Predictors of Breastfeeding among Women Admitted with Severe Preeclampsia Before 34 Weeks.

OBJECTIVE: Patients with severe preeclampsia (sPREX) face barriers to successful breastfeeding (BF), including an increased risk of maternal and newborn complications, prematurity, and low birth weight. Patients with early-onset sPREX (before 34 weeks' gestation) may be at even greater risk, yet there are little data available on factors associated with BF challenges in this population. We describe rates of BF initiation at hospital discharge and BF continuation at postpartum (PP) visit and identify factors associated with BF noninitiation and BF cessation among patients admitted with early-onset sPREX. STUDY DESIGN: Retrospective cohort study of women with sPREX admitted at less than 34 weeks' gestation to a single tertiary center (2013-2019). Demographic, antepartum, and delivery characteristics were evaluated. Factors associated with BF noninitiation at maternal discharge and with BF cessation at routine PP were assessed. Patients with intrauterine or neonatal demise and those missing BF data were excluded. Bivariate statistics were used to compare characteristics and Poisson regression was used to estimate relative risks (RR). RESULTS: Of 255 patients with early-onset sPREX, 228 (89.4%) had BF initiation at maternal hospital discharge. Initiation of BF occurred less frequently among patients with tobacco use in pregnancy (7.5 vs. 37.0%, χ2 p < 0.001, RR: 0.69 [95% confidence interval, CI: 0.52-0.92]). At 6 weeks' PP, 159 of 199 (79.9%) patients had BF continuation. Maternal age under 20 years (1.9 vs. 17.5%, χ2 p = 0.01, RR: 0.36 [95% CI: 0.14-0.91]) and experiencing maternal morbidity (25.2 vs. 45.0%, χ2 p = 0.01, RR: 0.80 [95% CI: 0.66-0.96]) were associated with BF cessation at the PP visit. CONCLUSION: Among patients with early sPREX, tobacco use in pregnancy was associated with noninitiation of BF at discharge, whereas young maternal age and maternal morbidity were associated with cessation of BF by routine PP visit. Further research is needed on how to support BF in this population, especially among patients with these associated factors. KEY POINTS: · Tobacco use was associated with BF noninitiation in patients with early preeclampsia.. · Maternal age < 20 and maternal morbidity were associated with BF cessation by PP visit.. · BF support for patients with risk factors is important for BF success PP..

Transvaginal Ovarian Cyst Drainage in Third Trimester to Facilitate Vaginal Delivery.

Adnexal masses in the third trimester of pregnancy may obstruct the pelvic outlet precluding labor induction and vaginal delivery. Expectant versus surgical management of adnexal cysts in pregnancy must carefully weigh maternal-fetal benefits and risks. Simple benign appearing cysts with low likelihood of malignancy may be amenable to percutaneous drainage as a bridge to interval postpartum laparoscopic cystectomy. We demonstrated posterior culdocentesis as a safe, minimally invasive technique to decompress a simple benign appearing left adnexal cyst obstructing the pelvic outlet in the third trimester at the time of labor induction to facilitate vaginal delivery and prevent primary cesarean delivery. Detailed sonographic cyst evaluation and counseling on underlying risk of malignancy must be considered to guide shared decision-making.

Does acute funisitis predict worse neonatal outcomes among term newborns?

BACKGROUND: Acute funisitis-the histologic diagnosis of inflammation within the umbilical cord-represents a fetal inflammatory response to infection. Although acute funisitis has been associated with an increased risk of adverse outcomes among preterm neonates, there are limited and conflicting data with term deliveries. OBJECTIVE: This study aimed to evaluate the association between acute funisitis and neonatal morbidity in neonates born at term to pregnant patients with a clinical diagnosis of intraamniotic infection. STUDY DESIGN: This was a retrospective cohort study of pregnant patients who had clinically diagnosed intraamniotic infection at term, delivered vaginally at a single tertiary institution from 2013 to 2019, and had histologic chorioamnionitis on placental pathology. Patients with intrauterine fetal demise or missing neonatal/placental pathology data were excluded. The primary outcome was a neonatal sepsis composite, defined as culture-positive bacteremia, neutropenia (absolute neutrophil count<3500/µL), or immature-to-total neutrophil ratio>0.2. The secondary outcomes included composite neonatal morbidity, defined as neonatal intensive care unit admission, 5-minute Apgar score <7, bacteremia, endotracheal intubation or need for continuous positive airway pressure, intraventricular hemorrhage (grade 3 or 4), necrotizing enterocolitis (stage 3 or 4), umbilical artery pH<7.1, umbilical artery base excess>12, and neonatal mortality. The components of these composites, neonatal intensive care unit length of stay, and Kaiser early-onset sepsis score were also measured. Neonates with acute funisitis on pathology were compared with those without acute funisitis using bivariate statistics. Regression was used to estimate the relative risk of outcomes. RESULTS: Of 184 neonates with deliveries complicated by intraamniotic infection, acute funisitis was present in 109 (59%) placental specimens. Composite neonatal sepsis was significantly higher among neonates with acute funisitis (relative risk, 1.85; 95% confidence interval, 1.13-3.03) than in those without acute funisitis. As a marker for sepsis, acute funisitis has a sensitivity of 39.4%, negative predictive value of 47.2%, specificity of 78.7%, and positive predictive value of 72.9%. An immature-to-total neutrophil ratio>0.2 (relative risk, 1.83; 95% confidence interval, 1.09-3.08) was also significantly associated with acute funisitis. Neonatal morbidity composite, intraventricular hemorrhage, necrotizing enterocolitis, neonatal intensive care unit admission, higher Kaiser early-onset sepsis scores, and other examined outcomes were not statistically associated with acute funisitis. CONCLUSION: In term deliveries complicated by intraamniotic infection, acute funisitis was associated with increased neonatal sepsis. Current approaches for estimating neonatal sepsis risk are limited by their reliance on indirect maternal factors such as maximum maternal temperature and intrapartum antibiotic use. This study suggests that acute funisitis may serve as a marker that could be utilized to augment risk stratification at birth if a protocol for evaluating the umbilical cord in real-time were widely adopted.

Cost-Effectiveness of Exome Sequencing versus Targeted Gene Panels for Prenatal Diagnosis of Fetal Effusions and Non-Immune Hydrops Fetalis.

BACKGROUND: Although exome sequencing has a greater overall diagnostic yield than targeted gene panels in the evaluation of nonimmune hydrops fetalis and fetal effusions, the cost-effectiveness of this approach is not known. OBJECTIVE: This study aimed to evaluate the costs and outcomes of targeted gene panels vs exome sequencing for prenatally diagnosed nonimmune hydrops fetalis and fetal effusions when next-generation sequencing is pursued following nondiagnostic standard nonimmune hydrops fetalis evaluations, including karyotype or chromosomal microarray. STUDY DESIGN: A decision-analytical model was designed using TreeAge Pro to compare 10 genetic testing strategies, including a single test only (RASopathy, metabolic, or nonimmune hydrops fetalis-targeted gene panel or exome sequencing), sequential testing (RASopathy panel followed by nonimmune hydrops fetalis panel, metabolic panel followed by nonimmune hydrops fetalis panel, RASopathy panel followed by exome sequencing, metabolic panel followed by exome sequencing, and nonimmune hydrops fetalis panel followed by exome sequencing), and no additional genetic testing. Our theoretical cohort included cases with normal karyotype and/or microarray and excluded cases of alloimmunization and congenital viral infections. As nonimmune hydrops fetalis and fetal effusions can present throughout gestation, whereas pregnancy management options vary depending on gestational age, outcomes were calculated for 3 time intervals: 10 to 18, 18 to 22, and >22 weeks of gestation. The primary outcome was incremental cost per quality-adjusted life year. Additional outcomes included termination of pregnancy, stillbirth, neonatal death, and neonates born with mild, moderate, and severe or profound disease phenotypes. The cost-effectiveness threshold was $100,000 per quality-adjusted life year. RESULTS: Among women <18 weeks of gestation, exome sequencing alone was the dominant strategy associated with the lowest costs ($221 million) and the highest quality-adjusted life years (10,288). Strategies with exome sequencing alone or as a sequential test resulted in more terminations but fewer stillbirths, neonatal deaths (NNDs), and affected infants than strategies without exome sequencing. Among women between 18 and 22 weeks of gestation, exome sequencing alone was also associated with the lowest costs ($188 million) and the highest quality-adjusted life years (8734), and similar trends were observed in pregnancy outcomes. Among patients >22 weeks of gestations, when termination was not available, exome sequencing was associated with lower costs ($300 million) and the highest quality-adjusted life years (8492). Exome sequencing was cost-effective up to a cost per test of $50,451 at <18 weeks of gestation, $50,423 at 18 to 22 weeks of gestation, and $9530 at >22 weeks of gestation. Targeted genetic panels and exome sequencing were cost-effective strategies compared with no additional genetic testing. CONCLUSION: For cases of nonimmune hydrops fetalis and fetal effusions with nondiagnostic karyotype or microarray, next-generation sequencing was cost-effective compared with a strategy without additional genetic testing. For those that undergo next-generation sequencing, exome sequencing was the cost-effective strategy compared with all other testing strategies using targeted gene panels, leading to lower costs and fewer adverse perinatal outcomes. Exome sequencing was cost-effective in a setting without the option for pregnancy termination. These data supported the routine use of exome sequencing when next-generation sequencing is pursued for establishing a genetic diagnosis underlying otherwise unexplained nonimmune hydrops fetalis and fetal effusions.

Maternal body-mass-index and neonatal brachial plexus palsy in a California cohort.

OBJECTIVE: To evaluate risk factors and describe the association between maternal pre-pregnancy body-mass-index (BMI) and neonatal brachial plexus palsy (BPP) in vaginal deliveries with and without shoulder dystocia. METHODS: This is a retrospective cohort study of singleton, non-anomalous, term vaginal deliveries in California (2007-2011). Deliveries were classified as with or without shoulder dystocia. Our primary outcome was BPP and the independent variable of interest was maternal pre-pregnancy BMI, which was categorized as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity I (30-34.9 kg/m2), obesity II (35-39.9 kg/m2) and obesity III (≥40 kg/m2). We evaluated demographics, maternal, labor, and neonatal characteristics using chi-squared tests and assessed the association of pre-pregnancy BMI with BPP using multivariable logistic regression models. RESULTS: In our cohort of 1,395,761 women, there were 21,463 deliveries with shoulder dystocia and 1,374,298 deliveries without shoulder dystocia. Among deliveries with shoulder dystocia, BPP was observed more frequently in neonates born to women with BMI categorized as overweight (32% vs. 29%; p < .001), obesity I (22% vs. 14%; p < .001), obesity II (10% vs. 6%; p < .001), and obesity III (8% vs. 3%; p < .001). After adjusting for confounders, the odds of BPP in deliveries with shoulder dystocia was significantly higher for women who were overweight (aOR = 1.65; 95% CI: 1.35-2.01), obesity I (aOR = 2.33; 95% CI: 1.86-2.90), obesity II (aOR = 2.56; 95% CI: 1.92-3.40), and obesity III (aOR = 3.80; 95% CI: 2.75-5.25). In deliveries without shoulder dystocia, BPP was more common in women with a BMI that was overweight (29% vs. 25%; p < .001), obesity I (17% vs. 11%; p < .001), obesity II (9% vs. 4%; p < .001), and obesity III (8% vs. 2%; p < .001). In this cohort, multivariable regression model showed similar results in women with a BMI that was overweight (aOR = 1.47; 95% CI: 1.19-1.81), obesity I (aOR = 1.99; 95% CI: 1.55-2.54), obesity II (aOR = 2.79; 95% CI: 2.04-3.83), and obesity III (aOR = 5.05; 95% CI: 3.63-7.03). CONCLUSION: Rising maternal pre-pregnancy BMI is associated with an increased risk of BPP in vaginal deliveries with and without shoulder dystocia. Preconception interventions targeting weight management may be beneficial in reducing BPP in all deliveries.

Incidence and Risk Factors for Postpartum Depression among Women with Preterm Prelabor Rupture of Membranes.

OBJECTIVE: Patients admitted for preterm prelabor rupture of membranes are more likely to have risk factors for postpartum depression, including preterm delivery, low-birthweight infants, and a stressful life event. However, there is a paucity of data characterizing the development of postpartum depression in this population. We aim to evaluate the incidence of and describe risk factors for postpartum depression among patients admitted with preterm prelabor rupture of membranes. STUDY DESIGN: This is a retrospective cohort study of patients admitted for preterm prelabor rupture of membranes in a single health system between 2013 and 2019. Patients who developed depression were compared with patients who did not develop depression. Demographic, antepartum/intrapartum/postpartum, and neonatal characteristics were compared. Bivariate statistics were used to compare outcomes and logistic regression was used to estimate adjusted odds ratios. RESULTS: Of 132 included patients with preterm prelabor rupture of membranes, 25 (18.9%) had postpartum depression. Factors significantly (p < 0.05) associated with postpartum depression included history of depression, anxiety, or any prior mental health condition. Earlier admission gestational age, rupture of membranes < 28 weeks, earlier delivery gestational age, neonatal morbidity, and neonatal necrotizing enterocolitis also were significantly associated with postpartum depression. Latency, maternal postpartum length of stay, and neonatal intensive care unit length of stay were not significantly associated. In regression models, only a history of depression (odds ratio [OR], 11.89; 95% confidence interval [CI], 2.78-50.95) and neonatal morbidity (OR, 5.01; 95% CI, 1.15-21.89) remained associated with postpartum depression. CONCLUSION: Postpartum depression occurred in nearly one in five patients with preterm prelabor rupture of membranes. Pre-existing depression and adverse neonatal outcomes strongly predicted postpartum depression. There is an urgent need to prioritize maternal mental health among patients with preterm prelabor rupture of membranes in the peripartum period. Further research is needed to identify optimal resources for mitigating the risk of postpartum depression in this cohort. KEY POINTS: · After PPROM, postpartum depression is common.. · Maternal depression and neonatal morbidity are risk factors for PPD.. · Hospital admission permits intervention for PPD..

The cost-effectiveness of genotyping versus sequencing for prenatal cystic fibrosis carrier screening.

OBJECTIVE: We investigated the cost-effectiveness of three sequential prenatal cystic fibrosis (CF) carrier screening strategies: genotyping both partners, genotyping one partner then sequencing the second, and sequencing both partners. METHOD: A decision-analytic model compared the strategies in a theoretical cohort of four million pregnant couples in the US population and five racial/ethnic sub-populations. Inputs were obtained from literature and varied in sensitivity analysis. Outcomes included cost per quality-adjusted life year (QALY), missed carrier couples, affected newborns, missed prenatal diagnoses, terminations, and procedure-related losses. The cost-effectiveness threshold was $100,000/QALY. RESULTS: Sequencing both partners identified 1099 carrier couples that were missed by genotyping both partners, leading to 273 fewer missed prenatal diagnoses, 152 more terminations, and 152 fewer affected newborns. A similar trend was observed in the genotyping followed by sequencing strategy. The incremental cost-effectiveness ratio of genotyping followed by sequencing compared to genotyping both partners was $180,004/QALY and the incremental cost-effectiveness ratio of sequencing both partners compared to genotyping followed by sequencing was $17.6 million/QALY. Sequencing both partners was cost-effective below $339 per test, genotyping/sequencing between $340 and $1837, and genotyping both partners above $1838. Sequencing was not cost-effective among five racial/ethnic sub-populations. CONCLUSION: Despite improved outcomes, sequencing for prenatal CF carrier screening was not cost-effective compared to genotyping. The clinical significance of the incremental cost-effectiveness of CF carrier screening is a matter of deliberation for public policy debate.

A Report of Tamoxifen and Parkinson's Disease in a US Population and a Review of the Literature.

BACKGROUND: Tamoxifen, a selective estrogen receptor modulator, has been shown to variably affect Parkinson's disease (PD) risk. OBJECTIVE: The aim of this study was to review epidemiological literature and evaluate the rate of PD in women with breast cancer with tamoxifen exposure in a US population. METHODS: A literature search was conducted to identify relevant studies. We performed a retrospective cohort analysis using the Nurses' Health Study Version One to report descriptive statistics. RESULTS: Most studies suggest there may be a time-dependent effect of tamoxifen on PD risk, with the risk increasing with time from exposure. However, rates of PD in persons exposed to tamoxifen overall appear to be low. In our cohort, PD was evident in 6.2 per 1,000 of those with tamoxifen use and 3.6 per 1,000 of those without tamoxifen use. Time from breast cancer to PD diagnosis was 9.7 years among women with tamoxifen exposure and 11.7 among women without. CONCLUSIONS: Tamoxifen may be associated with an increased risk for PD. Further research is needed to elucidate the role of estrogen and selective estrogen antagonism in PD. © 2021 International Parkinson and Movement Disorder Society.

Cell-free fetal DNA screening for detection of microdeletion syndromes: a cost-effectiveness analysis.

OBJECTIVE: Fetuses with genetic copy number variants are poorly detected through traditional prenatal screening. Microdeletions and duplications are clearly identified with diagnostic testing through chromosomal microarray, and screening of a select number of microdeletions has become available with cell-free DNA (cfDNA). Our study compares the costs and outcomes of cfDNA for five pathogenic microdeletions and aneuploidy to cfDNA for aneuploidy alone in conjunction with ultrasound. METHODS: A decision-analytic model was constructed using TreeAge software to compare cfDNA with microdeletions versus traditional cfDNA in a theoretical cohort of 4,000,000 pregnancies that would also be screened with ultrasound. Probabilities, costs, and utilities were derived from literature. The primary outcomes were the incremental cost per quality-adjusted life-year (QALY), terminations, and procedure-related losses. Because the microdeletion results are available, but not reported, on all cfDNA testing we set the incremental cost of the cfDNA microdeletion screening test to zero at baseline and varied the cost in sensitivity analysis. RESULTS: Screening with cfDNA for microdeletions among all pregnant women would result in 83 fewer anomalous neonates compared to traditional cfDNA with ultrasound. This reduction is due to increased diagnosis and termination of fetuses with microdeletions in this group. Routine use of cfDNA with microdeletions resulted in more procedure-related losses. cfDNA with microdeletions would improve effectiveness by 977 QALYs and decrease costs by $90,991,784. When we varied the specificity of the screening test, we found that it remained cost-effective down to a specificity of 91%. With a threshold of $100,000/QALY, microdeletion screening is cost-effective to an incremental increase in cost over cfDNA for aneuploidy alone of $47.10. CONCLUSION: For detection of fetal subchromosomal abnormalities, use of cfDNA with microdeletions is a cost-effective strategy compared to cfDNA for aneuploidy alone in conjunction with ultrasound. Cell-free DNA for microdeletions is not currently recommended as routine screening for low-risk obstetric populations by the American College of Obstetrics and Gynecologists or the Society for Maternal-Fetal Medicine. The test characteristics of cfDNA with microdeletions require greater examination before being routinely recommended.

A Cost-Effectiveness Analysis of Rooming-in and Breastfeeding in Neonatal Opioid Withdrawal.

OBJECTIVE: Our cost-effectiveness analysis investigated rooming-in versus not rooming-in to determine optimal management of neonates with neonatal opioid withdrawal (NOW). STUDY DESIGN: A decision-analytic model was constructed using TreeAge to compare rooming-in versus not rooming-in in a theoretical cohort of 23,200 newborns, the estimated annual number affected by NOW in the United States. Additional considerations included the effect of breast milk versus formula milk in evaluating the need for pharmacotherapy. Primary outcomes were needed for pharmacotherapy and neurodevelopment. We assumed a societal perspective in evaluating costs and maternal-neonatal quality-adjusted life years (QALYs) using a willingness-to-pay threshold of $100,000/QALY. Model inputs were derived from literature and varied in sensitivity analyses. RESULTS: Rooming-in resulted in fewer neonates requiring pharmacotherapy when compared with not rooming-in. The rooming-in group had more neonates with intact/mild neurodevelopmental impairment and fewer cases of moderate to severe impairment. Rooming-in resulted in cost savings of $509,652,728 and 12,333 additional QALYs per annual cohort. When the risk ratio of need for pharmacotherapy in rooming-in was varied across a clinically plausible range, rooming-in remained the cost-effective strategy. CONCLUSION: Maternal rooming-in with newborns affected by NOW leads to reduced costs and increased effectiveness. Management strategies should optimize nonpharmacological interventions as first-line treatment.

Point-of-care HIV viral load in pregnant women without prenatal care: a cost-effectiveness analysis.

BACKGROUND: Routine cesarean delivery has been shown to decrease mother-to-child-transmission of HIV in women with high viral load greater than 1000 copies/mL; however, women presenting late in pregnancy may not have viral load results before delivery. OBJECTIVE: Our study investigated the costs and outcomes of using a point-of-care HIV RNA viral load test to guide delivery compared with routine cesarean delivery for all in the setting of unknown viral load. STUDY DESIGN: A decision-analytic model was constructed using TreeAge software to compare HIV RNA viral load testing vs routine cesarean delivery for all in a theoretical cohort of 1275 HIV-positive women without prenatal care who presented at term for delivery, the estimated population of HIV-positive women without prenatal care in the United States annually. TreeAge Pro software is used to build decision trees modeling clinical problems and perform cost-effectiveness, sensitivity, and simulation analysis to identify the optimal outcome. The average cost per test was $15.22. To examine the downstream impact of a cesarean delivery and because most childbearing women in the United States will deliver 2 children, we incorporated a second pregnancy and delivery in the model. Primary outcomes were mother-to-child transmission, delivery mode, cesarean delivery-related complications, cost, and quality-adjusted life years. Model inputs were derived from the literature and varied in sensitivity analyses. The cost-effectiveness threshold was $100,000/quality-adjusted life year. RESULTS: Measuring viral load resulted in more HIV-infected neonates than routine cesarean delivery for all due to viral exposure during more frequent vaginal births in this strategy. There were no observed maternal deaths or differences in cesarean delivery-related complications. Quantifying viral load increased cost by $3,883,371 and decreased quality-adjusted life years by 63 compared with routine cesarean delivery for all. With the threshold set at $100,000/quality-adjusted life year, the viral load test is cost-effective only when the vertical transmission rate in women with high viral load was below 0.68% (baseline: 16.8%) and when the odds ratio of vertical transmission with routine cesarean delivery for all compared with vaginal delivery was above 0.885 (baseline: 0.3). CONCLUSIONS: For HIV-infected pregnant women without prenatal care, quantifying viral load to guide mode of delivery using a point-of-care test resulted in increased costs and decreased effectiveness when compared with routine cesarean delivery for all, even after including downstream complications of cesarean delivery.