Stephen R. Kandall

Neonatal seizures associated with narcotic withdrawal

Among 302 neonates passively addicted to narcotics, 18 had seizures that were attributed to withdrawal. Of those 18 infants, 10 were among the 127 infants exposed to methadone (7.8%), whereas only one of them was among the 83 infants exposed to heroin (1.2%). Generalized motor seizures and myoclonic jerks were the predominant convulsive manifestations. Paregoric was more effective than was diazepam in controlling and preventing these seizures once they occurred. Electroencephalograms were obtained on 13 neonates in the interictal period; 12 of these ECGs were normal. Three infants, two with myoclonic jerks, had paroxysmal brain wave activity at the time of the seizures.

Thrombocytosis and increased circulating platelet aggregates in newborn infants of polydrug users.

Thirty-three prospectively studied neonates born to mothers using methadone plus other drugs developed significant thrombocytosis by the second week of life compared to platelet counts performed during the first week. This increase persisted for over 16 weeks, with a further short-lived significant peak at 10 weeks of age. Platelet counts exceeding 1,000,000/mm3 were found in seven infants. Thrombocytosis was not related to withdrawal symptoms or treatment (phenobarbital or paregoric). No thrombocytosis was found in 36 normal control infants up to eight weeks of life. Twenty-eight of the study group infants were evaluated for circulating platelet aggregates. Thirteen patients had a normal aggregate index and a mean platelet count of 468,000/mm3; 15 patients had increased aggregates and mean platelet count of 754,000/mm3. The risk for increased circulating platelet aggregates correlated directly with an increase in platelet count. Thrombocytosis and increased circulating platelet aggregates may be factors in the pathogenesis of the focal infarcts, and subarachnoid and germinal plate hemorrhages, described at autopsy in infants of addicted mothers.

Possible effect of maternal promethazine therapy on neonatal immunologic functions

The effect of the administration of promethazine in the treatment of erythroblastosis fetalis was studied in four maternal-fetal pairs. The three infants exposed for a prolonged period of time had decreased neonatal number and function of T cells, and abnormal specific humoral immune responses. The possible role of promethazine in the induction of fetal immunoincompetence is discussed.

WEIGHT CHANGE PATTERNS IN NEONATAL ABSTINENCE

The impact of maternal drug dependency on weight changes after birth was assessed in 131 passively addicted infants. The maternal population included 40% who took methadone alone and 56% who abused other drugs concurrently with methadone. Abstinence was treated with phenobarbital (PH) in 53 infants and with paregoric (PA) in 45 infants by random design; the remaining 33 infants (C) did not require treatment to control mild abstinence signs. The three groups were comparable as to sex ratio, ethnic distribution, gestational age, and birth weight.Adjusting for birth weight and caloric intake, both PA and PH treated groups of addicted infants lost more weight than the untreated group on days 9-10, at which point untreated babies were discharged; PH-C=94 grams(p <.01),PA-C=96 grams(p<.01). On day 21 the PH group had gained significantly more weight than the PA group(p<.01). When patterns of weight loss and gain were corrected for abstinence severity based on a standard scoring system, both significant differences disappeared completely (r2=.91 on day 9, r2=.86 on day 21). These findings are consistent with the concept that severity of abstinence directly affects weight loss and gain within the first month of life. Infants requiring treatment for moderate or severe abstinence should receive caloric supplementation during that period.

1668 FOLLOW-UP OF INFANTS WITH NEONATAL ABSTINENCE-RELATED SEIZURES

Eighteen passively addicted infants who exhibited abstinence-related neonatal seizures were evaluated for periods up to one year of age. Seven mothers were maintained on methadone alone, 10 used methadone and other drugs, and one used heroin and cocaine during pregnancy. Thirteen seizures were myoclonic, 2 were generalized, and 3 were tonic-clonic in type. Thirteen of the initial EEGs performed 2-48 hours following onset of seizures were abnormal; the remaining five EEGs were normal. Of the 13 abnormal EEGs, 11 reverted to normal within 14 days, while 2 remained abnormal.Bayley Developmental Assessment in infant subsets at 3 months of age showed an MDI (Mental Developmental Index) of 109 ± 11.6 (SD) and PDI (Psychomotor Developmental Index) of 107.2 ± 11.5. MDI and PDI at 6 months of age were 98.6 ± 20.1 and 111.8 ± 12.1; MDI and PDI at 12 months of age were 106 ± 0 and 98.5 ± 0.7.Neurological examinations were normal except for hypertonicity in 7 of 13 infants seen at 3 months of age; 2 of those babies were normal at one year of age, while the remaining 5 await re-evaluation. Although developmental assessment appears to be normal, ongoing neurologic evaluation of these infants is necessary.

IMPACT OF DRUG DEPENDENCY DURING PREGNANCY ON NEONATAL MORPHOMETRICS

The impact of maternal drug dependency on neonatal morphometrics was studied in 150 mother-infant and 150 concurrent control pairs. The maternal population included 121 methadone-maintained women, of whom 80 abused other drugs concomitantly; the remaining 29 women used multiple street drugs. Mean birth weight of the passively addicted neonates(PA)(2.80 kg ± 0.55) (SD) differed significantly from controls(C)(3.25 kg ± 0.59)(p<.001). Mean head circumference of PA infants(32.6 cm ± 1.8)also differed significantly from C(33.8 cm ± 1.7)(p < .001). Mean weight and head circumference of PA newborns fell at the 25th percentile for gestational age, differing from the C group value(50-75th percentile)(p<001). Mean gestational age(PA 38.9 wks ± 2.2 vs C 39.3 wks ± 2.3) and prematurity rates(10% PA vs 7% C)did not differ, but IUGR was increased to 20% in the PA group vs 4% C(P < .001). Within the PA group, selected perinatal variables of maternal age, parity, weight gain during pregnancy, polydrug abuse, methadone dosage, and duration of drug and alcohol use were not significantly associated with either birth weight or head circumference.This demonstration of symmetrical IUGR in PA infants and the known association of small head size at birth with reduced neurobehavioral outcome mandates greater concern for “optimal” methadone maintenance during pregnancy.

983 POLYDRUG VS. METHADONE USE IN PREGNANCY: STUDIES ON OFFSPRING

Twenty-one neonates of drug-dependent mothers were studied prospectively. Of 19 mothers on methadone (M), 13 were polydrug abusers (PD); 2 mothers were heroin-dependent. Mean birth weight was 2675 grams ± 580 (SD); mean gestational age was 38.0 weeks ± 2.7 (SD). Eighteen of 21 had birth weights appropriate for dates; 3 were small for dates. All lengths were between 10th and 90th percentile. Eighteen of 21 head circumferences were between the 10th and 90th percentile; 3 fell below the 10th percentile.Mean maximal weight loss in the first postnatal week was 7.25% of body weight ± 3.67% (SD). From 7 to 30 days of age, 16 infants gained weight normally, 3 subnormally and 2 excessively. Weight gain corrected for caloric intake was inversely related to severity of withdrawal on day 14 (p<.05), but not on days 7 or 21.Drug withdrawal was assessed twice daily by standardized score. Mean time of symptom onset was 13.5 hours ± 0.7 (SD). No difference in withdrawal severity was seen between the M and PD groups. No correlation was found between withdrawal severity and maternal M dosage late in pregnancy or at delivery. Term infants showed more severe withdrawal than preterm infants. Infants randomly treated for moderate to severe symptoms with paregoric or phenobarbital showed no difference in modification of withdrawal severity or treatment time required.

584 PROLONGED ISOLATED THROMBOCYTOSIS IN INFANTS OF POLYDRUG ABUSERS

Nineteen infants of mothers using methadone plus other drugs developed significant thrombocytosis for more than 16 weeks. These prospectively studied newborns had varying degrees of withdrawal during the first week of life; one had seizures. All were formula fed. As part of a study, 10 received paregoric, 3 phenobarbital and 6 no drugs. Complete blood counts were done every 3 to 7 days in hospital and weekly after discharge. Platelet counts in the first week were the same in both study (mean 258,000±18,000/mm3 S.E.M.) and control (255,000±40,000) infants. Maternal platelet counts were all normal. By the second week there was significant thrombocytosis in study (521,000±68,000) versus control (240,000±45,000) infants (p<.001). Thrombocytosis persisted with a further significant increase at 10 weeks of age (745,000±97,000) (p<.05), platelets exceeding 1,000,000 in 4/19. Thrombocytosis was comparable regardless of treatment. All serial blood counts aside from platelets were normal. Marrow hypermegakaryocytosis suggests overproduction as the mechanism. Thrombocytosis appears to be related to postnatal changes associated with withdrawal and not to treatment. Thrombocytosis may be a factor in the pathogenesis of focal infarcts, and subarachnoid plus germinal plate hemorrhages described in some infants of addicted mothers, and thus may relate to potential long term sequelae in survivors.