Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress.

BACKGROUND: Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress. METHODS: In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis. RESULTS: A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03). CONCLUSIONS: In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

A double-blinded randomized controlled trial on the effects of increased intravenous hydration in nulliparas undergoing induction of labor.

BACKGROUND: Rates of labor induction are increasing, raising concerns related to increased healthcare utilization costs. High-dose intravenous fluid (250 cc/h) has been previously demonstrated to shorten the time to delivery in nulliparous individuals in spontaneous labor. Whether or not this relationship exists among individuals undergoing induction of labor is unknown. OBJECTIVE: Our study aimed to evaluate the effect of high-dose intravenous hydration on time to delivery among nulliparous individuals undergoing induction of labor. STUDY DESIGN: Nulliparous individuals presenting for induction of labor with a Bishop score of ≤6 (with and without rupture of membranes) were randomized to receive either 125 cc/h or 250 cc/h of normal saline. The primary outcome was length of labor (defined as time from initiation of study fluids to delivery). Both time to overall delivery and vaginal delivery were evaluated. Secondary outcomes included the lengths of each stage of labor, the percentage of individuals delivering within 24 hours, and maternal and neonatal outcomes, including cesarean delivery rate. RESULTS: A total of 180 individuals meeting inclusion criteria were enrolled and randomized. Baseline demographic characteristics were similar between groups; however, there was a higher incidence of diabetes mellitus in the group receiving 125 cc/h. Average length of labor was similar between groups (27.6 hours in 250 cc/h and 27.8 hours in 125 cc/h), as was the length of each stage of labor. Cox regression analysis did not demonstrate an effect of fluid rate on time to delivery. Neither the admission Bishop score, body mass index, nor other demographic characteristics affected time to delivery or vaginal delivery. There were no differences in maternal or neonatal outcomes, including overall cesarean delivery rate, clinically apparent iatrogenic intraamniotic infection, Apgar scores, need for neonatal phototherapy, or neonatal intensive care unit stay. CONCLUSION: There were no observed differences in the length of labor or maternal or neonatal outcomes with the administration of an increased rate of intravenous fluids among nulliparous individuals undergoing induction of labor.

Restorations Versus Stainless Steel Crowns in Primary Molars: A Retrospective Split-Mouth Study.

Purpose: The purpose of this study was to evaluate the treatment outcomes of multisurface caries in primary molars treated with intracoronal restorations versus stainless steel crowns (SSCs) through a retrospective split-mouth study. Methods: Dental records were screened for patients who had treatment of one primary molar with a multisurface restoration and one primary molar with an SSC. Teeth were followed until a loss to follow-up, exfoliation, or failure. Results: A total of 988 primary molars were evaluated, with a mean follow-up time of 22 months. The survival probabilities for: SSCs were 95.5 percent at one year of service and 92.8 percent at two years of service; and for intracoronal restorations were 92.0 percent at one year of service and 80.0 percent at two years of service. Overall survival analysis showed SSCs to be significantly more successful than restorations (P<0.001), particularly in children treated at ages four years and younger (P<0.001). No statistically significant difference (P=0.10) was found for children treated at ages five years and older. Conclusions: Stainless steel crowns have a higher survival probability versus restorations for multisurface caries. In children ages four years and younger, more aggressive treatment of multi-surface caries with SSCs should be considered, as conservative treatment leads to an increased need for retreatment.

Considerations for Protective Stabilization in Community General Dental Practice for Adult Patients with Special Healthcare Needs.

Protective stabilization (PS) is a method of medical restraint used for behavior management for children and adults with special needs for dental care. With the increase in availability and options for behavior management techniques, PS has become less popular and more controversial. This scoping review analyzes the use of PS for dental care for adults with special needs within the literature. METHODS: A review of publications between 1990 and 2020 was conducted in Ovid Medline, Embase, and Dentistry and Oral Sciences Source using the search terms as follows: "protective stabilization," "dentistry," "restraint," "patient positioning," and "immobilization," with Boolean operators "AND" and "OR." Articles were screened by title and abstract and included by full read review with consensus from the research team. RESULTS: A total of 298 articles were reviewed and 29 were included as part of the scoping review. The articles include original research, policy guidelines, and clinical commentary reviews. CONCLUSION: There is variable evidence regarding the use of PS as a method of behavioral management for adults with special needs. It is less popular for use due to improvements in alternative methods such as pharmacologic intervention and general anesthesia. PS still has applicable use among this population and is dependent on patient and parental consent, patient selection and safety, and clinician training.

Nonimmune hydrops fetalis: identifying the underlying genetic etiology.

PURPOSE: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. METHODS: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. RESULTS: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach-Merritt syndrome. CONCLUSION: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.

Mode of delivery preferences in a diverse population of pregnant women.

OBJECTIVE: The objective of the study was to assess women's preferences for vaginal vs cesarean delivery in 4 contexts: prior cesarean delivery, twins, breech presentation, and absent indication for cesarean. STUDY DESIGN: This was a cross-sectional study of pregnant women at 24-40 weeks' gestation. After assessing stated preferences for vaginal or cesarean delivery, we used the standard gamble metric to measure the strength of these preferences and the time tradeoff metric to determine how women value the potential processes and outcomes associated with these 2 delivery approaches. RESULTS: Among the 240 participants, 90.8% had a stated preference for vaginal delivery. Across the 4 contexts, these women indicated that, on average, they would accept a 59-75% chance of an attempted vaginal birth ending in a cesarean delivery before choosing a planned cesarean delivery, indicating strong preferences for spontaneous, uncomplicated vaginal delivery. Variations in preferences for labor processes emerged. Although uncomplicated labor ending in vaginal birth was assigned mean utilities of 0.993 or higher (on a 0-1 scale, with higher scores indicating more preferred outcomes), the need for oxytocin, antibiotics, or operative vaginal delivery resulted in lower mean scores, comparable with those assigned to uncomplicated cesarean delivery. Substantially lower scores (ranging from 0.432 to 0.598) were obtained for scenarios ending in severe maternal or neonatal morbidity. CONCLUSION: Although most women expressed strong preferences for vaginal delivery, their preferences regarding interventions frequently used to achieve that goal varied. These data underscore the importance of educating patients about the process of labor and delivery to facilitate incorporation of informed patient preferences in shared decision making regarding delivery approach.

Implementation of an obstetric hemorrhage risk assessment: validation and evaluation of its impact on pretransfusion testing and hemorrhage outcomes.

OBJECTIVE: To evaluate the impact of an obstetric hemorrhage risk assessment on pretransfusion testing and hemorrhage outcomes at a tertiary care, academic medical center. METHODS: A retrospective cohort study was performed among women delivering neonates≥24 weeks from 2009 to 2011. Demographics, pretransfusion testing rates and hemorrhage outcomes were compared between those delivering before and after implementation of the risk assessment. Multivariable analyses were used to determine predictors of postpartum hemorrhage and transfusion. RESULTS: There were 1388 women delivering before and 2121 women delivering after implementation of the risk assessment. More pretransfusion testing occurred after the assessment was initiated (22.8% versus 15.0%). Those who were considered high-risk were more likely to experience hemorrhage outcomes. In multivariable analyses, physician ordering practice in the pre-risk assessment period was a better prognosticator of both postpartum hemorrhage (aOR 9.98, 95% CI 5.02-19.82) and transfusion (aOR 31.14, 95% CI 14.97-64.82) than completion of a cross-match after implementation of the risk assessment (postpartum hemorrhage: aOR 2.10, 95% CI 1.20-3.66, transfusion: aOR 6.31, 95% CI 3.34-11.94). CONCLUSIONS: Pre-risk assessment practice may be better at identifying those in need of blood transfusion, strictly due to the necessity for pretransfusion orders for transfusion to occur. In contrast, the obstetric hemorrhage risk assessment accurately predicted those who were more likely to experience hemorrhage outcomes. Optimal utilization of the risk assessment has yet to be determined.

Temporal trends and morbidities of vacuum, forceps, and combined use of both.

OBJECTIVE: To assess trends over time of operative vaginal delivery and compare delivery-related morbidity between vacuum delivery, forceps delivery, or combined use of both in California. METHODS: California ICD-9 discharge data from 2001 to 2007 were used to identify cases of forceps and vacuum delivery. RESULTS: There was a decline in all operative delivery types (9.0% in 2001 to 7.6% in 2007), with the decline in the use of forceps most pronounced (7.26/1000 deliveries in 2001 to 3.85/1000 in 2007). Higher rates of third/fourth degree lacerations, postpartum hemorrhage, manual extraction of placenta, pelvic hematoma requiring evacuation, cervical laceration repair, and thromboembolic events were noted in forceps compared to vacuum deliveries. When both instruments were used, rates of third/fourth degree lacerations and postpartum hemorrhage were increased. Operative delivery failure was highest in combined use compared to forceps or vacuum alone. CONCLUSION: The incidence of operative vaginal delivery in California is declining, with decreasing use of forceps most notable. Several maternal morbidities are increased in forceps and combined deliveries compared to vacuum deliveries. There is a significantly higher risk of failure when two operative delivery methods are employed. These findings may be contributing to the declining willingness of providers to perform operative vaginal delivery.

Strength of preference for vaginal birth as a predictor of delivery mode among women who attempt a vaginal delivery.

OBJECTIVE: We sought to assess the relationship between strength of preference for vaginal birth and likelihood of vaginal delivery among women attempting this delivery mode. STUDY DESIGN: We conducted a longitudinal study of mode of delivery preferences among women who were <36 weeks' pregnant. Participants completed a sociodemographic and clinical questionnaire and were asked if they preferred vaginal or cesarean delivery. Participants who preferred vaginal delivery completed a standard gamble exercise to assess the strength of this preference on a 0-to-1 scale (higher scores indicate stronger preference for vaginal delivery); those preferring cesarean delivery were assigned a value of 0. Data on clinical characteristics and delivery mode were obtained via telephone interview or chart review. Logistic regression was used to identify predictors of delivery mode among women who attempted a vaginal delivery. RESULTS: Of 210 participants, 156 attempted a vaginal delivery. Their mean and median vaginal delivery preference scores were 0.70 (SD 0.31) and 0.75 (interquartile range, 0.50-0.99), respectively. In multivariate analyses, women with a prior cesarean delivery (adjusted odds ratio [aOR], 0.08; 95% confidence interval [CI], 0.02-0.39) or who delivered an infant ≥4000 g (aOR, 0.04; 95% CI, 0.01-0.28) had significantly lower odds of having a vaginal delivery. After controlling for potential confounders, participants with a stronger preference for vaginal delivery were at significantly higher odds of having a vaginal delivery (aOR, 1.54; 95% CI, 1.01-2.34 for every 0.2 increase on the 0-to-1 scale). CONCLUSION: Among women who attempt a vaginal delivery, the strength of preference for vaginal birth is predictive of the delivery mode ultimately undergone.

Phenotypic variation in trismus-pseudocamptodactyly syndrome caused by a recurrent MYH8 mutation.

We report a 20-year-old man with trismus-pseudocamptodactyly (TPS) syndrome who was found to have the same MYH8 mutation, p.R674Q, described in previous families with TPS syndrome and in one family with a Carney complex variant, trismus and pseudocamptodactyly. This patient had facial asymmetry, ptosis and downslanting palpebral fissures and multiple joint involvement, with bilateral hip dysplasia, reduced elbow supination, vertical tali and talipes in addition to the classical findings of trismus and pseudocamptodactyly. These findings broaden the phenotype associated with p.R674Q mutations and support the use of MYH8 testing in patients with a clinical diagnosis of TPS syndrome.