key: cord-0747601-dva3cbgb
authors: Rizzo, Giuseppe; Mappa, Ilenia; Maqina, Pavjola; Bitsadze, Victoria; Khizroeva, Jamilya; Makatsarya, Alexander; D’Antonio, Francesco
title: Effect of SARS‐CoV‐2 infection during the second half of pregnancy on fetal growth and hemodynamics: A prospective study
date: 2021-03-09
journal: Acta Obstet Gynecol Scand
DOI: 10.1111/aogs.14130
sha: 56685ffe46579241b39d8f6cbbaf8ae0afd9bd18
doc_id: 747601
cord_uid: dva3cbgb

INTRODUCTION: Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. MATERIAL AND METHODS: Prospective case‐control study of consecutive pregnancies complicated by SARS‐CoV‐2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups. Fetal growth was assessed by analyzing the growth velocity of head circumference, abdominal circumference, femur length, and estimated fetal weight between the second‐ and third‐trimester scans. Similarly, changes in the pulsatility index of uterine, umbilical, and middle cerebral arteries, and their ratios were compared between the two study groups. RESULTS: Forty‐nine consecutive pregnancies complicated, and 98 not complicated, by SARS‐CoV‐2 infection were included. General baseline and pregnancy characteristics were similar between pregnant women with and those without SARS‐CoV‐2 infection. There was no difference in head circumference, abdominal circumference, femur length, and estimated fetal weight z scores between pregnancies complicated and those not complicated by SARS‐CoV‐2 infection at both the second‐ and third‐trimester scans. Likewise, there was no difference in the growth velocity of all these body parameters between the two study groups. Finally, there was no difference in the pulsatility index of both maternal and fetal Doppler scans throughout gestation between the two groups. CONCLUSIONS: Pregnancies complicated by SARS‐CoV‐2 infection are not at higher risk of developing fetal growth restriction through impaired placental function. The findings from this study do not support a policy of increased fetal surveillance in these women.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major issue in public health since the beginning of 2020, with new cases of infection, hospitalization, admission to intensive care units, and deaths increasing on a daily basis worldwide. 1 The impact of SARS-CoV-2 infection on pregnancy is a major concern for obstetrical care providers. [2] [3] [4] [5] Since the beginning of the pandemic, pregnancy has been claimed to represent an independent risk factor for severe disease. Several systematic reviews and large observational cohorts have reported a higher risk of severe respiratory symptoms, need for mechanical ventilation, and admission to intensive care units in pregnant women with SARS-CoV-2 infection compared with non-pregnant women. [6] [7] [8] The viral agent responsible for coronavirus disease 2019 , SARS-CoV-2 enters host cells by interacting with the angiotensin-converting-enzyme receptor, the levels of which are increased in the pregnant uterus and placenta, making the latter a potential target for the infection. 9 , 10 This assumption has been subsequently strengthened by the reported increased prevalence of signs of decidual arteriopathy in pregnant women with SARS-CoV-2 infection, suggesting a potential connection between infection and impaired placental function. [11] [12] [13] On this basis, we hypothesized that placental changes due to SARS-CoV-2 infection may lead to impaired fetal growth in these pregnancies and alter fetal hemodynamics.

The primary aim of this study was to compare the fetal growth velocity in pregnancies complicated by, and in those not complicated by, SARS-CoV-2 infection. The secondary aim was to elucidate whether SARS-CoV-2 infection can alter maternal and fetal Doppler results.

This is a prospective case-control study including consecutive single- This cohort was compared with a control group of pregnancies not exposed to SARS-CoV-2 and managed in our center during the same time interval. The control group had the same exclusion criteria as the study group and was matched with the latter with regard to the main maternal and pregnancy characteristics with a 1:2 ratio. SARS-CoV-2 infection was confirmed by the presence of a positive real-time polymerase chain reaction result obtained by nasopharyngeal swab specimens during pregnancy. All women with confirmed SARS-CoV-2 infection experienced mild symptoms (fever, cough, sore throat, loss of smell and taste, diarrhea) and none required hospitalization.

Ultrasound assessment was performed at the time of the secondtrimester scan and then at 36 weeks of gestation. A third-trimester scan is offered to all women to confirm fetal well-being, ascertain fetal growth, and rule out impaired placental function and fetal growth restriction. Head circumference, abdominal circumference, and femur length were measured transabdominally according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines. 14 Estimated fetal weight was calculated with the Hadlock-4 formula. 15 Doppler velocity waveforms were obtained from the following vessels: uterine, umbilical (UA) and middle cerebral (MCA) arteries according to previously reported techniques. 16 Briefly, both uterine arteries were recorded at the apparent cross-over with the external iliac artery and the mean pulsatility index (PI) was calculated as the 

In pregnancies complicated by SARS-CoV-2 infection, fetal growth and growth velocity between the second and third trimesters of pregnancy were similar compared with pregnancies not exposed to the virus, not supporting a policy of increased fetal surveillance in these women.

with an angle of insonation <30°, in the absence of maternal and fetal movements and using an automated trace of at least three consecutive waveforms. Uterine artery velocity waveforms were recorded at both ultrasonographic recordings, whereas UA-PI and MCA-PI were evaluated only during the third-trimester scan.

Biometric variables, estimated fetal weight, and Doppler indices change with gestational age, so data were expressed as the number of standard deviations (z score) by which they diverged from the expected mean difference obtained from previously constructed reference limits. 16, 18, 19 A sample size analysis was performed to evaluate the sample size Categorical variables were presented as numbers (n) and percentages (%) and analyzed using chi-squared test. Continuous variables were presented as median and interquartile range and analyzed using Mann-Whitney U test.

Data were analyzed using SPSS version 23.0 (IBM Corp.) and

MedCalC Statistical softwares version 14.8 (MedCalc Software bvba). Two-tailed p values lower than 0.05 were considered statistically significant.

The study was approved by the institutional review board of our institution (#Ost4-2020 on 30 July 2020) and all included women gave their written informed consent to participate. (Figure 1 ) .

Finally, there was no difference in the PI of both maternal and fetal Doppler scans during gestation between the two groups ( Table 2 ).

The findings from this study show that in pregnancies complicated of pregnancy were similar compared with pregnancies not exposed to the virus. Likewise, there were no differences in the maternal and fetal Doppler findings between the two study groups. These data suggest that SARS-CoV-2 infection in pregnancy is unlikely to increase the risk of fetal growth restriction and that these pregnancies do not require additional scans to detect growth disorders.

To the best of our knowledge, this is the first study investigating A recent report isolated SARS-CoV-2 exclusively from the placenta but not from newborns, so questioning the actual risk of transmission. 27 Features of fetal and maternal vascular malperfusion characterized by decidual arteriopathy with atherosis, fibrinoid necrosis, and mural hypertrophy of decidual arterioles have been described in placentas from pregnant women with SARS-CoV-2 infection. [11] [12] [13] In this study, placental pathology was not analyzed, so we cannot address this question. Moreover, outside SARS-CoV-2 infection, every condition leading to maternal vascular hypoperfusion is potentially associated with higher risk of impaired placental function, growth restriction, and stillbirth. 28 The findings from this study do not support this theory, but show that pregnancies complicated by SARS-CoV-2 infection are not at higher risk of fetal growth restriction; so, additional scans through pregnancy to rule out these disorders are not required.

A likely explanation for the lack of association between SARS-CoV-2 infection and fetal growth restriction may rely on the inclusion of women with mild symptoms, which may represent only the milder spectrum of COVID-19. In this scenario, we cannot completely rule out that women experiencing more severe COVID-19 may be at higher risk of fetal growth restriction. Furthermore, the time at maternal infection may change the risk of developing placental lesions. Finally, we did not consider whether SARS-CoV-2 infection represents an additional risk factor in women.

One of the more debated issues when managing pregnancies 

Pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy are not at higher risk of developing fetal growth restriction. The findings from this study do not support a policy of increased fetal surveillance in these women. 

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis

SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis of clinical features and pregnancy outcomes

ISUOG Interim Guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium: information for healthcare professionals -an update

Novel coronavirus disease (COVID-19) in pregnancy: what clinical recommendations to follow?

Maternal and perinatal outcomes with COVID-19: a systematic review of 108 pregnancies

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Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19

COVID-19 susceptibility in pregnancy: immune/inflammatory considerations, the role of placental ACE-2 and research considerations

Is highly expressed ACE 2 in pregnant women "a curse" in times of COVID-19 pandemic?

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Chronic histiocytic intervillositis with trophoblast necrosis are risk factors associated with placental infection from Coronavirus disease 19 (COVID-19) and intrauterine maternal-fetal systemic acute respiratory Coronavirus 2 (SARSCoV-2) transmission in liveborn and stillborn infants

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Administration of antenatal corticosteroid is associated with reduced fetal growth velocity: a longitudinal study

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