Methotrexate, an anti-folate, and misoprostol, a prostaglandin E-analog, are both used for disease treatment and prevention, and for ectopic or intrauterine pregnancy termination, respectively. Methotrexate is a potent t...Methotrexate, an anti-folate, and misoprostol, a prostaglandin E-analog, are both used for disease treatment and prevention, and for ectopic or intrauterine pregnancy termination, respectively. Methotrexate is a potent teratogen after early pregnancy higher-dose administration. Methotrexate-embryopathy includes facial dysmorphism, craniosynostosis, heart defects and limb abnormalities, often accompanied by growth deficiency. Misoprostol, however, is associated with a smaller risk to the embryo, mainly for limb defects and for Mӧbius sequence. In this narrative review, the literature on the effect of early pregnancy exposure to these drugs on the embryo is discussed with critical evaluation of the evidence from the first signal to current knowledge, regarding the phenotype, dose, timing in pregnancy, biological plausibility, consistency between studies, and risk estimate. Some open questions and legal, social, and political aspects of their use are addressed. Despite the risk to the embryo, these medications have an important role in women's health.
Thyroid cancer encountered during pregnancy requires a systematic approach balancing risks and benefits to both maternal and fetal health specific to this unique phase of life. Thyroid nodules are common and are predomin...Thyroid cancer encountered during pregnancy requires a systematic approach balancing risks and benefits to both maternal and fetal health specific to this unique phase of life. Thyroid nodules are common and are predominantly evaluated to detect thyroid cancer. Clinical examination, serum thyroid stimulating hormone (TSH) measurement, ultrasonographic risk stratification, and fine needle aspiration biopsy when indicated are used to assess for malignancy. When thyroid cancer is diagnosed, further evaluation determines whether surgery during gestation is necessary or if delaying surgery until after delivery to minimize fetal and maternal risks is preferred. For patients who have undergone thyroidectomy for thyroid cancer, whether during pregnancy or before it, active management of levothyroxine therapy during pregnancy is recommended to ensure a sufficient thyroid hormone supply for both thyroid cancer treatment and optimal reproductive outcomes. This clinically oriented review summarizes key data, recommendations, and current trends regarding thyroid cancer care in pregnancy.
Pregnancy associated cancer is fortunately rare. However, cancer risk is age related, and the proportion of births to older women in the United States appears to be increasing. As a result of delayed childbearing and bet...Pregnancy associated cancer is fortunately rare. However, cancer risk is age related, and the proportion of births to older women in the United States appears to be increasing. As a result of delayed childbearing and better detection, cancer may be increasing in the obstetric population. A review of data from the United States Inpatient Sample found that from 2000 to 2019 the proportion of deliveries with an active cancer diagnosis doubled and deliveries with a diagnosis of a history of cancer more than tripled. These trends and associations are similar to findings from other registries and population-based studies which show that pregnancy associated cancer is increasing and associated with a range of adverse obstetric outcomes including severe maternal morbidity and preterm birth. Given these trends and findings it is likely pregnancy associated cancer will continue to be of public health and clinical importance and represent an ongoing challenge given the maternal and neonatal risks and specialized, coordinated care required to optimize outcomes.
In recent decades, the mean age of childbearing has increased in the United States and other developed countries, coinciding with a rise in cancer diagnoses during pregnancy. This trend is partly due to the increased use...In recent decades, the mean age of childbearing has increased in the United States and other developed countries, coinciding with a rise in cancer diagnoses during pregnancy. This trend is partly due to the increased use of assisted reproductive technologies and a decrease in the mean age of cancer onset for several malignancies. Concurrently, immune checkpoint inhibitors (ICIs) have become a standard treatment for various cancers, yet their safety during pregnancy remains under-researched. This article explores the complex intersection of cancer treatment and pregnancy, focusing on the use of ICIs. Despite societal concerns, data on the safety of ICIs during pregnancy are limited, primarily derived from preclinical animal studies and case reports. While most case reports suggest no significant adverse effects on live births, isolated incidents of severe neonatal complications have been documented. The potential for immune-related adverse events (irAEs) in neonates, such as thyroiditis or enterocolitis, underscores the need for caution. Given the lack of comprehensive data, clinicians face challenging decisions when treating pregnant cancer patients, particularly in metastatic settings where ICIs may be the only viable option. This article advocates for a careful risk-benefit analysis and informed patient discussions, emphasizing the need for further research to guide clinical decision-making in these complex scenarios.
Obstetric care for patients with cancer diagnoses during pregnancy is medically and ethically complex, and limited prospective data and national guidelines are available to guide care. Guiding principles for treatment ar...Obstetric care for patients with cancer diagnoses during pregnancy is medically and ethically complex, and limited prospective data and national guidelines are available to guide care. Guiding principles for treatment are to optimize maternal outcomes while minimizing neonatal morbidity. Oncologic work- up and management are dependent on the trimester of diagnosis, and are specific to the type, stage, and grade of the oncologic diagnosis. Obstetric care should occur within a multidisciplinary setting, with involvement of maternal fetal medicine, oncologic specialists, and mental health support.
OBJECTIVE: The objective of this manuscript is to review the epidemiology, diagnosis, treatment and outcomes of ovarian cancers diagnosed during pregnancy. FINDING: Ovarian cancer in pregnancy, although rare, is more lik...OBJECTIVE: The objective of this manuscript is to review the epidemiology, diagnosis, treatment and outcomes of ovarian cancers diagnosed during pregnancy. FINDING: Ovarian cancer in pregnancy, although rare, is more likely to be diagnosed early during pregnancy due to the increased use of high resolution ultrasound. Treatment will depend on a multidisciplinary team. These cancers are usually treated with surgery alone during pregnancy, optimally between 13-20 weeks to reduce the risk of miscarriage or preterm labor. Chemotherapy is usually given after delivery if appropriate to the tumor type, unless the patient has widely metastatic disease. CONCLUSION: The majority of ovarian cancers diagnosed during pregnancy are Stage I due to both young age and increased use of early ultrasound during pregnancy and have a better overall prognosis than the cancers detected in older women.
Malignancies arising during pregnancy are an infrequent occurrence, leading to a paucity of data on the optimal management of cancers during pregnancy. Unlike most solid tumors, the primary, and often curative, managemen...Malignancies arising during pregnancy are an infrequent occurrence, leading to a paucity of data on the optimal management of cancers during pregnancy. Unlike most solid tumors, the primary, and often curative, management of hematologic malignancies relies heavily on multiagent cytotoxic chemotherapies over surgery and other localized therapies, making their management during pregnancy even more complex and hazardous to both mother and fetus. Close multidisciplinary care and coordination between obstetrician, maternal fetal medicine, and oncologists are essential given the dangers to both in the management, from diagnosis and throughout treatment, even through delivery and survivorship. Due to the importance of this topic and the number of lives that could be impacted, guidelines have been published by interdisciplinary expert panels based on available data and clinical experience. This review addresses the management of both Hodgkin and non-Hodgkin lymphomas as well as acute and chronic leukemias. The optimal diagnostic approaches, and therapeutic schemes, including the use of cellular therapies, immunotherapies, targeted and cytotoxic agents, as well as guidance on decision making regarding management of the pregnancy weighing both the maternal and fetal risks and benefits of each approach are discussed herein.
Cutaneous melanoma is a malignant neoplasm of melanocytes that most frequently affects the skin. It is the most common malignancy in women of childbearing age, and accounts for almost one-third of all malignancies diagno...Cutaneous melanoma is a malignant neoplasm of melanocytes that most frequently affects the skin. It is the most common malignancy in women of childbearing age, and accounts for almost one-third of all malignancies diagnosed during gestation. The pathophysiology of melanoma, particularly during pregnancy, is not well understood, but there are several ways in which the physiologic state pregnancy may impact melanoma. Based on the available literature, pregnancy does not seem to worsen maternal outcomes with melanoma, and outside of placental and fetal metastases, melanoma does not seem to cause serious obstetric or fetal complications. Treatment of localized melanoma during pregnancy follows guidelines for the general population, but advanced melanoma in pregnancy poses unique challenges given the lack of unifying research and management recommendations. Herein, we review the current literature, highlighting diagnostic clinical pearls and key multidisciplinary management considerations with regard to melanoma in the child-bearing population.
Cervical cancer is one of the most common and challenging malignancies diagnosed during pregnancy, requiring a complex balance between effective oncological management and pregnancy preservation. This narrative review sy...Cervical cancer is one of the most common and challenging malignancies diagnosed during pregnancy, requiring a complex balance between effective oncological management and pregnancy preservation. This narrative review synthesizes current evidence and clinical experience regarding the management of cervical cancer in pregnant patients. While treatment should generally follow standard protocols for nonpregnant patients, emerging data suggest that pregnancy can often be safely maintained without compromising oncological outcomes. Nevertheless, robust prognostic data from larger patient cohorts are still needed. Individualized treatment approaches that incorporate the patient's preferences and values are crucial. Given the complexities involved, referral to specialized tertiary centers with expertise in the oncological and obstetric care of pregnant cancer patients is strongly recommended to ensure optimal outcomes for both mother and child.
Pregnancy-Associated Breast Cancer (PABC) is a rare but complex condition that presents both professional and ethical challenges. Diagnosis is often delayed due to breast changes associated with pregnancy and puerperium,...Pregnancy-Associated Breast Cancer (PABC) is a rare but complex condition that presents both professional and ethical challenges. Diagnosis is often delayed due to breast changes associated with pregnancy and puerperium, which can mask malignant findings. Management requires a multidisciplinary approach that carefully balances maternal and fetal risks. Chemotherapy is generally reserved for the second and third trimesters to avoid teratogenicity, with anthracyclines being the most well-studied and safest agents in this setting. Surgical decisions are influenced by factors such as cancer stage, gestational age, and the timing of potential radiation therapy. Notably, radiation therapy, endocrine therapy, and most targeted therapies are contraindicated during pregnancy due to potential harm to the fetus. Comprehensive care should include robust social and mental health support for the mother and her family to help navigate the physical and emotional challenges during this period.
Noninvasive ventilation (NIV) is increasingly used in neonatal care to reduce lung injury and improve respiratory outcomes. However, its effects on cardiovascular function and cardiopulmonary interactions, particularly i...Noninvasive ventilation (NIV) is increasingly used in neonatal care to reduce lung injury and improve respiratory outcomes. However, its effects on cardiovascular function and cardiopulmonary interactions, particularly in preterm neonates, remain unclear. This paper reviews the hemodynamic changes associated with NIV and provides an overview of how NIV influences cardiac preload, pulmonary vascular resistance, ventricular output, and systemic blood flow. NIV also affects these parameters in different ways in neonates with compromised cardiovascular stability, such as those with persistent pulmonary hypertension, patent ductus arteriosus and systemic hypotension. The synthesis of current evidence underscores that optimizing NIV requires careful titration of ventilatory parameters and highlights the potential role of targeted echocardiography and other clinical monitoring tools in guiding individualized management strategies. This review emphasizes the need for a nuanced approach that balances respiratory support with hemodynamic stability and calls for further research to establish best practices for the safe and effective use of NIV in neonates with hemodynamic compromise.
Bronchopulmonary dysplasia (BPD) is a major complication of prematurity, leading to long-term pulmonary morbidity. Invasive mechanical ventilation (IMV) is associated with ventilator-induced lung injury, oxygen toxicity,...Bronchopulmonary dysplasia (BPD) is a major complication of prematurity, leading to long-term pulmonary morbidity. Invasive mechanical ventilation (IMV) is associated with ventilator-induced lung injury, oxygen toxicity, and inflammation, all contributing to BPD pathogenesis. Non-invasive ventilation (NIV) has emerged as a key strategy to reduce the incidence and severity of BPD. We examine the role of various NIV strategies in the respiratory management of premature infants. We discuss the common forms of NIV, including nasal continuous positive airway pressure, nasal intermittent positive pressure ventilation, bilevel positive airway pressure, high-flow nasal cannula, and nasal high-frequency ventilation, with a focus on their mechanisms of action, benefits, and limitations. Several studies have demonstrated that early and appropriate NIV use can reduce the incidence of BPD, improve oxygenation, and promote lung growth. However, NIV is not without challenges, including patient selection, the timing of initiation, and potential difficulties in achieving adequate ventilation, especially in extremely low birth weight neonates. Adjunctive therapies such as early surfactant therapy, less invasive surfactant administration, and caffeine may enhance the effectiveness of NIV. In conclusion, NIV is a promising approach to decreasing BPD, yet its effectiveness relies on proper clinical application and integration with other therapies to maximize its benefits.
Providing most appropriate noninvasive ventilation (NIV) for preterm infants remains priority in neonatal intensive care units. Several newer modes of ventilation have evolved including continuous positive airway pressur...Providing most appropriate noninvasive ventilation (NIV) for preterm infants remains priority in neonatal intensive care units. Several newer modes of ventilation have evolved including continuous positive airway pressure, nasal intermittent positive pressure ventilation and noninvasive high frequency ventilation to meet patients' demands. Advanced level of monitoring is performed while patients are receiving NIV for optimization of the respiratory support. Point of care lung ultrasound and electrical impedance tomography are the newer tools that give insights towards aeration of the lungs. Pulmonary near infrared spectroscopy, electromyography of the diaphragm and advanced techniques of noninvasive pulmonary function testing provide data focusing on the performance of lungs. The hybrid modalities of ventilators used often in adults are needed in neonates to provide on demand individualized level of noninvasive respiratory support. Automated oxygen adjustment, inhaled nitric oxide and heliox can be benefcial when successfully provided through NIV. Delivery room NIV has a strong potential to improve neonatal outcomes. Further research should be focused taking into consideration physiologic needs and applying customized approach to meet patient's demands. Artificial intelligence leading to precision treatment is the way forward for providing individualized respiratory support for newborn infants.
Care of the extremely premature infant has been in constant state of re-evaluation as the population, technologies and knowledge continue to evolve. A growing population of extremely low gestational age neonates (ELGAN -...Care of the extremely premature infant has been in constant state of re-evaluation as the population, technologies and knowledge continue to evolve. A growing population of extremely low gestational age neonates (ELGAN - <28 weeks) and "nanopremies" (<24 weeks) are undergoing successful resuscitation, stabilization, and intensive care leading to improved survival. Respiratory care is the cornerstone of ELGAN management, as their lungs are at a critical stage of development. The lifesaving intensive care they require can lead to various injurious stimuli making them prone to bronchopulmonary dysplasia (BPD). Non-invasive ventilation (NIV), including continuous positive airway pressure ventilation (CPAP) and nasal intermittent positive pressure ventilation (NIPPV) has evolved and can appropriately support premature infants' breathing, while limiting the invasiveness and associated complications of mechanical ventilation. This review focuses on our current understanding, knowledge and evidence gathered via meta-analysis on these two modes of NIV in preterm infants, when used either as primary intent respiratory support post-birth or following extubation. We will summarize the current data of recent meta-analyses, their pitfalls, and the remaining questions to be addressed by future research to optimize the use of these modes of respiratory support in preterm infants most at risk for BPD.
Semin Perinatol
· 2025 Aug · PMID 40023691
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Full text
Nasal continuous positive airway pressure (CPAP) is the standard of care for the acute management of preterm infants with respiratory distress, however, the optimal duration of CPAP in stable preterm infants is unknown....Nasal continuous positive airway pressure (CPAP) is the standard of care for the acute management of preterm infants with respiratory distress, however, the optimal duration of CPAP in stable preterm infants is unknown. In utero, preclinical, and clinical data support the premise that mechanical stretch from CPAP can increase lung growth and development. This paper will review data to support this premise, studies examining weaning infants off CPAP, the current practices in the United States regarding CPAP application and duration, and clinical studies of the association of CPAP duration and subsequent lung growth and development. Pulmonary function testing will be presented as an important outcome throughout these trials.
Non-invasive high-frequency oscillatory ventilation (NHFOV) is the main non-conventional ventilatory mode used in newborn infants. NHFOV has been spreading, while knowledge about its physiology, mechanics and clinical ap...Non-invasive high-frequency oscillatory ventilation (NHFOV) is the main non-conventional ventilatory mode used in newborn infants. NHFOV has been spreading, while knowledge about its physiology, mechanics and clinical application has increased overtime. This is to be considered as a living review, since we here update the knowledge that was originally summarized in a previously published review. We first focus on physiology of such a complex respiratory support technique with practical data on interfaces, patient-ventilator interaction and devices to provide NHFOV. We then move to the evidence-based review of parallel randomized clinical trial published so far. We provide both qualitative and quantitative synthesis of results for the two commonest outcomes, i.e. need for intubation and invasive ventilation and CO elimination. We also provide our protocol to use NHFOV together with other respiratory support modes and we provide suggestions on parameters boundaries and identification of patients to treat. We finally identify still open questions needing future research to optimize the use of NHFOV In preterm infants.
Teratology, the study of congenital anomalies caused by environmental, chemical, and biological factors, derives from the Greek "teratos," meaning monster, reflecting historical intrigue with birth defects. While the fie...Teratology, the study of congenital anomalies caused by environmental, chemical, and biological factors, derives from the Greek "teratos," meaning monster, reflecting historical intrigue with birth defects. While the field is relatively modern, curiosity about anomalies spans millennia, as seen in ancient art and mythology. Over time, societal views shifted from curiosity to fear, recognizing birth defects as potential social, economic, and spiritual burdens. The 20th century brought pivotal advances. Discoveries such as the rubella-birth defect link, ionizing radiation effects, and the thalidomide disaster reshaped understanding and regulations. Wilson's "Six Principles of Teratology" established guidelines for how teratogens impact development, focusing on timing, dose-response relationships, and genetic susceptibility. Despite progress, birth defects still affect millions worldwide, underscoring the importance of education and counseling on teratogenic risks. Resources like TERIS, Reprotox, and MotherToBaby now provide healthcare professionals with evidence-based guidance, aiding informed decision-making and improving pregnancy outcomes. The ever-evolving field of teratology emphasizes the need for ongoing research and effective communication to manage and prevent birth defects.
Non-invasive ventilation (NIV) is a form of respiratory support provided primarily to preterm born infants in an effort to avoid any endotracheal intubation or as a weaning step following invasive ventilation. In the con...Non-invasive ventilation (NIV) is a form of respiratory support provided primarily to preterm born infants in an effort to avoid any endotracheal intubation or as a weaning step following invasive ventilation. In the context of the respiratory distress syndrome of the newborn, NIV could target and partially reverse specific pathophysiological phenomena, by improving alveolar recruitment and establishing adequate functional residual capacity. It can also assist in minimizing lung injury by avoiding excessive pressure delivery, which can be harmful for the developing lung. Non-invasive ventilation can unload the respiratory muscles and decrease the work of breathing as reported by studies that compare the measured work of breathing at increasing levels of non-invasive support. NIV can also be beneficial in moderating the frequency and intensity of apnea of prematurity. Unintended physiological effects of NIV include gaseous distension of the gastrointestinal tract and increased incidence of air-leak complications. During NIV there is also a lack of direct access to the trachea for suctioning and pulmonary toiletry. Insufficient non-invasive respiratory support could be associated with inadequate oxygenation and ventilation, insufficient gas exchange and atelectotrauma. Excessive provision of non-invasive support could be inefficient or harmful, as overdistention can be associated with decreased compliance of the respiratory system, impaired gas exchange and abnormal diaphragmatic function. An individualized physiological approach could, thus, aim to optimize the beneficial effects of non-invasive ventilation while avoiding inadequate or excessive levels of support.