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February 28, 1996, Vol 275, No. 8 >
ARTICLE | February 28, 1996

Neonatal Characteristics in Rapidly Progressive Perinatally Acquired HIV-1 Disease FREE

Marie-Jeanne Mayaux; Marianne Burgard, MD; Jean-Paul Teglas, MS; Jacqueline Cottalorda, MD; Anne Krivine, MD; François Simon, MD; Jacqueline Puel, MD; Catherine Tamalet, MD; Dominique Dormont, MD; Bernard Masquelier, MD; Anne Doussin, MD; Christine Rouzioux, PhD; Stéphane Blanche, MD; B. Pautard; D. Brault; J. Mamou; A. Broyart; M. Dandine; X. Hernandorena; P. Balde; E. Lachassine; D. Douard; H. Fleury; B. Masquelier; I. Gilles; A. Gantzer; A-M. Colin-Gorki; J. Brouard; F. Freymuth; L. Keros; P. Labrune; M. Vial; F. Mazy; C. Floch; P. Bourdon; M. Duval-Arnould; C. Huraux-Rendu; S. Lemerle; M. Boddaert; M-F. Denavit; K. Lahsinat; C. Pascal; A. Leblanc; A. May; C. Dallot; D. Dormont; B. Bader-Meunier; E. Dussaix; M. Tardieu; H. Seaume; P. Wipff; P. Deboisse; G. Michel; C. Tamalet; D. Vallée; C. Crumière; A. Saillant; B. Le Lorier; C. Botto; D. Seguy; P. Talon; C. Huret; J. Nicolas; J. Lalande; F. Mechineau-Lacroix; D. Berterottière; J. Cottalorda; A. Deville; F. Monpoux; A. de Crepy; F. Simon; S. Parat; G. Firtion; M. Ronzier; C. Brunner; N. Ciraru-Vigneron; B. Heller-Roussin; S. Blanche; M. Burgard; D. Girault; C. Rouzioux; J. Terris; F. Veber; J-M. Huraux; G. Noseda; M. Levine; E. Vilmer; A. Vallet; L. Marpeau; F. Parnet Mathieu; C. Aufrant; C. Francoual; A. Krivine; F. Hervé; C. Courpotin; C. Dollfus; C. Carlus Moncomble; M-C. Rousset; G. Mouchnino; V. Brossard; C. Buffet-Janvresse; M. Robin; F. Labbe-Filou; M. C. Allemon; J.-M. Retbi; P. Narcy; A.-M. Raison Boulley; J. Puel; J. Tricoire; F. Barin; J.-C. Borderon; R. Busuttil; A. Vinas; F. Guillot; A. Lacroix-Coutry.
[+] Author Affiliations

A complete list of the participants in this research study appears at the end of the article.

Reprint requests to Institut National de la Santé et de la Recherche Médicale, Unit 292, Hôpital Bicêtre, Secteur Bleu "Pierre-Marie"—Porte 26, 82 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France (Ms Mayaux).


JAMA. 1996;275(8):606-610. doi:10.1001/jama.1996.03530320030030
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References

Objective.  —To identify clinical and laboratory parameters at birth that are associated with the rapidly progressive form of human immunodeficiency virus type 1 (HIV-1) disease in children born to infected mothers.

Design.  —Multicenter, prospective study of infants born to HIV-seropositive mothers.

Setting.  —A total of 62 obstetric and pediatric centers in France.

Participants.  —Of 1386 children born to HIV-1—seropositive mothers at least 18 months before the cutoff date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before this age.

Main Outcome Measure.  —Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific encephalopathy, and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention classification during the first year of life, according to clinical, immunological, and virological findings at birth.

Results.  —The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1% vs 15.1%; relative risk [RR], 2.5; 95% confidence interval [CI], 1.4 to 6.0; P<.02) or a low proportion (<30%) of CD4+ cells at birth (45.5% vs 15.0%; RR, 3.0; 95% CI, 1.4 to 6.4; P<.005). Similarly, HIV-1 culture and/or polymerase chain reaction positivity during the first week of life was associated with a higher risk of the early, severe form of HIV infection (26.4% vs 9.3%; RR, 2.8; 95% CI, 1.3 to 6.1; P<.006). In case of positive antigenemia at birth, the risk was 50.0% vs 14.4% (RR, 3.5; 95% CI, 1.9 to 6.2; P<.001 ). These parameters, determined at birth, were strongly interrelated and could reflect active disease onset in utero in some cases of early, severe HIV-1 disease in childhood.

Conclusions.  —These prognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention.(JAMA. 1996;275:606-610)

REFERENCES

1 +
Auger I, Thomas P, De Gruttola V, et al.  Incubation periods for paediatric AIDS patients. Nature . 1988;;336:575-577.
2 +
Scott GB, Hutto C, Makuch RW, et al.  Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med . 1989;;321:1791-1796.
3 +
Blanche S, Tardieu M, Duliège A, et al.  Longitudinal study of 94 symptomatic infants with perinatally acquired human immunodeficiency virus infection: evidence for a bimodal expression of clinical and biological symptoms. AJDC . 1990;;144:1210-1215.
4 +
Italian Multicentre Study.  Epidemiology, clinical features and prognostic factors of pediatric HIV infection. Lancet . 1988;;2:1043-1046.
5 +
Lindgren S, Anzen B, Bohlin A-B, et al.  HIV and child-bearing: clinical outcome and aspects of mother-to-infant transmission. AIDS . 1991;;5:1111-1116.
6 +
Hutto C, Parks WP, Lai S, et al.  A hospital-based prospective study of perinatal infection with human immunodeficiency virus type 1. J Pediatr . 1991;;118:347-353.
7 +
Gabiano C, Tovo P-A, de Martino M, et al.  Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission. Pediatrics . 1992;;90:369-374.
8 +
Spinillo A, Iasci A, Dal Maso J, et al.  The effect of fetal infection with human immunodeficiency virus type 1 on birthweight and length of gestation. Eur J Obstet Gynecol Reprod Biol . 1994;;57:13-17.
9 +
European Collaborative Study.  Perinatal findings in children born to HIV-infected mothers. Br J Obstet Gynaecol . 1994;;101:136-141.
10 +
Nair P, Alger L, Hines S, et al.  Maternal and neonatal characteristics associated with HIV infection in infants of seropositive women. J Acquir Immune Defic Syndr . 1993;;6:298-302.
11 +
Lepage P, Msellati P, Van de Perre P, et al.  Characteristics of newborns and HIV1 infection in Rwanda. AIDS . 1992;;6:882-883.
12 +
Rogers MF, Ou CY, Rayfield M, et al.  Use of the polymerase chain reaction for early detection of the proviral sequences of human immunodeficiency virus in infants born to seropositive mothers. N Engl J Med . 1989;;320:1649-1654.
13 +
Burgard M, Mayaux MJ, Blanche S, et al.  The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. N Engl J Med . 1992;;327:1192-1197.
14 +
Krivine A, Firtion G, Cao L, et al.  HIV replication during the first weeks of life. Lancet . 1992;; 339:1187-1189.
15 +
De Rossi A, Giaquinto C, Ometto L, et al.  Replication and tropism of human immunodeficiency virus type 1 as predictors of disease outcome in infants with vertically acquired infection. J Pediatr . 1993;;123:929-936.
16 +
Borkowsky W, Krasinski K, Cao Y, et al.  Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes. J Pediatr . 1994;;125: 345-351.
17 +
Schupbach J, Doni J, Tomasik Z, et al.  Sensitive detection and early prognostic significance of p24 antigen in heat-denaturated plasma of human immunodeficiency virus type 1 infected infants. J Infect Dis . 1994;;170:318-324.
18 +
Mayaux MJ, Blanche S, Rouzioux C, et al.  Maternal factors associated with perinatal HIV-1 transmission: The French Cohort Study—7 years of follow-up observation. J Acquir Immune Defic Syndr . 1995;;8:188-194.
19 +
Rouzioux C, Burgard M, Blanche S, et al.  Quantitative PCR for the diagnosis of HIV-1 infection in newborns to seropositive mothers.  In: Andrieu J-M, ed. Viral Quantitation in HIV Infection . Paris, France: John Libbey Eurotext; 1991;:187-191.
20 +
Rouzioux C, Burgard M, Journot V, Aboulker JP. French quality control for quantitative plasma viremia. Presented at the First National Conference on Human Retroviruses and Related Infections; December 14, 1993; Washington, DC.
21 +
Caldwell MB, Oxtoby MJ, Simonds RJ, Lindegren ML, Rogers MF.  1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep . 1994;;43( (RR-12) ):1-10.
22 +
Brookmeyer R, Gail MH, Polk BF.  The prevalent cohort study and the acquired immunodeficiency syndrome. Am J Epidemiol . 1987;;126:14-24.
23 +
Pizzo PA, Wilfert CM, and the Pediatric AIDS Siena Workshop II.  Markers and determinants of disease progression in children with HIV infection. J Acquir Immune Defic Syndr . 1995;;8:30-44.
24 +
Delfraissy JF, Blanche S, Rouzioux C, Mayaux MJ.  Perinatal HIV transmission fact and controversies. Immunodef Rev . 1992;;3:305-327.
25 +
Blanche S, Mayaux MJ, Rouzioux C, et al.  Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery. N Engl J Med . 1994;;330:308-312.
26 +
Tovo PA, De Martino M, Gabiano C, et al.  AIDS appearance in children is associated with the velocity of disease progression in their mothers. J Infect Dis . 1994;;170:1000-1002.
27 +
Bryson YL, Wzuriaga K, Sullivan JL, Wara DW.  Proposed definitions for in utero versus intrapartum transmission of HIV-1. N Engl J Med . 1992;;327:1246-1247.
28 +
Blanche S, Le Deist F, Fischer A, et al.  Longitudinal study of 18 children with perinatal LAV/ HTLVIII infection: attempt at prognostic evaluation. J Pediatr . 1986;;109:965-970.
29 +
Jones DS, Byers RH, Bush TJ, Oxtoby MJ, Rogers MF.  Epidemiology of transfusion-associated acquired immunodeficiency syndrome in children in the United States, 1981 through 1989. Pediatrics . 1992;;89:123-127.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Auger I, Thomas P, De Gruttola V, et al.  Incubation periods for paediatric AIDS patients. Nature . 1988;;336:575-577.
2 +
Scott GB, Hutto C, Makuch RW, et al.  Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med . 1989;;321:1791-1796.
3 +
Blanche S, Tardieu M, Duliège A, et al.  Longitudinal study of 94 symptomatic infants with perinatally acquired human immunodeficiency virus infection: evidence for a bimodal expression of clinical and biological symptoms. AJDC . 1990;;144:1210-1215.
4 +
Italian Multicentre Study.  Epidemiology, clinical features and prognostic factors of pediatric HIV infection. Lancet . 1988;;2:1043-1046.
5 +
Lindgren S, Anzen B, Bohlin A-B, et al.  HIV and child-bearing: clinical outcome and aspects of mother-to-infant transmission. AIDS . 1991;;5:1111-1116.
6 +
Hutto C, Parks WP, Lai S, et al.  A hospital-based prospective study of perinatal infection with human immunodeficiency virus type 1. J Pediatr . 1991;;118:347-353.
7 +
Gabiano C, Tovo P-A, de Martino M, et al.  Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission. Pediatrics . 1992;;90:369-374.
8 +
Spinillo A, Iasci A, Dal Maso J, et al.  The effect of fetal infection with human immunodeficiency virus type 1 on birthweight and length of gestation. Eur J Obstet Gynecol Reprod Biol . 1994;;57:13-17.
9 +
European Collaborative Study.  Perinatal findings in children born to HIV-infected mothers. Br J Obstet Gynaecol . 1994;;101:136-141.
10 +
Nair P, Alger L, Hines S, et al.  Maternal and neonatal characteristics associated with HIV infection in infants of seropositive women. J Acquir Immune Defic Syndr . 1993;;6:298-302.
11 +
Lepage P, Msellati P, Van de Perre P, et al.  Characteristics of newborns and HIV1 infection in Rwanda. AIDS . 1992;;6:882-883.
12 +
Rogers MF, Ou CY, Rayfield M, et al.  Use of the polymerase chain reaction for early detection of the proviral sequences of human immunodeficiency virus in infants born to seropositive mothers. N Engl J Med . 1989;;320:1649-1654.
13 +
Burgard M, Mayaux MJ, Blanche S, et al.  The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. N Engl J Med . 1992;;327:1192-1197.
14 +
Krivine A, Firtion G, Cao L, et al.  HIV replication during the first weeks of life. Lancet . 1992;; 339:1187-1189.
15 +
De Rossi A, Giaquinto C, Ometto L, et al.  Replication and tropism of human immunodeficiency virus type 1 as predictors of disease outcome in infants with vertically acquired infection. J Pediatr . 1993;;123:929-936.
16 +
Borkowsky W, Krasinski K, Cao Y, et al.  Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes. J Pediatr . 1994;;125: 345-351.
17 +
Schupbach J, Doni J, Tomasik Z, et al.  Sensitive detection and early prognostic significance of p24 antigen in heat-denaturated plasma of human immunodeficiency virus type 1 infected infants. J Infect Dis . 1994;;170:318-324.
18 +
Mayaux MJ, Blanche S, Rouzioux C, et al.  Maternal factors associated with perinatal HIV-1 transmission: The French Cohort Study—7 years of follow-up observation. J Acquir Immune Defic Syndr . 1995;;8:188-194.
19 +
Rouzioux C, Burgard M, Blanche S, et al.  Quantitative PCR for the diagnosis of HIV-1 infection in newborns to seropositive mothers.  In: Andrieu J-M, ed. Viral Quantitation in HIV Infection . Paris, France: John Libbey Eurotext; 1991;:187-191.
20 +
Rouzioux C, Burgard M, Journot V, Aboulker JP. French quality control for quantitative plasma viremia. Presented at the First National Conference on Human Retroviruses and Related Infections; December 14, 1993; Washington, DC.
21 +
Caldwell MB, Oxtoby MJ, Simonds RJ, Lindegren ML, Rogers MF.  1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep . 1994;;43( (RR-12) ):1-10.
22 +
Brookmeyer R, Gail MH, Polk BF.  The prevalent cohort study and the acquired immunodeficiency syndrome. Am J Epidemiol . 1987;;126:14-24.
23 +
Pizzo PA, Wilfert CM, and the Pediatric AIDS Siena Workshop II.  Markers and determinants of disease progression in children with HIV infection. J Acquir Immune Defic Syndr . 1995;;8:30-44.
24 +
Delfraissy JF, Blanche S, Rouzioux C, Mayaux MJ.  Perinatal HIV transmission fact and controversies. Immunodef Rev . 1992;;3:305-327.
25 +
Blanche S, Mayaux MJ, Rouzioux C, et al.  Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery. N Engl J Med . 1994;;330:308-312.
26 +
Tovo PA, De Martino M, Gabiano C, et al.  AIDS appearance in children is associated with the velocity of disease progression in their mothers. J Infect Dis . 1994;;170:1000-1002.
27 +
Bryson YL, Wzuriaga K, Sullivan JL, Wara DW.  Proposed definitions for in utero versus intrapartum transmission of HIV-1. N Engl J Med . 1992;;327:1246-1247.
28 +
Blanche S, Le Deist F, Fischer A, et al.  Longitudinal study of 18 children with perinatal LAV/ HTLVIII infection: attempt at prognostic evaluation. J Pediatr . 1986;;109:965-970.
29 +
Jones DS, Byers RH, Bush TJ, Oxtoby MJ, Rogers MF.  Epidemiology of transfusion-associated acquired immunodeficiency syndrome in children in the United States, 1981 through 1989. Pediatrics . 1992;;89:123-127.

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