NEWBORN

Experiences with 118 Infants Born

to

Narcotic-using Mothers Does

a

Lowered Serum-lonized Calcium Level Contribute to the

Symptoms of Withdrawal? James M. Oleske, M.D., M.P.H.

HE

DATA on prevalence of drug addiction in the USA are most unreliable; but conservative estimates indicate that there are at least 400,000 heroin addicts in the United States.1-2 Most of the heroin addicts and the methadone maintenance programs are in urban centers. The pediatrician becomes involved because 85 per cent of female narcotic drug users are in the childbearing age span (15 to 40 years). Depending on the duration or intensity of narcotic use by the pregnant addict, the newborn is at risk of developing withdrawal symptoms. These symptoms can vary from very mild tremors up to convulsions and death. Some evidence suggests that narcotics affect growth and development of the fetus by direct cellular inhibition.3 The present study shows, as have others, the deleterious effects of maternal addiction on the infant both before and after birth. We also have found an alteration in calcium metabolism that may help to explain some of the physiologic alterations seen during withdrawal. ’

From the Departments of Pediatrics, Preventive MediCommunity Health, New Jersey Medical School, Newark, New Jersey. cine and

James M. Oleske, M.D., DepartCommunity Health, New Jersey Medical School, Newark, N.J. 07102. Correspondence

ment of

to:

Preventive Medicine and

Population

Studied

The

experiences of all infants born to narcotic-using mothers at the major teaching hospital of the New Jersey Medical School, the Martland Medical Center, during 1971 through 1973 have been studied from the newborn records. The attempt was made to follow discharged babies by examination of Clinic and Emergency Room records. The most difficult interpretation to be made from a retrospective chart review is the drugtaking history of the mother. Often, there is a

history of polydrug use (including smoking,

alcohol, barbiturates, heroin and methadone) over a

period

of months

to

years. In the

present analysis, a careful attempt was made to separate those women who gave a history

of predominantly heroin use from those who used mostly methadone during pregnancy. The charts of 118 infants born to 108 narcotic-using mothers from 1971 through 1973 were reviewed. Data collected included birth weights, head circumference, length of hospital stay, estimated gestational age by the criteria of Usher4 and Koenigsberger,5 maternal drug history and maternal obstetric record, clinical condition of the infant, days of chlorpromazine therapy (if treated for

418

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withdrawal) one-minute Apgar

score,

any additional diagnoses, serum ionized calcium levels as determined by the ion electrode method of Durst,~ discharge disposition, and findings in 47 pre-discharge home evaluations. Normal term birth weights for this population were calculated from 50 random males and 50 random females admitted to the normal nursery during 1971, 1972, and 1973. The control group for perinatal complications was all infants (2,752) born in 1972. Normal serum ionized calcium controls were from 16 term newborns, 3 of whom were small-for-date infants but otherwise normal. The difficulty in grading degrees of withdrawal symptoms required that all comparisons used in the study be based on whether treatment

was

required.

Infants of birth weight below 2,500 gm but between 38 and 42 weeks gestational age were classified as term small-for-dates. All infants clinically assessed at below 38 weeks

gestation

were

classified

as

premature.

TABLE Birth GG’e=i~fat in GmM-! 0/ 7’~rm t~e.statirara Borrz trr ~‘carr~ti~-r~tin~ ,ifnifivr.g t;rrm~r~rr~ct

Irifaizts

r~3a~fa C;anlrrrla h~~ Sc·x

General Data

Among the l18 infants, there were l 14 blacks and 4 Puerto Ricans; 65 females and 53 males. The average maternal age was 23.6 years; the mean gravidity, 3.3. Among the 108 mothers, there were 57 previous abortions with 33 per cent of all mothers having one or more abortions. Sixty-three mothers attended prenatal clinic, whereas 55 had not seen a doctor prior to delivery. Of the mothers, 100 used heroin; 18 used methadone, of whom 8 were in a methadone maintenance program. The mean Apgar score for all 118 infants, including 3 perinatal deaths, was 8. This reflects the experience of others; although at great risk of perinatal complications, infants of narcotic-using mothers are

vigorous

at

birth.~7

Measurement Parameters

The birth weights and head circumferences for all term infants and term small-for-date infants, when compared with controls as plotted in Figure I on the standard intrauterine growth grids of Lubchenco, were lower (see also Table 1). There was no difference in the birth weights of term infants of heroin versus methadone-using mothers (2,765 gm versus 2,736 gm). The causal path from poor prenatal care to low birth weight has received considerable recognition; surprisingly, however, among our infants, there was no difference in the mean birth weights of clinic or non-clinic narcotic-using mothers (Table 2). Perinatal Complications FIG. 1, ~Gc~rrelation of mean term gestation birth weight and head circumference of normal newborn controls, infants born to narcotic-using mothers and term smallfor-date infants in this study group.

Our in all

period

study infants had a significant increase complications during the neonatal when

compared

with the control

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TABLE 2.

Comparison of Term Birth Weights in Gram5 of Infants of Narcotic-using Mothers Attending and Not Attending Prenatal Clinic

*

P

=

NSS.

population (Table 3). The perinatal mortality for the study group was 3.4 per cent, compared with 2.32 per cent for the controls. rate

The narcotic users had almost a 5-fold greater number of small-for-date babies and 3 times as many prematures. This has long-term significance in view of reported higher rate of learning disabilities in small-for-date infants9. As in other studies, our narcotic-using group had more in utero hypoxia and stress states, as evidenced by the greater frequency of post-mature, meconium-stained, and asphyxiated babies. A similar and potential TABLE 3. Perinatal

~ 2,’7~~ controls

Complications in

were

118

all infants born

at

disabling complication in 4 infants was seizure disorder. Unlike other studies, there was no demonstrated diminution in hyperbilirubinemia of the newborn in our groups Infants born to narcotic addicts appear to run an excessive risk of infections, both acute and chronic. However, the tremors, diarrhea, vomiting, tachypnea, hypertonicity, and other withdrawal symptoms often suggest the possibility of infection in these infants. Our infants had a higher incidence of serologic tests for syphilis (2.5 per cent) than the controls, and 1 infant was diagnosed as

having congenital syphilis. As for hepatitis B infection, two of the 118 infants had blood positive for HBAG but cord blood samples were negative, and they had no anti-HBs. Thus, these infants may have been infected transplacentally during gestation or contaminated during delivery and infected by the fecal-oral route. This percentage of 1.7 positive HB,AG corresponds with what

Infants Born to Narcotic-using Mothers, Compared with 2,572

Martland Medical Center in 1972,

using mothers. t Includes 6 prematures also diagnosed as small for gestafonal age. t Includes only infants with significant staining as evidenced by deep § Indirect bilirubin above 10 mg.

11

IRDS

including

Control*

49 infants of 46 narcotic-

staining of skin, cord

and under nails.

ldiopathic respiratory distress syndrome. are all infections suspected or proven by culture requiring the infant to be on antibiotics. Documented by abnormal EEG and seizure activity. it Sum of all numbers except 1, 2, 5: total number of infants. This provides a crude relative morbidity =

f Included **

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value.

has been seen in other infants born to narcotic using women. The last line in Table 3 demonstrates the increased risk these infants suffer in comparison to the control population. The 118 study infants had 5-fold more complications than did the control group. The most dramatic complication shown by infants are the withdrawal symptoms. Most of our infants had some symptoms of withdrawal; and in 54.2 per cent the symptoms seemed severe enough to require treatment with chlorpromazine.

.

Biochemical Studies of Serum Calcium

Of the term infants in the study group, 54 had a serum ionized calcium level test done during the first 24 hours. Of these 33 had

enough to require chlorpromazine therapy. The differ-

withdrawal symptoms

severe

in ionized calcium level between these groups of infants (2.07 versus 2.17 mEg/1) not significant, though those with the

ence

two was

withdrawal symptoms, requiring treatment, had lower ionized calcium levels. When compared with our normal controls, all these patients had a significantly lower ionized calcium (2.11 versus 2.36 mEg/l, more severe

P< 0.01). Socioeconomic Parameters

variability was found in the length of hospital stay (L.O.S.) within this study group. Those infants born to heroin-using mothers and requiring treatment for withdrawal symptoms had a mean L.O.S. of 38.4 days. The treated infants of methadone-using mothers had a mean L.O.S. of 48.4 days. Those infants Great

treated for withdrawal symptoms had a mean L.O.S. of 14.3 days. The length of treatment for withdrawal symptoms between infants of heroin and methadone users was not statistically significant, though those treated for methadone withdrawal required a mean of 36.6 days compared with 22.2 for heroin withdrawal. Several of the infants needed a longer nursery stay because of difficulties in disnot



charge placement (Table 4). Regardless of the justification, an extended nursery stay is

TABLE 4.

L~~atht~r~e Dz.~pr~satiorz.s and Home Evaluation* of 7t!/af~.! ,~3aaa4ra to’l~7arcotit-~~.SZar~ ~Ltathers

* Only 47 home evaluations done by public health nurse. All infants of narcotic-using mothers are reported to P,’H.I~3. for predischarge home e~~aluaticsn; but visit often not completed because of poor compliance or wrong address.

heavy financial community. a

burden

Follow-Up Experience

of

on

the

hospital

and

Study Infants

long-term effects of maternal narcotic the child have only recently been examined. 11.Evaluation of single factors is difficult because of the often inadequate The

use

on

environment in which these children grow and develop. A further long-term complication demonstrated in this study and reported in four others is a propensity to the Sudden Infant Death Syndrome (SIDS). 12-l’ There was one documented case of SIDS, at 3 months of age, among our patients. Also, there were 5 cases of suspected child abuse and a 1-yearold child who was brought DOA to the hospital after maternal battering. Both the SIDS and battered children represent minimal numbers because most of the 118 study infants have been lost to follow-up care at Martland Medical Center. Comments number of premature and inutero growth-retarded infants, and the higher morbidity and mortality of these infants, speaks for itself. They are indeed ~.t.high risk and need special attention and care. The lower birth weights of the study infants at term was expected. However, there were no differences in birth weight or in incidence of The

large

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as related to whether or not a mother attended prenatal clinic. This experience at Martland Medical Center differs somewhat that of other centers, which report shorter treatment courses. 17 The long mean hospitalization of our infants reflected not only the length of chlorpromazine treatment but also their great range of social problems. Just over 20 per cent of all infants were discharged to someone other than the mother (Table 4). Of the 47 home evaluations, 72.3 per cent of reports described the home environment as unsuitable for the care of a newborn. Fourteen infants were discharged against medical advice; these may well be at greater risk of adverse home environment and are less likely to receive adequate preventive postnatal care. The growth of methadone maintenance programs (MMP) since 1968 was thought to be one answer to the &dquo;heroin epidemic.&dquo; The advantages of these programs have not been demonstrated for infants born to mothers using illicit methadone or registered in methadone maintenance programs. Unlike heroin, which is diluted several times, the potency of methadone is exact. Whereas a street &dquo;bag&dquo; of heroin may contain from no heroin to more than 10 mg,18 each 40 mg tablet of methadone meets U.S. pharmacopeia standards. Thus, the heroinusing pregnant women who changes, either legally or illegally, to methadone addiction often increases the fetus’ exposure to an active opiate. Additionally, evidence is increasing that many heroin addicts who enter a MMP show substantial increase in alcohol consumption.19.20 The adverse effects on the developing fetus of exposure to both alcohol and methadone, two central nervous system depressants, should be additive. The claims that women in methadone maintenance have substantial improvement in nutritional status, prenatal care, and general life style has not been demonstrated except in the most controlled settings.12 As the number of women of child-bearing age entering MMP increases, this degree of control will be diminished. In addition, it has been well demonstrated that the transfer from heroin

prematurity



methadone is associated with an increase in fertility.°i Certainly the risks involved in maternal methadone addiction must be kept in mind and the potential benefits of such a program must be carefully evaluated against the known and unknown risks. Classical hypocalcemic tetany is often acto

companied by hypertonicity, jitteriness, clonus, convulsions, hyperalertness and highpitched cry.22 These are precisely the symptoms encountered in the withdrawal syndrome. The findings of Glass al. on respiratory alkalosis~~ in withdrawal infants, those of Eldridge and Salzer on the effects of alka-

losis

on lactate,24 and the Durst findings of and lactate effects on ionized calcium6 could be related to our finding of a depression in ionized calcium in neonates having withdrawal symptoms. The observations here described are similar to those in other urban medical centers servicing large narcotic drug-using populations,18.25-27 but the magnitude of the adverse effects of maternal narcotic use on the infants appears greater. These 118 infants were at risk not only during the perinatal period but throughout early childhood. The medical and social consequences of narcotic use during pregnancy are continued by the drug-using behavior and life styles of the addicted mothers. Their infants have the double jeopardy of physical and social disadvantages. After discharge from the nursery these infants face the suggested increased risk of SIDS, increased exposure to and possibly development of the chronic hepatitis (HbsAg) carrier state, 28-31 parental battering and neglect, and diminished learning abilities secondary to their generally low birth weight.’ Until the long-term hazards of methadone on the fetus are known and the results of heavy use of alcohol by those enrolled in MMP are better delineated, mothers who want to have children and are now more fertile because of MMP should be encouraged to become &dquo;drug free&dquo; (including alcohol) before and during pregnancy. Furthermore, every effort should be extended to protect the woman joining MMP from having an unwanted pregnancy. The pediatrician has always been the

;

pH

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professional spokesman for the silent victims our society’s mishaps. This role, thus, must not end with the discharge of the newborn-every effort must be extended to im-

of

prove and maintain the health of these infants who are brought into this world in such adverse circumstances.

Acknowledgments The author thanks Drs. Donald Louria, Anthony Minnefor, Burton Fine, and Franklin Behrle for their

review and criticism; and Ms. Barbara Bush and ~(s. Jacque Muther for their technical assistance and aid in preparation of this manuscript.

References 1. Committee on Youth, American Academy of Pediatrics : Drugs in adolescence. Pediatrics 44: 131, 1969. 2. Blumstein, A., Sagi, P., and Wolfgang, A. E.: Problems of estimating the number of heroin addicts in drug use in America: Problem in perspective. In Social Response to Drug Use, Vol. II (Appendix), 1973. 3. Naeye, R. L., Blanc, W., Leblanc, W., and Khatamee, M. A.: Fetal complications of maternal heroin addition: Abnormal growth, infection and episodes of stress. J. Pediatr. 83: 1055, 1973. 4. Usher, R., McLeon, F., and Scott, K. E.: Judgement of fetal age. II. Clinical significance of gestational age and an objective method for its assessment. Pediatr. Clin. North Am. 13: 835, 1966. 5. Koenigsberger, M. R.: Judgement of Age. I. Neurological evaluation. Pediatr. Clin. North Am. 13:

823, 1966.

(Ed.): Ion-selective electrodes. National Bureau of Standards Special Publication 314, 1969. 7. Zelson, C., Sook, J. L., and Casalino, M.: Neonatal narcotic addiction: Comparative effects of maternal intake of heroin and methadone. N. 6. Durst, R. A.

8.

Engl. 289: 1216,J.1973. Med. Lubchenco, L. O.: Assessment of gestational age and development at birth. Pediatr. Clin. North Am. 17: 125, 1970.

9.

14.

poisoning

in children.

National Conference 1972, p. 174.

on

4th Methadone Treatment,

Proceedings of

Conference

Conference

Proceedings

on

on

of the 5th National

sudden infant death syndrome. Pediatrics 50: 964, 1972. 17. Zelson, C., Rubio, E., Wasserman, E.: Neonatal

narcotic addiction: Ten-year observation.

Pedi-

atrics 48: 178, 1971. 18. Zelson, C.: Infant of the addicted mother. N. Engl. J. Med. 288: 1393, 1973. 19. Bihari, B.: Alcoholism in M.M.T.P. patients: Etiological factors and treatment approaches. Pro-

of the 5th National Conference on Methadone Treatment, Vol. 1, 1973, p. 284. 20. Scott, R. N., Walter, W. W., and Gorman, D. G.: Epidemiology of alcoholism in a methadone maintenance program. Proceedings of the 5th National Conference on Methadone Treatment, Vol. 1,

ceedings

1973,p.

284.

21. Wallach, R. C., Jerez, E., and Blinick, G.: Pregnancy and menstrual function in narcotics addicts treated with methadone. Am. J. Obstet. Gynecol. 105: 1226, 1969. 22. Cockburn, F., Brown, J. K., Belton, N. R., and Forfar, J. O.: Neonatal convulsions associated with primary disturbance of calcium, phosphorus and magnesium metabolism. Arch. Dis. Child. 48: 99, 1973. 23. Glass, L., Rajegowda, B. K., Kahn, E. J., and Floyd, M. V.: Effect of heroin withdrawal on respiratory rate and acid-base status in newborn. N.

Engl. J. Med. 24.

25.

26.

27. 28.

286: 746, 1972.

Eldridge, F., and Salzer, J.:

Effect of

respiratory

alkalosis on blood lactate and pyruvate in humans. J. Appl. Physiol. 22: 461, 1967. Reddy, A. M., Harper, R. G., and Stern, G.: Observations on heroin and methadone withdrawal in the newborn. Pediatrics 48: 353, 1971. Kahn, E. J., Neumann, L., and Polk, G. A.: The course of the heroin withdrawal syndrome in newborn infants treated with phenobarbital or chlorpromazine. J. Pediatr. 75: 495, 1969. .: et al Rajegowda, B. K., Evans, H. E., Glass, L., Methadone withdrawal in newborn infants. J. Pediatr. 81: 532, 1972. Merrill, D. A., Dubois, R. S., and Kohler, P. F.:

hepatitis-associated antigen N. Engl. J. Med. 287: 1280, 1972. L., and Spears, R. H.: Hepatitis antigen in mother and infant. N. Engl.

Neonatal onset of the carrier state. 29. Schweitzer, I.

30.

p. 842,

R. G., Sia, C. G., and Blenman, S.: Observations on the sudden death of infants born to addicted mothers. Proceedings of the 5th

Harper,

of the 5th National p.

Methadone Treatment, 1973,

1133.

1973.

13.

Proceedings

on

Pierson, P. S., Kleber, H. D., and Howard, P.: Sudden deaths in infants born to methadonemaintained addicts. JAMA 220: 1733, 1972. : 16. Forsyth, W. B., Allen, J. E., Brinkley, et J. W., al Committee on Infant and Preschool Child: The

pregnancy and

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Methadone Treatment,

15.

associated

Blatman, S.: Methadone effects the newborn.

the

on

Harper, R. G., Solish, G. J., Snag, E., Purow, H., and Panepinto, W.: The effect of a methadone treatment program upon pregnant addicts and their infants.

Beargie, R. A., James, V. L., Jr., and Greene, J. W., Jr.: Growth and development of small for date

newborns. Pediatr. Clin. North Am. 17: 159, 1970. 10. Nathenson, G., Cohen, M. I., Litt, I. F., and McNahara, H.: Effect of maternal heroin addiction on neonatal jaundice. J. Pediatr. 81: 899, 1972. 11. Blatmen, S., and Lipsitz, P.: Children of females maintained on methadone: Accidental methadone

12.

National Conference 1973, p. 1122.

283: 570, 1970. J. Med. Keys, T. F., Sever, J. L., Hewitt, W. L., and Gitnick, G. L.: Hepatitis associated antigen in selected mothers and newborn infants. J. Pediatr. 80: 650, 1972.

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Krugman, S., and Giles, J. P.: Viral hepatitis: New 212 : 1019, 1970. light on an old disease. JAMA 423

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Experiences with 118 infants born to narcotic-using mothers. Does a lowered serum-ionized calcium level contribute to the symptoms of withdrawal?

NEWBORN Experiences with 118 Infants Born to Narcotic-using Mothers Does a Lowered Serum-lonized Calcium Level Contribute to the Symptoms of Wit...
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