Volume 51, Issue 7

Objectives Although the vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS Cov-2) is considered safe during pregnancy, vaccine hesitancy among pregnant women is high. The results of published observational studies addressing the issue of Covid-19 vaccination’s efficacy and safety during pregnancy need to be summarized. Content This systematic review compares the incidence of major maternal and neonatal outcomes between SARS Cov-2 vaccinated and unvaccinated pregnant women. The included studies enrolled pregnant women of any age and any trimester. Medline-Pubmed, Scopus, Cochrane Library, and grey literature were searched until the 28th of May 2022, and 2,947 studies were found. Summary Seven observational cohort studies, enrolling 67,274 pregnant women, were selected. When comparing vaccinated and unvaccinated pregnant women, SARS Cov-2 vaccines were not associated with major maternal and neonatal adverse events. The rate of SARS Cov-2 infections among vaccinated pregnant women compared to unvaccinated is significantly reduced by 43%. Outlook SARS Cov-2 vaccination in pregnant women is effective and safe. The results are promising, but caution is advised due to some limitations: only observational studies addressing this issue were found. Parallelly, the enrolled populations and the intervention (vaccination type and the number of doses) were not homogeneous.

Objectives In the face of limited fiscal and technical resources, improvised methods have been used to provide effective and sustainable ventilatory support in low-resource settings to reduce neonatal mortality associated with respiratory complications. This study assessed the use of improvised bubble continuous positive airway pressure (ibCPAP) ventilation among neonates with respiratory complications and determined its effect on neonatal outcomes in low- and middle-income countries (LMICs). Content Hospital-based studies conducted between 2010 and 2020 in LMICs were reviewed. Rayyan ® software for systematic review was used for screening and article selection. We used Stata ® Statacorp Texas USA software to estimate pooled prevalence, proportion estimates, weighted mean differences and 95% Confidence Interval (CI), using the random effects model. Summary A total of 193 articles were generated and 125 were reviewed. Thirteen articles with 806 neonates on ibCPAP ventilation were included. The pooled prevalence of ibCPAP use was 7.0% (95% CI: 3.0%–13.0%). There was a significant difference in mean oxygen saturation before and after ibCPAP use (−1.34% [95% CI: −1.65% to −1.02%, p<0.01). The duration of oxygen requirement among neonates on ibCPAP was 6.5 hours less than controls (0.27 days [95%CI: −0.49 to −0.05, p<0.01). Outlook IbCPAP had no effect on the respiratory rate, duration of admission, mortality and survival. IbCPAP use in LMIC hospitals is low and its use improved oxygen saturation and duration on oxygen among the neonates, but had no impact on length of stay, respiratory rate, mortality or survival.

Anger is an emotional state that occurs when unexpected things happen to or around oneself and is “an emotional state that varies in intensity from mild irritation to intense fury and rage.” It is defined as “a strong feeling of displeasure and usually of antagonism,” an emotion characterized by tension and hostility arising from frustration, real or imagined injury by another, or perceived injustice. It can manifest itself in behaviors designed to remove the object of the anger (e.g., determined action) or behaviors designed merely to express the emotion. For the Roman philosopher Seneca anger is not an uncontrollable, impulsive, or instinctive reaction. It is, rather, the cognitive assent that such initial reactions to the offending action or words are in fact unjustified. It is, rather, the cognitive assent that such initial reactions to the offending action or words are in fact unjustified. It seems that the year 2022 was a year when many Americans were plainly angry. “Why is everyone so angry?” the New York Times asked in the article “The Year We Lost It.” We believe that Seneca is correct in that anger is unacceptable. Anger is a negative emotion that must be controlled, and Seneca provides us with the tools to avoid and destroy anger. Health care professionals will be more effective, content, and happier if they learn more about Seneca’s writings about anger and implement his wisdom on anger from over 2000 years ago.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

The Journal of Perinatal Medicine helps me a lot to understand how impacted in my work as Neonatologist the crucial importance of permanently think on prenatal development and postnatal experiences of the newborn we are caring, and how the parents live the moment. We should produce High Technology but at the same time seriously consider High Prenatal life Advances. Possibly no other field of medicine has undergone such dramatic progress in reducing mortality and morbidity as the care of preterm newborns. In recent years, remarkable advances in the care of pregnant women and their babies have led to an increase in infant survival. However, advances in neonatal care need to be accompanied by mechanisms that help us deliver care safely to this most vulnerable population. Great progress has been made in perinatal care, but the health-care system must do much more. The health-care system faces a great challenge, the era of reflection between real progress and innovations. It means: Seriously consider what we are really doing and what we should really do.

Objectives Many physiological adaptations occur during pregnancy. It is not currently known how timing of COVID-19 infection impacts pregnancy. We hypothesize that maternal and neonatal outcomes are different if COVID-19 infection occurs in different trimesters of pregnancy. Methods This retrospective cohort study was conducted from 3/2020 to 6/2022. Pregnant patients with a positive COVID-19 infection more than 10 days before delivery (COVID-recovered) were identified and grouped by trimester of infection. Demographics and maternal, obstetric, and neonatal outcomes were analyzed. ANOVA, Wilcoxon rank-sum test, Pearson’s chi-squared test, and Fisher’s exact test were used to compare continuous and categorical data. Results A total of 298 COVID-recovered pregnant patients were identified. Of those, 48 (16 %) were infected in the 1st trimester, 123 (41 %) in the 2nd, and 127 (43 %) in the 3rd. There were no significant demographic differences between the study groups. Vaccination status was similar. Hospital admission rate and the need for oxygen therapy while infected were significantly higher in patients with 2nd or 3rd trimester infection (18 % & 20 % vs. 2 % and 13 % & 14 % vs. 0 %, respectively). Rates of preterm birth (PTB) and extreme PTB were higher in the 1st trimester infection group. Infants born to mothers infected in the 2nd trimester had more neonatal sepsis workups (22 % vs. 12 % & 7 %). Other outcomes were similar between groups. Conclusions First trimester COVID-recovered patients were more likely to have a preterm birth despite having lower rates of hospital admission and oxygen supplementation while infected than patients who recovered from a 2nd or 3rd trimester infection.

Objectives This study aimed to present perinatal outcomes, clinical challenges, and basic ICU management in pregnant women with severe-critical COVID-19 at our tertiary referral center. Methods In this prospective cohort study, patients were divided into two groups, whether they survived or not. Clinical characteristics, obstetric and neonatal outcomes, initial laboratory test results and radiologic imaging findings, arterial blood gas parameters at ICU admission, and ICU complications and interventions were compared between groups. Results 157 of the patients survived, and 34 of the patients died. Asthma was the leading health problem among the non-survivors. Fifty-eight patients were intubated, and 24 of them were weaned off and discharged healthfully. Of the 10 patients who underwent ECMO, only 1 survived (p<0.001). Preterm labor was the most common pregnancy complication. Maternal deterioration was the most common indication for a cesarean section. Higher neutrophil-to-lymphocyte-ratio (NLR) values, the need for prone positioning, and the occurrence of an ICU complication were important parameters that influenced maternal mortality (p<0.05). Conclusions Overweight pregnant women and pregnant women with comorbidities, especially asthma, may have a higher risk of mortality related to COVID-19. A worsening maternal health condition can lead to increased rates of cesarean delivery and iatrogenic prematurity.

Objectives This study was conducted to determine whether bacteria, fungi, or archaea are detected in the amniotic fluid of patients who underwent midtrimester amniocentesis for clinical indications. Methods Amniotic fluid samples from 692 pregnancies were tested by using a combination of culture and end-point polymerase chain reaction (PCR) techniques. Intra-amniotic inflammation was defined as an interleukin-6 concentration >2,935 pg/mL. Results Microorganisms were detected in 0.3% (2/692) of cases based on cultivation, 1.73% (12/692) based on broad-range end-point PCR, and 2% (14/692) based on the combination of both methods. However, most (13/14) of these cases did not have evidence of intra-amniotic inflammation and delivered at term. Therefore, a positive culture or end-point PCR in most patients appears to have no apparent clinical significance. Conclusions Amniotic fluid in the midtrimester of pregnancy generally does not contain bacteria, fungi, or archaea. Interpretation of amniotic fluid culture and molecular microbiologic results is aided by the assessment of the inflammatory state of the amniotic cavity. The presence of microorganisms, as determined by culture or a microbial signal in the absence of intra-amniotic inflammation, appears to be a benign condition.

Objectives In-vivo studies of the bioavailability of major components of the tumor necrosis factor alpha (TNFα) biosystem inside the gestational sac during embryogenesis have not been reported. We sought to determine the concentration of TNFα, soluble (s) TNFα receptors (sTNFR1, sTNFR2), and RANTES in the primate extraembryonic celomic fluid (ECF). Methods A validated timed-pregnant baboon animal model (N: 10) for experimental research in pregnancy was used to collect paired maternal blood and ECF samples in ongoing pregnancies. The concentrations (pg/dL) of TNFα, sTNFR1, sTNFR2, and RANTES were then determined by ELISA immunoassays. Results All animals delivered at term healthy newborns. The differential concentration of TNFα, sTNFR1, sTNFR2, and RANTES between the maternal plasma and the ECF could be determined with ratios for TNFα (5.4), sTNFR2 (1.85) and RANTES (3.59) that contrasted with that of sTNFR1 (0.07), which favored the gestational sac compartment. No significant correlations were noted between maternal plasma and ECF TNFR1, sTNFR2 and RANTES. There was a trend for a correlation between TNFα in maternal plasma and ECF (R=0.74; p=0.07). Conclusions We report the physiological concentrations of TNFα, sTNFR1, sTNFR2, and RANTES in extraembryonic celomic fluid during embryogenesis in primates.

Objectives Analyze the diagnostic and prognostic value of the sFlt-1/PlGF ratio in pregnant women with at least one sign/symptom of suspected/diagnosed pre-eclampsia. Methods This retrospective observational study included 170 pregnant women with at least one sign/symptom of pre-eclampsia, who had sFlt-1/PlGF ratio values. The following information was evaluated: pregnant women’s demographic data and clinical history; laboratory data (urine protein/creatinine ratio; sFlt-1/PlGF ratio); signs and symptoms presented; clinical outcome; fetal complications; data related to childbirth. Statistical analysis was performed by R Software Version 3.5.2. Results Among the 170 patients, 78 presented pre-eclampsia. The median sFlt-1/PlGF ratio was significantly higher [143.1 (2.2–2,927.1)] for women who presented pre-eclampsia than for women without pre-eclampsia [33.5 (0.8–400.2)]. The negative predictive value of sFlt-1/PlGF ratio <38 was 83.9 % (95 % CI, 71.7–92.4 %) and the positive predictive value of sFlt-1/PlGF ratio >85 or 110 (for late onset pre-eclampsia) was 76.4 % (95 % CI, 66.2–84.8 %). sFlt-1/PlGF >85 or 110 was associated with pre-eclampsia clinical development, fetal complications, shorter gestational age at birth, higher number of caesarean deliveries and lower birth weight. Conclusions The sFlt-1/PlGF ratio, together with the standard diagnostic criteria, can be used to rule out pre-eclampsia, identify high-risk patients and predict the occurrence of adverse outcomes.

Objectives The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years. Methods We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded. Results Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012–2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017–2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis. Conclusions Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.

Objectives The present study aimed to evaluate the performance of QuantusFLM ® software, which performs quantitative ultrasound analysis of fetal lung texture, in predicting lung maturity in fetuses of diabetic mothers. Methods The patients included in this study were between 34 and 38 weeks and 6 days gestation and were divided into two groups: (1) patients with diabetes on medication and (2) control. The ultrasound images were performed up to 48 h prior to delivery and analyzed using QuantusFLM ® software, which classified each fetus as high or low risk for neonatal respiratory morbidity based on lung maturity or immaturity. Results A total of 111 patients were included in the study, being 55 in diabetes and 56 in control group. The pregnant women with diabetes had significantly higher body mass index (27.8 kg/m 2 vs. 25.9 kg/m 2 , respectively, p=0.02), increased birth weight (3,135 g vs. 2,887 g, respectively, p=0.002), and a higher rate of labor induction (63.6 vs. 30.4 %, respectively, p<0.001) compared to the control group. QuantusFLM ® software was able to predict lung maturity in diabetes group with 96.4 % accuracy, 96.4 % sensitivity and 100 % positive predictive value. Considering the total number of patients, the software demonstrated accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 95.5 , 97.2, 33.3, 98.1 and 25 %, respectively. Conclusions QuantusFLM ® was an accurate method for predicting lung maturity in normal and DM singleton pregnancies and has the potential to aid in deciding the timing of delivery for pregnant women with DM.

Objectives The aim of this study was to evaluate the agreement between visual and automatic methods in assessing the adequacy of fetal cardiac views obtained during second trimester ultrasonographic examination. Methods In a prospective observational study frames of the four-chamber view left and right outflow tracts, and three-vessel trachea view were obtained from 120 consecutive singleton low-risk women undergoing second trimester ultrasound at 19–23 weeks of gestation. For each frame, the quality assessment was performed by an expert sonographer and by an artificial intelligence software (Heartassist™). The Cohen’s κ coefficient was used to evaluate the agreement rates between both techniques. Results The number and percentage of images considered adequate visually by the expert or with Heartassist™ were similar with a percentage >87 % for all the cardiac views considered. The Cohen’s κ coefficient values were for the four-chamber view 0.827 (95 % CI 0.662–0.992), 0.814 (95 % CI 0.638–0.990) for left ventricle outflow tract, 0.838 (95 % CI 0.683–0.992) and three vessel trachea view 0.866 (95 % CI 0.717–0.999), indicating a good agreement between the two techniques. Conclusions Heartassist™ allows to obtain the automatic evaluation of fetal cardiac views, reached the same accuracy of expert visual assessment and has the potential to be applied in the evaluation of fetal heart during second trimester ultrasonographic screening of fetal anomalies.

Objectives To study whether the free energy principle can explain fetal brain activity and the existence of fetal consciousness via a chaotic dimension derived using artificial intelligence. Methods In this observational study, we used a four-dimensional ultrasound technique obtained to collect images of fetal faces from pregnancies at 27–37 weeks of gestation, between February and December 2021. We developed an artificial intelligence classifier that recognizes fetal facial expressions, which are thought to relate to fetal brain activity. We then applied the classifier to video files of facial images to generate each expression category’s probabilities. We calculated the chaotic dimensions from the probability lists, and we created and investigated the free energy principle’s mathematical model that was assumed to be linked to the chaotic dimension. We used a Mann–Whitney test, linear regression test, and one-way analysis of variance for statistical analysis. Results The chaotic dimension revealed that the fetus had dense and sparse states of brain activity, which fluctuated at a statistically significant level. The chaotic dimension and free energy were larger in the sparse state than in the dense state. Conclusions The fluctuating free energy suggests consciousness seemed to exist in the fetus after 27 weeks.

Objectives This study aims to assess the diagnostic accuracy of targeted ultrasound examination in prenatal diagnosis of hypospadias and to evaluate the predictive values of defined ultrasonographic findings of hypospadias. Methods The cases diagnosed with hypospadias in our fetal medicine center were identified on an electronic database. The ultrasound reports, images and hospital records were reviewed retrospectively. The predictive value of prenatal ultrasound diagnosis and the predictive values of each sonographic finding were assessed according to the postnatal clinical examinations. Results Thirty-nine cases were diagnosed with hypospadias on ultrasound during the 6 years. Nine fetuses with missing postnatal examination records were excluded. Twentytwo of the remaining fetuses had their prenatal diagnosis of hypospadias confirmed in postnatal examinations, indicating a 73.3 % positive predictive value. Normal external genitalia was detected in postnatal examinations of three fetuses. Five fetuses were diagnosed with other external genital abnormalities, including micropenis (n=2), clitoromegaly (n=2), and buried penis with bifid scrotum (n=1) in postnatal examinations. The positive predictive value of prenatal ultrasound for any external genital abnormality was 90 %. Conclusions Although the positive predictive value of ultrasound for genital anomalies is satisfying, it is slightly lower for the specific diagnosis of hypospadias. This reflects overlapping ultrasound findings of different external genitalia anomalies. Standardized, systematic evaluation of the internal and external genital organs, karyotyping and genetic sex determination are essential to achieve a precise prenatal diagnosis of hypospadias.

Objectives Few studies have examined the molecular alterations in the auditory pathway of infants of diabetic mothers, notwithstanding the fact that maternal diabetes may have an impact on the development of the neonatal peripheral and central nervous systems. Male newborn rats were studied to determine how maternal diabetes affected the expression of gamma-aminobutyric acid (GABA Aα1 and GABA B1 ) and metabotropic glutamate (mGlu2) receptors in the inferior colliculus (IC) in this research. Methods Female rats were given a single intraperitoneal injection of streptozotocin (STZ) at a 65 mg/kg dose to develop a model of diabetic mothers. The study population was split into sham, diabetes without treatment, and diabetes with insulin groups. Their male neonatal rats were anesthetized on P0, P7, and P14 after mating and delivery. The receptors’ distribution pattern was studied using immunohistochemistry (IHC). Results Pairwise comparison in the groups revealed that the GABA receptors (Aα1 and B1) were significantly downregulated in the diabetes without treatment group (p<0.001). Furthermore, pairwise comparison in the groups indicated significant mGlu2 upregulation in the diabetes without treatment group (p<0.001). Regarding the concentration of all receptors, there was no discernible distinction between the diabetes with insulin and sham groups. Conclusions This investigation showed that the concentration of GABA Aα1 and GABA B1 receptors decreased significantly over time, whereas the concentration of mGlu2 receptors increased significantly over time in male neonatal rats born to streptozotocin-induced diabetic mothers .

Objectives Over the last decade, there has been increased use of end-tidal carbon dioxide (ETCO 2 ) and oxygen saturation (SpO 2 ) monitoring during resuscitation of prematurely born infants in the delivery suite. Our objectives were to test the hypotheses that low end-tidal carbon dioxide (ETCO 2 ) levels, low oxygen saturations (SpO 2 ) and high expiratory tidal volumes (VT E ) during the early stages of resuscitation would be associated with adverse outcomes in preterm infants. Methods Respiratory recordings made in the first 10 min of resuscitation in the delivery suite of 60 infants, median GA 27 (interquartile range 25–29) weeks were analysed. The results were compared of infants who did or did not die or did or did not develop intracerebral haemorrhage (ICH) or bronchopulmonary dysplasia (BPD). Results Twenty-five infants (42%) developed an ICH and 23 (47%) BPD; 11 (18%) died. ETCO 2 at approximately 5 min after birth was lower in infants who developed an ICH, this remained significant after adjusting for gestational age, coagulopathy and chorioamnionitis (p=0.03). ETCO 2 levels were lower in infants who developed ICH or died compared to those that survived without ICH, which remained significant after adjustment for gestational age, Apgar score at 10 min, chorioamnionitis and coagulopathy (p=0.004). SpO 2 at approximately 5 min was lower in the infants who died compared to those who survived which remained significant after adjusting for the 5-min Apgar score and chorioamnionitis (p=0.021). Conclusions ETCO 2 and SpO 2 levels during early resuscitation in the delivery suite were associated with adverse outcomes.

Objectives Therapeutic hypothermia (TH) is now standard of care for the neuroprotection of patients with moderate to severe hypoxic-ischemic encephalopathy (HIE). TH misuse results in increased medical complication rates and high health care resource utilization. Quality improvement (QI) methodology can address drift from clinical guidelines. Assessment of sustainability of any intervention over time is an integral part of the QI methodology. Methods Our prior QI intervention improved medical documentation using an electronic medical record-smart phrase (EMR-SP) and demonstrated special cause variation. This study serves as Epoch 3 and investigates the sustainability of our QI methods to decrease TH misuse. Results A total of 64 patients met the diagnostic criteria for HIE. Over the study period, 50 patients were treated with TH, and 33 cases (66%) used TH appropriately. The number of appropriate TH cases between cases of misuse increased to an average of 9 in Epoch 3 from 1.9 in Epoch 2. Of the 50 cases, 34 (68%) had EMR-SP documentation included. Length of stay and TH complication rates did not vary between cases of TH misuse and appropriate TH use. Conclusions Our study confirmed a sustained decrease in TH misuse, despite inconsistent use of EMR-SP. We speculate that culture change involving increased awareness of guidelines through education may have contributed more to a lasting change.

Objectives To estimate the correlation of cervical dilation between pocket-device point-of-care transperineal ultrasound (TPUS) and digital cervical examination (DCE). Methods Laboring pregnant individuals ≥37 weeks of gestation presenting were prospectively evaluated for cervical dilation with a handheld pocket-sized ultrasound (Butterfly iQ+ ® ) applied to the perineum, with a blinded DCE directly following. Subjects completed a survey to rate pain and for any preference from the examinations. To detect a moderate correlation (r=0.5) between TPUS and DCE, with an alpha of 0.05 and power of 80%, a sample size of 30 examinations were needed. Results From April 2022 to July 2022, 30 pregnant individuals were assessed. The median cervical dilation by TPUS vs. DCE was 5.1 and 5 cm, respectively, with a Pearson’s correlation coefficient, r=0.86 (95% CI 0.72 to 0.93), p<0.001. Transperineal ultrasound had a significantly less pain score than DCE, median pain score 0 vs. 2 for TPUS and DCE respectively, p<0.001. All individuals preferred the TPUS over the DCE. Conclusions Measurement of cervical dilation using a pocket-device point-of-care TPUS has a strong positive correlation with DCE and offers a non-invasive, convenient alternative to traditional digital exams in term, laboring patients.