Prophylactic Ureteral Stent Placement and Urinary Injury During Hysterectomy for Placenta Accreta Spectrum.

OBJECTIVE: To evaluate the association between prophylactic ureteral stent placement at the time of hysterectomy for placenta accreta spectrum and genitourinary injury. METHODS: We conducted a retrospective cohort study of patients with placenta accreta spectrum who underwent hysterectomy at two referral centers from 2001 to 2021. The exposure was prophylactic ureteral stent placement. The primary outcome, genitourinary injury, was a composite of bladder injury, ureteral injury, or vesicovaginal fistula. Secondary outcomes included components of the primary outcome. We evaluated differences between groups using χ 2 and t test. To evaluate differences in the primary outcome, we reported odds ratios (ORs) and adjusted odds ratios (aORs) using multivariable logistic regression analyses to control for potential confounding variables. We used a Cochran-Armitage χ 2 trend test to evaluate difference in stent use and injury over time. RESULTS: In total, 236 patients were included. Prophylactic ureteral stents were used in 156 surgeries (66%). Overall, genitourinary injury occurred less frequently in the stent group compared with the no stent group (28% vs 51%, OR 0.37, 95% CI 0.21-0.65). This association persisted after controlling for urgency of delivery, three or more prior cesarean deliveries, and whether a gynecologic oncologist was present (aOR 0.27, 95% CI 0.14-0.52). Unintentional bladder injury occurred less frequently in the stent group compared with the no stent group (13% vs 25%, P =.018), as did ureteral injury (2% vs 9%, P =.019). CONCLUSION: Prophylactic ureteral stent placement was associated with a decreased risk of genitourinary injury during hysterectomy for placenta accreta spectrum.

Human Mesenchymal Stem Cell Sheets Improve Uterine Incision Repair in a Rodent Hysterotomy Model.

OBJECTIVE: The study aimed to assess the feasibility of creating and transplanting human umbilical cord mesenchymal stem cell sheets applied to a rat model of hysterotomy, and additionally to determine benefits of human umbilical cord mesenchymal stem cell sheet transplantation in reducing uterine fibrosis and scarring. STUDY DESIGN: Human umbilical cord mesenchymal stem cell sheets are generated by culturing human umbilical cord mesenchymal stem cells on thermo-responsive cell culture plates. The temperature-sensitive property of these culture dishes facilitates normal cell culture in a thin contiguous layer and allows for reliable recovery of intact stem cell sheets without use of destructive proteolytic enzymes.We developed a rat hysterotomy model using nude rats. The rat uterus has two distinct horns: one horn provided a control/untreated scarring site, while the second horn was the cell sheet transplantation site.On day 14 following surgery, complete uteri were harvested and subjected to histologic evaluations of all hysterotomy sites. RESULTS: The stem cell sheet culture process yielded human umbilical cord mesenchymal stem cell sheets with surface area of approximately 1 cm2.Mean myometrial thickness in the cell sheet-transplanted group was 274 µm compared with 191 µm in the control group (p = 0.02). Mean fibrotic surface area in the human umbilical cord mesenchymal stem cell sheet-transplanted group was 95,861 µm2 compared with 129,185 µm2 in the control group. Compared with control horn sites, cell sheet-transplanted horns exhibited significantly smaller fibrotic-to-normal myometrium ratios (0.18 vs. 0.27, respectively, p = 0.029). Mean number of fibroblasts in cell sheet-transplanted horns was significantly smaller than the control horns (483 vs. 716/mm2, respectively, p = 0.001). CONCLUSION: Human umbilical cord mesenchymal stem cell sheet transplantation is feasible in a rat model of hysterotomy. Furthermore, use of stem cell sheets reduces fibroblast infiltration and uterine scar fibrotic tissue formation during hysterotomy healing, potentially mitigating risks of uterine scar formation. KEY POINTS: · Stem cell sheet transplanted to hysterotomy promotes myometrial regeneration and reduced fibrotic tissue formation.. · This study demonstrates the feasibility of using human umbilical cord mesenchymal stem cell sheets..

Routine third-trimester ultrasound in low-risk pregnancies and perinatal death: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to determine whether routine third-trimester ultrasounds in low-risk pregnancies decrease the rate of perinatal death compared with regular antenatal care with serial fundal height measurements. DATA SOURCES: This was a systematic review and meta-analysis of randomized control trials to identify relevant studies published from inception to October 2019. The databases used were Ovid, PubMed, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials using a combination of key words related to "third trimester ultrasound" and "low-risk." STUDY ELIGIBILITY CRITERIA: We included all randomized control trials of singleton, nonanomalous low-risk pregnancies that were randomized to either one or more third-trimester ultrasounds (ultrasound group) or serial fundal height (fundal height group). Exclusion criteria were patients with multiple gestations, maternal medical complications, or fetal abnormalities requiring a third-trimester ultrasound. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was the rate of perinatal death. The secondary outcomes were rates of fetal growth restriction, suspected large for gestational age, polyhydramnios, oligohydramnios, fetal anomalies, antenatal interventions, stillbirth, neonatal death, cesarean delivery, induction of labor, and other neonatal outcomes. This meta-analysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk or mean difference with a corresponding 95% confidence interval. RESULTS: A total of 7 randomized control trials with 23,643 participants (12,343 in the ultrasound group vs 11,300 in the fundal height group) were included. The total rate of perinatal death was similar among the groups (41 of 11,322 [0.4%] vs 34 of 10,285 [0.3%]; relative risk, 1.14; 95% confidence interval, 0.68-1.89). The rate of fetal growth restriction was higher in the ultrasound group (763 of 10,388 [7%] vs 337 of 9021 [4%]; relative risk, 2.11; 95% confidence interval, 1.86-2.39) and the rate of suspected large for gestational age (1060 of 3513 [30%] vs 375 of 3558 [11%]; relative risk, 2.84; 95% confidence interval, 2.6-3.2). Polyhydramnios was also significantly higher in the ultrasound group than the fundal height group (18 of 323 [6%] vs 4 of 322 [1%] relative risk, 3.93; 95% confidence interval, 1.4-11). The rates of the remainder of the secondary outcomes were similar among the groups. CONCLUSION: Routine third-trimester ultrasounds do not decrease the rate of perinatal death compared with serial fundal height in low-risk pregnancies. Ideally, an adequately powered trial is warranted to determine whether perinatal mortality in the fundal height group can be reduced by one-third with third-trimester ultrasound.

A comparison of placental pathology between small for gestational age infants at < 5 % versus 5-9.

INTRODUCTION: Among SGA newborns, those < 5th % for GA are more likely to have adverse outcomes than those at 5-9th %. The differential morbidity and mortality may be due to abnormal placental pathology between groups. Our purpose was to compare placental pathology characteristics and composite placental pathology among SGA infants with birth weights <5th % vs. 5-9th %. METHODS: This study is a secondary analysis of a multicenter, retrospective cohort study. Placental pathological variables and composite placental pathology (CPP) among SGA infants <5th % and 5-9th % were compared. Multivariable logistic regression was used to model the probability of an infant's birth weight being classified as <5th % based on pathology characteristics. RESULTS: Of 11,487 live singleton births, 925 SGA infants met inclusion criteria. Placental pathology was available for review in 407 (44 %) SGA infants: 210 (51.6 %) <5th % and 197 (48.4 %) 5-9th %. A decreased placental weight for GA, was more common in the <5th % group compared to the 5-9th % group (p = 0.0019). No significant differences in the distribution of pathological variables or in CPP (p = 0.3) was observed between the two centile groups. A decreased placental weight was the only reliable predictor of an infant's birth weight centile group (p = 0.0018). CONCLUSIONS: Placental hypoplasia, reflected by a decreased placental weight for GA, was significantly more common among SGA infants < 5th % compared to the 5-9th %. There was no difference in placental pathological features or CPP between the two centile groups of SGA infants.

Umbilical Cord Abnormalities and Stillbirth.

OBJECTIVE: Umbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors. METHODS: The Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index. RESULTS: Of 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords. CONCLUSION: Umbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.

Risks of cause-specific mortality in offspring of pregnancies complicated by hypertensive disease of pregnancy.

BACKGROUND: Fetal environment has a substantial influence on an individual's health throughout their life course. Animal models of hypertensive disease of pregnancy have demonstrated adverse health outcomes among offspring exposed to hypertensive disease of pregnancy in utero. Although there are numerous descriptions of the neonatal, infant, and pediatric outcomes of human offspring affected by hypertensive disease of pregnancy, there are few data in US populations on later life outcomes, including mortality. OBJECTIVE: To assess risk for early mortality among offspring of pregnancies complicated by hypertensive disease of pregnancy. STUDY DESIGN: This is a retrospective cohort study of offspring born to women with singleton or twin pregnancies between 1947 and 1967 with birth certificate information in the Utah Population Database. We identified offspring from delivery diagnoses of gestational hypertension, preeclampsia, or eclampsia. Offspring from these pregnancies (exposed) were matched to offspring of pregnancies without hypertensive disease of pregnancy (unexposed) by maternal age at delivery, birth year, sex, and multiple gestation. We also identified unexposed siblings of exposed offspring for a separate sibling analysis. Mortality follow-up of all offspring continued through 2016, at which time they would have been 49-69 years old. Adjusted hazard ratios for cause-specific mortality comparing exposed with unexposed offspring were estimated using Cox proportional hazard models. RESULTS: We compared mortality risks for 4050 exposed offspring and 6989 matched unexposed offspring from the general population and 7496 unexposed siblings. Mortality risks due to metabolic, respiratory, digestive, nervous, and external causes of death did not differ between exposed and unexposed groups. Mortality risks from cardiovascular disease were greater in exposed offspring compared with unexposed offspring (adjusted hazard ratio, 1.57; 95% confidence interval, 1.16-2.12). In sex-specific models among the general population, cardiovascular disease mortality was significantly associated with exposure among male patients (adjusted hazard ratio, 1.92; 95% confidence interval, 1.27-2.88) but not among female patients (adjusted hazard ratio, 0.97; 95% confidence interval, 0.81-1.94). An interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality was significant (P=.047), suggesting that the effect of hypertensive disease of pregnancy on cardiovascular disease mortality increased with higher birth order. Among siblings, the association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality was not significant (adjusted hazard ratio, 1.39; 95% confidence interval, 0.99-1.95), and this was also true for sex-specific analyses of males (adjusted hazard ratio, 1.26; 95% confidence interval, 0.81-1.94) and females (adjusted hazard ratio, 1.71; 95% confidence interval, 0.96-3.04). As in the general population, there was a significant interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality (P=.011). CONCLUSION: In a US population, overall mortality risks are greater for offspring of pregnancies complicated by hypertensive disease of pregnancy compared with unexposed offspring. Among siblings, there was not a significant association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality.

Uncomplicated Pregnancies and Ultrasounds for Fetal Growth Restriction: A Pilot Randomized Clinical Trial.

Objective The purpose of this multicenter pilot study was to determine the feasibility of randomizing uncomplicated pregnancies (UPs) to have third trimester ultrasonographic exams (USE) versus routine prenatal care (RPNC) to improve the detection of small for gestational age (SGA; birth weight < 10% for GA). Material and Methods At three referral centers, 50 UPs were randomized after gestational diabetes was ruled out. Women needed to screen, consenting, and loss to follow-up was ascertained, as was the detection rate of SGA in the two groups. Results During the study period at the three centers, there were 7,680 births, of which 64% were uncomplicated. Of the 234 women approached for randomization, 36% declined. We recruited 149 women and had follow-up delivery data on 97%. The antenatal detection rate of SGA in the intervention group was 67% (95% confidence intervals 31-91%) and 9% (0.5-43%) in control. Conclusion The pilot study provides feasibility data for a multicenter randomized clinical trial to determine if third trimester USE, compared with RPNC, improves the detection of SGA and composite neonatal morbidity.

False Alarms, Pseudoepidemics, and Reality: A Case Study with American College of Obstetricians and Gynecologists Practice Bulletins.

OBJECTIVES: The objectives of this review are to (1) ascertain the frequency with which odd ratio (OR) and relative risk (RR) are in the zone of potential bias or interest in the American College of Obstetricians and Gynecologists (ACOG) practice bulletins (PB); (2) the likelihood that false alarms have been linked to recommendations; and (3) if there are differences in obstetric versus gynecological PB, vis-à-vis OR and RR in the zone of bias or interest. DATA SOURCES: We reviewed all ACOG PBs published between May 1999 and March 2014. METHODS: Documents were searched for statements with mention of OR and RR. When the reported ORs fell between 0.33 and 3.0, it was categorized as "zone of potential bias"; if ORs fell outside the interval 0.25 to 4.0, it was "zone of potential interest." With RRs, the zones of bias and interest were 0.5 to 2.0 and 0.33 to 3.0, respectively. RESULTS: Of the 79 PBs reviewed, 22% (n = 17) had 44 statements with OR, with 41% (n = 18) of the ORs being in the zone of bias and 54% (n = 24) in the zone of potential interest. Overall, 84% of the ORs did not lead to an actual recommendation by ACOG. In 28% (n = 22) of PBs, there were 67 statements with RRs, with 58% (n = 39) of them being in the zone of bias and 28% (n = 19) were in the zone of interest. In 73% of the PBs the RR citations did not lead to any recommendations. Across the 79 PBs, ACOG made 733 recommendations, and among them only 1 and 2% were linked with ORs and RRs, respectively. CONCLUSIONS: Over 70% of ACOGPBs did not cite OR and RR. To better understand the evidence, ACOG should increase citation of OR and RR; whenever applicable OR and RR should be part of graded recommendations. LEVEL OF EVIDENCE: Level C. PRÉCIS: Less than a third of ACOG practice bulletins mention odds ratios or relative risks and over 95% of recommendations in them remain unsubstantiated.

Differential Morbidity in Preterm Small versus Appropriate for Gestational Age: Perhaps Unverifiable.

OBJECTIVE: The objective of this study was to determine the morbidity of preterm small for gestational age (SGA) infants compared with appropriate for GA (AGA). STUDY DESIGN: This is a secondary analysis of the randomized trial evaluating magnesium sulfate for the prevention of cerebral palsy (CP). We compared outcomes of preterm (< 37 weeks) nonanomalous infants who were SGA (birth weight < 10% for GA) versus AGA (birth weight 10-89% for GA). We compared (1) the parent trial primary outcome, a composite of stillbirth, infant death by 1 year of age, or moderate to severe CP at 2 years of age and (2) composite neonatal morbidity (CNM). RESULTS: Of the 1,948 infants who met inclusion criteria, 95% were AGA and 5% were SGA. The primary outcome was similar (10 and 15%, p = 0.08), as was the CNM (24 and 25%, p = 0.89). Sample size calculations indicate that detection of a one-third higher rate of CNM among SGA compared with AGA infants requires more than 93,900 preterm births; for a one-third difference in moderate to severe CP, more than 1.4 million infants. CONCLUSION: Owing to the prohibitive sample size required, ascertaining a difference in sequela between preterm SGA and AGA infants is possibly unverifiable.

Obstetric Recommendations in American Congress of Obstetricians and Gynecologists Practice Bulletins versus UpToDate: a comparison.

OBJECTIVE: To compare the obstetric recommendations in American Congress of Obstetricians and Gynecologists (ACOG) practice bulletins (PB) with similar topics in UpToDate (UTD). STUDY DESIGN: We accessed all obstetric PB and cross-searched UTD (May 1999-May 2013). We analyzed only the PB which had corresponding UTD chapter with graded recommendations (level A-C). To assess comparability of recommendations for each obstetric topic, two maternal-fetal medicine (MFM) subspecialists categorized the statement as similar, dissimilar, or incomparable. Simple and weighted kappa statistics were calculated to assess agreement between the two raters. RESULTS: We identified 46 ACOG obstetric PB and 86 UTD chapters. There were 50% fewer recommendations in UTD than in PB (181 vs. 365). The recommendations being categorized as level A, B, or C was significantly different (p < 0.001) for the two guidelines. While the overall concordance rate between the two MFM subspecialists was 83% regarding the recommendations for the same topic as similar, dissimilar, or incomparable, the agreement was moderate (kappa, 0.56; 95% confidence intervals, 0.48-0.65). CONCLUSION: Though obstetricians have two sources for graded recommendations, incongruity among them may be a source of consternation. Congruent recommendations from ACOG and UTD could enhance compliance and potentially optimize outcomes.

Peripartum complications with cesarean delivery: a review of Maternal-Fetal Medicine Units Network publications.

OBJECTIVE: Since 1997, the Maternal-Fetal Medicine Units (MFMU) have published 39 articles involving over 70,000 cesarean deliveries (CD), including primary, elective repeat (ERCD) or trial of labor after cesarean (TOLAC). The purpose of this review article is to summarize the peripartum morbidity or mortality (M/M) with CD (primary or ERCD) or TOLAC. METHODS: For 12 clinical scenarios and 17 M/M, we summarized 135 rates and, whenever feasible, calculated odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Of the 58 comparable scenarios, the M/M differed significantly in 48% (28). At term, the rate of blood transfusion was significantly greater in TOLAC (2%) versus ERC (1%; OR, 1.71; 95% CI, 1.41-2.08) but not in the likelihood of a hysterectomy or operative injury. The rate of neonatal seizure and perinatal mortality was similar between TOLAC and ERCD. CONCLUSIONS: Our analysis provides an overview of peripartum M/M with CD; it allows clinicians to counsel women who had or are having CD. It also permits study design, with an appropriate sample size, with the aim to minimize the morbidities.

Neonatal brachial plexus palsy with vaginal birth after cesarean delivery: a case-control study.

OBJECTIVE: The objective was to determine the rate of neonatal brachial plexus palsy (NBPP) among women with vaginal birth after cesarean delivery (VBAC) and to compare the peripartum characteristics with control subjects. STUDY DESIGN: The Maternal-Fetal Medicine Unit cesarean registry data were used to identify nonanomalous singleton pregnancies with VBAC and NBPP at gestational age of ≥37 weeks (term) and 4 control subjects (matched for gestational age and diabetes mellitus status but without brachial injury). Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Among 11,313 VBACs at term, there were 23 women with NBPP (rate of 2.0/1000 women). Newborn infants with NBPP, compared with control infants, were significantly more likely to weigh ≥4000 g (48% vs 10%, respectively; OR, 8.45; 95% CI, 2.58-28.44) and to require admission to the neonatal intensive care unit (30% vs 13%; OR, 12.98; 95% CI, 2.61-72.18). CONCLUSION: Women who desire VBAC should be informed about the low rate of NBPP and, if eligible, encouraged to have a trial of labor after cesarean delivery.