Sonja A. Rasmussen

H1N1 2009 influenza virus infection during pregnancy in the USA

BACKGROUND Pandemic H1N1 2009 influenza virus has been identified as the cause of a widespread outbreak of febrile respiratory infection in the USA and worldwide. We summarised cases of infection with pandemic H1N1 virus in pregnant women identified in the USA during the first month of the present outbreak, and deaths associated with this virus during the first 2 months of the outbreak. METHODS After initial reports of infection in pregnant women, the US Centers for Disease Control and Prevention (CDC) began systematically collecting additional information about cases and deaths in pregnant women in the USA with pandemic H1N1 virus infection as part of enhanced surveillance. A confirmed case was defined as an acute respiratory illness with laboratory-confirmed pandemic H1N1 virus infection by real-time reverse-transcriptase PCR or viral culture; a probable case was defined as a person with an acute febrile respiratory illness who was positive for influenza A, but negative for H1 and H3. We used population estimates derived from the 2007 census data to calculate rates of admission to hospital and illness. FINDINGS From April 15 to May 18, 2009, 34 confirmed or probable cases of pandemic H1N1 in pregnant women were reported to CDC from 13 states. 11 (32%) women were admitted to hospital. The estimated rate of admission for pandemic H1N1 influenza virus infection in pregnant women during the first month of the outbreak was higher than it was in the general population (0.32 per 100 000 pregnant women, 95% CI 0.13-0.52 vs 0.076 per 100 000 population at risk, 95% CI 0.07-0.09). Between April 15 and June 16, 2009, six deaths in pregnant women were reported to the CDC; all were in women who had developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. INTERPRETATION Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection. These data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs. FUNDING US CDC.

Zika Virus and Birth Defects — Reviewing the Evidence for Causality

Summary The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and birth outcomes, most notably microcephaly and other serious brain anomalies. To determine whether Zika virus infection during pregnancy causes these adverse outcomes, we evaluated available data using criteria that have been proposed for the assessment of potential teratogens. On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this causal relationship included Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants. Given the recognition of this causal relationship, we need to intensify our efforts toward the prevention of adverse outcomes caused by congenital Zika virus infection. However, many questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes. Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy.

Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study

BACKGROUND Downs syndrome is the most frequently identified cause of mental retardation, but information about mortality and comorbidity in people with Downs syndrome is limited. METHODS We used data from US death certificates from 1983 to 1997 to calculate median age at death and standardised mortality odds ratios (SMORs) for common medical disorders in people with Downs syndrome. FINDINGS Of 17897 people reported to have Downs syndrome, median age at death increased from 25 years in 1983 to 49 years in 1997, an average increase of 1.7 years per year studied (p<0.0001). Median age at death was significantly lower in black people and people of other races than in white people with Downs syndrome. As expected, death certificates with a diagnosis of Downs syndrome were more likely to list congenital heart defects (SMOR 29.1, 95% CI 27.8-30.4), dementia (21.2, 19.6-22.7), hypothyroidism (20.3, 18.5-22.3), or leukaemia (1.6, 1.4-1.8) than were those that did not report Downs syndrome. By contrast, malignant neoplasms other than leukaemia were listed on death certificates of people with Downs syndrome less than one-tenth as often as expected (0.07, 0.06-0.08). A strikingly low SMOR for malignancy was associated with Downs syndrome at all ages, in both sexes, and for all common tumour types except leukaemia and testicular cancer. INTERPRETATION Identification of factors responsible for the racial differences recorded could facilitate further improvement in survival of people with Downs syndrome. Reduced exposure to environmental factors that contribute to cancer risk, tumour-suppressor genes on chromosome 21, or a slower rate of replication or higher likelihood of apoptosis in Downs syndrome cells, could be possible reasons for paucity of cancer in people with Downs syndrome.

The National Birth Defects Prevention Study.

The National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7470 cases and 3821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nations leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.

Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States

CONTEXT Early data on pandemic 2009 influenza A(H1N1) suggest pregnant women are at increased risk of hospitalization and death. OBJECTIVE To describe the severity of 2009 influenza A(H1N1) illness and the association with early antiviral treatment among pregnant women in the United States. DESIGN, SETTING, AND PATIENTS Surveillance of 2009 influenza A(H1N1) in pregnant women reported to the Centers for Disease Control and Prevention (CDC) with symptom onset from April through December 2009. MAIN OUTCOME MEASURES Severity of illness (hospitalizations, intensive care unit [ICU] admissions, and deaths) due to 2009 influenza A(H1N1) among pregnant women, stratified by timing of antiviral treatment and pregnancy trimester at symptom onset. RESULTS We received reports on 788 pregnant women in the United States with 2009 influenza A(H1N1) with symptom onset from April through August 2009. Among those, 30 died (5% of all reported 2009 influenza A[H1N1] influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; relative risk [RR], 6.0; 95% confidence interval [CI], 3.5-10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. Updating these data with the CDCs continued surveillance of ICU admissions and deaths among pregnant women with symptom onset through December 31, 2009, identified an additional 165 women for a total of 280 women who were admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%); CONCLUSIONS Pregnant women had a disproportionately high risk of mortality due to 2009 influenza A(H1N1). Among pregnant women with 2009 influenza A(H1N1) influenza reported to the CDC, early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.

The Contribution of Preterm Birth to Infant Mortality Rates in the United States

OBJECTIVE. Although two thirds of infant deaths in the United States occur among infants born preterm (<37 weeks of gestation), only 17% of infant deaths are classified as being attributable to preterm birth with the standard classification of leading causes of death. To address this apparent discrepancy, we sought to estimate more accurately the contribution of preterm birth to infant mortality rates in the United States. METHODS. We identified the top 20 leading causes of infant death in 2002 in the US linked birth/infant death file. The role of preterm birth for each cause was assessed by determining the proportion of infants who were born preterm for each cause of death and by considering the biological connection between preterm birth and the specific cause of death. RESULTS. Of 27970 records in the linked birth/infant death file for 2002, the 20 leading causes accounted for 22273 deaths (80% of all infant deaths). Among infant deaths attributable to the 20 leading causes, we classified 9596 infant deaths (34.3% of all infant deaths) as attributable to preterm birth. Ninety-five percent of those deaths occurred among infants who were born at <32 weeks of gestation and weighed <1500 g, and two thirds of those deaths occurred during the first 24 hours of life. CONCLUSIONS. On the basis of this evaluation, preterm birth is the most frequent cause of infant death in the United States, accounting for at least one third of infant deaths in 2002. The extreme prematurity of most of the infants and their short survival indicate that reducing infant mortality rates requires a comprehensive agenda to identify, to test, and to implement effective strategies for the prevention of preterm birth.

Emerging Infections and Pregnancy

Immunologic changes of pregnancy may increase susceptibility to certain intracellular pathogens.

Mortality in neurofibromatosis 1: an analysis using U.S. death certificates.

Although neurofibromatosis 1 (NF1) is a relatively common autosomal dominant condition, information about its effect on mortality is limited. We used Multiple-Cause Mortality Files, compiled from U.S. death certificates by the National Center for Health Statistics, for 1983 through 1997. We identified 3,770 cases of presumed NF1 among 32,722,122 deaths in the United States, a frequency of 1/8,700, which is one-third to one-half the estimated prevalence. Mean and median ages at death for persons with NF1 were 54.4 and 59 years, respectively, compared with 70.1 and 74 years in the general population. Results of proportionate mortality ratio (PMR) analyses showed that persons with NF1 were 34 times more likely (PMR=34.3, 95% confidence interval [CI] 30.8-38.0) to have a malignant connective or other soft-tissue neoplasm listed on their death certificates than were persons without NF1. Overall, persons with NF1 were 1.2 times more likely than expected (PMR=1.21, 95% CI 1.14-1.28) to have a malignant neoplasm listed on their death certificates, but the PMR was 6.07 (95% CI 4.88-7.45) for persons who died at 10-19 years of age and was 4.93 (95% CI 4.14-5.82) for those who died at 20-29 years of age. Similarly, vascular disease was recorded more often than expected on death certificates of persons with NF1 who died at <30 years of age (PMR=3.26, 95% CI 1.31-6.71 at age <10 years; PMR=2.68, 95% CI 1.38-4.68 at age 10-19 years; and PMR=2.25, 95% CI 1.46-3.32 at 20-29 years) but not in older persons. This study supports previous findings of decreased life expectancy for persons with NF1 and, within the limitations of death certificates, provides population-based data about NF1 morbidity and mortality that are useful to clinicians caring for patients with NF1.

Decline in the Prevalence of Spina Bifida and Anencephaly by Race/Ethnicity: 1995–2002

Objective. In an effort to reduce the occurrence of neural tube defects (NTDs), folic acid fortification of US enriched grain products was authorized by the Food and Drug Administration in March 1996 and required by January 1998. Fortification has been shown to result in an important decline in the prevalence of spina bifida and anencephaly in the general US population; however, fortifications impact on specific racial/ethnic groups has not been well described. We sought to characterize the decline in the prevalence of spina bifida and anencephaly among specific racial/ethnic groups during the transition to mandatory folic acid fortification in the United States. Methods. Data from 21 population-based birth defects surveillance systems were used to examine trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups for the years 1995–2002. These years were divided into 3 periods: prefortification, optional fortification, and mandatory fortification. Race/ethnicity was defined as Hispanic, non-Hispanic white, and non-Hispanic black. Prevalence ratios were calculated for each racial/ethnic group by dividing the prevalence from the mandatory fortification period by the prevalence in the prefortification period. Results. The study included data on 4468 cases of spina bifida and 2625 cases of anencephaly. The prevalence of spina bifida and anencephaly was highest among Hispanic births, followed by non-Hispanic white births, with the lowest prevalence among non-Hispanic black births. Significant declines in spina bifida and anencephaly were observed among Hispanic births and non-Hispanic white births. The prevalence ratio for non-Hispanic black births was of borderline significance for spina bifida and was not significant for anencephaly. Conclusions. The results of this study suggest that folic acid fortification is associated with significant decreases in the prevalence of spina bifida and anencephaly among non-Hispanic white and Hispanic births. The magnitude of the reduction was similar between these 2 groups and was more pronounced for spina bifida than for anencephaly. The decline in the prevalence of spina bifida and anencephaly among non-Hispanic black births did not reach statistical significance. Efforts to increase folic acid consumption for the prevention of NTDs in pregnancies among women of all races/ethnicities should be continued, and studies to identify and elucidate other risk factors for NTDs are warranted.

Maternal obesity and risk of neural tube defects: a metaanalysis

We conducted a metaanalysis of published evidence on the relationship between maternal obesity and the risk of neural tube defects (NTDs). Eligible studies were identified from 3 sources: (1) PubMed search of articles that were published from January 1980 through January 2007, (2) reference lists of publications that were selected from the PubMed search, and (3) reference lists of review articles on obesity and maternal outcomes that were published from January 2000 through January 2007. Twelve studies met inclusion criteria. A Bayesian random effects model was used for the metaanalysis and metaregression. Unadjusted odds ratios for an NTD-affected pregnancy were 1.22 (95% CI, 0.99-1.49), 1.70 (95% CI, 1.34-2.15), and 3.11 (95% CI, 1.75-5.46) among overweight, obese, and severely obese women, respectively, compared with normal-weight women. None of the study characteristics included in the metaregression analysis affected the results significantly. Maternal obesity is associated with an increased risk of an NTD-affected pregnancy.