by
Matthew Oster;
Tiffany Riehle-Colarusso;
Regina M. Simeone;
Michelle Gurvitz;
Jonathan R. Kaltman;
Michael McConnell;
Geoffrey L. Rosenthal;
Margaret A. Honein
Congenital heart defects (CHDs) are the most common type of birth defect, affecting ≈1% of births per year.1 Although survival has been improving over time, there remain numerous gaps in the understanding of the public health impact of CHDs across the lifespan. Recognizing that there was “a lack of rigorous epidemiological and longitudinal data on individuals of all ages with congenital heart disease,” the US Congress provided funding through the Appropriations Act of 2012 to the US Centers for Disease Control and Prevention (CDC) to investigate the gaps in understanding of the public health impact of CHDs.2 Given the broad array of possible topics to address with limited resources, the CDC invited experts to a meeting on September 10–11, 2012, to seek individual input on the major gaps in the understanding of CHDs and to suggest public health strategies to address those gaps.
Fifty experts attended the meeting representing diverse specialties and perspectives including medical content (CHDs), methods (public health strategies), and personal experience. The group included persons and stakeholders from varied disciplines (physicians, surgeons, epidemiologists, public health officials, advocates, and patients) with a broad representation of public health, professional, and CHD advocacy organizations (the full list of experts is included in the section).
Prior to the meeting, participants received background information to lay the foundation for the meeting. Participants were asked to attend 1 of 2 live webinars hosted by the CDC to outline the public health framework for congenital heart defects. Participants also received articles covering key topics in public health and congenital heart defects for review on their own prior to the meeting.3–6 Finally, at the initiation of the meeting, background presentations were delivered on the current state of knowledge for each of the 4 key areas: epidemiology, health services, long-term morbidity/mortality, and long-term psychosocial and neurodevelopmental outcomes.
For the major activity of the conference, invitees participated in 1 of 4 focus groups centered on 1 of those key areas. Each group was charged with 3 tasks: (1) identifying the key gaps in public health for CHDs, (2) brainstorming potential strategies to address those gaps, and (3) suggesting a prioritization of the identified gaps and strategies based on their potential impact and feasibility. The results of each group, with notable overlaps, were discussed by the full panel of participants to help guide an overall list of suggested major focus areas. After a large group discussion of the 32 gaps identified, the gaps identified as prioritized, in no particular order, included prevalence of CHDs across the lifespan, risk factors for development of CHDs, long-term outcomes for persons with CHDs, health services delivery for persons with CHDs, and public awareness of the burden and impact of CHDs. As outlined in Table 1, we have synthesized the prioritized gaps and their accompanying strategies into a public health science agenda for CHDs.
by
Robert M. Silver;
Corette B. Parker;
Uma M. Reddy;
Robert Goldenberg;
Donald Coustan;
Donald J. Dudley;
George R. Saade;
Barbara Stoll;
Matthew A. Koch;
Deborah Conway;
Radek Bukowski;
Carol Hogue;
Halit Pinar;
Janet Moore;
Marian Willinger;
D. Ware Branch
Objective
To compare antiphospholipid antibodies in deliveries with and without stillbirth using a multicenter, population-based case-control study of stillbirths and live births.
Methods
Maternal sera were assayed for IgG and IgM anticardiolipin and anti-β2-glycoprotein-I antibodies. Assays were performed in 582 stillbirth deliveries and 1,547 live birth deliveries.
Results
Elevated levels of IgG anticardiolipin and IgG anti-β2-glycoprotein-I antibodies were associated with an approximate threefold increased odds of stillbirth; crude odds ratio (OR) 3.43 (95% confidence interval [CI] 1.79, 6.60) (3.8% versus 1.1%) and OR 3.17 (95% CI 1.30, 7.72) (1.9% versus 0.6%), respectively when all deliveries with stillbirth were compared with all deliveries with live birth. When the subset of stillbirths not associated with fetal anomalies or obstetric complications were compared with term live births, elevated IgG anticardiolipin antibodies were associated with stillbirth (5.0% versus 1.0%) (OR 5.30, 95% CI 2.39–11.76); IgG anti-β2-glycoprotein-I antibodies (1.9% versus 0.6%) had an OR of 3.00 (95% CI 1.01–8.90) and IgM anticardiolipin antibodies (6.0% versus 3.0%) had an OR of 2.03 (95% CI 1.09–3.76). Elevated levels of anticardiolipin and anti-β2-glycoprotein-I antibodies were associated with a threefold to fivefold increased odds of stillbirth.
Conclusions
Our data support consideration of testing for antiphospholipid antibodies in cases of otherwise unexplained stillbirth.
Spontaneous preterm birth (PTB, <37 weeks gestation) is a major public health concern, and children born preterm have a higher risk of morbidity and mortality throughout their lives. Recent studies suggest that fetal DNA methylation of several genes varies across a range of gestational ages (GA), but it is not yet clear if fetal epigenetic changes associate with PTB. The objective of this study is to interrogate methylation patterns across the genome in fetal leukocyte DNA from African Americans with early PTB (241/7–340/7 weeks; N = 22) or term births (390/7–406/7weeks; N = 28) and to evaluate the association of each CpG site with PTB and GA. DNA methylation was assessed across the genome with the HumanMethylation450 BeadChip. For each individual sample and CpG site, the proportion of DNA methylation was estimated. The associations between methylation and PTB or GA were evaluated by fitting a separate linear model for each CpG site, adjusting for relevant covariates. Overall, 29 CpG sites associated with PTB (FDR<.05; 5.7×10−10<p<2.9×10−6) independent of GA. Also, 9637 sites associated with GA (FDR<.05; 9.5×10−16<p<1.0×10−3), with 61.8% decreasing in methylation with shorter GA. GA-associated CpG sites were depleted in the CpG islands of their respective genes (p<2.2×10−16). Gene set enrichment analysis (GSEA) supported enrichment of GA-associated CpG sites in genes that play a role in embryonic development as well as the extracellular matrix. Additionally, this study replicated the association of several CpG sites associated with gestational age in other studies (CRHBP, PIK3CD and AVP). Dramatic differences in fetal DNA methylation are evident in fetuses born preterm versus at term, and the patterns established at birth may provide insight into the long-term consequences associated with PTB.
We previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity. To assess whether antioxidant supplementation would ameliorate endometriosis-associated symptoms, we performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamins E and C) in women with pelvic pain and endometriosis. Fifty-nine women, ages 19 to 41 years, with pelvic pain and history of endometriosis or infertility were recruited for this study. Patients were randomly assigned to 2 groups: vitamin E (1200 IU) and vitamin C (1000 mg) combination or placebo daily for 8 weeks before surgery. Pain scales were administered at baseline and biweekly. Inflammatory markers were measured in the peritoneal fluid obtained from both groups of patients at the end of therapy. Our results indicated that after treatment with antioxidants, chronic pain ("everyday pain") improved in 43% of patients in the antioxidant treatment group (P = 0.0055) compared with the placebo group. In the same group, dysmenorrhea ("pain associated with menstruation") and dyspareunia ("pain with sex") decreased in 37% and 24% patients, respectively. In the placebo group, dysmenorrhea-associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia. There was a significant decrease in peritoneal fluid inflammatory markers, regulated upon activation, normal T-cell expressed and secreted (P ≤ 0.002), interleukin-6 (P ≤ 0.056), and monocyte chemotactic protein-1 (P ≤ 0.016) after antioxidant therapy compared with patients not taking antioxidants. The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid.
Objective
To identify maternal and antenatal factors associated with stillbirths and neonatal deaths in rural Bangladesh.
Study Design
A prospective cohort study is being conducted to evaluate a maternal and child nutrition program in rural Bangladesh. Cases were all stillbirths and neonatal deaths that occurred in the cohort between March 7, 2011 and December 30, 2011. Verbal autopsies were used to determine cause of death. For each case, four controls were randomly selected from cohort members alive at age 3-months. Multivariable logistic regression was used to identify factors associated with these deaths.
Results
Overall, 112 adverse pregnancy outcomes (44 stillbirths, 19/1,000 births; 68 neonatal deaths, 29/1,000 live births) were reported. Of the stillbirths 25 (56.8%) were fresh. The main causes of neonatal death were birth asphyxia (35%), sepsis (28%) and preterm birth (19%). History of bleeding during pregnancy was the strongest risk factor for stillbirths (adjusted odds ratio 22.4 [95% confidence interval 2.5, 197.5]) and neonatal deaths (adjusted odds ratio 19.6 [95% confidence interval 2.1, 178.8]). Adequate maternal nutrition was associated with decreased risk of neonatal death (adjusted odds ratio 0.4 [95% confidence interval 0.2, 0.8]).
Conclusions
Identifying high-risk pregnancies during gestation and ensuring adequate antenatal and obstetric care needs to be a priority for any community-based maternal and child health program in similar settings.
BACKGROUND: Left ventricular noncompaction (LVNC) describes deep trabeculations in the left ventricular (LV) endocardium and a thinned epicardium. LVNC is seen both as a primary cardiomyopathy and as a secondary finding in other syndromes affecting the myocardium such as neuromuscular disorders. The objective of this study is to define the prevalence of LVNC in the Duchenne Muscular Dystrophy (DMD) population and characterize its relationship to global LV function. METHODS: Cardiac magnetic resonance (CMR) was used to assess ventricular morphology and function in 151 subjects: DMD with ejection fraction (EF) > 55% (n = 66), DMD with EF < 55% (n = 30), primary LVNC (n = 15) and normal controls (n = 40). The non-compacted to compacted (NC/C) ratio was measured in each of the 16 standard myocardial segments. LVNC was defined as a diastolic NC/C ratio > 2.3 for any segment. RESULTS: LVNC criteria were met by 27/96 DMD patients (prevalence of 28%): 11 had an EF > 55% (prevalence of 16.7%), and 16 had an EF < 55% (prevalence of 53.3%). The median maximum NC/C ratio was 1.8 for DMD with EF > 55%, 2.46 for DMD with EF < 55%, 1.54 for the normal subjects, and 3.69 for primary LVNC patients. Longitudinal data for 78 of the DMD boys demonstrated a mean rate of change in NC/C ratio per year of +0.36. CONCLUSION: The high prevalence of LVNC in DMD is associated with decreased LV systolic function that develops over time and may represent muscular degeneration versus compensatory remodeling.
Objectives: To study how reproductive risks and perinatal outcomes are associated with postpartum depression treated in specialised healthcare defined according to the International Classification of Diseases (ICD)-10 codes, separately among women with and without a history of depression.
Design: A retrospective population-based case-control study.
Setting: Data gathered from three national health registers for the years 2002-2010.
Participants: All singleton births (n=511 422) in Finland.
Primary outcome measures: Prevalence of postpartum depression and the risk factors associated with it.
Results: In total, 0.3% (1438 of 511 422) of women experienced postpartum depression, the prevalence being 0.1% (431 of 511 422) in women without and 5.3% (1007 of 18 888) in women with a history of depression. After adjustment for possible covariates, a history of depression was found to be the strongest risk factor for postpartum depression. Other strong predisposing factors for postpartum depression were fear of childbirth, caesarean birth, nulliparity and major congenital anomaly. Specifically, among the 30% of women with postpartum depression but without a history of depression, postpartum depression was shown to be associated with fear of childbirth (adjusted OR (aOR 2.71, 95% CI 1.98 to 3.71), caesarean birth (aOR 1.38, 95% CI 1.08 to 1.77), preterm birth (aOR 1.65, 95% CI 1.08 to 2.56) and major congenital anomaly (aOR 1.67, 95% CI 1.15 to 2.42), compared with women with no postpartum depression and no history of depression.
Conclusions: A history of depression was found to be the most important predisposing factor of postpartum depression. Women without previous episodes of depression were at an increased risk of postpartum depression if adverse events occurred during the course of pregnancy, especially if they showed physician-diagnosed fear of childbirth.
Background:Obstetric anal sphincter injury (OASIS) has been identified as a major preventable risk factor for anal incontinence.Objective:Aim was to measure national variation in incidence of OASIS by socioeconomic status (SES).Methods:A retrospective population based case-control study using the data derived from the Finnish Medical Birth Register for the years 1991-2010. A total population of singleton vaginal births was reviewed. We calculated unadjusted incidences of OASIS stratified by SES and vaginal parity, and adjusted risks for OASIS in each social class, after controlling for parity, birthweight, mode of delivery, maternal age and maternal smoking. SES was recorded into five categories based on mother's occupation at time of birth; upper white-collar workers such as physicians, lower white-collar workers such as nurses, blue-collar workers such as cleaners, others such as students, and cases with missing information.Results:Seven per thousand (6,404 of 980,733) singleton births were affected by OASIS. In nulliparae the incidence of OASIS was 18% higher (adjusted OR 1.18 95% CI 1.04-1.34) for upper white-collar workers and 12% higher (adjusted OR 1.12 95% CI 1.02-1.24) for lower white-collar workers compared with blue-collar workers. Among women in these higher SES groups, 40% of the excess OASIS risk was explained by age, non-smoking, birthweight and mode of delivery. Despite the large effect of SES on OASIS, inclusion of SES in multivariable models caused only small changes in estimated adjusted effects for other established risk factors.Conclusions:OASIS at the first vaginal delivery demonstrates a strong positive social gradient. Higher SES is associated with a number of risk factors for OASIS, including higher birthweight and non-smoking, but only 40% of the excess incidence is explained by these known risk factors. Further research should address other underlying causes including differences in lifestyle or environmental factors, and inequalities in healthcare provision.