zithromax and Premature-Birth

Macrolides such as azithromycin are commonly prescribed antibiotics during pregnancy. The good oral bioavailability and transplacental transfer of azithromycin make this drug suitable for the treatment of sexually transmitted diseases, toxoplasmosis, and malaria. Moreover, azithromycin is useful both in the management of preterm pre-labor rupture of membranes and in the adjunctive prophylaxis for cesarean delivery. The aim of this comprehensive narrative review is to critically analyze and summarize the available literature on the main aspects of azithromycin use in pregnant women, with a special focus on adverse offspring outcomes associated with prenatal exposure to the drug. References for this review were identified through searches of MEDLINE, PubMed, and EMBASE. Fetal and neonatal outcomes following prenatal azithromycin exposure have been investigated in several studies, yielding conflicting results. Increased risks of spontaneous miscarriage, major congenital malformations, cardiovascular malformations, digestive system malformations, preterm birth, and low birth weight have been reported in some studies but not in others. Currently, there is no conclusive evidence to support that azithromycin use by pregnant women causes adverse outcomes in their offspring. Therefore, this agent should only be used during pregnancy when clinically indicated, if the benefits of treatment are expected to outweigh the potential risks.

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Infant, Newborn; Pregnancy; Premature Birth

Considerable evidence has shown that intra-amniotic infection with Ureaplasma spp. increases the risk of chorioamnionitis and preterm labor. Ureaplasma spp. are among the smallest organisms, and their isolation is uncommon in routine clinical practice because of their size and high auxotrophy. Although Ureaplasma spp. have been reported as causative agents of preterm birth, they also have a high incidence in vaginal swabs collected from healthy reproductive-age women; this has led to questions on the virulence of Ureaplasma spp. and to them being considered as harmless commensal bacteria. Therefore, many efforts have been made to clarify the pathogenicity of Ureaplasma spp. at the molecular level. Ureaplasma spp. are surrounded by lipoproteins, including multiple-banded antigen. Both multiple-banded antigen and its derivative, that is, the synthetic lipopeptide, UPM-1, induce an inflammatory response in a preterm mice model, which was adequate to cause preterm birth or stillbirth. In this review, we present an overview of the virulence mechanisms of Ureaplasma spp. and treatment of ureaplasma infection during pregnancy to prevent possible serious sequelae in infants. In addition, relevant mechanisms underlying antibiotic resistance in Ureaplasma spp. are discussed. Ureaplasma spp. are naturally resistant against β-lactam antibiotics because of the lack of a cell wall. Azithromycin is one of the effective agents that can control intrauterine ureaplasma infection. In fact, macrolide- and fluoroquinolone-resistant isolates of Ureaplasma spp. have already been observed in perinatal practice in Japan.

Topics: Adult; Amniotic Fluid; Anti-Bacterial Agents; Azithromycin; Chorioamnionitis; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Ureaplasma; Ureaplasma Infections; Virulence

Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth.. We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16-24 and 28-32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality, birthweight, maternal malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76-1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (-0.08 to 0.40); mean birthweight (3.03 versus 2.99 kg), mean difference 0.04 (-0.005 to 0.08); perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53-1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84-1.49) and anaemia (44.1% versus 41.3%) at 28-32 weeks, OR 1.07 (0.88-1.30). Meta-analysis of the primary outcome results with seven other studies of routine antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86-1.22).. This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies.. Current Controlled Trials ISRCTN84023116

Topics: Azithromycin; Community Health Services; Female; Gestational Age; Humans; Malawi; Placebos; Pregnancy; Premature Birth; Residence Characteristics; Treatment Outcome; Young Adult

Exposure during pregnancy to malaria and sexually-transmitted infections is associated with adverse birth outcomes including low birth weight (LBW). This study aimed at assessing if the adjunction of two doses of azithromycin to sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy can reduce LBW.. A two parallel-groups, open-label randomized controlled trial involving pregnant women (16 to 35 years of age and 12 to 24 weeks of gestation as confirmed by last menstrual period or fundal height) was conducted in rural Burkina Faso. Women were assigned in a 1:1 ratio either to use azithromycin (1 g daily for 2 days) during the second and third trimesters of pregnancy plus monthly sulfadoxine-pyrimethamine (1500/75 mg) (SPAZ) (intervention) or to continue using a monthly sulfadoxine-pyrimethamine (1500/75 mg) (SP) (control). Primary outcome was a LBW (birth weight measured within 24 h after birth < 2500 g). Secondary outcomes including stillbirth, preterm birth or miscarriage are reported together with safety data.. A total of 992 pregnant women underwent randomization (496 per group) and 898 (90.5%) valid birth weights were available (450 in SPAZ and 448 in SP). LBW incidence was 8.7% (39/450) in SPAZ and 9.4% (42/448) in controls (p-value = 0.79). Compared with controls, pregnant women with SPAZ showed a risk ratio (RR) of 1.16 (95% confidence interval (CI 0.64-2.08]) for preterm births, 0.75 (95% CI 0.17-3.35) for miscarriage and 0.64 (95% CI 0.25-1.64) for stillbirths. No treatment-related serious adverse events (SAEs) have been observed, and there was no significant difference in the number of SAEs (13.5% [67/496] in SPAZ, 16.7% [83/496] in SP, p-value = 0.18) or AEs (17.1% [85/496] in SPAZ, 18.8% [93/496] in SP, p-value = 0.56).. Adequate prevention regimen with monthly sulfadoxine-pyrimethamine given to all pregnant women has been proved to reduce the risk of LBW in malaria endemic areas. Adding azithromycin to the regimen does not offer further benefits, as far as women receive a malaria prevention regimen early enough during pregnancy. Trial registration Pan African Clinical Trial Registry ( https://pactr.samrc.ac.za/Search.aspx ): PACTR201808177464681. Registered 21 August 2018.

Topics: Abortion, Spontaneous; Antimalarials; Azithromycin; Birth Weight; Burkina Faso; Drug Combinations; Female; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Malaria; Pregnancy; Premature Birth; Pyrimethamine; Stillbirth; Sulfadoxine

Preterm birth, especially at less than 30 weeks' gestation, is significantly associated with respiratory, neurodevelopmental and growth abnormalities. The AZTEC study has recruited 799 infants born at < 30 weeks' gestation to determine if a ten-day intravenous treatment with azithromycin improves survival without development of chronic lung disease of prematurity (CLD) at 36 weeks' post menstrual age (PMA) when compared to placebo. The follow-up studies will compare respiratory, neurodevelopmental and growth outcomes up to 2 years of corrected age between infants who received azithromycin and those who received placebo in the early neonatal period.. Survivors at 36 weeks' PMA from the main Azithromycin Therapy for Chronic Lung Disease of Prematurity (AZTEC) study with parental consent will continue to be followed up to discharge from the neonatal unit and to 2 years of corrected age. Length of stay, rates of home oxygen, length of supplemental oxygen requirement, hospital admissions, drug usage, respiratory illness, neurodevelopmental disability and death rates will be reported. Data is being collected via parentally completed respiratory and neurodevelopmental questionnaires at 1 and 2 years of corrected age respectively. Additional information is being obtained from various sources including hospital discharge and clinical letters from general practitioners and hospitals as well as from national databases including the National Neonatal Research Database and NHS Digital.. The AZTEC-FU study will assess mortality and important neonatal morbidities including respiratory, neurodevelopmental and growth outcomes. Important safety data will also be collected, including the incidence of potential consequences of early macrolide use, primarily pyloric stenosis. This study may have implications on future neonatal care.. The study was retrospectively registered on ISRCTN (ISRCTN47442783).

Topics: Azithromycin; Bronchopulmonary Dysplasia; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Oxygen; Premature Birth; Randomized Controlled Trials as Topic

Infection during pregnancy with Plasmodium falciparum is associated with maternal anaemia and adverse birth outcomes including low birth weight (LBW). Studies using polymerase chain reaction (PCR) techniques indicate that at least half of all infections in maternal venous blood are missed by light microscopy or rapid diagnostic tests. The impact of these subpatent infections on maternal and birth outcomes remains unclear.. In a cohort of women co-enrolled in a clinical trial of intermittent treatment with sulfadoxine-pyrimethamine (SP) plus azithromycin for the prevention of LBW (< 2500 g) in Papua New Guinea (PNG), P. falciparum infection status at antenatal enrolment and delivery was assessed by routine light microscopy and real-time quantitative PCR. The impact of infection status at enrolment and delivery on adverse birth outcomes and maternal haemoglobin at delivery was assessed using logistic and linear regression models adjusting for potential confounders. Together with insecticide-treated bed nets, women had received up to 3 monthly intermittent preventive treatments with SP plus azithromycin or a single clearance treatment with SP plus chloroquine.. A total of 9.8% (214/2190) of women had P. falciparum (mono-infection or mixed infection with Plasmodium vivax) detected in venous blood at antenatal enrolment at 14-26 weeks' gestation. 4.7% of women had microscopic, and 5.1% submicroscopic P. falciparum infection. At delivery (n = 1936), 1.5% and 2.0% of women had submicroscopic and microscopic P. falciparum detected in peripheral blood, respectively. Submicroscopic P. falciparum infections at enrolment or at delivery in peripheral or placental blood were not associated with maternal anaemia or adverse birth outcomes such as LBW. Microscopic P. falciparum infection at antenatal enrolment was associated with anaemia at delivery (adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI] 1.09, 3.67; P = 0.025). Peripheral microscopic P. falciparum infection at delivery was associated with LBW (aOR 2.75, 95% CI 1.27; 5.94, P = 0.010) and preterm birth (aOR 6.58, 95% CI 2.46, 17.62; P < 0.001).. A substantial proportion of P. falciparum infections in pregnant women in PNG were submicroscopic. Microscopic, but not submicroscopic, infections were associated with adverse outcomes in women receiving malaria preventive treatment and insecticide-treated bed nets. Current malaria prevention policies that combine insecticide-treated bed nets, intermittent preventive treatment and prompt treatment of symptomatic infections appear to be appropriate for the management of malaria in pregnancy in settings like PNG.

Topics: Adult; Anemia; Anti-Bacterial Agents; Antimalarials; Artemisinins; Asymptomatic Infections; Azithromycin; Female; Hemoglobin A; Humans; Infant, Low Birth Weight; Infant, Newborn; Malaria, Falciparum; Papua New Guinea; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Prospective Studies; Pyrimethamine; Sulfadoxine; Young Adult

In the group of 35 patients with cerclage, intermediate fetal mortality was reduced from 37.1% to 0 (p < 0.001); late fetal mortality rate from 8.5% to 2.8% (p = 0.606); prematurity from 65.7% to 5.7% (p < 0.001); newborn underweight from 11.4% to 5.7% (p = 0.671); newborns with very low weight from 34.2% to 0 (p < 0.001) and the abortion rate from 8.5% to 0 ( p  < 0.001). In the group of 19 patients without buckling, intermediate fetal mortality was reduced from 26.3% to 10.5% (p = 402); late fetal mortality from 63.1% to 0 (p < 0.001); prematurity 78.9% to 31.5% (p < 0.009); the newborn of low weight from 31.5% to 10.5% (p = 0.234); newborns with very low weight from 68.4% to 15.7% (p < 0.003) and the abortion rate from 36.8 to 0 (p < 0.001). In conclusion, we believe the results of this study demonstrate the effectiveness of therapeutic and prophylactic cervical cerclage associated with prolonged antibiotic therapy.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Cerclage, Cervical; Chorioamnionitis; Drug Administration Schedule; Female; Fetal Death; Humans; Pregnancy; Premature Birth; Prospective Studies; Risk Factors; Treatment Outcome

Preterm delivery, which is associated with infections during pregnancy, is common in sub-Saharan Africa. We enrolled 1,320 pregnant women into a randomized, controlled trial in Malawi to study whether preterm delivery and low birth weight (LBW) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections. The participants received either sulfadoxine-pyrimethamine (SP) twice (controls), monthly SP, or monthly SP and two doses of azithromycin (AZI-SP). The incidence of preterm delivery was 17.9% in controls, 15.4% in the monthly SP group (P = 0.32), and 11.8% in AZI-SP group (risk ratio = 0.66, P = 0.01). Compared with controls, those in AZI-SP group had a risk ratio of 0.61 (P = 0.02) for LBW. Incidence of serious adverse events was low in all groups. In conclusion, the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses.

Topics: Adolescent; Adult; Azithromycin; Drug Administration Schedule; Drug Combinations; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Malawi; Pregnancy; Pregnancy Complications, Parasitic; Premature Birth; Pyrimethamine; Sulfadoxine; Young Adult

Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth.. We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16-24 and 28-32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality, birthweight, maternal malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76-1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (-0.08 to 0.40); mean birthweight (3.03 versus 2.99 kg), mean difference 0.04 (-0.005 to 0.08); perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53-1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84-1.49) and anaemia (44.1% versus 41.3%) at 28-32 weeks, OR 1.07 (0.88-1.30). Meta-analysis of the primary outcome results with seven other studies of routine antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86-1.22).. This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies.. Current Controlled Trials ISRCTN84023116

Topics: Azithromycin; Community Health Services; Female; Gestational Age; Humans; Malawi; Placebos; Pregnancy; Premature Birth; Residence Characteristics; Treatment Outcome; Young Adult

The purpose of this study was to explore whether endometrial microbial colonization and plasma cell endometritis are risk factors for adverse pregnancy outcomes, and whether these outcomes are influenced by interactions between interconceptional antibiotics and the micro-flora.. Subgroup analyses of data from a double-blind, randomized, placebo-controlled trial of a course of metronidazole plus azithromycin given every 4 months to women with a prior preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histology were obtained at randomization and repeated 2 weeks after the first treatment. Fifty-nine on antibiotics versus 65 on placebo had pregnancy outcomes. Prevalence of adverse pregnancy outcomes (pregnancy loss or preterm birth < 37 weeks) was stratified by treatment group and endometrial characteristics. Subgroups were assessed and screened for potential interaction (P values for significance set a priori at < .01), prior to formal statistical testing for interaction (P values < .05).. The prevalence of adverse pregnancy outcome was 62.7% in the presence of endometrial microbial colonization at baseline (any microbe) and 50% in the absence of colonization (RR = 1.25; 99% CI 0.42-3.7). Prevalence of adverse pregnancy outcomes was 61.9% with plasma cell endometritis, and 70.8% without; RR = 0.87 (0.50-1.5). There was a nonsignificant reduction in adverse pregnancy outcome in the absence of Gardnerella vaginalis or gram-negative rods with RR (95% CI) = 0.60 (0.3-1.2) and 0.66 (0.4-1.2), respectively. In the presence of these microbes, antibiotics appeared to increase adverse outcomes: RR = 1.5 (1.1-2.0) and 1.5 (1.1-2.1), respectively. This reversal of impact represents a crossover interaction.. Neither baseline endometrial microbial colonization nor plasma cell endometritis were risk factors for adverse pregnancy outcome. However, colonization with specific microbes interacted with antibiotics to increase adverse outcomes.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Double-Blind Method; Endometritis; Endometrium; Female; Humans; Metronidazole; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth

We hypothesized that upper genital tract microbial infection associated with spontaneous preterm birth may precede conception. Our objective was to estimate if antibiotic administration during the interpregnancy interval in nonpregnant women with a previous preterm birth before 34 weeks' gestational age would reduce the rate of spontaneous preterm birth in the subsequent pregnancy.. Women with a spontaneous preterm birth < 34 weeks' gestational age were randomized at 4 months' postpartum to receive oral azithromycin 1 g twice (4 days apart) plus sustained-release metronidazole 750 mg daily for 7 days, or identical-appearing placebos. This regimen was repeated every 4 months until the subsequent pregnancy.. A total of 241 women were randomized; 124 conceived a subsequent pregnancy and were available for study, including 59 in the antibiotic group and 65 in the placebo group. In the antibiotic versus placebo group, neither subsequent spontaneous preterm birth (< 37 weeks: 52% vs 46%, P = .568; < 35 weeks: 40% vs 30%, P = .276; < 32 weeks: 31% vs 23%, P = .376) nor miscarriage (< 15 weeks: 12% vs 14%, P = .742) was significantly different. Although not statistically significant, mean delivery gestational age in the subsequent pregnancy was 2.4 weeks earlier in the antibiotic versus placebo group (32.0 +/- 7.9 vs 34.4 +/- 6.3 weeks, P = .082), and mean birth weight was lower in the antibiotic group (2046 +/- 1209 vs 2464 +/- 1067 g, P =.060).. Intermittent treatment with metronidazole plus azithromycin of nonpregnant women with a recent early spontaneous preterm birth does not significantly reduce subsequent preterm birth, and may be associated with a lower delivery gestational age and lower birth weight.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Female; Humans; Metronidazole; Preconception Care; Pregnancy; Premature Birth; Recurrence

Preterm birth (PTB) is one of the leading causes of neonatal mortality and morbidity worldwide. A shortened cervix is a recognised risk factor for PTB, and amniotic fluid sludge (AFS) diagnosed on ultrasound may be suggestive of underlying inflammation or infection.. The aim is to determine if azithromycin, administered in cases of a shortened cervix, results in prolongation of gestation with improvements in neonatal outcomes.. We performed a retrospective cohort study at three tertiary maternity services in Melbourne, Australia, between 2015 and 2020. Women with a singleton pregnancy were included if they had a cervical length of 15 mm or less at 13-24 weeks' gestation, with or without AFS. Exclusion criteria comprised multiple pregnancy, major fetal congenital anomaly, placenta praevia, prelabour premature rupture of membranes, vaginal bleeding and/or clinical signs suggestive of chorioamnionitis at the time of diagnosis of the short cervix. The results of antibiotic treatment with azithromycin were compared to those of no antibiotic treatment. The outcomes of interest were PTB, prelabour premature rupture of membranes (PPROM), chorioamnionitis and neonatal morbidity.. A total of 374 women were included in the study, of whom 129 received azithromycin and 245 received no antibiotics. When adjusting for potential confounders, the adjusted risk of PTB overall was higher in the treatment group (adjusted hazard ratio 1.36 (95% confidence interval 1.04-1.77) P = 0.023) with no differences found for PPROM, chorioamnionitis or neonatal morbidity.. These data do not support the routine use of azithromycin in women with a short cervix, including those with AFS detected on ultrasound.

Topics: Amniotic Fluid; Anti-Bacterial Agents; Azithromycin; Cervix Uteri; Chorioamnionitis; Cohort Studies; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Pregnancy; Premature Birth; Retrospective Studies; Sewage

Topics: Amniotic Fluid; Anti-Bacterial Agents; Azithromycin; Cerclage, Cervical; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Ureaplasma Infections; Vagina; Young Adult

This historical cohort study aimed to assess the relationship between antenatal maternal C-reactive protein (CRP) level and neonatal outcome preterm premature rupture of membranes (PPROM). We reviewed the records of 70 singleton pregnancies with PPROM between 24 and 34 weeks. Maternal CRP levels of neonates with respiratory distress syndrome, neonatal sepsis, grade 3-4 intraventricular haemorrhage and stage 2-3 necrotizing enterocolitis, perinatal mortality were compared with those without these complications. Administration of corticosteroid, tocolysis for two days and prophylactic antibiotics (intravenous ampicillin/sulbactam, and oral azithromycin) were the standard management protocol. The mean age at PPROM was 29 weeks 2 days (±3 weeks), the mean age at birth was 30 weeks 5 days (±20 days). CRP levels were not different between groups. Uni/multivariate analysis showed that maternal CRP levels were not related with neonatal outcomes. Neonatal complications in PPROM are related with the degree of prematurity and maternal WBC counts.

Topics: Adrenal Cortex Hormones; Adult; Ampicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; C-Reactive Protein; Cohort Studies; Drug Therapy, Combination; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Pregnancy; Pregnancy Outcome; Premature Birth; Tocolysis

To evaluate the risk of developing pulmonary edema in women exposed to nifedipine, magnesium sulfate (MgSO4), or both in a preterm setting.. We carried out a retrospective case-control study at a large tertiary care center from 2007 to 2012. Cases of pulmonary edema were age, and gestational age matched to controls at a ratio of 1 case to 4 controls. Logistic regression analysis was used to estimate the effect of nifedipine and/or MgSO4 on the development of pulmonary edema while controlling for predetermined confounding variables. Stepwise logistic regression analysis was used to evaluate additional risk factors of pulmonary edema.. A total of 150 charts were reviewed (28 cases and 122 controls). Nifedipine did not increase the odds of developing pulmonary edema [adjusted odds ratio (OR)=1.22 (confidence interval (CI) 0.50, 3.01), P=0.67], whereas exposure to MgSO4, or both MgSO4 and nifedipine, significantly increased the risk of developing pulmonary edema [adjusted OR=3.91 (CI 1.44, 10.65), P=0.008 and adjusted OR=4.75 (CI 1.15, 19.71), P=0.032, respectively]. In the stratified analysis, this association persisted even in nonpreeclamptic women [nifedipine: adjusted OR=0.91 (CI 0.33, 2.52), P=0.852; MgSO4: adjusted OR=3.51 (CI 1.26, 9.76), P=0.016; both: adjusted OR=3.39 (0.76, 15.07), P=0.108]. Other independent risk factors for pulmonary edema were multi-fetal pregnancy, azithromycin, and erythromycin administration.. MgSO4 treatment is strongly associated with the development of pulmonary edema when used either as a tocolytic agent or for seizure prophylaxis. In light of the availability of safer alternatives, MgSO4 should be used for tocolysis only in cases whereby the benefits clearly outweigh the risks.

Topics: Adult; Azithromycin; Case-Control Studies; Drug Synergism; Erythromycin; Female; Humans; Infant, Newborn; Logistic Models; Magnesium Sulfate; Nifedipine; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Premature Birth; Pulmonary Edema; Retrospective Studies; Risk Factors; Tocolysis; Tocolytic Agents; Young Adult

Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury.

Topics: Amniotic Fluid; Animals; Anti-Bacterial Agents; Azithromycin; Female; Maternal-Fetal Exchange; Placental Circulation; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Second; Premature Birth; Random Allocation; Sheep

We assessed the efficacy of a maternal multidose azithromycin (AZI) regimen, with and without antiinflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intraamniotic infection.. Long-term catheterized rhesus monkeys (n = 16) received intraamniotic inoculation of U parvum (10(7) colony-forming U/mL, serovar 1). After contraction onset, rhesus monkeys received no treatment (n = 6); AZI (12.5 mg/kg, every 12 h, intravenous for 10 days; n = 5); or AZI plus dexamethasone and indomethacin (n = 5). Outcomes included amniotic fluid proinflammatory mediators, U parvum cultures and polymerase chain reaction, AZI pharmacokinetics, and the extent of fetal lung inflammation.. Maternal AZI therapy eradicated U parvum intraamniotic infection from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted.. Specific maternal antibiotic therapy can eradicate U parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy, which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Chorioamnionitis; Dexamethasone; Drug Therapy, Combination; Female; Fetal Diseases; Indomethacin; Lung Injury; Macaca mulatta; Polymerase Chain Reaction; Pregnancy; Premature Birth; Treatment Outcome; Ureaplasma; Ureaplasma Infections

According to contemporary data Ureaplasma urealiticum and Mycoplasma hominis are considered to be the most frequently isolated causative microorganisms from the amniotic cavity. They cause intrauterine infection on preterm birth. The genital mycoplasma are detected in vaginal smears more than 25% of healthy pregnant women and the reason for their invasion towards the uterine cavity in some cases are still unknown. The aim of this study is to investigate the relation between vaginal mycoplasmal contamination and preterm birth. The observed cases are distributed into 2 groups:--patients with preterm birth--35 pregnant women,--term birth--31 pregnant women. The vaginal secretion was tested with a standard microbiological methods and with specific test mycoplasma detection and quantitative assessment. In the first group in five patients (14.3%) Ur. urealiticum was detected in association with other vaginal pathogens (bacterial vaginosis and GBS). In the term birth group 2 patients were mycoplasma positive (6.5%) and associated Enterococcus and Lactobacillus was found in them. All neonates of the mycoplasma positive mothers had sings of infection and underwent antimicrobial therapy course. The results did not demonstrate statistically significant difference in the incidence of vaginal mycoplasmal presence in preterm and term delivery but shows possible relationship between preterm birth caused by ascending mycoplasmal infection which is in association with other vaginal pathogens.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bulgaria; Enterococcus; Female; Humans; Lactobacillus; Mycoplasma hominis; Mycoplasma Infections; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Prospective Studies; Ureaplasma Infections; Ureaplasma urealyticum; Vaginosis, Bacterial