Breech Presentation in Twins as a Risk Factor for Developmental Dysplasia of the Hip.

INTRODUCTION: Identifying risk factors associated with developmental dysplasia of the hip (DDH) is essential for early diagnosis and treatment. Breech presentation is a major DDH risk factor, possibly because of crowding of the fetus within the uterus. In multifetal pregnancy, fetuses are generally smaller than singletons, which may obscure the effect of breech presentation on fetal hips. Only a few studies have investigated the occurrence of DDH in multifetal pregnancies. In this study, we aimed to evaluate whether the breech presentation is a major risk factor of DDH in twin pregnancies. METHODS: This retrospective study included 491 consecutive live births (after 23+0 weeks gestation) delivered through cesarean section with at least 1 baby with noncephalic presentation in single or twin pregnancies from April 2013 to October 2018. We analyzed the incidence of DDH and its associated factors, including sex, breech, and multifetal pregnancy, with a generalized linear mixed model. RESULTS: The incidence of DDH was 12.5% in singleton with breech presentation, 9.8% in twin-breech presentation, and 0.7% in twin-cephalic presentation. Multivariate analysis showed that singleton-breech presentation (P=0.003), twin-breech presentation (P=0.003), and female sex (P=0.008) were independent risk factors for DDH. CONCLUSION: Breech presentation is an independent risk factor for DDH in twin pregnancies, although twin pregnancy itself is not an independent risk factor for DDH.

The effect of postoperative vaginal progesterone in ultrasound-indicated cerclage to prevent preterm birth.

OBJECTIVES: To compare pregnancy outcomes according to the use of postoperative vaginal progesterone in patients who underwent ultrasound-indicated cerclage. METHODS: This was a retrospective cohort study of 86 consecutive asymptomatic singleton pregnancies who had undergone cerclage because of incidentally found short cervical length under 20 mm through transvaginal ultrasound between 16°/7 and 246/7 weeks' gestational age. Outcomes were compared according to the use of vaginal progesterone after cerclage. Primary outcome measure was preterm delivery < 34 weeks of gestation. RESULTS: (1) The frequency of preterm delivery < 34 weeks of gestation was significantly lower in patients with postoperative vaginal progesterone than those without (2.2 versus 18.4%, p = .021); (2) the median gestational age at delivery in the postoperative vaginal progesterone group was significantly longer than the control group (38.3 weeks (interquartile range, 37.5-39.1 weeks) versus 37.3 weeks (interquartile range 33.9-38.6 weeks), p = .020); (3) Multivariable logistic regression analysis demonstrated the use of vaginal progesterone after cerclage was found to be independently associated with decrease in preterm delivery before 34 weeks (Odds ratio 0.10; 95% confidence interval, 0.01-0.93) and 37 weeks (Odds ratio 0.24; 95% confidence interval, 0.07-0.85). CONCLUSIONS: The use of vaginal progesterone was associated with lower rates of preterm birth before 34 and 37 weeks of gestation in women who underwent ultrasound-indicated cerclage placement.

Subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis in women with spontaneous preterm delivery.

OBJECTIVE: To compare subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis (HCA) in women with spontaneous preterm delivery (SPTD). METHODS: Among 1,706 women who gave birth twice or more at our institution, 138 women delivered spontaneously at preterm (<37.0 weeks). Subsequent deliveries occurred at our institution and placental biopsy results were available. The study population was categorized into 2 groups based on the presence of acute HCA at the time of SPTD: HCA group (n=52) and non-HCA group (n=86). The primary outcome measures were gestational age at delivery, birthweight, and frequency of preterm delivery in subsequent pregnancies. RESULTS: The median gestational age at the time of SPTD was 34.0 weeks (interquartile range [IQR], 28.9-35.3 weeks), and the frequency of acute HCA was 52/138 (38%). There were no differences in gestational age at delivery, birthweight, and frequency of preterm delivery between the HCA group and non-HCA group (median gestational age at delivery, 38.0 weeks (IQR, 36.7-38.8 weeks) in the HCA group vs. 37.9 weeks (IQR, 35.7-39.0 weeks) in the non-HCA group; frequency of preterm delivery, 14/52 (27%) in the HCA group vs. 33/86 (38%) in the non-HCA group; and median birthweight, 3.14 kg (IQR, 2.64-3.45 kg) in the HCA group vs. 2.95 kg (IQR, 2.44-3.36 kg) in the non-HCA group; P>0.1 for all. CONCLUSION: The presence of acute HCA in women at prior SPTD did not significantly affect their subsequent pregnancy outcomes.

Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.

BACKGROUND: Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome. OBJECTIVE: To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation. STUDY DESIGN: The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm3) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation. RESULTS: Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases. CONCLUSION: In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.

Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes.

BACKGROUND: Intra-amniotic infection is present in 10% of patients with an episode of preterm labor, and is a risk factor for impending preterm delivery and neonatal morbidity/mortality. Intra-amniotic inflammation is often associated with intra-amniotic infection, but is sometimes present in the absence of detectable microorganisms. Antibiotic treatment of intra-amniotic infection has traditionally been considered to be ineffective. Intra-amniotic inflammation without microorganisms has a prognosis similar to that of intra-amniotic infection. OBJECTIVE: To determine whether antibiotics can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. MATERIALS AND METHODS: The study population consisted of women who met the following criteria: 1) singleton gestation between 20 and 34 weeks; 2) preterm labor and intact membranes; 3) transabdominal amniocentesis performed for the evaluation of the microbiologic/inflammatory status of the amniotic cavity; 4) intra-amniotic infection and/or intra-amniotic inflammation; and 5) received antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in a subset of patients. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed for Ureaplasma spp. Intra-amniotic infection was defined as a positive amniotic fluid culture or positive polymerase chain reaction, and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count or a positive result of a rapid test for matrix metalloproteinase-8. For this study, the final diagnosis of intra-amniotic inflammation was made by measuring the interleukin-6 concentration in stored amniotic fluid (>2.6 ng/mL). These results were not available to managing clinicians. Treatment success was defined as eradication of intra-amniotic infection and/or intra-amniotic inflammation or delivery ≥37 weeks. RESULTS: Of 62 patients with intra-amniotic infection and/or intra-amniotic inflammation, 50 received the antibiotic regimen. Of those patients, 29 were undelivered for ≥7 days and 19 underwent a follow-up amniocentesis. Microorganisms were identified by culture or polymerase chain reaction of amniotic fluid obtained at admission in 21% of patients (4/19) who had a follow-up amniocentesis, and were eradicated in 3 of the 4 patients. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19), and 1 other patient delivered at term, although resolution of intra-amniotic inflammation could not be confirmed after a follow-up amniocentesis. Thus, resolution of intra-amniotic inflammation/infection or term delivery (treatment success) occurred in 84% of patients (16/19) who had a follow-up amniocentesis. Treatment success occurred in 32% of patients (16/50) with intra-amniotic infection/inflammation who received antibiotics. The median amniocentesis-to-delivery interval was significantly longer among women who received the combination of antibiotics than among those who did not (11.4 days vs 3.1 days: P = .04). CONCLUSION: Eradication of intra-amniotic infection/inflammation after treatment with antibiotics was confirmed in 79% of patients with preterm labor, intact membranes, and intra-amniotic infection/inflammation who had a follow-up amniocentesis. Treatment success occurred in 84% of patients who underwent a follow-up amniocentesis and in 32% of women who received the antibiotic regimen.

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes.

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

Addition of adjuvant progesterone to physical-exam-indicated cervical cerclage to prevent preterm birth.

AIM: The aim of this study was to assess the effect of vaginal progesterone as an adjuvant therapy to physical-exam-indicated cervical cerclage (PEICC). METHODS: This retrospective cohort study included 53 consecutive singleton women who underwent PEICC because of acute cervical insufficiency at 17-24 gestational weeks. The study population was divided into two groups: the adjuvant progesterone group (n = 18) and the non-adjuvant group (n = 35). A 200-mg dose of vaginal micronized natural progesterone was administered after cerclage in the adjuvant progesterone group. Primary outcome measure was spontaneous preterm birth (SPTB) at <36 weeks. RESULTS: The SPTB rate at <36 weeks in the adjuvant group was significantly lower than in the non-adjuvant group (17% vs 51%, P < 0.05). Adjuvant progesterone therapy was significantly associated with a reduction in SPTB at <36 weeks (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.69, P < 0.05) even after adjusting for known covariates, including a visible membrane size of ≥4 cm, gestational age, prior SPTB, and use of amnioreduction. The frequency of SPTB at <32 weeks, birthweight < 2500 g, and neonatal intensive care unit admission was significantly lower in the adjuvant progesterone group than in the non-adjuvant group (P < 0.05 for all). CONCLUSION: Adjuvant vaginal progesterone therapy with PEICC was associated with reductions in SPTB, low birthweight, and neonatal intensive care unit admission.

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

PURPOSE: To identify non-invasive parameters to predict intra-amniotic infection and/or inflammation (IAI) in patients with cervical insufficiency or an asymptomatic short cervix (≤15 mm). METHODS: This retrospective cohort study included 72 asymptomatic women with cervical insufficiency (n = 54) or an asymptomatic short cervix (n = 18) at 17-28 weeks. 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. RESULTS: The prevalence of intra-amniotic inflammation and a positive AF culture was 22.2 % (16/72) and 8.3 % (6/72), respectively. The best cut-off value for AF IL-6 in predicting the presence of intra-amniotic infection was ≥7.6 ng/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. CONCLUSIONS: In 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.

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.

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

OBJECTIVE: To determine whether interleukin (IL)-1ß, 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). DESIGN: A prospective cohort study. SETTING: University teaching hospital. POPULATION: Women with singleton pregnancies presenting PPROM between 20 and 35 weeks of gestation (n = 76). METHODS: Cervicovaginal fluid samples were collected for IL-1ß, IL-6, and IL-8 measurements immediately before amniocentesis. Amniotic fluid obtained by amniocentesis was cultured and the white blood cell count was determined. Clinical risk factors analyzed included demographics and gestational age. Cervicovaginal concentrations of cytokines were measured using a multiplex bead array assay. MAIN OUTCOME MEASURE: A positive amniotic fluid culture. RESULTS: The prevalence of a positive amniotic fluid culture was 46.1% (35/76). Stepwise multivariate regression analysis yielded a model using cervicovaginal IL-6 and gestational age at sampling with the area under the curve (AUC) of 0.807 for predicting intra-amniotic infection. The AUC for this model was significantly higher than either parameter retained in this model but no differences were observed between the AUC of this model based on non-invasive variables, and amniotic fluid white blood cell count using invasive amniocentesis for the prediction of intra-amniotic infection. CONCLUSIONS: Among measured cytokines, the combination of cervicovaginal IL-6 and gestational age appears to be best in predicting intra-amniotic infection and allows for a considerably better accuracy than the use of either factor alone. Overall, this combination performed as well as amniotic fluid WBC count for predicting intra-amniotic infection.

Noninvasive prediction of intra-amniotic infection and/or inflammation in preterm premature rupture of membranes.

OBJECTIVE: To develop a model based on noninvasive parameters to predict the probability of intra-amniotic infection and/or inflammation (IAI) in women with preterm premature rupture of membranes (PPROMs). METHODS: Maternal blood was collected for determination of the C-reactive protein (CRP) level and white blood cell (WBC) count immediately after amniocentesis in 171 consecutive women with PPROMs. Intra-amniotic infection and/or inflammation was defined as a positive amniotic fluid (AF) culture and/or an elevated AF interleukin 6 level (≥2.6 ng/mL). RESULTS: A risk score based on a model including maternal blood CRP, WBC, parity, and gestational age was calculated for each patient. The model was shown to have an adequate goodness of fit (P = .516), and the area under the receiver-operating characteristic curve was 0.848, indicating very good discrimination. CONCLUSION: The noninvasive model based on maternal blood CRP, WBC, parity, and gestational age is highly predictive of IAI in women with PPROMs.

Prediction of imminent preterm delivery in women with preterm premature rupture of membranes.

AIMS: To develop a model based on non-invasive clinical parameters to predict the probability of imminent preterm delivery (delivery within 48 h) in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of imminent delivery based on the non-invasive model. METHODS: Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 102 consecutive women with PPROM at 23-33+6 weeks. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. RESULTS: Serum CRP, cervical length, and gestational age were chosen for the non-invasive model (model 1), which has an area under the curve (AUC) of 0.804. When adding AF IL-6 as an invasive marker to the non-invasive model, serum CRP was excluded from the final model (model 2) as not significant, whereas AF IL-6, cervical length, and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. CONCLUSIONS: The non-invasive model based on cervical length, gestational age, and serum CRP is highly predictive of imminent delivery in women with PPROM. However, invasive test results did not add predictive information to the non-invasive model in this setting.

The frequency and clinical significance of twin gestations according to zygosity and chorionicity.

BACKGROUND: Although the clinical importance of chorionicity in twin pregnancies has been studied widely, the significance of perinatal determination of zygosity using molecular genetic analyses remains controversial. The purpose of this study was to determine the frequency and clinical significance of twin gestations according to zygosity and chorionicity in a Korean population. METHODS: We enrolled 569 women who delivered twin newborns (> 24 weeks) at Seoul National University Hospital between 1999 and 2008. Chorionicity was established by histologic examination of placentae. Zygosity was determined with sex of neonates, chorionicity, and DNA analysis of umbilical cord blood. RESULTS: The frequency of dizygotic (DZ) twins was 71.0% (404/569 pairs) based on the opposite sex (238/404 [58.9%]) and DNA analyses (166/404 [41.1%]); that of monozygotic (MZ) twins was 29.0% (165/569), including monochorionic (MC) (72.1% [119/165]) and dichorionic (DC) twins (27.9% [46/165]), which was confirmed by DNA analyses. Among spontaneously conceived twins, the frequency of MZ twins was more than twice that of DZ twins. The risk of low birth weight was 1.8-fold higher among MZDC twins and 1.9-fold higher among MZMC twins than among DZDC twins (p < .05). Bronchopulmonary dysplasia occurred more frequently among MZMC twins than among DZDC twins (adjusted OR 8.42, 95% CI 1.82-39.08, p < .01). However, the frequencies of other neonatal morbidities were not significantly higher in the MZMC group than in the MZDC and DZDC groups. The perinatal mortality rate was 15 per 1000 total births in the DZDC twins, 20 per 1000 total births in the MZDC and 56 per 1000 total births in the MZMC (p < .01). CONCLUSIONS: Although monozygosity was shown to be a risk factor for perinatal death and accurate determination of zygosity plays a great role in the future consideration of organ transplantation and twin studies, the value of zygosity determination along with chorionicity in relation to overall neonatal morbidity was not definite.