Andreea A. Creanga

Pregnancy-related mortality in the United States, 2006-2010

OBJECTIVE: To update national population-level pregnancy-related mortality estimates and examine characteristics and causes of pregnancy-related deaths in the United States during 2006–2010. METHODS: We used data from the Pregnancy Mortality Surveillance System and calculated pregnancy-related mortality ratios by year and age group for four race–ethnicity groups: non-Hispanic white, non-Hispanic black, Hispanic, and other. We examined causes of pregnancy-related deaths by pregnancy outcome during 2006–2010 and compared causes of pregnancy-related deaths since 1987. RESULTS: The 2006–2010 pregnancy-related mortality ratio was 16.0 deaths per 100,000 live births (20,959,533 total live births). Specific race–ethnicity pregnancy-related mortality ratios were 12.0, 38.9, 11.7, and 14.2 deaths per 100,000 live births for non-Hispanic white, non-Hispanic black, Hispanic, and other race women, respectively. Pregnancy-related mortality ratios increased with maternal age for all women and within all age groups, non-Hispanic black women had the highest risk of dying from pregnancy complications. Over time, the contribution to pregnancy-related deaths of hemorrhage, hypertensive disorders of pregnancy, embolism, and anesthesia complications continued to decline, whereas the contribution of cardiovascular conditions and infection increased. Seven of 10 categories of causes of death each contributed from 9.4% to 14.6% of all 2006–2010 pregnancy-related deaths; cardiovascular conditions ranked first. CONCLUSION: Relative to previous years, during 2006–2010, the U.S. pregnancy-related mortality ratio increased as did the contribution of cardiovascular conditions and infection to pregnancy-related mortality. Although the identification of pregnancy-related deaths may be improving in the United States, the increasing contribution of chronic diseases to pregnancy-related mortality suggests a change in risk profile of the birthing population. LEVEL OF EVIDENCE: II

Severe Maternal Morbidity Among Delivery and Postpartum Hospitalizations in the United States

OBJECTIVES: To propose a new standard for monitoring severe maternal morbidity, update previous estimates of severe maternal morbidity during both delivery and postpartum hospitalizations, and estimate trends in these events in the United States between 1998 and 2009. METHODS: Delivery and postpartum hospitalizations were identified in the Nationwide Inpatient Sample for the period 1998–2009. International Classification of Diseases, 9th Revision codes indicating severe complications were used to identify hospitalizations with severe maternal morbidity and related in-hospital mortality. Trends were reported using 2-year increments of data. RESULTS: Severe morbidity rates for delivery and postpartum hospitalizations for the 2008–2009 period were 129 and 29, respectively, for every 10,000 delivery hospitalizations. Compared with the 1998–1999 period, severe maternal morbidity increased by 75% and 114% for delivery and postpartum hospitalizations, respectively. We found increasing rates of blood transfusion, acute renal failure, shock, acute myocardial infarction, respiratory distress syndrome, aneurysms, and cardiac surgery during delivery hospitalizations. Moreover, during the study period, rates of postpartum hospitalization with 13 of the 25 severe complications examined more than doubled, and the overall mortality during postpartum hospitalizations increased by 66% (P<.05). CONCLUSIONS: Severe maternal morbidity currently affects approximately 52,000 women during their delivery hospitalizations and, based on current trends, this burden is expected to increase. Clinical review of identified cases of severe maternal morbidity can provide an opportunity to identify points of intervention for quality improvement in maternal care. LEVEL OF EVIDENCE: III

Economic status, education and empowerment: Implications for maternal health service utilization in developing countries

Background Relative to the attention given to improving the quality of and access to maternal health services, the influence of womens socio-economic situation on maternal health care use has received scant attention. The objective of this paper is to examine the relationship between womens economic, educational and empowerment status, introduced as the 3Es, and maternal health service utilization in developing countries. Methods/Principal Findings The analysis uses data from the most recent Demographic and Health Surveys conducted in 31 countries for which data on all the 3Es are available. Separate logistic regression models are fitted for modern contraceptive use, antenatal care and skilled birth attendance in relation to the three covariates of interest: economic, education and empowerment status, additionally controlling for womens age and residence. We use meta-analysis techniques to combine and summarize results from multiple countries. The 3Es are significantly associated with utilization of maternal health services. The odds of having a skilled attendant at delivery for women in the poorest wealth quintile are 94% lower than that for women in the highest wealth quintile and almost 5 times higher for women with complete primary education relative to those less educated. The likelihood of using modern contraception and attending four or more antenatal care visits are 2.01 and 2.89 times, respectively, higher for women with complete primary education than for those less educated. Women with the highest empowerment score are between 1.31 and 1.82 times more likely than those with a null empowerment score to use modern contraception, attend four or more antenatal care visits and have a skilled attendant at birth. Conclusions/Significance Efforts to expand maternal health service utilization can be accelerated by parallel investments in programs aimed at poverty eradication (MDG 1), universal primary education (MDG 2), and womens empowerment (MDG 3).

Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.

OBJECTIVE: To examine 2009 H1N1 influenza illness severity and the effect of antiviral treatment on the severity of illness among pregnant women. METHODS: We abstracted medical records from hospitalized pregnant (n=62) and nonpregnant (n=74) women with laboratory-confirmed 2009 H1N1 influenza in New York City, May through June 2009. We compared characteristics of pregnant and nonpregnant women and of severe and moderate influenza illness among pregnant women, with severe defined as illness resulting in intensive care admission or death. RESULTS: The 2009 H1N1 hospitalization rate was significantly higher among pregnant than nonpregnant women (55.3 compared with 7.7 per 100,000 population). Eight pregnant (including two deaths) and 16 nonpregnant (including four deaths) cases were severe. Pregnant women represented 6.4% of hospitalized cases and 4.3% of deaths caused by 2009 H1N1 influenza. Only 1 in 30 (3.3%) pregnant women who received oseltamivir treatment within 2 days of symptom onset had severe illness compared with 3 of 14 (21.4%) and four of nine (44.4%) pregnant women who started treatment 3–4 days and 5 days or more after symptom onset, respectively (P=.002 for trend). Severe and moderate 2009 H1N1 influenza illness occurred in all pregnancy trimesters, but most women (54.8%) were in the third trimester. Twenty-two women delivered during their influenza hospitalization, and severe neonatal outcomes (neonatal intensive care unit admission or death) occurred among five of six (83.3%) women with severe illness compared with 2 of 16 (12.5%) women with moderate illness (P=.004). CONCLUSION: Our findings highlight the potential for severe illness and adverse neonatal outcomes among pregnant 2009 H1N1 influenza-infected women and suggest the benefit of early oseltamivir treatment. LEVEL OF EVIDENCE: II

Low use of contraception among poor women in Africa: an equity issue

OBJECTIVE To examine the use of contraception in 13 countries in sub-Saharan Africa; to assess changes in met need for contraception associated with wealth-related inequity; and to describe the relationship between the use of long-term versus short-term contraceptive methods and a womans fertility intentions and household wealth. METHODS The analysis was conducted with Demographic and Health Survey data from 13 sub-Saharan African countries. Wealth-related inequities in the use of contraception were calculated using household wealth and concentration indices. Logistic regression models were fitted for the likelihood of using a long-term contraceptive method, with adjustments for: wealth index quintile, fertility intentions (to space births versus to stop childbearing), residence (urban/rural), education, number of living children, marital status and survey year. FINDINGS The use of contraception has increased substantially between surveys in Ethiopia, Madagascar, Mozambique, Namibia and Zambia but has declined slightly in Kenya, Senegal and Uganda. Wealth-related inequalities in the met need for contraception have decreased in most countries and especially so in Mozambique, but they have increased in Kenya, Uganda and Zambia with regard to spacing births, and in Malawi, Senegal, Uganda, the United Republic of Tanzania and Zambia with regard to limiting childbearing. After adjustment for fertility intention, women in the richest wealth quintile were more likely than those in the poorest quintile to practice long-term contraception. CONCLUSION Family planning programmes in sub-Saharan Africa show varying success in reaching all social segments, but inequities persist in all countries.

Use of metformin in polycystic ovary syndrome: A meta-analysis

OBJECTIVE: To update the state of evidence on the efficacy of metformin, used either alone or in combination with clomiphene citrate in women with polycystic ovary syndrome, by examining three outcomes: ovulation, pregnancy, and live birth. Sources of heterogeneity among the published randomized controlled trials are systematically assessed. DATA SOURCES: An electronic literature search was performed using MEDLINE, EMBASE, SCOPUS, CENTRAL, Cochrane, and U.S. Food and Drug Administration databases, restricted to studies conducted on humans and published in English. METHODS OF STUDY SELECTION: Of the 406 potentially relevant articles identified, 17 met criteria for inclusion in the meta-analysis, rendering a total sample of 1,639 women. Study quality was examined in terms of randomization scheme, masking process, adequacy of allocation concealment, statistical power, and loss to follow-up; publication bias was also assessed. Meta-analytic procedures were used to compare metformin with placebo, and metformin plus clomiphene with clomiphene alone, for all study outcomes. Exploratory analyses were conducted to assess differences in treatment effects between clomiphene-resistant and nonresistant patients, obese and nonobese patients, and trials with long and short durations of follow-up. TABULATION, INTEGRATION, AND RESULTS: Metformin improved the odds of ovulation in women with polycystic ovary syndrome when compared with placebo (odds ratio [OR] 2.94; 95% confidence interval [CI] 1.43–6.02; number-needed-to-treat 4.0) and appears more effective for non–clomiphene-resistant women. Metformin and clomiphene increased the likelihood of ovulation (OR 4.39; 95% CI 1.94–9.96; number-needed-to-treat 3.7) and pregnancy (OR 2.67; 95% CI 1.45–4.94; number-needed-to-treat 4.6) when compared with clomiphene alone, especially in clomiphene-resistant and obese women with polycystic ovary syndrome. These treatment effects were greater for trials with shorter follow-up. CONCLUSION: Using all available evidence, this meta-analysis suggests that metformin increases the likelihood of ovulation and, in combination with clomiphene, increases the odds of both ovulation and pregnancy in women with polycystic ovary syndrome.

Maternal Mortality and Morbidity in the United States: Where Are We Now?

This article provides a brief overview of the work conducted by the Division of Reproductive Health at the Centers for Disease Control and Prevention on severe maternal morbidity and mortality in the United States. The article presents the latest data and trends in maternal mortality and severe maternal morbidity, as well as on maternal substance abuse and mental health disorders during pregnancy, two relatively recent topics of interest in the Division, and includes future directions of work in all these areas.

Trends in Ectopic Pregnancy Mortality in the United States: 1980-2007

OBJECTIVE: To estimate trends in ectopic pregnancy mortality and examine characteristics of recently hospitalized women who died as a result of ectopic pregnancy in the United States. METHODS: We used 1980–2007 national birth and death certificate data to calculate ectopic pregnancy mortality ratios (deaths per 100,000 live births) overall and stratified by maternal age and race. We performed nonparametric tests for trend to assess changes in ectopic pregnancy mortality over time and calculated projected mortality ratios for 2013–2017. Ectopic pregnancy deaths among hospitalized women were identified from 1998–2007 Nationwide Inpatient Sample data. RESULTS: Between 1980 and 2007, 876 deaths were attributed to ectopic pregnancy. The ectopic pregnancy mortality ratio declined by 56.6%, from 1.15 to 0.50 deaths per 100,000 live births between 1980–1984 and 2003–2007; at the current average annual rate of decline, this ratio will further decrease by 28.5% to 0.36 ectopic pregnancy deaths per 100,000 live births by 2013–2017. The ectopic pregnancy mortality ratio was 6.8 times higher for African Americans than whites and 3.5 times higher for women older than 35 years than those younger than 25 years during 2003–2007. Of the 76 deaths among women hospitalized between 1998 and 2007, 70.5% were tubal pregnancies; salpingectomy was performed in 80.6% of cases. Excessive hemorrhage, shock, or renal failure accompanied 67.4% of ectopic pregnancy deaths among hospitalized women. CONCLUSION: Despite a significant decline in ectopic pregnancy mortality since the 1980s, age disparities, and especially racial disparities, persist. Strategies to ensure timely diagnosis and management of ectopic pregnancies can further reduce related mortality and age and race mortality gaps.

Racial and ethnic disparities in severe maternal morbidity: a multistate analysis, 2008-2010

OBJECTIVE The purpose of this study was to examine racial and ethnic disparities in severe maternal morbidity during delivery hospitalizations in the United States. STUDY DESIGN We identified delivery hospitalizations from 2008-2010 in State Inpatient Databases from 7 states. We used International Classification of Diseases, 9th Revision, codes to create severe maternal morbidity indicators during delivery hospitalizations. We calculated the rates of severe maternal morbidity that were measured with and without blood transfusion for 5 racial/ethnic groups: non-Hispanic white, non-Hispanic black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women. Poisson regression models were fitted to explore the associations between race/ethnicity and severe maternal morbidity after we controlled for potential confounders. RESULTS Overall, severe maternal morbidity rates that were measured with and without blood transfusion were 150.7 and 64.3 per 10,000 delivery hospitalizations, respectively. Non-Hispanic black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women had 2.1, 1.3, 1.2, and 1.7 times (all P < .05), respectively, higher rates of severe morbidity that were measured with blood transfusion compared with non-Hispanic white women; similar increased rates were observed when severe morbidity was measured without blood transfusion. Other significant positive predictors of severe morbidity were age <20 and ≥30 years, self-pay or Medicaid coverage for delivery, low socioeconomic status, and presence of chronic medical conditions. CONCLUSION Severe maternal morbidity disproportionally affects racial/ethnic minority women, especially non-Hispanic black women. There is a need for a systematic review of severe maternal morbidities at the facility, state, and national levels to guide the development of quality improvement interventions to reduce the racial/ethnic disparities in severe maternal morbidity.

Maternal drug use and its effect on neonates: a population-based study in Washington State.

OBJECTIVE: To estimate the effect of maternal illicit and prescription drug use on neonates in Washington State between 2000 and 2008. METHODS: We used state-linked birth certificate and hospital discharge (mother and neonate) data to calculate prenatal drug exposure and neonatal abstinence syndrome rates, and compared state neonatal abstinence syndrome rates with national-level data from the Nationwide Inpatient Sample. We identified the drugs of exposure, examined predictors of drug exposure and neonatal abstinence syndrome, and assessed perinatal outcomes among drug-exposed and neonatal abstinence syndrome-diagnosed neonates compared with unexposed neonates. RESULTS: Drug exposure and neonatal abstinence syndrome rates increased significantly between 2000 and 2008, neonatal abstinence syndrome rates being consistently higher than national figures (3.3 compared with 2.8 per 1,000 births in 2008; P<.05). The proportion of neonatal abstinence syndrome-diagnosed neonates exposed prenatally to opioids increased from 26.4% in 2000 to 41.7% in 2008 (P<.05). Compared with unexposed neonates, drug-exposed and neonatal abstinence syndrome-diagnosed neonates had a lower mean birth weight, longer birth hospitalization, were more likely to be born preterm, experience feeding problems, and have respiratory conditions (all P<.001). CONCLUSION: Maternal use of illicit and prescription drugs was associated with considerable neonatal morbidity and significantly higher rates of drug exposure and neonatal abstinence syndrome in recent years. Data suggest that opioid analgesics contributed to the increase in prenatal drug exposure and neonatal abstinence syndrome in Washington State. In accordance with current guidelines, our findings emphasize the need for clinicians to screen pregnant women for illicit and prescription drug use and minimize use of opioid analgesics during pregnancy. LEVEL OF EVIDENCE: II