BACKGROUND: Primary psoas muscle abscess is rare and can be difficult to diagnose, particularly during pregnancy. CASE: To our knowledge, this is the first case of primary psoas muscle abscess diagnosed during pregnancy. Clinical investigation did not reveal any infection spreading from adjacent structures. Surgical drainage and simultaneous Cesarean delivery of the infant, combined with appropriate antibiotics, enabled a cure. CONCLUSION: The possibility of psoas muscle abscess should be taken into account when investigating lower back pain during pregnancy if conventional approaches are unsatisfactory.
BACKGROUND: Human papilloma virus (HPV) is the causative agent of cervical neoplasia and genital warts. A vaccine has recently been developed that may prevent infection with HPV. Vaccination for HPV may become a routine part of office gynecology. We surveyed members of the American College of Obstetricians and Gynecologists (ACOG) to determine their attitudes to HPV vaccination. METHODS: A survey was sent to Fellows of ACOG to evaluate gynecologists' attitudes. Vaccine acceptability was analyzed using 13 scenarios with the following dimensions and respective attributes: age of patient (13, 17 and 22 years); efficacy of vaccine (50% or 80%); ACOG recommendation (yes or no); and disease targeted (cervical cancer, warts or both). Each scenario was rated by means of an 11-point response format (0 to 100). Responses were evaluated using conjoint analysis. RESULTS: Of 1200 surveys that were sent out, 181 were returned and included in our analysis. ACOG recommendation was considered the most important variable in vaccine distribution (importance score = 32.2), followed by efficacy (24.5), age (22.4) and, lastly, disease targeted (20.9). Of these variables, higher efficacy was favored; preference was given to age 17 years, with a strong disinclination to vaccinate at age 13 years; and protection against cervical cancer, or genital warts, or both, was significantly favored over a vaccine against genital warts alone. Demographic characteristics of the gynecologists (i.e., age of physician, gender, practice setting and community size) did not play an important role in the decision to recommend vaccination. CONCLUSION: Professional society recommendation is important for acceptability of a potential HPV vaccine. Gynecologists are willing to include this vaccine in their office practice.
OBJECTIVE: To establish reliability and validity of real-time fluorescent PCR for early detection of bacterial invasion of the amniotic cavity. METHODS: Amniotic fluid samples from 40 patients undergoing mid-trimester genetic amniocentesis were incubated for 6 h at 37 degrees C and were cultured on media specific for group B streptococcus (GBS) and E. coli. Concurrently, samples were analyzed with real-time fluorescent PCR (Roche LightCycler) using DNA primers and probes designed to detect the CAMP factor encoding cfb gene and uidA gene of GBS and E. coli, respectively. For positive control and to simulate amniotic fluid colonization, 104 cfu/ml of GBS and E. coli were inoculated on sterile amniotic fluid and incubated for 6 h. Bacterial genomic DNA for the two organisms was extracted and purified via the two-step precipitation method using a commercial kit. The real-time PCR assays were also tested against 25 non-GBS and non-E. coli bacterial species. The lower limit of detection for each pathogen was established using serial dilution of bacterial genomic DNA. RESULTS: All patient samples were negative for evidence of GBS and E. coli with both culture and real-time PCR methods. Amniotic fluid samples inoculated with GBS and E. coli were positive with real-time PCR whereas the 25 bacterial species other than GBS or E. coli tested negative with the assay. Average total sample processing time including the pre-enrichment step was 7 h 40 min. The average cost for DNA extraction and PCR testing was 8.50 dollars per test. CONCLUSION: Real-time fluorescent PCR is a valid and reliable method for detection of specific pathogens in amniotic fluid. This technique is sensitive for low inoculation levels. Real-time fluorescent PCR has potential to impact clinical management as a rapid, reliable detection method for GBS and E. coli in chorioamnionitis.
OBJECTIVE: To evaluate the effect of implementation of a human immunodeficiency virus (HIV) educational intervention on universal screening for HIV in a prenatal clinic setting. METHODS: In this retrospective cohort study, frequencies of offering and acceptance of HIV testing were compared before and after an educational intervention performed by an HIV-focused nurse. The records of 293 women seeking prenatal care before the intervention and 206 women seeking prenatal care after the intervention were reviewed for offering and acceptance of HIV testing. Fisher's exact test and logistic regression were used to evaluate the relationship between the educational intervention and the offering and acceptance of HIV testing. RESULTS: The frequency of HIV test offering at first visit and test acceptance before the educational intervention were 96.5% and 74.8%, respectively, and after the intervention were 99.5% and 84.3%, respectively. This improvement in offering (3% change) and acceptance (9.5% change) was statistically significant (offering at first visit: OR = 7.27, 95% CI = 1.02 to 316.9; test acceptance: OR = 1.82, 95% CI = 1.14 to 2.88). Test acceptance was statistically significantly improved in the post-intervention group after controlling for confounding variables (OR = 2.02, 95% CI = 1.2 to 3.39). CONCLUSION: The addition of an HIV-focused nurse to a clinic setting improved the frequency of test offering at first visit and of acceptance of HIV testing by pregnant women.
BACKGROUND: Cases of endometriosis with no tubal damage are associated with infertility, suggesting an immunological rather than mechanical barrier to reproduction. Laparoscopy and falloposcopy results of clinically asymptomatic women undergoing investigation of infertility were correlated with the outcomes of microbiological screening for Chlamydia trachomatis, Mycoplasma pneumoniae, Mycoplasma hominis, ureaplasma species, Neisseria gonorrhoeae, Neisseria meningitidis and Chlamydia pneumoniae. METHODS: A total of 44 women presenting to a hospital IVF service for laparoscopic or laparoscopic/falloposcopic investigation of infertility provided endocervical swabs, fallopian tube washings, and peripheral whole blood for analysis. RESULTS: Of these 44 women, 15.9% (7) showed evidence of C. trachomatis infection as detected by either PCR or EIA serology. Of these 7 women, 5 (71%) had no or mild endometriosis and 2 (29%) had moderate or severe endometriosis. Of the remaining 37 women who showed no evidence of chlamydial infection, 15 (40.5%) had no or mild endometriosis. CONCLUSION: Women with infertility, but without severe endometriosis at laparoscopy, showed a trend towards tubal damage and a higher rate of previous C. trachomatis infection. Although not statistically significant, this trend would suggest that, where moderate to severe tubal damage is found to be the primary cause of infertility, C. trachomatis infection could be a likely cause for such tubal damage.
Specific morphotypic profiles of normal and abnormal vaginal flora, including bacterial vaginosis (BV), were characterized. A prospective study of 350 women yielded concurrent Gram-stain data and clinical assessment (n = 3455 visits). Microbiological profiles were constructed by Gram stain. Eight profile definitions were based on dichotomizing the levels of Lactobacillus, Gardnerella, and curved, Gram-negative bacillus (Mobiluncus) morphotypes. Of these, two were rare, and the other six demonstrated a graded association with the clinical components of BV. The proposed profiles from the Gram stain reflect the morphotypic categories describing vaginal flora that may enable clearer elucidation of gynecologic and obstetric outcomes in various populations.
BACKGROUND: Pregnant women acutely infected with human parvovirus B19 (B19) may transmit the virus to the developing fetus. The mechanism whereby the virus interacts with the placenta is unknown. It is known that globoside receptor is required for successful infection of the target cells, which are the highly undifferentiated, actively dividing colony and burst-form units of the erythroid series. Globoside is present on trophoblast cells which have intimate contact with maternal blood, and may therefore serve as a potential route for B19 transmission into the fetal compartment. OBJECTIVES: The purpose of this study was to determine whether B19 VP2 capsids could bind to villous trophoblast cells in vitro and whether globoside was involved. METHODS: Binding of B19 VP2 empty capsid to first-trimester villous trophoblast cells was assessed by multiple approaches, including ICC using either biotinylated B19 VP2 empty capsid or unlabeled B19 VP2 empty capsid. Quantification of viral binding involved I125-labeled B19 VP2 empty capsid. Competition studies included excess unlabeled empty capsids or pretreatment with globoside-specific IgM antibody. RESULTS: Linear binding of B19 VP2 capsid to purified villous trophoblast cells in vitro was clearly demonstrated (R2= 0.9524). Competition studies revealed specificity of I125-labeled B19 VP2 capsid binding to villous trophoblast cells when pretreatment with either 60-fold excess unlabeled B19 capsid or globoside-specific IgM antibody took place. The results illustrated B19's ability to bind in a specific manner to globoside-containing villous trophoblast cells. CONCLUSION: We speculate that the globoside present on trophoblast cells may play a role in viral binding in vivo, which may facilitate B19 transmission across the maternal-fetal interface.
OBJECTIVES: To present sales figures of antifungal drugs for treatment of genital Candida infections in females, which had been purchased in the Swedish county of Skåne (with approximately 1.2 million inhabitants) during the 1990s. To study the relative proportions of the drugs sold by prescription and as over-the-counter (OTC) products. METHODS: Sales figures of antifungal drugs for therapy of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC), for the years 1990--99, were collected from the 'ACS' database of the National Corporation of Swedish Pharmacies. RESULTS: The study showed an increase in sales of the type of drugs studied from 45,000 packages in 1990 until mid-93/94, when approximately 70,000 packages were sold (mainly azoles for topical use and fluconazole for oral intake). Thereafter there was a decrease until the end of November 1999, when 54,000 packages were purchased. Of the total sales, 93% were OTC products. Sales of clotrimazole and econazole (for vaginal installation) in 1993--1994 were equal to 85-90 packages/1000 women in the age group 15-45 years. Extremely high sales volumes of fluconazole and itraconazole, for one single year each, could be explained by marketing-related activities directed to the medical community. CONCLUSIONS: As many women with RVVC are not cured by iatrogenic initiatives and women consider themselves able to diagnose episodes of genital Candida infection, affected women generally turn to self-medication with antifungal OTC products. This stresses the role of pharmacy counseling. Short-term marked alterations in sales volumes may be due to marketing factors rather than changes in the epidemiology of genital Candida infections.
BACKGROUND: Despite recommendations by Centers for Disease Control and the American College of Obstetricians and Gynecologists, pH testing is infrequently performed during the evaluation of vaginitis. Consequently, little information exists on its use in a primary care setting. OBJECTIVE: The aim of this study was to describe our experience with routine pH testing, particularly the relationship between symptoms, pH and wet-mount microscopy. METHOD: A retrospective chart review was performed on 203 consecutive cases evaluated for vaginitis by wet-mount microscopy. RESULTS: Of the 203 cases, 21 had normal pH and no symptoms and 182 had symptoms, elevated pH or both; 85% of cases had abnormal wet-mount findings, including 75% with clue cells, 14% with Trichomonas vaginalis, 13% with yeast and 14% with mixed infections. Asymptomatic infection was present in 42% of cases with clue cells alone, 44% of cases with Trichomonas vaginalis alone, 38% of all trichomoniasis cases and 33% of cases with mixed infections. Elevated pH was associated with clue cells (p < 0.001), trichomoniasis (p = 0.01) and mixed infections (p = 0.003). Normal pH was associated with negative wet mount (p < 0.001) and to a lesser degree with uncomplicated vulvovaginal candidiasis (p = 0.06). CONCLUSION: Routine pH testing increased detection of trichomoniasis and bacterial vaginosis by prompting microscopy in a significant proportion of asymptomatic cases.
BACKGROUND: The epidemiology of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC) has been difficult to study as the majority of episodes of these conditions are self-treated by the women affected. In Sweden, all pharmacies are owned by the state and all prescriptions and over-the-counter (OTC) products, such as antifungals, are registered in a database, which offers unique possibilities to study the epidemiology of VVC/RVVC. OBJECTIVES: To analyze all prescriptions and OTC products purchased for therapy of VVC/RVVC and to establish reasons for any observed variation in the sales figures. METHODS: Sales figures in the Swedish county of Skåne of antifungal drugs for therapy of VVC/RVVC were analyzed by the aid of the 'ACS' database of the National Corporation of Swedish Pharmacies for the years 1990--1999. The size of the female population in the county is approximately half a million. RESULTS: The study showed that 93% of all antifungal drugs for VVC/RVVC were sold as OTC products. An increase in sales of the drugs occurred until mid- 1993/94, followed by a decrease until end of the study period in 1999. Demographic factors (e.g. the number of female inhabitants in the county, pharmacies and health-care units), the pregnancy rate and pharmacy-dependent factors (such as the introduction of shelves for self-selection of antifungal products) did not explain the observed variations in sales. Distinct short-term variations in the number of prescriptions of fluconazole and itraconazole could be explained by drugs company sales campaigns and logistics factors in drug distribution. The sales volumes in the 33 municipalities in the county correlated with the density of the population, which was not the case for the total number of prescriptions made in the county during the 1990s. The variation in antifungal drug sales was similar to that of hormonal intrauterine devices, but this was not the case for oral contraceptives. The total Swedish usage of antibiotics showed a similar variation to that of the antifungal drugs analyzed. CONCLUSION: The study stresses the limited impact on the treatment of VVC/RVVC by the medical community. Behavior-related factors in the female population are the most likely explanation for the marked variations found in the usage of drugs for the two conditions.
OBJECTIVES: To determine maternal-fetal transplacental passage of vancomycin in the ex vivo human placental perfusion model. METHODS: Six term placentas were collected immediately after delivery and perfused with physiologic medium using the single cotyledon perfusion system. Vancomycin was added to the maternal medium and perfused through the maternal circulation of the cotyledon. Over a 1-h period in an open system, samples of the perfusate were collected at defined intervals from the fetal venous catheter and from the maternal effluence to assess vancomycin transfer. Thereafter, the system was closed for 1-5 h to establish accumulation. Transport fraction and clearance indexes were calculated by perfusing antipyrine 14C (positive control). Vancomycin was estimated by high pressure liquid chromatography and antipyrine 14C concentration was determined by liquid scintillation. RESULTS: Mean vancomycin maternal peak and trough concentrations ranged from 30.0 to 51.5 microg/ml and 7.7 to 16.4 microg/ml, respectively. Clearance indexes were minimal with a mean peak range of 0.000-0.080 and a mean trough range of 0.00-0.17. For each placenta, transport fraction for antipyrine 14C was > 1.85 with a single pass of > 40%. No accumulation of vancomycin was noted when the system was closed for 1-5 h. The mean peak clearance index was zero after perfusing the placenta for up to 5 h with 35.8 microg/ml of vancomycin. CONCLUSION: Transplacental passage of vancomycin was minimal in the ex vivo human placental perfusion model, with no detectable accumulation.
OBJECTIVES: This investigation examined human papillomavirus (HPV) in pregnant women in order to characterize viral prevalence, types and concordance between infection in the cervix and in the oral cavity. METHODS: A total of 577 pregnant women seeking routine obstetric care were evaluated for HPV infection in their cervix during gestation and immediately before delivery, and in the oral cavity during gestation. Male partners present during the gestational clinic visit also provided a specimen from their oral cavity. HPV assessment was performed by PCR, dot blot hybridization and DNA sequencing. A sexual and health questionnaire was completed by the pregnant women. RESULTS: HPV prevalence in women was 29% in the cervix and 2.4% in the oral cavity. Among those with both gestational and delivery specimens, 35% were infected at least once and 20% had infection at both intervals. At delivery, 68% of infected women had an oncogenic HPV type in the cervix. There was no type-specific HPV concordance between the two cervical specimens, nor cervical and oral results in women, nor with cervical and oral findings between partners. CONCLUSION: The lack of association in HPV positivity and types between the cervix and oral cavity in these women suggests that self-inoculation is uncommon. This source of infection does not appear to be from oral contact with a current male partner, since there also was no concordance between partners. These results suggest either other modes of HPV transmission or differences in susceptibility to HPV infection or its clearance in the oral cavity and genital mucosa.
OBJECTIVE: The genital mycoplasmas, Ureaplasma urealyticum and Mycoplasma hominis, are commonly identified in the vagina of healthy pregnant women. However, these microorganisms are the most common isolates from the amniotic fluids of women in preterm labor. The mechanisms responsible for vaginal colonization and ascent to the uterus remain undetermined. We evaluated the association between U. urealyticum and M. hominis vaginal colonization and the presence of pro-inflammatory and anti-inflammatory interleukin-1 system components in asymptomatic pregnant women of different ethnicities. METHODS: Vaginal specimens, obtained from 224 first trimester pregnant women, were assayed for interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) concentrations by ELISA. U. urealyticum and M. hominis vaginal colonization were identified by polymerase chain reaction (PCR). RESULTS: Vaginal colonization with M. hominis was identified in 37 (16.5%) women, and was more prevalent in black (18.9%) and Hispanic (20.9%) than in white (4.2%) women (p = 0.01). U. urealyticum was present in 84 (37.5%) women and there was no ethnic disparity in its detection. M. hominis colonization was associated with elevated median vaginal IL-1beta concentrations in both black women (p = 0.02) and Hispanic women (p = 0.04), and was unrelated to vaginal IL-1ra concentrations. In marked contrast, U. urealyticum colonization was associated with elevations in vaginal IL-1ra levels, but not with IL-1beta concentrations, in black women (p = 0.02) and Hispanic women (p < 0.0001) and marginally in white women (p = 0.06). CONCLUSION: M. hominis colonization in healthy pregnant women is associated with localized pro-inflammatory immune activation, while U. urealyticum colonization is associated with immune suppression.
OBJECTIVES: To determine the in vitro resistance of group B streptococcus (GBS) to 12 antibiotics. To determine if there has been any decrease in sensitivity to the penicillins or other antibiotics currently used for GBS chemoprophylaxis in pregnant women. Find suitable alternative antibiotics to penicillin. Find an antibiotic that will have minimal selective pressure for resistance among the endogenous resident vaginal microflora. METHODS: The antibiotic susceptibility profiles of 52 clinical isolates of GBS were evaluated to 12 antibiotics: ampicillin, azithromycin, cefamandole, cefazolin, ceftriaxone, ciprofloxacin, clindamycin, erythromycin, nitrofurantoin, ofloxacin, penicillin and vancomycin. Antibiotic sensitivities were determined using disk diffusion and microdilution methods according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: All isolates were sensitive to vancomycin, ofloxacin, ampicillin, ciprofloxacin, nitrofurantoin and penicillin. However, the following number of clinical isolates exhibited intermediate or decreased sensitivity, nine (17%) to ampicillin, eight (15%) to penicillin, 14 (32%) to ciprofloxacin and one (2%) to nitrofurantoin. Thirty-one percent of the isolates were resistant to azithromycin and ceftriaxone, 19% to clindamycin, 15% to cefazolin and 13% to cefamandole. Eighteen (35%) of the clinical isolates tested were resistant to 6 of the 12 antibiotics tested. CONCLUSIONS: The relatively high rates of resistance for 6 of the 12 antibiotics tested suggest that for women allergic to penicillin and colonized with GBS, antibiotic sensitivities to their isolates should be determined. The antibiotic selected for intrapartum chemoprophylaxis should be guided by the organism's antibiotic sensitivity pattern. Patients with GBS bacteriuria should be treated with nitrofurantoin.
BACKGROUND: Prior reported cases of stillbirth and neonates infected with enteroviruses suggest transplacental infection. We present a case of fetal infection with coxsackievirus B3, diagnosed antenatally and resulting in live birth. CASE: A pregnant woman presented at 26 weeks with fetal tachycardia and non-immune hydrops fetalis. Coxsackievirus B3 was cultured from amniotic fluid. Maternal antibody to coxsackievirus B3 was positive at 1:512. At 32 weeks, the fetus deteriorated and was delivered. Cord blood antibody to coxsackievirus B3 was positive at a higher titer. Following neonatal death, brain and placental tissues were positive for enterovirus ribonucleic acid by polymerase chain reaction. CONCLUSION: Intrauterine infection by enteroviruses should be considered in the differential diagnosis of non-immune hydrops fetalis. Antenatal diagnosis of coxsackievirus B3 infection is associated with poor outcome.
OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) among women seeking urgent gynecological care. METHODS: Women were asked to complete a short self-assessment screening of HCV risk. Those answering yes to any of the screening questions were offered HCV testing and were asked to complete a more detailed questionnaire. RESULTS: Among the 125 women who completed the screening questionnaire, 80% (100) answered yes to one or more of the screening questions. Of the 99 women who underwent testing, six (6.1%) were HCV seropositive; a history of injection drug use was the only finding associated with HCV seropositivity (R.R 9.7: 95% CI 1.90-49.40). CONCLUSIONS: Women seeking urgent outpatient gynecological care, particularly those who are injection drug users, are at a substantial risk of HCV infection. A careful risk assessment should be completed in order to identify women who should be offered HCV testing.
OBJECTIVES: In this study, 210 women with vaginal discharge and other symptoms/signs of genital pathology suggestive of vulvovaginal candidiasis (VVC) were involved in order to distinguish true WC and cytolytic vaginosis (CV) cases. METHODS: Fungal cultures, 10% potassium hydroxide (KOH) and Gram stained preparations and pH measurements were performed on the vaginal discharge material of each patient. RESULTS: Fifteen patients (7.1%) were diagnosed with cytolytic vaginosis according to their clinical and microbiological findings, including abundant lactobacilli, fragmented epithelial cells and/or free nuclei due to cytolysis, seen in their discharge materials on microscopic examination, but no fungal growth. CONCLUSIONS: The results of this study may contribute to the reports in the literature indicating the importance of such disorders, which are generally misdiagnosed as candidiasis.
BACKGROUND: Genital tract infections in females secondary to Streptococcus pneumoniae (pneumococcus) are unusual. Tubo-ovarian abscess resulting from such an infection is a rare occurrence and diagnosis is not always easy. This report demonstrates the problems of recognizing this condition and summarizes the pathomechanism, investigations leading to a diagnosis and the subsequent management. CASE: A rare case of a tubo-ovarian abscess caused by pneumococcus, occurring in a previously healthy 48-year-old woman, is presented. The tubo-ovarian abscess may have developed insidiously and probably had an acute exacerbation prior to presentation. CONCLUSION: This case is unusual in that there were no identifiable initiating events for the source of the pneumococcal infection. Early recognition of a tubo-ovarian abscess is important in order to prevent the associated morbidity and mortality. This condition has the propensity to mimic a neoplasm.
OBJECTIVE: To compare the Affirm VPIII Microbial Identification Test for detection and identification of Candida species, Gardnerella vaginalis and Trichomonas vaginalis to clinical and microscopic criteria commonly used to diagnose vaginitis. METHODS: Women that were symptomatic for vaginitis/vaginosis and asymptomatic women being seen for routine obstetric or gynecological care were included in this study. Women treated with antibiotics or antifungals within one week or women who had douched within 24 hours were excluded. Two vaginal swab specimens were simultaneously obtained from each patient, one swab was placed in sterile physiological saline for immediate microscopic wet mount examination and KOH testing. The other swab was placed in the Affirm collection tube for Affirm VPIII testing based on previously demonstrated methods. RESULTS: The Affirm assay was significantly more likely to identify Gardnerella and Candida than wet mount. 190 (45%) were positive for Gardnerella by Affirm compared to 58 (14%) by wet mount; 45 (11%) were positive for Candida by Affirm compared to 31 (7%) by wet mount; and 30 (7%) were positive for Trichomonas by Affirm compared to 23 (5%) by wet mount. Symptomatic women were significantly more likely to be positive by Affirm only (23% vs. 10%), wet mount only (3% vs. 2%) or Affirm and wet mount (15% vs. 1%). Asymptomatic women were significantly more likely to be negative for Affirm and wet mount (43% vs. 5%). CONCLUSIONS: The Affirm VPIII test is a more sensitive diagnostic test for detection and identification of symptomatic vaginitis/vaginosis than conventional clinical examination and wet mount testing.
OBJECTIVE: The aim of the present review was to close the gap in the approach to pregnant women with visceral leishmaniasis (kala-azar) by providing up-to-date information to obstetricians about physiopathology, epidemiology, vertical transmission, drugs and treatment during pregnancy. BACKGROUND: Infection with Leishmania chagasi during pregnancy is rare and deserves special attention since little information is available regarding the occurrence of visceral leishmaniasis during gestational period and the real possibility of vertical transmission of this disease. Because specific areas in the world are endemic for the disease and considering the continuous growth of the population, cases of pregnant women with visceral leishmaniasis are becoming more frequent. Unfortunately, textbooks on infectious diseases do not include this specific group of patients, and studies in the literature on aspects related to pregnancy and visceral leishmaniasis are scarce. CONCLUSIONS: Vertical transmission of leishmaniasis is possible and the institution of treatment is imperative in cases of pregnant women with kala-azar. Amphotericin B is strongly recommended as the first choice drug due to its fewer maternal-fetal adverse effects.