Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10-8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

Society for Maternal-Fetal Medicine Consult Series #68: Sickle cell disease in pregnancy.

Pregnant individuals with sickle cell disease have an increased risk of maternal and perinatal morbidity and mortality. However, prepregnancy counseling and multidisciplinary care can lead to favorable maternal and neonatal outcomes. In this consult series, we summarize what is known about sickle cell disease and provide guidance for sickle cell disease management during pregnancy. The following are Society for Maternal-Fetal Medicine recommendations.

Clinical Trials That Have Changed Obstetric Practice: The Chronic Hypertension and Pregnancy (CHAP) Trial.

We describe the evolution of treatment recommendations for chronic hypertension (CHTN) in pregnancy, the CHTN and pregnancy (CHAP) trial, and its impact on obstetric practice. The US multicenter CHAP trial showed that antihypertensive treatment for mild CHTN in pregnancy [blood pressures (BP)<160/105 mm Hg] to goal<140/90 mm Hg, primarily with labetalol or nifedipine compared with no treatment unless BP were severe reduced the composite risk of superimposed severe preeclampsia, indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death. As a result of this trial, professional societies in the United States recommended treatment of patients with CHTN in pregnancy to BP goal<140/90 mm Hg.

Systematic Review of Lymphangioleiomyomatosis Outcomes in Pregnancy and a Proposed Management Guideline.

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease that primarily affects women of reproductive age. Disease progression has been linked to estrogen exposure, and as such many patients are advised to avoid pregnancy. Data are limited regarding the interaction between LAM and pregnancy, and as such we performed a systematic review to summarize available literature reporting outcomes of pregnancies complicated by maternal LAM. STUDY DESIGN: This was a systematic review including randomized controlled trials, observational studies, systematic reviews, case reports, clinical practice guidelines, and quality improvement studies with full-text manuscripts or abstracts in the English language with primary data on pregnant or postpartum patients with LAM. The primary outcome was maternal outcomes during pregnancy as well as pregnancy outcomes. Secondary outcomes were neonatal outcomes and long-term maternal outcomes. This search occurred in July 2020 and included MEDLINE, Scopus, clinicaltrials.gov, Embase, and Cochrane Central. Risk of bias was ascertained using the Newcastle-Ottawa Scale. Our systematic review was registered with PROSPERO as protocol number CRD 42020191402. RESULTS: A total of 175 publications were identified in our initial search; ultimately 31 studies were included. Six (19%) studies were retrospective cohort studies and 25 (81%) studies were case reports. Patients diagnosed during pregnancy had worse pregnancy outcomes compared to those diagnosed with LAM prior to pregnancy. Multiple studies reported a significant risk of pneumothoraces during pregnancy. Other significant risks included preterm delivery, chylothoraces, and pulmonary function deterioration. A proposed strategy for preconception counseling and antenatal management is provided. CONCLUSION: Patients diagnosed with LAM during pregnancy generally experience worse outcomes including recurrent pneumothoraces and preterm delivery as compared to patients with a LAM diagnosis prior to pregnancy. Given that there are limited studies available, and that the majority are low-quality evidence and subject to bias, further investigation of the interaction between LAM and pregnancy is warranted to guide patient care and counseling. KEY POINTS: · Data are limited on the effects of lymphangioleiomyomatosis on pregnancy outcomes.. · We performed a systematic review to summarize pregnancy outcomes complicated by LAM.. · Patients diagnosed with LAM during pregnancy experience worse outcomes..

Placental Pathology in Maternal Ornithine Transcarbamylase Deficiency.

INTRODUCTION: Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, inherited in an X-linked manner. Males are severely affected. Female phenotypes vary from asymptomatic to severe, and symptoms may be triggered by high metabolic states like childbirth. Literature on OTC deficiency in pregnancy and placental pathology is limited. METHODS: Pathology records were searched at a single referral center from 2000-2020 and identified three placental cases from two mothers heterozygous for OTC deficiency. Placental pathology and maternal and neonatal history were reviewed in detail. RESULTS: The placenta from one symptomatic mother carrying an affected male fetus showed widespread high-grade fetal vascular malperfusion (FVM) lesions of varying age. These lesions were not seen in the two placentas from the asymptomatic mother. DISCUSSION: In cases of symptomatic maternal OTC deficiency, our findings highlight the need for placental examination. Since thrombotic events in the placenta have the potential to associate with fetal and neonatal endothelial damage, a high index of suspicion for neonatal thrombosis may be warranted.

Extracellular Vesicles From Women With Severe Preeclampsia Impair Vascular Endothelial Function.

BACKGROUND: Preeclampsia (PE) manifesting as hypertension and organ injury is mediated by vascular dysfunction. In biological fluids, extracellular vesicles (EVs) containing microRNA (miRNA), protein, and other cargo released from the placenta may serve as carriers to propagate injury, altering the functional phenotype of endothelial cells. PE has been consistently correlated with increased levels of placenta-derived EVs (pEVs) in maternal circulation. However, whether pEVs impaired endothelial cell function remains to be determined. In this study, we hypothesize that pEVs from pregnant women with severe PE (sPE) impair endothelial function through altered cell signaling. METHODS: We obtained plasma samples from women with sPE (n = 14) and normotensive pregnant women (n = 15) for the isolation of EVs. The total number of EV and pEV contribution was determined by quantifying immunoreactive EV-cluster of designation 63 (CD63) and placental alkaline phosphatase (PLAP) as placenta-specific markers, respectively. Vascular endothelial functional assays were determined by cell migration, electric cell-substrate impedance sensing in human aortic endothelial cells (HAECs), and wire myography in isolated blood vessels, preincubated with EVs from normotensive and sPE women. RESULTS: Plasma EV and pEV levels were increased in sPE when compared to normotensive without a significant size distribution difference in sPE (108.8 ± 30.2 nm) and normotensive-EVs (101.3 ± 20.3 nm). Impaired endothelial repair and proliferation, reduced endothelial barrier function, reduced endothelial-dependent vasorelaxation, and decreased nitrite level indicate that sPE-EVs induced vascular endothelial dysfunction. Moreover, sPE-EVs significantly downregulated endothelial nitric oxide synthase (eNOS and p-eNOS) when compared to normotensive-EV. CONCLUSIONS: EVs from sPE women impair endothelial-dependent vascular functions in vitro.

Racial disparities in reliable contraceptive use in women with heart disease.

OBJECTIVE: The aim of the study was to investigate the differences in reliable contraceptive use between black women and white women with maternal cardiac disease. METHODS: The study comprised a retrospective cohort of women with maternal cardiac disease managed by the University of Alabama at Birmingham (UAB) Comprehensive Pregnancy and Heart Program (CPHP). Women were included if they had attended one or more prenatal visits at the UAB CPHP and delivered at the UAB hospital between March 2015 and June 2019. The primary outcome was reliable contraceptive use within 2 months postpartum, defined by receipt of long-acting reversible contraception (i.e., an intrauterine contraceptive device or an etonogestrel implant) or female sterilisation. All outcomes were compared based on self-reported race. RESULTS: One hundred and forty-nine women met the inclusion criteria. Black women (n = 63) were more likely than white women (n = 86) to use reliable contraception (65% vs 43%; p = 0.008). Black women were less likely than white women to be undecided or decline contraception at the time of admission (13% vs 27%; p = 0.037). There was no difference in reliable contraceptive use between black women (n = 20, 63%) and white women (n = 23, 72%) with modified World Health Organisation (WHO) class III/IV lesions (p = 0.42). CONCLUSION: Black women with maternal cardiac disease were more likely than white women to receive reliable contraception. Interventions to prevent unintended pregnancy in women with maternal cardiac disease should focus on improving reliable contraceptive use, especially for women with modified WHO class III/IV lesions.

Thrombin-Induced Decidual Colony-Stimulating Factor-2 Promotes Abruption-Related Preterm Birth by Weakening Fetal Membranes.

Preterm premature rupture of membranes (PPROM) and thrombin generation by decidual cell-expressed tissue factor often accompany abruptions. Underlying mechanisms remain unclear. We hypothesized that thrombin-induced colony-stimulating factor-2 (CSF-2) in decidual cells triggers paracrine signaling via its receptor (CSF2R) in trophoblasts, promoting fetal membrane weakening and abruption-associated PPROM. Decidua basalis sections from term (n = 10), idiopathic preterm birth (PTB; n = 8), and abruption-complicated pregnancies (n = 8) were immunostained for CSF-2. Real-time quantitative PCR measured CSF2 and CSF2R mRNA levels. Term decidual cell (TDC) monolayers were treated with 10-8 mol/L estradiol ± 10-7 mol/L medroxyprogesterone acetate (MPA) ± 1 IU/mL thrombin pretreatment for 4 hours, washed, and then incubated in control medium with estradiol ± MPA. TDC-derived conditioned media supernatant effects on fetal membrane weakening were analyzed. Immunostaining localized CSF-2 primarily to decidual cell cytoplasm and cytotrophoblast cell membranes. CSF-2 immunoreactivity was higher in abruption-complicated or idiopathic PTB specimens versus normal term specimens (P < 0.001). CSF2 mRNA was higher in TDCs versus cytotrophoblasts (P < 0.05), whereas CSF2R mRNA was 1.3 × 104-fold higher in cytotrophoblasts versus TDCs (P < 0.001). Thrombin enhanced CSF-2 secretion in TDC cultures fourfold (P < 0.05); MPA reduced this effect. Thrombin-pretreated TDC-derived conditioned media supernatant weakened fetal membranes (P < 0.05), which MPA inhibited. TDC-derived CSF-2, acting via trophoblast-expressed CSFR2, contributes to thrombin-induced fetal membrane weakening, eliciting abruption-related PPROM and PTB.

Randomized Controlled Trials of Headache Treatments in Pregnancy: A Systematic Review.

OBJECTIVE: Headaches affect 88% of reproductive-aged women. Yet data are limited addressing treatment of headache in pregnancy. While many women experience improvement in pregnancy, primary and secondary headaches can develop. Consequently, pregnancy is a time when headache diagnosis can influence maternal and fetal interventions. This study was aimed to summarize existing randomized control trials (RCTs) addressing headache treatment in pregnancy. STUDY DESIGN: We searched PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS from January 1, 1970 through June 31, 2019. Studies were eligible if they were English-language RCTs addressing treatment of headache in pregnancy. Conference abstracts and studies investigating postpartum headache were excluded. Three authors reviewed English-language RCTs addressing treatment of antepartum headache. To be included, all authors agreed each article to meet the following criteria: predefined control group, participants underwent randomization, and treatment of headache occurred in the antepartum period. If inclusion criteria were met no exclusions were made. Our systematic review registration number was CRD42019135874. RESULTS: A total of 193 studies were reviewed. Of the three that met inclusion criteria all were small, with follow-up designed to measure pain reduction and showed statistical significance. CONCLUSION: Our systematic review of RCTs evaluating treatment of headache in pregnancy revealed only three studies. This paucity of data limits treatment, puts women at risk for worsening headache disorders, and delays diagnosis placing both the mother and fetus at risk for complications.

Prenatal Tobacco Exposure and Childhood Neurodevelopment among Infants Born Prematurely.

OBJECTIVE: Nicotine is an established neuroteratogen, and prenatal tobacco exposure alters the structure of the developing nervous system. An association between prenatal tobacco exposure and impaired neurologic function is less well established. We examine the association between prenatal tobacco exposure and childhood neurodevelopment among infants born preterm. STUDY DESIGN: Secondary analysis of a multicenter randomized controlled trial assessing the benefits of magnesium sulfate for the prevention of cerebral palsy in preterm infants. Women were included if they delivered a singleton and nonanomalous infant before 37 weeks. Exposure was any self-reported prenatal tobacco use. Primary outcome was the original trial composite outcome of moderate or severe cerebral palsy at 2 years of age, or stillbirth, or infant death by 1 year of age. Secondary outcomes included components of the composite and mild cerebral palsy at 2 years, Bayley Scales of Infant Development II motor and mental scores, death before two years, and use of auditory aids or corrective lenses. Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals. RESULTS: Of 1,826 women included, 503 (27.5%) used tobacco. Tobacco users were more likely to be older, unmarried, and white; have a prior preterm birth; have received no prenatal care; and to use illicit drugs or alcohol. Gestational age at delivery, betamethasone exposure, and magnesium exposure were not different between groups. There were no differences in the composite primary outcome or in rates of cerebral palsy by tobacco use. Moderate developmental delay was more common among tobacco exposed in bivariate but not adjusted analysis (20.5 vs. 15.9%, p = 0.035). In adjusted analysis, tobacco exposure was associated with increased use of corrective lenses (5.0 vs. 2.9%, aOR: 2.28, 95% confidence interval: 1.28-4.07). CONCLUSION: Prenatal tobacco exposure is not associated with neurodevelopmental impairment in infants born preterm. However, tobacco exposure may be associated with impaired vision. KEY POINTS: · Tobacco exposure is not associated with impaired neurodevelopment in this preterm population.. · Prenatal tobacco exposure is associated with increased need for corrective lenses.. · Tobacco use in pregnancy may be a risk factor for poorer visual acuity in children..

Chronic hypertension in pregnancy.

Chronic hypertension and associated cardiovascular disease are among the leading causes of maternal and perinatal morbidity and death in the United States. Chronic hypertension in pregnancy is associated with a host of adverse outcomes that include preeclampsia, cesarean delivery, cerebrovascular accidents, fetal growth restriction, preterm birth, and maternal and perinatal death. There are several key issues related to the diagnosis and management of chronic hypertension in pregnancy where data are limited and further research is needed. These challenges and recent guidelines for the management of chronic hypertension are reviewed. Well-timed pregnancies are of utmost importance to reduce the risks of chronic hypertension; long-acting reversible contraceptive options are preferred. Research to determine optimal blood pressure thresholds for diagnosis and treatment to optimize short- and long-term maternal and perinatal outcomes should be prioritized along with interventions to reduce extant racial and ethnic disparities.

Prevention, Diagnosis, and Management of Hypertensive Disorders of Pregnancy: a Comparison of International Guidelines.

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy (HDP)-gestational hypertension, preeclampsia, and eclampsia-are a leading cause of adverse maternal and perinatal outcomes internationally. Prevention, timely diagnosis, and prompt management can reduce associated morbidity. The purpose of this review is to compare international guidelines pertaining to HDP. RECENT FINDINGS: Fourteen HDP guidelines were compared relative to guidelines for the United States (US) where the authors practice. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. Recommended dose and gestational age at initiation vary. Diagnoses of chronic hypertension, gestational hypertension, and preeclampsia in pregnant women are similar, although blood pressure (BP) thresholds for antihypertensive medication initiation and treatment targets vary due to the limitations in high-quality evidence. There are differences among international HDP guidelines related to dose and timing of aspirin initiation, thresholds for antihypertensive medication initiation, and BP targets. However, all guidelines acknowledge the significant morbidity associated with HDP and advocate for timely diagnosis and management to reduce associated morbidity and mortality. More research is needed to understand optimal BP thresholds at which to initiate antihypertensive medication regimens and BP targets in pregnancy.

Neonatal Abstinence Syndrome among Infants Born to Mothers with Sickle Cell Hemoglobinopathies.

OBJECTIVE: The objective of this study is to examine risk factors for neonatal abstinence syndrome (NAS) among infants born to mothers with sickle cell hemoglobinopathies (SCH). STUDY DESIGN: Retrospective cohort study of nonanomalous, singleton infants born to mothers with laboratory confirmed SCH. Infants were included if they were diagnosed with NAS prior to hospital discharge. The outcome of interest was the association of maternal variables with NAS. RESULTS: Of 131 infants born to mothers with SCH, 4% (n = 5) were diagnosed with NAS. Mothers of infants with NAS were more likely to have SC disease (80%) compared with other SCH (20%), p = 0.001. Fifteen women had antepartum (AP) admissions for pain and/or sickle crisis. Of these patients, four infants (29%) were diagnosed with NAS. The median (5th and 95th percentile) maternal AP length of stay for women with infants diagnosed with NAS to mothers with sickle cell disease was 132 (5, 180) days (p = 0.02). CONCLUSION: Incidence of NAS among mothers with SCH is low; severe disease characterized by AP sickle cell crisis requiring prolonged AP admission for pain control significantly increases the risk of NAS. Further studies are needed to investigate the association of maternal opioid dose and NAS.

The added value of screening fetal echocardiography after normal cardiac views on a detailed ultrasound.

OBJECTIVE: Evaluate fetal echocardiography's ability to detect critical (lesions requiring immediate neonatal intensive care) congenital heart disease (CHD) after normal anatomic cardiac views on detailed ultrasound. METHODS: Singletons with both a detailed ultrasound at 18 + 0 to 22 + 6 weeks and echocardiogram performed at least 14 days later and at 20 + 0 to 24 + 6 weeks. Cases with cardiac pathology on detailed ultrasound were excluded. Different combinations of cardiac views were described: Basic (four-chamber, outflow tracts), Expanded (plus three-vessel view), and Complete (plus ductal/aortic arches). "Normal" was defined on either 2D gray scale or color Doppler. Primary outcome was rates of critical CHD missed on ultrasound but seen on fetal echocardiogram. RESULTS: One thousand two hundred twenty-three women had normal Basic cardiac views. One thousand one hundred ninety (97.3%) were confirmed normal on echocardiogram. Twenty-one (1.71%) total CHDs were missed, and three were critical (0.25%; 95% CI, 0.03%-0.53%). Of the 1,223 women, 763 had Complete views. Ten (1.31%) total CHDs were missed and one (0.13%; 95% CI, 0.13%-0.36%) was confirmed critical. CONCLUSION: Fetal echocardiography can increase CHD detection despite normal cardiac anatomy on detailed ultrasound; however, CHDs missed are rarely critical. Approximately 750 fetal echocardiograms need to be performed to detect one critical CHD with Complete normal cardiac views on detailed ultrasound.

Sonographic markers associated with adverse neonatal outcomes among fetuses with gastroschisis: an 11-year, single-center review.

BACKGROUND: Gastroschisis complicates 1 in 2000 births and is readily identifiable during prenatal ultrasound scans. Outcomes in fetuses that are affected by gastroschisis vary widely from stillbirth or neonatal death to uncomplicated surgical correction, which makes prenatal counseling challenging. OBJECTIVE: The goal of our study was to identify sonographic markers that are associated with perinatal death and morbidity that include significant bowel injury, necrotizing enterocolitis, and the need for bowel resection in fetuses with gastroschisis. STUDY DESIGN: We identified a cohort of fetuses that were diagnosed with gastroschisis from 2003-2014. Sonographic markers that were reviewed included growth restriction, abdominal circumference, oligohydramnios, bowel dilation, and gastric bubble characteristics. We evaluated these markers both at diagnosis and near delivery. Four adverse perinatal outcomes were assessed: perinatal death, necrotizing enterocolitis, need for bowel resection, and a composite of significant bowel injury, which included a diagnosis of bowel atresia or necrosis at the time of surgical exploration. Logistic regression was performed to calculate odds ratios and 95% confidence intervals for each marker and outcome. RESULTS: One hundred seventy-seven patients were identified, and 154 of these patients met inclusion criteria after exclusions for delivery <24 weeks gestation, other associated anomalies, lethal karyotype, or lost to follow-up evaluation. Markers at the time of diagnosis (median gestational age, 21 weeks [25th,75th interquartile range, 19, 24 weeks]) that were associated with perinatal death were abdominal circumference <5th percentile (odds ratio, 5.56; 95% confidence interval, 1.25-24.76), abnormal gastric bubble (odds ratio, 11.20; 95% confidence interval, 2.15-58.33), and abnormal stomach location (odds ratio, 17.1; 95% confidence interval, 2.99-97.85). An abnormal stomach location (odds ratio, 5.53; 95% confidence interval, 1.03-29.72) before delivery was associated with perinatal death. Gastric dilation before delivery (odds ratio, 4.36; 95% confidence interval, 1.10-17.34)] was associated with the need for bowel resection. CONCLUSION: Early sonographic markers of increased perinatal mortality rates include abdominal circumference <5th percentile and an abnormal gastric bubble.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications.

#37: Diagnosis and management of vasa previa.

Vasa previa occurs when fetal blood vessels that are unprotected by the umbilical cord or placenta run through the amniotic membranes and traverse the cervix. If membranes rupture, these vessels may rupture, with resultant fetal hemorrhage, exsanguination, or even death. Prenatal diagnosis of vasa previa by ultrasound scans is approximately 98%. Approximately 28% of prenatally diagnosed cases result in emergent preterm delivery. Management of prenatally diagnosed vasa previa includes antenatal corticosteroids between 28-32 weeks of gestation, considerations for preterm hospitalization at 30-34 weeks of gestation, and scheduled delivery at 34-37 weeks of gestation.

The GoMo study: a randomized clinical trial assessing neonatal pain with Gomco vs Mogen clamp circumcision.

OBJECTIVE: Our objective was to compare the pain/stress levels of newborns among the 2 most common circumcision techniques after resident-wide education. STUDY DESIGN: The study period of this randomized control trial was October 2012 through March 2014. Following informed consent, full-term males from uncomplicated singleton pregnancies were randomized to Gomco (n=137) or Mogen (n=137) devices. Resident-wide education for an obstetrics and gynecology residency program at a single institution was performed to ensure standardized training. All infants received a subcutaneous ring block before the procedure and oral sucrose intraoperatively. The primary outcome was neonatal pain assessed physiologically by salivary cortisol levels (enzyme-linked immunosorbent assay) and clinically by a validated neonatal pain score (crying, requires increased oxygen administration, increased vital signs, expression, sleeplessness [CRIES]). Secondary outcomes were immediate complications, duration of procedure, and short-term outcomes as reported by mothers and pediatricians. A sample size of 274 (accounting for 20% loss of follow-up) was determined sufficient to detect a mean difference of 1.22 µg/dL in cortisol levels (Gomco, SD±3.34; Mogen, SD±0.81) with 80% power, P=.05 level of significance. RESULTS: A total of 251 infants completed the protocol. There were no significant differences in maternal or neonatal demographics including preoperative heart rate and mean arterial pressure. In the Mogen circumcision, the percentage change of cortisol was significantly lower than Gomco (279.1±498.15 vs 167.75±272.22; P=.049). There were no differences in postoperative CRIES scores. Postoperative heart rate was higher in infants undergoing Gomco circumcision than Mogen circumcision (138.7±16.5 vs 133.4±17.5; P=.015) as was mean arterial blood pressure (63.3±9.2 vs 60.4±8.6; P=.012). Mogen circumcisions were shorter (7.00±2.97 vs 3.65±1.84 minutes; P<.001). There were no significant differences in bleeding complications. A total of 168 maternal surveys were completed, with 98.7% maternal satisfaction in Gomco vs 98.9% in Mogen. There were no reports of bleeding after discharge or circumcision revisions in either group to date. CONCLUSION: Mogen clamp is associated with less neonatal pain physiologically by significantly lower percentage change in salivary cortisol, lower heart rate, and mean arterial blood pressure. There was no difference in CRIES scores. Mogen clamp circumcision duration is significantly shorter than Gomco clamp. Both methods demonstrate satisfactory maternal and pediatrician short-term follow-up.