Study design and site
This study is a retrospective observational study that was conducted to collect data for pregnant women with known antimicrobial utilization during pregnancy at Johns Hopkins Aramco Healthcare (JHAH) which is located in Eastern province of Saudi Arabia in Al Dhahran city. The data was collected from patients’ electronic medical records (EMRs).
Sampling technique and sample selection procedure
Medical records for pregnant women as confirmed by positive Human Chorionic Gonadotropin test (hCG) who have delivered either through vaginal delivery or Caesarean section at JHAH were collected. Total number of pregnant women in December 2017 to February 2019 with positive hCG was 5124 and all of them have been screened. A sum of 2440 of these pregnant women had antimicrobial prescriptions and 344 of pregnant women who had prescribed antimicrobials between ages of 15-50 years old were selected randomly and included as the sample size in our study with a total number of 688 prescriptions.
Sample size calculation
To determine sample size for this study we have used power study. To prove the sample size adequacy for a study this is a very useful and frequently used tool in health research. The prevalence of antimicrobial drugs use among pregnant women in a Saudi Arabia is 3 percent(14). Since our population size is unknown, to obtain an appropriate sample size from this population, we use the following formula: (see Formula 1 in the Supplementary Files)
Considering 20 percent missing/non response error rate, the adjusted sample size is 316.87. This is the minimum number, finally our targeted sample size for this study will be 320.
Pregnant women who had normal pregnancy, attended to JHAH and received antimicrobial medications between December 2017 to February 2019 and delivered their babies at JHAH.
Age of patients ranged between 15-50 years as some women may got married earlier than 18th years old.
Women with abortion or ectopic pregnancy. Women who were prescribed with antimicrobials for normal delivery prophylaxis and women with post cesarean delivery prophylaxis.
Demographic data, clinical data, anti-infective medications and comorbidities were collected for pregnant women who met the study inclusion criteria. If the woman was prescribed antimicrobial agents at any point of pregnancy, all antimicrobial courses during her pregnancy were considered.
Definition of the study variables
Age of the pregnant at time of receiving antimicrobial (gestational age) was categorized to 15-24, 25-34, 35-44, and equal or older than 45 years of age.
Pregnancy Trimester was calculated after the woman's last menstrual period (LMP). It was divided into: First Trimester (1-12 weeks), Second Trimester (13-27 weeks) and Third Trimester (28-40 weeks).
FDA established five letter risk categories to indicate safety drug use during pregnancy as A, B, C, D or X. Drugs undergo FDA categories A or B are considered to be safe to use during pregnancy. FDA categories C could be given if benefit outweighs risk but for D and X categories, they are considered as harmful drugs, especially X drugs (if any) which are absolutely contraindicated.
Allergies towards drug or food have also been documented.
Drug resistance defined as the reduction in effectiveness of antimicrobials that happens when microorganisms change after exposure to antimicrobial drugs. The pathogen drug resistance was taken as reported by physicians in patients’ EMRs.
Mode of delivery either vaginal or caesarean section (C-section) was also recorded.
Indication of the prescribed antimicrobials either for treatment of a known infection or as prophylaxis for pregnant women who are at high risk to get infection was also documented.
Complication that may occur for the pregnant women during the pregnancy period which is divided in this study to complication for preterm pregnancies (when baby born before 37 weeks of pregnancy) or complication for abortions. In addition to this, data about fetal complications if the fetus has been exposed to any complications or abnormalities during the pregnancy period was also collected. Maternal co-morbidities variable was defined as the presence of one or more additional diseases or disorders occurring with the infection during pregnancy. Gravida variable describes the total number of confirmed pregnancies that a woman has had, regardless of the outcome. Living children means children who lived beyond neonatal period. Duration of medication (Days) indicates duration of treatment of antimicrobials for the pregnant women.
Prescribed medications include antimicrobial agents which have been used to either kill or slow the growth of microbes, including antibacterial, antiviral, antifungal, and anti-parasitic drugs.
Pattern of infection designates the type of infection the pregnant woman has experienced which includes bacterial, fungal, viral, and parasitic diseases.
Data was analyzed by Statistical Package for Social Sciences (SPSS) software. Descriptive statistics was used to describe the study variables and items. Chi-square test/Fisher’s exact test was utilized to compare the proportions among groups. P-value below 0.05 is considered statistically significant.
The study received an ethical approval from the University IRB under the following number (IRB – UGS – 2018 – 5 – 048). It has also been approved by the Johns Hopkins Aramco Healthcare (JHAH) institution Review Board (IRB) under (IRB number 18-07).