due to lack of earlier investigation, were not shown to be excreting CMV until after the newborn period. Serologic tests showed no persisting antibody to toxoplasma or rubella. The intervals between the birth of the first child and the onset of the next pregnancy varied from 4.5 to 43 months. All subsequent siblings were of normal birth weight. The total IgM in cord serum was normal in the seven instances in which it was tested. As shown in Table 2, the complement fixation titers to CMV at birth ranged from 1:32 to 1:256 but no antibody to CMV could be measured at the 1:8 level in the IgM fraction by the complement fixation or indirect hemagglutination techniques in the eight children in whom the IgM fraction was separated and tested.
456
Downloaded from cpj.sagepub.com at Monash University on June 17, 2015
v
TABLE.2,..Laboratory Findings in Subsequent Siblings of Children with Congenital Cytomegalovirxes Infections
* N.D.
=
not
done.
obtained from all subsequent siblings except one, and all with negative results. At the time of follow-up, all 10 children who were more than 6 months of age had CMV complement fixation titers as measured uf ~ 1: $. Titers were also
