Arthur M. Baker

A Nested Case-Control Study of Midgestation Vitamin D Deficiency and Risk of Severe Preeclampsia

CONTEXT Vitamin D may be important in the pathogenesis of severe preeclampsia. Given the few effective preventive strategies for severe preeclampsia, studies establishing this link are needed so that effective interventions can be developed. OBJECTIVE Our objective was to assess whether midgestation vitamin D deficiency is associated with development of severe preeclampsia. DESIGN AND SETTING We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between January 2004 and November 2008. PATIENTS Participants included women with singleton pregnancies in the absence of any chronic medical illnesses. From an overall cohort of 3992 women, 51 cases of severe preeclampsia were matched by race/ethnicity with 204 women delivering at term with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. MAIN OUTCOME MEASURE The main outcome was severe preeclampsia. RESULTS Midgestation maternal 25(OH)D concentration was lower in women who subsequently developed severe preeclampsia compared with controls [median (interquartile range), 75 (47-107) nmol/liter vs. 98 (68-113) nmol/liter; P = 0.01]. Midgestation maternal 25(OH)D of less than 50 nmol/liter was associated with an almost 4-fold odds of severe preeclampsia (unadjusted odds ratio, 3.63; 95% confidence interval, 1.52-8.65) compared with midgestation levels of at least 75 nmol/liter. Adjustment for known confounders strengthened the observed association (adjusted odds ratio, 5.41; 95% confidence interval, 2.02-14.52). CONCLUSION Maternal midgestation vitamin D deficiency was associated with increased risk of severe preeclampsia. Vitamin D deficiency may be a modifiable risk factor for severe preeclampsia.

First‐trimester maternal vitamin D status and risk for gestational diabetes (GDM) a nested case‐control study

Vitamin D deficiency may contribute to impaired glucose metabolism. There are sparse data regarding vitamin D and the development of gestational diabetes (GDM). The objective of this study was to assess if first‐trimester vitamin D deficiency is more prevalent in women later diagnosed with GDM compared with women with uncomplicated pregnancies.

A nested case-control study of first-trimester maternal vitamin D status and risk for spontaneous preterm birth

We assessed if first-trimester vitamin D deficiency is more prevalent in women who experienced a spontaneous preterm birth compared with women who delivered at term. We conducted a nested case-control study of pregnant women who had previously given blood for first-trimester combined screening for trisomy 21 and subsequently delivered at a tertiary hospital between November 2004 and July 2009. From an overall cohort of 4225 women, 40 cases of spontaneous preterm birth (≥ 23 (0/7) and ≤ 34 (6/7) weeks) were matched by race/ethnicity with 120 women delivering at term (≥ 37 (0/7) weeks) with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. The prevalence of first-trimester maternal vitamin D deficiency [25(OH)D < 50 nmol/L] was comparable among women who subsequently delivered preterm compared with controls (7.5% versus 6.7%, P  = 0.90). The median 25(OH)D level for all subjects was 89 nmol/L (interquartile range, 73 to 106 nmol/L). Seventy-three percent (117/160) of the cohort had sufficient vitamin D levels [25(OH)D ≥ 75 nmol/L]. In a cohort of pregnant women with mostly sufficient levels of first-trimester serum 25(OH)D, vitamin D deficiency was not associated with spontaneous preterm birth.

Obstetric and newborn infant outcomes in human immunodeficiency virus-infected women who receive highly active antiretroviral therapy.

OBJECTIVE Our aim was to examine perinatal outcomes in women who are infected with human immunodeficiency virus (HIV) and who receive highly active antiretroviral therapy compared with the general population. STUDY DESIGN In this retrospective cohort study, we compared 151 HIV-positive and 302 HIV-negative women. We defined highly active antiretroviral therapy as concomitant use of at least 3 antiretroviral drugs. We calculated frequencies and odds ratios for adverse pregnancy outcomes. RESULTS Compared with control subjects, smoking (odds ratio, 4.62; 95% confidence interval [CI], 2.58-8.27), drug abuse (odds ratio, 5.48; 95% CI, 2.21-13.59), and spontaneous preterm birth (adjusted odds ratio, 2.27; 95% CI, 1.22-4.25) were more common among HIV-positive women. HIV-positive women were more likely to deliver a small-for-gestational-age infant, but this was due to higher tobacco and cocaine use. Neonatal outcomes were otherwise similar. CONCLUSION HIV-positive women are at increased risk for preterm birth and lower birthweight infants; therefore, antenatal surveillance should include fetal growth assessment. Highly active antiretroviral therapy use does not increase maternal complications.

Maternal serum dyslipidemia occurs early in pregnancy in women with mild but not severe preeclampsia

OBJECTIVE We sought to determine whether serum lipids at midgestation differ between normotensive women and women developing mild and severe preeclampsia. STUDY DESIGN A case-control study of 50 women with preeclampsia (mild = 26; severe = 24) and 100 women with uncomplicated term deliveries was conducted. Maternal serum collected at 15-20 weeks was used to measure lipid profiles. RESULTS The groups were similar with respect to demographic characteristics. Women with mild preeclampsia had higher triglyceride levels and a higher total cholesterol to high-density lipoprotein ratio than control subjects (200 +/- 79.5 mg/dL vs 164 +/- 56.2 mg/dL; P = .02; and 3.31 +/- 1.06 mg/dL vs 2.91 +/- 0.59; P = .02). Women with severe preeclampsia had lower levels of low-density lipoprotein than control subjects (85.5 +/- 21.3 mg/dL vs 102 +/- 30.0 mg/dL; P = .04) and a less atherogenic lipid profile than control subjects. CONCLUSION Midgestation dyslipidemia is associated with mild but not severe preeclampsia. These findings may aid in elucidating the different pathologic processes between mild and severe preeclampsia.

Midgestation Maternal Serum 25-Hydroxyvitamin D Level and Soluble Fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio as Predictors of Severe Preeclampsia

Recent studies have shown that low serum 25-hydroxyvitamin D (25[OH]D) level is a risk factor for preeclampsia. The clinical significance of in vitro findings that vitamin D regulates vascular endothelial growth factor production is unclear. We sought to determine whether there is an association between midgestation serum 25(OH)D levels and angiogenic factor activity and to compare their predictive value for the development of severe preeclampsia. We conducted a nested case-control study of women with severe preeclampsia (n=41) versus women with uncomplicated term birth (n=123) who had second trimester genetic screening (15–20 weeks). Using banked frozen serum, we measured levels of 25(OH)D, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, and placental growth factor and compared their correlations and predictive values. We found no correlation between serum 25(OH)D and angiogenic factors levels. 25(OH)D alone was comparable to vascular endothelial growth factor and soluble fms-like tyrosine kinase 1/placental growth factor ratio as a predictive marker for severe preeclampsia. A composite of both 25(OH)D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio was more predictive than either alone (area under curve: 0.83 versus 0.74 and 0.67, respectively). In conclusion, combining midpregnancy 25(OH)D level with soluble fms-like tyrosine kinase 1/placental growth factor ratio provides a better prediction for the development of severe preeclampsia.

Prevalence of Epstein-Barr virus reactivation in pregnancy.

Recent evidence suggests a link between Epstein-Barr virus (EBV) reactivation and chronic stress in nonpregnant adults, possibly due to decreased cellular immune response. Our objective was to determine the prevalence of EBV seropositivity in a diverse cohort of pregnant women and whether maternal demographic characteristics were associated with EBV reactivation. In this cross-sectional study, we evaluated midpregnancy serum specimens from 64 healthy pregnant women for presence of EBV viral capsid antigen, EBV nuclear antigen, and EBV early antigen. The subjects were reported as EBV seronegative, EBV seropositive with reactivation, and EBV seropositive without reactivation. The maternal demographics of the seropositive women with EBV reactivation were compared with their nonreactivated counterparts. Chi-square and Student T test were used for statistical analysis. In our pregnant cohort, 63 (98%) of the 64 women were EBV seropositive. Among these seropositive women, 22 (35%) women demonstrated EBV reactivation in pregnancy. EBV reactivation was not associated with maternal age, race, parity, or insurance type. In our diverse pregnant cohort, 98% of women analyzed were EBV seropositive with 35% demonstrating EBV reactivation in the pregnancy by the second trimester. The pathophysiology and clinical implications of EBV reactivation during pregnancy need further study.

Do pregnant women with depression have a pro‐inflammatory profile?

We tested the hypothesis that maternal depression is associated with a pro‐inflammatory state in pregnancy.

Maternal depression and epstein-barr virus reactivation in early pregnancy

OBJECTIVE: Recent evidence suggests a link between Epstein-Barr virus reactivation and chronic stress due to decreased cellular immune responses. Maternal depression complicates 10% to 20% of pregnancies and is accompanied by stress. We sought to estimate the association of Epstein-Barr virus reactivation with depression in pregnancy. METHODS: In this cohort study, prevalence of Epstein-Barr virus reactivation was compared between 100 pregnant women with depression before pregnancy and a computer-generated referent group of 100 healthy women not known to be depressed. We included only those women with documented Diagnostic and Statistical Manual of Mental Disorders depression diagnoses in the current pregnancy. Serum samples were analyzed for presence of Epstein-Barr virus viral capsid antigen, nuclear antigen, and early antigen antibodies. Epstein-Barr virus reactivation was defined by presence of viral capsid antigen or nuclear antigen immunoglobulin (Ig) G, along with early antigen IgG, viral capsid antigen IgM, or both early antigen IgG and viral capsid antigen IgM. RESULTS: Maternal demographics were similar between the groups except for older age (34.1 compared with 32.7 years, P=.05), and lower body mass index (27.3 compared with 28.9, P=.03) among the depressed individuals. Ninety-five percent of the women were seropositive for Epstein-Barr virus. Women with depression were more likely to have Epstein-Barr virus reactivation (48% compared with 30%, P=.01) when compared with referent participants. Epstein-Barr virus reactivation remained associated with maternal depression (adjusted odds ratio 1.97, 95% confidence interval 1.10–3.77, P=.03) after controlling for potential confounders. CONCLUSION: Women with depression have higher prevalence of Epstein-Barr virus reactivation, possibly due to increased stress. LEVEL OF EVIDENCE: II

Risk Factors for Uteroplacental Vascular Compromise and Inflammation

OBJECTIVE The purpose of this study was to identify potentially modifiable risk factors of placental injury that reflect maternal uteroplacental vascular compromise (UPVC) and acute and chronic placental inflammation. STUDY DESIGN A prospective epidemiologic study was conducted. A total of 1270 placentas were characterized by gross and microscopic examination. Placental pathologic condition was coded for features of amniotic fluid infection syndrome (AFIS), chronic villitis, UPVC, and fetal vascular obstructive lesions. Odds ratios between UPVC, the acute and the chronic inflammatory lesions, and risk factors of interest were calculated. RESULTS After adjustment for confounders, we found that women with a history of preterm birth had 1.60 times the odds of chronic inflammation (95% CI, 1.10, 2.55). Women with a previous elective termination had 3.28 times the odds of acute inflammation (95% CI, 1.89, 5.70). The odds of chronic villitis increased with parity; the odds of AFIS decreased with parity. CONCLUSION We have identified several predictors of UPVC, AFIS, and chronic villitis. Further studies are needed to examine whether interventions to alter UPVC, AFIS, and chronic villitis will lead to improved pregnancy outcomes.