Efficacy and Safety of Aspirin 162 mg for Preeclampsia Prophylaxis in High-Risk Patients.

OBJECTIVE: The aim of this study was to compare the safety and efficacy of aspirin 162 mg to the standard recommended dose of 81 mg for preeclampsia prevention. STUDY DESIGN: A retrospective cohort study of patients at risk for preeclampsia who delivered between January 2013 and December 2020 at Henry Ford Health was performed. Patients were divided into three groups: a no aspirin group, a group treated under an 81 mg aspirin preeclampsia prophylaxis protocol, and a group treated under a 162 mg protocol. Univariate and multivariable logistic regression analyses compared rates of preeclampsia and secondary outcomes between groups. Clinical side effects traditionally associated with aspirin use were also assessed. RESULTS: Of 3,597 patients, 2,266 (63%) were in the no aspirin group, 944 (26%) were in the 81 mg group, and 387 (11%) were in the 162 mg group. The rate of preeclampsia was significantly lower in the 162 mg group (10.1%, odds ratio, 0.68; 95% confidence interval, 0.46-0.99) compared with the 81 mg group (14.2%). The rate of preeclampsia was identical in the no aspirin and 81 mg groups. The rate for postpartum hemorrhage, postpartum hematoma, and intraventricular hemorrhage of the newborn were not significantly different between patients in the 162 and 81 mg groups. CONCLUSION: We observed a significantly lower rate of preeclampsia in high-risk patients who were treated with the 162 mg dose of aspirin for preeclampsia prophylaxis, and bleeding complications were not seen with the higher dose. Our study suggests that aspirin 162 mg may be considered for prophylaxis in patients at high risk for preeclampsia. KEY POINTS: · Aspirin 81 mg is currently standard for preeclampsia prophylaxis.. · Preeclampsia rate is significantly lower among high-risk patients taking aspirin 162 mg compared with 81 mg.. · Bleeding complications are not increased among those taking aspirin 162 mg..

Evidence that intra-amniotic infections are often the result of an ascending invasion - a molecular microbiological study.

Background Microbial invasion of the amniotic cavity resulting in intra-amniotic infection is associated with obstetrical complications such as preterm labor with intact or ruptured membranes, cervical insufficiency, as well as clinical and histological chorioamnionitis. The most widely accepted pathway for intra-amniotic infection is the ascension of microorganisms from the lower genital tract. However, hematogenous dissemination of microorganisms from the oral cavity or intestine, retrograde seeding from the peritoneal cavity through the fallopian tubes, and introduction through invasive medical procedures have also been suggested as potential pathways for intra-amniotic infection. The primary reason that an ascending pathway is viewed as most common is that the microorganisms most often detected in the amniotic fluid are those that are typical inhabitants of the vagina. However, thus far, no studies have shown that microorganisms in the amniotic cavity are simultaneously present in the vagina of the woman from which they were isolated. The objective of the study was to determine the frequency with which microorganisms isolated from women with intra-amniotic infection are also present in the lower genital tract. Methods This was a cross-sectional study of women with intra-amniotic infection with intact membranes. Intra-amniotic infection was defined as a positive culture and elevated concentrations of interleukin-6 (IL-6) (>2.6 ng/mL) in amniotic fluid and/or acute histologic chorioamnionitis and funisitis. Microorganisms isolated from bacterial cultures of amniotic fluid were taxonomically identified through matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and 16S ribosomal RNA (rRNA) gene sequencing. Vaginal swabs were obtained at the time of amniocentesis for the identification of microorganisms in the lower genital tract. The overall bacterial profiles of amniotic fluids and vaginal swabs were characterized through 16S rRNA gene sequencing. The bacterial profiles of vaginal swabs were interrogated for the presence of bacteria cultured from amniotic fluid and for the presence of prominent (>1% average relative abundance) operational taxonomic units (OTUs) within the overall 16S rRNA gene bacterial profiles of amniotic fluid. Results (1) A total of 75% (6/8) of women had bacteria cultured from their amniotic fluid that are typical residents of the vaginal ecosystem. (2) A total of 62.5% (5/8) of women with bacteria cultured from their amniotic fluid also had these bacteria present in their vagina. (3) The microorganisms cultured from amniotic fluid and also detected in the vagina were Ureaplasma urealyticum, Escherichia coli, and Streptococcus agalactiae. (4) 16S rRNA gene sequencing revealed that the amniotic fluid of women with intra-amniotic infection had bacterial profiles dominated by Sneathia, Ureaplasma, Prevotella, Lactobacillus, Escherichia, Gardnerella, Peptostreptococcus, Peptoniphilus, and Streptococcus, many of which had not been cultured from the amniotic fluid samples. (5) Seventy percent (7/10) of the prominent (>1% average relative abundance) OTUs found in amniotic fluid were also prominent in the vagina. Conclusion The majority of women with intra-amniotic infection had bacteria cultured from their amniotic fluid that were typical vaginal commensals, and these bacteria were detected within the vagina at the time of amniocentesis. Molecular microbiological interrogation of amniotic fluid from women with intra-amniotic infection revealed that the bacterial profiles of amniotic fluid were largely consistent with those of the vagina. These findings indicate that ascension from the lower genital tract is the primary pathway for intra-amniotic infection.

Trends in Preeclampsia Risk Factors in the US From 2010 to 2021.

This population-based retrospective study uses data from the National Vital Statistics System to evaluate trends in risk factors for preeclampsia in the US between 2010 and 2021.

Clinical chorioamnionitis at term VII: the amniotic fluid cellular immune response.

OBJECTIVES: 1) To characterize the cellular composition of the amniotic fluid of patients diagnosed with clinical chorioamnionitis at term, as a function of the presence or absence of microorganisms determined by cultivation techniques, and 2) to characterize the cytokine production by white blood cells present in the amniotic fluid using flow cytometry-based techniques. MATERIALS AND METHODS: Amniotic fluid samples from 20 women who had the diagnosis of clinical chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas). Amniotic fluid IL-6 concentrations were determined by an enzyme-linked immunosorbent assay. Amniotic fluid leukocytes were visualized by using hematoxylin and eosin staining and immunofluorescence. Immunophenotyping of surface markers and cytokines was performed in amniotic fluid leukocytes using flow cytometry. RESULTS: 1) Neutrophils (CD45+CD15+ cells) were the most common leukocyte subset found in the amniotic fluid, followed by monocytes (CD45+CD14+ cells); other white blood cells (such as lymphocytes and natural killer cells) were scarce in the amniotic fluid; 2) the absolute counts of neutrophils and monocytes were significantly higher in patients with microorganisms found in the amniotic fluid than in those without detectable microorganisms, using cultivation techniques; 3) there was a significant correlation between the absolute counts of neutrophils and monocytes determined by flow cytometry (Spearman's correlation=0.97; P<0.001); 4) there was a significant correlation between the absolute white blood cell count determined with a hemocytometer chamber and by flow cytometric analysis (Spearman's correlation=0.88; P<0.001); and 5) the profile of cytokine expression differed between monocytes and neutrophils; while neutrophils predominantly produced TNF-α and MIP-1ß, monocytes expressed higher levels of IL-1ß and IL-1α. CONCLUSION: Flow cytometry analysis of the amniotic fluid of patients with intra-amniotic infection and clinical chorioamnionitis at term demonstrated that neutrophils and monocytes are the most common cells participating in the inflammatory process. We have characterized, for the first time, the differential cytokine expression by these cells in this important complication of pregnancy.

Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques.

INTRODUCTION: The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection. METHODS: The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration ≥2.6 ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations. RESULTS: 1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive for microorganisms in 59% (27/46) ­ combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2) Ureaplasma urealyticum (n=8) and Gardnerella vaginalis (n=10) were the microorganisms most frequently identified by cultivation and PCR/ESI-MS, respectively. 3) When combining the results of AF culture, PCR/ESI-MS and AF IL-6 concentrations, 15% (7/46) of patients did not have intra-amniotic inflammation or infection, 6.5% (3/46) had only MIAC, 54% (25/46) had microbial-associated intra-amniotic inflammation, and 24% (11/46) had intra-amniotic inflammation without detectable microorganisms. 4) Placental lesions consistent with acute AF infection were significantly more frequent in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [70.8% (17/24) vs. 28.6% (2/7); P=0.04]. CONCLUSION: Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.

False-Positive Human Immunodeficiency Virus Screening Results in Pregnancy During the Coronavirus Disease 2019 (COVID-19) Pandemic.

False-positive human immunodeficiency virus (HIV) test results are rare but have been documented in the setting of certain underlying conditions such as Epstein-Barr virus, metastatic cancer, and certain autoimmune conditions. A retrospective cohort study in a large hospital system was conducted to compare the occurrence of false-positive HIV fourth-generation test results before and after the coronavirus disease 2019 (COVID-19) pandemic in a population of pregnant patients (N=44,187; 22,073 pre-COVID and 22,114 during COVID). The COVID cohort had a significantly higher frequency of false-positive HIV test results compared with the pre-COVID cohort (0.381 vs 0.676, P =.002). Within the COVID cohort, 25% of patients had a positive polymerase chain reaction test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preceding their false-positive HIV test results. When this subgroup was excluded, the difference in frequency of false-positive HIV test results between the cohorts was no longer significant (0.381 vs 0.507, P =.348). Our findings suggest that SARS-CoV-2 seropositivity was associated with an increased frequency of false-positive HIV test results in the pregnant population.

Provider adherence to aspirin prophylaxis prescription guidelines for preeclampsia.

OBJECTIVE: To evaluate provider adherence to aspirin prophylaxis prescription guidelines for patients at risk. STUDY DESIGN: A retrospective chart review was performed at Henry Ford Health (HFH) between October 2015 and December 2020. In October 2015, low-dose aspirin was recommended for women who met high risk criteria for preeclampsia at HFH; in February 2019, aspirin recommendation expanded to include women who met either moderate or high-risk criteria. A total of 46,016 pregnancies occurred between Oct 2015 and Dec 2020 of which 15,167 (33.0%) met high and moderate risk criteria. RESULTS: From the population at risk, 1,255 (8.3%) had a history of preeclampsia, 2,534 (16.7%) had a history of chronic hypertension, 1,418 (9.3%) had a history of diabetes, 7,470 (49.3%) were nulliparous, 4,038 (26.6%) were 35 years of age or older, 6,395 (42.2%) had a body mass index greater than 30 kg/m2, and 8,174 (54.5%) were African Americans. Only 630 out of 3,584 (17.6%) of women meeting the high-risk criteria for preeclampsia between Oct 2015 and Jan 2019 received low-dose aspirin and only 891 out of 5,874 (15.2%) of women meeting the high or moderate risk criteria for preeclampsia between Feb 2019 and Dec 2020 received low-dose aspirin prophylaxis. CONCLUSION: Adherence to aspirin prophylaxis guidelines was low. Most urban healthcare systems serve diverse, high-risk populations with multiple comorbidities rendering many women at risk for preeclampsia. Educational efforts to improve provider knowledge regarding this important preventative measure are indicated. Recommendation for implementing universal aspirin in such high-risk populations should also be considered.

Suspected vitamin K-dependent coagulation factor deficiency in pregnancy: A case report.

Hereditary combined vitamin K-dependent clotting factor deficiency (VKCFD) is a rare autosomal recessive congenital bleeding disorder. There are no established guidelines for the care for pregnant women and newborns within the context of VKCFD. A 39-year-old multigravida woman with a family history of VKCFD was referred for high-risk maternal fetal medicine care. Prenatal testing for fetal VKCFD was declined. The patient received vitamin K1 from 36 weeks of gestation and had an uncomplicated vaginal delivery. The baby had normal head ultrasound results, vital signs, and physical examination, with no signs of bleeding: factor levels and coagulation factors were within reference range. Follow-up showed no evidence of VKCFD. A thorough care plan is required for pregnant women whose newborns are at risk for VKCFD.

Expectant management of a heterotopic interstitial pregnancy - a case report.

Heterotopic pregnancy is the simultaneous occurrence of two pregnancies at two different implantation sites, mostly intrauterine and extrauterine sites. An interstitial ectopic pregnancy as part of a heterotopic pregnancy is very rare. This report highlights the case of a 40-year-old woman with heterotopic pregnancy who had conceived via assisted reproductive technology. The patient had an interstitial ectopic pregnancy and a viable intrauterine pregnancy. She was treated expectantly and had cesarean delivery of the intrauterine pregnancy at 38 weeks of gestation. Although management options for heterotopic pregnancies include surgical and medical, it may be reasonable to consider expectant management for select cases while weighing risks. In such cases, close monitoring of symptoms and serial ultrasound examinations should be standard.

Recurrence Rate for Isolated Elevated Maternal Serum Alpha-Fetoprotein Levels and Pregnancy Outcomes.

Objective: To examine the rate of recurrence for elevated isolated maternal serum alpha-fetoprotein (MSAFP) and its associated adverse outcomes during a subsequent pregnancy. Materials and Methods: A retrospective cohort study of pregnant multiparous women who had elevated MSAFP levels during an initial and a subsequent pregnancy between 1994 and 2020. Results: Twenty-seven out of 344 (7.8%) women with elevated MSAFP had recurrent elevated MSAFP in a subsequent pregnancy. Four women were excluded due to missing data. Of the 23 women included, 5 (22%) had fetal growth restriction (FGR), 2 (9%) had pre-eclampsia, 9 (35%) had preterm births, and 2 (9%) had fetal death/miscarriage in their subsequent pregnancy. Looking at individual outcomes, 60% of women had recurrence of preterm labor, 33% had recurrence of fetal death, and 25% had recurrence of FGR. Conclusion: Women with elevated MSAFP levels during an initial pregnancy should be informed during preconception counseling about their risk of recurring elevated MSAFP and its associated adverse outcomes risks.

Benign Recurrent Intrahepatic Cholestasis in Pregnancy: Fetal Death at 36 Weeks of Gestation.

INTRODUCTION: Benign recurrent intrahepatic cholestasis is a rare hepatologic disorder characterized by recurrent, self-limited episodes of severe pruritus, jaundice, and elevated bile acids. While there are guidelines for the management of intrahepatic cholestasis of pregnancy, the literature regarding benign recurrent intrahepatic cholestasis and pregnancy is limited. CASE: A 29-year-old G1P0 woman, with history of liver toxicity, had elevated total serum bile acid levels and liver enzymes documented at 8 weeks of gestation and throughout her pregnancy. She had a reactive nonstress test just 3 days prior to her induction. Fetal demise was noted when she presented at 36 weeks for her induction. CONCLUSION: We recommend that women with elevated total serum bile acid early in pregnancy due to a separate entity relative to intrahepatic cholestasis of pregnancy be managed in a more individualized approach.

Ovarian torsion in utero diagnosed at 37 weeks of pregnancy: A case report.

BACKGROUND: Fetal ovarian masses are common abdominal anomalies in female fetuses, often diagnosed in the third trimester. Most masses are benign and tend to resolve spontaneously within a few months after birth, but larger masses may present complications such as torsion. CASE: A 21-year-old primagravid woman was noted to have a complex avascular solid mass in the fetal left pelvis, which was consistent with complex fetal left ovarian torsion. The patient underwent induction of labor at 39 weeks for possible intervention. The infant underwent surgery at 5 weeks of age and a torsed, necrotic ovary was discovered. CONCLUSION: The diagnosis of ovarian torsion in utero is rare, and prenatal and postnatal guidelines are needed on frequency of monitoring, timing of delivery, and postnatal follow-up.

Severe COVID-19 infection in pregnancy requiring intubation without preterm delivery: A case report.

BACKGROUND: Coronavirus-2019 (COVID-19) is a global health crisis, but there is limited guidance for the critical care management of pregnant patients experiencing respiratory collapse. We describe our management of a peri-viable pregnant patient requiring intubation; discussion includes pharmacologic interventions, mechanical ventilation adjustments, and consideration of fetal interventions, including delivery timing. CASE: A 36-year-old, gravida 2, para 1 woman positive for COVID-19 at 23 weeks of gestation with severe disease required admission to the intensive care unit and intubation. She completed 5 days of hydroxychloroquine and 7 days of prednisone. She was successfully intubated after 8 days and discharged home in a stable condition without preterm delivery on hospital day 11. CONCLUSION: Fortunately, the patient responded to aggressive respiratory support with intubation and mechanical ventilation early upon presentation. It is unclear whether our institution's empiric use of hydroxychloroquine and prednisone facilitated her recovery. We hope that our report helps other institutions navigate the complex care surrounding pregnant patients with severe COVID-19 pneumonia requiring intensive care.

Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense.

OBJECTIVE: Neutrophil extracellular traps (NETs) control microbial infections through their antimicrobial activities attributed to DNA, histones, granules, and cytoplasmic proteins (eg, elastase). Intra-amniotic infection is characterized by the influx of neutrophils into the amniotic cavity; therefore, the aim of this study was to determine whether amniotic fluid neutrophils form NETs in this inflammatory process. METHODS: Amniotic fluid samples from women with intra-amniotic infection (n = 15) were stained for bacteria detection using fluorescent dyes. Amniotic fluid neutrophils were purified by filtration. As controls, neutrophils from maternal blood samples (n = 3) were isolated by density gradients. Isolated neutrophils were plated onto glass cover slips for culture with and without 100 nM of phorbol-12-myristate-13-acetate (PMA). NET formation was assessed by 4',6-diamidino-2-phenylindole (DAPI) staining and scanning electron microscopy. Different stages of NET formation were visualized using antibodies against elastase and histone H3, in combination with DAPI staining, by confocal microscopy. Finally, maternal or neonatal neutrophils were added to amniotic fluid samples from women without intra-amniotic infection (n = 4), and NET formation was evaluated by DAPI staining. RESULTS: (1) NETs were present in the amniotic fluid of women with intra-amniotic infection; (2) all of the amniotic fluid samples had detectable live and dead bacteria associated with the presence of NETs; (3) in contrast to neutrophils from the maternal circulation, amniotic fluid neutrophils did not require PMA stimulation to form NETs; (4) different stages of NET formation were observed by co-localizing elastase, histone H3, and DNA in amniotic fluid neutrophils; and (5) neither maternal nor neonatal neutrophils form NETs in the amniotic fluid of women without intra-amniotic infection. CONCLUSION: NETs are detectable in the amniotic fluid of women with intra-amniotic infection.

Placental lesions associated with acute atherosis.

OBJECTIVE: Acute atherosis is a lesion of the spiral arteries characterized by fibrinoid necrosis of the vessel wall, an accumulation of fat-containing macrophages, and a mononuclear perivascular infiltrate, which can be found in patients with preeclampsia, fetal death, small-for-gestational age, spontaneous preterm labor/premature prelabor rupture of membrane, and spontaneous mid-trimester abortion. This lesion is thought to decrease blood flow to the intervillous space which may lead to other vascular lesions of the placenta. The objective of this study was to test whether there is an association between acute atherosis and placental lesions that are consistent with maternal vascular underperfusion (MVU), amniotic fluid infection (AFI), fetal vascular thrombo-occlusive disease (FVTOD) or chronic inflammation. MATERIAL AND METHODS: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women's Hospital/Detroit Medical Center was conducted examine 16 457 placentas. The frequency of placenta lesions (diagnosed using the criteria of the Perinatal Section of the Society for Pediatric Pathology) was compared between pregnancies with and without acute atherosis. RESULTS: Among 16 457 women who were enrolled, 10.2% (1671/16 457) were excluded, leaving 14 786 women who contributed data for analysis. Among them, the prevalence of acute atherosis was 2.2% (326/14 786). Women with acute atherosis were more than six times as likely as those without to have placental lesions consistent with maternal underperfusion (adjusted odds ratio - aOR: 6.7; 95% CI 5.2-8.6). To a lesser degree, acute atherosis was also associated with greater risks of having either lesions consistent with FVTOD (aOR 1.7; 95% CI 1.2-2.3) or chronic chorioamnionitis (aOR 1.9; 95% CI 1.3-3), but not with other chronic inflammatory lesions, after adjusting for gestational age at delivery. In contrast, women with acute atherosis were 60% less likely to have lesions consistent with AFI, adjusting for gestational age at delivery (aOR 0.4; 95% CI 0.3-0.5). CONCLUSIONS: Acute atherosis is associated with increased risks of having placental lesions consistent with MVU, and to a lesser extent, chronic chorioamnionitis and those consistent with FVTOD.

The frequency of acute atherosis in normal pregnancy and preterm labor, preeclampsia, small-for-gestational age, fetal death and midtrimester spontaneous abortion.

OBJECTIVE: Acute atherosis is characterized by subendothelial lipid-filled foam cells, fibrinoid necrosis and perivascular lymphocytic infiltration. This lesion is generally confined to non-transformed spiral arteries and is frequently observed in patients with preeclampsia. However, the frequency of acute atherosis in the great obstetrical syndromes is unknown. The purpose of this study was to determine the frequency and topographic distribution of acute atherosis in placentas and placental bed biopsy samples obtained from women with normal pregnancy and those affected by the "great obstetrical syndromes". We also examined the relationship between acute atherosis and pregnancy outcome in patients with preeclampsia. MATERIAL AND METHODS: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women's Hospital/Detroit Medical Center was conducted to examine 16, 345 placentas. Patients were classified into the following groups: (1) uncomplicated pregnancy; (2) spontaneous preterm labor (sPTL) and preterm prelabor rupture of membranes (PPROM); (3) preeclampsia; (4) gestational hypertension; (5) small-for-gestational age (SGA); (6) chronic hypertension; (5) fetal death; (6) spontaneous abortion and (7) others. A subset of patients had placental bed biopsy. The incidence of acute atherosis was compared among the different groups. RESULTS: (1) The prevalence of acute atherosis in uncomplicated pregnancies was 0.4% (29/6961) based upon examination of nearly 7000 placentas; (2) the frequency of acute atherosis was 10.2% (181/1779) in preeclampsia, 9% (26/292) in fetal death, 2.5% (3/120) in midtrimester spontaneous abortion, 1.7% (22/1,298) in SGA neonates and 1.2% (23/1,841) in sPTL and PPROM; (3) among patients with preeclampsia, those with acute atherosis than in those without the lesion had significantly more severe disease, earlier onset, and a greater frequency of SGA neonates (p < 0.05 all) and (4) the lesion was more frequently observed in the decidua (parietalis or basalis) than in the decidual segment of the spiral arteries in patients with placental bed biopsies. CONCLUSIONS: Acute atherosis is rare in normal pregnancy, and occurs more frequently in patients with pregnancy complications, including preeclampsia, sPTL, preterm PROM, midtrimester spontaneous abortion, fetal death and SGA.

Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes.

OBJECTIVE: The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. METHODS: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes. RESULTS: (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p = 0.001]. CONCLUSIONS: (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.

Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy.

Restless legs syndrome (RLS) and nausea and vomiting of pregnancy (NVP) are both common maternal conditions affecting quality of life. Gabapentin is currently FDA-approved for treating RLS and preliminary results have shown it may be effective for treating the most severe form of NVP, hyperemesis gravidarum (HG). Because NVP and HG symptoms peak early in pregnancy, the potential teratogenicity of gabapentin needs to be considered. We reviewed published pregnancy registries and cohorts for pregnancy outcomes associated with maternal gabapentin use. Gabapentin exposures from 5 pregnancy registries, 1 HG pilot study and 2 additional cases were reviewed. Among 294 first trimester gabapentin-monotherapy exposures, there were 5 major congenital malformations (MCMs) reported (1.7%), which favorably compares to the MCM rate in the general population (1.6-2.2%). Two of the registries reported maternal gabapentin use among 261 singleton pregnancies to be associated with roughly equivalent rates of premature birth, birth weight after correction for gestational age at delivery and maternal hypertension/eclampsia as those that have been reported in the general population. These data support the safety of gabapentin use in pregnancy; however, the number of exposures to date is still small. If future pregnancy registry data confirm this positive safety profile, gabapentin therapy would likely be a safe and effective treatment for RLS during pregnancy. Controlled, clinical trials are needed to assess gabapentin's effectiveness for HG.