Maternal barbiturate utilization and neonatal withdrawal symptomatology

doi:10.1016/S0022-3476(72)80577-8

The Journal of Pediatrics

Volume 80, Issue 2, February 1972, Pages 190-197

https://doi.org/10.1016/S0022-3476(72)80577-8 Get rights and content

Infants born to mothers who receive barbiturates throughout pregnancy or throughout the last trimester may manifest symptoms similar in many respects to those characteristically seen in infants of mothers addicted to opiates during pregnancy. However, symptoms tend to begin at a later age in “barbiturate infants” and undernutrition at birth is not a feature. These factors may make detection of such infants in the nursery more difficult since symptomatology tends to begin after discharge from the nursery.

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Passive Addiction and Teratogenic Effects
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Drugs can exert major effects on the developing central nervous system (CNS). In the broadest sense, drugs may disturb specific developmental events in the brain and, in turn, produce teratogenic effects. In addition, maternal ingestion of certain drugs can result in passive addiction of the fetus and postnatally lead to a neonatal withdrawal or abstinence syndrome. Although some effects may be transient, most are likely to persist in some form into childhood and adolescence with multiple systems affected spanning cognition, motor function, language, and behavior. This chapter provides a comprehensive overview of the neurological effects of a range of licit and illicit drugs on the infant and growing child. Drugs reviewed include fetal exposure to alcohol, antiepileptic drugs, stimulants, opioids, selective serotonin reuptake inhibitors (SSRIs), sedatives, anesthetics, and marijuana. Clinical considerations in the evaluation and care of the drug-exposed neonate are also discussed.
Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy
2016, Journal of Pharmaceutical and Biomedical Analysis
Citation Excerpt :
The prevalence of epilepsy in pregnant women has been reported to be about 0.3–0.6%, and PB therapy might induce a pattern of minor and major anomalies including congenital heart defects, cleft palate and developmental retardation in fetus. Combination use of PB with the other antiepileptic drugs especially diphenylhydantoin increases its teratogenic effects and causes “hydantoin syndrome” based on morphological after birth findings [14–22]. Several studies showed that the stimulation of maternal immune system can decrease or prevent drugs induced fetus anomalies.
Biospectroscopic investigations have attracted attention of both the clinicians and basic sciences researchers in recent years. Scientists are discovering new areas for FTIR biospectroscopy applications in medicine. The aim of this study was to measure the possibility of FTIR-MSP application for the recognition and detection of fetus abnormalities after exposure of pregnant mouse to phenobarbital (PB) and levamisole (LEV) alone or in combination. PB is one of the most widely used antiepileptic drugs (AEDs), with sedative and hypnotic effects. When used by pregnant women, it is known to be a teratogenic agent. LEV is an antihelminthic drug with some applications in immune-deficiency as well as colon cancer therapy. Four groups of ten pregnant mice were selected for the experiments as follows: one control group received only standard diet, one group was injected with 120 mg/kg of BP, one group was injected with 10 mg/kg of LEV, and the last group was treated simultaneously with both BP and LEV at the above mentioned doses. Drugs administration was performed on gestation day 9 and fetuses were dissected on pregnancy day 15. Each dissected fetus was fixed, dehydrated and embedded in paraffin. Sections of liver (10 μm) were prepared from control and treated groups by microtome and deparaffinized with xylene. The spectra were taken by FTIR-MSP in the region of 4000–400 cm⁻¹. All the spectra were normalized based on amide II band (1545 cm⁻¹) after baseline correction of the entire spectrum, followed by classification using PCA, ANN and SVM. Both morphological and spectral changes were shown in the treated fetuses as compared to the fetuses in the control group. While cleft palate and C-R elongation were seen in PB injected fetuses, developmental retardation was mostly seen in the LEV injected group. Biospectroscopy revealed that both drugs mainly affected the cellular lipids and proteins, with LEV causing more changes in amide I and lipid regions than PB. Application of PCA, ANN and SVM methods were able to successfully classify these FTIR spectroscopic data and discriminate between control and treated groups of fetuses, making it a new potential tool for drugs teratogenic investigations.
Gender issues
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Citation Excerpt :
Although the potential problem of neonatal withdrawal from AEDs is well recognized, there is little recent literature. Neonatal withdrawal from barbiturates occurred within 2–3 days following delivery, and included irritability, hypotonia, and vomiting (Desmond et al., 1972; Erith, 1975). Neonatal hypoglycemia after maternal valproate treatment was common (13/22 infants) in a prospective study, with the lowest blood glucose concentration being 1.0 nmol/L but all neonates were asymptomatic.
Epilepsy and unprovoked seizures have been reported to be more common in men than in women. However, the risk of developing epilepsy differs between men and women according to age, being similar until about 50 years of age and then significantly higher in men. In women nonhormonal methods of contraception can be used, but there is a risk of contraception failure when a hormonal method is used in combination with an enzyme-inducing antiepileptic drug (AED). Fertility is slightly reduced and there is an increased incidence of anovulatory cycles and the polycystic ovary syndrome. Preconception counseling is important as there is a risk of fetal malformation of approximately 3% (with carbamazepine having the lowest risk). Sodium valproate should be avoided if possible during pregnancy. Women with catamenial epilepsy tend to have an exacerbation of their seizure disorder in the menopause, but, often, seizure control improves after the menopause. Hormone replacement therapy may lead to deterioration of seizure control. The ongoing normal reduction in bone mass in postmenopausal women may be further exacerbated by the use of certain AEDs. In men there is a correlation between sexual function and anxiety/depression but not with testosterone levels. Studies of testosterone levels and testicular function have produced conflicting results, but there is probably a decrease in biologically active testosterone in men on enzyme-inducing AEDs. Men exposed to AEDs are more likely to have reduced spermatozoa concentrations and abnormalities of sperm motility and morphology.
Epilepsy and Pregnancy
2011, Neurological Disorders and Pregnancy
This chapter examines the available evidence for treatment of epilepsy. Seizures are the most common neurologic problem encountered during pregnancy. Women who have epilepsy can safely have children but there is an increased risk to the mother and especially the child due to the effects of seizures and their treatment. There are a number of complications of pregnancy that are more common in women who have epilepsy. The chance for vaginal bleeding, hyperemesis, eclampsia, and placental abruption are all increased by double over the general population. There is an increased chance of preterm labor and cesarean section as well. Some of these effects are the direct result of seizures while others may be a combination of the effects of antiepileptic drugs and seizures. Maintaining seizure control is still the best way to prevent these complications. Seizures can be a problem during labor and delivery. Generalized tonic–clonic seizures are particularly troublesome. They can produce acidosis and hypoxia in the mother with subsequent risk to the baby. The fetal heart rate can be lowered by a convulsive seizure, which probably contributes to statistics showing low Apgar scores and other evidence of hypoxia.
Maternal Drug Abuse: Effects on the Fetus and Neonate
2011, Fetal and Neonatal Physiology E-Book, Fourth Edition
Epilepsy and Pregnancy
2010, Neurological Disorders and Pregnancy
This chapter examines the available evidence for treatment of epilepsy. Seizures are the most common neurologic problem encountered during pregnancy. Women who have epilepsy can safely have children but there is an increased risk to the mother and especially the child due to the effects of seizures and their treatment. There are a number of complications of pregnancy that are more common in women who have epilepsy. The chance for vaginal bleeding, hyperemesis, eclampsia, and placental abruption are all increased by double over the general population. There is an increased chance of preterm labor and cesarean section as well. Some of these effects are the direct result of seizures while others may be a combination of the effects of antiepileptic drugs and seizures. Maintaining seizure control is still the best way to prevent these complications. Seizures can be a problem during labor and delivery. Generalized tonic–clonic seizures are particularly troublesome. They can produce acidosis and hypoxia in the mother with subsequent risk to the baby. The fetal heart rate can be lowered by a convulsive seizure, which probably contributes to statistics showing low Apgar scores and other evidence of hypoxia.

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^**: Supported by the Maternal and Child Health Service, Maternity and Infant Care Project, No. 535, The John A. Hartford Foundation, Inc., and The American Legion Erna and Albert Siegmund Child Welfare and Rehabilitation Foundation.

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Original articleMaternal barbiturate utilization and neonatal withdrawal symptomatology**

Am. J. Obstet. Gynecol.

Pediatr. Clin. North Am.

Am. J. Obstet. Gynecol.

J. Pediatr.

Lancet

Lancet

Lancet

Lancet

Congenital morphinism

J. A. M. A.

The effect of maternal narcotic addiction in the newborn infant: Review of the literature and report of 22 cases

Pediatrics

Congenital neonatal narcotic addiction: A natural history

Am. J. Public Health

Studies on the accumulation of certain barbiturates in the brain of the human foetus

Acta Obstet. Gynecol. Scand.

Original article
Maternal barbiturate utilization and neonatal withdrawal symptomatology**