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Maternal infection and cerebral palsy in term infants with periventricular leucomalacia
S154 SMFM Abstracts
December 2003 Am J Obstet Gynecol
336
MATERNAL INFECTION AND CEREBRAL PALSY IN TERM INFANTS WITH PERIVENTRICULAR LEUCOMALACIA BO JACOBSSON1, GUDRUN HAGBERG2, HENRIK HAGBERG1, 1Perinatal Center, Go¨teborg, Sweden 2 Dept. of Pediatrics, Go¨teborg, Sweden OBJECTIVE: Previous studies have investigated maternal infection during delivery as a possible risk factor for cerebral palsy (CP) in term infants. Infants born at term with diagnosed CP and periventricular leukomalacia (PVL) have, however, been excluded. The aim of this study was to investigate the relationship between maternal infections during pregnancy and PVL combined with CP in the offspring. STUDY DESIGN: A population-based case-control study. Term infants with CP and PVL (CP/PVL) (n = 44) born in 1983-94 were included and matched with a control group (n = 88). All records were scrutinized for any infectious disease or use of antibiotics during pregnancy. Cystic and atrophic PVL were diagnosed by a computed tomographic scan. RESULTS: Mothers with any event of infectious disease noted in their records had an increased risk of having a child with CP/PVL (19/44 cases, 21/88 controls [OR 2.42 {1.12-5.25}]), and if the mothers had suffered any event of a more serious infectious disease during pregnancy, they had an even higher risk (6/44 cases, 1/88 controls [OR 13.74 {1.60-118}]). Apgar score < 7 at 1, 5, or 10 minutes did not constitute a risk factor for CP in this particular subgroup of infants. CONCLUSION: Infection in pregnant women was significantly associated with CP/PVL in term infants, especially in those pregnancies complicated by a more severe maternal infection. In spite of a previously demonstrated close correlation between Apgar score at birth and unexplained CP in term infants, depressed viability at birth did not confer an increased risk of CP/PVL. Speculatively, maternal infection during late mid-pregnancy may inflict fetal white matter injury, but not preterm birth, resulting in PVL/CP in infants born at term without signs of intrapartal asphyxia.
338
MONOCYTE CHEMOTACTIC PROTEIN-2 AND -3 IN AMNIOTIC FLUID IS RELATED TO MICROBIAL INVASION OF THE AMNIOTIC FLUID, INTRAAMNIOTIC INFLAMMATION, AND PRETERM DELIVERY BO JACOBSSON1, BENGT ANDERSSON2, HENRIK HAGBERG1, 1Perinatal Center, Go¨teborg, Sweden 2Dept. Immunology, Go¨teborg, Sweden OBJECTIVE: Monocyte chemotactic protein (MCP)-1 has been implicated in the mechanisms of preterm and term parturition. MCP-2 and MCP-3 are also chemokines capable of recruiting and activating monocytes/macrophages. This study was undertaken to determine if MCP-2 and MCP-3 are detectable in amniotic fluid (AF) and related to preterm delivery, intra-amniotic inflammation (IAI), and microbial invasion of the amniotic fluid (MIAF). STUDY DESIGN: Women were included with singleton pregnancies ( < 34 weeks) presenting with preterm labor (PTL) (n = 58) or women at term scheduled for an elective cesarean section (n = 36). AF was retrieved transabdominally. MCP-2 and MCP-3 were analyzed with ELISA, and the detection limit for MCP-2 was < 63 pg/mL, and for MCP-3, < 32 pg/mL. IAI was defined in a previous study of the same patients as elevated interleukin-6 and -8. RESULTS: (1) MCP-2 (range: 80-583 pg/mL) and MCP-3 (range: 36-649 pg/mL) was detectable in 7 of 58 women in PTL, but not necessarily the same women. (2) MCP-2 was not detectable in non-laboring women at term, and MCP-3, only once (90 pg/mL). (3) Women in PTL had significantly more often detectable levels of MCP-3 in AF if they delivered within 7 days from amniocentesis (P < 0.001), before 34 weeks of gestation (P = 0.002), had an IAI (P < 0.001), or if they had MIAF (P = 0.003). (4) Women in PTL had significantly more often detectable levels of MCP-2 if they delivered before 34 weeks of gestation (P = 0.038) or had an IAI (P = 0.042). CONCLUSION: MCP-2 and especially MCP-3 are detectable in women with intra-amniotic inflammation and preterm birth, but not in non-laboring women at term. MCP-2 and MCP-3 are chemokines, which might be mediators of IAI in the more pronounced cases.
337
CEREBRAL PALSY IN TERM INFANTS: A POPULATION-BASED CASECONTROL STUDY OF INFECTIOUS ANTENATAL AND INTRAPARTAL RISK FACTORS BO JACOBSSON1, KRISTINA AHLIN1, GUDRUN HAGBERG2, BENGT HAGBERG2, ULLA-BRITT WENNERHOLM1, HENRIK HAGBERG1, 1Perinatal Center, Go¨teborg, Sweden 2Dept. of Pediatrics, Go¨teborg, Sweden OBJECTIVE: To analyze infection-related risk factors during pregnancy and delivery for spastic CP in infants born at term in a large case-control study. STUDY DESIGN: A population-based series of infants with spastic unexplained CP born at term (n = 166) between 1983 and 1994 were included and matched with a control group (n = 332). Maternal, antenatal, and intrapartal variables were retrieved from obstetric records, focusing on infectious factors defined in advance. RESULTS: In general, few episodes of fever were observed in the records, and only one case of clinical chorioamnionitis. Fever ($38 degrees) before onset of the delivery (OR 1.01 [0.18-5.55]) or fever during the delivery (OR 1.02 [0.19-5.64]) was not associated with CP, but fever ($38 degrees two times with at least 4 h apart) within 48 h after delivery was associated with CP (7/163 cases, 4/ 330 controls [OR 3.66 {1.055-12.68}]). Use of antibiotics before onset of delivery (OR 2.73 [0.60-12.36]) was not associated with CP, but use of antibiotics during delivery correlated with CP (8/157 cases, 0/311 controls [OR 16.64 {2.062134.4}]). There was an association between any infectious disease during pregnancy and CP (59/166 cases, 77/332 controls [OR 1.82 {1.21-2.74}]), but we did not find an increased risk of CP among women having a more severe infection during pregnancy (OR 1.17 [0.45-3.04]). Bacteruria during pregnancy was related to CP (16/166 cases, 6/332 controls [OR 5.80 {2.22-15.1}]). Low viability at birth (Apgar <7 at 1, 5, and 10 minutes) constituted a high risk for unexplained CP in infants born at term. CONCLUSION: No clear association between fever or other infectious signs during delivery and CP were found in term infants. Fever post partum might have been recorded more accurately than during birth and might therefore represent an indicator of intrapartal infection. Any infectious disease or bacteruria noted in the mother’s record during pregnancy constituted a moderately increased risk of CP.
339
A CASE-CONTROL STUDY OF PERINATAL OUTCOMES (PNO) IN GROWTH-RESTRICTED (IUGR) TWINS COMPARED WITH AGEMATCHED GROWTH-RESTRICTED SINGLETONS ANTHONY ODIBO1, RAEGAN MCDONALD2, DORIS CHOU2, SERDAR URAL2, GEORGE MACONES2, 1University of Pennsylvania Medical System, Department of Obstetrics and Gynecology, Philadelphia, PA 2University of Pennsylvania, Obstetrics and Gynecology, Philadelphia, PA OBJECTIVE: To compare the PNO in IUGR twins to a matched group of IUGR singletons. STUDY DESIGN: A case-control study evaluating the PNO in IUGR (birthweight < 10th centile for gestational age) twins matched for gestational age at delivery (GADEL) to IUGR singletons in a 1:4 ratio. The PNO evaluated include rates of admission to NICU, uncorrected perinatal mortality (PNM), respiratory distress syndrome (RDS), grades 3 or 4 intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL), and length of NICU stay. Cases with twin IUGR were compared with the control IUGR singletons for PNO. RESULTS: Of 18,406 deliveries over a 5-year period, there were 99 (0.5%) IUGR twins. These were matched with 396 singleton IUGR. The mean GADEL for the cases was 34 ± 3.8 weeks and 35 ± 3.5 weeks for the control, P = 0.11. See Table below for outcomes. The PNM and morbidities in twins were significantly higher than in singletons CONCLUSION: Compared with age-matched singletons, twins with IUGR have higher perinatal mortality and morbidity rates. This suggests a need for increased antenatal surveillance in IUGR twins.
Perinatal outcomes Twins (%) NICU admissions PNM RDS IVH NEC PVL Length of NICU stay (days ± SD)
71 (72) 13 (13) 26 (26) 8 (8) 0 (0) 0 (0) 31.7 ( ± 33)
Singletons (%) 168 25 29 14 4 2 23.1
(43) (6) (7) (3) (1) (0.5) ( ± 33)
OR (95% CI)
P value
3.8 2.2 4.5 2.4
0.0001 0.02 0.0001 0.05 0.31 0.48 0.02
(2.3-6.3) (1.1-4.6) (2.5-8) (1-5.9)
December 2003 Am J Obstet Gynecol
336
MATERNAL INFECTION AND CEREBRAL PALSY IN TERM INFANTS WITH PERIVENTRICULAR LEUCOMALACIA BO JACOBSSON1, GUDRUN HAGBERG2, HENRIK HAGBERG1, 1Perinatal Center, Go¨teborg, Sweden 2 Dept. of Pediatrics, Go¨teborg, Sweden OBJECTIVE: Previous studies have investigated maternal infection during delivery as a possible risk factor for cerebral palsy (CP) in term infants. Infants born at term with diagnosed CP and periventricular leukomalacia (PVL) have, however, been excluded. The aim of this study was to investigate the relationship between maternal infections during pregnancy and PVL combined with CP in the offspring. STUDY DESIGN: A population-based case-control study. Term infants with CP and PVL (CP/PVL) (n = 44) born in 1983-94 were included and matched with a control group (n = 88). All records were scrutinized for any infectious disease or use of antibiotics during pregnancy. Cystic and atrophic PVL were diagnosed by a computed tomographic scan. RESULTS: Mothers with any event of infectious disease noted in their records had an increased risk of having a child with CP/PVL (19/44 cases, 21/88 controls [OR 2.42 {1.12-5.25}]), and if the mothers had suffered any event of a more serious infectious disease during pregnancy, they had an even higher risk (6/44 cases, 1/88 controls [OR 13.74 {1.60-118}]). Apgar score < 7 at 1, 5, or 10 minutes did not constitute a risk factor for CP in this particular subgroup of infants. CONCLUSION: Infection in pregnant women was significantly associated with CP/PVL in term infants, especially in those pregnancies complicated by a more severe maternal infection. In spite of a previously demonstrated close correlation between Apgar score at birth and unexplained CP in term infants, depressed viability at birth did not confer an increased risk of CP/PVL. Speculatively, maternal infection during late mid-pregnancy may inflict fetal white matter injury, but not preterm birth, resulting in PVL/CP in infants born at term without signs of intrapartal asphyxia.
338
MONOCYTE CHEMOTACTIC PROTEIN-2 AND -3 IN AMNIOTIC FLUID IS RELATED TO MICROBIAL INVASION OF THE AMNIOTIC FLUID, INTRAAMNIOTIC INFLAMMATION, AND PRETERM DELIVERY BO JACOBSSON1, BENGT ANDERSSON2, HENRIK HAGBERG1, 1Perinatal Center, Go¨teborg, Sweden 2Dept. Immunology, Go¨teborg, Sweden OBJECTIVE: Monocyte chemotactic protein (MCP)-1 has been implicated in the mechanisms of preterm and term parturition. MCP-2 and MCP-3 are also chemokines capable of recruiting and activating monocytes/macrophages. This study was undertaken to determine if MCP-2 and MCP-3 are detectable in amniotic fluid (AF) and related to preterm delivery, intra-amniotic inflammation (IAI), and microbial invasion of the amniotic fluid (MIAF). STUDY DESIGN: Women were included with singleton pregnancies ( < 34 weeks) presenting with preterm labor (PTL) (n = 58) or women at term scheduled for an elective cesarean section (n = 36). AF was retrieved transabdominally. MCP-2 and MCP-3 were analyzed with ELISA, and the detection limit for MCP-2 was < 63 pg/mL, and for MCP-3, < 32 pg/mL. IAI was defined in a previous study of the same patients as elevated interleukin-6 and -8. RESULTS: (1) MCP-2 (range: 80-583 pg/mL) and MCP-3 (range: 36-649 pg/mL) was detectable in 7 of 58 women in PTL, but not necessarily the same women. (2) MCP-2 was not detectable in non-laboring women at term, and MCP-3, only once (90 pg/mL). (3) Women in PTL had significantly more often detectable levels of MCP-3 in AF if they delivered within 7 days from amniocentesis (P < 0.001), before 34 weeks of gestation (P = 0.002), had an IAI (P < 0.001), or if they had MIAF (P = 0.003). (4) Women in PTL had significantly more often detectable levels of MCP-2 if they delivered before 34 weeks of gestation (P = 0.038) or had an IAI (P = 0.042). CONCLUSION: MCP-2 and especially MCP-3 are detectable in women with intra-amniotic inflammation and preterm birth, but not in non-laboring women at term. MCP-2 and MCP-3 are chemokines, which might be mediators of IAI in the more pronounced cases.
337
CEREBRAL PALSY IN TERM INFANTS: A POPULATION-BASED CASECONTROL STUDY OF INFECTIOUS ANTENATAL AND INTRAPARTAL RISK FACTORS BO JACOBSSON1, KRISTINA AHLIN1, GUDRUN HAGBERG2, BENGT HAGBERG2, ULLA-BRITT WENNERHOLM1, HENRIK HAGBERG1, 1Perinatal Center, Go¨teborg, Sweden 2Dept. of Pediatrics, Go¨teborg, Sweden OBJECTIVE: To analyze infection-related risk factors during pregnancy and delivery for spastic CP in infants born at term in a large case-control study. STUDY DESIGN: A population-based series of infants with spastic unexplained CP born at term (n = 166) between 1983 and 1994 were included and matched with a control group (n = 332). Maternal, antenatal, and intrapartal variables were retrieved from obstetric records, focusing on infectious factors defined in advance. RESULTS: In general, few episodes of fever were observed in the records, and only one case of clinical chorioamnionitis. Fever ($38 degrees) before onset of the delivery (OR 1.01 [0.18-5.55]) or fever during the delivery (OR 1.02 [0.19-5.64]) was not associated with CP, but fever ($38 degrees two times with at least 4 h apart) within 48 h after delivery was associated with CP (7/163 cases, 4/ 330 controls [OR 3.66 {1.055-12.68}]). Use of antibiotics before onset of delivery (OR 2.73 [0.60-12.36]) was not associated with CP, but use of antibiotics during delivery correlated with CP (8/157 cases, 0/311 controls [OR 16.64 {2.062134.4}]). There was an association between any infectious disease during pregnancy and CP (59/166 cases, 77/332 controls [OR 1.82 {1.21-2.74}]), but we did not find an increased risk of CP among women having a more severe infection during pregnancy (OR 1.17 [0.45-3.04]). Bacteruria during pregnancy was related to CP (16/166 cases, 6/332 controls [OR 5.80 {2.22-15.1}]). Low viability at birth (Apgar <7 at 1, 5, and 10 minutes) constituted a high risk for unexplained CP in infants born at term. CONCLUSION: No clear association between fever or other infectious signs during delivery and CP were found in term infants. Fever post partum might have been recorded more accurately than during birth and might therefore represent an indicator of intrapartal infection. Any infectious disease or bacteruria noted in the mother’s record during pregnancy constituted a moderately increased risk of CP.
339
A CASE-CONTROL STUDY OF PERINATAL OUTCOMES (PNO) IN GROWTH-RESTRICTED (IUGR) TWINS COMPARED WITH AGEMATCHED GROWTH-RESTRICTED SINGLETONS ANTHONY ODIBO1, RAEGAN MCDONALD2, DORIS CHOU2, SERDAR URAL2, GEORGE MACONES2, 1University of Pennsylvania Medical System, Department of Obstetrics and Gynecology, Philadelphia, PA 2University of Pennsylvania, Obstetrics and Gynecology, Philadelphia, PA OBJECTIVE: To compare the PNO in IUGR twins to a matched group of IUGR singletons. STUDY DESIGN: A case-control study evaluating the PNO in IUGR (birthweight < 10th centile for gestational age) twins matched for gestational age at delivery (GADEL) to IUGR singletons in a 1:4 ratio. The PNO evaluated include rates of admission to NICU, uncorrected perinatal mortality (PNM), respiratory distress syndrome (RDS), grades 3 or 4 intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL), and length of NICU stay. Cases with twin IUGR were compared with the control IUGR singletons for PNO. RESULTS: Of 18,406 deliveries over a 5-year period, there were 99 (0.5%) IUGR twins. These were matched with 396 singleton IUGR. The mean GADEL for the cases was 34 ± 3.8 weeks and 35 ± 3.5 weeks for the control, P = 0.11. See Table below for outcomes. The PNM and morbidities in twins were significantly higher than in singletons CONCLUSION: Compared with age-matched singletons, twins with IUGR have higher perinatal mortality and morbidity rates. This suggests a need for increased antenatal surveillance in IUGR twins.
Perinatal outcomes Twins (%) NICU admissions PNM RDS IVH NEC PVL Length of NICU stay (days ± SD)
71 (72) 13 (13) 26 (26) 8 (8) 0 (0) 0 (0) 31.7 ( ± 33)
Singletons (%) 168 25 29 14 4 2 23.1
(43) (6) (7) (3) (1) (0.5) ( ± 33)
OR (95% CI)
P value
3.8 2.2 4.5 2.4
0.0001 0.02 0.0001 0.05 0.31 0.48 0.02
(2.3-6.3) (1.1-4.6) (2.5-8) (1-5.9)