Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012-13, 2013-14, and 2014-15.

INTRODUCTION: A recent study reported an association between inactivated influenza vaccine (IIV) and spontaneous abortion (SAB), but only among women who had also been vaccinated in the previous influenza season. We sought to estimate the association between IIV administered in three recent influenza seasons and SAB among women who were and were not vaccinated in the previous influenza season. METHODS: We conducted a case-control study over three influenza seasons (2012-13, 2013-14, 2014-15) in the Vaccine Safety Datalink (VSD). Cases (women with SAB) and controls (women with live births) were matched on VSD site, date of last menstrual period, age group, and influenza vaccination status in the previous influenza season. Of 1908 presumptive cases identified from the electronic record, 1236 were included in the main analysis. Administration of IIV was documented in several risk windows, including 1-28, 29-56, and >56 days before the SAB date. RESULTS: Among 627 matched pairs vaccinated in the previous season, no association was found between vaccination in the 1-28 day risk window and SAB (adjusted odds ratio (aOR) 0.9; 95% confidence interval (CI) 0.6-1.5). The season-specific aOR ranged from 0.5 to 1.7 with all CIs including the null value of 1.0. Similarly, no association was found among women who were not vaccinated in the previous season; the season-specific aOR in the 1-28 day risk window ranged from 0.6 to 0.7 and the 95% CI included 1.0 in each season. There was no association found between SAB and influenza vaccination in the other risk windows, or when vaccine receipt was analyzed relative to date of conception. CONCLUSION: During these seasons we found no association between IIV and SAB, including among women vaccinated in the previous season. These findings lend support to current recommendations for influenza vaccination at any time during pregnancy, including the first trimester.

Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010-11 and 2011-12.

INTRODUCTION: Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB). METHODS: We conducted a case-control study over two influenza seasons (2010-11, 2011-12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1-28days before the SAB. RESULTS: The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1-28days was 3.7 (95% CI 1.4-9.4) in 2010-11 and 1.4 (95% CI 0.6-3.3) in 2011-12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season. This effect modification was observed in each season. CONCLUSION: SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.

Trivalent inactivated influenza vaccine and spontaneous abortion.

OBJECTIVE: To estimate the association between spontaneous abortion and influenza vaccine receipt with a case-control study utilizing data from six health care organizations in the Vaccine Safety Datalink. METHODS: Women aged 18-44 years with spontaneous abortion during the autumn of 2005 or 2006 were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes. Cases of spontaneous abortion at 5-16 weeks of gestation were confirmed by medical record review; date of fetal demise was based on ultrasound information when available. Control group individuals with a live birth were individually matched to case group individuals by health care organization and date of last menstrual period (LMP). The primary exposure of interest was influenza vaccination during the 28 days preceding the date of spontaneous abortion of the matched pair. Conditional logistic regression models adjusted for maternal age, health care utilization, maternal diabetes, and parity. RESULTS: Our final analysis included 243 women with spontaneous abortion and 243 matched control group women; 82% of women with spontaneous abortion had ultrasound confirmation of fetal demise. Using clinical diagnosis and ultrasound data, the mean gestational age at fetal demise was 7.8 weeks. Mean ages at LMP of case group women and control group women were 31.7 and 29.3 years, respectively (P<.001). Sixteen women with spontaneous abortion (7%) and 15 (6%) matched control group women received influenza vaccine within the 28-day exposure window. There was no association between spontaneous abortion and influenza vaccination in the 28-day exposure window (adjusted matched odds ratio 1.23, 95% confidence interval 0.53-2.89; P=.63). CONCLUSION: There was no statistically significant increase in the risk of pregnancy loss in the 4 weeks after seasonal inactivated influenza vaccination. LEVEL OF EVIDENCE: II.

Trends in maternal and child health outcomes: where does Wisconsin rank in the national context?

BACKGROUND: The infant mortality rate (IMR), low birth weight (LBW) rate, and first trimester entry into prenatal care (PNC) are indicators that reflect the health of a population. OBJECTIVE: To examine these indicators in Wisconsin from 1979 through 2001 and compare them to those of the United States, looking at trends and relative rank compared with other states. METHODS: Three-year averages for IMR, LBW, and PNC were analyzed for the periods 1979-1981, 1984-1986, 1989-1991, 1994-1996, and 1999-2001 from data sources published by the Centers for Disease Control and Prevention. Wisconsin's rank relative to other states was compared for the overall, black, and white populations. RESULTS: Wisconsin's overall IMR was consistently at, or slightly better than, the national IMR. From 1979-1981 to 1999-2001, the US black IMR decreased by 37.4%, while the Wisconsin black IMR declined 12.4%; thus, Wisconsin's rank among the states fell from third best to 32 among 34 states with a sufficient number of black births. LBW rates for Wisconsin's black population were consistently at least twice that of the white population. In 1979-1981, early entry into PNC for all Wisconsin women (82.9%) was significantly higher than that of the US population (74.1%). Wisconsin's early PNC entry rates improved slightly; as other states also improved, Wisconsin's ranking dropped. Wisconsin's relative ranks for IMR, LBW, and PNC declined for all 3 indicators from 1979-1991 to 1999-2001. DISCUSSION: Birth outcome disparities in Wisconsin pose challenges for physicians, public health, and private agencies; all must collaborate and act to improve health, housing, employment, education, and the social capital and support that makes up the fabric of our society.

Pregnancy-associated deaths and pregnancy-related deaths in Wisconsin, 1998-2001.

BACKGROUND: Although the risk of dying during childbirth or from complications afterward has been greatly reduced during the past 100 years, the current rate of approximately 1 death in 10,000 live births is still too high. The goal of the US Department of Health and Human Services is to reduce this rate by more than half by the year 2010. OBJECTIVE: To present Wisconsin data regarding pregnancy-associated deaths and pregnancy-related deaths. METHODS: Cases in which a woman had died during pregnancy or within 1 year of the end of her pregnancy were identified, and case-specific data were collected. The Wisconsin Maternal Mortality Review Team then conducted systematic reviews of the information, summarized issues related to maternal mortality, considered the relationship to pregnancy and factors of avoidability, and made recommendations to improve maternal health and survival. Finally, pregnancy-associated and pregnancy-related mortality ratios were calculated. RESULTS: From 1998 through 2001, 23 Wisconsin women died as a result of their pregnancy or from complications up to a year later. This gives a Wisconsin pregnancy-related mortality ratio of 8.4 per 100,000 live births. This ratio was higher in African American women and in women who smoked. The primary cause of death was embolic disease. Almost half of the pregnancy-related deaths (48%) occurred during the postpartum period, and nearly one-quarter (22%) were avoidable. CONCLUSIONS: The disparity in pregnancy-related mortality ratios among ethnic groups and the finding of avoidable deaths are areas that should be targeted by health care providers and public health workers. Six areas on which to focus include the following: addressing racial disparities, assuring the performance of autopsies, lifestyle changes related to obesity and smoking, and management of embolic and cardiovascular disease, as well as postpartum hemorrhage.