Consensus Panel Recommendations for the Pharmacological Management of Breastfeeding Women with Postpartum Depression.

INTRODUCTION: Our consensus statement aims to clarify the use of antidepressants and anxiolytics during breastfeeding amidst clinical uncertainty. Despite recent studies, potential harm to breastfed newborns from these medications remains a concern, leading to abrupt discontinuation of necessary treatments or exclusive formula feeding, depriving newborns of benefits from mother's milk. METHODS: A panel of 16 experts, representing eight scientific societies with a keen interest in postpartum depression, was convened. Utilizing the Nominal Group Technique and following a comprehensive literature review, a consensus statement on the pharmacological treatment of breastfeeding women with depressive disorders was achieved. RESULTS: Four key research areas were delineated: (1) The imperative to address depressive and anxiety disorders during lactation, pinpointing the risks linked to untreated maternal depression during this period. (2) The evaluation of the cumulative risk of unfavorable infant outcomes associated with exposure to antidepressants or anxiolytics. (3) The long-term impact on infants' cognitive development or behavior due to exposure to these medications during breastfeeding. (4) The assessment of pharmacological interventions for opioid abuse in lactating women diagnosed with depressive disorders. CONCLUSIONS: The ensuing recommendations were as follows: Recommendation 1: Depressive and anxiety disorders, as well as their pharmacological treatment, are not contraindications for breastfeeding. Recommendation 2: The Panel advocates for the continuation of medication that has demonstrated efficacy during pregnancy. If initiating an antidepressant during breastfeeding is necessary, drugs with a superior safety profile and substantial epidemiological data, such as SSRIs, should be favored and prescribed at the lowest effective dose. Recommendation 3: For the short-term alleviation of anxiety symptoms and sleep disturbances, the Panel determined that benzodiazepines can be administered during breastfeeding. Recommendation 4: The Panel advises against discontinuing opioid abuse treatment during breastfeeding. Recommendation 5: The Panel endorses collaboration among specialists (e.g., psychiatrists, pediatricians, toxicologists), promoting multidisciplinary care whenever feasible. Coordination with the general practitioner is also recommended.

Depression Treatment in Pregnancy: Is It Safe, or Is It Not?

Prenatal depression carries substantial risks for maternal and fetal health and increases susceptibility to postpartum depression. Untreated depression in pregnancy is correlated with adverse outcomes such as an increased risk of suicidal ideation, miscarriage and neonatal growth problems. Notwithstanding concerns about the use of antidepressants, the available treatment options emphasize the importance of specialized medical supervision during gestation. The purpose of this paper is to conduct a brief literature review on the main antidepressant drugs and their effects on pregnancy, assessing their risks and benefits. The analysis of the literature shows that it is essential that pregnancy be followed by specialized doctors and multidisciplinary teams (obstetricians, psychiatrists and psychologists) who attend to the woman's needs. Depression can now be treated safely during pregnancy by choosing drugs that have no teratogenic effects and fewer side effects for both mother and child. Comprehensive strategies involving increased awareness, early diagnosis, clear guidelines and effective treatment are essential to mitigate the impact of perinatal depression.

Shedding of Syncytiotrophoblast-Derived Extracellular Vesicles Is Increased in Placenta Previa and Accreta Spectrum.

Placenta accreta spectrum (PAS) refers to excessive placental invasion into the maternal uterus and it is associated with high risk of obstetric haemorrhage and adverse maternal-neonatal outcomes. Currently, no specific circulating biomarkers of PAS have been identified. Given that in PAS disorders, the depth and the extension of placental invasion into the uterus are expected to be increased, in this study, we analysed plasma levels of syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with placenta previa (PP), at a high risk of PAS disorders, and pregnant women with normal placentation. Venous blood samples were collected from 35 women with ultrasonographic diagnosis of PP and 35 women with normal placentation, matched for gestational age. Plasma samples were ultracentrifuged at 120.000 g to collect extracellular vesicles (EVs). To identify and quantify plasma placenta-derived EVs (or STBEVs), EVs were analysed by flow cytometry using a monoclonal antibody against placental alkaline phosphatase (PLAP). Plasma levels of STBEVs were significantly higher in PP patients compared to controls. Plasma levels of STBEVs in women with PP and PAS showed a trend to a higher concentration compared to women with PP without PAS, although not reaching a statistical significance. Circulating STBEVs are potential candidates as biological markers to be integrated to ultrasonography in the antenatal screening programme for PAS. More studies are needed to confirm our observation in a larger cohort of patients and to analyse a possible association between high circulating levels of STBEVs and PAS.

Cesarean section rate: navigating the gap between WHO recommended range and current obstetrical challenges.

The cesarean section (CS) rate is very heterogeneous all over the world, reflecting the differences in the access to healthcare services. In higher-income countries, changes observed in the obstetrical population brought to an increased rate of cesarean section for maternal request. Besides, clinicians are facing an increasing number of induction of labor, with the consequent risk of CS if the management is inappropriate. Analyzing the rate of primary CS, the interpretation of intrapartum CTG and a tailored management of labor are also red flags that must be considered. In this optic, the implementation of obstetrics training and simulation programs and the improvement of clinical protocols with the latest evidence can lead to the reduction of unnecessary CS.

Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders.

INTRODUCTION: The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. METHODS: For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. RESULTS: The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. CONCLUSIONS: Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder.

Case report: vertical transmission of Plesiomonas shigelloides. Is it time to strengthen information on safety concerns for raw seafood dietary exposure in pregnancy?

The consumption of raw seafood, generally considered to be a healthy food, has greatly increased worldwide. Pathogens of fish can cause foodborne illnesses in humans, especially following the consumption of raw seafood from contaminated water.Foodborne illness in pregnant women is seldom the cause of neonatal infection, but, as in the reported cases, it has been associated with a high degree of morbidity and mortality.We present the case of a newborn with septicemia and meningitis caused by Plesiomonas shigelloides acquired via the transplacental route. There was a maternal history of ingestion of raw seafood 1 week prior to delivery. A few similar cases are described in the existing literature, which reports 7 neonatal deaths.Therefore, the primary objective of this paper is to highlight the fact that the popularity of raw seafood such as sushi, sashimi, and oysters, requires an improvement in dietary advice regarding unsafe choices in pregnancy in order to avoid preventable foodborne diseases, sometimes fatal for the newborn.

Large Pelvic Mass in a Female Adolescent: Atypical Presentation and Successful Treatment of Extraskeletal Ewing Sarcoma.

Extraskeletal Ewing sarcoma is a rare soft tissue tumor primarily affecting pediatric patients. The treatment is currently based on a multidisciplinary approach which allows, in cases of localized disease, good survival rates. We report the case of a 15-year-old female patient with a rapidly growing suspected pelvic mass misdiagnosed following the preliminary radiological exams, which assessed the findings as a mass of ovarian origin. The girl underwent surgery and, thanks to histopathological, immunohistochemical and real-time polymerase chain reaction (RT-PCR) examinations, it was possible to make the right diagnosis and to administer the best treatment in terms of surgery, chemotherapy and radiotherapy, obtaining a long disease-free interval and no recurrence to date.

SARS-CoV-2 IgG "heritage" in newborn: A credit of maternal natural infection.

Description of transplacental passage of specific SARS-CoV-2 IgG from mothers who contracted natural infection to their newborns. Retrospective cohort analysis including pregnant women diagnosed with SARS-CoV-2 and their newborns both tested for SARS-CoV-2 specific IgG and IgM with antibody titration at delivery. Nasopharyngeal swab were taken from both mothers and neonates, and tested for SARS-CoV-2 using polymerase chain reaction (PCR). IgM and IgG were analyzed in maternal and neonatal serum of 143 mother-infant dyads. 86% of women with a positive SARS-CoV-2 PCR >14 days before delivery developed specific IgG and 84% of their infants showed transplacental passage of IgG. Pregnant women infected with SARS-CoV-2 achieve antibody seroconversion following the kinetics described in the general population, and transplacental transfer of IgG specific antibodies occurs. No conclusion can be drawn on passive immunity efficacy or duration.

Contrast Agents during Pregnancy: Pros and Cons When Really Needed.

Many clinical conditions require radiological diagnostic exams based on the emission of different kinds of energy and the use of contrast agents, such as computerized tomography (CT), positron emission tomography (PET), magnetic resonance (MR), ultrasound (US), and X-ray imaging. Pregnant patients who should be submitted for diagnostic examinations with contrast agents represent a group of patients with whom it is necessary to consider both maternal and fetal effects. Radiological examinations use different types of contrast media, the most used and studied are represented by iodinate contrast agents, gadolinium, fluorodeoxyglucose, gastrographin, bariumsulfate, and nanobubbles used in contrast-enhanced ultrasound (CEUS). The present paper reports the available data about each contrast agent and its effect related to the mother and fetus. This review aims to clarify the clinical practices to follow in cases where a radiodiagnostic examination with a contrast medium is indicated to be performed on a pregnant patient.

Neoadjuvant Chemotherapy in Pregnant Patients with Cervical Cancer: A Monocentric Retrospective Study.

BACKGROUND: To date, little and discordant data still exists on the management of cervical cancer (CC) during pregnancy. In this paper, we report our experience of the treatment of these patients analyzing the oncologic, obstetric, and neonatal outcomes. METHODS: Between January 2010 and December 2021, 13 patients were diagnosed with CC during pregnancy. All patients underwent platinum-based neoadjuvant chemotherapy (NACT) and 11/13 patients underwent a cesarean radical hysterectomy (CRH). RESULTS: All 13 patients were diagnosed with squamous-cell carcinoma, FIGO-2018 stage between IB2-IIIC1. The majority of patients had a partial (61.5%) or complete (15.4%) response to NACT. Most patients had a regular course of pregnancy and the obstetric complications observed were gestational diabetes mellitus in 23.1% and IUGR in 15.4% of cases. CRH was performed in the absence of major complications. Only 2 patients (15.4%) had disease recurrence and only 1 patient (7.7%) died of disease. All children are currently healthy. At birth, we observed mainly prematurity-related complications (38.5% respiratory distress syndrome and 7.7% neonatal jaundice) and only a case of congenital malformation (hypospadias). In our pediatric population, we reported a case of malignancy (acute myeloid leukemia). CONCLUSION: NACT seems to be safe and efficacious in controlling tumor burden during pregnancy. CRH following NACT appears to be feasible, avoiding repeated surgery and treatment delays. This approach is also reasonably safe from a maternal, obstetric, and neonatal point of view.

Waterbirth: current knowledge and medico-legal issues.

Water immersion during labour and birth has become increasingly popular and widespread in many countries, in particular in midwifery-led care settings. Nevertheless, there is a dearth of quality data about waterbirth, with currently available findings mostly arising from observational studies and case series. The lack of high-quality evidence and the controversial results reported by different studies determined a "behavioral gap" without clearly objective, consistent indications allowing for a sound and evidence-based decision making process. Although water immersion in the first stage of labour is generally considered a safe and cost-effective method of pain management for women in labor, concerns still linger as to the safety of immersion during the second stage of labor and delivery, particularly in terms of neonatal risks and medico-legal implications.

Congenital Zika Syndrome: Genetic Avenues for Diagnosis and Therapy, Possible Management and Long-Term Outcomes.

Zika virus (ZIKV) was discovered in Uganda in 1947 and was originally isolated only in Africa and Asia. After a spike of microcephaly cases in Brazil, research has closely focused on different aspects of congenital ZIKV infection. In this review, we evaluated many aspects of the disease in order to build its natural history, with a focus on the long-term clinical and neuro-radiological outcomes in children. The authors have conducted a wide-ranging search spanning the 2012-2021 period from databases PubMed, PubMed Central, Web of Science, Medline, Scopus. Different sections reflect different points of congenital ZIKV infection syndrome: pathogenesis, prenatal diagnosis, clinical signs, neuroimaging and long-term developmental outcomes. It emerged that pathogenesis has not been fully clarified and that the clinical signs are not only limited to microcephaly. Given the current absence of treatments, we proposed schemes to optimize diagnostic protocols in endemic countries. It is essential to know the key aspects of this disease to guarantee early diagnosis, even in less severe cases, and an adequate management of the main chronic problems. Considering the relatively recent discovery of this congenital infectious syndrome, further studies and updated long-term follow-up are needed to further improve management strategies for this disease.

Adult Granulosa Cell Tumor in Pregnancy: A New Case and a Review of the Literature.

Granulosa cell tumors are rare ovarian tumors that can arise during pregnancy. We present a new case of recurrent adult granulosa cell tumor (AGCT) in pregnancy and a systematic review of the literature. The new case described is a 41-year-old woman G5P1122 with a prior history of AGCT that was referred to our center at 29 weeks because of a symptomatic abdominal mass, compatible with a possible recurrence of AGCT. At 36 + 3 weeks, she underwent a cesarean delivery for preterm labor and a total hysterectomy with a radical surgical staging. A healthy female infant was delivered. The patient received a platinum-based chemotherapy, with a 26-month follow-up negative for recurrence. Analyzing our case with the four identified by the literature review, three were recurrent and two were primary AGCT. Only one required surgery for AGCT at 15 weeks, while another underwent chemotherapy in pregnancy. In the other three cases, surgery for AGCT was done at the time of cesarean delivery. There were three cases of preterm delivery. All five pregnancies resulted in the birth of live babies with weight adequate for gestational age. In conclusion, AGCT diagnosed in pregnancy is rare, reported in only five cases. All gave birth to live babies in the third trimester, and maternal outcome at up to 18 months showed no recurrence.

Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification.

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair.

Surgical Treatment of "Large Uterine Masses" in Pregnancy: A Single-Center Experience.

Uterine myomas or uterine fibroids are the most common benign uterine masses affecting women. The management of large myoma during pregnancy is challenging, and surgical treatment is a possible option. We report nine cases of pregnant women affected by uterine masses larger than 10 cm, who underwent surgical treatment during the second trimester of pregnancy. In all cases, the masses were preconceptionally unknown and diagnosed during the first trimester. In eight cases, no maternal and fetal complications arose during or after surgical treatment and delivery occurred at full term of pregnancy. In one case, spontaneous abortion was recorded. In all cases, histologic diagnosis demonstrated the benign nature. Women affected by large uterine masses diagnosed for the first time in pregnancy could be taken into consideration for surgical treatment in a referral center during the second trimester.

Flu and Tdap Maternal Immunization Hesitancy in Times of COVID-19: An Italian Survey on Multiethnic Sample.

BACKGROUND: Tdap and flu immunization in pregnancy has been proven to be both effective and safe. Despite this, the vaccination rate in pregnant women is low in Italy. The COVID-19 pandemic has focused the attention of public opinion on communicable diseases, underlining the importance of primary prevention measures such as vaccination. We conducted a survey to investigate the behavior of pregnant women during the COVID-19 pandemic regarding maternal immunization to identify the reasons for vaccine hesitancy in order to overcome them. The new challenge is COVID-19 vaccination in pregnancy, and preliminary data show hesitancy towards it. Our analysis may be useful to improve immunization in the pregnant population, including through the COVID-19 vaccine. METHODS: A targeted survey was performed in Italy including 520 women who experienced in the first trimester of pregnancy, prior to the novel coronavirus spread, the 2019-2020 influenza vaccination campaign and the Tdap vaccine recommendation in the third trimester during the COVID pandemic. They represent a unique model to investigate if the new coronavirus outbreak might have changed attitudes towards vaccination in pregnancy in the same patients. Data were collected from a self-completed paper questionnaire. Descriptive statistics were calculated and percentages were compared using the chi-2 test or Fisher's exact test. RESULTS: We obtained data from 195 of the 520 women who gave birth during the inclusion period; 325 cases declined to participate in the survey. A total of 8.7% (17 cases) performed flu vaccination in the first trimester of pregnancy (pre-COVID era), 50.8% (99 cases) accepted Tdap immunization during their third trimester of gestation (COVID-19 pandemic) and 6.7% (13 cases) received both vaccines during pregnancy. For both the flu and Tdap shots, pregnant patients were more likely to accept the vaccines if they were recommended by a healthcare provider, whereas the main reason not to be vaccinated was the lack of such a recommendation. CONCLUSIONS: Our survey shows that the COVID-19 experience, which has raised awareness as to the role of vaccines in preventable diseases, may positively change attitudes toward immunization in pregnancy. Vaccination must be recommended to all pregnant women and organized during routine prenatal care as an important element for the prevention of communicable diseases. Vaccination hesitancy can be minimized through consistent recommendation to all pregnant women offered by obstetric staff during routine prenatal care. This approach is likely to be effective in terms of building trust in flu and Tdpa immunization among pregnant women, as well as to avoid unjustified hesitancy towards the more recent COVID-19 vaccines.

Differences between influenza and pertussis vaccination uptake in pregnancy: a multi-center survey study in Italy.

BACKGROUND: A suboptimal maternal vaccination coverage in 2017-18 has been reported in Italy. The study aims were to (i) assess changes in maternal influenza and tetanus, diphtheria and acellular pertussis vaccination coverage during 2018-19 influenza season compared to the previous season (ii) estimate influenza vaccine coverage among maternal care providers (MCPs) and (iii) explore the characteristics of vaccine delivery to pregnant women. METHODS: We conducted a cross-sectional survey among pregnant women and MCPs about influenza and pertussis immunization during pregnancy. We also collected information regarding prenatal care characteristics and vaccine delivery among four centers in Italy. RESULTS: We recruited 483 pregnant women and 452 MCPs. The influenza and pertussis vaccine uptake among pregnant women for the season 2018-19 was 14.9% and 60.9%, respectively. MCPs' influenza vaccine uptake was 33.6%. Knowing that the flu vaccine was safe for mothers and their infants and being vaccinated in the previous influenza season were associated with higher vaccine uptake. Regarding pertussis, being a housewife was associated to lower vaccine uptake, while knowing the vaccine is effective and safe for mothers and newborns were associated with higher pertussis vaccine uptake. The single most important factor associated to higher coverage of both influenza and pertussis vaccines was receiving a health-care provider's vaccine advice. Most pregnant women (69.4%) stated that they preferred to be vaccinated in their same prenatal care setting. CONCLUSIONS: Receiving a health-care provider's vaccine advice and the availability of vaccines during prenatal care visits might improve vaccination coverage among pregnant women.

Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer.

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse.