Abstract
There is a strong debate existing on the utility of drugs aimed at treating psychological illnesses frequently encountered during pregnancy, and therefore the origin of drug-induced birth defects could not be ascertained properly. Large studies are essential to evaluate their efficacy and risk.
Available studies report that the use of certain drugs namely, selective serotonin-reuptake inhibitors (SSRI) or antipsychotics for treating psychological illnesses is not associated with birth defects. However, although sporadic cases of birth abnormalities have been reported, data is insufficient for compelling evidence.
A group of 1000 women subjects would be screened by implementing methods like approaching private clinical centers and government hospitals, home surveys, and institutional notice displays, and selected after informed consent. Their pregnancy outcomes will be matched to their drug history basing on the exposure during the first, second, and third trimesters.
An equal number of infants with normal births and whose mothers were not been exposed to drugs would be selected as control groups. The information about drug exposure from both the subjects and control mothers would be retrieved by an interview. Birth abnormalities would be classified in to different categories and assigned to a specific drug exposure by a professional medical officer.
Introduction
The present report is an attempt to propose a study entitled “Mass study of Antipsychotic/Antidepressant associated birth defects.” It is not known whether these drugs are fully considered safe for a pregnant woman. McKenna et al. (2005) conducted a study to determine the extent of the antipsychotic effect on the general population and examine the rates of abortions and birth defects. Their study has observed a majority of live births compared to the relatively low number of abortions and revealed that there is no likely association between antipsychotic drugs and risk of major deformities. Hence, this study may indicate the safety of antipsychotic drugs.
In another study, it was shown that the use of a special class of antidepressants, serotonin reuptake inhibitors (SSRIs), was not associated with congenital or any other birth defects and the risk is very meager (Sura Alwan et al., 2007).
Similar studies also revealed and strengthened the weak connection between SSRI and birth defects (Carol Louik et al., 2007). However, despite these findings, recent workers have suggested proper monitoring of the use of psychotropic drugs during pregnancy to ensure safety to pregnant women and their children at all times of exposure (Maschi et al., 2008).
So, it may be inferred that antipsychotics or antidepressants have been considered as the drugs of choice for a pregnant woman to overcome mental illnesses and there is still a problem in identifying the birth defects believed to be connected with the use of these drugs.
This is indirectly a birth defect-associated population problem and is important to focus on because natality is omnipresent and the widespread recommendation of drugs during pregnancy may affect the number of outcomes, and subsequently a recurrence in habitual abortions would be more frequent (Baker et al., 2008).
So, the likely development of child deformities if not assessed or detected earlier may transform into life-threatening problems at a later age thereby increasing the complexity of the case. There would be an overall reduction in normal live births and an increase in mortality rates.
The study was designed keeping in view existing hypotheses and would be focused to understand the effects of both antipsychotic and antidepressant drugs and the term ‘drugs’ is common in this description. Women attending maternity wards and fertility centers at both government and private hospitals would be selected. They will be evaluated till the outcome of their pregnancies. Birth defects, if any would be recorded and matched with the drug history of the mothers. An equal number of women who had infants without any birth abnormalities would be selected and will be interviewed to get information about the drugs used during the term. The data obtained will be compared between both the groups and also with the findings of earlier research.
The process of recruiting will be as follows.
A group of 1000 pregnant women will be approached at private clinical centers and government hospitals and informed about the study after approval by the university boards and medical authorities.
In addition, people will also be recruited by conducting a home survey. A novel method that involves a display of the brief significance of the study on notice boards of various institutions would also be employed to attract the voluntary participants.
Those willing to participate would be selected after obtaining written consent. Staff members like nurses and attenders would also be informed about the study and asked to provide information about patients flow and case sheet details like age, body mass index (BMI), history of mental illness, history of other illness, infections, drug history, smoking, alcohol consumption, and diet habits.
An equal number of age-matched healthy women found with no history of antidepressant or antipsychotic drug therapy during the term and their normal infants will be selected as control groups. Infants with trivial complaints would be excluded from the study.
Materials and procedures
Pregnant women selected for the study are interviewed to provide details about the drugs that have been in use, an approach followed by earlier workers (Carol Louik et al., 2007). For further confirmation, the patient detailing was verified with the hospital records. Here the doctors or staff members would be especially requested to maintain a separate proforma of patients exclusively for the benefit of the study.
Next, patients found with consistent drug therapy would be kept under close surveillance and the likely date of delivery would be found out.
Patients will be interviewed as soon as possible after the delivery. They would be shown a list of drug names and asked to identify them and their route of delivery. Here, it is assumed that apart from doctor’s prescription, any patient self- medication would be a possibility. Patients would also be asked to reveal the drugs used independently or in combination with any other drugs like Digene, Ranitidine, H2– blockers etc.
This process of questionnaire will be continued from the next day of delivery to four months. The interview will also be focused on socioeconomic conditions of the patients.
Control subjects who had normal infant births would also be interviewed to determine the drugs used, diet habits and life style during the term period.
After the day of delivery, infants would be screened by experts to detect abnormalities as described in an earlier research (Sura Alwan et al., 2007).
Infants found with genetic abnormalities would be excluded from the study.
Infants found with birth abnormalities would be matched to the drug therapy of their mothers by reviewing their previously recorded interview detailing and case sheets.
The details of dosage and the manufacturing company of the drug would also be taken into consideration to assess the magnitude of the risk. The procedure of assigning the abnormalities to the drug usage would be done according to a recommended criterion for risk evaluation under highly qualified medical expertise (Sura Alwan et al., 2007).
Patients with abortion cases would be interviewed to determine whether there were any instances of overusage of drugs for getting instant relief from mental illnesses. Patient would be especially asked if they had any previous drug allergies or discontinued therapy due to the manifestation of allergic symptoms. If they reveal any allergic development, they would be further questioned about the characteristics of symptoms, their duration, and any treatment taken to overcome such conditions.
Patients are also asked to furnish information about their close relatives who had any previous history of gynecological or obstetric complaints. If any cases of abnormalities were revealed they would be further asked to furnish about the factors claimed to be responsible for such outcome. This information would help in rapid assigning of the complaints with the drug usage or any other risk contributing factor.
Similar strategy would be followed for the women having infants with congenital or other birth defects. The defects later assigned would be recorded and compared with any similar cases previously entered in the hospital records, for obtaining a consistent data.
This study would be focusing on the use of drugs in all trimesters in contrast to only one as observed in previous reports (Carol Louik et al., 2007).
Based on the information obtained regarding the use of drugs, patients will be categorized into five groups.
First group comprises of patients who use drugs in the first trimester only, the remaining two groups comprises of patients who use drugs only in the second and third trimesters, respectively. However, they may be some patients with a history of mental illness and consistent drug usage in all trimesters. For these patients fourth group will be assigned.
A fifth group will be assigned for those patients who show some irregularities or inconsistencies in drug usage throughout the term and neither fall into any of the four categories. This strategy would be employed with the objective of understanding the long-term and short-term effects of drugs on the development of fetus.
Further, to find the differences between the drugs and assigning their association with a particular trimester, drugs would be assigned alphabetical codes.
For example, if drug A was found to be used by all the groups and a birth defect was detected, then drug ‘A’ would be a strongly suspected candidate.
If drug ‘B’ was found to be used in one trimester by one group and drug ‘A’ was used in the second and third trimesters by the remaining groups, then it would be assumed that both the drugs are having the same potential in influencing the risk, provided there is birth defect.
This strategy would be expanded for a broad range of drugs used and a large data generated would be analyzed by a professional statistician.
From the data interpretation results, information will be assigned to a spectrum of birth abnormalities. While assessing the risk, ethnicity of the subjects would be given much priority. Patients found with increased exposure to drugs would be further investigated by a novel functional genomic approach to determine their genetic predisposition to the drugs.
For this purpose, patients would be requested to participate in a small genome wide study, after obtaining another written consent. Patients would also be asked to reveal any behavior problems faced during the exposure to drugs.
The data obtained from various clinical centers will be coordinated. Here, the data of both subject and control groups entered into the records since the beginning day of the study will be carefully retrieved and a database is prepared using a computer programme. Finally, the data obtained from the patients with all the categories of infant birth defects would be compared with the women controls having no obstetric complaints.
Information about previous birth defect cases would also be collected from all the centers by requesting the past records of the admitted patients. Information about the flow of prescriptions, counter sales and the availability of range of drugs will be obtained from the chemists.
Further, chemists will also be interviewed to determine any possible chances of substitutes as such cases may prove central to contributing the risk.
The data finally obtained from all the sources will be tabulated using special computer software. The approximate time for this pilot study would be initially three years with one year follow up study.
This study does not involve any supplementation or therapy from outside for the research benefit. However, ethical committee will be informed and their guidelines will be followed while dealing with the pregnant women and the infants. Hence, pregnant women would be explained and given complete risk free assurance of the study. They would not be pressurized under any circumstances in any form to participate.
Therefore, only patients willing to participate would be asked a written consent. The data will be stored in specially created databases by assigning codes and maintained by a team of only two research members to keep the information confidential.
A duplicate database would also be created to retrieve any information lost from the original one due to human errors. In addition, the data will also be stored in neatly complied paper files to overcome any software associated problems, with different codes maintained by another team.
The over all data obtained in the proposed study, will be considered for establishing a strong link with the earlier findings. The estimated cost for this project would be around 50000 to 100000 USD.
The only benefits for the participation would be that, individuals are ensured valuable health information and care during and after the completion of the study.
But, they would not be revealed any information that might interfere with the study hypotheses. The participants would be given free diet counseling organized by nutrition experts after the completion of the study. They would be offered free medical check ups and consultations at referred clinical centers for a period of one year and assured free pediatric care.
This research is proposed with the objective of providing the general information to the society on the possible adverse effects of drugs. People can better avoid unnecessary urgency and expenditure while choosing such drugs.
Large population would be saved from the death rates associated with drug induced spontaneous abortions. People would become familiar with some medical complications reported earlier like craniosynostosis, omphalocele, looping, laterality, single-ventricle defects, and septal defects (Carol Louik et al., 2007). They will understand the need of knowing brand and chemical names of drugs, manufacturer’s names, possible risk associated with substitutes, overusage or usage without prescriptions.
They will also understand the potential implications of drugs with novel combinations. This process would enable them to eliminate any misconceptions and ensures rapid detection of errors associated with suspected drugs.
Further, psychology related complications would be considered cautiously and appropriate therapeutic regimen with minimum risk will be chosen under medical supervision.
Society will be better adapted mentally to provide information without any hesitation and may show good willingness to participate in more number of studies.
The research may boost confidence in people such that they can better evaluate themselves for any possible outcome. People can change life style and would choose nutritious diet or any other supplementations known to play beneficial role in modulating the disease conditions. They would be approaching for safer remedies rather than risk involved drug therapies.
Children with malformations would be easily identified for efficient diagnosis. Society might help the medical researchers in assigning the problems to drug usage up to some extent. Further, with the available familiarity recurrence of any condition for example, abortions will be lessened. The main advantage of this proposed study is, the knowledge gained by the society members from the research will educate them which would mutually benefit the researchers in building a risk free society.
On the whole, the benefit of this study would not only help to strengthen the connection between antipsychotic or antidepressant drugs and birth defects but also may provide information about other parameters that are strongly suspected to be contributing to the risk.
References
McKenna, K., Koren, G., Tetelbaum, M., Wilton, L., Shakir, S., Diav-Citrin, O., et al. (2005). Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. The Journal Of Clinical Psychiatry, 66, 444.
Carol Louik, Angela E. Lin, Martha M. Werler, Sonia Hernandez Diaz, Allen A. Mitchell (2007). First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects. N Engl J Med, 356, 2675-83.
Sura Alwan, Jennita Reefhuis, Sonja A. Rasmussen, Richard S. Olney,Jan M. Friedman.(2007). First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects. N Engl J Med, 356, 2684-92.
Maschi, S., Clavenna, A., Campi, R., Schiavetti, B., Bernat, M., & Bonati, M. (2008). BJOG: An International Journal of Obstetrics And Gynaecology, 115, 283-289.
Baker MK, Kolling P, Van denberg PB , De valle HE , De jong Vanderberg LT.(2008). Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. Br J Clin Pharamacol, 65, 600-6.