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\s=b\ A large prospective study inves- relate to risks for cerebral palsy, as was not the result of recognized progres¬
tigated prenatal and perinatal ante- evaluated in univariate analyses. A sive disease. Children with meningomyelo-
cedents of chronic motor dysfunction companion article will consider ante¬ celes and those with motor deficits ac¬
(cerebral palsy [CP]), evaluating approx- cedents of cerebral palsy (CP) and of quired through infection or injury after the
imately 400 characteristics of the moth- its clinical subtypes, employing multi¬ first month of life were not included. Unlike
ers, pregnancies, or deliveries. In addi- variate techniques.
several previous reports from the NCPP,
tion to confirming some, but not all, of this report includes mild, as well as moder¬
the classic risk factors for CP, this study ate and severe, CP.
observed relatively large increases in SUBJECTS AND METHODS The statistical test used to evaluate four¬
the CP rate in association with maternal fold contingency table assessments of di-
mental retardation, seizure disorders, Approximately 54,000 pregnancies were chotomous antecedents for CP for signifi¬
hyperthyroidism, or with the administra- studied at 12 cooperating university hospi¬ cance was the 2 with 1 df (using a
tion of thyroid hormone and estrogen in tals between 1959 and 1966. The study continuity correction), except where other¬
pregnancy. Some risk factors were pre- sample was approximately 46% white and wise indicated. Fisher's exact test was used
dictive of CP only insofar as they were 46% black; women of Hispanic descent where cell size warranted it. Polychot-
associated with low birth weight or low made up a majority of the remaining sub¬ omous antecedents were analyzed for glo¬
Apgar scores. Among factors not signifi- jects. The socioeconomic level of the NCPP bal significance using the R x C contin¬
cantly related to CP rate were maternal population was somewhat lower than for gency table format. Fourfold comparisons
age, parity, socioeconomic status, the total population of the United States as of subgroups within larger contingency ta¬
smoking history, maternal diabetes, first assessed by the Bureau of the Census.1 bles were made only when the 2 test for the
trimester vaginal bleeding, kidney or Information relating to the sample and to larger table was significant at the .05 level.
bladder infection, moderate hyperten- study procedures is available elsewhere.z'3 Given the many 2 tests made within this
sion, long cord, use of anesthetic At the initial prenatal visit, medical, large dataset, some were likely to achieve
agents, or use of oxytoxics for initiation obstetric, and family histories were re¬ nominal levels of statistical significance by
or augmentation of labor. Duration of corded. At each subsequent visit, medical chance alone. We did not adjust signifi¬
labor, whether precipitate or prolonged, and obstetric events and medication intake cance levels using multiple comparison
was not a risk factor for CP. were noted. Patients were examined on techniques, which would lessen the chance
(AJDC 1985;139:1031-1038) admission in labor, and the course of labor of observing some clinically important risk
and delivery was observed.3 After delivery, factors.5 Rather, we chose to consider the
rPhe Collaborative Perinatal Project a physician reviewed all prenatal and labor significance values simply as indicators for
of the National Institute of Neu¬ and delivery records, including documenta¬ risk factors that are candidates for confir¬
tion of medical and surgical conditions of mation in future studies.
rological and Communicative Disor¬ the gravida before or during the pregnancy. Most continuous variables were exam¬
ders and Stroke (NCPP), a large pro¬
Ascertainment of drug exposure and its ined in both dichotomous and polychot-
spective study, was undertaken to timing was as described by Heinonen et al,4 omous forms. Intervals were chosen a pos¬
investigate the association of maternal except that we considered drug exposure teriori, based on observed risk. Evaluation
and pregnancy conditions and events for the entire pregnancy. Neonatal infor¬ of possible linear trends in the risk of CP for
of labor, delivery, and the neonatal mation was derived from delivery room and polychotomous variables used weighted
period, with chronic neurologic disor¬ nursery records. least-squares regression analysis of the ob¬
ders of childhood. This article reports Examinations in the first year of life were served probabilities of risk, with weights
the major results of the NCPP as they the basis for the recognition of congenital determined by the number of patients at
malformations. A pediatric and neurologic each observation point.
examination performed when children To examine whether variables signifi¬
were 7 years old provided the basis for cantly related to CP for the total population
From the Developmental Neurology Branch
(Dr Nelson), and the Biometry and Field Studies diagnoses of CP. Children with a CP diag¬ were operative solely or chiefly through
Branch, Intramural Research Program (Dr El- nosis at 1 year of age who died before 7 their association with low birth weight, we
lenberg),National Institute of Neurological and years of age were included. Cerebral palsy evaluated each variable significant for all
Communicative Disorders and Stroke, Bethesda,
was defined as a chronic disability charac¬ birth weights, for relationship to CP within
Md.
Reprint requests to 7550 Wisconsin Ave, Room terized by aberrant control of movement or the 91% of the population with birth
8C-04, Bethesda, MD 20205 (Dr Nelson). posture that appeared early in life and that weights over 2,500 g.
ship was not present in children of pregnancies in which there were six or marked neutrophilic infiltration of the
ototoxicity.18 ber and variety of characteristics ex¬ as pathways for the expression of cer¬
Of children with CP, 37% received plored, expand the set of questions tain earlier pathogenetic factors.
antibiotics in the newborn nursery; in asked relating to the etiology of CP. A few factors or clusters of factors
24% of children with CP this was de¬ This study could thus generate hy¬ identified empirically rather than by
spite the absence of definite or sus¬ potheses on etiology but not provide prior hypothesis were found to have
pected infection. definitive tests of them. reasonably high RRs or to occur in a
This study could rule out associa¬ substantial proportion of cases of CP.
COMMENT tions insofar as sample size permitted. Of these, polyhydramnios and hor¬
In a recent monograph that re¬ A study that differed only by its larger mone administration in pregnancy,
viewed the literature on the etiology of size might have found statistical signif¬ and associated factors, raise tantaliz¬
CP, Alberman and Stanley19 discussed icance for some uncommon or weakly ing questions. Administration of thy¬
the paucity of methodologically ade¬ acting factors not found to be impor¬ roid hormone and estrogen in an effort
quate studies on the subject. As they tant in this study. However, such ante¬ to prevent early pregnancy loss is a
remarked, "The study of the cerebral cedents could not account for a large regimen no longer in use. Interest in
palsies presents epidemiologists with proportion of CP. whether these agents, given in preg¬
every possible pitfall." The NCPP was Some of the prenatal and perinatal nancy, might have contributed to
designed to evaluate the antecedents risk factors evaluated for CP were motor disorders in the offspring de¬
of CP, employing epidemiologie ap¬ indeed found to be fairly risky, in that rives from the more general possibility
proaches that aimed to avoid a few of an individual possessing such charac¬ that aspects of maternal endocrine sta¬
those pitfalls. teristics was at a risk of developing CP tus might in some cases be related to
The prospective structure of the severalfold greater than that for indi¬ childhood motor disorders. The find¬
NCPP allowed identification of viduals without the characteristics. ing that long or unusual menstrual
mother-child pairs before outcome was However, even conditions with fairly cycles were among the few maternal
known, and data were collected in the high relative risks were not associated characteristics predictive of CP is com¬
same manner for mother-child pairs in with high absolute rates of CP, and patible with this possibility.