Effects on the Baby

Drugs Used for Medical Disorders in Pregnancy 

Sex Hormones –in Pregnancy

There is good evidence that stilbestrol given during pregnancy predisposes to minor histological changes in the vagina, to minor developmental distortions of the vagina and uterus and to instances of vaginal adenocarcinoma in teenage female offspring. Abnormalities of the genital tract of male offspring may also occur.

                Porgestagens of the 19-nor-groups, such as ethisterone, norethisterone and norethynodrel, given in pregnancy have a small change of causing clitoral enlargement in female babies, which resolves without treatment, and rare cases of labioscrotal fold fusion, which require incision. The 17α-hydroxy compounds such as progesterone, hydroxyprogesterone and medroxyprogeserone do not have this effect.

                There seems to be a very small risk, between 1 in 500 and 1 in 5000, of drug-associated anomalies in the babies of women taking full-dose combined estrogen-progestagen oral contraceptives or given hormone pregnancy tests risk in early pregnancy. The babies affected are mostly male. Whether or not any risk persists with the low doses of synthetic steroids now in oral contraceptives is not clear.

Ovulation Stimulants –in pregnancy

Clomiphene induction of ovulation gives rise to 6% of multiple conceptions very nearly all twin pregnancies, but not to congenital anomalies. The abnormality rate is slightly increased if use of the drug is continued through the first trimester. Menotrophin gives a higher proportion of multiple pregnancies. Some of these ate due to failure to monitor administration with frequent estrogen estimations, resulting in overdose and multiple ovulations. Bromocriptine is not teratogenic, even if continued through the first trimester.

Sedatives and tranquillizers in Pregnancy

Attempts have made to incriminate the use of sedative doses of both barbitutates and benzondiazepines but there is clear evidence that either group of drugs is teratogenic in humans. The babies of women taking regular doses of these groups of drugs before delivery are liable to a newborn withdrawal syndrome. Barbiturates may be more likely to depress the baby, but they are enzyme inducers, which may help if there is a risk of neonatal jaundice, and they are more rapidly eliminated by the newborn than benzodiazepines.

                There is not clear evidence that phenothiazines, monoamine oxidase inhibitors or tricyclic antidepressants, have teratogenic affects on the fetus, though transient neonatal effects such as extra pyramidal reactions after large doses of phenothiazines given to the mother have been recorded.

                Lithuim given in the first trimester may cause small proportion of fetal abnormalities, mainly of the cardiovascular system. If plasma levels are not strictly controlled at the end of pregnancy there is a risk of neonatal lithium toxicity with hypotonia and cyanosis.

Hypotensive Drugs –in Pregnancy

Ganglion-blockers were associated with a 50% fetal loss, mainly from neonatal ileus. Reserpine depresses the baby and causes nasal congestion. The most widely used hypotensive drugs in pregnancy, methyldopa and hydralazine, do not cause congenital anomalis in humans. Methyldopa occasionally gives rise to a positive Coombs test in the baby; neonatal hemolysis has not been reported. Unusually large doses of methyladopa can cause neonatal ileus. Propranolol and other beta-sympaholytics seem to be harmless if treatment with moderate doses for mild hypertension or arrhythmias is initiated before pregnancy, but large doses used to trate severe hypertension developing in mid- or late pregnancy have been associated with a high perinatal lose. It is possible this may be due to impairment of sympathetic vasodilatation in the placental blood supply or of autonomic reflexes in the fetus. Thiazide diuretics can rarely cause neonatal thrombocytopenia.

Hypoglycemic Drugs –in Pregnancy

Women with diabetes mellitus have an increased risk or producing a baby with a congenital abnormality, particularly if this disease is ill-controlled during pregnancy. Insulin or oral hypoglycemic agents do not appear to increase the risk, and the former drug, used to control the diabetes may protect the fetus.

Corticosteroids –in Pregnancy

There is evidence that these drugs cause abortion, intrauterine growth retardation or perinatal death and with some medical disorders the risks these problems may be reduced with adequate steroid treatment. The incidence of fetal cleft palate is less than 1%; the spontaneous incidence of this abnormality is between 0.1 and 0.5%. It has been suggested that this complication is related to the use of large doses in the first trimester, but this has not been clearly differentiated from the effects of the diseases for which the steroids are given. Steroids given o induce pulmonary maturation of the fetus before premature deliveries have been found not to affect the newborn adversely or to impair mental or physical development of the resulting infants.

Cardiotonic Drugs –in Pregnancy

Digitalis is harmless to the fetus unless the mother receives a toxic dose. If heart disease in pregnancy istreated with large doses of frusemide hem concentration may predispose to placental insufficiency.

Antiemetics –in Pregnancy

With the exception pormethazine, each of these drugs has in turn been accused of low level tertogenic effects and subsequently exonerated.