Essential Medication Prescription and Associated Maternal Characteristic among Hospitalized Pregnant Women: A Retrospective Population Based Study

Basutkar, Raja, Divya, Das, and Ponnusankar: Essential Medication Prescription and Associated Maternal Characteristic among Hospitalized Pregnant Women: A Retrospective Population Based Study

Authors

INTRODUCTION

The drug use during pregnancy can be a major concern either by temporary and permanent structural and functional adverse effects on both the foetus and mother. This will pose a major challenge and also warrants for a careful consideration of many aspects that would influence the decision to determine the medication use for each selected indication by health care providers during the antenatal care.1 To attain the safe use of drug throughout the pregnancy, the United States Food and Drug Administration (US FDA) has classified the drugs into major categories A, B, C, D X and unknown according to the risk to foetal health. Most of the drugs used in the pregnancy are classified under category C due to lack of data. Whereas categories D and X have an evidence of foetal risk.2,3 Many drug utilization studies have reported that around 44 to 99 per cent of pregnant women use medications.4 In one study conducted in Denmark found that 18% of pregnant women during their antenatal care have been prescribed with at least one drug and 1% reported to have ≥ 5 prescriptions that can cause potential harmful effects on the foetus. In other study conducted in France, 59% of the pregnant women were prescribed with category D, 79% received the drug whose pregnancy risk classification is unknown. 1.6% of the pregnant women received category X drug.5 Thus the inappropriate use of medications has been reported extensively among the pregnant women worldwide.6,7 In India, many use the prescription drug with very less information on the extent and type of drug use, which pregnant women further emphasis on definition for rational prescription.7,8 In the present set up of secondary care Government District Headquarters Hospital, Udhagamandalam, there was no such study conducted to evaluate the safety and effectiveness use of medications among pregnant women. Hence, this retrospective survey was conducted to find most recent prescribing pattern and most possible teratogenicity risk to foetus in hospitalised pregnant women during their antenatal care.

MATERIAL AND METHODS

The present study was a retrospective survey conducted at a secondary care 420 bedded hospital located in Udhagamandalam the Nilgiris district, Tamilnadu, India. The primary objective of the study was to analyze the prescription pattern of C, D and X (as per FDA guidelines) among the hospitalized pregnant women at obstetrics and gynecology unit. The data was collected retrospectively for duration of six months (June to December 2015) from medical records of hospitalized pregnant women with pregnancy confirmed by ultrasonography results. Medical records were reviewed and included for the study as per the inclusion and exclusion criteria. The pregnant women who were prescribed with at least one prescription for any treatment at the in-patient set up are considered as exposed to medication and their medical records were included. Those pregnant women in whom the prescription drug information is not available were excluded from the study. Information on maternal and obstetrics characteristics of the pregnant women such as age, plurality (that is, number of foetuses of the present pregnancy), parity (based on numbers of live births and stillbirths), gravidae (number of pregnancy), socio-demographic information, drugs prescribed, dosage form, route of administration, main diagnosis, and the trimester during drug administration was collected in a specially designed proforma. The collected data was checked for completeness manually by the Clinical Pharmacist. Drugs that were dispensed, were identified and classified according to the FDA risk classification (A, B, C, D, and X) and therapeutic class. Based on International Classification of Diseases 10th revision was used. The study was approved by the Institutional Review Board, JSS College of Pharmacy, Ootacamund (JSSCP/DPP/IRB/02 2015-16) before initiation.

The collected data were categorized and analysed. Descriptive analysis was performed for demographic characteristics, pregnancy information, medical condition, prescribed drugs and its pattern. Pearson Chi-square Fisher’s exact tests were used to observe the association between the independent variables and outcome variables. Adjusted odds ratios (ORs) and 95% CIs were also estimated. Each outcome variables whose levels were with a P (< 0.05) was significant. All analyses were performed using GraphPad Prism version 6.04 for Windows (GraphPad Software, La Jolla California USA, (www.graphpad.com) and SPSS version 22.0 (SPSS Inc., Chicago II, USA) for windows.

RESULTS

Among the 520 pregnant women hospitalized during the study period a total of 505 received 2840 medications during the study period. 83.16% of the women were in the age group of 21-34 years and the mean age was found to be 24.17±3.5 years demonstrating normal reproductive age group. While 73 women (14.47%) were in the age of ≤ 20 and 12 (2.37%) women were in the age of ≥35. Out of 505 pregnant women, 49.50% were secundum gravidae, 34.85% were primigravidae and 15.65% were multi gravidae.

Most of the pregnant women are hospitalized during the third trimester (75.24%), followed by second trimester (12.88%) and (11.88%) during the first trimester. Out of 505 pregnant women 109 (21.58%) had a previous incidence of abortion. 3.17% pregnant women were found to have comorbid conditions.

From the total study population (39.41%) pregnant women were prescribed with ≤5 drugs and remaining (60.59%) were prescribed with ≥5 drugs during their hospitalized period. 52.07% pregnant women stayed ≤ 4 days in the hospital, (38.4%) pregnant women stayed 5 to 9 days and remaining 48 (9.5%) pregnant women stayed ≥10 days for their treatment. It was observed that the average duration of pregnancy was 8.8 months among the study population.

The most common medical condition experienced by the pregnant women was Iron deficiency anaemia (25.43%) (with code D 50 as per ICD-10 version), followed by (12.14%) experienced Urinary Tract Infection (with code O 23.4 as per ICD-10 version) during all the trimester. Table 1 describes the most common drugs received by the pregnant women. It was found Tablet Ferrous sulphate for the treatment of iron deficiency anaemia was highly prescribed (12.61%), followed by Vitamin B Complex (12.08%), Tablet Calcium lactate (11.44%) as a part of routine medications to be taken by all pregnant women and Inj. Cefotaxime 1g IV (7.74%) towards the management of Urinary tract infection and the less common drugs prescribed was Tablet Ibuprofen 400 mg (0.03%) and Tablet Dicyclomine 20 mg (0.03%). Majority of the patient received the drugs during the third trimester. Most of the patient received medication per oral (76.10%); followed by (23.72%) injectable and 0.17% received Topical preparations.

Table 1

The most common drugs received by the pregnant women during the study.

Therapeutic classSpecific MedicineATC groupTotal frequency n(%)
Analgesic (N02)T.ParacetamolN02BE01200(7.04%)
Inj. ParacetamolN02BE0119(0.67%)
Inj. PentazocineN02AD012(0.07%)
Anesthetics (S02)Inj. LignocaineS02DA0110(0.35%)
Antianemic (B03)T.Folic AcidB03BB0130(1.06%)
T.FerrousSulphateB03AA07358(12.61%)
Antibacterial for systemic use (J01)Inj. AmpicillinJ01CA0170(2.46%)
Inj. CiprofloxacinJ01MA024(0.14%)
T.CiprofloxacinJ01MA027(0.25%)
C.AmoxycillinJ01CA0477(2.71%)
T.NorfloxacinJ01MA065(0.18%)
Inj.CefotaximeJ01DD01226(7.96%)
C.CephalexineJ01DB0160(2.11%)
Inj. CeftriaxoneJ01DD0413(0.46%)
Antibiotics and chemotheraputics and dermatological use (D06)Liq. Gentamycin Eye DropD06AX077(0.25%)
Inj.GentamycinJ01GB0320(0.70%)
Inj. AmikacinD06AX128(0.28%)
Antidiarrheals (A07)Oral rehydration saltA07CA14(0.49%)
Antihistamines for systemic use (R06)T. CetrizineR06AE077(0.25%)
Anthelmintics (P02)T. AlbendazoleP02CA036(0.21%)
Antihistamines for systemic use (R06)T. Chlorpheniramine maleateR06AB021(0.04%)
Syp. Cough syrup (ChlorpheniramineMeleate)13(0.46%)
Anti-inflammatory (M01)T.IbuprofenM02AA131(0.04%)
T.Diclofenac SodiumM01AB0572(2.54%)
Inj. Diclofenac SodiumM01AB0573(2.57%)
Anti -infectives for systemic use (J07)Inj. Tetanus toxoid (Absorbed)J07AM019(0.32%)
Anti –Microbial (A01)T.MetronidazoleA01AB17175(6.16%)
Inj. MetronidazoleA01AB1751(1.80%)
Anti septics and disinfectants (D08)Cetrimide CreamD08AJ044(0.14%)
Cardiac vascular system (C0)T. LabetalolC07AG0145(1.58%)
T.NifedipineC08CA0520(0.70%)
Inj. FurosemideC03CA012(0.07%)
Inj.DopamineC01CA042(0.07%)
Corticosteroid (R01AD)Betamethasone valerate ointmentR01AD068(0.28%)
Diagnostic Radiopharmaceuticals ( V09 )Inj.CyanocobalamineV09XX011(0.04%)
Drugs used for acid related disorders. (A0)T.RanitidineA02BA02189(6.65%)
Inj. RanitidineA02BA02152(5.35%)
C.OmeprazoleA02BC013(0.11%)
Liq.Antacid (Aluminum Hydroxide Gel, Magnesium Trisilicate, Methyl Polysiloxane)A06AD152(0.07%)
Drugs for constipation (A06)T. BisacodylA06AB021(0.04%)
T.Magnesium SulfateA06AD048(0.28%)
Drugs used in diabetes (A10 )T.MetforminA10BA025(0.18%)
Inj.Human insulin (short acting)A10AD011(0.04%)
Inj.Human insulin (intermediate acting)A10AD011(0.04%)
Drugs for functional gastrointestinal disorders (A03)Inj. MetaclopramideA03FA0112(0.42%)
T.DicyclomineA03AA0732(1.13%)
Inj.DicyclomineA03AA071(0.04%)
T.DomperidoneA03FA0320(0.70%)
Drugs for obstructive airway diseases (R03)T. TheophyllineR03DA045(0.18%)
Neb.SalbutamolR03AC0215(0.53%)
IV Solutions (B05B)Inj.DextroseB05BA032(0.07%)
Mineral supplements (A12)T.Calcium LactateA12AA05325(11.44%)
Pituitary and hypothalamic hormones (H01)Inj. OxytocinH01BB0210(0.35%)
Psycholeptic ( N05)T.DiazepamN05BA011(0.04%)
Stomatological preparations (A01A)Inj.DexamethasoneA01AC0215(0.53%)
Thyroid Therapy (H03)T. Thyroxine sodiumH03AA0111(0.39%)
Uterotonics (G02A)T.MisoprostolG02AD0612(0.42%)
Vitamins( A11)T.Vitamin B ComplexA11EA343(12.08%)
T.Ascorbic AcidA11GA0153(1.87%)
T.Multivitamin1(0.04%)
2840

Table 2 shows the frequency distribution of prescription of FDA drug category. Among the drugs, FDA B category 1280 (45.07%) are the mostly prescribed medications, followed by category C 994 (35.00%). FDA Category D and A, 116 (4.08%) and 428 (15.08%) respectively are least prescribed. 22 (0.77%) of pregnant women received FDA Category X. Misoprostol (FDA Category X) during first and second trimester l3.62% and 0.73% respectively was prescribed for medical abortion (with code O 04.4 as per ICD -10 version). In third trimester the same drug was prescribed towards the management of induction of labour after intrauterine foetal death (with code O 36.4 as per ICD-10 version). Out of total drug prescribed, category C, D and X accounted for 39.85% of prescriptions.

Table 2

Frequency of distribution of FDA drug category of the drug prescribed to pregnant women.

US FDA drug categoriesFirst trimester (n=249) (%)Second trimester (n=274) (%)Third trimester (n=2317)(%)Total (n=2840) (%)
A.35 (14.05)47(17.16)346 (14.93)428 (15.07)
B.110(44.18)106(38.68)1064(45.93)1280 (45.07)
C.83(33.34)99(36.14)812(35.05%)994(35.00)
D.12(4.82)20(7.29)84(3.62)116(4.08)
X.9(3.61)2(0.73)11(0.47%)22(0.78%)

Table 3, describes the rates and adjusted odds of exposure and factors associated to prescription of FDA category C and D drugs among the pregnant women. Based on odds ratio, the odds of women with the age group of ≥ 35 years showed increased risk of exposure to FDA category C and D; OR 1.417, 95% CI:( 0.4633,4.232) although the age of the pregnant women did not show any significant association to prescription of FDA category C and D drugs. The pregnancy related factors like parity, gravida and previous abortion history when analysed, most of the variables showed significant association to the prescription of FDA C and D category drugs. Whereas the factors like co-morbid condition, chronic and non-chronic conditions did have significant association towards the prescription of FDA category C and D drugs. The total number of medications prescribed, and duration of hospital day had significant association with the prescription of FDA category C and D drugs (P<0.0001). And the odds of exposure FDA category C and D drugs is more with respect to duration of hospital stay, OR 2.926, 95% CI:(1.876,0.4562) for 5 to 9 days.

Table 3

The rates and odds of exposure to FDA category C and D drugs with maternal characteristics of the pregnant women.

CharacteristicsNo of population n(%)Without CDWith CDOR (95% CI)P value**
Age (Years)≤ 2073 (14.47)12510.6120 (0.3128,1.198)0.1647
21 - 34420 (83.16)100255Reference---
≥ 3512 (2.37)5091.417 (0.4633,4.232)0.5520
ParityNuli-para120 (23.76)4957Reference---
1284 (56.24)561740.3744 (0.2302,0.6084)<0.0001
≥2101 (20)12740.1866(0.09184,0.3875)<0.0001
Gravida1176 (34.85)5399Reference---
2250 (49.50)511500.6351(0.4006,1.007)0.0595
≥379 (15.65)13560.4336(0.2176,0.8642)0.0174
Abortion HistoryNo396 (78.42)1012340.5221(0.2892,0.9424)0.0315
Yes109(21.58)1671
Co morbid ConditionsNo489 (96.83)1112961.778(0.6184,5.111)0.3765
Yes16 (3.17)609
ConditionsChronic condition18 (3.56)6120.5904 (0.2166,1.610)0.3908
Non-chronic conditions487 (96.44)111376
Total No of MedicationsLess than 5199 (39.41)101860.05343(0.2987,0.09556)<0.0001
≥5306(60.59)16255
Length of hospital stay (days)<4263 (52.07)17564Reference---
5 – 9194(38.41)60752.926(1.876,0.4562)<0.0001
≥1048 (9.52)6270.08127(0.03206,0.2060)<0.0001

** P-value is based on a chi-square test or Fisher’s exact test.

Table 4, describes FDA pregnancy risk classification of medications of C, D and X against the pregnancy stages. With respect to prescription of FDA category C drugs and pregnancy stage of the women there was no significant association. Category D drugs prescribed to the pregnant women during all three trimesters also had a no significant association. There was a significant association to the prescription of FDA category X drug and different stages of pregnancy (P<0.0001). Based on the odds ratio, the odds of exposure of pregnant women to FDA Category X drug is higher OR 7.437, 95% CI :( (3.146,17.58). When accounted for both FDA category of C and D drugs and pregnancy stage, there is no significant association.

Table 4

FDA pregnancy risk class of medications C, D, and X drugs vs pregnancy stage of the women.

TrimesterFDA Category C
n(%)OR (95% CI)P value
1st (n=249)83(33.34)Reference
2nd(n=274)99(36.14)0.8838 (0.6161,,1.268)0.5210
3rd (n=2317)812(35.05)0.9267 (0.7025,1.223)0.6393
TrimesterFDA Category D
1st (n=249)12(4.82)Reference
2nd (n=274)20 (7.29)0.6430 (0.3070,1.344)0.2754
3rd (n=2317)84(3.62)1.346 (0.7243,2.501)0.5893
TrimesterFDA Category X
1st and 2nd (n=523)11 (2.10)Reference
7.437(3.146,17.58)<0.0001
3rd (n=2317)11(0.47)
TrimesterFDA Category CD
1st (n=249)95(38.15%)Reference
2nd (n=274)119(43.43%)0.8035 (0.5662,1.140)0.2472
3rd (n=2317)996(42.98%)0.8182 (0.6254,1.070)0.1619

[i] **P-value is based on a chi-square test or Fisher’s exact test.

DISCUSSION

The information regarding the safety use of medications during pregnancy is the utmost concerns.9,10 It is apparent from the several studies that there is lot of variation of the medication use between the countries, the health care settings and the prescribing practice.11 Thus the present study was undertaken to evaluate the prescription pattern of the drug during pregnancy as there is very limited information in the present hospital set up. 505 subjects were enrolled in the study and were in their normal reproductive age. The hospitalized pregnant women were in their secundum gravida and this is the like study conducted by Belay M, et al.12 In our study 39.41% of the pregnant women were prescribed with less than five drugs. 3.17% of them had co-morbid conditions and 3.56% experienced chronic conditions. The number of medications used in the study is comparatively less when compared with the results of the studies performed in South Africa (59.3%), Palestine (56%), Egypt (86%) and USA.13 In this study 81.58% of medications were prescribed during third trimester, and the findings are comparable with the study conducted by Yang T et al.14

The common medical conditions seen are anemia; urinary tract infection and majority of drugs prescribed were ferrous sulphate tablets and injection ferrous sucrose and antibiotics which belong to FDA category of category A and B.

Oral dosage form was the significant dosage form used across all trimesters (76.10%) as it is the simplest and easiest way for any patient to take a medication. 15.07% were prescribed with FDA category drug a were routine medications that included ferrous sulphate, Vitamin B complex. When compared to the studies conducted in the USA, it is shown that smaller number of category A drugs were prescribed, the findings are similar.6

In this study, about 45.07% of medications prescribed are of FDA category B which was antibiotics towards management of urinary tract infections; this finding is similar from various studies.15 35% received FDA category C drugs in all the trimesters and when compared to studies performed in USA it is relatively less. There are reports of potentially harmful medications use during pregnancy (category D drugs-1.5% to 4.8% and category X drugs 0.2 to 4.6%) both from developed and developing countries.16,17 In this study, category D drugs are prescribed only in 0.21% of pregnant women, who received Inj. Oxytocin and Inj. Magnesium sulphate respectively towards management of incomplete abortion18 during the first trimester and for the induction of labor 19 and postpartum hemorrhage during the third trimester 20 and magnesium sulphate were prescribed towards the management of eclampsia.21 Inj.Gentamicin was prescribed in about 3.06% before delivery and continued during postnatal period. Diazepam was prescribed for one patient for the treatment of preeclampsia. FDA category X Drug Misoprostol was prescribed in first, second and third trimester gestation 0.56%, 0.07% and 0.17% respectively. Seven patients used this drug and two women to terminate pregnancy during first and second trimester gestations. This is in line with Goldberg, Greenberg and Darney et al observation. And five women were administered to induce labor after intrauterine fetal death.22

In the age group of ≥ 35 years there was increased risk of exposure to category C and D drugs with OR 1.417, 95% CI:(0.4633,4.232) but there is no significant association. Whereas the study conducted by Lee et al, found that young maternal age were associated with exposure to category C, D and X.23,24 The study conducted by Riley et al, found that multiparous women and (especially) women with chronic health conditions were more likely to use category D or X drugs.25 In the present study, there were tendencies for increased risk of exposure to FDA category C and D drugs was with number days of length of hospital stay of 5 to 9 days and co-morbid condition (OR 2.926, 95% CI: (1.876,0.4562) and 1.778 (0.6184,5.111) respectively. During third trimester there is an increased exposure to category D and X drugs. This observation suggests that in later gestation period, the prescription of drugs with potential fetal risk were more likely to be used for necessary maternal illness.6 Limitations in the present study includes that certain variables like maternal education, income, life style and habits were not available and their influence on our study results could not be analysed. It is observed that prescription pattern of drugs during pregnancy and among countries worldwide is in accordance to US FDA guidelines and risk categories. In this study it is witnessed that Iron, folic acid and vitamin supplements are mostly prescribed drugs by the health care providers to pregnant women depending on the risk and benefit ratio.

CONCLUSION

The present study concludes that even though there is compliance to FDA safety drugs use in pregnancy, the mother and the fetus might be at the risk, as certain variables in this study with respect to maternal characteristics showed the odds of exposure to potentially harmful medications such as elderly pregnancy, co-morbid conditions and length of hospital. Thus, there is a need for detailed description of patterns of pregnancy exposure to prescription drugs with potential risk and rate of exposure during different gestation period. The current study indicates that the drug use in pregnancy should be observed by treating physician and must be made aware of the potential risk to fetus in advance when prescribed. Also, there is need of such studies periodically to update the therapeutic use of drugs during pregnancy and provide rational drug use.

ABBREVIATIONS USED

FDA

Food and Drug Administration

ICD

International Classification of Disease

ACKNOWLEDGEMENT

The authors would like to thank and acknowledge the support provided by the Government District Headquarters Hospital, Udhagamandalam.

Notes

[3] Conflicts of interest CONFLICT OF INTEREST The authors declare no conflict of interest.

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