Evolution of Fetal Growth in Symptomatic Sars-Cov-2
                    Pregnancies

Jens Hachenberg; Julia Guenther; Lena Steinkasserer; Lars Brodowski; Ansgard Lena Dueppers; Maria Delius; Loredana Delle Chiaie; Silvia Lobmaier; Marina Sourouni; Manuela F. Richter; Jula Manz; Olaf Parchmann; Saskia Schmidt; Jennifer Winkler; Pia Werring; Katrina Kraft; Mirjam Kunze; Maike Manz; Christian Eichler; Viola Schaefer; Martin Berghaeuser; Dietmar Schlembach; Sven Seeger; Ute Schäfer-Graf; Ioannis Kyvernitakis; Michael K. Bohlmann; Babette Ramsauer; Christine Angela Morfeld; Mario Ruediger; Ulrich Pecks; Constantin von Kaisenberg

doi:10.1055/a-2224-2262

Zeitschrift für Geburtshilfe und Neonatologie, Table of Contents

Z Geburtshilfe Neonatol 2024; 228(01): 57-64
DOI: 10.1055/a-2224-2262

Original Article

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies

Entwicklung des fetalen Wachstums bei symptomatischen SARS-CoV-2-Schwangerschaften

Jens Hachenberg

¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany

,

Julia Guenther

¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany

,

Lena Steinkasserer

¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany

,

Lars Brodowski

¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany

²Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany

,

Ansgard Lena Dueppers

¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany

,

Maria Delius

³Obstetrics and Gynecology, LMU, München, Germany

,

Loredana Delle Chiaie

⁴Department of Gynecology and Obstetrics, City of Stuttgart Hospitals, Stuttgart, Germany

,

Silvia Lobmaier

⁵Frauenheilkunde und Geburtshilfe, Klinikum rechts der Isar der Technischen Universitat München, München, Germany

,

Marina Sourouni

⁶Department of Gynecology and Obstetrics, University Hospital Münster, Münster, Germany

,

Manuela F. Richter

⁷Neonatologie, KKB, Hannover, Germany

,

Jula Manz

⁸Department of Gynecology and Obstetrics, Darmstadt Hospital, Darmstadt, Germany

,

Olaf Parchmann

⁹Department of Gynecology and Obstetrics, HELIOS Klinik Sangerhausen, Sangerhausen, Germany

,

Saskia Schmidt

¹⁰Department of Gynecology and Obstetrics, Sana Klinikum Lichtenberg, Berlin, Germany

,

Jennifer Winkler

¹¹Department of Gynecology and Obstetrics, Dresden University Hospital, Dresden, Germany

,

Pia Werring

¹²Department of Gynecology and Obstetrics, Christophorus-Kliniken GmbH Betriebsstätte Sankt-Vincenz-Hospital Coesfeld, Coesfeld, Germany

,

Katrina Kraft

¹³Department of Gynecology and Obstetrics, München Klinik Harlaching, München, Germany

,

Mirjam Kunze

¹⁴Frauenklinik, Universitätsklinik Freiburg, Freiburg, Germany

,

Maike Manz

¹⁵Department of Obstetrics and Gynaecology, Klinikum Darmstadt, Darmstadt, Germany

,

Christian Eichler

¹⁶Department of Obstetrics and Gynecology, St Franziskus-Hospital Münster GmbH, Münster, Germany

,

Viola Schaefer

¹⁷Department of Gynecology and Obstetrics, University Hospital Marburg Department of Gynaecology and Obstetrics, Marburg, Germany

,

Martin Berghaeuser

¹⁸Department of Gynecology and Obstetrics, Florence-Nightingale-Krankenhaus, Düsseldorf, Germany

,

Dietmar Schlembach

¹⁹Klinik für Geburtsmedizin, Vivantes Klinikum Neukölln, Berlin, Germany

,

Sven Seeger

²⁰KH St. Elisabeth und St. Barbara Halle, Klinik für Frauenheilkunde und Geburtshilfe, Perinatalzentrum, Halle/Saale, Germany

,

Ute Schäfer-Graf

²¹Klinik für Geburtshilfe, St Joseph Krankenhaus Berlin-Tempelhof, Berlin, Germany

,

Ioannis Kyvernitakis

²²Dept. of Obstetrics and Gynecology, Philipps-University of Marburg, Marburg, Germany

,

Michael K. Bohlmann

²³Frauenheilkunde und Geburtshilfe, St Elisabethen-Krankenhaus Lörrach gGmbH, Lörrach, Germany

,

Babette Ramsauer

²⁴Department of Gynecology and Obstetrics, Vivantes Klinikum Neukölln, Berlin, Germany

,

Christine Angela Morfeld

²⁵Perinatalzentrum, DIAKOVERE gGmbH, Hannover, Germany

,

Mario Ruediger

²⁶Department of Neonatology, Dresden University Hospital, Dresden, Germany

,

Ulrich Pecks

²⁷Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Kiel, Germany

,

Constantin von Kaisenberg

¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany

› Author Affiliations

Abstract

Introduction SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth.

Materials & Methods CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2–4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile.

Results Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively.

Conclusion FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

Key words

SARS-CoV-2 - fetal growth restriction - large for gestational age - pregnancy - COVID-19 - outcome

Schlüsselwörter

SARS-CoV-2 - Fetale Wachstumsbeschränkung - Large for gestational age - Schwangerschaft - COVID-19 - Outcome

Full Text

References

References
1 Khan DSA, Pirzada AN, Ali A. et al. The differences in clinical presentation, management, and prognosis of laboratory-confirmed Covid-19 between pregnant and non-pregnant women: A systematic review and meta-analysis. Int J Environ Res Public Health 2021; 18: 5613
2 Longardt AC, Winkler VP, Pecks U. SARS-CoV-2 and perinatal aspects. Z Geburtshilfe Neonatol 2020; 224: 181-186
3 Robbins JR, Skrzypczynska KM, Zeldovich VB. et al. Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes. PLoS Pathog 2010; 6: e1000732
4 Delorme-Axford E, Donker RB, Mouillet JF. et al. Human placental trophoblasts confer viral resistance to recipient cells. Proc Natl Acad Sci U S A 2013; 110: 12048-12053
5 Hamming OJ, Terczyńska-Dyla E, Vieyres G. et al. Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses. EMBO J 2013; 32: 3055-3065
6 Armistead B, Kadam L, Drewlo S. et al. The role of NFκB in healthy and preeclamptic placenta: Trophoblasts in the spotlight. Int J Mol Sci 2020; 5: 1775
7 Kumar N, Bhatia V. Maternal SARS-CoV-2 infection, its vertical transmission, and impact on overall perinatal outcomes: A narrative review. Curr Pediatr Rev 2022; 18: 103-109
8 Menter T, Haslbauer JD, Nienhold R. et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 2020; 77: 198-209
9 Ackermann M, Verleden SE, Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020; 383: 120-128
10 Tarnawski AS, Ahluwalia A. Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs. World J Gastroenterol 2022; 28: 275-289
11 Sharps MC, Hayes DJL, Lee S. et al. A structured review of placental morphology and histopathological lesions associated with SARS-CoV-2 infection. Placenta 2020; 101: 13-29
12 Shanes ED, Mithal LB, Otero S. et al. Placental pathology in COVID-19. Am J Clin Pathol 2020; 154: 23-32
13 Baergen RN, Heller DS. Placental pathology in Covid-19 positive mothers: preliminary findings. Pediatr Dev Pathol 2020; 23: 177-180
14 Pecks U, Kirschner I, Wölter M. et al. Mass spectrometric profiling of cord blood serum proteomes to distinguish infants with intrauterine growth restriction from those who are small for gestational age and from control individuals. Transl Res 2014; 164: 57-69
15 Okai CA, Russ M, Wölter M. et al. Precision diagnostics by affinity –mass spectrometry: A novel approach for fetal growth restriction screening during pregnancy. J Clin Med 2020; 9: 1374
16 Pecks U, Mand N, Kolben T. et al. SARS-CoV-2 infection during pregnancy–an analysis of clinical data from Germany and Austria from the CRONOS registry. Dtsch Arztebl Int 2022; 119: 588-594
17 Kleinwechter HJ, Weber KS, Mingers N. et al. Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS). Am J Obstet Gynecol 2022; 227: 631.e1-631.e19
18 Mand N, Iannaccone A, Longardt A-C. et al. Neonatal outcome following maternal infection with SARS-CoV-2 in Germany: COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS). Arch Dis Child Fetal Neonatal Ed 2022; 107: 454-456
19 Ziert Y, Abou-Dakn M, Backes C. et al. Maternal and neonatal outcomes of pregnancies with COVID-19 after medically assisted reproduction: results from the prospective COVID-19-Related Obstetrical and Neonatal Outcome Study. Am J Obstet Gynecol 2022; 227: 495.e1-495.e11
20 Piekos SN, Roper RT, Hwang YM. et al. The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study. Lancet Digit Heal 2022; 4: e95-e104
21 Wilkinson M, Johnstone ED, Simcox LE. et al. The impact of COVID-19 on pregnancy outcomes in a diverse cohort in England. Sci Rep 2022; 12: 942
22 Giesbrecht GF, Rojas L, Patel S. et al. Fear of COVID-19, mental health, and pregnancy outcomes in the pregnancy during the COVID-19 pandemic study: Fear of COVID-19 and pregnancy outcomes. J Affect Disord 2022; 299: 483-491
23 McGoldrick E, Stewart F, Parker R. et al. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2020; 12: CD004454
24 Bandoli G, Palmsten K, Forbess Smith CJ. et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am 2017; 43: 489-502
25 Braun T, Sloboda DM, Tutschek B. et al. Fetal and neonatal outcomes after term and preterm delivery following betamethasone administration. Int J Gynaecol Obstet 2015; 130: 64-69