Kyung Joon Oh

Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta

OBJECTIVEnTo compare the relative predictive values of amniotic fluid (AF) matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and serum C-reactive protein (CRP) for histologic chorioamnionitis and intra-amniotic infection in women with preterm labor or preterm premature rupture of membranes (PROM).nnnSTUDY DESIGNnThis retrospective cohort study included 99 consecutive women with preterm labor or preterm PROM (21-35 weeks gestation) who delivered within 72xa0h of transabdominal amniocentesis. The AF was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas and was assayed for MMP-9 and IL-6 levels. Maternal serum CRP was measured immediately after amniocentesis. The placentas were examined histologically.nnnMAIN OUTCOME MEASURESnhistologic chorioamnionitis and intra-amniotic infection.nnnRESULTSnThe prevalence of histologic chorioamnionitis and a positive AF culture was 44% (44/99) and 28% (28/99), respectively. In predicting intra-amniotic infection, AF MMP-9 had a significantly higher area under the curve (AUC: 0.94 [95% CI, 0.87-0.98]) than AF IL-6 (0.87 [95% CI, 0.78-0.84]; Pxa0<xa00.05) and serum CRP (0.76 [95% CI, 0.66-0.84]; Pxa0<xa00.001) and a higher sensitivity and specificity than serum CRP (Pxa0<xa00.01, respectively). However, in predicting histologic chorioamnionitis, there were no significant differences in AUCs among the three tests (AF MMP-9: 0.78 [95% CI, 0.68-0.85]; AF IL-6: 0.76 [95% CI, 0.66-0.84]; serum CRP: 0.76 [95% CI, 0.66-0.84]). In a sub-analysis of 71 women without intra-amniotic infection, histologic chorioamnionitis was associated with an elevated serum CRP level (Pxa0<xa00.05), but not with the level of AF IL-6 or MMP-9 (Pxa0=xa00.232 and Pxa0=xa00.402, respectively).nnnCONCLUSIONSnThe AF MMP-9 has a better overall diagnostic performance than the AF IL-6 and maternal serum CRP in predicting intra-amniotic infection. However, the serum CRP level obtained up to 72xa0h before delivery appears to be an important marker for early identification of histologic chorioamnionitis in women without intra-amniotic infection.

Predictive value of combined cervicovaginal cytokines and gestational age at sampling for intra‐amniotic infection in preterm premature rupture of membranes

To determine whether interleukin (IL)‐1β, IL‐6, and IL‐8 in cervicovaginal fluid, alone or in combination with clinical risk factors, could predict intra‐amniotic infection in women with preterm premature rupture of membranes (PPROM).

Intra-Amniotic Infection/Inflammation as a Risk Factor for Subsequent Ruptured Membranes after Clinically Indicated Amniocentesis in Preterm Labor

The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) was associated with subsequent ruptured membranes in women with preterm labor and intact membranes who had a clinically indicated amniocentesis. This retrospective cohort study included 237 consecutive women with preterm labor (20-34.6 weeks) who underwent amniocentesis. The clinical and laboratory parameters evaluated included demographic variables, gestational age, C-reactive protein (CRP) and amniotic fluid (AF) white blood cell, interleukin-6 (IL-6) and culture results. IAI was defined as a positive AF culture and/or an elevated AF IL-6 level (>2.6 ng/mL). The primary outcome was ruptured membranes in the absence of active labor occurring within 48 hours of amniocentesis. Preterm premature rupture of membranes subsequently developed in 10 (4.2%) women within 48 hr of amniocentesis. Multivariate analysis demonstrated that only IAI was independently associated with the ruptured membranes occurring within 48 hr of amniocentesis. In the predictive model based on variables assessed before amniocentesis, only CRP level was retained. IAI is an independent risk factor for subsequent ruptured membranes after clinically indicated amniocentesis in preterm labor. Prior to amniocentesis, measurement of serum CRP level can provide a risk assessment for the subsequent development of ruptured membranes after the procedure.

Relationship between maternal serum C-reactive protein, funisitis and early-onset neonatal sepsis.

The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (≥ 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients.

Comparison between sonographic cervical length and Bishop score in preinduction cervical assessment: a randomized trial

To compare sonographically measured cervical length with the Bishop score in determining the requirement for prostaglandin administration for preinduction cervical ripening in nulliparae at term.

Non‐invasive prediction of intra‐amniotic inflammation in women with preterm labor

To develop a model based on non‐invasive variables to predict the probability of intra‐amniotic inflammation in women with preterm labor and intact membranes.

The Relationship Between Cord Blood Cytokine Levels and Perinatal Factors and Retinopathy of Prematurity: A Gestational Age-Matched Case-Control Study

PURPOSEnTo investigate the relationship between cytokine levels in cord blood and perinatal factors and retinopathy of prematurity (ROP) in gestational age-matched, preterm, newborn infants.nnnMETHODSnEach of 20 premature singleton infants with ROP (gestational age < 32 weeks) was matched for gestational age, birth weight, and sex with two control infants without ROP. The concentration of 10 cytokines in cord blood extracted at birth was measured using a multiplex bead array assay. Data on maternal factors, labor and delivery characteristics, and neonatal parameters were also collected from both groups. The variables obtained were compared using the conditional logistic regression model.nnnRESULTSnNo differences in the levels of inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, interferon-γ, and TNF-α) and growth factors (insulin-like growth factor-1 and VEGF) were detected between the two groups. Multivariate conditional logistic regression analysis indicated that elevated maternal leukocyte count on admission and low Apgar scores at 5 minutes were significantly associated with an increased risk of ROP.nnnCONCLUSIONSnCytokine levels in cord blood are not associated with the risk of ROP, whereas elevated maternal blood leukocyte count and low Apgar score are associated with ROP. These data suggest that the determination of cytokine levels in cord blood samples in premature infants may be of little value for predicting ROP.

The change in cervical length over time as a predictor of preterm delivery in asymptomatic women with twin pregnancies who have a normal mid-trimester cervical length.

AIMnTo determine whether or not the change in cervical length (CL) over time is valuable in predicting spontaneous preterm delivery (SPTD) in asymptomatic twin pregnancies with a normal mid-trimester CL (>25 mm).nnnMETHODSnThis was a prospective study including 190 consecutive asymptomatic twin gestations with a CL>25 mm at 20-24 weeks. The women underwent an initial CL measurement at the time of routine ultrasound examination between 20 and 24 weeks gestation, followed 4-5 weeks later by a repeat CL measurement. The primary outcome measure was SPTD at <32 completed weeks gestation. Multicollinearity was a concern in the multivariable model since change in CL and follow-up CL were highly correlated.nnnRESULTSnThe rate of SPTD at <32 weeks was 4.2%. Multiple logistic regression analyses demonstrated that the change in CL and the follow-up CL were significantly associated with SPTD before 32 weeks after adjusting for baseline covariate such as in vitro fertilization. The best cut-off values for the prediction of SPTD at <32 weeks gestation were 13% for the change in CL with a sensitivity of 87.5% and a specificity of 63.2%. There was no significant difference in the area under the receiver operating characteristic curves between the change in CL and the follow-up CL.nnnCONCLUSIONSnA greater change in CL is a good predictor of SPTD in asymptomatic twin pregnancies with a normal mid-trimester CL. However, the change in CL cannot provide data beyond the follow-up CL. In the setting of a normal mid-trimester CL, a follow-up CL measurement should be considered in asymptomatic twin pregnancies.

Non-invasive prediction of intra-amniotic infection and/or inflammation in patients with cervical insufficiency or an asymptomatic short cervix (≤15 mm)

PurposeTo identify non-invasive parameters to predict intra-amniotic infection and/or inflammation (IAI) in patients with cervical insufficiency or an asymptomatic short cervix (≤15xa0mm).MethodsThis retrospective cohort study included 72 asymptomatic women with cervical insufficiency (nxa0=xa054) or an asymptomatic short cervix (nxa0=xa018) at 17–28xa0weeks. Maternal blood was collected for the determination of the C-reactive protein (CRP) level and white blood cell (WBC) count, and sonography was performed to measure the cervical length shortly after amniocentesis. Amniotic fluid (AF) was cultured and interleukin-6 (IL-6) level and WBC count were determined.ResultsThe prevalence of intra-amniotic inflammation and a positive AF culture was 22.2xa0% (16/72) and 8.3xa0% (6/72), respectively. The best cut-off value for AF IL-6 in predicting the presence of intra-amniotic infection was ≥7.6xa0ng/mL and was used to diagnose the presence of intra-amniotic inflammation. Women with intra-amniotic inflammation, regardless of culture results, were at increased risk for preterm delivery and adverse outcomes compared to women without intra-amniotic inflammation. In multivariable regression, CRP was the only non-invasive variable statistically significantly associated with IAI. Moreover, the area under the curves for the CRP and AF WBC were not significantly different.ConclusionsIn women with cervical insufficiency or a short cervix, the risk for IAI can be predicted fairly and non-invasively by measurements of serum CRP. Overall, this non-invasive parameter appears to have similar accuracy to the AF WBC counts for predicting IAI.

The Association of Family History of Premature Cardiovascular Disease or Diabetes Mellitus on the Occurrence of Gestational Hypertensive Disease and Diabetes

Background Gestational hypertensive diseases (GHD) and gestational diabetes mellitus (GDM) increase the risk of cardiovascular disease (CVD) later in life. However, the association between gestational medical diseases and familial history of CVD has not been investigated to date. In the present study, we examined the association between familial history of CVD and GHD or GDM via reliable questionnaires in a large cohort of registered nurses. Methods The Korean Nurses’ Survey was conducted through a web-based computer-assisted self-interview, which was developed through consultation with cardiologists, gynecologists, and statisticians. We enrolled a total of 9,989 female registered nurses who reliably answered the questionnaires including family history of premature CVD (FHpCVD), hypertension (FHH), and diabetes mellitus (FHDM) based on their medical knowledge. Either multivariable logistic regression analysis or generalized estimation equation was used to clarify the effect of positive family histories on GHD and GDM in subjects or at each repeated pregnancy in an individual. Results In this survey, 3,695 subjects had at least 1 pregnancy and 8,783 cumulative pregnancies. Among them, 247 interviewees (6.3%) experienced GHD and 120 (3.1%) experienced GDM. In a multivariable analysis adjusted for age, obstetric, and gynecologic variables, age at the first pregnancy over 35 years (adjusted OR 1.61, 95% CI 1.02–2.43) and FHpCVD (adjusted OR 1.60, 95% CI 1.16–2.22) were risk factors for GHD in individuals, whereas FHH was not. FHDM and history of infertility therapy were risk factors for GDM in individuals (adjusted OR 2.68, 95% CI 1.86–3.86; 1.84, 95% CI 1.05–3.23, respectively). In any repeated pregnancies in an individual, age at the current pregnancy and at the first pregnancy, and FHpCVD were risk factors for GHD, while age at the current pregnancy, history of infertility therapy, and FHDM were risk factors for GDM. Conclusions The FHpCVD and FHDM are significantly associated with GHD and GDM, respectively. Meticulous family histories should be obtained, and women with family histories of these conditions should be carefully monitored during pregnancy.