Cerebral Palsy in PreTerm Infants: a Population-Based Case–Control Study of AnteNatal and Intrapartal Risk Factors
Acta Pædiatr 2002; 91: 946–951. Stockholm. ISSN 0803-5253
Jacobsson B, Hagberg G, Hagberg B, Ladfors L, Niklasson A, Hagberg H
Perinatal Center, Departments of Obstetrics and Gynecology , Sahlgrensk a University Hospital and 1Departments of Pediatrics, Queen Silvia Children’s Hospital, Institute for the Health of Women and Children, Go¨ teborg, Sweden
[ED/BR: This 2002 study showed the 60% higher risk of CP (Cerebral Palsy) for children of mothers with prior IAs (Induced Abortions); yet this information is only found in a table — Table 2 — and there is ZERO mention of any CP/IA risk in the main text. — Brent Rooney (MSc), Research Director, Reduce Preterm Risk Coalition, http://www.justiceforkids.webs.com]
Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants.
The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32–36 wk), born in 1983–90, were included and matched with a control group (n = 296).
In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long
interval between rupture of membranes and birth, admission–delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk.
Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups.
Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group.
Conclusion: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.
Preterm birth is the most important risk factor for cerebral palsy (CP). The risk of CP is inversely proportional to gestational age and the relative risk is 60 times higher at <28 wk of gestation than at term (1, 2). Only 6.1% of infants were born preterm (<37 wk of gestation) during the period 1983–1990 in western Sweden, but they accounted for 41.5% of that region’s CP cases (1, 2).
The number of preterm infants with CP has increased since 1970, mainly related to the parallel decrease in perinatal mortality (1, 2). Although perinatal and neonatal risk factors for CP appear to dominate in the preterm group, further investigation into antenatal and intrapartal risk factors is interesting, as they can act as antecedents to the brain damage resulting in CP. In previous analyses of antenatal risk factors for CP in preterm infants no single risk factor has been consistent across all or even most studies (3–16).
Recent studies suggest that foetoplacental uterine infection/inflammation is important in the initiation of preterm labour and for the development of central nervous system injury and CP (16, 17). The western Swedish population is characterized by a low frequency of perinatal infections (18, 19) and a low rate of preterm birth.
Testing the hypothesis that infection is a risk factor for CP in this population as part of the ongoing CP project (1, 2, 20), applying the uniform and internationally accepted definition of this condition (21), may thus be interesting from a pathophysiological standpoint…..
The term “bad obstetric history” was used when one of following criteria was fulfilled: more than three subsequent spontaneous abortions, one spontaneous abortion after 20 wk of gestation, intrauterine foetal death or an earlier case of perinatal death.
Maternal disease was defined as the presence of any of the following diseases at the onset of the pregnancy: diabetes, hypertension, severe psychiatric disease, asthma, active neoplasia, epilepsy and glomerulonephritis…
The distribution of spastic CP types according to gestational age is shown in Table 1.
Most antenatal/ intrapartal factors were unrelated to CP, and the results
are given for the more frequently reported factors and for variables with significant or borderline significant association to outcome.
Maternal characteristics were comparable in CP and controls (Table 2).
Table 2. Selected maternal factors in cerebral palsy (CP) cases and controls.
CP cases Controls OR (95% CI) or
(n = 148) (n = 296) p-value
Maternal age 27 (24–33) 28 (24–33) p = 0.46
Nulliparous 66 (45) 159 (54) 0.83 (0.67–1.02)
Infertility >1 y 13 (9) 32 (11) 0.78 (0.38–1.50)
Maternal disease 10 (7) 19 (6) 1.05 (0.50–2.21)
Bad obstetric history 17 (11) 19 (6) 1.89 (0.94–3.76)
Previous legal abortion 37 (25) 51 (17) 1.60 (0.99–2.58)
Data are a mean (interquartile range), or n (%).
OR: odds ratio; 95% CI: 95% confidence interval.
The birthweight, standardized for gestational age and gender, did not differ significantly between cases and controls (12% cases and 14% controls were below ¡2 SD). Infectious factors [clinical chorioamnionitis/pyelonephritis, histological chorioamnionitis and long duration of preterm prelabour rupture of membranes (pPROM)] were
associated with an increased risk of CP, whereas treatment with anti-inflammatory corticosteroids was associated with a significantly lower risk (Table 3).
There was a significant association between CP and an admission–delivery interval <4 h (Table 4). Hypertensive disease, cervical insufficiency and iatrogenic reasons for delivery were all associated with a lower occurrence of CP, whereas no difference was found between cases and controls with regard to spontaneous onset of labour [pPROM and p
reterm labour (PTL)] (Table 4).
Decreased viability at birth (low Apgar scores at 1, 5 and 10 min) occurred more frequently in CP cases than in controls (Table 5).
Risk factors for CP were also analysed separately for very and moderately preterm infants, as well as for spastic diplegic and hemiplegic forms of CP (Table 6).
Abruptio placentae and low Apgar scores were associated with a higher risk of CP, especially in the hemiplegic and moderately preterm (32–36 wk) group.
Indicators of infection, such as antibiotics during pregnancy, were associated with diplegic CP.
Fever before onset of delivery was an antecedent of CP in the very preterm (<32 wk) and the diplegic groups (Table 6).
…The strengths of the present study are that virtually all cases of spastic CP in a geographically defined area (birth 1983–1990) were included, the size of the study and the fact that all children with CP were at least 4 y old at diagnosis…
Acknowledgements.—This study was supported by the Swedish Medical Research Council (09455), the Go¨teborg Medical Society, the Folke Bernadotte Foundation for Children with Cerebral Palsy and by Swedish government grants to researchers in public health service (ALF).
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Received Aug. 13, 2001; revisions received Dec. 12, 2001, and Apr. 15, 2002; accepted Apr. 17, 2002
Acta Paediatr 91: 946-951. 2002