Determinants of Fetal Inflammatory Exposure at Term
Condition: Maternal-Fetal Relations
Study type: Observational

Summary: 
      The hypothesis of this study is that maternal and fetal biologic variation in the balance
      between pro-inflammatory and anti-inflammatory mediators can be measured by currently
      available techniques. In addition, the investigators hypothesize that a pro-inflammatory
      maternal phenotype increases the risk of fetal exposure to intrauterine hyperthemia and
      inflammatory cytokines; and that intrapartum events, especially known risk factors for fever
      at term such as epidural analgesia and prolonged rupture of membranes, may interact with
      underlying maternal factors to increase fetal exposure to inflammatory cytokines.

      This experiment aims to establish the first large-scale cohort to evaluate biomarkers for
      maternal and fetal inflammation in term pregnancy and to elucidate the relative antepartum
      and intrapartum contributions to fetal inflammation.
    

Detailed description: 
      It has been demonstrated that intrapartum fever >100.4 degrees Fahrenheit is associated with
      increased maternal and fetal levels of interleukin-6 (IL-6) at delivery. Maternal and fetal
      IL-6 levels are highly correlated, and placental transport of cytokines has been
      demonstrated. While intrapartum fever is traditionally attributed to acquired infection
      (chorioamnionitis), our data indicate that the maternal inflammatory balance assessed prior
      to the onset of labor may be a significant determinant of subsequent intrapartum fever. The
      increased risk of neonatal brain injury may be cytokine mediated or may, in part, be
      secondary to increased vulnerability to hypoxic injury in the setting of elevated fetal brain
      temperature.

      The baseline prevalence of intrapartum fever at term is 1-5%. Factors associated with an
      increased risk of intrapartum fever include maternal age, nulliparity (75%), Hispanic race,
      induction and longer labor. However, in recent years, the most potent risk factor for
      intrapartum fever has clearly been epidural analgesia - which is selected for intrapartum
      pain relief by the majority of mothers in the US especially in the first, most painful birth.
      We have demonstrated that the risk of fever after epidural analgesia increases with
      increasing duration of epidural analgesia - therefore, the risk of fever after epidural
      analgesia is largely confined to nulliparous women. Multiparous women deliver shortly after
      the onset of active labor, resulting in a short duration of exposure to epidural analgesia,
      and are not at increased risk. Randomized studies demonstrate that the independent
      contribution of epidural analgesia to intrapartum fever risk is 3 to 7-fold. Rates of
      intrapartum fever >100.4 degrees Fahrenheit in nulliparas with epidural analgesia range from
      14.5% to 33%. Rates at the upper end of this range are observed in large, public hospitals
      with primarily Hispanic populations. Conversely, lower rates are observed at private
      hospitals with primarily Caucasian populations.

      This study will make observations based upon:

        1. 10 mL of blood drawn the day of enrollment

        2. 10 mL of blood drawn upon admission to Labor and Delivery

        3. A sample of spinal fluid if a spinal epidural is chosen by the patient

        4. Blood collected from the placenta and umbilical cord

      In addition, the mother's temperature will be taken every hour during labor.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        600 racially and ethnically diverse nulliparas who present to the Prenatal Wellness Center
        at Cannon Place and Northwoods Clinic with a full term (>37 weeks) pregnancy and who
        deliver in the Labor and Delivery Suite at MUSC Hospital
      
Biospecimen description: 
      Whole blood, blood serum, placenta, spinal fluid (for some subjects)
    
Keywords: Fetal Inflammation; Birth Outcome; Pregnancy