Nancy L. Stanwood

Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function

STUDY QUESTIONnWhat is the effect of pravastatin on antiphospholipid antibody (aPL) modulation of human first trimester trophoblast function?nnnSUMMARY ANSWERnPravastatin does not prevent the effects of aPL on human first trimester trophoblast cell function.nnnWHAT IS KNOWN ALREADYnAntiphospholipid syndrome (APS) is associated with recurrent pregnancy loss and late pregnancy complications, such as pre-eclampsia, owing to direct targeting of the placenta by aPL. While treatment with heparin reduces the rate of pregnancy loss, the risk for severe pre-eclampsia remains high. Thus, there is a need to find alternative treatments for the prenatal management of patients with APS. Statins have recently been shown to prevent aPL-mediated fetal loss in mice but their effects on a human pregnancy model of APS have not yet been studied.nnnDESIGN, DATA COLLECTION, METHODSnThe human first trimester trophoblast cell line, HTR8, and human first trimester trophoblast primary cultures were incubated with or without a mouse anti-human beta 2 glycoprotein I (β(2)GPI) monoclonal antibody in the presence or absence of pravastatin. Cytokine and angiogenic factor secretion were measured by enzyme-linked immunosorbent assay and multiplex analysis. Cell migration was measured using a colorimetric two-chamber migration assay.nnnMAIN FINDINGSnUsing the human first trimester trophoblast cell line, HTR8, pravastatin significantly augmented, compared with no treatment, aPL-dependent secretion of interleukin (IL)-8 (P< 0.05), IL-1β (P< 0.05) and soluble endoglin (P< 0.01) but had no effect on aPL-induced up-regulation of vascular endothelial growth factor, placenta growth factor or growth-related oncogene alpha secretion. Furthermore, pravastatin alone limited basal HTR8 cell migration (P< 0.01), and did not mitigate the adverse effect of aPL on trophoblast migration. Pravastatin also had no impact on the secretion of pro-inflammatory cytokines and angiogenic factors by primary human first trimester trophoblast cells exposed to aPL.nnnLIMITATIONS AND WIDER IMPLICATIONS OF THE FINDINGSnWhile our in vitro findings suggest that pravastatin may not be effective in preventing pregnancy complications in patients with APS, the in vivo condition may be more complex, and thus, more studies are needed to determine the effectiveness of pravastatin in the prevention of aPL-associated pregnancy complications in humans.nnnSTUDY FUNDING/COMPETING INTEREST(S)nThis work was supported by the American Heart Association.

Vitamin D Reverses aPL‐induced Inflammation and LMWH‐induced sFlt‐1 Release by Human Trophoblast

Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt‐1 release, an anti‐angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH.

Complications of surgical termination of second-trimester pregnancy in obese versus nonobese women ☆ ☆☆

BACKGROUNDnObesity is becoming increasingly common in obstetric and gynecologic populations, which may affect the safety of surgical termination of pregnancy.nnnSTUDY DESIGNnWe performed a retrospective review of all patients undergoing second-trimester surgical termination of pregnancy by under ultrasound guidance termination between 13 0/7 and 24 0/7 weeks of gestational age (GA) to compare perioperative risks in obese and nonobese women. Complication rates, operative times and anesthesia times were compared between obese [body mass index (BMI) ≥30 kg/m²] and nonobese women (BMI <30).nnnRESULTSnOf 1044 women, 29.0% were obese. The mean complication rate was 6.1% and similar between groups (5.5% nonobese, 7.6% obese, p=.20). Operative times were 4.4 min longer and mean anesthesia times were 5 min longer in obese patients (p<.001 for each). There was a nonsignificant trend toward more complications with gestational ages above 18 weeks (5.5% vs. 7.7%, p=.20). A history of one or more cesarean sections had an independent association with major complications after adjustment for confounders (adjusted odds ratio 4.2, p=.001).nnnCONCLUSIONSnBoth anesthesia and operative times were modestly increased in obese women versus nonobese women undergoing second-trimester surgical termination, without significant differences in complication rates. For patients at advanced GA with prior cesarean delivery, clinicians should be aware of the potential increase in complications as well as increased operative time in obese women, and counsel appropriately.

Potassium Chloride-Induced Fetal Demise A Retrospective Cohort Study of Efficacy and Safety

Induction of fetal demise before second‐trimester termination is performed for a number of reasons. One method for inducing fetal demise is via sonographically guided intracardiac potassium chloride (KCl) injection. We performed a retrospective cohort study to determine the efficacy and safety of intracardiac KCl injection as a method of second‐trimester induced fetal demise.

Pregnancy context and women’s health-related quality of life

OBJECTIVEnThe objective was to quantify the association of pregnancy context and health-related quality of life (HRQoL).nnnSTUDY DESIGNnEnglish- or Spanish-speaking women, aged 16-44, with pregnancies <24 weeks gestation were enrolled in this cross-sectional study between June 2014 and June 2015. Participants completed self-assessments of pregnancy context, including timing, intention, wantedness, desirability, happiness, and planning (measured with the London Measure of Unplanned Pregnancy). HRQoL was measured using the Patient Reported Outcomes Measurement Information System Global Short Form. Associations between measures of pregnancy context and HRQoL scores in the lowest tertile were examined using multivariable logistic regression to adjust for potential confounding variables.nnnRESULTSnWe enrolled 161 participants (mean age=27.2±6.6 years). Only 14% self-identified as White, non-Hispanic; 42% Hispanic; 37% Black, non-Hispanic; and 7% multiracial. Most (79%) participants were unmarried, and 75% were parenting. Mean gestational age was 9±4.6 weeks. In unadjusted models, women reporting mixed feelings about wanting to have a baby, an undesired pregnancy or feeling unhappy about learning of their pregnancy more frequently had low mental and physical HRQoL compared to women reporting wanted, desired, happy pregnancies. Women with an unplanned pregnancy or pregnancy occurring at the wrong time also had lower physical HRQoL than women reporting pregnancies that were planned or happened at the right time. However, after multivariate adjustment, including history of depression, pregnancy contexts were not associated with low mental or physical HRQoL.nnnCONCLUSIONSnAfter adjusting for multiple confounders, pregnancy context is not significantly associated with HRQoL.nnnIMPLICATIONSnThe focus on pregnancy intention in public health programs may not sufficiently assess multidimensional aspects of pregnancy context and may not align with patient-centered outcomes such as HRQoL.

Are pregnancy planning and timing associated with preterm or small for gestational age births

OBJECTIVEnTo investigate whether unplanned or poorly timed pregnancies (self-reported at enrollment) are associated with preterm or small for gestational age births.nnnDESIGNnProspective cohort study.nnnSETTINGnNot applicable.nnnPATIENT(S)nTwo thousand six hundred fifty-four pregnant women <18 weeks estimated gestational age with a singleton pregnancy.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nPreterm and small for gestational age births.nnnRESULT(S)nIn adjusted analyses, pregnancy planning was not statistically significantly associated with preterm (odds ratio [OR] 1.18; 95% confidence interval [CI], 0.85-1.65) or small for gestational age birth (OR 1.17; 95% CI, 0.69-1.97). Similarly, poorly timed pregnancies were not statistically significantly associated with preterm (OR 0.85; 95% CI, 0.53-1.38) or small for gestational age birth (OR 0.92; 95% CI, 0.65-1.29). Combining pregnancy planning (yes/no) and timing (yes/no) into a 4-level category showed no statistically significant association with preterm birth or small for gestational age.nnnCONCLUSION(S)nIn a large cohort with antenatally assessed pregnancy planning and timing, outcome data collected from medical record abstraction, and robust analysis adjusting for multiple confounding factors including maternal demographics, medical conditions, and other risk factors, neither pregnancy planning nor pregnancy timing showed a statistically significant association with preterm or small for gestational age infants. This study improves upon previous analyses that lacked adjustment for confounding and used retrospective self-reporting to assess pregnancy planning and timing, and preterm and small for gestational age births. Findings may differ in higher risk populations with higher prevalence of preterm or small for gestational age births.

Are pregnancy planning and pregnancy timing associated with maternal psychiatric illness, psychological distress and support during pregnancy?

BACKGROUNDnPregnancy planning and timing may be associated with psychiatric illness, psychological distress and support during pregnancy.nnnMETHODSnWe performed secondary analyses of a prospective cohort of 2654 pregnant women evaluating the impact of depression on preterm birth. We used multivariable logistic regression to test associations between pregnancy planning (Was this pregnancy planned? Yes/No) and/or timing (Do you think this is a good time for you to be pregnant?) with Composite International Diagnostic Interview generated psychiatric diagnoses and measures of psychological distress and support.nnnRESULTSn37% and 13% of participants reported an unplanned or poorly timed pregnancy, respectively. Unplanned pregnancies were associated with a Major Depressive Episode (MDE) (adjusted odds ratio (aOR) 1.69, 95%CI 1.23-2.32) and the Cohen Perceived Stress Scales (CPSS) highest quartile (aOR 1.74, 95%CI 1.40-2.16). Poorly timed pregnancies were associated with a MDE (aOR 3.47, 95%CI 2.46-4.91) and the CPSSs highest quartile (aOR 5.20, 95%CI 3.93-6.87). Poorly timed pregnancies were also associated with General Anxiety Disorder (GAD; aOR 1.60, 95%CI 1.07-2.40), and the modified Kendler Social Support Inventorys (MKSSI) lowest quartile (aOR 1.64, 95%CI 1.25-2.16). Psychiatric conditions were strongly associated with planned pregnancies that were subsequently deemed poorly timed (MDE=aOR 5.08, 95%CI 2.52-10.25; GAD=aOR 2.28, 95%CI 1.04-5.03); high CPSS=aOR 6.48, 95%CI 3.59-11.69; and low MKSSI=aOR 3.19, 95%CI 1.81-5.62.nnnLIMITATIONSnParticipant characteristics may limit generalizability of findings.nnnCONCLUSIONSnPregnancy timing was a stronger predictor of maternal psychiatric illness, psychological distress and low social support than pregnancy planning in our cohort.