Shari E. Gelber

Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis

OBJECTIVE Recent data suggest vitamin D deficiency (VDD) is associated with bacterial vaginosis (BV) during pregnancy. We hypothesized that VDD is a risk factor for BV in nonpregnant women. STUDY DESIGN Using National Health and Nutrition Examination Survey data, we conducted multivariable logistic regression analyses stratified by pregnancy. RESULTS VDD was associated with BV only in pregnant women (adjusted odds ratio [AOR], 2.87; 95% confidence interval [CI], 1.13-7.28). Among nonpregnant women, douching (AOR, 1.72; 95% CI, 1.25-2.37), smoking (AOR, 1.66; 95% CI, 1.23-2.24), and black race (AOR, 2.41; 95% CI, 1.67-3.47) were associated with BV; oral contraceptive use was inversely associated with BV (AOR, 0.60; 95% CI, 0.40-0.90). VDD moderated the association between smoking and BV in nonpregnant women. CONCLUSION Risk factors for BV differ by pregnancy status. VDD was a modifiable risk factor for BV among pregnant women; evaluation of vitamin D supplementation for prevention or adjunct therapy of BV in pregnancy is warranted.

Group B Streptococcus β-hemolysin/Cytolysin Breaches Maternal-Fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

BACKGROUND Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. METHODS We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection. RESULTS Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. CONCLUSIONS Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis.

Evidence for the clinical management of chorioamnionitis

Acute chorioamnionitis or intra-amniotic infection is defined by maternal fever in association with at least one additional clinical criterion including maternal or fetal tachycardia, maternal leukocytosis, uterine tenderness, or foul amniotic fluid odor. In clinically uncertain cases, the diagnosis can be augmented by routine laboratory studies (e.g. white blood cell count and differential count and acute phase reactants) and assays done on amniotic fluid. In general, the clinical management of chorioamnionitis is based on observational or cohort studies; only a few randomized controlled trials have been done. Prompt administration of antibiotics and delivery decrease maternal and neonatal morbidity. The most commonly used antibiotic regimen is ampicillin and gentamicin. Recent evidence supports daily rather than three-times-daily dosing of gentamicin for greater efficacy and decreased fetal toxicity. There is no evidence demonstrating harm with the administration of corticosteroids (to promote fetal lung maturity) in women with acute chorioamnionitis. Cesarean delivery should be reserved for standard obstetric indications.

Contemporary practice patterns and beliefs regarding tocolysis among u.s. Maternal-fetal medicine specialists.

OBJECTIVE: To estimate maternal–fetal medicine specialists’ practice patterns and perceived risks and benefits to tocolysis. METHODS: We performed a mail-based survey of all Society for Maternal–Fetal Medicine (SMFM) members in the United States. Subjects were asked whether they would recommend tocolysis and what would be their first-line tocolytic in five scenarios: 1) acute preterm labor; 2) maintenance tocolysis after arrested preterm labor; 3) repeat acute preterm labor; 4) preterm premature rupture of membranes (PROM) without contractions; and 5) preterm PROM with contractions. RESULTS: A total of 827 (46%) SMFM members responded. Ninety-six percent, 56%, 56%, 32%, and 29% would recommend tocolysis for acute preterm labor, repeat acute preterm labor, preterm PROM with contractions, preterm PROM without contractions, and maintenance tocolysis, respectively. The most common first-line tocolytic was magnesium for acute preterm labor (45%) and repeat acute preterm labor (41%); nifedipine was the most common maintenance tocolysis (79%). Eighty percent believed tocolysis was associated with moderate or significant benefit in the setting of acute preterm labor; however, fewer than 50% responded similarly for the other four scenarios. In all five scenarios, more than 50% of respondents indicated there was minimal or no risk associated with tocolysis. Having a nonacademic practice was independently associated with the recommendation for tocolysis. CONCLUSION: Almost all maternal–fetal medicine specialists recommend tocolysis in the setting of acute preterm labor, and many recommend tocolysis for other indications. Magnesium and nifedipine are the most commonly prescribed first-line tocolytics. LEVEL OF EVIDENCE: III

The recommendation for bed rest in the setting of arrested preterm labor and premature rupture of membranes

OBJECTIVE The objective of the study was to estimate practice patterns regarding bed rest in women with preterm premature rupture of membranes (PPROM) and arrested preterm labor. STUDY DESIGN This was a mail-based survey of all Society for Maternal-Fetal Medicine members in the United States asking whether they would recommend bed rest in the setting of arrested preterm labor or PPROM at 26 weeks. Bed rest was defined as no more than 1-2 hours per day out of bed, with permitted activities including bathroom use, bathing, and brief ambulation inside the home/hospital. RESULTS Seventy-one percent and 87% would recommend bed rest for women with cervical dilation and arrested preterm labor and women with PPROM, respectively, even though the majority believed bed rest was associated with minimal or no benefit. Female sex, nonacademic practice, and practice location in the South or West were independently associated with the recommendation for bed rest. CONCLUSION Despite the belief that bed rest is associated with minimal or no benefit, most maternal-fetal medicine specialists recommend bed rest for arrested preterm labor and PPROM. Randomized, prospective trials are needed to evaluate the efficacy of bed rest in these settings.

ApoE Receptor 2 Mediation of Trophoblast Dysfunction and Pregnancy Complications Induced by Antiphospholipid Antibodies in Mice

Pregnancies in women with the antiphospholipid syndrome (APS) are frequently complicated by fetal loss and intrauterine growth restriction (IUGR). How circulating antiphospholipid antibodies (aPL) cause pregnancy complications in APS is poorly understood. We sought to determine whether the low‐density lipoprotein receptor family member apolipoprotein E receptor 2 (ApoER2) mediates trophoblast dysfunction and pregnancy complications induced by aPL.

Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency

Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.

Gelsolin down-regulates lipopolysaccharide-induced intraamniotic tumor necrosis factor-α production in the midtrimester of pregnancy

OBJECTIVE The purpose of this study was to identify gelsolin in midtrimester amniotic fluid and evaluate its interaction with lipopolysaccharide (LPS). STUDY DESIGN Supernatants from 40 midtrimester amniotic fluid samples were incubated with Escherichia coli LPS, and gelsolin binding was measured by enzyme-linked immunosorbent assay. Unfractionated aliquots of 25 of the fluids were cultured ex vivo for 24 hours in the presence of LPS and supernatants tested for tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 production, and the influence of antigelsolin antibody was evaluated. RESULTS Each amniotic fluid was positive for gelsolin that bound to LPS. LPS-induced TNF-alpha production was inversely proportional to the amniotic fluid concentrations of LPS-bound gelsolin (r = -0.5047; P = .006). Preincubation with monoclonal antibody to gelsolin led to an increase in LPS-induced TNF-alpha production (P = .01). There was no relationship between gelsolin and IL-10 production. CONCLUSION Gelsolin is present in midtrimester amniotic fluid, binds to LPS, and inhibits the induction of TNF-alpha.

Physical and Sexual Activity during Pregnancy and Near Delivery

OBJECTIVE Prior research indicates that pregnant women rarely engage in strenuous physical activity during pregnancy and significantly reduce their sexual activity towards the end of pregnancy. We sought to determine if this was true among patients in a modern urban academic medical center. METHODS This was a descriptive questionnaire-based survey of 425 primiparous women in the immediate postpartum period at one institution. Subjects were asked to describe their physical and sexual activity during the third trimester, during the 2 weeks prior to delivery, and during the 2 days prior to delivery. RESULTS Most subjects spent at least 5 hours on their feet per day, even in the 2 days before delivery. During the third trimester, 60% of subjects reported performing strenuous physical activity (working out), and 62% reported having sexual intercourse. From 2 weeks before labor until 2 days before labor, 49% of subjects reported performing strenuous physical activity (working out), and 40% reported having sexual intercourse. During the 2 days before labor, 33% of subjects reported performing strenuous physical activity, and 17% reported having sexual intercourse. CONCLUSIONS In our population, physical and sexual activity during pregnancy is more common than previously reported, even in the last 2 days before labor.

History-indicated cerclage: practice patterns of maternal-fetal medicine specialists in the USA.

Abstract Objective: There is limited evidence supporting the effectiveness of history-indicated cerclage in preventing spontaneous pregnancy loss or preterm birth. This study was undertaken to estimate the practice patterns of maternal-fetal medicine specialists in regards to history-indicated cerclage. Methods: We performed a mail-based survey of all SMFM specialists in the US. Subjects were asked whether they would recommend a history-indicated cerclage at 12–14 weeks in a patient whose prior pregnancy was her first pregnancy and ended in a spontaneous, painless loss at 19 weeks with no identifiable cause. Results: A total of 827 (46%) of SMFM members responded of which 75% would recommend a history-indicated cerclage for this patient. Twenty-one percent would not recommend one, but would place one if desired by the patient. Only 4% would not place a history-indicated cerclage in this scenario. A total of 71% believed a history-indicated cerclage was associated with moderate or significant benefit, and 89% believed it involved minimal or no risk. Female gender, non-academic practice, practicing in the southern region and greater interval since residency training were all independently associated with the recommendation for a history-indicated cerclage. Conclusions: Despite limited level-I evidence supporting its use, a history-indicated cerclage is recommended by most maternal-fetal medicine specialists.