Benzodiazepines: A risk Factor in Sudden Infant Death?

Benzodiazepines (BDZs) are still being prescribed to pregnant women today, although a recent reminder from the CSM in (1997) [1] may have caused some reduction. In 1994 an estimated 30 - 40% of all pregnant women would take antianxiety drugs at some stage of pregnancy, the majority of which would be Benzodiazepines [2]. If this figure takes into account the numbers of pregnant BDZ misusers, it may be an underestimate as illicit BDZ use continues to rise.

It is established that prenatal BDZ exposure can be dangerous to the newborn in two ways:

  • due to the direct effects of the drug, (if the baby cannot fully metabolise it).
  • Neonatal withdrawal syndrome.

Both can be severe and prolonged, needing specialist treatment.

A link between Sudden Infant Death Syndrome(SIDS) and BDZ exposure during pregnancy has not as yet been fully investigated, but sufficient evidence points to BDZS as a contributory factor.

The recent increase in drug-related deaths from respiratory failure in drug misusers has been attributed to the widespread use of BDZs with opiates [3].
As it is etablished that prenatal opiate exposure increases the risk of SIDS,[4] this is compounded in a baby prenatally exposed to BDZs and opiates.

The following suggests BDZs may be a risk factor in SIDS:

  • The foetus receives BDZ through the placenta at high concentrations and some babies cannot metabolise it after birth [5], resulting in apnoea, respiratory depression, hypoactivity, "floppy" muscles, hypothermia and feeding difficulties, which can last for months. [2]

  • Levels of active benzodiazepines and metabolites have been measured in ten week old infants (and beyond).
    The unpredictable nature of BDZ metabolism is poorly understood. It has been observed [6] in prenatally exposed rats, that BDZS concentrate in the brain at birth, migrate to the major organs and then return to the brain. It is not known if this occurs in human babies, but an unpredictable course of toxicity and abstinence syndrome of late onset have been observed.

  • Disturbances in respiratory function and thermoregulation [7] have been associated with SIDS and both can be caused by prenatal BDZ exposure in the neonate. BDZ-induced respiratory disturbance is only one aspect of many hazards faced by newborns exposed to these drugs.

  • It established that BDZs "work" therapeutically by altering the function of the GABA system in the brain. [8] Return of receptors to the pre-drug state can be protracted, in part explaining the lengthy withdrawal syndrome [9] (months to years), associated with these drugs.

  • The pontine pneumotaxic centre (Kollicker-Fuse) in the brain modulates respiratory rhythm and also processes respiratory reflexes including the Hering Breuer reflex and the diving reflex. The diving reflex causes apnoea, slowed heart rate and peripheral vasoconstriction). Recent research shows that GABAa receptors play a primary role in the control of this system. the blockade of GABAa by the administration bicuculline in the Kollicker - Fuse area results in apnoea [10].

  • In a letter to the Lancet, [11] one of the first to warn of the dangers of prenatal BDZ exposure came from Dr Nigel Speight who, describing a baby admitted to special care due to BDZ exposure stated that the baby might have died on a postnatal ward of an apnoeic episode had he not been admitted to a special care nursery.

  • An increased death rate in children with epilepsy treated with nitrazepam (many of them sudden) has been reported [12]. and the incidence of apnoea, sudden death and respiratory difficulties in these fatalities was high.

  • Death or serious incidents with the use of BDZs alone [13], or in combination with opiates in surgical procedures, due to hypoxia, apnoea, respiratory distress and laryngospasm have been reported [14].

  • BDZs can cause or exacerbate apnoea and respiratory problems - [15] reflected both in recent manufacturer's product information [16] and frequent anecdotal reports.

  • Successful reversal of the above effects of BDZs with flumazenil, (a BDZ antagonist), in prenatally exposed babies, [17,18,19], patients undergoing surgical procedures [20] and in overdosage, isolates the BDZ as the primary cause.

  • In light of the above, in spite of a lack of empirical data, newborn babies of BDZ using mothers are being exposed to unacceptably high risks, compounded by the addition of opiates. Currently, little is been done to inform potential parents of these risk, particularly those misusing BDZs.

    Significant advances in understanding SIDS have dramatically reduced its incidence, but should this exclude investigation into a link between BDZs and SIDS?

    * NB: The owner of this site wishes to make clear that a significant proportion of people who take benzodiazepines (both babies and adults) do not suffer the adverse consequences featured here. The concern of Benzact is the significant proportion of those who are adversely affected by benzodiazepines.

    DISCLAIMER: Information on this site is not intended as medical advice in any context and personal health concerns should be directed to a relevant qualified professional.

    All the views expressed on this site are not necessarily the views of the owner.
    S. Bibby 2000