Objective
To create a predictive model for preterm birth (PTB) from available clinical data and serum analytes.
Study Design
Serum analytes, routine pregnancy screening plus cholesterol and corresponding health information were linked to birth certificate data for a cohort of 2699 Iowa women with serum sampled in the first and second trimester. Stepwise logistic regression was used to select the best predictive model for PTB.
Results
Serum screening markers remained significant predictors of PTB even after controlling for maternal characteristics. The best predictive model included maternal characteristics, first trimester total cholesterol (TC), TC change between trimesters and second trimester alpha-fetoprotein and inhibin A. The model showed better discriminatory ability than PTB history alone and performed similarly in subgroups of women without past PTB.
Conclusions
Using clinical and serum screening data a potentially useful predictor of PTB was constructed. Validation and replication in other populations, and incorporation of other measures that identify PTB risk, like cervical length, can be a step towards identifying additional women who may benefit from new or currently available interventions.
Metabolic syndrome is a growing problem globally, and is a contributor to non-communicable diseases such as type II diabetes and cardiovascular disease. The risk of developing specific components of the metabolic syndrome such as obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar has been largely attributed to environmental stressors including poor nutrition, lack of exercise, and smoking. However, large epidemiologic cohorts and experimental animal models support the “developmental origins of adult disease” hypothesis, which posits that a significant portion of the risk for adult metabolic conditions is determined by exposures occurring in the perinatal period. Maternal obesity and the rate of complications during pregnancy such as preterm birth, preeclampsia, and gestational diabetes continue to rise. As our ability to reduce perinatal morbidity and mortality improves the long-term metabolic consequences remain uncertain, pointing to the need for further research in this area.
Regular physical activity has been shown to improve pregnancy outcomes. We sought to identify barriers to exercise during the first trimester of pregnancy. Five hundred forty-nine pregnant women in their first trimester rated barriers to exercise on a scale of 1 (not a barrier) to 5 (a huge barrier) and recorded physical activity (minutes/week). Women were placed into one of three classifications, nonexercisers (zero exercise), infrequent exercisers (<150 minutes/week), or exercisers (≥150 minutes/week). The greatest barriers (mean) were nausea/fatigue (3.0) and lack of time (2.6). Exercisers reported significantly lower barrier levels. Nausea/fatigue was a greater barrier for nonexercisers compared to exercisers (3.6 vs 2.8, p < .001). Focusing education and interventions on these barriers may help pregnant women achieve healthy exercise levels.
Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant morbidity and mortality. Recently, genetic associations have been found in idiopathic pulmonary arterial hypertension. We performed a family-based candidate gene study to examine a genetic association to PPHN and sequenced the BMPR2 gene in 72 individuals. We enrolled 110 families with infants diagnosed with PPHN based on inclusion criteria. After medical chart review, 22 subjects were excluded based on predefined criteria, DNA samples from 88 affected infants and at least one parent were collected and genotyped. Thirty-two single nucleotide polymorphisms (SNPs) in twelve genes involved in vasoconstriction/vasodilation, lung development, surfactant regulation, or vascular endothelial cell function were investigated using family-based association tests. PPHN was significantly (p<0.05) associated with genetic variants in corticotropin releasing hormone receptor 1, CRHR1 (rs4458044, p=9.9×10−5; rs173365, p=0.02) and corticotropin releasing hormone-binding protein, CRHBP (rs10062367, p=0.009 and rs10055255, p=0.003). Association with CRHR1 rs4458044 passed the Bonferroni threshold for significance. No mutations were found in the BMPR2 gene. We describe previously unreported genetic associations between PPHN and CRHR1 and CRHBP. These findings may have implications for further understanding the pathophysiology of PPHN and treatment.
Few published studies have examined the relationship between exercise during pregnancy, quality of life (QOL), and postpartum depressive symptoms in healthy pregnant women. A prospective cohort of 578 healthy pregnant women were followed during their pregnancy through 6 months postpartum. Levels of self-reported exercise and QOL before, during, and following pregnancy were assessed using standardized questionnaires during each trimester of pregnancy and 6 months postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 28 weeks gestation and 6 weeks postpartum. Participants were classified as having "sufficient exercise" if they achieved at least 150 min of exercise per week. Sufficient exercisers reported significantly higher ratings on most domains of QOL during each trimester of pregnancy and in the postpartum follow-up, compared with insufficient exercisers. There were no significant between-group differences in depressive symptoms. In examining the impact of exercise during each trimester, active women who became sedentary during their third trimester demonstrated a decline in their QOL. Achieving recommended levels of exercise during pregnancy was associated with higher QOL during pregnancy and the postpartum in healthy pregnant women. Decreasing the amount of exercise during pregnancy was associated with reduced QOL. These results suggest that it may be important for health care professionals to counsel healthy pregnant women about both the benefits of being physically active during pregnancy, and to provide guidance on how to remain physically active during a healthy pregnancy.
Objective
To determine whether pregnancies resulting in early preterm birth (< 30 weeks) were more likely than term pregnancies to have elevated mid-trimester tumor necrosis factor alpha (TNF-α) levels co-occurring with lipid patterns suggestive of hyperlipidemia.
Study Design
Patterns were examined using stored non-fasted serum samples from 108 California and 734 Iowa singleton pregnancies collected as part of statewide prenatal screening. The frequency of elevated mid-pregnancy serum TNF-α levels and lipid patterns suggestive of hyperlipidemia (e.g. elevated total cholesterol (TC), low-density-lipoproteins (LDLs), or triglycerides (TGs), decreased high-density lipoproteins (HDLs)) (considered independently and by co-occurrence) were compared in pregnancies resulting in early preterm birth to those resulting in term birth using logistic regression models.
Results
While no differences between preterm and term pregnancies were evident when TNF-α or target lipid abnormalities occurred in isolation, early preterm pregnancies were two to four times more likely than term pregnancies to have elevated TNF-α levels co-occurring with indicators of hyperlipidemia (37.5% versus 13.9% in the California sample (adjusted OR 4.0, 95% CI 1.1 – 16.3) and 26.3% versus 14.9% in the Iowa sample (adjusted OR 2.7, 95% CI 1.1 – 6.3)). Observed differences were not explicable to any maternal or infant characteristics.
Conclusion
Pregnancies resulting in early preterm birth were more likely than term pregnancies to have elevated mid-pregnancy TNF-α levels co-occurring with lipid patterns suggestive of hyperlipidemia. Patterns offer clues for further study of the signaling of early parturition in preterm birth.
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