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Importance: The emergence and promise of generative artificial intelligence (AI) represent a turning point for health care. Rigorous evaluation of generative AI deployment in clinical practice is needed to inform strategic decision-making. Objective: To evaluate the implementation of a large language model used to draft responses to patient messages in the electronic inbox. Design, Setting, and Participants: A 5-week, prospective, single-group quality improvement study was conducted from July 10 through August 13, 2023, at a single academic medical center (Stanford Health Care). All attending physicians, advanced practice practitioners, clinic nurses, and clinical pharmacists from the Divisions of Primary Care and Gastroenterology and Hepatology were enrolled in the pilot. Intervention: Draft replies to patient portal messages generated by a Health Insurance Portability and Accountability Act-compliant electronic health record-integrated large language model. Main Outcomes and Measures: The primary outcome was AI-generated draft reply utilization as a percentage of total patient message replies. Secondary outcomes included changes in time measures and clinician experience as assessed by survey. Results: A total of 197 clinicians were enrolled in the pilot; 35 clinicians who were prepilot beta users, out of office, or not tied to a specific ambulatory clinic were excluded, leaving 162 clinicians included in the analysis. The survey analysis cohort consisted of 73 participants (45.1%) who completed both the presurvey and postsurvey. In gastroenterology and hepatology, there were 58 physicians and APPs and 10 nurses. In primary care, there were 83 physicians and APPs, 4 nurses, and 8 clinical pharmacists. The mean AI-generated draft response utilization rate across clinicians was 20%. There was no change in reply action time, write time, or read time between the prepilot and pilot periods. There were statistically significant reductions in the 4-item physician task load score derivative (mean [SD], 61.31 [17.23] presurvey vs 47.26 [17.11] postsurvey; paired difference, -13.87; 95% CI, -17.38 to -9.50; P < .001) and work exhaustion scores (mean [SD], 1.95 [0.79] presurvey vs 1.62 [0.68] postsurvey; paired difference, -0.33; 95% CI, -0.50 to -0.17; P < .001). Conclusions and Relevance: In this quality improvement study of an early implementation of generative AI, there was notable adoption, usability, and improvement in assessments of burden and burnout. There was no improvement in time. Further code-to-bedside testing is needed to guide future development and organizational strategy.
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Centros Médicos Académicos , Inteligencia Artificial , Estados Unidos , Humanos , Estudios Prospectivos , Instituciones de Atención Ambulatoria , Agotamiento PsicológicoRESUMEN
On January 30, 2023, the Biden Administration announced its intention to end the existing COVID-19 public health emergency declaration. The transition to a "postpandemic" landscape presents a unique opportunity to sustain and strengthen pandemic-era changes in care delivery. With this in mind, we present 3 critical lessons learned from a primary care perspective during the COVID-19 pandemic. First, clinical workflows must support both in-person and internet-based care delivery. Second, the integration of asynchronous care delivery is critical. Third, planning for the future means planning for everyone, including those with potentially limited access to health care due to barriers in technology and communication. While these lessons are neither unique to primary care settings nor all-encompassing, they establish a grounded foundation on which to construct higher-quality, more resilient, and more equitable health systems.
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COVID-19 , Telemedicina , Humanos , Pandemias/prevención & control , Comunicación , Intención , Atención Primaria de SaludRESUMEN
INTRODUCTION: Although the prevalence of pain persisting after pregnancy or labour decreases with time, up to 35 % of women report pain 8 months to 12 years after childbirth. To prevent the development and reduce the impact of chronic pain, researchers and clinicians emphasize the importance of early diagnosis as well as timely and appropriate treatment. Previous studies have shown that when women with post-childbirth morbidities consult healthcare professionals during the first year following birth, their problems are often neglected, and they do not receive adequate treatment. OBJECTIVE: To explore how women with pain persisting for eight months after childbirth experienced encounters with healthcare. METHODS: A descriptive qualitative design with 20 face-to-face, semi-structured interviews. Data were analysed using inductive qualitative content analysis. RESULTS: "Pain ignored by healthcare" was identified as an essential theme and included four categories: "Questioned pain experience," "Inadequate pain management," "Lost in healthcare," and "Insufficient postpartum care " CONCLUSION: The women experienced that their pain was often not recognized or adequately treated, but instead ignored or trivialized. Recurring were descriptions of experienced knowledge gaps among the healthcare providers regarding pain and its management. There was an overall desire among women for a well-defined and well-functioning chain of care with better accessibility and scope.
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Parto Obstétrico , Trabajo de Parto , Embarazo , Femenino , Humanos , Dolor/etiología , Investigación Cualitativa , Atención a la Salud , PartoRESUMEN
BACKGROUND: Artificial intelligence-powered voice assistants (VAs), such as Apple Siri, Google Assistant, and Amazon Alexa, interact with users in natural language and are capable of responding to simple commands, searching the internet, and answering questions. Despite being an increasingly popular way for the public to access health information, VAs could be a source of ambiguous or potentially biased information. OBJECTIVE: In response to the ongoing prevalence of vaccine misinformation and disinformation, this study aims to evaluate how smartphone VAs respond to information- and recommendation-seeking inquiries regarding the COVID-19 vaccine. METHODS: A national cross-sectional survey of English-speaking adults who owned a smartphone with a VA installed was conducted online from April 22 to 28, 2021. The primary outcomes were the VAs' responses to 2 questions: "Should I get the COVID vaccine?" and "Is the COVID vaccine safe?" Directed content analysis was used to assign a negative, neutral, or positive connotation to each response and website title provided by the VAs. Statistical significance was assessed using the t test (parametric) or Mann-Whitney U (nonparametric) test for continuous variables and the chi-square or Fisher exact test for categorical variables. RESULTS: Of the 466 survey respondents included in the final analysis, 404 (86.7%) used Apple Siri, 53 (11.4%) used Google Assistant, and 9 (1.9%) used Amazon Alexa. In response to the question "Is the COVID vaccine safe?" 419 (89.9%) users received a direct response, of which 408 (97.3%) had a positive connotation encouraging users to get vaccinated. Of the websites presented, only 5.3% (11/207) had a positive connotation and 94.7% (196/207) had a neutral connotation. In response to the question "Should I get the COVID vaccine?" 93.1% (434/466) of users received a list of websites, of which 91.5% (1155/1262) had a neutral connotation. For both COVID-19 vaccine-related questions, there was no association between the connotation of a response and the age, gender, zip code, race or ethnicity, and education level of the respondent. CONCLUSIONS: Our study found that VAs were much more likely to respond directly with positive connotations to the question "Is the COVID vaccine safe?" but not respond directly and provide a list of websites with neutral connotations to the question "Should I get the COVID vaccine?" To our knowledge, this is the first study to evaluate how VAs respond to both information- and recommendation-seeking inquiries regarding the COVID-19 vaccine. These findings add to our growing understanding of both the opportunities and pitfalls of VAs in supporting public health information dissemination.
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Pregnancy is a naturally occurring hypercoagulable state, and COVID-19 can cause profound changes in the coagulation system associated with thromboinflammation. We report a case of a pregnant woman with moderate symptoms of COVID-19 and a severe coagulopathy with unexpected low levels of fibrinogen and factor VIII as well as atypical thrombelastometry results. She developed a severe placental dysfunction with intrauterine fetal distress and perinatal death. The case did not fulfil the criteria for preeclampsia or sepsis, and the adverse outcome was assessed as a direct effect of the COVID-19 infection with placental insufficiency, despite absence of serious maternal pulmonary symptoms. Atypical persistent coagulopathy may serve as an important marker of a serious obstetrical situation in COVID-19.
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BACKGROUND: Access to information is essential to achieving individual empowerment; meaning the ability to exercise control, manage one's own condition and make informed decisions. However, studies have shown that information provided to women regarding physiological changes during the postpartum period and postpartum health was inadequate, incorrect, or inconsistent. METHODS: The aim of this study was to explore informational support about pain persisting after childbirth and its consequences. A sequential explanatory mixed methods design was used. In the first, quantitative phase, 1,171 women, who gave birth eight months earlier, completed a self-administered questionnaire. In the second, qualitative phase, 20 women who experienced chronic pain were interviewed. Descriptive statistics and qualitative content analysis were used to analyse the data. RESULTS: The majority of the women did not receive information about pain persisting after childbirth, or the information was insufficient or incorrect. They did not know when and where to seek help and did not consult health care professionals. In addition, the lack of information had a negative impact on women's psychological well-being. All women expressed the need to be informed by health care professionals, irrespective of the individual risk of developing chronic pain. CONCLUSIONS: Health services should ensure availability of information to give the women opportunity to achieve empowerment to make good health decisions, increase control over their health and well-being as well as to enhance their self-efficacy. We propose that a booklet or leaflet with relevant information about the risk of developing chronic pain, symptoms and treatment, along with advice about appropriate health care settings should be provided as part of antenatal or postnatal care.
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Dolor Crónico , Dolor Crónico/etiología , Dolor Crónico/terapia , Parto Obstétrico/efectos adversos , Parto Obstétrico/psicología , Femenino , Humanos , Parto/psicología , Periodo Posparto/psicología , Embarazo , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Cesárea , Femenino , Sufrimiento Fetal , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Placenta/irrigación sanguínea , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Estudios Retrospectivos , SARS-CoV-2 , Mortinato/epidemiologíaRESUMEN
CONTEXT.: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
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COVID-19 , Muerte Perinatal , Placenta , Complicaciones Infecciosas del Embarazo , COVID-19/complicaciones , Femenino , Fibrina , Humanos , Hipoxia/patología , Hipoxia/virología , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Muerte Perinatal/etiología , Placenta/patología , Embarazo , Complicaciones Infecciosas del Embarazo/mortalidad , Complicaciones Infecciosas del Embarazo/patología , Complicaciones Infecciosas del Embarazo/virología , Estudios Retrospectivos , SARS-CoV-2 , MortinatoRESUMEN
BACKGROUND: Postpartum hemorrhage is an important cause of maternal death and morbidity. However, it is unclear whether women who experience postpartum hemorrhage are at an increased risk of postpartum depression. OBJECTIVES: To examine whether postpartum hemorrhage is associated with postpartum depression. METHODS: We conducted a national register-based cohort study of 486,476 Swedish-born women who had a singleton livebirth between 2007 and 2014. We excluded women with pre-existing depression or who filled a prescription for an antidepressant before childbirth. We classified postpartum depression up to 12 months after giving birth by the presence of an International Classification of Diseases, version 10 (ICD-10) diagnosis code for depression or a filled outpatient prescription for an antidepressant. We used Cox proportional hazard models, adjusting for maternal sociodemographic and obstetric factors. RESULTS: Postpartum depression was identified in 2.0% (630/31,663) of women with postpartum hemorrhage and 1.9% (8601/455,059) of women without postpartum hemorrhage. In our unadjusted analysis, postpartum hemorrhage was not associated with postpartum depression (unadjusted hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.97-1.15). After adjusting for maternal age, parity, education, cohabitation status, maternal smoking status, and early pregnancy maternal BMI, gestational age, and birthweight, the association did not appreciably change, with confidence intervals overlapping the null (adjusted HR = 1.08, 95% CI 0.99, 1.17). CONCLUSIONS: Within a population-based cohort of singleton women in Sweden with no prior history of depression, postpartum hemorrhage was not associated with postpartum depression.
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Depresión Posparto/diagnóstico , Hemorragia Posparto/patología , Adolescente , Adulto , Estudios de Cohortes , Depresión Posparto/epidemiología , Depresión Posparto/etiología , Escolaridad , Femenino , Humanos , Edad Materna , Embarazo , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Suecia/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To describe women's experiences of chronic pain related to childbirth approximately one year after labour. DESIGN: A qualitative design with face-to-face interviews analysed using inductive qualitative content analysis. PARTICIPANTS: Twenty women who reported chronic pain, with onset during pregnancy and/or following labour, approximately one year after childbirth. FINDINGS: The analysis revealed an essential theme, "Grieving over the past and struggling forward", and three categories "Mourning the losses", "Struggling with the present" and "Managing the future". CONCLUSIONS: This study provides new knowledge about women's experiences of chronic pain one year after childbirth. The pain severely reduced women´s previous ability to perform physical and social activities, negatively impacted psychological well-being and altered their self-image. Most of the women adopted a positive attitude and hoped for improved health in the future, although constantly struggling with the pain and its consequences. IMPLICATIONS FOR PRACTICE: This knowledge is particularly important as chronic pain may not diminish with time in predisposed individuals who may need help and support from health professionals in their endeavour to manage their pain. Healthcare providers, i.e. midwives, gynaecologists and general practitioners need to understand women´s experiences of chronic pain from their own perspective to improve identification and treatment of pain following childbirth, thus preventing women's suffering and potential long-term health problems. Future studies are warranted to further explore and discuss women's coping strategies, health seeking behaviour and experiences of health care.
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Dolor Crónico , Parto Obstétrico , Femenino , Pesar , Humanos , Parto , Embarazo , Investigación CualitativaRESUMEN
Background and aims Although several studies have been conducted, knowledge about chronic pain and dyspareunia after childbirth is still limited. The aim of this study was to explore the prevalence of chronic pain 8 months after childbirth in a cohort of Swedish women. The characteristics of chronic pain, such as, pain intensity, localization and frequency as well as pain interference with daily activities were examined. An additional aim was to describe the prevalence and intensity of dyspareunia. Methods Data were obtained through two self-administered questionnaires and the patient record system, Obstetrix. The first questionnaire was distributed on the maternity ward, 24-36 h after labour, to Swedish-speaking women who had given birth to a living child (n = 1,507). The second questionnaire was sent by post 8 months after childbirth. We collected data about demographic and social characteristics, pain presence and its onset, as well as pain intensity, frequency, bodily localization and pain interference with activities of women's daily life. Results In total, 1,171 (77.7%) responded to both questionnaires and were included in the analysis. Eight months after giving birth, totally 16.7% (195/1,171) of the women reported chronic pain related to childbirth. Of these, 9.1% (106/1,171) of women reported chronic pain with onset during pregnancy, 4.5% (53/1,171) experienced chronic pain with onset following labour and 3.1% (36/1,171) of women had both chronic pain with onset during pregnancy and chronic pain with onset following labour (each participant could only appear in one of the groups). Women reported a lower prevalence of chronic pain after vaginal delivery than caesarean section (61/916, 6.7% vs. 28/255, 11%, p = 0.021, OR 1.73, 95% CI 1.1-2.8). Moreover, 19.2% (211/1,098) of women experienced dyspareunia. There was no difference regarding prevalence of dyspareunia and the mode of delivery. Of those women who had a vaginal delivery, 19.5% (167/858) experienced pain during intercourse and the corresponding number for women after caesarean section was 18.3% (44/240) (p = 0.694, OR 0.929, CI 0.6-1.3). Approximately 80% of women with chronic pain, and 60% of women that experienced dyspareunia, rated their worst pain as moderate or severe (NRS 4-10). The corresponding number regarding average chronic pain was between 50 and 70%. More than 35% of the women with chronic pain scored pain interference with daily activities as ≥4 on a 0-10 NRS. Conclusions In our study, chronic pain 8 months after childbirth was reported by one in six women and one in five of the women experienced dyspareunia. The intensity of both chronic pain and dyspareunia was reported as moderate to severe in a significant proportion of women and chronic pain interfered considerably with daily activities. Implications There is a need to raise awareness among healthcare providers of this clinical problem as well as to revise and upgrade education regarding pain after childbirth to prevent potential long-term health problems, women's suffering and increased need for health care. The development of strategies for prevention, follow-up and treatment of pain is warranted. More research, including women's experiences of pain as well as intervention studies, are also needed.
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Dolor Crónico/epidemiología , Dispareunia/epidemiología , Actividades Cotidianas , Adulto , Femenino , Humanos , Persona de Mediana Edad , Parto , Periodo Posparto , Embarazo , Complicaciones del Embarazo/epidemiología , Prevalencia , Estudios Prospectivos , Encuestas y Cuestionarios , Suecia/epidemiologíaRESUMEN
INTRODUCTION: Preterm delivery is a major global public health challenge. The objective of this study was to determine how preterm delivery rates differ in a country with a very high human development index and to explore rural vs urban environmental and socioeconomic factors that may be responsible for this variation. MATERIAL AND METHODS: A population-based study was performed using data from the Swedish Medical Birth Register from 1998 to 2013. Sweden was chosen as a model because of its validated, routinely collected data and availability of individual social data. The total population comprised 1 335 802 singleton births. A multiple linear regression was used to adjust gestational age for known risk factors (maternal smoking, ethnicity, maternal education, maternal age, height, fetal sex, maternal diabetes, maternal hypertension, and parity). A second and a third model were subsequently fitted allowing separate intercepts for each municipality (as fixed or random effects). Adjusted gestational ages were converted to preterm delivery rates and mapped onto maternal residential municipalities. Additionally, the effects of six rural vs urban environmental and socioeconomic factors on gestational age were tested using a simple weighted linear regression. RESULTS: The study population preterm delivery rate was 4.12%. Marked differences from the overall preterm delivery rate were observed (rate estimates ranged from 1.73% to 6.31%). The statistical significance of this heterogeneity across municipalities was confirmed by a chi-squared test (P < 0.001). Around 20% of the gestational age variance explained by the full model (after adjustment for known variables described above) could be attributed to municipality-level effects. In addition, gestational age was found to be longer in areas with a higher fraction of built-upon land and other urban features. CONCLUSIONS: After adjusting for known risk factors, large geographical differences in rates of preterm delivery remain. Additional analyses to look at the effect of environmental and socioeconomic factors on gestational age found an increased gestational age in urban areas. Future research strategies could focus on investigating the urbanity effect to try to explain preterm delivery variation across countries with a very high human development index.
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Disparidades en Atención de Salud/estadística & datos numéricos , Trabajo de Parto Prematuro/epidemiología , Nacimiento Prematuro/epidemiología , Características de la Residencia/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Sistemas de Información Geográfica , Humanos , Recién Nacido , Recien Nacido Prematuro , Embarazo , Medición de Riesgo , Factores Socioeconómicos , Suecia/epidemiología , Adulto JovenRESUMEN
Infertility is a global health problem with an estimated incidence of 15%. Exposure to chemicals is a potential causal factor, and there is a lack of studies examining the effects on female germ cells. Here, we have studied the impact of different aryl hydrocarbon receptor (AHR) modulators on human ovarian follicles using a human ovarian tissue culture model. Expression of AHR was analyzed in tissue samples, and effects of the selected ligands resveratrol (RSVL), 6-formylindolo(3,2-b)carbazole (FICZ), and alpha-naphthoflavone (aNF) on AHR transactivation studied in a granulosa cell tumor line. Cortical human ovarian tissue containing preantral follicles was exposed to the ligands or vehicle (dimethylsulfoxide, DMSO) for seven days in vitro. Follicle growth was assessed by counting and measuring follicles from serial tissue sections, cell death quantified using in situ Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay, and steroid hormone production measured using a newly developed ultra-performance liquid chromatography method. AHR was expressed in all donated ovarian tissue samples. FICZ induced AHR transactivation in the granulosa cell line while aNF antagonised it. Compared to DMSO control, FICZ had no effect on follicles in culture, RSVL increased the proportion of growing follicles, and aNF increased cell death, disrupted growth of secondary follicles, increased testosterone, and reduced estradiol levels. We conclude that RSVL supports and aNF disrupts growth of human ovarian follicles in culture. We further conclude that the human ovarian tissue culture model is suitable for studying effects of chemicals on follicular biology.
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Benzoflavonas/farmacología , Folículo Ovárico/efectos de los fármacos , Estilbenos/farmacología , Adulto , Carbazoles/farmacología , Muerte Celular/efectos de los fármacos , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Folículo Ovárico/crecimiento & desarrollo , Receptores de Hidrocarburo de Aril/efectos de los fármacos , Receptores de Hidrocarburo de Aril/genética , Resveratrol , Técnicas de Cultivo de TejidosRESUMEN
We have examined the cellular localization and human amniotic fluid content of endothelin-1 (ET-1) and macrophage colony-stimulating factor (M-CSF). The study material consisted of amniotic fluid from 20 patients referred for amniocentesis, and placental samples from normal deliveries. ET-1 and M-CSF were analysed by radioimmunoassay and enzyme-linked immunosorbent assay respectively. The cellular localization of ET-1 and M-CSF in the amnion membranes was analysed by double-labelling immunocytochemistry using fluorescein isothiocyanate- and Cy3-labelled secondary antibodies. Release of ET-1 and M-CSF was studied in cultured amniocytes. We found that the mean +/- SD concentrations of ET-1 and M-CSF in fetal amniotic fluid were 45.6 +/- 17.3 pmol/l (range 16.8-85.5) and 7323 +/- 3415 ng/l (range 2640-12 110) respectively. Double-labelling immunocytochemistry showed that both M-CSF and ET-1 were co-localized in the same cells to a high extent. Further analysis revealed that levels of M-CSF, but not ET-1, were significantly correlated with pregnancy length. Both M-CSF and ET-1 were released from cultured amniocytes in response to interleukin-1. These findings show that ET-1 and M-CSF are partly co-localized to specific cells in the human amniotic membrane. As both M-CSF and ET-1 were released from cultured amniocytes in vitro, this suggests that they both may be secreted into fetal amniotic fluid in vivo as well.