481
Diagnosis of recurrent suffocation of children SiR,—Although diagnosis of recurrent suffocation of children is important, mothers of babies with recurrent apnoea should not be
falsely accused of suffocating their babies. There are three statements in your July 11 editorial that may lead doctors falsely to suspect or accuse mothers of suffocation.
First, you say "the onset of these episodes always occurs in the presence of one carer, usually the mother". Infants spend most of their time with their mother and very little with someone else watching, even in hospital. Therefore, most instances of natural postneonatal apnoea, even when recurrent, are initially reported by the mother. Second, you also say "the need for recurrent cardiopulmonary resuscitation started by a carer but continued by professionals is a suggestive feature". I fail to understand the logic of this statement. If a mother has a baby with recurrent apnoeic attacks, what is she expected to do? A caring mother is bound to attempt to resuscitate her baby. If the baby was so ill that resuscitation was continued by professionals, this is more likely to be genuine severe apnoea rather than suffocation. Third, you state "the parents are often concerned and cooperative (’model parents’)". Most parents of my patients would fit into this category. This must be one of the "softest" signs ever proposed in medicine. Before these signs are accepted as part of the criteria for diagnosing suffocation, their proponents should provide evidence of their statistical efficacy-ie, sensitivity, specificity, positive predictive value, and false-positive rate. Proposing these as important pointers to the diagnosis of suffocation would teach doctors to suspect most mothers whose infants have recurrent apnoea, just at the time when they most need sympathetic help and support. You also propagate the unproven idea that, "If arterial oxygen saturation, breathing movements, electrocardiogram, heart rate, and nasal airflow are monitored simultaneously a characteristic pattern of changes is observed during suffocation". There are many reasons for sudden large body movements that are associated with apnoea, hypoxia, tachycardia, and bradycardia-for example struggling, arching the back, fits, or obstructive apnoea due to natural causes such as laryngeal spasm after gastro-oesophageal reflux. Continued breathing movements with absent airflow certainly suggest obstruction to the airway. However, this cannot be regarded as characteristic of suffocation, which must be the rarest cause of such findings. In Samuels and co-workers’ report,’ their figure purporting to show a recording of suffocation does not fulfil their own criteria since air flow was not recorded and therefore absent air flow cannot be confirmed; there was no tachycardia or bradycardia; and the abdominal movement monitor showed increased movement but at the same rate as the normal breathing. Suffocation cannot be diagnosed from recordings alone; these can be interpreted accurately only if they are correlated with a direct witness of the event and preferably a video recording. If we are persuaded to accept some of these unproven ideas, innocent mothers will be accused of a serious crime from which they will fmd it hard to defend themselves. Department of Paediatrics, University of Cambridge School
of Clinical Medicine,
Addenbrook’s Hospital,
Cambridge CB2 2QQ, UK
COLIN MORLEY
1 Samuels MP, McClaughlin W. Jacobson RR, Poets CF, Southall DP. Fourteen cases of imposed upper airway obstruction. Arch Dis Child 1992; 67: 162-70
SiR,—In your July 11editorial you state that "long-term multichannel physiological recordings can provide essential diagnostic information" for imposed upper airway obstruction (IUAO); that its combination with personal and maternal history "may seem conclusive but will be insufficient to convince some people"; if not, "the diagnosis can be confirmed by covert video surveillance"; but covert videoing "must be used sparingly". This leads to a dangerous result-namely, dependence on unsupervised physiological monitoring for the diagnosis of IUAO, which is not justified by the facts.
The
only physiological recording
in the
original paper’
did
not
record oxygen saturation or nasal airflow, was not coincident with video recording, and does not conform to their characteristic pattern of IUAO. No records of other infants during IUAO have been reported. Furthermore, recordings during covert video surveillance are unlikely to produce any characteristic pattern because of their brevity, which is caused by observer intervention (20 s). A newborn baby can recruit many mechanisms in response to IUAO, such as arousal, breath-hold, and hyperventilation, which vary greatly according to sleep state, age, maturation, and wellbeing. During these responses, heart-rate responses are not only related to respiratory effort and hypoxaemia; furthermore, non-invasive sensors attached to the body are unlikely to record these accurately. Many spontaneous actions-such as stretching, moving, regurgitation, seizure, and spontaneous upper airway obstructionproduce similar events. Thus most sleep laboratories depend on video recording in addition to detailed polysomnographic recording to characterise events during the procedure. Recently, at the end of a recording, in which a healthy infant appeared to have a severe vasovagal episode associated with regurgitation, our video system failed; the sequence of movements and cardiorespiratory events paralleled those described as being characteristic of IUAO.1 After the event, whether changes in the multichannel recording were caused by the mother or one of the two investigators present during their assistance to the distressed infant was difficult to establish. Nor was their subsequent recall helpful in identifying the sequence of events on the recordings. With respect to validity of the methods used at home,1 transcutaneous oxygen tension (tcpOz) operated at suboptimum temperature indicates some non-linear relation with arterial oxygen tension (and is itself of unproven value for quantifying arterial oxygenation) and is set to alarm at 2-66 kPa. Breathing movements are detected by a single Graseby pressure capsule, which is not a reliable method. The system is not a long-term recorder, it only records events when tcp02 is below 2-66 kPa. Improved methods, including better sensors and continuous recording of all data, provide much more information on cardiorespiratory function and neurobehaviour of the infant, including any events. Even with these facilities, a European Community working party on non-laboratory monitoring standards for infants endorsed the need for the addition of video. The need for all monitors to record their measurements is paramount and now possible. However, the use of recordings as proposed is likely to lead many parents to refuse better continuously recording monitors, even for the increasing number of infants now discharged home, who need this advanced care. Why should parents risk incrimination based solely on opinion from an, as yet, unproven technique? Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
PAUL JOHNSON
1. Samuels
MP, McClaughlin W, Jacobson RR, Poets CF, Southall DP. Fourteen of imposed upper airway obstruction. Arch Dis Child 1992; 67: 162-70.
Inappropriate sensor application oximetry
in
cases
pulse
SiR,—We have been recording and studying signals derived from N200, the most widely, validated oximeter in paediatrics.l-4 We always examine the amplitude and shape of the individual light plethysmograph (pulse) waveforms on the recordings before accepting the accuracy of any oxygen saturation (Sa 02) value. We are aware of the importance of ensuring that all light from the emitting diodes passes through the tissue bed under the sensor before reaching the receiving diodes. We were alarmed recently that, despite these precautions, we had recorded a prolonged episode of apparent hypoxaemia (SaOz 80-82%) in which the light plethysmograph signals were similar to, although smaller than, those recorded from a second oximeter, which read 98% (figure). The bouncing light displays on both oximeters showed good signals and the 10-week-old infant was asleep. The sensors (D20 infant probe) encompassed the right and left big toes and were secured with compliant tape (Sleek, 3M). the Nellcor
482
HHV-6.’ Even if the attack rate of 60% is overestimated by diagnostic error, we can estimate that at least 50% (60 x 0-8 50) of Japanese infants are attacked by ES. This attack rate of ES in Japan is much higher than that in the USA. Different endemicity of HHV-6 and/or difference ofimmunogenetic backgrounds between Japan and western countries may be the explanation.
to
=
KOICHI KUSUHARA KOHJI UEDA CHIAKI MIYAZAKI KENJI OKADA KEN TOKUGAWA
Department of Pediatrics, Faculty of Medicine, Kyushu Unniversity, Fukuoka 812, Japan
Recording from 10-week-old infant. Traces show arterial oxygen saturation (Sa02), light plethysmographic waveforms from pulse oximeters, breathing movements from volumatic and transcutaneous capsule (Graseby), P02 (Kontron), electroencephalogram (ECG) Arrow marks where oximeter with incorrectly applied oxysensor was disconnected, and appropriately applied sensor was reconnected to recorder.
A close examination of the sensor reading Sa02 80-82 % revealed that a proportion of the emitted light was "shunting" past the tissue bed directly onto the receiving diodes. On readjustment of the position of this sensor, values of between 97-100% were obtained. In clinical practice such discrepancies could lead to the excessive administration of additional inspired oxygen, which in the preterm infant, could result in an increased risk of retinopathy and other possible manifestations of oxygen toxicity. Our observation illustrates the importance of in-service training in the use of pulse oximetry, as well as regular checking by nursing and medical staff of sensor application, including that fresh adhesive is used in securing the sensor on the patient to avoid the possibility of slippage after prolonged monitoring. Ideally, pulse oximeters should be able to identify this abnormal light transmission to the user. Academic Department of Paediatrics, North Staffordshire Hospital Centre, Stoke-on-Trent ST4 6QG, UK
DAVID P. SOUTHALL MARTIN SAMUELS
1. Bucher HU, Fanconi S, Baeckert P, Duc G. Hyperoxemia in newborn infants: detection by pulse oximetry. Pediatrics 1989; 84: 226-30. 2. Southall DP, Bignall S, Stebbens VA, Alexander JR, Rivers R, Lissauer T. Pulse oximeter and transcutaneous arterial oxygen measurements in neonatal and paediatric intensive care. Arch Dis Child 1987; 62: 882-88. 3. Poets CF, Stebbens VA, Alexander JR, Arrowsmith WA, Salfield SAW, Southall DP. Arterial oxygen saturation in preterm infants at discharge from hospital and six weeks later. J Pediatrics 1992; 120: 447-54. 4. Stebbens VA, Poets CF, Alexander JA, Arrowsmith WA, Southall DP. Oxygen saturations and breathing patterns in infancy I: fullterm infants in the second month of life. Arch Dis Child 1991; 569: 573.
Attack rate of exanthem subitum in
Japan
SIR,-Exanthem subitum (ES) is a common exanthematous early infancy and is a manifestation of human
disease in
herpesvirus-6 (HHV-6) infection.1,2 About 30% of all infants develop apparent ES in western countriesWe have the impression that Japanese infants are more affected by ES than infants in the west. However, the attack rate of ES among infants in Japan is unknown. We sent a questionnaire in January, 1991, to 76 paediatricians about history of ES in their children older than 12 months of age. All these paediatricians were trainees on the paediatric wards of our university hospital and its affiliated hospitals between 1975 and 1986. Our diagnostic criteria for ES were age less than 3 years, preceding fever of 2 or 4 days’ duration, and appearance of pink maculopapular rash mainly on trunk and coincident with abatement of fever. Replies on 115 children (57 male and 58 female) from 56 paediatricians (74%) were obtained. Among these 115 children, 70 (61%) had a history of ES. No difference was observed between males (61 %) and females (60%). The ages of onset of E S ranged from 2 to 21 months, and peaked at 6 months. In our serological study, in 81 % of patients, clinical ES was due
1. Yamanishi K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2. Ueda K, Kusuhara K, Hirose M, et al. Exanthem subitum and antibody to human herpesvirus-6. J Infect Dis 1989; 159: 750-52. 3. Krugman S, Katz SL, Gershon AA, et al. Infectious diseases of children. 9th ed. St Louis: Mosby, 1992: 377-80. 4. Ueda K, Miyazaki C, Okada K, et al. Human herpesvirus-6 (HHV-6): clinical and epidemiologic aspects on exanthema subitum. First International Herpesvirus Symposium in Japan, June 23-24, 1992: 19 (abstr).
Intrauterine transmission of human
herpesvirus 6 SIR,-Primary infection with human herpesvirus 6 (HHV-6) is the cause of exanthem subituml and acute febrile illness without rash2 in young children. Serological studies showed that HHV-6 infection generally occurs early in life, after the disappearance of maternal HHV-6 antibodies.3 Dr Dunne and Dr Demmler’s (July 11, p 121) finding of HHV-6-specific IgM antibody in cord-blood sera suggests the possibility of congenital infection. We provide direct evidence of intrauterine HHV-6 transmission. We have analysed thymus samples from 52 fetuses for the presence of HHV-6 by the polymerase chain reaction (PCR). Fetuses were obtained through induced abortion from HIV-1seropositive women who had decided to interrupt their pregnancy because of HIV infection and had given their informed consent for the study. Fetal organs and body fluids were immediately extracted with special care to avoid any cross contamination and kept frozen at 800C until virological study. Genomic DNA was prepared and PCR was done as previously described4 with two distinct HHV-6 -
primer pairs. HHV-6 specific DNA sequences were detected in one thymus sample only, and were also found in the peripheral blood mononuclear cells (PBMCs), liver, spleen, brain, and cerebrospinal fluid from the same fetus. This fetus was obtained after 26 weeks of gestation and did not have any apparent abnormality. No HIV-1specific DNA sequence was detected in the sample from this fetus by PCR with the primer pairs SK38jSK39,S and P3/P4By contrast, both HIV-1and HHV-6 DNA sequences were present in the PBMCs obtained from the mother at the time of abortion. Restriction patterns of HHV-6-specific amplified products from the fetus were identical to those from the mother and showed that the virus belonged to HHV-6 group IL4 IgG antibody titre to HHV-6 was measured by indirect immunofluorescence assay:’ maternal serum and fetal plasma showed a similar titre of 640, substantially higher than those seen in healthy subjects with the same assay.7 No HHV-6-specific IgM antibody was detected in either sample. The presence of HHV-6 DNA in fetal tissues might have been due to the contamination by maternal blood at the time of abortion and, in this case, the apparent lack of HI V transmission could be due to a low HIV-1 copy number in fetus. To exclude blood contamination, we quantified in parallel PCR runs the amount of HIV-1and HHV-6 DNA sequences in PBMCs from mother and fetus with serial five-fold dilutions of cell DNA. The end-point dilutions of DNA for the detection of HIV-1 and HHV-6 were 4 ng (lane 3, figure) and 0-8 ng (lane 4), respectively, in the mother, and more than 5 ug (lane 7) and less than 1-6 ng (lane 12) in the fetus. Therefore, the ratios of end-point HIV-1-positive dilution to end-point HHV-6-positive dilution were 5 in the mother and greater than 3125 in the fetus. This striking difference could not fit with maternal blood contamination since, in this case, these ratios should be similar.
Diagnosis of recurrent suffocation of children SiR,—Although diagnosis of recurrent suffocation of children is important, mothers of babies with recurrent apnoea should not be
falsely accused of suffocating their babies. There are three statements in your July 11 editorial that may lead doctors falsely to suspect or accuse mothers of suffocation.
First, you say "the onset of these episodes always occurs in the presence of one carer, usually the mother". Infants spend most of their time with their mother and very little with someone else watching, even in hospital. Therefore, most instances of natural postneonatal apnoea, even when recurrent, are initially reported by the mother. Second, you also say "the need for recurrent cardiopulmonary resuscitation started by a carer but continued by professionals is a suggestive feature". I fail to understand the logic of this statement. If a mother has a baby with recurrent apnoeic attacks, what is she expected to do? A caring mother is bound to attempt to resuscitate her baby. If the baby was so ill that resuscitation was continued by professionals, this is more likely to be genuine severe apnoea rather than suffocation. Third, you state "the parents are often concerned and cooperative (’model parents’)". Most parents of my patients would fit into this category. This must be one of the "softest" signs ever proposed in medicine. Before these signs are accepted as part of the criteria for diagnosing suffocation, their proponents should provide evidence of their statistical efficacy-ie, sensitivity, specificity, positive predictive value, and false-positive rate. Proposing these as important pointers to the diagnosis of suffocation would teach doctors to suspect most mothers whose infants have recurrent apnoea, just at the time when they most need sympathetic help and support. You also propagate the unproven idea that, "If arterial oxygen saturation, breathing movements, electrocardiogram, heart rate, and nasal airflow are monitored simultaneously a characteristic pattern of changes is observed during suffocation". There are many reasons for sudden large body movements that are associated with apnoea, hypoxia, tachycardia, and bradycardia-for example struggling, arching the back, fits, or obstructive apnoea due to natural causes such as laryngeal spasm after gastro-oesophageal reflux. Continued breathing movements with absent airflow certainly suggest obstruction to the airway. However, this cannot be regarded as characteristic of suffocation, which must be the rarest cause of such findings. In Samuels and co-workers’ report,’ their figure purporting to show a recording of suffocation does not fulfil their own criteria since air flow was not recorded and therefore absent air flow cannot be confirmed; there was no tachycardia or bradycardia; and the abdominal movement monitor showed increased movement but at the same rate as the normal breathing. Suffocation cannot be diagnosed from recordings alone; these can be interpreted accurately only if they are correlated with a direct witness of the event and preferably a video recording. If we are persuaded to accept some of these unproven ideas, innocent mothers will be accused of a serious crime from which they will fmd it hard to defend themselves. Department of Paediatrics, University of Cambridge School
of Clinical Medicine,
Addenbrook’s Hospital,
Cambridge CB2 2QQ, UK
COLIN MORLEY
1 Samuels MP, McClaughlin W. Jacobson RR, Poets CF, Southall DP. Fourteen cases of imposed upper airway obstruction. Arch Dis Child 1992; 67: 162-70
SiR,—In your July 11editorial you state that "long-term multichannel physiological recordings can provide essential diagnostic information" for imposed upper airway obstruction (IUAO); that its combination with personal and maternal history "may seem conclusive but will be insufficient to convince some people"; if not, "the diagnosis can be confirmed by covert video surveillance"; but covert videoing "must be used sparingly". This leads to a dangerous result-namely, dependence on unsupervised physiological monitoring for the diagnosis of IUAO, which is not justified by the facts.
The
only physiological recording
in the
original paper’
did
not
record oxygen saturation or nasal airflow, was not coincident with video recording, and does not conform to their characteristic pattern of IUAO. No records of other infants during IUAO have been reported. Furthermore, recordings during covert video surveillance are unlikely to produce any characteristic pattern because of their brevity, which is caused by observer intervention (20 s). A newborn baby can recruit many mechanisms in response to IUAO, such as arousal, breath-hold, and hyperventilation, which vary greatly according to sleep state, age, maturation, and wellbeing. During these responses, heart-rate responses are not only related to respiratory effort and hypoxaemia; furthermore, non-invasive sensors attached to the body are unlikely to record these accurately. Many spontaneous actions-such as stretching, moving, regurgitation, seizure, and spontaneous upper airway obstructionproduce similar events. Thus most sleep laboratories depend on video recording in addition to detailed polysomnographic recording to characterise events during the procedure. Recently, at the end of a recording, in which a healthy infant appeared to have a severe vasovagal episode associated with regurgitation, our video system failed; the sequence of movements and cardiorespiratory events paralleled those described as being characteristic of IUAO.1 After the event, whether changes in the multichannel recording were caused by the mother or one of the two investigators present during their assistance to the distressed infant was difficult to establish. Nor was their subsequent recall helpful in identifying the sequence of events on the recordings. With respect to validity of the methods used at home,1 transcutaneous oxygen tension (tcpOz) operated at suboptimum temperature indicates some non-linear relation with arterial oxygen tension (and is itself of unproven value for quantifying arterial oxygenation) and is set to alarm at 2-66 kPa. Breathing movements are detected by a single Graseby pressure capsule, which is not a reliable method. The system is not a long-term recorder, it only records events when tcp02 is below 2-66 kPa. Improved methods, including better sensors and continuous recording of all data, provide much more information on cardiorespiratory function and neurobehaviour of the infant, including any events. Even with these facilities, a European Community working party on non-laboratory monitoring standards for infants endorsed the need for the addition of video. The need for all monitors to record their measurements is paramount and now possible. However, the use of recordings as proposed is likely to lead many parents to refuse better continuously recording monitors, even for the increasing number of infants now discharged home, who need this advanced care. Why should parents risk incrimination based solely on opinion from an, as yet, unproven technique? Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
PAUL JOHNSON
1. Samuels
MP, McClaughlin W, Jacobson RR, Poets CF, Southall DP. Fourteen of imposed upper airway obstruction. Arch Dis Child 1992; 67: 162-70.
Inappropriate sensor application oximetry
in
cases
pulse
SiR,—We have been recording and studying signals derived from N200, the most widely, validated oximeter in paediatrics.l-4 We always examine the amplitude and shape of the individual light plethysmograph (pulse) waveforms on the recordings before accepting the accuracy of any oxygen saturation (Sa 02) value. We are aware of the importance of ensuring that all light from the emitting diodes passes through the tissue bed under the sensor before reaching the receiving diodes. We were alarmed recently that, despite these precautions, we had recorded a prolonged episode of apparent hypoxaemia (SaOz 80-82%) in which the light plethysmograph signals were similar to, although smaller than, those recorded from a second oximeter, which read 98% (figure). The bouncing light displays on both oximeters showed good signals and the 10-week-old infant was asleep. The sensors (D20 infant probe) encompassed the right and left big toes and were secured with compliant tape (Sleek, 3M). the Nellcor
482
HHV-6.’ Even if the attack rate of 60% is overestimated by diagnostic error, we can estimate that at least 50% (60 x 0-8 50) of Japanese infants are attacked by ES. This attack rate of ES in Japan is much higher than that in the USA. Different endemicity of HHV-6 and/or difference ofimmunogenetic backgrounds between Japan and western countries may be the explanation.
to
=
KOICHI KUSUHARA KOHJI UEDA CHIAKI MIYAZAKI KENJI OKADA KEN TOKUGAWA
Department of Pediatrics, Faculty of Medicine, Kyushu Unniversity, Fukuoka 812, Japan
Recording from 10-week-old infant. Traces show arterial oxygen saturation (Sa02), light plethysmographic waveforms from pulse oximeters, breathing movements from volumatic and transcutaneous capsule (Graseby), P02 (Kontron), electroencephalogram (ECG) Arrow marks where oximeter with incorrectly applied oxysensor was disconnected, and appropriately applied sensor was reconnected to recorder.
A close examination of the sensor reading Sa02 80-82 % revealed that a proportion of the emitted light was "shunting" past the tissue bed directly onto the receiving diodes. On readjustment of the position of this sensor, values of between 97-100% were obtained. In clinical practice such discrepancies could lead to the excessive administration of additional inspired oxygen, which in the preterm infant, could result in an increased risk of retinopathy and other possible manifestations of oxygen toxicity. Our observation illustrates the importance of in-service training in the use of pulse oximetry, as well as regular checking by nursing and medical staff of sensor application, including that fresh adhesive is used in securing the sensor on the patient to avoid the possibility of slippage after prolonged monitoring. Ideally, pulse oximeters should be able to identify this abnormal light transmission to the user. Academic Department of Paediatrics, North Staffordshire Hospital Centre, Stoke-on-Trent ST4 6QG, UK
DAVID P. SOUTHALL MARTIN SAMUELS
1. Bucher HU, Fanconi S, Baeckert P, Duc G. Hyperoxemia in newborn infants: detection by pulse oximetry. Pediatrics 1989; 84: 226-30. 2. Southall DP, Bignall S, Stebbens VA, Alexander JR, Rivers R, Lissauer T. Pulse oximeter and transcutaneous arterial oxygen measurements in neonatal and paediatric intensive care. Arch Dis Child 1987; 62: 882-88. 3. Poets CF, Stebbens VA, Alexander JR, Arrowsmith WA, Salfield SAW, Southall DP. Arterial oxygen saturation in preterm infants at discharge from hospital and six weeks later. J Pediatrics 1992; 120: 447-54. 4. Stebbens VA, Poets CF, Alexander JA, Arrowsmith WA, Southall DP. Oxygen saturations and breathing patterns in infancy I: fullterm infants in the second month of life. Arch Dis Child 1991; 569: 573.
Attack rate of exanthem subitum in
Japan
SIR,-Exanthem subitum (ES) is a common exanthematous early infancy and is a manifestation of human
disease in
herpesvirus-6 (HHV-6) infection.1,2 About 30% of all infants develop apparent ES in western countriesWe have the impression that Japanese infants are more affected by ES than infants in the west. However, the attack rate of ES among infants in Japan is unknown. We sent a questionnaire in January, 1991, to 76 paediatricians about history of ES in their children older than 12 months of age. All these paediatricians were trainees on the paediatric wards of our university hospital and its affiliated hospitals between 1975 and 1986. Our diagnostic criteria for ES were age less than 3 years, preceding fever of 2 or 4 days’ duration, and appearance of pink maculopapular rash mainly on trunk and coincident with abatement of fever. Replies on 115 children (57 male and 58 female) from 56 paediatricians (74%) were obtained. Among these 115 children, 70 (61%) had a history of ES. No difference was observed between males (61 %) and females (60%). The ages of onset of E S ranged from 2 to 21 months, and peaked at 6 months. In our serological study, in 81 % of patients, clinical ES was due
1. Yamanishi K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2. Ueda K, Kusuhara K, Hirose M, et al. Exanthem subitum and antibody to human herpesvirus-6. J Infect Dis 1989; 159: 750-52. 3. Krugman S, Katz SL, Gershon AA, et al. Infectious diseases of children. 9th ed. St Louis: Mosby, 1992: 377-80. 4. Ueda K, Miyazaki C, Okada K, et al. Human herpesvirus-6 (HHV-6): clinical and epidemiologic aspects on exanthema subitum. First International Herpesvirus Symposium in Japan, June 23-24, 1992: 19 (abstr).
Intrauterine transmission of human
herpesvirus 6 SIR,-Primary infection with human herpesvirus 6 (HHV-6) is the cause of exanthem subituml and acute febrile illness without rash2 in young children. Serological studies showed that HHV-6 infection generally occurs early in life, after the disappearance of maternal HHV-6 antibodies.3 Dr Dunne and Dr Demmler’s (July 11, p 121) finding of HHV-6-specific IgM antibody in cord-blood sera suggests the possibility of congenital infection. We provide direct evidence of intrauterine HHV-6 transmission. We have analysed thymus samples from 52 fetuses for the presence of HHV-6 by the polymerase chain reaction (PCR). Fetuses were obtained through induced abortion from HIV-1seropositive women who had decided to interrupt their pregnancy because of HIV infection and had given their informed consent for the study. Fetal organs and body fluids were immediately extracted with special care to avoid any cross contamination and kept frozen at 800C until virological study. Genomic DNA was prepared and PCR was done as previously described4 with two distinct HHV-6 -
primer pairs. HHV-6 specific DNA sequences were detected in one thymus sample only, and were also found in the peripheral blood mononuclear cells (PBMCs), liver, spleen, brain, and cerebrospinal fluid from the same fetus. This fetus was obtained after 26 weeks of gestation and did not have any apparent abnormality. No HIV-1specific DNA sequence was detected in the sample from this fetus by PCR with the primer pairs SK38jSK39,S and P3/P4By contrast, both HIV-1and HHV-6 DNA sequences were present in the PBMCs obtained from the mother at the time of abortion. Restriction patterns of HHV-6-specific amplified products from the fetus were identical to those from the mother and showed that the virus belonged to HHV-6 group IL4 IgG antibody titre to HHV-6 was measured by indirect immunofluorescence assay:’ maternal serum and fetal plasma showed a similar titre of 640, substantially higher than those seen in healthy subjects with the same assay.7 No HHV-6-specific IgM antibody was detected in either sample. The presence of HHV-6 DNA in fetal tissues might have been due to the contamination by maternal blood at the time of abortion and, in this case, the apparent lack of HI V transmission could be due to a low HIV-1 copy number in fetus. To exclude blood contamination, we quantified in parallel PCR runs the amount of HIV-1and HHV-6 DNA sequences in PBMCs from mother and fetus with serial five-fold dilutions of cell DNA. The end-point dilutions of DNA for the detection of HIV-1 and HHV-6 were 4 ng (lane 3, figure) and 0-8 ng (lane 4), respectively, in the mother, and more than 5 ug (lane 7) and less than 1-6 ng (lane 12) in the fetus. Therefore, the ratios of end-point HIV-1-positive dilution to end-point HHV-6-positive dilution were 5 in the mother and greater than 3125 in the fetus. This striking difference could not fit with maternal blood contamination since, in this case, these ratios should be similar.
