Pregnancy is a complicated state when a female body undergoes a plethora of changes. The body evolves and develops to assist the growth and development of the placenta and the unborn child. The changes in physical appearance, hormonal levels, metabolic functions, dietary preferences, etc. are significant in a pregnant woman when compared to a non-pregnant or normal woman. The primary concern in clinical treatment arises while treating a pregnant woman, rather than a non-pregnant lady. Many disorders surface during pregnancy that is otherwise not present and disappear once the gestation period is over.
Besides, a majority of the drugs are either restricted or have causative usage warnings for use during pregnancy. Thus, it poses a great hindrance in treating pregnant women that otherwise would have been quite easy in normal non-pregnant females. The following write up will highlight some facts about why the treatment of pregnant and non-pregnant ladies are different.(1)
Treating Pregnant Vs Non-Pregnant Women
Changes In Pregnant Women As Compared To Non-Pregnant Women
Non-pregnant women witness no sudden transitions in their physical activity, behaviour, dietary cravings, etc. that pregnant women generally experience. All these changes are reflected during the nine months of gestation. And the main reason for these changes can be traced back to the hormonal upheavals that occur during pregnancy. On the other hand, a non-pregnant woman has normal hormonal balance and thus, there is no need to alter any treatment method or restrict the use of certain drugs while treating them. Some of the common changes observed in pregnant women as compared to the non-pregnant women are as follows:
- Physical Activity and Sedentary Lifestyle: Non-pregnant women are relatively more active physically when compared to pregnant women. As the pregnancy moves forward to the second and third trimester, and the fetus starts to grow, extreme physical activities and heavy work are restricted for the expecting mother. It leads to a sedentary lifestyle and often results in gaining extra weight and being obese. The condition furthermore changes the BMI of the body during pregnancy due to an effect on metabolism. However, if a woman is not pregnant, there are no such chances of obesity due to sedentary lifestyle and limited physical movements. It keeps the metabolism in check and does not prove to be a hindrance to drug action.
- Insulin Sensitivity and Secretion: In pregnancy, the insulin sensitivity drops down by 40 to 60% as compared to the insulin sensitivity in non-pregnant women. The decline in insulin sensitivity with other metabolic and hormonal changes during pregnancy is likely to impair systemic glucose regulation. It can also lead to gestational diabetes throughout the pregnancy duration, which is otherwise not present when the same woman was not pregnant. The general protocol of diabetes cannot be used to treat such conditions as it is not a persistent lifestyle disorder, instead of a pregnancy-developed condition.(2)
- Dietary Changes: During pregnancy, the dietary pattern is profoundly altered as the expecting mother requires superfluous nutrition and supplements to support the growth of the fetus. There is also a restriction on some food items as well as the consumption of alcohol and tobacco during pregnancy to avoid harm to the unborn child. Regardless there is no such restriction on non-pregnant women.(3)
- Biochemical Profile: The most remarkable difference that is observed between a pregnant and non-pregnant woman is their biochemical profile. During pregnancy, hormonal and metabolic alterations exert their effect on physiological functions as well as on the metabolism of lipoprotein and fats to meet the demands of the growing child. The distortion in the biochemical levels is a reflection of the adaptive modification that the body of a pregnant mother makes as compared to that of a non-pregnant female. The serum levels of estrogen, progesterone, Tc, Tg, LDL are significantly higher in a pregnant woman than a non-expecting female. The rapid upswing of cholesterol and triglyceride level in pregnant women can lead to harmful adverse effects if not controlled. These increased biochemical levels restrict the use of various drugs and treatment modalities during pregnancy to avoid harm to the fetus.(4)
Alteration of Drug Metabolism In Pregnant Women
The complication concerning the treatment of pregnant and non-pregnant women is based on the fact that pregnancy alters the function of enzymes and transporters responsible for drug metabolism. With bolstered levels of female hormones like estrogen, prolactin, progesterone, and placental growth hormones, the hepatic metabolism, as well as excretion of the drug, is highly affected. Drug handling in pregnancy is quite critical when compared to that of in a not pregnant female due to various reasons as follows:
In a non-pregnant woman, the rate of drug absorption is normal, but during pregnancy, the increased cardiac and pulmonary output results in enhanced drug uptake. Intramuscular and subcutaneous drugs are also absorbed quickly on pregnant females.
The peak plasma levels of oral drugs are delayed during pregnancy. The reduced gastric motility and acid secretion delay the gastric emptying time, and the drug is retained for a longer period. period drugs can prove toxic is their gastric retention time is increased
The normal level of plasma in non-pregnant women shoots up once pregnancy sets in. It also increases the blood volume, body mass, as well as the total water content of the body. It reduces the serum levels of the drug, and thus a high dose is required to achieve the desired therapeutic effect. For example, if a non-pregnant is taking a fixed dose of digoxin, she might need a higher dose for the same therapeutic effect during the gestation period.
Pregnancy witnesses a good amount of fat accumulation in females. The extra adipose tissue increases the binding of lipophilic drugs in pregnant females than the non-pregnant ones. High lipophilic affinity leads to the slow release of the drug and a prolonged duration of effect.
The alterations in drug metabolism during pregnancy is a potential threat to the fetus if the drug crosses the placenta. In pregnancy, the level drugs binding protein albumin decreases, it, in turn, results in the availability of free drugs in the plasma. Some common medicines that exhibit high plasma levels in pregnant women as compared to non-pregnant women are diazepam, warfarin, anti-inflammatory drugs, salicylates, nonsteroidal anti-inflammatory agents, steroids, and anticonvulsant. The reduced efficiency of plasma proteins to bind these drugs makes them available to cross the placental barrier and harm the fetus.
Hepatic clearance of the drugs is altered when a woman is pregnant. For medications like antibiotics, phenytoin, acetaminophen, pancuronium, and neuromuscular agents, the hepatic metabolism is slowed. It increases the retention time of such drugs in the body as compared to the retention time in females who are not pregnant. It increases the threat of thermogenic metabolites that can potentially harm the fetus if it stays in circulation for too long.
High glomerular filtration rate in pregnant ladies reduces the efficacy of drugs like penicillin, digoxin, cephalosporins, lithium, sulfonamides, and aminoglycosides. The reduced half-life becomes insignificant for clinical outcome, and the high side at frequent intervals are required.
This alteration of drug metabolism, transport, and clearance returns to normal once the non-pregnant status arrives after delivery.(5,6)
Treatment of Ovarian Cyst In Pregnant Vs Non-Pregnant Women
The conventional treatment method to treat ovarian cysts is through laparoscopy or laparotomy. However, the fine needle aspiration is not used in pregnant women as it can cause harm to the placenta and the fetus. For pregnant patients with ovarian cysts where any surgical method of treatment is not feasible, the laparoscopy is done transvaginally to prevent placental contact.(7)
The Dilemma Faced By Health Workers While Treating Pregnant Women As Compared To The Non-Pregnant Patients
There is a severe lack of evidence for the use of various drugs during pregnancy. It renders the health worker slightly confused whether to use a particular drug during pregnancy or not as it might have an adverse effect on both the mother and the child. Such incidences are highly unfavourable as most of the time; a pregnant woman is deprived of medication due to uncertainty of its effect on the child.
Need for Increased Involvement Of Pregnant Women In Clinical Trials
The involvement of pregnant women in clinical trials is restricted as the experimental intervention can cause harm to the child and mother. The vulnerability can lead to premature delivery, or complication, and even fatality in some cases. However, the use of medicine in pregnancy is highly limited due to the lack of safety and efficacy data in the pregnant population. Non-pregnant women face no such issue regarding their treatment. Thus, increased participation in clinical trials by pregnant women should be encouraged by fostering a sense of trust and security. It will help the doctors to determine doses and therapeutic efficacy of various drugs that are currently not used in pregnant women.(8,9)
The treatment modalities profoundly differ in pregnant and non-pregnant women. It is attributed to the physical, biochemical, and metabolic changes that exert an effect on drug absorption, metabolism, binding, and clearance. Thus, medicines should be used with caution in pregnant females as their therapeutic levels and bioavailability are different from those in non-pregnant women.
- Feghali, M., Venkataramanan, R., & Caritis, S. (2015, November). Pharmacokinetics of drugs in pregnancy. In Seminars in perinatology (Vol. 39, No. 7, pp. 512-519). WB Saunders.
- Gradmark, A., Pomeroy, J., Renström, F., Steiginga, S., Persson, M., Wright, A., … & Franks, P. W. (2011). Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women. BMC pregnancy and childbirth, 11(1), 44.
- Verbeke, W., & De Bourdeaudhuij, I. (2007). Dietary behaviour of pregnant versus non-pregnant women. Appetite, 48(1), 78-86.
- Alemu, A., Abebe, M., Biadgo, B., Terefe, B., & Baynes, H. W. (2018). Biochemical profiles of pregnant and non-pregnant women attending at the University of Gondar Hospital, Northwest Ethiopia: a comparative cross-sectional study. Ethiopian journal of health sciences, 28(3), 331-340.
- Isoherranen, N., & Thummel, K. E. (2013). Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?. Drug Metabolism and Disposition, 41(2), 256-262.
- Blackburn, S. (2012). Pharmacokinetic changes in the pregnant woman. The Journal of perinatal & neonatal nursing, 26(1), 13-14.
- Khaw, K. T., & Walker, W. J. (1990). Ultrasound guided fine needle aspiration of ovarian cysts: diagnosis and treatment in pregnant and non-pregnant women. Clinical radiology, 41(2), 105-108.
- The, L. H. (2019). To treat, or not to treat: the dilemma for pregnant women. The Lancet. Haematology, 6(2), e58.
- Monteiro, T. M., Katz, L., Bento, S. F., Amorim, M. M., Moriel, P. C., & Pacagnella, R. C. (2019). Reasons given by pregnant women for participating in a clinical trial aimed at preventing premature delivery: a qualitative analysis. BMC pregnancy and childbirth, 19(1), 97.