Impact of Maternal Health and Disease on Neonatal Outcome

Low birth weight (LBW) and preterm births make babies more vulnerable for disease and death in the neonatal period in India and worldwide (Estimates generated by the WHO and Maternal and Child Epidemiology Estimation Group (MCEF) 2018: leading causes of neonatal deaths in India. http://data.unicef.org). Of the 20 million LBW babies born globally each year, 97% are born in low-middle income countries (40% in India), and 80% of neonatal deaths occur in this group. Unlike LBW, preterm births are prevalent in both high- and low-income countries and are the most common cause of disability and death. Of more than 15 million preterm births (10.6% of total live births), 81% are in Asia and sub-Saharan Africa. In India, premature birth rate is 14 per 1000 live births. Worldwide, 10% of all neonatal deaths occur in premature births (in Indian up to 44% mortality). This risk is on the rise with the increase in preterm birth rate in many countries. Neonatal mortality rate (NMR) is an indicator of a country's health status. Indian NMR has decreased from 5.7% to 4.1% over 10 years, as in 2017 (Estimates generated by the WHO and Maternal and Child Epidemiology Estimation Group (MCEF) 2018: leading causes of neonatal deaths in India. http://data.unicef.org). Of the various factors impacting NMR, maternal factors (undernutrition, anaemia, and diseases) are most important affecting fetal growth, maturation, and overall neonatal outcome. Surgical mortality in neonates is also very high, varying on a country's health infrastructure and development, ranging from 6.7% in South Korea (Lee et al., J Korean Assoc Pediatr Surg 2006, http://www.koreamed.org/SearchBasic.php?RID=0053JKAPS/2006.12.2.137andDT=1) to 7.5% in Japan (Taguchi, Surg Today 38:379-89, 2008) and 35% in India (Gangopadhyay et al., Indian J Pediatr 75:1025-30, 2008) to 45% in Nigeria (Chirdan et al., Semin Pediatr Surg 21:151-9, 2012). This chapter will discuss the impact of maternal health and common medical diseases on fetal growth and development and the risks in the baby after birth. This will also affect perioperative morbidity and mortality in the surgical neonates. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Can Prenatal Ultrasound Predict Adverse Neonatal Outcomes in SARS-CoV-2 Affected Pregnancies?

BACKGROUND: Based on available data, at least one ultrasound assessment of pregnancies recovering from SARS-CoV-2 infection is recommended. Reports, however, on prenatal imaging findings and potential associations with neonatal outcomes following SARS-CoV-2 infection in pregnancy have been inconclusive. OBJECTIVE: We aim to describe the sonographic characteristics of pregnancies after confirmed SARS-CoV-2 infection and assess the association of prenatal ultrasound (US) findings with adverse neonatal outcomes (ANO). STUDY DESIGN: This is an observational prospective cohort study of pregnancies diagnosed with SARS-CoV-2 by reverse transcription polymerase chain reaction between March 2020 and May 2021. Prenatal US evaluation was performed at least once after diagnosis of infection with the following parameters measured: standard fetal biometric measurements, umbilical and middle cerebral artery Dopplers, placental thickness, amniotic fluid volume, and anatomic survey for infection-associated findings. The primary outcome was composite ANO, defined as one or more of the following: preterm birth, NICU admission, small for gestational age (SGA), respiratory distress, intrauterine fetal demise, neonatal demise, or other neonatal complications. Secondary outcomes were sonographic findings stratified by trimester of infection and severity of SARS-CoV-2 infection. Prenatal US findings were compared with neonatal outcomes, severity of infection, and trimester of infection. RESULTS: A total 103 SARS-CoV-2 affected mother-infant pairs with prenatal US evaluation were identified; 3 cases were excluded due to known major fetal anomalies. Of the 100 included cases, neonatal outcomes were available in 92 pregnancies (97 infants); of these, 28 (29%) had a composite ANO. Twenty-three (23%) had at least one abnormal prenatal US finding. The most common abnormalities seen on US were placentomegaly (11/23, 47.8%) and fetal growth restriction (FGR) (8/23, 34.8%). FGR was associated with a higher rate of a composite ANO (25% vs 1.5%; aOR: 22.67; 95% 95% CI, 2.63-194.91; p<0.001), even when SGA was removed from the composite ANO. Cochran-Mantel Haensel test controlling for possible FGR confounders continued to show this association (relative risk, 3.7; 95% confidence interval, 2.6-5.9; p<0.001). Median estimated fetal weight (EFW) and birthweight were lower in patients with a composite ANO (p<0.001). Infection in the third trimester was associated with lower median percentile of EFW (p=0.019). An association between placentomegaly and third trimester SARS CoV-2 infection was noted (p=0.045). CONCLUSION: In our study of SARS-CoV-2 affected maternal-infant pairs, rates of FGR were comparable to the general population. However, composite ANO rates were high. Pregnancies with FGR after SARS-CoV-2 infection were associated with an increased risk for ANO and may require close surveillance.

ASSOCIATION BETWEEN NEW CORONAVIRUS INFECTION AND FETAL GROWTH RESTRICTION.

Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.

ASSOCIATION BETWEEN NEW CORONAVIRUS INFECTION AND FETAL GROWTH RESTRICTION.

Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.

ASSOCIATION BETWEEN NEW CORONAVIRUS INFECTION AND FETAL GROWTH RESTRICTION.

Objective: To investigate the laboratory and instrumental characteristics of fetal growth restriction (FGR) secondary to novel coronavirus infection (NCI) to identify pathogenetically relevant predictive markers. Material(s) and Method(s): During the epidemic activity of the NCI Delta strain, 140 high-risk pregnant women were tested at 18-21 weeks and 26-34 weeks of gestation. Retrospectively, taking into account the fact of NCI disease and the exclusion of severe somatic and obstetric comorbidities, 2 groups were formed. Group 1 (n=32) included pregnant women with FGR, without a history of NCI. Group 2 (n=41) included pregnant women with FGR who recovered from NCI by the end of the second and third trimesters. Thirty healthy pregnant women served as the controls. In addition to ultrasound assessment of the fetal placental unit, patients underwent testing for markers of inflammation, endothelial hemostasis dysfunction, decidualization, placental angiogenesis, and pathological insulin resistance. Result(s): Pregnant women with a history of NCI had a higher incidence of FGR (1.3 times;OR 2.41 [95% CI 1.12-5.17]), more severe forms of FGR (2 times;OR 3.27 [95% CI 1.22-8.76]), more severe fetal-placental blood flow abnormalities (3.5-fold;OR 11.07 [95% CI 3.68-33.27]), and oligohydramnios (4.5-fold;OR 8.94 [95% CI 3.65-30.17]). The impact of NCI on the formation of placental insufficiency was expressed by an increase in systemic changes (thrombopoiesis, apoptosis), modulation of local processes (decidualization, placental angiogenesis), and the development of pathological insulin resistance and hyperinsulinemia, an immunopathological process of endotheliocytes. The identification of the most informative markers of FGR due to NCI allowed the development of a predictive index. Conclusion(s): An in-depth study of the impact of NCI on the formation of FGR has important scientific and practical implications for the optimization of FGR prediction, which may help identify appropriate patient management strategies for high-risk pregnant women.Copyright © 2023, Bionika Media Ltd.. All rights reserved.

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study.

OBJECTIVE: To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. METHODS: Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. RESULTS: Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3-1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. CONCLUSIONS: Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians' threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection. The proportion affected by pre-eclampsia amongst participants was not higher than would be expected, although we report a higher than expected proportion affected by eclampsia. There appears to be no effect on birthweight or congenital malformations in women affected by SARS-CoV-2 infection in pregnancy and neonatal infection is uncommon. This study reflects a population with a range of infection severity for SARS-COV-2 in pregnancy, generalisable to whole obstetric populations.

Large Ovarian Dermoid, a Cause for Fetal Growth Restriction and Oligohydramnios: Rare Instance in Literature

Ovarian dermoids mostly remain asymptomatic during pregnancy. Large dermoids may present with torsion, hemorrhage, or rupture. However, a dermoid cyst causing fetal growth restriction (FGR) and oligohydramnios is a very rare entity. The authors report a case of a large ovarian dermoid (15 x 12 cm) hampering intrauterine fetal growth. Due to the coronavirus disease-2019 (COVID-19) lockdown, the patient was unable to get ultrasound examinations in early gestation, and thereby, surgical intervention was not possible during the second trimester. As a result, this growing teratoma finally led to FGR by either exerting a pressure effect upon the uterus or by dwindling its blood supply. Copyright © The Author(s). 2022.

Impact of asymptomatic and mild COVID-19 infection on fetal growth during pregnancy.

BACKGROUND: During pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR). STUDY DESIGN: This is a single institution, retrospective cohort study of patients ages 16-55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. RESULTS: Among 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). CONCLUSION: Asymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.

Risk of preeclampsia in patients with symptomatic COVID-19 infection.

OBJECTIVES: Recent studies suggest an association between COVID-19 infection during pregnancy and preeclampsia. Nonetheless, these studies are subject to numerous biases. We compared the onset of preeclampsia in a group with symptomatic COVID-19 during pregnancy to that in a group whose non-exposure to the virus was certain, in a center where pregnancy management was identical in both groups. STUDY DESIGN: This was a single-center study comparing exposed and unexposed patients. The exposed group included pregnant women with symptomatic COVID-19 infection (diagnosed by RT-PCR or CT scan), who gave birth between March and December, 2020. The unexposed group included pregnant women who gave birth between March and December, 2019. Only cases of preeclampsia that occurred after COVID-19 infection were considered. A multivariate analysis was performed to study the existence of an association between COVID-19 and preeclampsia. A sensitivity analysis was performed among nulliparous patients. RESULTS: The frequency of preeclampsia was 3.2% (3/93) in the exposed group, versus 2.2% (4/186) in the unexposed group (P = 0.58). Among the nulliparous patients, the frequency of preeclampsia was 4.9% (2/41) in the exposed group versus 0.9% (1/106) in the unexposed group (P = 0.13). The association between COVID-19 and preeclampsia was not significant after multivariate analysis (OR 3.12, 95% CI 0.39-24.6). CONCLUSION: Symptomatic COVID-19 infection during pregnancy does not appear to increase the risk of preeclampsia strongly, although the size of our sample prevents us from reaching a conclusion about a low or moderate risk. It therefore does not appear necessary to reinforce preeclampsia screening in patients with symptomatic COVID-19 infection during pregnancy.

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome.

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.

Impacts and effects of COVID-19 infection in pregnancy.

OBJECTIVES: To explore the trimester wise significance of the primary outcome in pregnant women during coronavirus disease-19 (COVID-19) pandemic. METHODS: Retrospective observational study of pregnant women who were infected with COVID-19 from April 2020 until March 2021 at Bahrain Defense Force Hospital, Riffa, Bahrain. The study focused on the effects in relation to gestational age (GA), association with variables, severity, and treatment. A p-value of ≤0.05 was considered significant. RESULTS: During the study period, 74 COVID-19 cases were identified from the recorded 2944 pregnant women. The mean GA at diagnosis was 33.5±12.2 weeks, and the mean GA at birth was 38.4±1.8 weeks. Analysis of the obstetric complications revealed fetal growth restriction (FGR) had a p-value of <0.001. According to the trimester wise analysis, between the gestational period at diagnosis and the outcome of pregnancy, significant p-value of <0.01 was found in miscarriage. There were no significant associations found in GA at diagnosis and delivery, complications in relation to maternal age and body mass index, and no maternal morbidities or mortalities. CONCLUSION: In our study, FGR and miscarriage were the identified complications. However, the maternal and neonatal end result of COVID-19 was satisfactory.

ACE2: a key modulator of the renin-angiotensin system and pregnancy.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.

Catastrophic antiphospholipid syndrome during pregnancy.

Catastrophic antiphospholipid syndrome (CAPS) is an uncommon and the most severe form of antiphospholipid syndrome (APS). A 33-week pregnant patient with Klippel-Trenaunay syndrome, past SARS-CoV-2 infection and type I fetal growth restriction with shortening of the fetal long bone was diagnosed in our center with a probable CAPS. Cesarean section was performed four days after the diagnosis due to the torpid evolution of the patient. Clinical improvement was noted a few days later and the mother and baby were discharged within a week. We review the current literature on CAPS during pregnancy and provide an updated view.

Pregnancy and neonatal outcomes of COVID-19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries.

OBJECTIVE: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry. METHODS: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection. RESULTS: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM. CONCLUSIONS: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd.

Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology.

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS-CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.