trimethoprim--sulfamethoxazole-drug-combination and Premature-Birth

The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy.. We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes.. Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported.. For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.

Topics: Abortion, Spontaneous; Anti-Infective Agents; Child; Female; Humans; Infant, Newborn; Male; Plague; Pregnancy; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes. Concentrations of CHI3L1, CRP, IL-18BP, IL-6, sICAM-1, and sTNFR2 were quantified by ELISA in 1115 plasma samples collected over pregnancy from 326 women. MiP was associated with increased sTNFR2, sICAM-1 and IL-18BP concentrations across pregnancy. Women who delivered preterm had elevated concentrations of sTNFR2 and altered levels of IL-6 during pregnancy. Women with sTNFR2 concentrations in the highest quartile within 6 weeks of delivery had an increased relative risk of preterm birth. Our results indicate that despite daily TMP/SXT, MiP in WLHIV induced a systemic inflammatory response that was associated with an increased risk of preterm birth. These findings highlight the need for additional strategies to protect WLHIV from malaria infection in pregnancy to promote healthy outcomes for mother and child.

Topics: Adult; Anti-Retroviral Agents; Cohort Studies; Female; HIV; HIV Infections; Humans; Incidence; Infant, Newborn; Inflammation; Malaria; Pregnancy; Premature Birth; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp).. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count.. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ μ L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ μ L, 95% CI: -58.6, -8.8).. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Infant, Low Birth Weight; Malaria; Malawi; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cotrimoxazole prophylaxis is recommended for subgroups of human immunodeficiency virus (HIV)-infected adults and children to reduce all-cause morbidity and mortality. We investigated whether antenatal cotrimoxazole prophylaxis begun during pregnancy for HIV-infected pregnant women with low CD4 cell counts would affect birth outcomes.. Cotrimoxazole prophylaxis was introduced as a routine component of antenatal care for HIV-infected women with CD4 cell counts <200 cells/ micro L during the course of a trial of mother-to-child HIV transmission in Lusaka, Zambia. Rates of preterm delivery, low birth weight, and neonatal mortality were compared for women with low CD4 cell counts before and after its introduction.. Among 255 women with CD4 cell counts <200 cells/ micro L, the percentage of preterm births (< or =34 weeks of gestation) was lower (odds ratio [OR], 0.49 [95% confidence interval {CI}, 0.24-0.98]) after cotrimoxazole prophylaxis was introduced than before; there was a significant decrease in neonatal mortality (9% to 0%; P=.01) and a trend toward increased birth weight ( beta =114 g [95% CI, -42 to 271 g]). In contrast, there were no significant changes in these parameters over the same time interval among women with CD4 cell counts > or =200 cells/ micro L.Conclusion. Antenatal provision of cotrimoxazole for HIV-infected pregnant women with low CD4 cell counts may have indirect benefits for neonatal health.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Infant; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

To examine the association between trimethoprim/sulfamethoxazole, other US Food and Drug Administration (FDA) C and D anti-infectives, and non anti-infective FDA C, D, and X drugs used during pregnancy with preterm birth and low birth weight.. We carried out a retrospective cohort study based on a 50% random sample of women who gave birth in the Canadian province of Saskatchewan from 1997 to 2000. The association between trimethoprim/sulfamethoxazole, other FDA C and D anti-infectives (fluconazole, clarithromycin, doxycycline, and tetracycline), and non anti-infective FDA C, D, and X drugs used during pregnancy with preterm birth and low birth weight was evaluated using multiple logistic regression, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) as association measures.. A total of 17 939 women were included in the final analysis. Trimethoprim/sulfamethoxazole was associated with significantly increased risks for preterm birth (aOR 1.51, 95% CI 1.10, 2.08) and low birth weight (aOR 1.67, 95% CI 1.14, 2.46). Exposure to non anti-infective FDA category C, D and X drugs was also associated with increased risks for preterm birth (aOR 1.17, 95% CI 1.09, 1.31) and low birth weight (aOR 1.14, 95% CI 0.92, 1.42), but to a lesser degree. Other FDA C and D anti-infectives were not (statistically) significantly associated with increased risks for preterm birth (aOR 0.93, 95% CI 0.49, 1.77) or low birth weight (aOR 0.65, 95% CI 0.27, 1.60).. Among FDA C, D and X drugs, trimethoprim/sulfamethoxazole, a folic acid antagonist, has the strongest association with preterm birth and low birth weight.

Topics: Adult; Age Factors; Anti-Infective Agents; Chronic Disease; Cohort Studies; Confidence Intervals; Databases, Factual; Drug Prescriptions; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Logistic Models; Parity; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Retrospective Studies; Risk Factors; Saskatchewan; Socioeconomic Factors; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Food and Drug Administration; Young Adult

Maternal urinary tract infections in pregnancy showed an association with a higher rate of preterm birth in previous studies. The aim of this study was to check this relationship, and in addition to evaluate the efficacy of recent medical treatments. The population-based large control (without any defects) data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities was evaluated. Of 38,151 newborn infants, 2188 (5.7%) had mothers with urinary tract infections during pregnancy, and 90% of these maternal diseases were prospectively and medically recorded. The prevalence of pre-eclampsia and polyhydramnios showed an association with urinary tract infections during pregnancy. Pregnant women with urinary tract infections in pregnancy had a somewhat shorter gestational age (0.1 week) and a higher proportion of preterm births (10.4% vs 9.1%). These differences were correlated with the severity of urinary tract infections. However, the preterm-inducing effect of maternal urinary tract infections is preventable by some antimicrobial drugs such as ampicillin, cefalexin and cotrimoxazole. In conclusion, maternal urinary tract infections during pregnancy increase pre-eclampsia and polyhydramnios, and in addition the rate of preterm birth; however, the latter is preventable by appropriate drug treatments.

Topics: Adolescent; Adult; Ampicillin; Anti-Bacterial Agents; Case-Control Studies; Cephalexin; Child; Female; Health Surveys; Humans; Hungary; Infant, Newborn; Male; Polyhydramnios; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Q fever is a zoonosis caused by Coxiella burnetii. During pregnancy, it may result in obstetric complications, such as spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, and premature delivery. Pregnant women are exposed to the risk of chronic Q fever.. We included 53 pregnant women who received a diagnosis of Q fever. We compared the incidence of obstetric and maternal Q fever complications for women who received long-term cotrimoxazole treatment (n=16) with that for women who did not receive long-term cotrimoxazole treatment (n=37); long-term cotrimoxazole treatment was defined as oral administration of trimethoprim-sulfamethoxazole during at least 5 weeks of pregnancy.. Obstetric complications were observed in 81.1% of pregnant women who did not receive long-term cotrimoxazole therapy: 5 (13.5%) women experienced spontaneous abortions, 10 (27%) experienced intrauterine growth retardation, 10 (27%) experienced intrauterine fetal death, and 10 (27%) experienced premature delivery. Oligoamnios was observed in 4 patients (10.8%). Obstetric complications were found to occur significantly more often in patients infected during their first trimester of pregnancy than in those infected later (P=.032). The outcome of the pregnancy was found to depend on placental infection by C. burnetii (P=.013). Long-term cotrimoxazole treatment protected against maternal chronic Q fever (P=.001), placental infection (P=.038), and obstetric complications (P=.009), especially intrauterine fetal death (P=.018), which was found to be related to placental infection (P=.008).. Q fever during pregnancy results in severe obstetric complications, including oligoamnios. Because of its ability to protect against placental infection, intrauterine fetal death, and maternal chronic Q fever, long-term cotrimoxazole treatment should be used to treat pregnant women with Q fever.

Topics: Abortion, Spontaneous; Adolescent; Adult; Anti-Infective Agents; Coxiella burnetii; Drug Administration Schedule; Female; Fetal Death; Fetal Growth Retardation; Follow-Up Studies; France; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Q Fever; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; Humans; Infant Mortality; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination