Factors Associated with Progression to Preeclampsia with Severe Features in Pregnancies Complicated by Mild Hypertensive Disorders.

In this retrospective cohort study, we aimed to investigate the variables associated with progression to preeclampsia with severe features in parturients already diagnosed with mild hypertensive disorders of pregnancy. The study was conducted in a single university-affiliated medical center between 2018 and 2020. All women admitted due to hypertensive disorders were included. Data collected was compared between parturients who progressed and did not progress to preeclampsia with severe features. Among 359 women presenting without severe features, 18 (5%) developed severe features, delivered smaller babies at lower gestational age, and with higher rates of cesarean delivery (p < 0.001 for all). Chronic hypertension, maternal diabetes, any previous gestational hypertensive disorder, gestational diabetes, number of hospitalizations, earlier gestational age at initial presentation, and superimposed preeclampsia as the preliminary diagnosis were all associated with preeclampsia progression to severe features. Previous delivery within 2-5 years was a protective variable from preeclampsia progression. Following regression analysis and adjustment to confounders, only gestational age at initial presentation and superimposed preeclampsia remained significant variables associated with progression to severe features (aOR 0.74 (0.55-0.96) and 34.44 (1.07-1111.85), aOR (95% CI), respectively, p < 0.05 for both) with combined ROC-AUC prediction performance of 0.89, 95% CI 0.83-0.95, p < 0.001. In conclusion, according to our study results, early gestational age at presentation and superimposed preeclampsia as the preliminary diagnosis are the only independent factors that are associated with progression to severe features in women already diagnosed with mild hypertensive disorders during pregnancy.

Single Sporadic Deceleration during Reactive Nonstress Test-Clinical Significance and Risk for Cesarean Delivery.

OBJECTIVE: Evidence regarding the clinical significance of a single sporadic variable deceleration (SSD) in reactive non-stress test (NST) is scarce, and optimal management has yet to be established. We aim to evaluate whether SSD during a reactive NST at term is associated with a higher risk for fetal heart rate decelerations during labor and the need for intervention. METHODS: This was a retrospective, case-control study of singleton term pregnancies at one university-affiliated medical center in 2018. The study group consisted of all pregnancies with an SSD in an otherwise reactive NST. For each case, two consecutive pregnancies without SSD were matched in a 1:2 ratio. The primary outcome was the rate of cesarean delivery (CD) due to non-reassuring fetal heart rate monitoring (NRFHRM). RESULTS: 84 women with an SSD were compared to 168 controls. SSD during antenatal fetal surveillance did not increase the rate of CD overall or for NRFHRM (17.9% vs. 13.7% and 10.7% vs. 7.7%, respectively, p > 0.05). Rates of assisted deliveries and maternal and neonatal complications were similar between the groups. CONCLUSIONS: SSD during a reactive NST in term pregnancies is not associated with an increased risk for adverse perinatal outcomes. SSD should not necessarily require induction of labor, and expectant management is a reasonable alternative.

Unintended uterine extension at the time of cesarean delivery - risk factors and associated adverse maternal and neonatal outcomes.

OBJECTIVE: To identify risk factors, maternal and neonatal adverse outcomes related to unintended lower segment uterine extension during cesarean delivery (CD). METHODS: A retrospective cohort analysis in a single, university-affiliated medical center between 1 January 2018 and 31 December 2019. All singleton pregnancies delivered by CD were included. Univariate and multivariate analyses were performed to identify maternal and obstetrical predictors for uterine extension during CD. For secondary outcomes, we assessed the correlation between uterine extension and any adverse maternal or neonatal outcome. Risk factors were analyzed using ROC statistics to measure their prediction performance for a uterine extension. RESULTS: Overall, 1746 (19.3%) CDs were performed during the study period. Of them, 121 (6.9%) CDs were complicated by unintended uterine extension. There was no difference in maternal demographics and clinical data stratified by uterine extension at CD. Uterine extensions were significantly more common following induction of labor, intrapartum fever, premature rupture of membranes, a trial of labor after cesarean, advanced gestational age, emergent CD, and in particular CD during the second stage of labor (37.2% vs. 6.5%) and after failed vacuum extraction (6.6% vs. 1.1%), p < .05 for all. The incidence of postpartum hemorrhage and re-laparotomy did not differ between the groups. Most of the extensions were caudal-directed (40.4%), and were closed by a two-layer closure (92%). Mean extension size was 4.5 ± 1.7 cm. Using multivariable analysis, the only factor that remained significant was CD at the second stage of labor (adjusted odds ratio (aOR) 54.2, 95% CI 4.5-648.9, p = .002), with an area under the ROC curve 0.653 (95% CI 0.595-0.712, p < .001). Emergent CD, body mass index, birth weight, failed vacuum attempt, and trial of labor after cesarean were not significant. For secondary outcomes, an unintended uterine extension was associated with longer operation time, higher estimated blood loss, greater pre- to post-CD hemoglobin difference, increased blood products transfusion, puerperal fever, and longer hospital stay. No clinically significant neonatal adverse outcomes were observed. CONCLUSIONS: In our cohort, second-stage CD was the strongest predictor for an unintended uterine extension. Following uterine extension, women had increased infectious and blood-loss morbidity.

Mild neonatal morbidity in twins by planned mode of delivery: a secondary analysis of the Twin Birth Study.

BACKGROUND: The Twin Birth Study showed no differences in major severe adverse neonatal outcomes between those with planned vaginal delivery and those with planned cesarean delivery. OBJECTIVE: This was a secondary analysis of the Twin Birth Study in which mild neonatal morbidities, not previously reported, were compared between parturients with planned cesarean deliveries and those with planned vaginal delivery in twin births. STUDY DESIGN: This was a secondary analysis of the Twin Birth Study. In this study, women with a twin pregnancy at 32+0/7 to 38+6/7 weeks of gestation with the first twin in cephalic presentation and with an estimated weight between 1500 and 4000 g were randomized to either planned cesarean delivery or planned vaginal delivery. The primary outcome of this study was a composite mild neonatal outcome of respiratory and neurologic morbidities and neonatal intensive care unit admission that were not reported in the original Twin Birth Study at 34+0/7 to 38+6/7 weeks of gestation. A multivariable logistic regression analysis was used to identify factors associated with the composite adverse neonatal outcomes. Neonatal outcomes were further stratified by gestational age at delivery and by actual mode of delivery. RESULTS: A total of 1304 women and 1326 women were randomly assigned to planned cesarean delivery and planned vaginal delivery, respectively. Demographic and obstetrical characteristics were similar between the study groups. The rate of cesarean delivery was 90.1% in the planned cesarean delivery group and 40.1% in the planned vaginal delivery group. There was no significant difference in the primary composite outcome between the groups (10.6% vs 11.3%; P=.45) neither by planned mode of delivery nor by actual mode of delivery. Stratification by gestational age found a lower rate of the primary outcomes at ≥38+0/7 weeks of gestation in the planned cesarean delivery group when compared with the planned vaginal delivery group (4.8% vs 10.8%, respectively; P=.02). Furthermore, a lower risk for some individual outcomes was reported in the planned cesarean delivery group when compared with the planned vaginal delivery group, including intraventricular hemorrhage stage 1 to 2 (0.2% vs 0.6%; P<.05), low Apgar scores (0.8% vs 2.3%; P<.05), pH <7.0 (0.3 vs 1%; P<.05), and assisted ventilation needed at delivery (0.4% vs 0.9%; P<.05). CONCLUSION: In twin deliveries, with the first twin in the cephalic presentation, composite mild neonatal morbidity was not affected by the planned mode of delivery. These findings reinforce the original results of the Twin Birth Study. Nevertheless, an increased composite outcome after 38 weeks' gestation and a higher risk for some individual morbidities in the planned vaginal delivery group might be viewed as a concerning signal for the safety of vaginal delivery in twin deliveries and requires further research.

Greater risk of type 2 diabetes progression in multifetal gestations with gestational diabetes: the impact of obesity.

BACKGROUND: The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE: This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN: A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS: Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION: Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.

Persistence of abnormal uterine artery flow postpartum: Case-control study.

Cohort study of singleton pregnancies with risk factors for placental insufficiency, managed at St. Michael's Hospital in Toronto, Canada. Patients undergone UA Doppler assessment at 18-22 weeks' gestation and 6 weeks postpartum. 15 pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR) (cases) were compared to 17 unaffected pregnancies (controls). Cases with preeclampsia and/or IUGR had higher UA PI at 18-22 weeks than controls. By 6 weeks' postpartum, the corresponding mean values were 2.60 and 2.14 (p = 0.20). This preliminary study suggests a potential different trajectory for physiologic recovery of UA flow after a pregnancy affected by placental insufficiency.

The expression of heparanase in term and preterm human placentas.

PURPOSE: Heparanase is an endo-ß-glucuronidase that cleaves side chains of heparan-sulfate proteoglycans, an integral constituent of the extra cellular matrix. The abundance of heparanase in placental trophoblast cells implies its role in the processes of placentation and trophoblast invasion. This study aims to explore the involvement of heparanase in parturition and preterm deliveries (PTD). METHODS: Sixteen human placentas were collected following singleton spontaneous onset term vaginal deliveries (n = 6), spontaneous onset preterm vaginal deliveries (n = 7) and term elective cesarean sections (n = 3). Placentas were excluded in case of any maternal chronic illness, pregnancy or delivery complications apart from PTD. Placental tissue samples were dissected, homogenized and proteins were extracted. Additionally, cryosections were prepared from the placental tissues. Heparanase expression was evaluated utilizing western blot analysis and immunofluorescence staining using heparanase specific antibodies. Heparanase expression was compared between the study groups qualitatively and quantitatively. RESULTS: Western blot analysis results demonstrated higher expression of both pro-heparanase and heparanase in PTD placentas compared to term vaginal placentas. Accordingly, immunofluorescence staining shows elevated heparanase expression in PTD placentas compared to term vaginal placentas (5.1 ± 0.92 vs. 1.2 ± 0.18, p < .005). Expression level of heparanase was higher in term cesarean section placentas as compared to term vaginal deliveries placentas, but did not reach statistical significance (1.8 ± 0.39 vs. 1.2 ± 0.18, p = .06). CONCLUSION: This study demonstrates for the first time that preterm vaginal deliveries are associated with higher expression of heparanase in placental tissue. This may imply a direct effect of heparanase on preterm labor. Further studies should evaluate the functional role by which heparanase influence preterm delivery.

Preeclampsia-Like Syndrome in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Hypertension, proteinuria, and hepatic dysfunction have been described as manifestations of coronavirus disease 2019 (COVID-19) and are generally accepted as poor prognostic factors. However, these same findings can also occur in pregnant women with preeclampsia, thus creating a diagnostic challenge. CASE: We report a case of COVID-19 infection in an otherwise healthy pregnant patient with secondary hypertension, proteinuria, and significant hepatic dysfunction. Maternal placental growth factor (PlGF) testing was used to rule out preeclampsia. The patient received supportive care and improved significantly. She went on to have a spontaneous vaginal term delivery of a healthy male baby. CONCLUSION: COVID-19 infection in pregnancy may present as preeclampsia-like syndrome. PlGF testing can be used to differentiate preeclampsia from COVID-19 and facilitate appropriate management.

The association between congenital uterine anomalies and perinatal outcomes - does type of defect matters?

OBJECTIVE: To evaluate the association between congenital uterine anomalies (CUA) and adverse perinatal outcomes stratified by type of anomaly. METHODS: A retrospective cohort study of all women delivered in one university-affiliated medical center between 2010 and 2017 with CUA. Multiple pregnancies and pregnancies complicated by fetal anomalies were excluded. Maternal and short-term neonatal outcomes were evaluated and compared between women with unification defects (unicornuate, bicornuate, or uterus didelphys), and canalization defects represented by septate uterus. Univariate analysis was utilized followed by multivariate analysis to adjust for confounders. p < .05 was considered significant. RESULTS: Among 167 pregnancies with CUA, 92 (55.1%) had bicornuate uterus, 32 (19.1%) septate uterus, 26 (15.6%) didelphys uterus, and 17 (10.1%) unicornuate uterus. Maternal demographics and obstetric characteristics were similar between women with unification and canalization defects. The entire cohort had high rates of preterm delivery (PTD), malpresentation, and cesarean delivery (CD) (25.7%, 42.5%, and 63.5%, respectively). In comparison to unification defects, pregnancies in women with canalization defects (septate uterus), had increased risk for PTD <32 weeks (12.5% vs. 2.9%, p = .02), and placental abruption (12.5% vs. 3%, p = .02), however, a lower overall rate of CD (46.9% vs. 67.4%, p = .03). Following adjustment to confounders (age, BMI, nulliparity, chronic hypertension, and smoking) none of the results remained statistically significant. There were no differences in neonatal outcomes between the groups. CONCLUSIONS: Overall, women with CUA have a high prevalence of adverse pregnancy outcomes. However, outcome does not differ by type of anomaly.

Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes.

OBJECTIVE: To evaluate maternal and neonatal outcomes in pregnancies complicated by hypoglycemia on 100-g oral glucose tolerance test (OGTT). METHODS: A retrospective cohort analysis of all live-born deliveries in a single medical center during 2018 and 2019 with available OGTT results and birth outcomes. Preterm deliveries (<34 weeks), multiple pregnancies and major anomalies were excluded. Hypoglycemia during OGTT was defined as at least one glucose value below 60 mg/dl. Maternal characteristics and perinatal outcomes were compared between three groups: Hypoglycemia on OGTT, Normal OGTT and Abnormal OGTT. Univariate followed by multivariate analyses were used to control for confounders. RESULTS: Overall, 2079 women were entered into the analysis. Of these, 216 (10.4%) had at least one hypoglycemic value, 1072 (51.6%) had normal OGTTs and 791 (38%) abnormal OGTTs. Hypoglycemia in OGTT was more prevalent in multiparous women and was associated with fetal male gender. Absolute birth weight, low birth weight and small for gestational age differed between groups; however, there was no difference between groups in overall birth weight centiles (60.1 ± 26.8 versus 63 ± 26 versus 60.9 ± 27; P > 0.05). Following adjustment of confounders, hypoglycemia was not associated with rates of low birth weight or small for gestational age (P < 0.05). There were no other differences in perinatal outcomes between groups. CONCLUSION: Hypoglycemia in OGTT is not associated with maternal or neonatal adverse outcomes.

Flat Oral Glucose Tolerance Test During Pregnancy: Maternal Characteristics and Risk for Adverse Outcomes.

Flat oral glucose tolerance test (OGTT) curve is characterized by low glucose levels, seemingly nonresponsive to glucose load. Few studies have explored flat OGTT during pregnancy and have yielded conflicting results, some suggesting risk for fetal growth restriction. This study evaluated the characteristics and perinatal outcomes of women with a flat OGTT during pregnancy. We found that a flat OGTT curve occurs in younger, leaner pregnant women. Also, flat OGTT curve was significantly associated with a male fetus and higher levels of pregnancy-associated plasma protein A at the first-trimester screening. Although flat OGTT can possibly reflect some degree of hyperinsulinemia, it is generally not associated with adverse maternal or neonatal outcomes.

Parity and Interval from Previous Delivery-Influence on Perinatal Outcome in Advanced Maternal Age Parturients.

OBJECTIVE: To investigate the effect of parity and interpregnancy interval (IPI) on perinatal outcomes in advanced maternal age (AMA) parturients. METHODS: A population-based retrospective cohort study of all women older than 40 years, who had a singleton live birth after 24 weeks in the United States in 2017 Women were categorized to three groups by parity and interval from last delivery: primiparas, multiparas with IPI ≤ 5 years, and multiparas with IPI > 5 years. Primary outcome was composite adverse neonatal outcome (preterm delivery <34 weeks, birthweight <2000 g, neonatal seizure, neonatal intensive care unit admission, Apgar score <7 at 5 min, or assisted ventilation >6 h). Secondary outcome was composite adverse maternal outcome and other adverse perinatal outcomes. Univariate and multivariate analysis were used to compare between groups. RESULTS: During 2017, 3,864,754 deliveries were recorded into the database. Following exclusion, 109,564 AMA gravidas entered analysis. Of them, 24,769 (22.6%) were nulliparas, 39,933 (36.4%) were multiparas with IPI ≤ 5 years, and 44,862 (40.9%) were multiparas with IPI > 5 years. Composite neonatal outcome was higher in nulliparas and in multiparas with IPI > 5 years, in comparison to multiparas with IPI ≤ 5 years (16% vs. 13% vs. 10%, respectively, p < 0.05). Maternal composite outcome was similar between groups. In the multivariable analysis, relative to nulliparas, only multiparity with IPI ≤ 5 years had a protective effect against the composite neonatal outcome (aOR 0.97, 95% CI 0.95-0.99, p < 0.001). CONCLUSION: Among AMA gravidas, multiparity with IPI ≤ 5 years has a significant protective effect against adverse neonatal outcomes when compared to nulliparas. Multiparity with IPI > 5 years is no longer protective.

Cesarean scar pregnancy managed with local and systemic methotrexate: A single center case series.

OBJECTIVE: To report the efficacy of combined systemic and local methotrexate treatment for cesarean scar pregnancy and review data from selected, similar case series. STUDY DESIGN: A retrospective case series of 12 patients with cesarean scar pregnancy treated in a university hospital between 2014 and 2018. The intervention was combined treatment of systemic and local methotrexate. RESULTS: Twelve patients were treated with combined systemic and local methotrexate. Clinical characteristics, clinical course and treatment efficacy were evaluated. Mean gestational age at diagnosis was 7.5 weeks (range 5.9-9.1). ßhCG levels at diagnosis ranged from 1581 to 345,427 U/L with a mean of 77,795 U/L. All 12 patients were successfully treated without surgical intervention and with no significant side-effects. Mean hospitalization duration was 9 days (5.8-12.6) and mean time to normalization of ßhCG levels was 98 days (63-132). CONCLUSIONS: Treatment of cesarean scar pregnancy with a combination of systemic and local methotrexate was effective and safe. Although the treatment course tends to be longer than with other modalities, this protocol offers excellent success rates, with fertility preservation and few complications.

Pre-cesarean Staphylococcus aureus nasal screening and decolonization: a prospective randomized controlled trial.

OBJECTIVE: Staphylococcus aureus (S. aureus) is a common pathogen in surgical site infections (SSIs). Mupirocin ointment is an effective treatment for nasal carriers. We aimed to investigate whether screening for nasal colonization of S. aureus and treating carriers prior to a cesarean section (CS) decreases the likelihood of SSI. METHODS: This is a randomized controlled trial. All participants underwent nasal culture prior to the CS. Nasal carriers of S. aureus were treated with Mupirocin ointment according to a standardized protocol. In the control group, nasal cultures were obtained immediately prior to surgery and carriers were not treated. RESULTS: We recruited 568 patients. Demographic characteristics were comparable between the groups. S. aureus nasal colonization rates were 20.1% and 14.9% in the intervention and control groups, respectively (p = 0.12). S. aureus eradication rate with Mupirocin treatment was 88%. SSI rates were similar in the intervention and control groups (13.1% versus 12.1%, respectively, p = 0.78) and in treated carriers, untreated carriers, and non-carriers (7.4% versus 13.0% versus 13.1%, respectively, p = 0.69). Previous CS was the only factor found to independently predict SSI (OR 2.5, CI 1.09-5.65 p = 0.029). CONCLUSION: Pre-cesarean screening for nasal S. aureus carriage and decolonization does not appear to be an effective intervention in reducing SSI rates.