Emerging and re-emerging infectious diseases in pregnant women in an amazonian region: a large retrospective study from French Guiana.

PURPOSE: Over the past decade, the Amazon basin has faced numerous infectious epidemics. Our comprehension of the actual extent of these infections during pregnancy remains limited. This study aimed to clarify the clinical and epidemiological features of emerging and re-emerging infectious diseases during pregnancy in western French Guiana and along the Maroni River over the previous nine years. METHODS: This retrospective cohort study enrolled pregnant women living in west French Guiana territory and giving birth in the only local referral center after 22 weeks of gestation between 2013 and 2021. Data on symptomatic or asymptomatic biologically confirmed emerging or re-emerging diseases during pregnancy was collected. RESULTS: Six epidemic waves were experienced during the study period, including 498 confirmed Zika virus infections (2016), 363 SARS-CoV-2 infections (2020-2021), 87 chikungunya virus infections (2014), 76 syphilis infections (2013-2021), and 60 dengue virus infections (2013-2021) at different gestational ages. Furthermore, 1.1% (n = 287) and 1.4% (n = 350) of pregnant women in west French Guiana were living with HIV and HTLV, respectively. During the study period, at least 5.5% (n = 1,371) faced an emerging or re-emerging infection during pregnancy. CONCLUSION: These results highlight the diversity, abundance, and dynamism of emerging and re-emerging infectious agents faced by pregnant women in the Amazon basin. Considering the maternal and neonatal adverse outcomes associated with these infections, increased efforts are required to enhance diagnosis, reporting, and treatment of these conditions.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study.

BACKGROUND: Because selective termination (ST) for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. OBJECTIVE: To determine whether perinatal outcomes were more favorable following deferred rather than immediate ST. STUDY DESIGN: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with ST for fetal conditions which were diagnosed before 24 WG. Pregnancies with additional risk factors for late miscarriage were excluded. We defined two groups according to the intention to perform ST within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate ST) or to wait until the third trimester (deferred ST). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 WG and preterm delivery. RESULTS: Of 390 pregnancies, 258 were in the immediate ST group and 132 in deferred ST group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate ST group vs 100% (132/132) in the deferred ST group (p<0.01). Preterm birth < 37 weeks' gestation was lower in the immediate than in the deferred ST group (66.7% vs 20.2%, p<0.01); preterm birth < 28 WG and < 32 WG did not differ significantly (respectively 1.7% vs 0.8%, p=0.66 and 8.26% vs 11.4%, p=0.36). In the deferred ST group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. CONCLUSION: Overall survival after ST was high regardless of the gestational age at which the procedure was performed. Postponing ST until the third trimester seems to improve survival, while immediate ST reduces the risk of preterm delivery. Furthermore, deferred ST requires an expert center capable of performing the ST procedure on an emergency basis if required.

Maternal and neonatal outcomes of French prospective multicenter cohort study COVIPREG during the first two COVID-19 waves.

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).

Prenatal and Postnatal Ocular Abnormalities Following Congenital Zika Virus Infections: A Systematic Review.

OBJECTIVE: To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons. METHODS: A systematic review and meta-analysis was conducted by a team of obstetricians and ophthalmologists. RESULTS: Studies reporting ocular abnormalities during the prenatal (n = 5) and postnatal (n = 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed. CONCLUSION: This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188.

Arboviruses and pregnancy: are the threats visible or hidden?

Mosquito-borne arboviral diseases are a global concern and can have severe consequences on maternal, neonatal, and child health. Their impact on pregnancy tends to be neglected in developing countries. Despite hundreds of millions of infections, 90% pregnancies being exposed, scientific data on pregnant women is poor and sometimes non-existent. Recently and since the 2016 Zika virus outbreak, there has been a newfound interest in these diseases. Through various neuropathogenic, visceral, placental, and teratogenic mechanisms, these arbovirus infections can lead to fetal losses, obstetrical complications, and a wide range of congenital abnormalities, resulting in long-term neurological and sensory impairments. Climate change, growing urbanization, worldwide interconnectivity, and ease of mobility allow arboviruses to spread to other territories and impact populations that had never been in contact with these emerging agents before. Pregnant travelers are also at risk of infection with potential subsequent complications. Beyond that, these pathologies show the inequalities of access to care on a global scale in a context of demographic growth and increasing urbanization. It is essential to promote research, diagnostic tools, treatments, and vaccine development to address this emerging threat.Background The vulnerability of pregnant women and fetuses to emergent and re-emergent pathogens has been notably illustrated by the outbreaks of Zika virus. Our comprehension of the complete scope and consequences of these infections during pregnancy remains limited, particularly among those involved in perinatal healthcare, such as obstetricians and midwives. This review aims to provide the latest information and recommendations regarding the various risks, management, and prevention for pregnant women exposed to arboviral infections.

The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

OBJECTIVE: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. DATA SOURCES: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www. CLINICALTRIALS: gov), and gray literature sources were searched from inception to March 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. METHODS: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. RESULTS: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12-0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19-0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14-0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22-0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. CONCLUSION: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.

Causes and consequences of fever in Amazonian pregnant women: A large retrospective study from French Guiana.

OBJECTIVE: The aim of this study was to describe different causes and consequences of fever during pregnancy in Western French Guiana and along the Maroni River. STUDY DESIGN: A retrospective single-center study including all patients with a history of documented fever ≥ 38°C during pregnancy at the West French Guiana Hospital for 9 years. Postpartum fever and nosocomial infections were excluded. We focused on medical history and on clinical and biological findings. Causes were characterized as confirmed or uncertain and then classified as preventable or non-preventable. RESULTS: A total of 940 pregnant women who experienced at least one episode of fever were included and compared to 23,811 deliveries who occurred during the same period without documented fever. Among them, 43.7% (411/940) were in labor. About 3.7% (35/940) of febrile pregnant women had at least two episodes of fever, while 0.3% (3/940) had a coinfection at the time of diagnosis, resulting in a total of 978 febrile episodes. Among them, causes remained unknown or uncertain in 7.6% (75/978) and 0.9% (9/978) of cases, respectively. Among confirmed causes of fever throughout pregnancy (n = 483), the most common known cause was arbovirus infection (146/483, 30.2%), followed by urinary tract infection (134/483, 27.7%), chickenpox (27/483, 5.6%), and gastrointestinal (14/483, 2.9%) and pulmonary infections (10/483, 2%). Mothers with fever had a higher risk of cesarean section (19.8% vs 15.5%, aOR 1.3 [95% CI 1.14-1.6], stillbirth (5.5% versus 1.9%, aOR 2.7 [95% CI 2-3.7]), and preterm delivery < 34 weeks of gestation (7.2% vs 4.7%, aOR 1.5 [95% CI 1.2-2]. CONCLUSIONS: In the Amazon region, causes of fever are diverse and often associated with epidemic waves, notably arboviruses. This must be considered when exploring possible causes of fever during pregnancy in these localities, including fetal anomalies and/or fetal loss. Physicians should consider the epidemiological context and avoid generalizations. Given the impact of emergent agents such as arboviruses on pregnancy, particular attention must be paid to the epidemiological context. This study can also help clinicians when managing fever in pregnant travelers or in their partner after having visited exposed areas. In this context, fetal abnormalities and adverse obstetric outcomes should be explored accordingly.

Impact of COVID-19 on pregnant women's health: Consequences in obstetrics two years after the pandemic.

The pandemic linked to SARS-CoV-2 has profoundly disrupted the health systems and many studies have led to a better understanding of this virus, which is responsible for severe disease, particularly during pregnancy. Pregnancy is a risk factor for severe COVID-19. Term of pregnancy and vaccination status is the main risk factor in addition to classic comorbidities like general population. COVID-19 during pregnancy is responsible for more maternal death, stillbirth, pre-eclampsia spontaneous and induced prematurity. Vaccination is therefore strongly recommended for pregnant patients. In addition, the COVID-19 pandemic has highlighted a psychological and social dimension that should not be neglected in the management of a pregnant patient. Correlation between immunological changes and clinical impact are described in this review. Many conclusions can now be made and are summarized in this article in order to discuss possible future research.

Induction or spontaneous labor for pregnant patients on anticoagulants?

OBJECTIVE: There are two approaches to peripartum management for pregnant patients undergoing anticoagulation treatments: spontaneous labor or scheduling an induction. A long interval without anticoagulation is a thrombosis risk factor, while a short interval leads to risks of delivery without epidural analgesia or post partum hemorrhage. Our objective was to evaluate the impact of planned induction versus spontaneous labor on obtaining neuraxial analgesia. MATERIALS AND METHODS: A retrospective single-center study was conducted from 2012 to 2020 including all patients on preventive or curative low molecular-weight heparin at the time of delivery, excluding planned cesarean sections. The rates of neuraxial analgesia were compared between two groups: spontaneous labor and induction, as well as the intervals without anticoagulants. RESULTS: 127 patients were included. In the spontaneous labor group, 78% (44/56) received neuraxial analgesia versus 88% (37/42) in the induction group (p = 0.29). For curative dose treatment, the rate of neuraxial analgesia was 45,5% in the spontaneous group versus 78,6% (p = 0.12). The median time without anticoagulation was 34 h [26-46] in the spontaneous labor group and 43 h [34-54] in the induction group (p = 0.01), without an increased incidence of thrombosis. The rate of postpartum hemorrhage did not differ between the two groups. CONCLUSION: Planned induction tended to increase the rate of neuraxial analgesia, without reaching significance, and most women in spontaneous labor accessed analgesia. Peripartum management should be a shared decision with the patient considering the obstetrical and thrombosis risk context for each patient.

Transplacental transfer of anti-SARS-CoV-2 neutralizing antibodies in comparison to other pathogens total antibodies.

BACKGROUNDS: Due to immaturity of their immune system, passive maternal immunization is essential for newborns during their first months of life. Therefore, in the current context of intense circulation of SARS-CoV-2, identifying factors influencing the transfer ratio (TR) of neutralizing antibodies against SARS-CoV-2 (NAb) appears important. METHODS: Our study nested in the COVIPREG cohort (NCT04355234), included mothers who had a SARS-CoV-2 PCR positive during their pregnancy and their newborns. Maternal and neonatal NAb levels were measured with the automated iFlash system. RESULTS: For the 173 mother-infant pairs included in our study, the median gestational age (GA) at delivery was 39.4 weeks of gestation (WG), and 29.7 WG at maternal SARS-CoV-2 infection. Using a multivariate logistic model, having a NAb TR above 1 was positively associated with a longer delay from maternal positive SARS-CoV-2 PCR to delivery (aOR 1.09, 95% CI: 1.03 - 1.17) and with a later GA at delivery (aOR = 1.58, 95% CI: 1.09 - 2.52). It was negatively associated with being a male newborn (aOR 0.21, 95% CI: 0.07 - 0.59). In 3rd trimester SARS-CoV-2 infected mothers, NAb TR was inferior to VZV, toxoplasmosis, CMV, measle and rubella's TR. However, in 1st or 2nd trimester infected mothers, only measle TR was different from NAb TR. CONCLUSION: Male newborn of mothers infected by SARS-CoV-2 during their pregnancy appear to have less protection against SARS-CoV-2 in their first months of life than female newborns. Measle TR was superior to NAb TR even in case of 1st or 2nd trimester maternal SARS-CoV-2 infection. Future studies are needed to investigate possible differences in transmission of NAb following infection vs vaccination and its impact on TR.

Abnormalities of the corpus callosum. Can prenatal imaging predict the genetic status? Correlations between imaging phenotype and genotype.

OBJECTIVE: Recent studies have evaluated prenatal exome sequencing (pES) for abnormalities of the corpus callosum (CC). The objective of this study was to compare imaging phenotype and genotype findings. METHOD: This multicenter retrospective study included fetuses with abnormalities of the CC between 2018 and 2020 by ultrasound and/or MRI and for which pES was performed. Abnormalities of the CC were classified as complete (cACC) or partial (pACC) agenesis of the CC, short CC (sCC), callosal dysgenesis (CD), interhemispheric cyst (IHC), or pericallosal lipoma (PL), isolated or not. Only pathogenic (class 5) or likely pathogenic (class 4) (P/LP) variants were considered. RESULTS: 113 fetuses were included. pES identified P/LP variants for 3/29 isolated cACC, 3/19 isolated pACC, 0/10 isolated sCC, 5/10 isolated CD, 5/13 non-isolated cACC, 3/6 non-isolated pACC, 8/11 non-isolated CD and 0/12 isolated IHC and PL. Associated cerebellar abnormalities were significantly associated with P/LP variants (OR = 7.312, p = 0.027). No correlation was found between phenotype and genotype, except for fetuses with a tubulinopathy and an MTOR pathogenic variant. CONCLUSIONS: P/LP variants were more frequent in CD and in non-isolated abnormalities of the CC. No such variants were detected for fetuses with isolated sCC, IHC and PL.

Impact of SARS-CoV-2 Infection on Unvaccinated Pregnant Women: Non-Reassuring Fetal Heart Rate Tracing Because of Placentitis.

In 2020, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. SARS-CoV-2 infection has been shown to be highly morbid in pregnant women, being a risk factor for several obstetric conditions leading to increased maternal and neonatal mortality. A few studies since 2020 have shown SARS-CoV-2 maternal-fetal transmission and noted placental abnormalities grouped under the term placentitis. We hypothesized that these placental lesions could be responsible for abnormalities in placental exchange and therefore abnormalities in cardiotocographic monitoring, leading to premature fetal extraction. The objective is to identify the clinical, biochemical, and histological determinants associated with the occurrence of non-reassuring fetal heart rate (NRFHR) outside labor in fetuses of SARS-CoV-2-infected mothers. We conducted a retrospective multicenter case series of the natural history of maternal SARS-CoV-2 infections resulting in fetal delivery outside labor due to NRFHR. Collaboration was sought with the maternity hospitals in the CEGORIF, the APHP and Brussels hospitals. The investigators were contacted by e-mail on three successive occasions over a period of one year. Data from 17 mothers and 17 fetuses were analyzed. Most women had a mild SARS-CoV-2 infection; only two women presented severe infection. No woman was vaccinated. We found a substantial proportion of maternal coagulopathy at birth: elevation of APTT ratio (62%), thrombocytopenia (41%) and liver cytolysis (58.3%). Iatrogenic prematurity was noted in 15 of 17 fetuses, and 100% were born by cesarean delivery due to emergency criteria. One male neonate died on the day of birth due to peripartum asphyxia. Three cases of maternal-fetal transmission were recorded following WHO criteria. Placental analysis in 15 cases revealed eight cases of SARS-CoV-2 placentitis, causing placental insufficiency. In total, 100% of the placentas analyzed showed at least one lesion suggestive of placentitis. SARS-CoV-2 maternal infection during pregnancy is likely to generate neonatal morbidity in relation to placental damage resulting in placental insufficiency. This morbidity may be the consequence of induced prematurity as well as acidosis in the most severe situations. Placental damage occurred in unvaccinated women and in women with no identified risk factor, in contrast to severe maternal clinical forms.

Incidence, causes, and risk factors of stillbirth in an Amazonian context: Saint Laurent du Maroni maternity ward 2016-2021.

Objective: We aimed to describe the epidemiology of intrauterine fetal deaths in multiethnic western French Guiana and to assess its main causes and risk factors. Study design: A retrospective descriptive study was conducted based on data from January 2016 to December 2021. All information on stillbirth with a gestational age ≥20 weeks in the Western French Guiana Hospital Center was extracted. Terminations of pregnancy were excluded. We focused on medical history, clinical investigation, biological findings, placental histology, and autopsy examination to elucidate the cause of death. We used the Initial Cause of Fetal Death (INCODE) classification system for assessment. Univariable and multivariable logistic regression analyses were performed. Results: Overall, 331 fetuses in 318 stillbirth deliveries were reviewed and compared to live births that occurred during the same period. The rate of fetal death varied between 1.3 % and 2.1 %, with an average of 1.8 % over the 6-year period. Poor antenatal care (104/318, 32.7 %), obesity ≥30 kg/m2 (88/318, 31.7 %), and preeclampsia (59/318, 18.5 %) were the main risk factors associated with fetal death in this group. Four hypertensive crises were reported. According to the INCODE classification, the main causes of fetal death were obstetric complications (112/331, 33.8 %), particularly intrapartum fetal death with labor-associated asphyxia under 26 weeks (64/112, 57.1 %), and placental abruption (29/112, 25.9 %). Maternal-fetal infections were common, particularly mosquito-borne diseases (e.g., Zika virus, dengue, and malaria), re-emerging infectious agents such as syphilis, and severe maternal infections (8/331, 2.4 %). 19.3 % of fetal deaths (64/331) remained unexplained. Conclusion: Change in lifestyle as well as social deprivation and isolation adversely affect pregnancy in western French Guiana, in the context of a poor health care system that is similar to what is found in the Amazonian basin. Particular attention must be paid to emerging infectious agents in pregnant women and travelers returning from the Amazon region.

Primary, Secondary, and Tertiary Prevention of Congenital Cytomegalovirus Infection.

Cytomegalovirus infection is the most common congenital infection, affecting about 1% of births worldwide. Several primary, secondary, and tertiary prevention strategies are already available during the prenatal period to help mitigate the immediate and long-term consequences of this infection. In this review, we aim to present and assess the efficacy of these strategies, including educating pregnant women and women of childbearing age on their knowledge of hygiene measures, development of vaccines, screening for cytomegalovirus infection during pregnancy (systematic versus targeted), prenatal diagnosis and prognostic assessments, and preventive and curative treatments in utero.

[Monkeypox: Proposals for care in pregnancy]. / Variole du singe : propositions de conduite à tenir chez les femmes enceintes.

Although the 2022 Monkeypox virus epidemic mostly affects males, particularly men having sex with men, transmission to women may also occur. In case of MPXV infection in pregnancy, transmission to the fetus can result in very severe disease. Thus, caregivers should be aware of the measures to be taken according to the available evidence, in case of exposure or in case of symptoms particularly skin rash compatible with this diagnosis in a pregnant woman. Pregnant women should have access to vaccination, vaccinia immunoglobulin or antiviral medications as required.

Nasopharyngeal SARS-CoV-2 load and perinatal outcomes after maternal infection diagnosed close to delivery.

BACKGROUND: The occurrence of COVID-19 during the pregnancy can cause several negative maternal and neonatal outcomes. Nasopharyngeal viral load is associated with inflammatory markers and might influence the disease severity in non-pregnant patients, but there are no data about the relationship between viral load and perinatal outcomes in pregnant patients. OBJECTIVE: To investigate the hypothesis that nasopharyngeal SARS-CoV-2 load (estimated with real-time polymerase chain reaction delta cycle (ΔCt), measured in hospital clinical laboratories) is associated with perinatal outcomes, when COVID-19 is diagnosed in the third trimester of pregnancy. STUDY DESIGN: International, retrospective, observational, multi-center, cohort study enrolling 390 women (393 neonates, three pairs of twins), analyzed with multivariate generalized linear models with skewed distributions (gamma) and identity link. The analyses were conducted for the whole population and then followed by a subgroup analysis according to the clinical severity of maternal COVID-19. RESULTS: The estimated viral load in maternal nasopharynx is not significantly associated with gestational age at birth (adjusted B: -0.008 (95%CI: -0.04; 0.02); p = 0.889), birth weight (adjusted B: 4.29 (95%CI: -25; 35); p = 0.889), weight Z-score (adjusted B: -0.01 (95%CI: -0.03; 1); p = 0.336), 5' Apgar scores (adjusted B: -0. -9.8e-4 (95%CI: -0.01; 0.01); p = 0.889), prematurity (adjusted OR: -0.97 (95%CI: 0.93; 1.03); p = 0.766) and the small for gestational age status (adjusted OR: 1.03 (95%CI: 0.99; 1.07); p = 0.351). Similar results were obtained in subgroup analyses according to COVID-19 clinical severity. CONCLUSIONS: The estimated maternal nasopharyngeal viral load in pregnant women affected by COVID-19 during the third trimester is not associated with main perinatal outcomes.

Contribution of amniocentesis in fetuses small for gestational age without other sonographic signs.

OBJECTIVE: Our study evaluated the contribution of amniocentesis in the diagnostic approach of small-for-gestational-age fetuses (SGA) without morphological abnormality identified on ultrasound by studying FISH (fluorescence in situ hybridization) for chromosomes 13, 18 and 21, CMV PCR (cytomegalovirus polymerase chain reaction), karyotype and CGH (genomic hybridization array) METHODS: Our single-center retrospective cohort study included pregnant women referred for prenatal diagnosis for a SGA fetus in whom amniocentesis was performed between 2016 and 2019. A SGA fetus was defined as a fetus with an estimated fetal weight (EFW) below the 10th percentile according to referral growth curves in use. We evaluated the number of amniocenteses with an abnormal result and identified factors that may be associated with this outcome. RESULTS: Among the 79 amniocenteses performed, there were 5 (6.3%) abnormalities: karyotype (1.3%) and CGH (5.1%). No complications were described. We did not find any statistically significant factors associated with abnormal amniocentesis findings even if some elements seemed reassuring such as late discovery (p = 0.31), moderate SGA (p = 0.18), normal head, abdomen and femur measurements (p = 0.57), but without statistically significant difference. CONCLUSION: Our study found 6.3% pathological analysis of amniocenteses, of which several would have been missed by conventional karyotyping. Patients must be informed about the risk of detecting abnormalities of low severity, with low penetrance or with unknown fetal consequences that could be source of anxiety.