Drugs in pregnancy

Drug use during pregnancy can have temporary or permanent effects on the fetus. Any drug that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen. Drugs may refer to both pharmaceutical drug and recreational drugs.

Pharmaceutical drugs

. The apprehension is not necessarily data driven and is a cautionary response to the lack of clinical studies in pregnant women. The indication is a trade-off between the adverse effects of the drug, the risks associated with intercurrent diseases and pregnancy complications, and the efficacy of the drug to prevent or ameliorate such risks. In some cases, the use of drugs in pregnancy carries benefits that outweigh the risks. For example, high fever is harmful for the fetus in the early months, thus the use of paracetamol (acetaminophen) is generally associated with lower risk than the fever itself. Similarly, diabetes mellitus during pregnancy may need intensive therapy with insulin to prevent complications to mother and baby. Pain management for the mother is another important area where an evaluation of the benefits and risks is needed. NSAIDs such as Ibuprofen and Naproxen are probably safe for use for a short period of time, 48-72 hours, once the mother has reached the second trimester.^[1] If taking aspirin for pain management the mother should never take a dose higher than 100mg.^[2]

Pregnancy categories

American law requires that certain drugs and biological products must be labelled very specifically. Title 21, Part 201.57 (9)(i) of the Code of Federal Regulations lists specific requirements regarding the labelling of drugs with respect to their effects on pregnant populations, including a definition of a "pregnancy category". These rules are enforced by the Food and Drug Administration.

To supplement this information, FDA publishes additional rules regarding Pregnancy and Lactation Labeling.

The FDA does not regulate labeling for all hazardous and non-hazardous substances. Many substances, including alcohol, are widely known to cause serious hazards to pregnant women and their fetus, including fetal alcohol syndrome. Many other pollutants and hazardous materials are similarly known to cause reproductive harm. However, some of these substances are not subject to drug labeling laws, and are therefore not assigned a "Pregnancy Category" per 21 CFR 201.57.

Examples

Antibacterial agents

• Category B : Penicillin, nitrofurantoin, clindamycin, terbinafine, some macrolides e.g. azithromycin, erythromycin

• Category C : Some aminoglycosides, chloroquine, quinolones, mebendazole, fluconazole

• Category D : Tetracyclines, gentamicin, tobramycin

Cardiovascular drugs

• Category B : Low molecular weight heparin

• Category C : Unfractionated heparin, beta blockers, (dihydropyridine) calcium antagonists, furosemide, digoxin, methyldopa

• Category D : ACE inhibitors, angiotensin II receptor blockers (ARBs), coumarins, thiazides, diltiazem

Central nervous system drugs

• Category B : Acetaminophen,

• Category C : Acetylsalicylic acid (ASA or Aspirin), clonidine, rofecoxib, risperidone, caffeine

• Category D : Carbamazepine, valproic acid, diazepam, lithium

Others

• Category C : Vaccines such as tetanus toxoid, polio vaccine, BCG vaccine, hepatitis A vaccine, hepatitis B vaccine and rabies vaccine.

• Category X: Isotretinoin is a teratogen highly likely to cause birth defects if taken by women during pregnancy or even a short time before conception.

Anticonvulsants

Valproic acid, and its derivatives such as sodium valproate and divalproex sodium, causes cognitive deficit in the child, with an increased dose causing decreased intelligence quotient.^[3] On the other hand, evidence is conflicting for carbamazepine regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure.^[3] Similarly, children exposed lamotrigine or phenytoin in the womb do not seem to differ in their skills compared to those who were exposed to carbamazepine.^[3]

Alcohol

Alcohol passes easily through the placenta from the mother's bloodstream into the bloodstream of the fetus. Unlike adults, a fetus does not yet have a blood filtration system, and is therefore unprotected from the effects of alcohol.^[4]

Potential Effects

In the first two weeks following fertilization, maternal alcohol consumption may prevent proper implantation of the fertilized egg, usually terminating the pregnancy before the mother realizes she is pregnant.^[5]

Potential problems during pregnancy:

• Decreased fetal breathing
• Delayed development of the nervous system ^[4]
• Facial feature abnormalities, especially during the third through sixth weeks following fertilization
• Beginning in the fourth week - rapid cardiac development. Exposure to alcohol may result in atrial and/or ventricular abnormalities, issues with valve formation, and a potential increase in the risk for heart disease in adulthood.
• Sixth and seventh weeks - the corpus callosum, the structure that divides the left and right hemispheres of the brain and is responsible for communication between the two hemispheres, is most vulnerable to alcohol exposure. Exposure to alcohol may lead to its incomplete development, thus resulting in issues with neural communication.
• After 8 weeks gestation, the fetus is not as vulnerable to organ-specific birth defects. The central nervous system overall, however, remains vulnerable, as well as the overall growth of the fetus.
• Infertility, miscarriage, stillbirth, low birth weight, preterm delivery ^[5]

Potential effects in children exposed to alcohol during prenatal development:

• Development of a Fetal Alcohol Spectrum Disorder
• Neurological disorders - ranging from attention deficit disorder (ADD), hyperactivity, mood disorders
• Impaired attention, learning, memory, and information processing
• Poor bonding and difficulty forming social relationships
• Higher rates of antisocial and delinquent behaviors
• Difficulty with executive functions
• Very high risk of mental health disorders (92% of people diagnosed with Fetal Alcohol Spectrum Disorders have also been diagnosed with a mental health disorder) ^[6]

Fetal Alcohol Spectrum Disorder: and umbrella term used to describe a variety of potential outcomes for prenatal exposure to alcohol. These outcomes include -

• Fetal Alcohol Syndrome (FAS)
• Partial Fetal Alcohol Syndrome
• Alcohol-Related Neurodevelopmental Disorder (ARND)
• Fetal Alcohol Effects (FAE)
• Alcohol Related Birth Defects (ARBD) ^[6]

Recreational drugs

Recreational drug use during pregnancy can cause various pregnancy complications.

Cannabis

Cannabis in pregnancy is the subject of various scientific studies, usually regarding whether it has effects on the child later in life.

Smoking

A number of studies have shown that tobacco use is a significant factor in miscarriages among pregnant smokers, and that it contributes to a number of other threats to the health of the fetus.^[7][8] Smoking and pregnancy, combined, cause twice the risk of premature rupture of membranes, placental abruption and placenta previa.^[9] Also, it causes 30% higher odds of the baby being born prematurely.^[10]

Others

• Prenatal cocaine exposure is associated with, for example, premature birth, birth defects and attention deficit disorder.

• Prenatal methamphetamine exposure can cause premature birth and congenital abnormalities.^[11] Other investigations have revealed short-term neonatal outcomes to include small deficits in infant neurobehavioral function and growth restriction when compared to control infants.^[12] Also, prenatal methamphetamine use is believed to have long-term effects in terms of brain development, which may last for many years.^[11]
• Marijuana can cause low birth weight, tremors, poor eyesight, late start of breathing, and a hole in the heart. In the first six months of life babies who have been exposed to marijuana have a higher chance of having breathing problems such as asthma, chest infections, and wheezing. By the age of three or four the child might be fearful, reckless, inattentive, restless, irresponsible, and may have poor memory, verbal, and reasoning ability; at age ten these problems can continue along with depression, anxiety, reading and spelling problems.^[13]

By pregnancy stage

Pregnancy and fetal development progress through various changes. The period of one week from fertilisation to implantation of the fertilized egg is called the preimplantation period. This is an 'all or none' period, .i.e. an insult can either cause death or complete recovery can occur. The period from the eighth day to the end of eighth week is the period of organogenesis during which the organs are formed in the fetus. This is the most crucial time with regards to 'structural malformations' and concern over teratogenicity of drugs. From the third month to the end of nine months is the period of fetal maturation. Intake of drugs during this period may modify the 'function' of the fetal organs rather than causing gross structural malformations in the fetus; for example, aminoglycosides can affect the functioning of the kidneys as well as the hearing mechanism.

References