Birth Weight and Gestational Children With Cerebral Palsy or Seizure Disorders Jonas H.

Ellenberg, PhD,

in

Karin B. Nelson, MD

\s=b\ Birth weight and gestational age of single-born children with cerebral palsy (CP) and those with seizure disorders were compared with norms for 40,000 single-born children in the same prospectively identified population. Low birth\x=req-\ weight and short gestation were important

risk factors for CP, but these characteristics were uncommon, and the majority of children with CP were of normal birth weight and term gestational age. Preterm children with CP by age 7 years tended to have been even smaller at birth than was appropriate for their short gestations. Among term infants with later CP, the birth weights of the majority were appropriate for dates, but a subgroup were noticeably small for dates at term. Low birth weight, preterm birth, and smallness for dates at term were not significantly related to the risk of seizure disorders in children free of CP. (Am J Dis Child 133:1044-1048, 1979)

In 1861,

Age

W. J. Little1 drew attention

to the relationship between pre¬ mature birth and subsequent motor

disability. Although low birth weight is now widely recognized to be a risk factor for cerebral palsy (CP),s"ä it is not well established to what degree low birth weight contributes to the total burden of CP in the population. Because of biases in the selection of patient populations in existing stud¬ ies, Brown" could write in 1976 that "we still do not have a good estimate of the prevalence of a history of low birth weight in children with cerebral

From the Office of Biometry and Epidemiology (Dr Ellenberg), and Developmental Neurology Branch (Dr Nelson), National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Md. Reprint requests to Room 8 C-04, 7550 Wisconsin Ave, Bethesda, MD 20205 (Dr Nelson).

palsy, or of the prevalence of cerebral palsy in infants of low birthweight."

The hazards to which low-birthchildren are vulnerable as neonates differ according to their gestational ages. Complications in preterm infants often relate to imma¬ turity of organ systems, especially of the respiratory system, whereas in¬ fants small for dates are at increased risk of hypoglycemia, pulmonary hemorrhage, aspiration of amniotic fluid, and problems attributed to asphyxia.7 Preterm and small-for-date infants may also differ from one another in their risks for long-term neurologic morbidity.89 The present report examines the relationship of prenatal growth and duration of preg¬ nancy to the risk of CP and seizure disorders in a population defined before the birth of the children and followed up to the age of 7 years.

weight

SUBJECTS AND METHODS

Approximately 54,000 children in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke (NCPP) were born between 1959 and 1966 in 12 participating urban teaching hospi¬ tals. Of these children, 46% were white, 46% black, with the remainder chiefly Puerto Rican. The population of the NCPP is described elsewhere.1" Registrants were evaluated with a regular schedule of exam¬ inations, including general physical and neurologic examinations at 1 year and 7 years of age. The presence of CP was determined on the basis of neurologic examination at age 7 years or by examina¬ tion at 1 year of age in children who died between the ages of 1 and 7 years. The cohort studied was single-born children surviving to 1 year of age, whose outcome was known at 7 years. Cerebral palsy was defined as a chronic

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disability characterized by aberrant con¬ trol of movement or posture, appearing early in life, and not the result of recog¬ nized progressive disease. Children with motor deficits acquired through infection or injury after the first month of life were excluded, as were those with meningomyelocele. Spastic diplegia indicated a form of CP

in

which

reflexes, and

abnormalities of tone,

motor control of the

legs

exceeded abnormalities in the arms. The occurrence of seizures in an NCPP child was ascertained by interview with the mother or other primary caretaker when the child was 4, 8,12,18, and 24 months old, and annually thereafter to the age of 7 years. Medical records were obtained from the physician or medical facility for each medically attended seizure reported, and parental description was also recorded. All records of children with any documenta¬ tion of seizures were reviewed for uniform classification. Included in this study were children with afebrile seizures between the ages of 1 month and 7 years. Children in whom each seizure episode was thought to be sympto¬ matic of acute illness involving the CNS were excluded. Children who had CP as well as seizures, who constituted 19% of children with seizures, were included among the CP sample but were excluded from the group with seizure disorder with¬ out CP. The two samples are thus nonoverlapping. The purpose of this separation was to avoid double-counting of children with both disorders and to permit evalua¬ tion of the relationship of birth weight and gestational age to seizure disorders in a group in which the inclusion of children with CP did not account for any relation¬ ship observed. Birth weight was measured within an hour of birth and was recorded to the nearest ounce and was later converted to grams. Gestational age was calculated as the interval between the first day of the last menstrual period, as reported by the mother at the first prenatal visit, and the

It was recorded to the nearest week. Infants were classified by

day of delivery.

weight and gestational age in a system adapted from Yerushalmy." For brevity, the term "well grown" was used to indicate children born weighing 2,501 g or more, at 37 to 42 weeks' gestational age. birth

Percentile birth weight

norms were

established for

by week of gestation and by race based on all live-born singleton chil¬ dren in the NCPP. The sample size in the total population was at least 25 cases for whites (100 for blacks) at each early week of gestation, and by 33 weeks, it exceeded 100

cases

at each week for whites

blacks), and by 37 weeks, it both

was

(300 for 1,000 for

races.

The statistical test used to evaluate four¬ fold contingency table comparisons for significance was the 2 with 1 df (using continuity correction) except where other¬ wise indicated. Fourfold comparisons of subgroups within the context of the larger contingency tables were made only when the - test for the larger table was signifi¬ cant at the .05 level (in all instances, the significance level was at least .001). Total CP

Spastic Diplegia

RESULTS Cerebral Palsy Risk to the Infant by Birth Weight and Gestational Age.—Low birth weight and short gestation increased the risk of CP. Compared with children born weighing more than 2,500 g and being of term gestational age (the well grown), the increase in risk among children born weighing less than 1,501 g was 27-fold (90.4 vs 3.3/1,000;

X2

=

337,


37 weeks), the compari¬ son being 22.9 vs 6.7/1,000 ( 2 14.2, The frequency of CP < .001). among these immature small infants was about seven times the rate in well-grown babies ( 2 116, < .001), whereas the increase for small-for-date-at-term babies was two-fold ( 2 4.3, se .038. The in¬ crease in CP among infants small for dates at term was significantly greater than among well-grown in¬ fants only for spastic diplegia (3.3 vs 0.6/1,000; 2 14, < .001); the risk of CP other than spastic diplegia was not increased in infants born small for dates at term. White male infants of very low birth weight (< 1,501 g) showed a 44-fold increase in rate of CP over well-grown white male infants (Table =

=

=

=

1,214 vs 4.9/1,000; 2

Birth Weight, g

Gestation, wk




2,501/> 43 7 (8.5) 3 (3.7) 5 (6.6) 0 (0.0) 10(6.1) 5 (3.4) 12 (7.2) 5(3.1) 17(5.2)

>

2,501/37-42 34 (4.9) 18(2.8) 20 (3.2) 15(2.4) 52 (3.9) 35 (2.8) 57(4.1) 34 (2.6) 91 (3.4)

Total* 65 (7.5) 39 (4.8) 48 (5.2) 29 (3.1) 104 (6.2)

77(4.1) 116 (6.2) 73 (4.0) 189 (5.1)

Table 2—Birth

(CP)

or

Weights and Gestational Ages of Children Seizures

as

Compared

With Cerebral

With The Unaffected

Palsy

Population

Birth

Gestational

Weight, g

Age, wk Any

1,501 1,501-2,500 1,501-2,500 : 2,501 > 2,501 2: 2,501


36 37 36

>

43

;

37-42

Total No. of cases

No. (%) of Afebrile

17(9.1) 33(17.7) 12(6.5) 16(8.6) 17(9.1) 91 (48.9)

(%) Spastic Diplegia 6(10.5) 22 (38.6) 6(10.5) 5 (8.8) 3 (5.3) 15(26.3)

186(99.9)

57(100.0)

No.

No. (%) of Children Not Affected

Seizures, NoCP 1

(0.4) 9 (3.4) 21 (7.8) 27(10.1) 24 (9.0) 186(69.4)

=

.001); for total CP, 58%; and for children with no CP, 82%. For CP other than spastic diplegia, then, there was a difference (70% vs 82%; X2 13, < .001), but not a dramatic
.05). Very low birth weight (< 1,501 g) and low birth weight with short gestation were not attended by an increase in risk of not

=

seizures without CP. Of children with seizure disorders and no CP, 69% were well grown, as compared with 73% of unaffected children; this difference not

was

statistically significant (Ta¬

ble 2). Low birth weight, immaturity, and smallness for dates at term were not important antecedents of afebrile seizure disorders in children free of CP. COMMENT

It has been general experience that groups of children with CP have lower mean birth weights than groups of Table 3.—Distribution of Birth

Weights

of Children with Cerebral Palsy Gestational Age

as

ity of the reproducing population. A previous study from the NCPP

indicated that of children with moder¬ ate or severe CP and severe mental retardation (IQ < 50), 69% were born at term with a birth weight of 2,501 g or

more."

Other investigators have examined the relationship of birth weight to gestational age as these relate to CP. Drillien," evaluating a sample limited to infants with birth weights of 2,000 g or less, considered there to be "little difference in the incidence of overt cerebral palsy between the small for dates infants and those larger for gestational age." Hagberg et al·' compared the birth weights for gesta¬ tional age of 357 children with CP with norms for the population of Sweden. They found that after the 35th week, but not before 29 weeks, there was a lower mean birth weight at the given gestational age among children with CP. These authors suggest that smallness for dates at or near term, from which they infer a "foetal deprivation of supply," is a major pathogenetic factor in CP. Twins were overrepresented by a factor of four among children with CP in this series. It is well documented that after 29 weeks of gestation, the growth of twins slows progressively as compared with singletons.'",T The contribution of the excess of twins to the lower mean birth weight of chil¬ dren with CP was not examined in the report of Hagberg et al. Sabel and «workers'8 also stressed the impor¬ tance of smallness for dates. However, their sample contained only eight chil-

Compared

With

Expectation, by Race and

% Observed Black

White Percentile for Birth Weight


5th, < 10th 10th, < 50th 50th, < 90th 90th, < 95th

> : :

>

95th

Total

x*t

%

£

Expected*

(N

36 wk

>

34)

(N

=

5.0 5.0

5.9 0.0

40.0 40.0

73.5 20.6

5.0 5.0 100.0

0.0 0.0 100.0

17.9t

Total

37 wk =

69)

(N

=

103)




28)

(N

=

11.6

9.7

7.1

7.3 31.9 46.4 1.5 1.5 100.2

4.9 45.6 37.9 1.0 1.0

10.7

100.1 12.6

99.9

11.5§

37 wk =

18.1t

=

76)

11.8

4.2

6.6 54.0

43.8 3.6 0.0

Total

(N

14.6

33.3 4.2 0.0 100.1

12.2§

"Expected distribution based on total Collaborative Perinatal Project of the National Institute of Neurological and Communicative population of single-born children. tx2 (5 df) computed as deviation of observed values for each race and gestational age grouping compared with expectation. tDouble dagger indicates significant at 1% level. §Section sign indicates significant at 5% level.

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48)

23.7 4.0 0.0 100.1

20.1t

Disorders and Stroke

dren with CP, and of these, all four who were small for dates were also twins. The overrepresentation of twins adds difficulty to the interpretation of the report of Hagberg et al, but that series and the present one are in reasonable agreement with regard to the presence of a small-for-date group among babies born at or after term in whom CP developed. Our observation that preterm ba¬ bies who later had CP were more deviant from the norm for their gesta¬ tional age than were babies born early who did not have CP is quite different from the conclusion of Hagberg et al. It differs also from the report of Scherzer and Mike,4 who studied a group of CP children who weighed less than 2,268 g (5 lb) at birth and who examined the distribution of these birth weights according to gestational age as compared with the Colorado Intrauterine Growth Chart. Both Scherzer and Mike and Hagberg et al found birth weight means of prema¬ turely born children with CP to exceed the means for babies without CP. Both found the deviation from the norm to increase with decreasing

gestational

age.

Neither of these studies stated a definition of gestational age. Since both used control groups derived from other populations, it is possible that different methods of determining gestational age were used for cases as compared with controls. Differences in definitions or methodology or differences in the populations studied may account for some of the discrep¬ ancy between the present study and findings regarding preterm infants in the reports of Hagberg et al and Scherzer and Mike. The observation that preterm in¬ fants with later CP were dispropor¬ tionately small even for their relative¬ ly brief gestations lends credence to the old speculation"' that some of such children were growing poorly, and perhaps experiencing other develop¬ mental problems, even before their premature births. With regard to the relationship of epilepsy to birth weight or gestational age, Lilienfeld and Pasamanick2" found an excess of epilepsy among children whose weight at birth was 2,500 g or less, but other investiga¬ tors21-24 did not. McDonald" examined

the frequency of seizures in the first five years of life among children born weighing 1,800 g or less and found the rate to be "higher... than would be expected in the general population" and, in particular, higher than re¬ ported in the Newcastle upon Tyne series.26 Van den Berg and Yerushalmy,27 using groupings similar to those in the present study, found that an excess of children with nonfebrile seizures came from the group born weighing 1,500 to 2,500 g, and espe¬ cially from those of this birth-weight range who were born at term. The present material also demonstrated a slightly higher rate of seizure disor¬ ders among children small for dates at term, but it was not a statistically significant finding. Degen28 has re¬ ported a high frequency of premature birth in children with focal seizures and a lesser excess of premature infants among those with generalized convulsions. Neither he nor other authors he cites who relate low birth weight to seizure disorders, nor van den Berg and Yerushalmy,27 examined this relationship in children with seizures who were free of motor dis¬ ability. It seems from data presented here that except where CP and seizure disorders coexist, these two conditions differ in their relationship to birth weight and gestational age. The Collaborative Study of Cerebral Palsy, Mental Retardation and Other Neurological and Sensory Disorders of Infancy and Childhood is supported by the National Institute of Neurolog¬ ical and Communicative Disorders and Stroke. The following institutions participate: Boston Lying-in Hospital; Brown University, Provi¬ dence, RI; Charity Hospital, New Orleans; Chil¬ dren's Hospital of Buffalo; Children's Hospital of Philadelphia; Children's Medical Center, Boston; Columbia University, New York; Johns Hopkins University, Baltimore; Medical College of Virgin¬ ia, Richmond; New York Medical College; Penn¬ sylvania Hospital, Philadelphia; University of Minnesota, Minneapolis; University of Oregon, Portland; University of Tennessee, Memphis; Office of Biometry and Epidemiology and the Developmental Neurology Branch, NINCDS, Be¬ thesda, Md. Kristan Lucas provided secretarial assistance.

References 1. Little WJ: On the influence of abnormal

parturition, difficult labour, premature birth, and asphyxia neonatorum on the mental and physical condition of the child, especially in rela-

tion to deformities. Lancet 2:378-380, 1861. 2. Childs B, Evans P: Birth weights of children with cerebral palsy. Lancet 1:642-645, 1954. 3. Alberman E: Birth weight and length of gestation in cerebral palsy. Dev Med Child Neurol 5:388-394, 1963. 4. Scherzer AL, Mik\l=e'\V: Cerebral palsy and the low-birth-weight child. Am J Dis Child 128:199\x=req-\ 203, 1974.

Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/14/2015

5. Saint-Anne Dargassies S: Long-term neurological follow-up study of 286 truly premature infants: I. Neurological sequelae. Dev Med Child

Neurol 19:462-478, 1977. 6. Brown GW: Berkson fallacy revisited: Spurious conclusions from patient surveys. Am J Dis Child 130:56-60, 1976. 7. Jones MD Jr, Battaglia FC: Intrauterine growth retardation. Am J Obstet Gynecol 127:540\x=req-\

549, 1977.

8. Fitzhardinge PM, Steven EM: The small\x=req-\ for-date infant: II. Neurological and intellectual sequelae. Pediatrics 50:50-57, 1972. 9. Hagberg G, Hagberg B, Olow I: The changing panorama of cerebral palsy in Sweden 1954\x=req-\ 1970: III. The importance of foetal deprivation of supply. Acta Paediatr Scand 65:403-408, 1976. 10. Niswander KR, Gordon M: The Women and Their Pregnancies, No. 73-379. US Dept of Health, Education, and Welfare, 1972. 11. Yerushalmy J: The classification of newborn infants by birth weight and gestational age. J Pediatr 71:164-172, 1967. 12. Hoffman HJ, Lundin FE Jr, Bakketeig LS, et al: Classification of births by weight and gestational age for future studies of prematurity, Reed DW, Stanley FJ (eds): The Epidemiology of Prematurity, Baltimore, Munich Urban & Schwarzenberg, 1977, pp 297-333. 13. Nelson KB, Ellenberg JH: Epidemiology of cerebral palsy, in Schoenberg BS (ed): Advances in Neurology. New York, Raven Press, 1978, vol 19, pp 419-432. 14. Nelson KB, Broman SH: Perinatal risk factors in children with serious motor and mental handicaps. Ann Neurol 2:371-377, 1977. 15. Drillien CM: Aetiology and outcome in low-birthweight infants. Dev Med Child Neurol 14:563-574, 1972. 16. Naeye RL, Benirschke K, Hagstrom JWC, et al: Intrauterine growth of twins as estimated from liveborn birthweight data. Pediatrics 37:409-416, 1966. 17. Daw E, Walker J: Biological aspects of twin pregnancy in Dundee. Br J Obstet Gynaecol 82:29-34, 1975. 18. Sabel K-G, Oleg\l=a%o\rdR, Victorin L: Remaining sequelae with modern perinatal care. Pediatrics 57:652-658, 1976. 19. Freud S: Infantile Cerebral Paralysis, 1897, Russin LA (trans). Coral Gables, Fla, University of Miami Press, 1968, pp 257-259. 20. Lilienfeld AM, Pasamanick B: Association of maternal and fetal factors with the development of epilepsy: I. Abnormalities in the prenatal and paranatal periods. JAMA 155:719-724, 1954. 21. Henderson M, Goldstein H, Rogot E, et al: Perinatal factors associated with epilepsy in Negro children. Public Health Rep 79:501-509, 1964. 22. Bandera EA, Churchill JA: Prematurity and neurological disorders. Henry Ford Hosp Med Bull 9:414-418, 1961. 23. Drillien CM: The Growth and Development of the Prematurely Born Infant. Baltimore, Williams & Wilkins Co, 1964. 24. Lier L, Zachau-Christiansen B: Pre- and perinatal etiological factors in children with epilepsy and other convulsive disorders: A prospective study. Acta Paediatr Scand, suppl 206, 1970, pp 27-29. 25. McDonald A: Fits in children of very low birth weight. Dev Med Child Neurol 6:144-148, 1964. 26. Miller FJ, Court SD, Walton WS, et al: Growing up in Newcastle upon Tyne. London, Oxford University Press, 1960. 27. Van den Berg BJ, Yerushalmy J: Studies on convulsive disorders in young children: I. Incidence of febrile and nonfebrile convulsions by age and other factors. Pediatr Res 3:298-304, 1969. 28. Degen R: Epilepsy in children: An etiological study based on their obstetrical records. J Neurol 217:145-158, 1978.

Birth weight and gestational age in children with cerebral palsy or seizure disorders.

Birth Weight and Gestational Children With Cerebral Palsy or Seizure Disorders Jonas H. Ellenberg, PhD, in Karin B. Nelson, MD \s=b\ Birth weight...
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