ObjectivesTo evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19.MethodsSecondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI).ResultsMean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09–1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3–7.9; p=0.001) were independently associated with composite adverse fetal outcome.ConclusionsEarly gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Despite the increasing number of published studies, objective evidence is still needed to draw any conclusion on the course of SARS-COV-2 infection acquired during pregnancy. What are the clinical implications of this work? The study showed that in pregnancies complicated by SARS-COV-2, the risk of maternal mortality was 0.8%, but about 11% of women required admission to ICU. Pregnancies affected by SARS-COV-2 were also complicated by 23% rate preterm birth, and 4.1% rate of perinatal death. The risk of vertical transmission was negligible.

Objectives: To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods: Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratoryconfirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerasechain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results: Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/ 265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions: Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Objectives To evaluate maternal and perinatal outcomes in high compared to low-risk pregnancies complicated by SARS-COV-2 infection. Methods This was a multinational retrospective cohort study including women with laboratory-confirmed SARS-COV-2 from 76 centers from 25 different countries in Europe, United States, South America, Asia and Australia from 04 April 2020 till 28 October 2020. The primary outcome was a composite measure of maternal mortality and morbidity including admission to intensive care unit (ICU), use of mechanical ventilation, or death. Secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal (NND) and perinatal (PND) death, and admission to neonatal intensive care unit. All these outcomes were assessed in high-risk compared to low-risk pregnancies. Pregnancies were considered as high risk in case of either pre-existing chronic medical conditions pre-existing pregnancy or obstetric disorders occurring in pregnancy. Fisher-test and logistic regression analysis were used to analyze the data. Results 887 singleton pregnancies tested positive to SARS-COV-2 at RT-PCR nasal and pharyngeal swab were included in the study. The risk of composite adverse maternal outcome was higher in high compared to low risk-pregnancies with an OR of 1.52 (95% CU 1.03-2.24; p= 0.035). Likewise, women carrying a high risk-pregnancies were also at higher risk of hospital admission (OR: 1.48, 95% CI 1.07-2.04; p= 0.002), presence of severe respiratory symptoms (OR: 2.13, 95% CI .41-3.21; p= 0.001), admission to ICU (OR: 2.63, 95% CI 1.42-4.88) and invasive mechanical ventilation (OR: 2.65, 95% CI 1.19- 5.94; p= .002). When exploring perinatal outcomes, high-risk pregnancies were also at high risk of adverse perinatal outcome with an OR 0f 1.78 (95% CI .15-2.72; p= 0.009). However, such association was mainly due to the higher incidence of miscarriage in high risk compared to low risk pregnancies (5.3% vs 1.6%, p= 0.008), while there was no difference as regard as the other explored outcomes between the two study groups. At logistic regression analysis, maternal age (OR: 1.12, 95% CI 1.02-1.22, p= 0.023) and the presence of a high-risk pregnancies (OR: 4.21, 95% CI 3.90-5.11, p<0.001) were independently associated with adverse maternal outcome. Conclusions High-risk pregnancies complicated by SARS-COV-2 infection are at higher risk of adverse maternal outcome compared to low-risk gestations.

Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd.

Consumption of drugs of abuse, tobacco and alcohol throughout pregnancy is a serious public health problem and results in an important economic cost to the health system. Drug and/or metabolites determination in biological matrices from mother and newborn is an objective measure of in utero drug exposure. We reviewed methods published for the determination of in utero drug exposure from 2007 to 2014, with special focus on meconium, placenta, umbilical cord and newborn hair. Accurate bioanalytical procedures are essential to obtain high-quality data to perform interventions and to establish correlations between analytical measures and clinical outcomes. We included a brief overview of clinical implications of in utero drug exposure to better understand the importance of this serious health issue.

Objectives Anosmia/hyposomia have been described as early signs of COVID-19 infection in adults, including young asymptomatic patients who commonly refer olfactory disfunction as their only clinical manifestation. Very few studies involving paediatric age patients have been published until now. This study aims to determine the presence of olfactory dysfunction in children with COVID-19 infection through the use of a self-reported questionnaire and a new olfactory screening tool. Methods Nested case-control study. All paediatric patients screened by reverse transcription polymerase chain reaction (RT-PCR) and Anti-SARS-CoV-2 antibodies for COVID-19 infection, during the study period (March-May 2020), were asked to respond to a questionnaire about symptoms of olfactory disfunction. Patients above six years old also performed an odor identification test based on seven odorants (Kradeo®). This test was designed based on our cultural context and eating habits. Results 126 patients were recruited, including 33 with COVID-19 infection. 15% of the infected children referred anosmia and/or dysgeusia on the questionnaire, all of them were older than eleven years. The results of the odor test (69 patients) revealed subtle disturbances in the infected group (mostly misrecognition of odorants). Median odorant recognition was 3 odors [Interquartile range (IQR) 2-4] in case group and 4 [IQR 3-5] in controls. Male patients showed significantly larger disturbances than girls in both groups (p=0.03). Conclusion Self-referred prevalence of olfactory disfunction in our sample of infected children is lower than that described in adults, especially among the youngest ones, maybe due to immature development of angiotensin-converting enzyme 2 (ACE2) receptors expressed in nasal mucosa. Nevertheless, one month after infection, subtle disturbances (misrecognition of odors) were identified among the infected children. This screening olfactory test provides a hygienic, user-friendly tool, suitable for screening children older than six years of age.

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