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.

Major Teratogenic Effects on Pregnancy

Major Teratogenic Effects on Pregnancy

Drugs which should not be used in pregnancy except in except in exceptional circumstances can be regarded as falling in this class. They are few in number. Thalidomide is not longer available. Its mode of actins was probably a combination of impairment of folic acid, riboflavin and glutamic acid metabolism, together with effects on the primordial neurons, particularly those related to the affected limbs.

 Cytotoxic Drugs –in Pregnancy

These are all potentially teratogenic in the first trimester, with their specific action on rapidly dividing cells. Some of them have proved less dangerous than was at first thought. Of the alkyl ting agents, cyclophosphamide and chlorambucil have been reported to cause major abnormalities, though successful pregnancies have also been recorded. With busulphan the abnormality rate is about 10%. Of the antimetabolities, the antifolate agents’ aminopterin and methotraxate cause abortion in 50% of women and a proportion of the surviving fetuses are grossly abnormal. In contrast, many women have had normal babies after taking 6- mercaptopurine throughout pregnancy and azathioprine seems to be benign in humans. There are some grounds for avoiding cytarabine, which affects the developing brain in animal experiments, and the antimitotic alkaloids such as actnomcin with their widespread toxic effects on mucleic acid synthesis, but there is no clear evidence of these effects in humans. Whilst data are limited, none of the cytotoxic agents has been demonstrated to be teratogenic in humans when given in the second and third trimesters.

Teracycline Drugs –in Pregnancy

 The teracyclines pass through to the fetus, chelate with calcium ortho-phosphate in the developing deciduous teeth and cause hypoplasia and brown Staining due to an oxidation product. In the third trimester, developing secondary dentition can also be affected.

Radioactive isotopes –in Pregnancy

Radioactive ¹³¹ I can pass through to the fetus and cause neonatal goiter and bypothroidism. Technetium can be used for radioactive scans –its radioactivity is minimal and its half-life short. ³² P may localize in the fetal bones and perhaps affect fetal bone marrow activity deleteriously.

Role of progesterone and hCG Treatment in Early Pregnancy

Role of progesterone and hCG Treatment in Early Pregnancy

Once implantation occurs, the pregnancy hormone Human chorionic Gonadotropin (HCG) will develop and begin to rise.

When the egg is fertilized, the corpus luteum will continue to produce progesterone for the developing pregnancy until the placenta takes over around ten weeks. Progesterone is the hormone that helps maintain the pregnancy until birth. Sometimes, the failure of the corpus luteum to adequately support the pregnancy with progesterone can result in an early pregnancy loss. Progesterone inhibits immune responses, decreases prostaglandins, and prevents the onset of uterine contractions.

With both hcg and progesterone levels, it is not he single value that can predict a healthy pregnancy out come. It is more important to evaluate two different values to see if the numbers are increasing. Levels of hCG should be increasing by at least 60% every 2-3 days, but ideally doubling every 48-72 hours. Progesterone levels rise much differently than hCG levels, with an average of 13-ng/ml every couple days until they reach their peak for that trimester. In situation when there is a concern of an ectopic pregnancy or miscarriage, hcg levels will often start out normal, but will not show a significant increase or will stop rising all together, and progesterone levels will be low from the beginning.

Efficacy and Safety of Progestogens as a Preventative Therapy against Miscarriage

The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups and no statistically significant difference in the incidence of adverse effect in either mother or baby.

In a subgroup analysis of three trials involving women who had recurrent showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment. No Statistically significant differences were found between the route of administration of progestogen versus placebo or no treatment.

Authors’ personal opinion is that there is evidence to support the routine use of progestogen to prevent miscarriage in early to mid pregnancy in those patients who have a history or diagnose to have luteal phase deficiency. However, further trials in women with a history of recurrent miscarriage may be warranted, given the trend for improved live birth rates in these women and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence.

After Pregnancy - Drugs Used During Breastfeeding- Effects on Newborn Baby

After Pregnancy - Drugs Used During Breastfeeding- Effects on Newborn Baby

Before prescribing any medication to a lactating mother pediatrician should consider the following conditions:

a.       Is drug therapy absolutely necessary

b.      Whether infant has got ability to metabolize the medication

c.       How far we can minimize drug exposure to infant

d.      The pharmacokinetics of the drug

e.      Will the drug interact with the medication the infant is prescribed, whether the drug may have adverse effect in the nursing infants and lastly

f.        To choose the safest drug as far as possible

Types of Drugs Prescribed

Cytotoxic Drug- after Pregnancy

Cyclophosphamide, cyclosporine, doxorubicin and methotrexate, etc. were thought to interfere with cellular metabolism in nursing infants. Immune-suppression, and neutropenia may cause in the nursing infant Effects of growth and carcinogenesis are not known.

Drug of Abuse- After Pregnancy

Amphetamine, cocaine, heroin, marijunana, phencyclidine may lead to poor sleeping and irritability- vomiting, diarrhea, tremors, seizures, restlessness, poor feeding, decreased weight gain in infants and possible increased respiratory illness in the infants.

Psychotropic Drugs- After Pregnancy

Antianxiety, Antidepression, Antipsychotic drugs. These drugs usually appear in breast milk in low concentration leads to limited adverse effects in infants but its long-term effects although unknown but colic, irritability, feeding and sleep disorders and slow weight gain are reported with fluoxetine, chlorpromazine may lead to drowsiness and lethargy and declining development score has been reported.

Padioactive Compounds- After Pregnancy

Drug like copper 64, ¹³¹ I, etc. when prescribed in a nursing mother is better to be avoided. A short acting radio nucleotide may be appropriate. It is very much important to screen milk samples, to find out any radioactive drugs in the milk before receiving feeding.

Other Drugs- After Pregnancy

Amiodarone may cause hypothyroidism, cholraphenicol leads to idiosyncratic bone marrow suppression. Metronidazole and tinidazole are in vitro mutagenic agents. Clofazimine may increase skin pigmentation. Atenolol cause cyanosis and bradycardia. Phonobarbitone may lead to sedation, infantile spasm and methemogloginemia and ergotamine may cause vomiting, diarrhea and convulsions.