Anna Palatnik

Association of duration of neuroprotective magnesium sulfate infusion with neonatal and maternal outcomes.

OBJECTIVE: To evaluate the association of duration of magnesium sulfate infusion with stillbirth or death, cerebral palsy, and select adverse maternal and neonatal outcomes. METHODS: This is a secondary cohort analysis of women randomized to receive magnesium sulfate within a previously reported Maternal-Fetal Medicine Units Network prospective clinical trial. The association of antenatal infusion of magnesium sulfate for less than 12 hours, 12–18 hours, and greater than 18 hours on maternal and perinatal outcomes was compared. The primary outcome was cerebral palsy of any severity or death. Secondary outcomes included cerebral palsy, death, and select maternal and neonatal outcomes. Stratified and logistic regression analyses were used. The models were adjusted for race, gestational age at birth, time since last magnesium sulfate, any magnesium sulfate at delivery, and eligibility criteria as appropriate. RESULTS: Of 933 women available for analysis, 356, 341, and 236 received antenatal magnesium sulfate infusion for a total of less than 12 hours, 12–18 hours, or greater than 18 hours, respectively. Any cerebral palsy or death occurred in 39 women (11.7%) who received magnesium sulfate less than 12 hours, 34 women (10.3%) who received 12–18 hours of magnesium sulfate, and 20 women (8.8%) who received greater than 18 hours of magnesium sulfate. There was no difference in death or cerebral palsy among groups (less than 12 hours as reference; adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 0.60–1.77 for 12–18 hours; adjusted OR 1.08, 95% CI 0.57–2.03 for greater than 18 hours). Select maternal adverse drug affects and neonatal morbidities were also similar across groups. CONCLUSION: The duration of antenatal magnesium sulfate infusion is not associated with risk of death or cerebral palsy. The optimal treatment duration needed for maximal neuroprotection remains unknown. LEVEL OF EVIDENCE: II

Induction of labor versus expectant management for women with a prior cesarean delivery

OBJECTIVE Previous studies of induction of labor in the setting of trial of labor after cesarean have compared women undergoing trial of labor after cesarean to those undergoing spontaneous labor. However, the clinically relevant comparison is to those undergoing expectant management. The objective of this study was to compare obstetric outcomes between women undergoing induction of labor and those undergoing expectant management ≥39 weeks of gestation. STUDY DESIGN This was a secondary analysis of data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Cesarean Registry that included women with singleton gestations at a gestational age of ≥39 weeks and a history of 1 low transverse cesarean delivery. Outcomes of induction at 39, 40, and 41 weeks were compared to expectant management beyond each gestational age period using univariable and multivariable analyses. Women with scheduled repeat cesarean deliveries done for the indication of prior cesarean delivery were excluded from the analysis. RESULTS In all, 12,676 women were eligible for analysis. The rate of vaginal birth after cesarean (VBAC) was higher among women undergoing induction of labor at 39 weeks compared to expectant management (73.8% vs 61.3%, P < .001). The risk of uterine rupture also was higher among women undergoing induction of labor at 39 weeks compared to expectant management (1.4% vs 0.5%, P = .006, respectively). In multivariable analysis, induction of labor at 39 weeks remained associated with a significantly higher chance of VBAC and uterine rupture (odds ratio, 1.31; 95% confidence interval, 1.03-1.67; and odds ratio, 2.73; 95% confidence interval, 1.22-6.12, respectively). CONCLUSION Induction of labor at 39 weeks, when compared to expectant management, was associated with a higher chance of VBAC but also of uterine rupture.

What is the optimal follicular size before triggering ovulation in intrauterine insemination cycles with clomiphene citrate or letrozole? An analysis of 988 cycles

OBJECTIVE To determine the optimal size of the leading follicle before human chorionic gonadotropin (hCG) administration in cycles with clomiphene citrate (CC) and letrozole, and to examine any differences in the optimal leading follicle size between cycles with CC and letrozole. DESIGN A retrospective study. SETTING University hospital-based reproductive center. PATIENT(S) 1,075 women undergoing intrauterine insemination cycles with CC or letrozole. INTERVENTION(S) Leading follicle diameters and endometrial thickness were recorded 24 hours before hCG administration, together with other cycles parameters, and were compared between pregnant and nonpregnant patients. MAIN OUTCOME MEASURE(S) Leading follicle diameter and intrauterine insemination outcome. RESULT(S) Eight percent of patients (n = 87) were excluded because their leading follicle was less than 18 mm by days 11 to 13. Pregnancy was recorded as clinical pregnancy with fetal heart activity seen at 6- to 7-week transvaginal ultrasound. For both CC and letrozole, higher pregnancy rates were achieved when the leading follicles were in the 23 to 28 mm range. The optimal size of the leading follicle was not statistically significantly different between cycles using CC or letrozole. However, for each endometrial thickness, the optimal follicular size of the leading follicle was different. Each additional millimeter of endometrial thickness increased the optimal follicular size by 0.5 mm. Thicker endometrial lining led to a higher probability of pregnancy. CONCLUSION(S) The optimal size of the leading follicle in ovulation induction with CC and letrozole is similar for both drugs and is closely related to the endometrial thickness.

Association between Cerebral Palsy or Death and Umbilical Cord Blood Magnesium Concentration.

OBJECTIVE This study aims to evaluate whether magnesium sulfate (MgSO4) infusion at the time of delivery or magnesium cord blood concentration is associated with cerebral palsy (CP) or death diagnosed by the age of 2 years. METHODS Secondary analysis of data from a randomized trial of MgSO4 versus placebo for prevention of CP or death among offspring of women with anticipated preterm delivery. This study cohort included singleton, nonanomalous fetuses, whose mothers received MgSO4 as neuroprophylaxis. The primary outcomes were CP or death diagnosed by the age of 2 years. RESULTS A total of 936 neonates (93 with CP or death, 843 controls) were included in the analysis. Infants in the group with CP or death had MgSO4 infusing at delivery at a similar frequency to that of controls (49 [52.7%] vs. 463 [54.9%], p = 0.68). Mean concentrations of cord blood magnesium, available for 596 neonates, also were not different between the two groups (2.7 ± 0.9 vs. 2.6 ± 0.9 mEq/L, p = 0.66, respectively). Multivariable analyses did not alter these findings. CONCLUSION Among the offspring of women exposed to MgSO4, in utero, neither MgSO4 infusion at the time of delivery nor magnesium cord blood concentration is associated with CP or death.

Extramedullary hematopoiesis involving uterus, fallopian tubes, and ovaries, mimicking bilateral tuboovarian abscesses.

Extramedullary hematopoiesis (EMH) is normal during fetal life, but after birth, the presence of EMH is considered to be abnormal. The most common sites for EMH are the liver, the spleen, and paraspinal regions of the thorax; however, it has been reported to involve virtually any organ or tissue. To our knowledge, this is the first reported case of EMH involving the entire upper genital tract, including the uterus, fallopian tubes, and ovaries. A 43-yr-old African American woman presented with a tender pelvic mass and a markedly elevated white blood cell count. Imaging was consistent with bilateral tuboovarian abscesses. Laparotomy and removal of uterus, tubes, and ovaries and bone marrow biopsy confirmed chronic myelogenous leukemia in the chronic phase and EMH in the cervix, endometrium, and ovaries, and no evidence of infection. We believe this to be the first reported case of EMH involving all organs of the upper genital tract presenting in a patient who has chronic myelogenous leukemia but not in blast crisis. This case illustrates the importance of a broad differential diagnosis when managing a patient with a pelvic mass and the value of a multidisciplinary team approach.

Association of Isolated Single Umbilical Artery With Small for Gestational Age and Preterm Birth.

OBJECTIVE: To assess the association of an isolated single umbilical artery with small for gestational age (SGA) and preterm birth. METHODS: In this retrospective cohort study, 219 consecutive women carrying a fetus with an isolated single umbilical artery diagnosed during routine second-trimester anatomic survey were compared with 219 women carrying a fetus with a three-vessel cord. Pregnancies with fetal anomalies or aneuploidy were excluded from the analysis. Outcomes included pregnancy-induced hypertension, gestational age at birth, birth weight, SGA, defined as birth weight less than the 10th percentile, and indicated or spontaneous preterm birth, defined as delivery before 37 weeks of gestation. RESULTS: In univariable analysis, the presence of an isolated single umbilical artery was significantly associated with lower birth weight (3,146 compared with 3,430 g) and with SGA (11.9% compared with 2.7%; P<.001 for each outcome). The rates of pregnancy-induced hypertension (7.3% compared with 1.8%, P=.01) and indicated but not spontaneous preterm delivery (5.5% compared with 0.9%, P=.01 for indicated and 8.2% compared with 4.6%, P=.12 for spontaneous) were also more common in pregnancies with an isolated single umbilical artery. In multivariable analysis controlling for potential confounders, an isolated single umbilical artery remained associated with SGA, pregnancy-induced hypertension, and medically indicated preterm birth (adjusted odds ratio [OR] 3.97, confidence interval [CI] 1.55–10.12; adjusted OR 3.50, CI 1.10–11.18; adjusted OR 7.35, CI 1.60–33.77, respectively). CONCLUSION: Pregnancies complicated by isolated single umbilical artery are at increased risk for SGA and pregnancy-induced hypertension but not for spontaneous preterm birth. LEVEL OF EVIDENCE: II

The relationship between first-trimester subchorionic hematoma, cervical length, and preterm birth

OBJECTIVE The objective of the study was to evaluate the association between a sonographically diagnosed subchorionic hematoma (SCH) in the first trimester and subsequent midtrimester cervical length and preterm birth. STUDY DESIGN In this cohort study, 512 women with an SCH on their first-trimester ultrasound were compared with 1024 women without a first-trimester SCH. All women underwent routine transvaginal cervical length measurement between 18 and 22 weeks. Women with multifetal gestation, cerclage, or a uterine anomaly were excluded. A multivariable linear regression was performed to assess the independent association of SCH with cervical length, and a logistic regression was done to determine whether the presence of SCH was associated with preterm birth independent of the cervical length. RESULTS In a univariable analysis, the presence of a SCH was significantly associated with a shorter mean cervical length as well as a cervical length less than the 10th percentile (4.27 cm vs 4.36 cm, P = .038; 1.9% vs 0.5%, P = .006, respectively). Preterm birth also was more common in women with an SCH (12.5% vs 7.3%, P = .001). Even after adjusting for potentially confounding factors, a significant negative association existed between the presence of an SCH and cervical length (centimeters) (linear regression coefficient, -0.08; 95% confidence interval, -0.17 to -0.005). In a multivariable regression, SCH remained associated with preterm birth, even with cervical length entered into the equation as a covariate (adjusted odds ratio, 1.58; 95% confidence interval, 1.09-2.32). CONCLUSION First-trimester SCH is associated with both a shorter cervical length and preterm birth. Our data suggest, however, that mechanisms other than cervical shortening may be involved in preterm birth among women with SCH.

Association of Early Amniotomy After Foley Balloon Catheter Ripening and Duration of Nulliparous Labor Induction.

OBJECTIVE: To evaluate the association between early amniotomy after ripening with a Foley balloon catheter and duration of labor induction. METHODS: In this retrospective matched cohort study, 546 nulliparous women with a singleton viable gestation undergoing cervical ripening with a Foley balloon catheter were compared based on timing of amniotomy after catheter removal: early (defined as artificial rupture of membranes less than 1 hour after Foley removal) compared with no artificial rupture of membranes in the first hour. Women in the early amniotomy group were matched to women in the control group according to health care provider type, cervical examination after Foley removal, and indication for induction in a one-to-one ratio. Bivariable and multivariable analyses were performed to determine whether early amniotomy was associated with vaginal delivery within 24 hours and other adverse maternal and neonatal outcomes. Cox proportional hazard regression was used to compare time intervals from catheter removal to complete dilation and from catheter removal to delivery. RESULTS: In univariable analysis, the frequency of vaginal delivery within 24 hours of Foley placement was higher in women with early amniotomy (42.9% compared with 33.0%, P=.02). The median time intervals from Foley catheter removal to complete dilation (9.0 hours compared with 12.1 hours) and to delivery (10.6 hours compared with 13.8 hours) were also significantly shorter for women who underwent early amniotomy (P<.001 for both). There were no significant differences in any other adverse maternal or neonatal outcomes. In multivariable analysis, early amniotomy remained associated with higher odds of vaginal delivery within 24 hours and shorter times from catheter removal to complete dilation and to delivery. CONCLUSION: Early amniotomy after Foley balloon catheter removal is associated with shorter duration of labor induction among nulliparous women.

Association among Maternal Obesity, Cervical Length, and Preterm Birth.

Objective The objective of this study was to determine if mid‐trimester cervical length is associated with the inverse relationship between maternal body mass index (BMI) at delivery and spontaneous preterm birth (SPTB). Materials and Methods This was a retrospective cohort of women with a singleton pregnancy without prior SPTB who underwent routine transvaginal cervical length assessment between 18 and 24 weeks. Women were categorized into four BMI groups: (1) 18.5 to 24.9, (2) 25 to 29.9, (3) 30 to 34.9, and (4) ≥ 35 kg/m2. Univariable and multivariable analyses were conducted to determine whether BMI group was associated with SPTB at < 37, 34, or 32 weeks independent of the cervical length. Results Of the 18,100 women in this analysis, 43.5% had a BMI ≥ 30. In univariable analysis, increasing BMI group was associated with longer cervical length but not with cervical length < 10th percentile. SPTB at < 37, 35, and 32 weeks was less common among women with higher BMI. In multivariable regression, a higher BMI group was associated with a lower frequency of SPTB at 37 weeks (adjusted odds ratios [aORs] of 0.64, 0.68, and 0.51), at 34 weeks (aORs of 0.53, 0.54, and 0.31) and at 32 weeks (aORs of 0.47, 0.60, and 0.27) for BMI groups 2 to 4, respectively. This association persisted even when cervical length was entered into the model as a covariate. Conclusion Women with a higher BMI group had longer mid‐trimester cervical length, and correspondingly reduced SPTB. However, the decreased risk of SPTB was not associated with cervical length. The reason for the potential protective effect from prematurity is unknown and its mechanisms require further investigation.

Correction: Identification of a serum-induced transcriptional signature associated with metastatic cervical cancer

Objective Tumor cells that escape local tissue control can convert inflammatory cells from tumor suppressors to tumor promoters. Moreover, soluble immune-modulating factors secreted from the tumor environment can be difficult to identify in patient serum due to their low abundance. We used an alternative strategy to infer a metastatic signature induced by sera of cervical cancer patients. Methods Sera from patients with local and metastatic cervical cancer were used to induce a disease-specific transcriptional signature in cultured, healthy peripheral blood mononuclear cells (PBMCs). An empirical Bayesian method, EBarrays, was used to identify differentially expressed (DE) genes with a target false discovery rate of <5%. Ingenuity Pathway Analysis (IPA) software was used to detect the top molecular and cellular functions associated with the DE genes. IPA and in silco analysis was used to pinpoint candidate upstream regulators, including cancer-related microRNAs (miRNAs). Results We identified enriched pathways in the metastatic cervical group related to immune surveillance functions, such as downregulation of engulfment, accumulation, and phagocytosis of hematopoietic cells. The predicted top upstream genes were IL-10 and immunoglobulins. In silco analysis identified miRNAs predicted to drive the transcriptional signature. Two of the 4 miRNAs (miR-23a-3p and miR-944) were validated in a cohort of women with local and metastatic cervical cancer. Conclusions This study supports the use of a cell-based assay that uses PBMC “reporters” to predict biologically relevant factors in patient serum. Further, disease-specific transcriptional signatures induced by patient sera have the potential to differentiate patients with local versus metastatic disease.