Publications by authors named "Irene Cetin"

178 Publications

Mitochondrial and Oxidative Unbalance in Placentas from Mothers with SARS-CoV-2 Infection.

Antioxidants (Basel) 2021 Sep 24;10(10). Epub 2021 Sep 24.

Department of Biomedical and Clinical Sciences Luigi Sacco, Università degli Studi di Milano, 20157 Milano, Italy.

SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative features in COVID-19 and healthy mothers. mtDNA levels, DNA oxidative damage, expression levels of genes involved in antioxidant defenses, mitochondrial dynamics and respiratory chain subunits were investigated in placentas from singleton pregnancies of 30 women with SARS-CoV-2 infection during the third trimester (12 asymptomatic, 18 symptomatic) and 16 controls. mtDNA levels decreased in COVID-19 placentas vs. controls and inversely correlated with DNA oxidative damage, which increased in the symptomatic group. Antioxidant gene expressions decreased in SARS-CoV-2 mothers (, ). Symptomatic cases also showed a lower expression of respiratory chain (, , ) and mt dynamics (, ) genes. Alterations in placental mitochondrial features and oxidative balance in COVID-19-affected mothers might be due to the impaired intrauterine environment, generated by systemic viral effects, leading to a negative vicious circle that worsens placental oxidative stress and mitochondrial efficiency. This likely causes cell homeostasis dysregulations, raising the potential of possible long-term effects.
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http://dx.doi.org/10.3390/antiox10101517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533135PMC
September 2021

Right ventricular outflow tract abnormalities in monochorionic twin pregnancies without twin-to-twin transfusion syndrome: Prenatal course and postnatal long-term outcomes.

Prenat Diagn 2021 Sep 28. Epub 2021 Sep 28.

Department of Women, Mother and Newborn, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.

Objectives: Right ventricular outflow tract abnormalities (RVOTA) have been mostly reported in recipient twins (RT) of monochorionic/diamniotic (MC/DA) twin pregnancies with twin-to-twin transfusion syndrome (TTTS). Aim of the study was to describe RVOTA detected in MC/DA pregnancies without TTTS.

Methods: Cases of RVOTA were retrieved from our database among all MC/DA pregnancies without TTTS from 2009 to 2018.

Results: Out of 891 MC/DA twin pregnancies without TTTS, 14 (1.6%) were associated with RVOTA: 10 pulmonary stenosis (PS), one steno-insufficiency, one insufficiency and two atresia (PA). In 93% of cases (13/14), pregnancy was complicated either by amniotic fluid discrepancy (AFD) or by TAPS or mostly by selective fetal growth restriction (sFGR) (11/13: 85%), involving predominantly (10/11: 91%) the large twin, with high incidence (9/11: 82%) of sFGR and AFD coexistence. Eight out of 14 (57%) survived after the perinatal period (7 PS, 1 PA). Five (62%) underwent pulmonary balloon valvuloplasty, whereas 3 children still showed persistent mild PS at cardiac follow up after 1 year of life.

Conclusions: RVOTA can occur in MC/DA pregnancies without TTTS, particularly when other complications coexist. In complicated cases specialized fetal echocardiographic evaluation is recommended during pregnancy; RVOTA cases should be delivered in a tertiary level center, where cardiologists are available.
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http://dx.doi.org/10.1002/pd.6052DOI Listing
September 2021

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

Eur J Public Health 2021 Sep 28. Epub 2021 Sep 28.

Unit of Obstetrics and Gynecology, Buzzi Hospital-ASST Fatebenefratelli Sacco, University of Milan, Milan, 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.
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http://dx.doi.org/10.1093/eurpub/ckab095DOI Listing
September 2021

Impact of optimizing pre-analytical phase on the diagnosis of gestational diabetes and related outcomes.

Clin Chem Lab Med 2021 Aug 27. Epub 2021 Aug 27.

UOC Patologia Clinica, Milan, Italy.

Objectives: Pre-analytical plasma glucose (PG) sampling methodology may significantly affect gestational diabetes mellitus (GDM) incidence, but no studies directly examined the impact on perinatal outcomes. We compared the effect on oral glucose tolerance test (OGTT) results of using for blood sampling the traditional sodium fluoride (NaF) tubes, batched at controlled temperature, and the more effective citrate-buffered tubes, in terms of GDM diagnosis and related outcomes.

Methods: We evaluated 578 pregnant women performing OGTT between 24- and 28-weeks' gestation. Paired NaF and citrate blood samples were drawn and analyzed for PG. GDM diagnosis was made by applying the 'one-step' American Diabetes Association strategy. Data on perinatal outcomes were collected in a subset of 330 women who delivered in our hospital network.

Results: Using the standard NaF approach, 69 (11.9%) GDM women were detected. Using citrate PG values, 90 women were additionally identified as GDM, increasing the GDM prevalence to 27.5%. Perinatal outcomes were analyzed according to the different diagnostic allocation (NaF-diagnosed GDM, additional citrate-diagnosed GDM, and no GDM). NaF-diagnosed GDM showed a higher incidence of large for gestational age (LGA) (p=0.034), and of cesarean and preterm delivery (p<0.01) vs. no GDM. The only outcome remaining more frequent in the additional citrate diagnosed GDM when compared with no GDM group was LGA (17.2 vs. 6.8%, p=0.025).

Conclusions: If a health care system plans to use citrate tubes for GDM diagnosis, considerations about clinical implications are mandatory by balancing higher sensitivity in detecting a poor glycemic control with effects on outcomes to avoid "overdiagnosis".
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http://dx.doi.org/10.1515/cclm-2021-0706DOI Listing
August 2021

MiRNA Profiling in Plasma and Placenta of SARS-CoV-2-Infected Pregnant Women.

Cells 2021 07 15;10(7). Epub 2021 Jul 15.

Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy.

MicroRNAs are gene expression regulators associated with several human pathologies, including those generated by viral infections. Their role in SARS-CoV-2 infection and COVID-19 has been investigated and reviewed in many informative studies; however, a thorough miRNA outline in SARS-CoV-2-infected pregnant women (SIPW), at both systemic and placental levels, is missing. To fill this gap, blood and placenta biopsies collected at delivery from 15 asymptomatic SIPW were immediately analysed for: miRNA expression ( = 84) (QPCR array), antiviral/immune mRNA target expression ( = 74) (QGene) and cytokine/chemokines production ( = 27) (Multiplex ELISA). By comparing these results with those obtained from six uninfected pregnant women (UPW), we observed that, following SARS-CoV-2 infection, the transcriptomic profile of pregnant women is significantly altered in different anatomical districts, even in the absence of clinical symptoms and vertical transmission. This characteristic combination of miRNA and antiviral/immune factors seems to control both the infection and the dysfunctional immune reaction, thus representing a positive correlate of protection and a potential therapeutic target against SARS-CoV-2.
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http://dx.doi.org/10.3390/cells10071788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305278PMC
July 2021

The use of biological agents in pregnant women affected by autoimmune disorders: Why we need more research of this neglected area.

Pharmacol Res 2021 09 24;171:105786. Epub 2021 Jul 24.

Department of Woman, Mother and Neonate, "V. Buzzi" Children Hospital, ASST Fatebenefratelli Sacco, 20141 Milan, Italy; Department of Biomedical and Clinical Sciences, "Luigi Sacco", University of Milan, 20157 Milan, Italy.

Women of childbearing age are largely affected by several autoimmune disorders (the estimates range between 1.5 and 10 per 10,000). The increasing number of effective biological agents has dramatically revolutionized the treatment of these clinical conditions, ameliorating the patient's quality of life. The use of these agents by women during pregnancy is growing to ensure the disease activity control and avoid adverse health outcomes. However, for many newer biological agents, the degree of information concerning their use in pregnancy is often incomplete to perform a conclusive risk assessment on fetal and maternal health given the exclusion of this specific population from pharmacological clinical trials. More recently, the COVID-19 pandemic has confirmed the unacceptable inequities of pharmacological research and medical treatment for pregnant and lactating women, exacerbating the need for filling the gaps of quantitative and qualitative pharmacology data in this sensitive population. ere we summarize (i) what is already known about safety and effectiveness of biological agents in this understudied population (with specific focus on pregnancy-related health outcomes), and what we are going to learn from the on-going studies among pregnant women treated with biological agents; (ii) the methodological and ethical considerations that characterize the pharmacological research in pregnancy, also discussing emerging evidence on the use of therapeutic drug monitoring (TDM) in this clinical setting.
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http://dx.doi.org/10.1016/j.phrs.2021.105786DOI Listing
September 2021

A closer look at discordant placental echogenicity: two cases under the microscope.

Clin Case Rep 2021 Jul 21;9(7):e04506. Epub 2021 Jul 21.

Fetal Therapy Unit Umberto Nicolini Department of Woman, Mother and Neonate Vittore Buzzi Children's Hospital ASST Fatebenefratelli Sacco University Hospital Milano Italy.

Discordant placental echogenicity is observed in MC pregnancies complicated with twin anemia-polycythemia sequence, but could also belong to complicated singleton gestation.
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http://dx.doi.org/10.1002/ccr3.4506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294047PMC
July 2021

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

Am J Obstet Gynecol 2021 09 26;225(3):289.e1-289.e17. Epub 2021 Jun 26.

Bayero University Kano, Nigeria; Aminu Kano Teaching Hospital, Kano State, Nigeria.

Background: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors.

Objective: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality.

Study Design: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21 protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions.

Results: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios.

Conclusion: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.
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http://dx.doi.org/10.1016/j.ajog.2021.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233533PMC
September 2021

Placental pathology in COVID-19 affected pregnant women: A prospective case-control study.

Placenta 2021 07 5;110:9-15. Epub 2021 May 5.

Department of Obstetrics and Gynecology, Vittore Buzzi Hospital, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences "Luigi Sacco", Università Degli Studi di Milano, Milano, Italy. Electronic address:

Introduction: During pregnancy, SARS-CoV-2 infection may cause an abnormal development of the placenta, thus influencing maternal and fetal outcomes. Few studies have reported data on placental morphology and histology in infected pregnant patients, although not compared with carefully matched controls. The aim of this study is to compare placental morphology and histology of pregnant women affected by SARS-CoV-2 to non-infected controls.

Methods: This is a prospective multicenter case-control study on 64 pregnant women affected by SARS-CoV-2 who delivered at term or late-preterm. Data were collected about pregnancy course, maternal and fetal outcomes, placental biometry and macro- and microscopical morphology. 64 not-infected women were identified as controls, matched by age, body mass index and ethnicity.

Results: Cases and controls had similar fetal and maternal outcomes. No significant differences were observed in placental macro- or microscopical morphology between the two groups. In the cases treated with antivirals, chloroquine, LMWH or antibiotics, placentas were heavier but not more efficient than the non-treated, since the fetal/placental weight ratio did not differ. Moreover, delayed villous maturation was more frequent in treated women, although not significantly. The newborns whose mothers received oxygen therapy as treatment had higher levels of umbilical cord pO₂ at birth.

Discussion: In this prospective case-control study, SARS-CoV-2 infection during the third trimester did not influence placental histological pattern. Pharmacological and oxygen therapy administered to women affected by this viral infection could impact maternal and fetal outcomes and be associated to placental histological alterations.
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http://dx.doi.org/10.1016/j.placenta.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096756PMC
July 2021

Childbirth Care among SARS-CoV-2 Positive Women in Italy.

Int J Environ Res Public Health 2021 04 16;18(8). Epub 2021 Apr 16.

Servizio Assistenza Territoriale, Direzione Generale Cura Della Persona, Salute e Welfare, Emilia-Romagna Region, 40127 Bologna, Italy.

The new coronavirus emergency spread to Italy when little was known about the infection's impact on mothers and newborns. This study aims to describe the extent to which clinical practice has protected childbirth physiology and preserved the mother-child bond during the first wave of the pandemic in Italy. A national population-based prospective cohort study was performed enrolling women with confirmed SARS-CoV-2 infection admitted for childbirth to any Italian hospital from 25 February to 31 July 2020. All cases were prospectively notified, and information on peripartum care (mother-newborn separation, skin-to-skin contact, breastfeeding, and rooming-in) and maternal and perinatal outcomes were collected in a structured form and entered in a web-based secure system. The paper describes a cohort of 525 SARS-CoV-2 positive women who gave birth. At hospital admission, 44.8% of the cohort was asymptomatic. At delivery, 51.9% of the mothers had a birth support person in the delivery room; the average caesarean section rate of 33.7% remained stable compared to the national figure. On average, 39.0% of mothers were separated from their newborns at birth, 26.6% practised skin-to-skin, 72.1% roomed in with their babies, and 79.6% of the infants received their mother's milk. The infants separated and not separated from their SARS-CoV-2 positive mothers both had good outcomes. At the beginning of the pandemic, childbirth raised awareness and concern due to limited available evidence and led to "better safe than sorry" care choices. An improvement of the peripartum care indicators was observed over time.
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http://dx.doi.org/10.3390/ijerph18084244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074190PMC
April 2021

Placental Antioxidant Defenses and Autophagy-Related Genes in Maternal Obesity and Gestational Diabetes Mellitus.

Nutrients 2021 Apr 15;13(4). Epub 2021 Apr 15.

Department of Biomedical and Clinical Sciences "Luigi Sacco", Università degli Studi di Milano, 20157 Milano, Italy.

Maternal obesity and gestational diabetes mellitus (GDM) are increasing worldwide, representing risk factors for both mother and child short/long-term outcomes. Oxidative stress, lipotoxicity and altered autophagy have already been reported in obesity, but few studies have focused on obese pregnant women with GDM. Antioxidant and macro/chaperone-mediated autophagy (CMA)-related gene expressions were evaluated herein in obese and GDM placentas. A total of 47 women with singleton pregnancies delivered by elective cesarean section were enrolled: 16 normal weight (NW), 18 obese with no comorbidities (OB GDM(-)), 13 obese with GDM (OB GDM(+)). Placental gene expression was assessed by real-time PCR. Antioxidant gene expression (, , ) decreased, the pro-autophagic gene increased and the chaperone-mediated autophagy regulator decreased in OB GDM(-) vs. NW. On the other hand, expression increased in OB GDM(+) vs. OB GDM(-). When analyzing results in relation to fetal sex, we found sexual dimorphism for both antioxidant and CMA-related gene expressions. These preliminary results can pave the way for further analyses aimed at elucidating the placental autophagy role in metabolic pregnancy disorders and its potential targetability for the treatment of diabetes outcomes.
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http://dx.doi.org/10.3390/nu13041303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071310PMC
April 2021

Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

JAMA Pediatr 2021 08;175(8):817-826

College of Medicine, University of Ibadan, Ibadan, Nigeria.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed.

Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals.

Design, Setting, And Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge.

Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms.

Main Outcomes And Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity.

Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity.

Conclusions And Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.
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http://dx.doi.org/10.1001/jamapediatrics.2021.1050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063132PMC
August 2021

Methodology for Biometrical Analysis of the Placenta: Feasibility and Reproducibility.

Reprod Sci 2021 05 11;28(5):1277-1280. Epub 2021 Mar 11.

Department of Obstetrics and Gynecology, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.

The role of a healthy placenta as the interface between mother and fetus, which regulates the intrauterine environment and affects fetal and pregnancy outcomes, points to placental examination as a potentially useful diagnostic tool. Placental macroscopic and microscopic patterns are routinely evaluated when pregnancy complications occur. Moreover, placental measures particularly the ratio between fetal and placental weight have been reported to correlate with maternal characteristics, such as BMI as well as with birth-weight and fetal gender. Our pilot study evaluates the feasibility of the placental measures' reproducibility intra-operators. We enrolled 50 consecutive singleton pregnancies including physiological pregnancies and any pre-existing maternal disease or maternal and fetal complication. We conducted a macroscopic analysis of fetal adnexa with four different operators assessing pathological findings or other abnormalities. Intra-class correlation coefficient (ICC) and Cohen and Fleiss kappa coefficient were used to assess the degree of consistency between operators. The results of our study show that the placental morphometric analysis is a reproducible method.
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http://dx.doi.org/10.1007/s43032-021-00463-zDOI Listing
May 2021

Breastfeeding and COVID-19 vaccination: position statement of the Italian scientific societies.

Ital J Pediatr 2021 Feb 27;47(1):45. Epub 2021 Feb 27.

Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

The availability of a COVID-19 vaccine has raised the issue of its compatibility with breastfeeding. Consequently, the Italian Society of Neonatology (SIN), the Italian Society of Pediatrics (SIP), the Italian Society of Perinatal Medicine (SIMP), the Italian Society of Obstetrics and Gynecology (SIGO), the Italian Association of Hospital Obstetricians-Gynecologists (AOGOI) and the Italian Society of Infectious and Tropical Diseases (SIMIT) have made an ad hoc consensus statement. Currently, knowledge regarding the administration of COVID-19 vaccine to the breastfeeding mother is limited. Nevertheless, as health benefits of breastfeeding are well demonstrated and since biological plausibility suggests that the health risk for the nursed infant is unlikely, Italian scientific societies conclude that COVID-19 vaccination is compatible with breastfeeding.
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http://dx.doi.org/10.1186/s13052-021-00998-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912459PMC
February 2021

Vestibular Mucosa Thickness Measured by Ultrasound in Patients Affected by Vestibulodynia: A Case-Control Study.

Sex Med 2021 Apr 13;9(2):100320. Epub 2021 Feb 13.

Lower Genital Tract Disease Unit, V. Buzzi Hospital-University of the Study of Milan, Milan, Italy.

Introduction: A multifactorial etiology has been implicated in the development and maintenance of vestibulodynia (VBD), and atrophic changes of the vestibular mucosa have been observed in many patients.

Aim: To assess the vestibular mucosa thickness in patients with VBD by comparing this sample with a control group of healthy fertile women and postmenopausal patients with symptoms of genitourinary syndrome of menopause (GSM).

Methods: Vestibular mucosa thickness was measured with a 20 MHz ultrasound probe (DermaScan C, Cortex Technology, Denmark), including both the epidermis and dermis.

Main Outcome Measures: All women were evaluated by anamnesis, physical examination, and self-report symptoms. Thickness of the vestibular mucosa (expressed in micrometers) was determined by the B-mode, excluding the hyperechogenic entrance echo and hypoechogenic subcutis. Clinical data related to VBD and GSM were recorded using a 0- to 10-point visual analog scale related to dyspareunia and vulvar pain/burning (0 = no pain; 10 = worst possible pain).

Results: A total of 85 patients were recruited: 24 with VBD, 20 with GSM-related symptoms, and 20 matched controls. Vestibular mucosa thickness measurements were not significantly different between the VBD (mean ± DS: 1,092.5 ± 226.1 μm) and GSM groups (1,059.7 ± 221.5 μm), while the parameter was significantly lower (P < .01) than the control group (1,310.6 ± 250.0 μm). Correlation analysis in the VBD and GSM groups between low vestibular mucosa thickness and symptom intensity (burning/pain and dyspareunia) showed a significant correlation.

Conclusion: Patients with VBD have a vestibular mucosa with a lower thickness than healthy women of the same age, with an almost identical value to that found in postmenopausal women. Furthermore, a low vestibular mucosa thickness in the VBD and GSM groups showed a significant correlation with burning/pain intensity and dyspareunia severity. F Murina, S Barbieri, C Lubrano, MD, et al. Vestibular Mucosa Thickness Measured by Ultrasound in Patients Affected by Vestibulodynia: A Case-Control Study. Sex Med 2021;9:100320.
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http://dx.doi.org/10.1016/j.esxm.2020.100320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072142PMC
April 2021

Maternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease.

Int J Mol Sci 2021 Feb 9;22(4). Epub 2021 Feb 9.

Department of Woman, Mother and Neonate, 'V. Buzzi' Children Hospital, ASST Fatebenefratelli Sacco, 20141 Milan, Italy.

Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.
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http://dx.doi.org/10.3390/ijms22041732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914818PMC
February 2021

Home fetal heart rate monitoring in anti Ro/SSA positive pregnancies: Literature review and case report.

Eur J Obstet Gynecol Reprod Biol 2021 Apr 28;259:1-6. Epub 2021 Jan 28.

Department of Woman, Mother and Neonate, "V. Buzzi" Children Hospital, ASST Fatebenefratelli Sacco, Milan, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy.

Anti-Ro/SSA antibodies are associated with a risk of 1-2 % to develop complete atrioventricular block (AVB) in fetuses of positive mothers. Complete AVB is irreversible, but studies suggest that anti-inflammatory treatment during the transition period from a normal fetal heart rate (FHR) to an AVB might stop this progression and restore sinus rhythm. The most efficient method for diagnostic evaluation of this arrhythmia is the pulsed-Doppler fetal echocardiography. However, weekly or bi-weekly recommended fetal echocardiographic surveillance can rarely identify an AVB in time for treatment success, also because the transition from a normal rhythm to a third degree AVB is very fast. Daily FHR monitoring in a medical facility could increase the chances of identifying the AVB onset but is difficult to realize. For this reason, an alternative method of FHR monitoring, performed directly by mothers in their home context, has been recently proposed. We present a case report utilizing this approach and review the current evidence about this condition.
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http://dx.doi.org/10.1016/j.ejogrb.2021.01.031DOI Listing
April 2021

Breastfeeding: Biological and Social Variables in Different Modes of Conception.

Life (Basel) 2021 Feb 1;11(2). Epub 2021 Feb 1.

Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, via G.B. Grassi 74, 20157 Milan, Italy.

Background: Breastfeeding has effects on health throughout the lives of mothers and babies. In 2014 in Italy, 10,976 babies were born through ART (assisted reproductive technology), accounting for 2.2% of annual births. The study aims to assess how both social and biological variables and the mode of conception influence breastfeeding.

Methods: This observational study involves 161 pregnancies from three different modes of conception: homologous in vitro fertilization, ovum donation, and spontaneous pregnancies. Neonatal and maternal characteristics were collected from the hospital database, while breastfeeding outcomes were obtained through telephone interviews.

Results: The mode of conception did not influence any of the breastfeeding outcomes. Breastfeeding duration was negatively affected by smoking. Vaginal delivery, birth weight > 2500 g, delivery > 37 gestational weeks, breastfeeding intention, and rooming-in are positively associated with the initiation of breastfeeding, while skin-to-skin contact and receiving information concerning breastfeeding are the most significant variables associated with its exclusivity and duration.

Conclusions: The duration and exclusivity of breastfeeding are mainly related with information thereon, promotion, and breastfeeding support, but not with the mode of conception. It is essential to adequately support women from the outset in breastfeeding, as recommended by the World Health Organization (WHO) guidelines.
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http://dx.doi.org/10.3390/life11020110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912739PMC
February 2021

Neuroimaging and neurodevelopmental outcome after early fetal growth restriction: NEUROPROJECT-FGR.

Pediatr Res 2021 Jan 19. Epub 2021 Jan 19.

Department of Woman, Mother and Child, Buzzi Hospital, University of Milan, via Castelvetro 32, 20154, Milan, Italy.

Background: Adverse neurodevelopmental outcomes and MRI alterations are reported in infants born after fetal growth restriction (FGR). This study evaluates the additional role of FGR over prematurity in determining brain impairment.

Methods: Retrospective observational study comparing 48 FGR and 36 appropriate for gestational age infants born between 26 and 32 weeks' gestation who underwent a cerebral MRI at term equivalent age. Exclusion criteria were twins, congenital anomalies, and findings of overt brain lesions. Main outcomes were total maturation score (TMS) and cerebral areas independently measured by two neuro-radiologists and Griffiths or Bayley scale III scores at median age of 2 years.

Results: TMS was not significantly different between the groups. Inner calvarium and parenchyma's areas were significantly smaller in FGR cases. There were no significant differences in the average quotient scores. A positive correlation between parenchyma area and cognitive score was found (r = 0.372, p = 0.0078) and confirmed after adjusting for sex, gestational age, and birth weight (p = 0.0014). Among FGR, the subgroup with umbilical arterial Doppler velocimetry alterations had significantly worse gross motor scores (p = 0.005).

Conclusions: FGR plays additional role over prematurity in determining brain impairment. An early structural dimensional MRI evaluation may identify infants who are at higher risk.

Impact: Fetal growth-restricted infants showed smaller cerebral parenchymal areas than preterm controls. There is a positive correlation between the parenchyma area and the cognitive score. These results highlight the already known link between structure and function and add importance to the role of a structural dimensional MRI evaluation even in the absence of overt brain lesions.
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http://dx.doi.org/10.1038/s41390-020-01333-1DOI Listing
January 2021

Effects of α-lipoic acid and myo-inositol supplementation on the oocyte environment of infertile obese women: A preliminary study.

Reprod Biol 2020 Dec 21;20(4):541-546. Epub 2020 Oct 21.

Università degli Studi di Milano, "Luigi Sacco" Department of Biomedical and Clinical Sciences, Milano, Italy. Electronic address:

Obesity is becoming pandemic and is associated with impaired reproductive potential. Oxidative stress, low-grade chronic inflammation and mitochondrial dysfunctions, which characterize obesity, strongly affect oocyte environment and function. Supplementation with antioxidant and anti-inflammatory compounds has been suggested to improve fertility. Here we evaluated the effect of α-lipoic acid and myo-inositol supplementation on the oocyte environment of infertile obese women. Nineteen normal-weight and twenty-three obese women, infertile for non-ovarian reasons, were recruited. For two months before ovarian stimulation, all women received 400 μg/die folic acid, whereas 15 obese were additionally supplemented with 800 mg α-lipoic acid, 2 g myo-inositol/die. Antioxidant capacity was measured in follicular fluid by enzymatic assay; mitochondrial DNA (mtDNA) content and mRNA levels of two respiratory chain subunits were analyzed in granulosa cells by Real-time PCR. Pregnancy rate was similar between normal-weight and treated obese, and lower in untreated obese patients. Supplemented women showed significantly higher antioxidant levels in follicular fluid compared to the two groups taking only folic acid. Conversely, granulosa cells mtDNA content was decreased in treated and higher in untreated obese patients compared to normal-weight women, suggesting mtDNA increases to compensate for oxidative-stress damages. Reduced expression of respiratory subunits in untreated obese may confirm mitochondria impairment. Interestingly, mtDNA levels inversely correlated to both total and metaphase II oocyte number. In this preliminary study, combined supplementation of α-lipoic acid and myo-inositol in infertile obese women was associated with amelioration in the oxidative status of the oocyte environment, possibly contributing to a higher pregnancy rate.
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http://dx.doi.org/10.1016/j.repbio.2020.10.002DOI Listing
December 2020

Correlation between pharmacokinetics and pharmacogenetics of Selective Serotonin Reuptake Inhibitors and Selective Serotonin and Noradrenaline Reuptake Inhibitors and maternal and neonatal outcomes: Results from a naturalistic study in patients with affective disorders.

Hum Psychopharmacol 2021 May 30;36(3):e2772. Epub 2020 Nov 30.

Psychiatry Unit 2, ASST Fatebenefratelli Sacco, L. Sacco University Hospital, Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.

Objective: Some studies have linked the use of selective serotonin reuptake inhibitors and selective serotonin and noradrenaline reuptake inhibitors (SSRIs/SNRIs) to the risk of perinatal complications. This study explored the relationship between pharmacokinetics and pharmacogenetics, SSRIs/SNRIs tolerability and effectiveness and maternal and newborn outcomes.

Methods: Fifty-five pregnant women with Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnoses of affective disorders, treated with SSRIs/SNRIs, were recruited and, during the third trimester, their blood samples were collected for pharmacokinetic and pharmacogenetic analyses. Plasma levels and metabolic phenotypes were then related to different obstetrical and maternal outcomes.

Results: The pharmacokinetic data were more stable for Sertraline, Citalopram, and Escitalopram compared to other molecules (p = 0.009). The occurrence of postnatal adaptation syndrome onset was associated with higher plasma levels for Sertraline (median at delivery: 16.7 vs. 10.5 ng/ml), but not for fluoxetine and venlafaxine. Finally, the subgroup within range plasma concentrations had less blood loss than the below range subgroup (p = 0.030).

Conclusions: Plasma levels of Sertraline, Citalopram and Escitalopram were more frequently in range in late pregnancy when compared to other drugs. Drug plasma concentrations do not strictly correlate with worse perinatal outcomes, but with possible differences between the different drugs.
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http://dx.doi.org/10.1002/hup.2772DOI Listing
May 2021

Placental proteome abnormalities in women with gestational diabetes and large-for-gestational-age newborns.

BMJ Open Diabetes Res Care 2020 11;8(2)

International Center for T1D Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy

Introduction: Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood.

Research Design And Methods: A proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs).

Results: Here, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p<0.05) as compared with those with GDM but without LGA. Among these proteins, 10 are involved in regulating tissue differentiation and/or fetal growth and development, with bone marrow proteoglycan (PRG2) and dipeptidyl peptidase-4 (DPP-4) being highly expressed. Both PRG2 and DPP-4 altered the transcriptome profile of stem cells differentiation markers when tested in vitro in hESCs, suggesting a potential role in the onset of fetal abnormalities.

Conclusions: Our findings suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Once established on a larger population, inhibitors of the pathways involving those altered factors may be tested in conditions such as GDM and LGA, in which therapeutic approaches are still lacking.
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http://dx.doi.org/10.1136/bmjdrc-2020-001586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668299PMC
November 2020

The role of obesity and gestational diabetes on placental size and fetal oxygenation.

Placenta 2021 01 13;103:59-63. Epub 2020 Oct 13.

Department of Obstetrics and Gynecology, Vittore Buzzi Hospital, University of Milan, Via L. Castelvetro 32, Milan, Italy; Department of Obstetrics and Gynecology, Luigi Sacco Hospital, University of Milan, Via GB Grassi 74, Milan, Italy; Department of Biomedical and Clinical Sciences Luigi Sacco, Università degli Studi di Milano, Milan, Italy. Electronic address:

Introduction: Maternal pregestational obesity is a significant risk factor for adverse pregnancy outcomes, such as gestational diabetes. Both these conditions can have an impact on placental development and affect maternal-fetal exchanges, compromising fetal metabolic status. The aim of the study is to investigate the influence of pre-pregnancy BMI on placental size and to evaluate the role of obesity and gestational diabetes mellitus (GDM) on fetal oxygenation in overweight and obese pregnant women.

Methods: 208 normal weight (NW), 57 overweight (OW) and 69 obese (OB) women were studied at elective cesarean section (CS) at term. 10 OW and 24 OB women were affected by GDM. Maternal, fetal and placental data were collected. Respiratory gases and acid-base balance were measured in umbilical venous and arterial blood.

Results: Placental weight and thickness were higher in OB pregnancies. Lower fetal-placental ratios (F/P) were found in GDM pregnancies, both OW and OB. Fetuses from OB mothers were more hypoxic and acidemic compared to NW, particularly when complicated by GDM.

Discussion: In agreement with previous studies, our data show that placentas from OB and GDM pregnancies are heavier and thicker, suggesting that an unbalanced pregestational nutritional status can decrease the placental efficiency in maternal-fetal exchanges. Fetuses from obese women are also hypoxic and acidemic, while fetuses from gestational diabetic mothers are hypoxic, reflecting that an altered pre-pregnancy BMI can affect fetal oxygenation, and GDM can play an additional detrimental role, thus worsening placental function and fetal oxygenation.
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http://dx.doi.org/10.1016/j.placenta.2020.10.013DOI Listing
January 2021

Analysis of SARS-CoV-2 vertical transmission during pregnancy.

Nat Commun 2020 10 12;11(1):5128. Epub 2020 Oct 12.

Unit of Obstetrics and Gynecology, ASST Fatebenefratelli-Sacco, Department of Biological and Clinical Sciences, University of Milan, Milan, Italy.

The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.
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http://dx.doi.org/10.1038/s41467-020-18933-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552412PMC
October 2020

Misleading meta-analyses of observational studies may generate unjustified alarms: The case of medications for nausea and vomiting in pregnancy.

Pharmacol Res 2021 01 5;163:105229. Epub 2020 Oct 5.

National Centre of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.

Objectives: Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic risks of antiemetic agents in pregnancy since a large observational study recently showed that first-trimester exposure to doxylamine-pyridoxine was associated with significantly increased risk of congenital malformations as a whole, as well as central nervous system defects, and previous observational studies did not show such associations. A meta-analysis on this issue was carried out with the aim to illustrate how differential exposure and outcome misclassifications may lead to uncertain conclusions.

Methods: Medline, searched to October 2019 for full text papers in English. Summary Odds Ratios (ORs) with confidence intervals (CIs) were calculated using random-effect models. Probabilistic sensitivity analyses were performed for evaluating the extension of differential misclassification required to account for the exposure-outcome association.

Results: Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 % CI, 0.99-1.29) and 1.17 (95 % CI, 0.99-1.38).

Conclusion: Observational investigations and meta-analyses of observational studies need cautious interpretations. Their susceptibility to several, often sneaky, sources of bias should be carefully evaluated.
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http://dx.doi.org/10.1016/j.phrs.2020.105229DOI Listing
January 2021

Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy.

PLoS One 2020 15;15(9):e0239173. Epub 2020 Sep 15.

Department of Obstetrics and Gynecology, Division of Obstetrics, MBBM foundation at San Gerardo Hospital, Monza, Italy.

Objectives: 1. To assess the performance of an extended questionnaire in identifying cases of SARS-CoV-2 infection among obstetric patients. 2. To evaluate the rate of infection among healthcare workers involved in women's care.

Study Design: A prospective cohort study of obstetric patients admitted to MBBM Foundation and Buzzi Hospital (Lombardy, Northern Italy) from March 16th to May 22nd, 2020. Women were screened on admission by a questionnaire investigating major and minor symptoms of infection and high-risk contacts in the last 14 days. SARS-CoV-2 assessment was performed by RT-PCR on nasopharyngeal swabs. Till April 7th, a targeted SARS-CoV-2 testing triggered by a positive questionnaire was used; from April 8th, a universal testing approach was implemented.

Results: There were 1,177 women screened by the questionnaire, which yielded a positive result in 130 (11.0%) cases. SARS-CoV-2 RT-PCR was performed in 865 (73.5%) patients, identifying 51 (5.9%) infections. During the first period, there were 29 infected mothers, 4 (13.8%) of whom had a negative questionnaire. After universal testing implementation, there were 22 (3%, 95% CI 1.94% - 4.04%) infected mothers, 13 (59.1%) of whom had a negative questionnaire; rate of infection among asymptomatic women was 1.9%. Six of the 17 SARS-CoV-2-positive women with a negative questionnaire reported symptoms more than 14 but within 30 days before admission. Isolated olfactory or taste disorders were identified in 15.7% of infected patients. Rate of infection among healthcare workers was 5.8%.

Conclusions: An exhaustive triage questionnaire can effectively discriminate women at low risk of SARS-CoV-2 infection in the context of a targeted and a universal viral testing approach. In 15.7% of infected women, correct classification as a suspected case of infection was due to investigation of olfactory and taste disorders. Extension of the assessed time-frame to 30 days may be worth considering to increase the questionnaire's performance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491723PMC
September 2020

Fractional Pixel CO2 laser treatment for decubitus ulcer in advanced pelvic organ prolapse: a case report.

Menopause 2020 09;27(9):1093-1095

Lower Genital Tract Disease Unit, V. Buzzi Hospital-University of the Study of Milan, Milan, Italy.

Objective: Cervicovaginal decubitus ulceration is a complication of advanced pelvic organ prolapse that is very difficult to manage. Here, we report on the effectiveness of fractional CO2 laser treatment for a wide decubitus ulcer over an apical vaginal vault prolapse.

Methods: We report a case of a postmenopausal woman with a wide decubitus ulcer over a vaginal vault prolapse. A fractional microablative CO2 Pixel laser system (Alma Lasers, Cesarea, Israel), equipped with an appropriate probe for the vulva, was used to treat the ulceration of a 78-year-old patient across three laser sessions with 30-day intervals.

Results: A significant improvement in the decubitus ulcer was noted in a check-up held 2 months after the final laser session, with approximately 95% wound healing observed. No side effects were reported during or after the laser therapy.

Conclusions: This case demonstrates that fractional Pixel CO2 laser treatment is a viable option for managing decubitus ulcers before definitive surgery in postmenopausal women with advanced pelvic organ prolapse.
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http://dx.doi.org/10.1097/GME.0000000000001618DOI Listing
September 2020

Multiple Micronutrients and Docosahexaenoic Acid Supplementation during Pregnancy: A Randomized Controlled Study.

Nutrients 2020 Aug 13;12(8). Epub 2020 Aug 13.

Department of Woman, Mother and Neonate, Buzzi Children Hospital, ASST Fatebenefratelli Sacco, 20154 Milan, Italy.

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting-an important finding considering the essential roles of DHA and vitamin D.
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http://dx.doi.org/10.3390/nu12082432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468952PMC
August 2020

Congenital isolated clubfoot: Correlation between prenatal assessment and postnatal degree of severity.

Prenat Diagn 2020 12 27;40(12):1547-1552. Epub 2020 Aug 27.

Fetal Therapy Unit "U.Nicolini", Department of Obstetrics and Gynecology, Buzzi Children's Hospital, University of Milan, Milan, Italy.

Objective: Since prenatal diagnosis of isolated clubfoot has a false positive rate (FP) of 10%-40%, fetal parameters that might correlate with post-natal confirmation and grade of severity were investigated.

Method: Retrospective analysis (2013-2019) of cases analysed with three-dimensional multiplanar view. The following data were recorded: the angle between the long axis of foot and lower leg; width, length and width-to-length ratio (W/L) of the foot; tibia length and calf width (T/C) ratio. Severity after birth was assessed using the Pirani classification.

Results: Diagnosis was confirmed in 45/53 neonates (84.9%, FP 15%). Values were higher for both angle and W/L in true vs false positive cases (median angle 100.4° versus 69.55°, p <.000; median W/L 0.53 vs 0.45, p = .001), no difference for T/C (3.77 vs 3.48, p = .8). The area under the curve for angle was 0.98 (CI 0.94-1.00), with a diagnostic cut-off of 84.7° (PPV of 100%, NPV of 66.7%). Median Pirani score, available for 33 neonates (73.3%) was 3 (IQR 3-4): only angle correlated with Pirani score (Spearman coefficient 0.36, p = .04) CONCLUSION: Measuring the angle between the foot and lower leg can reduce the FP rate of prenatal congenital clubfoot diagnosis and better predict the need for postnatal treatment.
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http://dx.doi.org/10.1002/pd.5808DOI Listing
December 2020
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