Anne M. Lynch

Social and cultural barriers to Papanicolaou test screening in an urban population

OBJECTIVE: To define screening behaviors, attitudes, and beliefs regarding cancer and its treatment among women with cervical cancer. METHODS: Between August 2000 and July 2002, 148 consecutive women with invasive cervical cancer were queried about barriers to screening. Women presented to outpatient clinics, emergency departments, or inpatient units of 3 urban hospitals. Two groups of women were identified: those who denied having had a Papanicolaou (Pap) test and those who had recalled having Pap test in the past. Responses were compared using t tests, &khgr;2 tests, and binary logistic regression. RESULTS: The 146 (99%) respondents were predominantly African Americans (50%) or Hispanic (27%). Thirty-six (25%) women reported no prior screening. Women never screened were significantly more likely to be Hispanic (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.4–6.7), recent immigrants (OR 5.7, 95% CI 2.0–16), less educated (OR 3.6, 95% CI 1.6–8.0), and uninsured (OR 3.9, 95% CI 1.6–9.7). They were more likely to lack family support (adjusted OR 3.5, 95% CI 1.1–11) and lack knowledge about their risk for cervical cancer (adjusted OR 2.6, 95% CI 1.1–6.4). Unscreened women displayed fatalistic attitudes, believing cancer is bad luck (adjusted OR 2.6, 95% CI 1.0–6.9) and not wanting to know they had cancer (adjusted OR 3.0, 95% CI 1.0–9.4).. CONCLUSION: We have identified factors and beliefs that are barriers to Pap test screening in urban cervical cancer patients. Further studies should evaluate effects of addressing cultural, cognitive, and financial barriers on Pap test compliance. LEVEL OF EVIDENCE: III

Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study

BACKGROUND Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors. OBJECTIVE We estimated associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) overall and in early pregnancy, midpregnancy, and late pregnancy with neonatal adiposity. DESIGN Participants were 826 women enrolled in a Colorado prebirth cohort who delivered term infants (2010-2013). GWG to 39 wk of gestation was predicted by using mixed models, and early pregnancy, midpregnancy, and late pregnancy rates of GWG (0-17, 17-27, and 27 wk to delivery) were calculated from repeated weight measures. Neonatal body composition was measured by using air-displacement plethysmography ≤3 d after birth. RESULTS Each1-kg/m(2) increase in maternal BMI was associated with increased neonatal fat mass (5.2 g; 95% CI: 3.5, 6.9 g), fat-free mass (7.7 g; 95% CI: 4.5, 10.9 g), and percentage of body fat (0.12%; 95% CI: 0.08%, 0.16%). Each 0.1-kg/wk increase in predicted GWG was associated with increased fat mass (24.0 g; 95% CI: 17.4, 30.5 g), fat-free mass (34.0 g; 95% CI: 21.4, 46.6 g), and percentage of body fat (0.55%; 95% CI: 0.37%, 0.72%). No interaction was detected between BMI and GWG in their effects on neonatal body composition. Early pregnancy, midpregnancy, and late pregnancy rates of GWG were independently associated with fat mass and percentage of body fat. Midpregnancy and late pregnancy GWGs were associated with fat-free mass. An observed GWG that exceeded recommendations was associated with higher neonatal fat mass and fat-free mass but not percentage of body fat relative to adequate GWG. CONCLUSIONS Maternal prepregnancy BMI and GWG, including period-specific GWG, were positively and independently associated with neonatal adiposity. Associations of early and midpregnancy weight gain with neonatal adiposity support the hypothesis that greater maternal weight gain during pregnancy, regardless of prepregnancy BMI, is directly related to offspring adiposity at birth. The Healthy Start study was registered as an observational study at clinicaltrials.gov as NCT02273297.

Neonatal Outcomes After Elective Cesarean Delivery

OBJECTIVE: To examine the outcomes of neonates born by elective repeat cesarean delivery compared with vaginal birth after cesarean (VBAC) in women with one prior cesarean delivery and to evaluate the cost differences between elective repeat cesarean and VBAC. METHODS: We conducted a retrospective cohort study of 672 women with one prior cesarean delivery and a singleton pregnancy at or after 37 weeks of gestation. Women were grouped according to their intention to have an elective repeat cesarean or a VBAC (successful or failed). The primary outcome was neonatal intensive care unit (NICU) admission and measures of respiratory morbidity. RESULTS: Neonates born by cesarean delivery had higher NICU admission rates compared with the VBAC group (9.3% compared with 4.9%, P=.025) and higher rates of oxygen supplementation for delivery room resuscitation (41.5% compared with 23.2%, P<.01) and after NICU admission (5.8% compared with 2.4%, P<.028). Neonates born by VBAC required the least delivery room resuscitation with oxygen, whereas neonates delivered after failed VBAC required the greatest degree of delivery room resuscitation. The costs of elective repeat cesarean were significantly greater than VBAC. However, failed VBAC accounted for the most expensive total birth experience (delivery and NICU use). CONCLUSION: In comparison with vaginal birth after cesarean, neonates born after elective repeat cesarean delivery have significantly higher rates of respiratory morbidity and NICU-admission and longer length of hospital stay. LEVEL OF EVIDENCE: II

Behaviors and perceptions regarding seasonal and H1N1 influenza vaccination during pregnancy.

We examined vaccination rates during pregnancy against both seasonal and pandemic H1N1 influenza and reasons for nonadherence to recommended guidelines during the 2009 through 2010 influenza season. Demographic and vaccination data were collected using a cross-sectional approach. Among 813 postpartum women, 520 (64%) reported receiving the seasonal influenza vaccination and 439 (54%) reported receiving the H1N1 influenza vaccination during pregnancy. Most received vaccinations at their obstetricians office. Major reasons for not receiving vaccination were: not knowledgeable about the vaccine importance (25%), concerns for effects on fetal and maternal health (18% and 9%, respectively), and not knowledgeable about where to obtain vaccination (9%). Reported H1N1 influenza vaccination rates were significantly lower in blacks (37%) compared with non-Hispanic whites, Hispanics, and Asian/other (57%, 59%, and 58%, respectively; P < .0001). Subsequent campaigns for improving vaccination rates in pregnancy should focus on educating patients about vaccine importance and safety.

Dysregulated Complement Activation as a Common Pathway of Injury in Preeclampsia and Other Pregnancy Complications

The complement system protects the host against invading organisms, initiates inflammation and dispose of immune complexes and the products of inflammatory injury. The complement system provides an important link between the innate and adaptive immune systems. Experimental observations suggest that increased complement activation causes and/or perpetuates inflammation during pregnancy. Recent studies suggest a link between complement activation and preeclampsia. Excessive activation or insufficient regulation of complement recruits leukocytes and unleashes potent inflammatory and anti-angiogenic mediators associated with placental insufficiency and maternal endothelial dysfunction characteristic of preeclampsia. We review the animal and human studies that link complement activation and pathogenic events in preeclampsia, present evidence that activation of the complement system is associated with the development of preeclampsia and provides new targets to prevent its complications.

Early elevations of the complement activation fragment C3a and adverse pregnancy outcomes.

OBJECTIVE: To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS: A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS: One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION: Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. LEVEL OF EVIDENCE: II

Predictors of glyburide failure in the treatment of gestational diabetes.

OBJECTIVE: Our objective was to identify among women with gestational diabetes mellitus (GDM) the patient characteristics that predict treatment failure with glyburide. METHODS: Historical cohort of 95 GDM women offered glyburide after dietary failure with defined entry criteria. RESULTS: From November 2000 to May 2005, 118 women had 124 pregnancies and were offered glyburide therapy by the 2 codirectors of our Diabetes Clinic. All but 2 women elected glyburide, and 27 pregnancies were excluded due to criteria defined a priori to the study. A cohort of 95 women with 95 pregnancies were included for analysis. Nineteen percent failed glyburide. Significant predictors of failure were maternal age (34 years compared with 29 years, P = .001), earlier diagnosis of GDM (23 weeks compared with 28 weeks, P = .002), higher gravidity (P = .01) and parity (P = .03), and a higher mean fasting blood glucose (112 compared with 100 mg/dL; P = .045) compared with those successfully treated. After adjustment in the multivariable logistic regression analysis, GDM women diagnosed at a gestational age less than 25 weeks were 8.3 times more likely to fail glyburide compared with those diagnosed after 25 weeks. Maternal and fetal outcomes were favorable with a cesarean delivery rate of 25% and macrosomia rate of 7%. CONCLUSION: Glyburide was more likely to fail in women diagnosed earlier in pregnancy, of older age and multiparity, and with higher fasting glucoses, suggesting that earlier glucose intolerance and a reduced capacity to respond to an insulin secretagogue may distinguish this group. The time for glyburide as an alternative treatment has come; however, it should be prescribed after careful consideration of these patient characteristics to minimize the likelihood of failure. LEVEL OF EVIDENCE: II-2

The interrelationship of complement‐activation fragments and angiogenesis‐related factors in early pregnancy and their association with pre‐eclampsia

Please cite this paper as: Lynch A, Murphy J, Gibbs R, Levine R, Giclas P, Salmon J, Holers V. The interrelationship of complement‐activation fragments and angiogenesis‐related factors in early pregnancy and their association with pre‐eclampsia. BJOG 2010; 117:456–462.

Preeclampsia in multiple gestation: the role of assisted reproductive technologies.

OBJECTIVE To estimate the relationship of assisted reproductive technologies and ovulation‐inducing drugs with preeclampsia in multiple gestations. METHODS This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. RESULTS Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty‐nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P < .05 level. CONCLUSION Women who conceive multiple gestations through assisted reproductive technologies have a 2.1‐fold higher risk of preeclampsia than those who conceive spontaneously.

A Randomised Trial to Evaluate the Effects of Low‐dose Aspirin in Gestation and Reproduction: Design and Baseline Characteristics

BACKGROUND Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses. METHODS We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period. RESULTS There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >