Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort.

BACKGROUND: Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent progestogen with cerclage leaving uncertainty regarding best clinical practice. OBJECTIVE: This study aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies. METHODS: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use progestogen or who started progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no progestogen use during the entire pregnancy or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. RESULTS: During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States. CONCLUSION: Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone.

Short-term neonatal outcomes of pregnancies complicated by maternal obesity.

BACKGROUND: Maternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear. OBJECTIVE: This study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity. STUDY DESIGN: This study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m2), obese (body mass index, 30.0-39.9 kg/m2), morbidly obese (body mass index, 40.0-49.9 kg/m2), and super morbidly obese (body mass index, ≥50 kg/m2) patients were compared. Patients in the reference group were matched in a 1:1 ratio with those in all other groups with obesity using the baseline characteristics of age, race and ethnicity, previous cesarean delivery, preexisting diabetes mellitus, chronic hypertension, parity, cigarette use, and insurance status. The primary outcome was composite neonatal morbidity, including fetal or neonatal death, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, sepsis, birth injury, seizures, or ventilator use. We used a modified Poisson regression to examine the associations between body mass index and composite neonatal outcome. Preterm delivery at <37 weeks of gestation and the presence of maternal preeclampsia or eclampsia were included in the final model because of their known associations with neonatal outcomes. RESULTS: Overall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neonates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64). CONCLUSION: Compared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity.

Racial and Ethnic Disparities in Adverse Perinatal Outcomes at Term.

OBJECTIVE: This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. STUDY DESIGN: We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy. RESULTS: Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04-1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71-0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94-1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81-1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75-0.96 for Black; aRR = 0.68, 95% CI: 0.59-0.78 for Hispanic). CONCLUSION: Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. KEY POINTS: · Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes.. · After adjustment for confounders, higher risk for neonates of Black patients is no longer observed.. · Disparities in outcomes are strongly related to insurance status..

Association of Maternal Body Mass Index and Maternal Morbidity And Mortality.

OBJECTIVE: This study aimed to assess the association of maternal body mass index (BMI) with a composite of severe maternal outcomes. STUDY DESIGN: Secondary analysis of a cohort of deliveries on randomly selected days at 25 hospitals from 2008 to 2011. Data on comorbid conditions, intrapartum events, and postpartum course were collected. The reference group (REF, BMI: 18.5-29.9kg/m2), obese (OB; BMI: 30-39.9kg/m2), morbidly obese (MO; BMI: 40-49.9kg/m2), and super morbidly obese (SMO; BMI ≥ 50kg/m2) women were compared. The composite of severe maternal outcomes was defined as death, intensive care unit (ICU) admission, ventilator use, deep venous thrombosis/pulmonary embolus (DVT/PE), sepsis, hemorrhage, disseminated intravascular coagulation (DIC), unplanned operative procedure, or stroke. Patients in the REF group were matched 1:1 with those in all other obesity groups based on propensity score using the baseline characteristics of age, race/ethnicity, previous cesarean, preexisting diabetes, chronic hypertension, parity, cigarette use, and insurance status. Multivariable Poisson's regression was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the association between BMI and the composite outcome. Because cesarean delivery may be in the causal pathway between obesity and adverse maternal outcomes, models were then adjusted for mode of delivery to evaluate potential mediation. RESULTS: A total of 52,162 pregnant patients are included in the analysis. Risk of composite maternal outcomes was increased for SMO compared with REF but not for OB and MO [OB: aRR=1.06, 95% CI: 0.99-1.14; MO: aRR=1.10, 95% CI: 0.97-1.25; SMO: aRR=1.32, 95% CI: 1.02-1.70]. However, in the mediation analysis, cesarean appears to mediate 46% (95% CI: 31-50%) of the risk of severe morbidity for SMO compared with REF. CONCLUSION: Super morbid obesity is significantly associated with increased serious maternal morbidity and mortality; however, cesarean appears to mediate this association. Obesity and morbid obesity are not associated with maternal morbidity and mortality. KEY POINTS: · Super morbid obesity is associated with increased morbidity.. · Cesarean appears to mediate the association between super morbid obesity and morbidity.. · Obesity and morbid maternal obesity are not associated with morbidity..

Pregnancy Outcomes Associated With Use of Tobacco and Marijuana.

Tobacco and marijuana are the most common drugs of abuse among pregnant women. Cigarettes have been extensively studied and increase the risk of miscarriage, preterm birth, premature rupture of membranes, placental dysfunction, low birth rate, stillbirth, and infant mortality. There are sparse data on the specific effects of electronic cigarettes and smokeless tobacco in pregnancy. Literature on marijuana in pregnancy is limited by confounding, bias, and the retrospective nature of studies that do not capture contemporary trends in use. However, several studies suggest an association between marijuana and fetal growth restriction, low birth weight, and neurodevelopmental differences in offspring.

Accidente cerebrovascular isquémico de la arteria cerebral media / Middle cerebral artery ischemic cerebrovascular accident

Introducción: La segunda causa de muerte a nivel mundial corresponde a los ataques cerebrovasculares (ACV), de los cuales más de dos terceras partes son de origen isquémico. Causan discapacidad a largo plazo por lo que conocer la anatomía de la circulación cerebral y las posibles manifestaciones clínicas del ACV isquémico permite sospechar, diagnosticar y brindar un manejo oportuno y apropiado, reduciendo el impacto en la salud y la calidad de vida del paciente y sus cuidadores. Objetivo: relacionar los últimos hallazgos en la anatomía arterial cerebral, los mecanismos fisiopatológicos y las manifestaciones clínicas del ACV isquémico de la arteria cerebral media (ACM). Materiales y métodos: revisión de la literatura mediante la búsqueda con términos MeSH en la base de datos Medline, incluyendo estudios, ensayos y metaanálisis publicados entre 2000 y 2020 en inglés y español, además de otras referencias para complementar la información. Resultados: se seleccionaron 59 publicaciones, priorizando las de los últimos 5 años y las más relevantes del rango temporal consultado. Conclusiones: son escasos los estudios sobre la presentación clínica de los ACV, lo que sumado a la variabilidad interindividual de la irrigacióncerebral, dificulta la determinación clínica de la localización de la lesión dentro del lecho vascular. La reperfusión del área de penumbra isquémica como objetivo terapéutico se justifica por los mecanismos fisiopatológicos de la enfermedad.

Introduction: Cerebrovascular accidents (CVAs) are the second leading cause of death worldwide, of which more than two thirds are ischemic. They cause long-term disability, therefore, knowledge on the cerebral circulation anatomy and possible clinical manifestations of ischemic CVAs allows us to suspect, diagnose and provide timely and appropriate management, reducing the negative impact on the health and quality of life of patients and caregivers. Objective: to list the latest findings on cerebral arterial anatomy, pathophysiological mechanisms and clinical manifestations of ischemic middle cerebral artery (MCA) CVAs. Materials and methods: a literature review using a MeSH terms search in the Medline database, including studies, trials and meta-analyses published in English and Spanish between 2000 and 2020, using other complementary references. Results: 59 publications were selected prioritizing those published in the past 5 years and the most relevant in said period. Conclusions: there are few studies on the clinical presentation of CVAs, which, added to the interindividual variability of cerebral circulation anatomy, makes clinical identification of lesion location, within the vascular bed, difficult. Reperfusion of the ischemic penumbra region, as a therapeutic objective, is based on the pathophysiological mechanisms of the disease.

Neonatal and Maternal Composite Adverse Outcomes Among Low-Risk Nulliparous Women Compared With Multiparous Women at 39-41 Weeks of Gestation.

OBJECTIVE: To estimate whether the frequency of adverse maternal and neonatal outcomes differs between low-risk nulliparous and multiparous women at 39-41 weeks of gestation. METHODS: This is a secondary analysis of an observational obstetrics cohort of maternal-neonatal dyads at 25 hospitals. Low-risk women with nonanomalous singletons who delivered between 39 0/7 and 41 6/7 weeks of gestation were included. The composite neonatal adverse outcome included 5-minute Apgar score less than five, ventilator support or cardiopulmonary resuscitation, seizure, hypoxic ischemic encephalopathy, sepsis, bronchopulmonary dysplasia, persistent pulmonary hypertension, necrotizing enterocolitis, birth injury or perinatal death. The composite maternal adverse outcome included infection, third- or fourth-degree perineal laceration, thromboembolism, transfusion of blood products, or maternal death. Small for gestational age (SGA), large for gestational age (LGA), and shoulder dystocia requiring maneuvers were also evaluated. Multivariable regression was used to estimate adjusted relative risks (aRRs) and adjusted odds ratios (aORs) with 95% CIs. RESULTS: Of the 115,502 women in the overall cohort, 39,870 (34.5%) met eligibility criteria for this analysis; 18,245 (45.8%) were nulliparous. The risk of the composite neonatal adverse outcome (1.5% vs 1.0%, aRR 1.80, 95% CI 1.48-2.19), composite maternal adverse outcome (15.1% vs 3.3%, aRR 5.04, 95% CI 4.62-5.49), and SGA (8.9% vs 5.8%, aOR 1.45, 95% CI 1.33-1.57) was significantly higher in nulliparous than multiparous patients. The risk of LGA (aOR 0.65, 95% CI 0.60-0.71) and shoulder dystocia with maneuvers (aRR 0.68, 95% CI 0.60-0.77) was significantly lower in nulliparous rather than multiparous patients. CONCLUSION: The risk of composite adverse outcomes and SGA among low-risk nulliparous women at 39-41 weeks of gestation is significantly higher than among multiparous counterparts. However, nulliparous women had a lower risk of shoulder dystocia with maneuvers and LGA.

Duration of Operative Vaginal Delivery and Adverse Obstetric Outcomes.

OBJECTIVE: This study aimed to evaluate whether the number of vacuum pop-offs, the number of forceps pulls, or the duration of operative vaginal delivery (OVD) is associated with adverse maternal and perinatal outcomes. STUDY DESIGN: This is a secondary analysis of a multicenter observational cohort of women who underwent an attempted OVD. Women were stratified by the duration of OVD and the number of pop-offs (vacuum) or pulls (forceps) attempted. Severe perineal lacerations, failed OVD, and a composite adverse neonatal outcome were compared by the duration of OVD and number of pop-offs or pulls. RESULTS: Of the 115,502 women in the primary cohort, 5,325 (4.6%) underwent an attempt at OVD: 3,594 (67.5%) with vacuum and 1,731 (32.5%) with forceps. After adjusting for potential confounders, an increasing number of pop-offs was associated with an increased odds of the composite adverse neonatal outcome. However, an increasing duration of vacuum exhibited a stronger association with the composite adverse neonatal outcome. Similarly, the number of forceps pulls was less strongly associated with the composite adverse neonatal outcome compared with the duration of forceps application. CONCLUSION: The duration of OVD may be more associated with adverse neonatal outcomes than the number of pop-offs or pulls.

Sharpey-Schafer Lecture 2019: From retroviruses to human birth.

NEW FINDINGS: What is the topic of this review? The timing of birth is an important determinant of future health and well-being. This review examines the role of endogenous retroviruses as upstream regulators of key biological functions of the placenta, including cell-cell fusion, modulation of the maternal immune system, and the production of key pregnancy hormones. What advances does it highlight? Endogenous retroviruses are an obligate requirement for successful human reproduction. The products of retroviral elements, incorporated into the germline millions of years ago, have been co-opted to serve vital biological roles within the placenta that ultimately dictate the length of human pregnancy and therefore well-being trajectories. ABSTRACT: Gestational length at the time of birth is an important determinant of future health and well-being, yet the physiological regulation of the onset of labour in humans remains obscure. The evolution of egg formation and internal fertilisation in amniotes required a mechanism to suppress the contractile activity of the oviduct that is provided by progesterone. Delivery of the egg is then associated with the withdrawal of progesterone and a return of contractile activity to the reproductive tract. In mammals, the process of pregnancy is complicated further by the need to protect the fetus from potential attack by the maternal immune system. There is increasing evidence that retroviruses incorporated into the mammalian germline in the evolutionary past play a key role in suppressing the maternal immune reaction to the developing conceptus, organising the development of the placenta and perhaps, in humans, modulating the action of progesterone, determining gestational length and the onset of labour. It seems that the presence of an endogenous retrovirus is an obligate requirement for human reproduction.

The precursor for nerve growth factor (proNGF) is not a serum or biopsy-rinse biomarker for thyroid cancer diagnosis.

BACKGROUND: Nerves and neurotrophic growth factors are emerging promoters of cancer growth. The precursor for Nerve Growth Factor (proNGF) is overexpressed in thyroid cancer, but its potential role as a clinical biomarker has not been reported. Here we have examined the value of proNGF as a serum and biopsy-rinse biomarker for thyroid cancer diagnosis. METHODS: Patients presenting for thyroid surgery or biopsy were enrolled in separate cohorts examining serum (n = 204, including 46 cases of thyroid cancer) and biopsy-rinse specimens (n = 188, including 26 cases of thyroid cancer). ProNGF levels in clinical samples were analysed by ELISA. Univariate and multivariate statistical analyses were used to compare proNGF levels with malignancy status and clinicopathological parameters. RESULTS: ProNGF was not detected in the majority of serum samples (176/204, 86%) and the detection of proNGF was not associated with thyroid cancer diagnosis. In the few cases where proNGF was detected in the serum, thyroidectomy did not affect proNGF concentration, demonstrating that the thyroid was not the source of serum proNGF. Intriguingly, an association between hyperthyroidism and serum proNGF was observed (OR 3.3, 95% CI 1.6-8.7 p = 0.02). In biopsy-rinse, proNGF was detected in 73/188 (39%) cases, with no association between proNGF and thyroid cancer. However, a significant positive association between follicular lesions and biopsy-rinse proNGF was found (OR 3.3, 95% CI 1.2-8.7, p = 0.02). CONCLUSIONS: ProNGF levels in serum and biopsy-rinse are not increased in thyroid cancer and therefore proNGF is not a clinical biomarker for this condition.

The Precursor for Nerve Growth Factor (proNGF) in Thyroid Cancer Lymph Node Metastases: Correlation with Primary Tumour and Pathological Variables.

Metastases in thyroid cancer are associated with aggressive disease and increased patient morbidity, but the factors driving metastatic progression are unclear. The precursor for nerve growth factor (proNGF) is increased in primary thyroid cancers, but its expression or significance in metastases is not known. In this study, we analysed the expression of proNGF in a retrospective cohort of thyroid cancer lymph node metastases (n = 56), linked with corresponding primary tumours, by automated immunohistochemistry and digital quantification. Potential associations of proNGF immunostaining with clinical and pathological parameters were investigated. ProNGF staining intensity (defined by the median h-score) was significantly higher in lymph node metastases (h-score 94, interquartile range (IQR) 50-147) than in corresponding primary tumours (57, IQR 42-84) (p = 0.002). There was a correlation between proNGF expression in primary tumours and corresponding metastases, where there was a 0.68 (95% CI 0 to 1.2) increase in metastatic tumour h-score for each unit increase in the primary tumour h-score. However, larger tumours (both primary and metastatic) had lower proNGF expression. In a multivariate model, proNGF expression in nodal metastases was negatively correlated with lateral neck disease and being male. In conclusion, ProNGF is expressed in locoregional metastases of thyroid cancer and is higher in lymph node metastases than in primary tumours, but is not associated with high-risk clinical features.

Child Neurodevelopmental Outcomes by Prepregnancy Body Mass Index and Gestational Weight Gain.

OBJECTIVE: To study the association of prepregnancy body mass index (BMI) and gestational weight gain with child neurodevelopmental outcomes. METHODS: We performed a secondary analysis of data from two parallel, multicenter, randomized, double-blind, placebo-controlled thyroxine replacement trials in pregnant women with either hypothyroxinemia or subclinical hypothyroidism who delivered at term. Body mass index was categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30 or greater). We also evaluated early (20 weeks of gestation or less), late (greater than 20 weeks of gestation), and total gestational weight gain and categorized gestational weight gain as inadequate, adequate, and excessive per 2009 Institute of Medicine guidelines. Neurodevelopmental outcomes included 5-year Wechsler Preschool and Primary Scale of Intelligence and 3-year Differential Ability Scales-II. Linear and logistic regression analyses were performed and adjusted for maternal age, race-ethnicity, education, insurance status, parity, smoking and alcohol use, thyroid status (subclinical hypothyroidism or hypothyroxinemia), treatment group, gestational age at delivery, and neonatal sex. RESULTS: Of the 948 women included, 380 (40%), 305 (32%), and 263 (28%) had normal, overweight, and obese prepregnancy BMI, respectively. A total of 106 (11%), 212 (22%), and 630 (66%) of women had inadequate, adequate, and excessive total rates of gestational weight gain, respectively. Maternal differences among the BMI categories included race-ethnicity, education, insurance type, parity, and thyroid status (all P<.01), whereas the gestational weight gain groups only differed by parity (P<.001). In unadjusted analysis, children of obese (93.2±12.8; 88.5±13.3) and overweight (94.1±15.6; 89.6±16.0) women had lower Wechsler Preschool and Primary Scale of Intelligence and Differential Ability Scales-II scores, respectively, than normal-weight women (97.4±15.4; 93.9±16.0; P<.001 for all comparisons); however, in adjusted analysis, there were no differences in neurodevelopmental outcomes by maternal BMI. The association was primarily accounted for by race-ethnicity and education. In unadjusted and adjusted analyses, there were no differences in neurodevelopmental outcomes by adequacy of early, late, or total gestational weight gain. CONCLUSION: In women with either subclinical hypothyroidism or hypothyroxinemia, neither prepregnancy BMI nor gestational weight gain was associated with neurodevelopmental outcomes among children born at term in adjusted analyses.

Smoking cessation in pregnancy: a continuing challenge in the United States.

Despite significant population level declines, smoking during pregnancy remains a major public health issue in the United States (US). Approximately 360,000-500,000 smoke-exposed infants are born yearly, and prenatal smoking remains a leading modifiable cause of poor birth outcomes (e.g. birth < 37 gestational weeks, low birth weight, perinatal mortality). Women who smoke during pregnancy are more likely to be younger and from disadvantaged socioeconomic and racial and ethnic groups, with some US geographic regions reporting increased prenatal smoking rates since 2000. Such disparities in maternal prenatal smoking suggests some pregnant women face unique barriers to cessation. This paper reviews the current state and future direction of smoking cessation in pregnancy in the US. We briefly discuss the etiology of smoking addiction among women, the pathophysiology and effects of tobacco smoke exposure on pregnant women and their offspring, and the emerging issue of electronic nicotine delivery systems. Current population-based and individual smoking cessation interventions are reviewed in the context of pregnancy and barriers to cessation among US women. Finally, we consider interventions that are on the horizon and areas in need of further investigation.

Association Between Gestational Weight Gain and Perinatal Outcomes.

OBJECTIVE: To evaluate the association between gestational weight gain and maternal and neonatal outcomes in a large, geographically diverse cohort. METHODS: Trained chart abstractors at 25 hospitals obtained maternal and neonatal data for all deliveries on randomly selected days over 3 years (2008-2011). Gestational weight gain was derived using weight at delivery minus prepregnancy or first-trimester weight and categorized as below, within, or above the Institute of Medicine (IOM) guidelines in this retrospective cohort study. Maternal (primary or repeat cesarean delivery, third- or fourth-degree lacerations, severe postpartum hemorrhage, hypertensive disease of pregnancy) and neonatal (preterm birth, shoulder dystocia, macrosomia, hypoglycemia) outcomes were compared among women in the gestational weight gain categories in unadjusted and adjusted analyses with odds ratios (ORs) and 95% CI reported. Covariates included age, race-ethnicity, tobacco use, insurance type, parity, prior cesarean delivery, pregestational diabetes, hypertension, and hospital type. RESULTS: Of the 29,861 women included, 51% and 21% had gestational weight gain above and below the guidelines, respectively. There was an association between gestational weight gain above the IOM guidelines and cesarean delivery in both nulliparous women (adjusted OR 1.44, 95% CI 1.31-1.59) and multiparous women (adjusted OR 1.26, 95% CI 1.13-1.41) and hypertensive diseases of pregnancy in nulliparous and multiparous women combined (adjusted OR 1.84, 95% CI 1.66-2.04). For the neonatal outcomes, gestational weight gain above the IOM guidelines was associated with shoulder dystocia (adjusted OR 1.74, 95% CI 1.41-2.14), macrosomia (adjusted OR 2.66, 95% CI 2.03-3.48), and neonatal hypoglycemia (adjusted OR 1.60, 95% CI 1.16-2.22). Gestational weight gain below the guidelines was associated with spontaneous (adjusted OR 1.50, 95% CI 1.31-1.73) and indicated (adjusted OR 1.34, 95% CI 1.12-1.60) preterm birth. CONCLUSION: In a large, diverse cohort with prospectively collected data, gestational weight gain below or above guidelines is associated with a variety of adverse pregnancy outcomes.

Targeting the TSH receptor in thyroid cancer.

Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid-stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid-stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for individual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.

Antenatal Betamethasone for Women at Risk for Late Preterm Delivery.

BACKGROUND: Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities. METHODS: We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery. RESULTS: The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001). CONCLUSIONS: Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).

Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort.

BACKGROUND: Although preterm birth <37 weeks' gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates. OBJECTIVE: We sought to describe the contemporary frequencies of neonatal death, neonatal morbidities, and neonatal length of stay across the spectrum of preterm gestational ages. STUDY DESIGN: This was a secondary analysis of an obstetric cohort of 115,502 women and their neonates who were born in 25 hospitals nationwide, 2008 through 2011. All liveborn nonanomalous singleton preterm (23.0-36.9 weeks of gestation) neonates were included in this analysis. The frequency of neonatal death, major neonatal morbidity (intraventricular hemorrhage grade III/IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II/III, bronchopulmonary dysplasia, persistent pulmonary hypertension), and minor neonatal morbidity (hypotension requiring treatment, intraventricular hemorrhage grade I/II, necrotizing enterocolitis stage I, respiratory distress syndrome, hyperbilirubinemia requiring treatment) were calculated by delivery gestational age; each neonate was classified once by the worst outcome for which criteria was met. RESULTS: In all, 8334 deliveries met inclusion criteria. There were 119 (1.4%) neonatal deaths. In all, 657 (7.9%) neonates had major morbidity, 3136 (37.6%) had minor morbidity, and 4422 (53.1%) survived without any of the studied morbidities. Deaths declined rapidly with each advancing week of gestation. This decline in death was accompanied by an increase in major neonatal morbidity, which peaked at 54.8% at 25 weeks of gestation. As frequencies of death and major neonatal morbidity fell, minor neonatal morbidity increased, peaking at 81.7% at 31 weeks of gestation. The frequency of all morbidities fell >32 weeks. After 25 weeks, neonatal length of hospital stay decreased significantly with each additional completed week of pregnancy; among babies delivered from 26-32 weeks of gestation, each additional week in utero reduced the subsequent length of neonatal hospitalization by a minimum of 8 days. The median postmenstrual age at discharge nadired around 36 weeks' postmenstrual age for babies born at 31-35 weeks of gestation. CONCLUSION: Our data show that there is a continuum of outcomes, with each additional week of gestation conferring survival benefit while reducing the length of initial hospitalization. These contemporary data can be useful for patient counseling regarding preterm outcomes.

The placental protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza.

BACKGROUND: Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza. METHODS AND FINDINGS: Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1ß were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-α; p<0.0001 and IFN-λ; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1ß. CONCLUSIONS: Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.