Objective
We sought to investigate whether placental infarction determined by macroscopic examination was associated with risk of cerebral palsy (CP).
Study Design
This was a population-based study of macroscopic placental infarcts in singletons >35 weeks’ gestational age, in 158 perinatal deaths, 445 infants with CP, and 491 controls matched with CP cases for gestational age.
Results
Placental infarcts were recorded in 2.0% of controls, 4.4% of deaths (relative risk [RR], 2.2; 95% confidence interval [CI], 0.8–5.6]), 5.2% of infants with CP ( P < .05, RR, 2.5; 95% CI, 1.2–5.3), and 8.4% with spastic quadriplegic CP ( P = .0026; RR, 4.4; 95% CI, 1.8–10.6). In children with CP, unlike controls, placental infarction was associated with reduced fetal growth, older maternal age, more prior miscarriages, and poor neonatal condition, but not with maternal preeclampsia.
Conclusion
Placental infarction identified by macroscopic examination was associated with increased risk of CP and the CP subtype, spastic quadriplegic CP. Antecedents of placental infarction differed in children with CP compared with control children.
The placenta is the life support system for the fetus in utero. Disorders of the placenta may contribute to neurologic abnormalities manifested soon after birth, such as neonatal encephalopathy (NE) or perinatal stroke.
For Editors’ Commentary, see Table of Contents
Several clinical case series have linked infarction of the placenta with brain lesions in infants who died in the perinatal period. There are indications that placental infarction may also play a role in long-term neurologic disability in survivors: in 2 population-based studies, term-born children with later-diagnosed cerebral palsy (CP) had a higher rate of macroscopically identified placental infarcts than controls. One of these, a study from the Danish Cerebral Palsy Registry, found macroscopic placental infarction in growth-restricted (GR) infants to be associated especially with the spastic quadriplegic (SQ) subtype of CP.
In a prospective case-control investigation within a population-based study of placental infarction identified on macroscopic examination, we asked 2 questions. First, can we confirm that placental infarcts are associated with increased risk of adverse outcome: perinatal death, neurologic abnormality in the newborn period, or later CP? Second, is the association, if any, of placental infarcts with outcome influenced by the presence of fetal GR or maternal preeclampsia or both?
Materials and Methods
The case-control study of CP and perinatal death from which this report comes was designed to investigate factors associated with risk of CP, defined as a disorder of movement and/or posture and of motor function due to a nonprogressive interference/lesion or abnormality of the developing immature brain. Including all births in Western Australia from 1980 through 1995 (n = 380,918), perinatal and vital outcome data are available in a database linking birth and death registries with pregnancy and delivery information collected by the attending midwife, and including >99.5% of registered births.
In Western Australia, each birth is attended by a midwife regardless of whether a physician is in attendance. This midwife is responsible for completing the statutory “notification of birth attended” form that is filed with the Western Australian Department of Health. Midwives receive instruction on normal placental anatomy during university training. Midwives observing abnormalities may consult with senior nurses and with physicians, who are often present for deliveries, especially in urban areas where the majority of births occur, concerning placental description. The information collected on placental infarction consisted of a yes/no item asking the presence of infarction. Except for placental weight, further information on placental features including number or size of infarcts was not gathered, and submission of placentas to the laboratory was not mandated.
The other information requested on this form included hospital of delivery, gestational duration, date and plurality of birth, and pregnancy complications. More detailed clinical data were collected from medical records for 3 groups: (1) all children with CP not acquired postneonatally and whose functional motor impairment was evident in activities of daily living; (2) neonatal survivors without CP, individually matched to each CP case for date of birth (within 12 months), gestational age (GA) at delivery (within 1 week), and plurality of birth; and (3) a representative sample of intrapartum stillbirths or neonatal deaths delivered during study years and not the result of medical termination of pregnancy or lethal birth defects.
For each study pregnancy, medical records were sought from the hospitals of birth and any additional transferring or receiving hospitals, general practitioners, or obstetricians identified in the medical record as involved. Data were collected by reviewers blind to case status.
Preeclampsia was considered present if blood pressure exceeded 140/90 mm Hg or there was a rise of 20 mm Hg systolic or 15 mm Hg diastolic. GR was considered present if the birthweight fell <2 SD below estimated optimal (ie, a proportion of optimal birthweight [POBW] <77.3%), or, to minimize false negatives, if the neonatal notes recorded that the neonate appeared GR, whether or not birthweight met the first criterion. Optimal birthweight for singletons was estimated from a statistical model with terms for fetal gender, maternal height and parity, and gestational duration, derived from a population of births not exposed to commonly occurring pathological factors associated with growth abnormality, including maternal smoking. This estimate of optimal birthweight is therefore a standard rather than a population reference and POBW constitutes a measure of appropriateness of intrauterine growth.
Although we prefer the more general term “neonatal encephalopathy,” a diagnosis of hypoxic-ischemic encephalopathy (HIE) was recorded if there was a clinical diagnosis in the newborn period of birth asphyxia or HIE.
This study was approved by the Princess Margaret Hospital/King Edward Memorial Hospital Ethics Committee, the Confidentiality of Health Information Committee of the Western Australia Department of Health, and by individual hospital and regional ethics committees, whose documents can be provided on request.
Statistics
The frequency of reported placental infarction was compared between case status groups (control, perinatal death, and CP) and comparisons reported as relative risks (RRs) (with 95% confidence interval [CI]). Similarly the frequencies of placental infarction were compared within case groups stratified by other exposures.
Results
Among the 386,159 infants born in Western Australia from 1980 through 1995, there were 376,541 (97.5%) singleton births of whom 363,747 (96.6%) delivered ≥35 weeks’ gestation. This cohort included 688 neonatal deaths, 993 intrapartum stillbirths, and 362,126 neonatal survivors of whom 539 (1.4 per thousand) were included on the Western Australia Cerebral Palsy Register, and of whom 445 (82.6%) had a description of the placenta available. From neonatal survivors not on the CP register, 508 were selected as controls, of whom 491 (96.7%) had a description of the placenta available. A sample of 175 singleton perinatal deaths without lethal malformations born ≥35 weeks’ gestation was selected for more detailed study, of whom 158 (90.3%) had available information on placental infarction.
Placental infarcts were associated with adverse outcome, being reported in 2.0% (10/491) of control infants, in 4.4% of perinatal deaths (compared with controls, RR, 2.2; 95% CI, 0.8–5.6), and in 5.2% (23/445) of those with later-diagnosed CP ( P < .05, RR, = 2.5; 95% CI, 1.2–5.3) ( Figure 1 , A ). Of the 107 children with SQ CP, 9 (8.4%) had placental infarction ( P = .0026, RR 4.1; 95% CI, 1.7–9.9).
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