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Problem Inflammatory cytokines and matrix metalloproteinases (MMPs) contribute to preterm labor pathophysiology. The objective of this study was to test anti-inflammatory properties of simvastatin in human fetal membranes exposed to lipopolysaccharide (LPS). Method of study Normal term human fetal membrane explants (n = 11) were allocated to one of the six study groups: control, LPS only (100 ng/mL), simvastatin only (125 ng/mL), simvastatin given 6 hrs prior to LPS (S-L), simvastatin given 6 hrs post-LPS (L-S), and simvastatin and LPS given simultaneously (L+S). Explants were incubated for 24 hrs. Multiplex ELISA for cytokines: IL-1β, IL-6, IL-10, and TNF-α; soluble cytokine receptors: sIL-1R2, sIL-6R, sTNFR1, and R2; MMPs (1, 2, 7, 9, and 10); and tissue inhibitor of metalloproteinase-2 (TIMP-2) was performed on tissue culture supernatants. Pairwise comparison between different groups was conducted by least square mean estimates. Results Compared with controls, LPS stimulation increased cytokine production and their tissue bioavailability (measured as the molar ratio of cytokine to its soluble receptor), thus confirming membrane immune reactivity (P

To identify metabolic changes associated with early spontaneous preterm birth (PTB;34 weeks) and term births, using high-throughput metabolomics of amniotic fluid (AF) in African American population.In this study, AF samples retrieved from spontaneous PTB (34 weeks [n = 25]) and normal term birth (n = 25) by transvaginal amniocentesis at the time of labor prior to delivery were subjected to metabolomics analysis. Equal volumes of samples were subjected to a standard solvent extraction method and analyzed using gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS. Biochemicals were identified through matching of ion features to a library of biochemical standards. After log transformation and imputation of minimum observed values for each compound, t test, correlation tests, and false discovery rate corrections were used to identify differentially regulated metabolites. Data were controlled for clinical/demographic variables and medication during pregnancy.Of 348 metabolites measured in AF samples, 121 metabolites had a gestational age effect and 116 differed significantly between PTB and term births. A majority of significantly altered metabolites could be classified into 3 categories, namely, (1) liver function, (2) fatty acid and coenzyme A (CoA) metabolism, and (3) histidine metabolism. The signature of altered liver function was apparent in many cytochrome P450-related pathways including bile acids, steroids, xanthines, heme, and phase II detoxification of xenobiotics with the largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8-fold more abundant in PTB.Global metabolic profiling of AF revealed alteration in hepatic metabolites involving xenobiotic detoxification and CoA metabolism in PTB. Maternal and/or fetal hepatic function differences may be developmentally related and its contribution PTB as a cause or effect of PTB is still unclear.

Intrapartum asphyxia (IA) as a cause of neonatal encephalopathy (NE) and cerebral palsy (CP) is a concern for obstetric providers due to the significant neonatal sequelae that ensue. CP is a nonprogressive static neuromuscular disorder appearing early after birth that occurs in 2 per 1,000 births. NE is a clinical syndrome of disturbed neurologic function in the first week after birth, and it occurs in 6 per 1,000 live births. Only ∼6% of all term infants diagnosed with CP have a history of NE, and without the development of NE, IA cannot be considered as the sole cause of CP. There are various preconceptional, antepartum, and intrapartum risk factors associated with CP. Obstetric interventions, including various modalities of fetal monitoring and cesarean delivery, have not led to improvement in outcomes or a reduction in the incidence of CP. The goal of this review was to discuss the association of IA with NE and CP in term and near-term infants, with a focus on the diagnosis and risk factors for IA and potential obstetric interventions.

Both mood disorders and thyroid dysfunction are common in pregnancy and the postpartum period and have significant short and long-term implications to the mothers and their infants. Thyroid hormones have a multitude of effects on the central nervous system, undergo significant changes during pregnancy, and it is now widely recognized that disturbances of mood and cognition often emerge in association with putative disturbance of thyroid metabolism in the brain. Several small studies have shown associations between clinical and subclinical thyroid dysfunction and depression during pregnancy or the postpartum period. Unfortunately, this relationship between maternal thyroid dysfunction and perinatal depression is not well studied.

Objective To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. Methods Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM ( n = 2,300). Those with fasting glucose and insulin between 22 and 26 weeks ( n = 717) were analyzed for IR by homeostatic model assessment of IR (normal, ≤ 75th percentile). WHR and BMI were categorized as normal (WHR, 2 ); overweight (WHR, 0.8–0.84; BMI, 25–29.9 kg/m 2 ); and obese (WHR, ≥ 0.85; BMI ≥ 30 kg/m 2 ). Receiver operating characteristic curves and logistic regression models were used. Results Compared with normal, the risks of GDM or IR were higher in obese by BMI or WHR. The subgroup with obesity by WHR but not by BMI had no increased risk of GDM. BMI was a better predictor of IR (area under the curve [AUC]: 0.71 [BMI], 0.65 [WHR], p = 0.03) but similar to WHR for GDM (AUC: 0.68 [BMI], 0.63 [WHR], p = 0.18). Conclusion Increased WHR and BMI in early pregnancy are associated with IR and GDM. BMI is a better predictor of IR compared with WHR. Adding WHR to BMI does not improve its ability to detect GDM or IR.

Objective The objective of the study was to determine the effect of statins on lipopolysaccharide (LPS)-induced inflammatory response in a mouse model of preterm birth (PTB). Study Design Day 15 CD1 mice were randomly allocated to intraperitoneal LPS injection (100 μg) or control. Mice in the LPS group were pretreated, 16 and 2 hours prior, with pravastatin (10 μg/g), simvastatin (10 μg/g), or vehicle control. Animals were sacrificed 6 hours after LPS. Cytokine messenger ribonucleic acid (mRNA) expression in the uterus and cervix, and concentrations in the maternal serum and amniotic fluid (AF) were determined. Results Pravastatin reduced interleukin (IL)-1β and IL-6 mRNA expression in the uterus and cervix, respectively, and serum IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. Simvastatin reduced IL-1β and IL-6 mRNA expressions in the uterus, IL-6 and tumor necrosis factor alpha (TNF-α) in the cervix, and IL-1β, IL-2, IL-12p70, IL-13, TNF-α, GM-CSF, and interferon-γ concentrations in the serum and IL-6 in AF. Conclusion Statins reduce the LPS-induced inflammatory responses in a mouse model of PTB.

We studied the pattern of indeterminate HIV serological tests among pregnant women with follow-up testing in the postpartum period. Medical records of pregnant women were reviewed over a 2-year period. Of 16,596 pregnant women, 127 (0.8%) had positive HIV enzyme-linked immunoassay (ELISA) result. With Western blot (WB) test, 54 (0.33%) were positive, 43 (0.26%) were negative, and 30 (0.18%) were indeterminate. One of the 30 women (3.3%) with indeterminate WB converted to positive WB during pregnancy. White and black women were more likely to have an unconfirmed positive ELISA (indeterminate or negative WB) than Hispanics ( P = 0.021). The positive WB rate for black women was significantly higher ( P < 0.001) than other racial/ethnic groups. The postpartum follow-up testing of 14 women with indeterminate WB varied between 4 to 20 weeks; 16 did not have any postpartum follow-up test. The common bands in indeterminate WB were P24, P18, and nonviral proteins. The pattern of indeterminate WB result and its follow-up was variable during pregnancy and postpartum period. There is a need for development of national standards of care for indeterminate WB mothers and their infants in the postpartum period. Additional studies are needed to determine the cause of indeterminate tests, reducing their occurrence in the testing process, and the optimum time for testing in the postpartum period.

gain, fetal weights, placental weights or number of pups between the RV and control groups. Treatment with RV had no significant effect on baseline myometrial contractility nor on contractility after indomethacin or nifedipine treatment. CONCLUSION: Unlike its effect on vascular smooth muscle, resveratrol does not seem to affect myometrial contractility nor potentiate the effect of tocolytics in pregnant mice.