Pregnant women and drugs: Can they go together?

Every year Singapore's Mount Elizabeth Hospital organizes an annual seminar on a wide variety of medical topics. This year's seminar, held between Nov. 12 and Nov. 14 at the Westin Stamford hotel in Singapore, focused on the latest research in obstetrics and gynecology. The following article is based on one of the papers presented at last Sunday's main conference.

SINGAPORE (JP): Pregnancy is not a disease and does not warrant medication but when the mother has a medical disorder drugs are used, said a noted physician.

Dr. S. Arulkumaran, professor of obstetrics and gynecology at the University of Nottingham, United Kingdom, told the audience that evidence of the effectiveness and the side effects of drugs used in pregnancy is not based on large clinical trials, but is largely circumstantial.

The three-day seminar focused on various issues connected with maternal and female health including ovarian cancer, breast cancer, hormone replacement therapy, perinatal, urinary incontinence, infertility and other health problems.

The seminar is in conjunction with the 20th anniversary of Mount Elizabeth Hospital, one of hospitals managed by the Parkway Group Healthcare, which will fall in December.

The seminar featured a number of prominent figures in the medical world including Prof. S. Arulkumaran, Dr. Ian Hammond from the King Edward Memorial Hospital for Women, Western Australia, Dr. P.C. Wong and Dr. S. Sivasankaran.

The professor said during his session entitled Prescribing for the Pregnant Patient-Is There Any Safe Drug? that the effect of any drug depends on its type, dosage, duration of use, other drugs used concurrently with it, associated conditions, the genetic predisposition of the patient and, most importantly, the length of gestation when the drug is used.

Some women may be on long term medication. They should be counseled regarding the possibility of a drugs' harmful effects. In the absence of any reason to the contrary, the treatment should not be withheld, the professor advised.

"It is important to recognize that the causes of 60 to 70 percent of birth defects are not known," he said.

Arulkamaran explained it is estimated that about 20 percent of birth defects are due to genetic transmission, three to five percent are chromosonal, two to three percent are due to infection and one to two percent are due to maternal metabolic disorders. Drugs and chemicals are estimated to cause four to six percent of birth defects, he said.

They may induce chromosomal abnormalities, prevent implantation to the conceptus, cause resorption or abortion of the early embryo, cause structural malformation, intrauterine growth restriction or fetal death.

Some effects may present themselves later, in the form of functional impairment of the fetus (e.g deafness), behavioral abnormalities and/or rarely mental retardation, he said.

The professor said a fetus is most vulnerable during the period of maximum differentiation, the first 10 weeks of the pregnancy (12 weeks from the last menstrual period). It is considered that the first 17 days of conception constitute the pre-embryonic period, and toxic insult at this time may cause total damage and miscarriage. If the damage is slight, the remaining cells multiply and repair themselves and the pregnancy continues without any harm.

The importance of drug versus genetic factor varies. For example, 1 percent of fetuses exposed to Phenytoin may be affected by cleft palate whilst with Thalidominade or Isorotenioin 50 to 100 percent may be affected. The relative risk of malformations for the following has been estimated based on collations of adverse reports; Aspirin 1.04 percent, Sulfisoxazole 1.04 percent, Penicillins 1.07 percent, Tetracycline 1.14 percent, Phenytoin 1.56 percent, Phenpbarbitone 1.03 percent, Prochlorperazine 1.18 percent, Doxylamine 1.06 percent and Insulin 2.09 percent.

The recurrent pattern of malformation with a given drug gives information of its teratogenic potential. The following associations are known. Lithium: cardiovascular defect; iodine: fetal goiter, anti-convulsants, facial defects and mental retardation; Streptomycine: deafness, vestibular damage and warfarin nasal hypoplasia; and Cytotoxic drugs: abortion, growth restriction, stillbirth and other defects.

Arulkamaran also warned that care should be taken when prescribing to mothers who breast-feed their infants. The drugs which may have effect the newborn are; Amiodaronehydrochloride: iodine content may cause neonatal hypothyroidism; Aspirin: may cause risk of Reye's syndrome; Carbimazole: hypothyroidism (use lowest effective doze); while combined oral contraceptives may diminish milk supply and reduce the protein content and nitrogen of breast milk.

The effects of drugs on breast-feeding women are variable and the list given above is not exhaustive.

Most drugs carry the warning "Not to be used while pregnant unless the benefits outweigh the risks." This puts a heavy responsibility on the physicians and makes women reluctant to take the prescribed drug.

"Counseling before prescribing is important. Knowledge of the drugs known to be harmful is useful and, when in doubt, it is best to consult to a colleague," he reminded.

Dr. S. Sivasankaran, consultant pediatrician at the Mount Elizabeth Medical Center, presented a paper on another important subject: Perinatal mortality in Singapore.

"Perinatal mortality is important because it reflects the standard of obstetric and neonatal care as well as social and health conditions," Dr. Siva explained.

Perinatal mortality rates (PMR) rates have been declining in all countries. This decline mainly results from improvements in late fetal and neonatal mortality rates.

Developed countries have consistently shown better results than developing countries.

In Singapore there has been a tremendous improvement in these statistics due to improving living standards and healthcare, as well as rapid advances in neonatal intensive care, which have resulted in a significant decrease in neonatal mortality rates.

In l998 PMR in Singapore was 4.9 percent per 1,000 births. This figure is comparable to most developed countries.

The use of exogenous surfacants on these infants has revolutionized the treatment and this has reduced PMR to a certain extent. Antenatal steroids are being given to mothers who go into premature labor in increasing numbers. This has resulted in decreased incidence of respiratory distress syndrome in premature infants, which has also had an effect on the PMR.

In a special interview, Dr. Siva expressed concern over the high maternal and mortality rates in Indonesia, especially since the economic crisis.

According to Dr. Myrnawati from the University of Indonesia, the infant mortality rate in Indonesia is still very high compared to other South East Asian countries.

In her doctoral dissertation she found that Indonesian mortality rates are 58 per 1,000 live births, and the mortality rate of under-five-year olds is 81 per 1,000 live births.

"The crisis has caused a tremendous blow to maternal and infant health care in Indonesia. I hope that we can do something to help Indonesian people cope with the problem," Dr. Siva said. (raw)