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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
<issn pub-type="epub">2296-858X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2025.1540685</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Medicine</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Evaluating the efficacy of low-molecular-weight heparin in managing umbilical artery thrombosis during pregnancy: does it offer therapeutic benefits?</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Zhao</surname> <given-names>Peng</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1573834/overview"/>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Lu</surname> <given-names>Yicheng</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Liu</surname> <given-names>Sitong</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Zhang</surname> <given-names>Lidan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2919832/overview"/>
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<contrib contrib-type="author">
<name><surname>Chen</surname> <given-names>Chong</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Yang</surname> <given-names>Xiaofu</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Department of Obstetrics, Women&#x2019;s Hospital, Zhejiang University School of Medicine</institution>, <addr-line>Hangzhou</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Ultrasonography, Women&#x2019;s Hospital, Zhejiang University School of Medicine</institution>, <addr-line>Hangzhou</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001"><p>Edited by: Margherita Neri, University of Ferrara, Italy</p></fn>
<fn fn-type="edited-by" id="fn0002"><p>Reviewed by: Abraham A. Pouliakis, National and Kapodistrian University of Athens, Greece</p><p>Dimitrios Varrias, Lenox Hill Hospital, United States</p></fn>
<corresp id="c001">&#x002A;Correspondence: Yicheng Lu, <email>5515023@zju.edu.cn</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>24</day>
<month>03</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>12</volume>
<elocation-id>1540685</elocation-id>
<history>
<date date-type="received">
<day>06</day>
<month>12</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>03</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Zhao, Lu, Liu, Zhang, Chen and Yang.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Zhao, Lu, Liu, Zhang, Chen and Yang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Introduction</title>
<p>Umbilical artery thrombosis (UAT) is a rare but serious pregnancy complication, potentially causing fetal growth restriction, distress, and stillbirth. Diagnosis relies on Doppler ultrasound and pathological assessment. Close monitoring and potential low-molecular-weight heparin (LMWH) therapy aim to prolong gestation and improve outcomes, but debate persists on its efficacy compared to expectant management.</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>A retrospective study, conducted between January 2013 and December 2023, enrolled singleton pregnant women diagnosed with UAT during pregnancy. The experiment group included pregnant women who underwent LMWH with anti-coagulation therapy during pregnancy, while the expectant group comprised pregnancies that received standard prenatal care without any specific intervention for UAT.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>The expectant group showed a significant increase in birth weight (expectant vs. experiment: 2434.40&#x202F;&#x00B1;&#x202F;770.20&#x202F;g vs. 1874.46&#x202F;&#x00B1;&#x202F;717.83&#x202F;g, <italic>P</italic> &#x003C;&#x202F;0.05) and a significant decrease in the incidence of births before 34&#x202F;weeks (expectant vs. experiment: 42.24% vs. 82.75%, <italic>P</italic>&#x202F;&#x003C; 0.05). Gestational age at birth was notably higher in the expectant group as compared to the experiment group (35.32&#x202F;&#x00B1;&#x202F;3.89 vs. 33.59&#x202F;&#x00B1;&#x202F;4.17), although the difference did not reach statistical significance (<italic>p</italic>&#x202F;=&#x202F;0.110). The multi-factor ANOVA revealed statistically significant effects of anti-coagulation therapy (<italic>F</italic>&#x202F;=&#x202F;4.479, <italic>p</italic>&#x202F;=&#x202F;0.039) and gestational age at birth (<italic>F</italic>&#x202F;=&#x202F;179.110, <italic>p</italic>&#x202F;=&#x202F;0.000) on birth weight. This study found that the relationship between these variables can be formulated as: birth weight&#x202F;=&#x202F;&#x2212;3314.782&#x2013;256.106&#x202F;&#x00D7;&#x202F;anti-coagulation therapy (coded as 1 if yes and 0 if no) +161.858&#x202F;&#x00D7;&#x202F;gestational age at birth.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>Our study suggests that expectant therapy may offer substantial benefits compared to experimental therapy involving the administration of LMWH.</p>
</sec>
</abstract>
<kwd-group>
<kwd>umbilical artery thrombosis</kwd>
<kwd>expectant management</kwd>
<kwd>low molecular weight heparin</kwd>
<kwd>birth weight</kwd>
<kwd>anti-coagulation therapy</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="15"/>
<page-count count="6"/>
<word-count count="3085"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Obstetrics and Gynecology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<title>Introduction</title>
<p>Umbilical artery thrombosis (UAT), a rare pregnancy complication, has an estimated incidence ranging from 0.0025 to 0.045% (<xref ref-type="bibr" rid="ref1">1</xref>). This condition can lead to fetal growth restriction, fetal distress, and stillbirth (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref3">3</xref>). Currently, the diagnosis of UAT relies primarily on Doppler ultrasound imaging and pathological assessment of the umbilical cord after delivery.</p>
<p>UAT carries the risk of sudden fetal death, deciding to terminate pregnancy a potentially viable option in the third trimester to avoid intrauterine fetal death; however, it is imperative to acknowledge that this course of action may result in an increased risk of iatrogenic preterm birth. Therefore, close monitoring of fetal conditions and growth trends via therapeutic management has been recognized as a strategy that potentially prolongs the gestational period and enhances neonatal outcomes (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref4">4</xref>, <xref ref-type="bibr" rid="ref5">5</xref>). For instance, Wang et al. reported that the administration of low-molecular-weight heparin (LMWH) to prevent the progression of UAT holds the potential to enhance pregnancy outcomes (<xref ref-type="bibr" rid="ref6">6</xref>). Additionally, Li noted that anticoagulation therapy of LMWH combined with aspirin could reduce the occurrence of adverse pregnancy outcomes (<xref ref-type="bibr" rid="ref7">7</xref>). However, in other research on expectant management where the application of LMWH was not used, similar perinatal outcomes were achieved (<xref ref-type="bibr" rid="ref3">3</xref>, <xref ref-type="bibr" rid="ref5">5</xref>, <xref ref-type="bibr" rid="ref8">8</xref>, <xref ref-type="bibr" rid="ref9">9</xref>). The question of whether LMWH holds a distinct advantage over expectant management remains a subject of ongoing debate, particularly in terms of its potential therapeutic benefits. Consequently, we conducted the current study to evaluate the efficacy of LMWH in managing UAT during pregnancy.</p>
</sec>
<sec sec-type="methods" id="sec6">
<title>Methods</title>
<p>This study was conducted retrospectively, involving a comprehensive review of all delivery cases recorded at the Women&#x2019;s Hospital, Zhejiang University School of Medicine, between January 2013 and December 2023. Patients suspected of having UAT, based on either ultrasonographic imaging or pathological examination, underwent a comprehensive review by ultrasonography experts and pathology experts, respectively. Following this thorough evaluation, only those participants with a confirmed diagnosis of UAT were selected and included in the study.</p>
<sec id="sec7">
<title>Ultrasonographic imaging</title>
<p>The ultrasound screening is performed by the direct visualization of the umbilical cord or by tracking the umbilical arteries around the fetal bladder with color Doppler technology (<xref ref-type="bibr" rid="ref10">10</xref>). The diagnosis of UAT is established when an initial ultrasound examination in the first trimester of pregnancy indicates normal umbilical artery flow, but later scans reveal the presence of a single umbilical artery.</p>
</sec>
<sec id="sec8">
<title>Pathological examination</title>
<p>Upon staining with Hematoxylin&#x2013;Eosin, sections of the umbilical cord revealed the presence of thrombosis (specifically, fibrinous, mixed, or red thrombus) within one of the umbilical arteries. This thrombosis exhibited features that ranged from total or partial necrosis of the artery wall to cases where no evident necrosis was observed (<xref ref-type="bibr" rid="ref11">11</xref>).</p>
</sec>
<sec id="sec9">
<title>Group assignment</title>
<p>The study population was assigned into two distinct groups: the experimental group and the expectant group, based on the treatment regimen they received. Participants in the experimental group received LMWH (nadroparin calcium 4,100&#x202F;U daily or enoxaparin sodium 4,000&#x202F;U daily) for anti-coagulation therapy, underwent rigorous ultrasound surveillance, non-stress testing beyond 28&#x202F;weeks of gestation, and were instructed to closely monitor fetal movements. In contrast, participants in the expectant group received only standard prenatal care.</p>
</sec>
<sec id="sec10">
<title>Data collection</title>
<p>Data pertaining to maternal age, gravidity, parity, gestational weeks at diagnosis, gestational weeks at delivery, and neonatal outcomes such as birth weight, Apgar scores, cesarean delivery, fetal distress, neonatal morbidity, and newborn intensive care unit (NICU) admission were collected and analyzed.</p>
</sec>
<sec id="sec11">
<title>Statistical analysis</title>
<p>Statistical analysis was carried out with SPSS 25.0 for Microsoft Windows (IBM Corp., Armonk, NY, USA). Comparisons of continuous variables between groups were performed using Student&#x2019;s t-test (for data that were normally distributed) or Mann&#x2013;Whitney U-test (for data that exhibited non-normal distribution), while comparisons of categorical variables were conducted with the &#x03C7;<sup>2</sup> test. Multi-factor ANOVA was used to investigate the effects of independent variables on birth weight. Multivariable logistic regression models were utilized to explore the association between the independent variables and birth weight. A <italic>p</italic>-value of &#x003C;&#x202F;0.05 was considered statistically significant.</p>
</sec>
</sec>
<sec sec-type="results" id="sec12">
<title>Results</title>
<sec id="sec13">
<title>Participants selection</title>
<p>During the study period, a total of 182,942 deliveries were recorded. Among these, 65 pregnancies were diagnosed with UAT. However, eight cases were subsequently excluded due to fetal death at presentation. Finally, a total of 57 participants with UAT were included in the analysis, with 29 participants assigned to the experiment group and the remaining 28 designated to the expectant group. Details are presented in <xref ref-type="fig" rid="fig1">Figure 1</xref>.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Flow diagram.</p>
</caption>
<graphic xlink:href="fmed-12-1540685-g001.tif"/>
</fig>
</sec>
<sec id="sec14">
<title>Clinical characteristics</title>
<p>The results of the comparison pertaining to baseline clinical characteristics between the experiment group and the expectant group are presented in <xref ref-type="table" rid="tab1">Table 1</xref>. Consequently, no significant differences were noted in terms of maternal age (30.14&#x202F;&#x00B1;&#x202F;4.23 vs. 30.79&#x202F;&#x00B1;&#x202F;3.92, <italic>p</italic>&#x202F;=&#x202F;0.552), BMI (26.75&#x202F;&#x00B1;&#x202F;4.99 vs. 26.05&#x202F;&#x00B1;&#x202F;3.09, <italic>p</italic>&#x202F;=&#x202F;0.527), gravidity (1.97&#x202F;&#x00B1;&#x202F;1.38 vs. 2.07&#x202F;&#x00B1;&#x202F;1.33, <italic>p</italic>&#x202F;=&#x202F;0.769), primigravida (48.28% vs. 46.43%, <italic>p</italic>&#x202F;=&#x202F;1.000), parity (0.41&#x202F;&#x00B1;&#x202F;0.68 vs. 0.43&#x202F;&#x00B1;&#x202F;0.57, <italic>p</italic>&#x202F;=&#x202F;0.930), primipara (31.03% vs. 39.29%, <italic>p</italic>&#x202F;=&#x202F;0.585), and gestational age at diagnosis (29.90&#x202F;&#x00B1;&#x202F;4.62 vs. 31.00&#x202F;&#x00B1;&#x202F;4.31, <italic>p</italic>&#x202F;=&#x202F;0.497).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Comparison of clinical characteristics between the experiment group and expectant group.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th align="center" valign="top">Experiment group<break/><italic>N</italic>&#x202F;=&#x202F;29</th>
<th align="center" valign="top">Expectant group<break/><italic>N</italic>&#x202F;=&#x202F;28</th>
<th align="center" valign="top"><italic>p</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Maternal age</td>
<td align="center" valign="top">30.14&#x202F;&#x00B1;&#x202F;4.23</td>
<td align="center" valign="top">30.79&#x202F;&#x00B1;&#x202F;3.92</td>
<td align="center" valign="top">0.552</td>
</tr>
<tr>
<td align="left" valign="top">BMI</td>
<td align="center" valign="top">26.75&#x202F;&#x00B1;&#x202F;4.99</td>
<td align="center" valign="top">26.05&#x202F;&#x00B1;&#x202F;3.09</td>
<td align="center" valign="top">0.527</td>
</tr>
<tr>
<td align="left" valign="top">Gravidity</td>
<td align="center" valign="top">1.97&#x202F;&#x00B1;&#x202F;1.38</td>
<td align="center" valign="top">2.07&#x202F;&#x00B1;&#x202F;1.33</td>
<td align="center" valign="top">0.769</td>
</tr>
<tr>
<td align="left" valign="top">Primigravida</td>
<td align="center" valign="top">14 (48.28)</td>
<td align="center" valign="top">13 (46.43)</td>
<td align="center" valign="top" rowspan="2">1.000</td>
</tr>
<tr>
<td align="left" valign="top">Multigravida</td>
<td align="center" valign="top">15 (51.72)</td>
<td align="center" valign="top">15 (53.57)</td>
</tr>
<tr>
<td align="left" valign="top">Parity</td>
<td align="center" valign="top">0.41&#x202F;&#x00B1;&#x202F;0.68</td>
<td align="center" valign="top">0.43&#x202F;&#x00B1;&#x202F;0.57</td>
<td align="center" valign="top">0.930</td>
</tr>
<tr>
<td align="left" valign="top">Primipara</td>
<td align="center" valign="top">20 (68.97)</td>
<td align="center" valign="top">17 (60.71)</td>
<td align="center" valign="top" rowspan="2">0.585</td>
</tr>
<tr>
<td align="left" valign="top">Multipara</td>
<td align="center" valign="top">9 (31.03)</td>
<td align="center" valign="top">11 (39.29)</td>
</tr>
<tr>
<td align="left" valign="top">Gestational age at diagnosis (weeks)</td>
<td align="center" valign="top">29.90&#x202F;&#x00B1;&#x202F;4.62</td>
<td align="center" valign="top">31.00&#x202F;&#x00B1;&#x202F;4.31</td>
<td align="center" valign="top">0.497</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec15">
<title>Clinical outcomes</title>
<p>The results of the comparison of clinical outcomes between the experiment group and the expectant group are presented in <xref ref-type="table" rid="tab2">Table 2</xref>. The birth weight in the experiment group was significantly lower compared to the expectant group (1874.46&#x202F;&#x00B1;&#x202F;717.83 vs. 2434.40&#x202F;&#x00B1;&#x202F;770.20, <italic>p</italic> =&#x202F;0.008), while the proportion of births before 34&#x202F;weeks was significantly higher in the experiment group than the expectant group (82.75% vs. 42.24%, <italic>p</italic> =&#x202F;0.001), indicating a higher prevalence of early preterm delivery (&#x003C;34&#x202F;weeks of gestation) and lower birth weight in the experiment group. Gestational age at birth was notably lower in the experiment group as compared to the expectant group, although the difference did not reach statistical significance. No significant differences were noted in terms of Apgar scores, cesarean delivery, fetal distress, neonatal morbidity, and NICU stay.</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Perinatal outcomes of the experiment group and expectant group.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Outcomes</th>
<th align="center" valign="top">Experiment group<break/><italic>N</italic> =&#x202F;29</th>
<th align="center" valign="top">Expectant group<break/><italic>N</italic> =&#x202F;28</th>
<th align="center" valign="top"><italic>p</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">&#x003C;34&#x202F;weeks</td>
<td align="center" valign="top">24 (82.75)</td>
<td align="center" valign="top">11 (42.24)</td>
<td align="center" valign="top">0.001</td>
</tr>
<tr>
<td align="left" valign="top">&#x003C;32&#x202F;weeks</td>
<td align="center" valign="top">17 (58.62)</td>
<td align="center" valign="top">9 (32.14)</td>
<td align="center" valign="top">0.064</td>
</tr>
<tr>
<td align="left" valign="top">&#x003C;30&#x202F;weeks</td>
<td align="center" valign="top">13 (44.82)</td>
<td align="center" valign="top">6 (21.43)</td>
<td align="center" valign="top">0.092</td>
</tr>
<tr>
<td align="left" valign="top">&#x003C;28&#x202F;weeks</td>
<td align="center" valign="top">5 (17.24)</td>
<td align="center" valign="top">3 (10.71)</td>
<td align="center" valign="top">0.706</td>
</tr>
<tr>
<td align="left" valign="top">Gestational age at birth (weeks)</td>
<td align="center" valign="top">33.59&#x202F;&#x00B1;&#x202F;4.17</td>
<td align="center" valign="top">35.32&#x202F;&#x00B1;&#x202F;3.89</td>
<td align="center" valign="top">0.110</td>
</tr>
<tr>
<td align="left" valign="top">Birth weight</td>
<td align="center" valign="top">1874.46&#x202F;&#x00B1;&#x202F;717.83</td>
<td align="center" valign="top">2434.40&#x202F;&#x00B1;&#x202F;770.20</td>
<td align="center" valign="top">0.008</td>
</tr>
<tr>
<td align="left" valign="top">Apgar score 1&#x202F;min</td>
<td align="center" valign="top">8.54&#x202F;&#x00B1;&#x202F;2.47</td>
<td align="center" valign="top">9.40&#x202F;&#x00B1;&#x202F;1.29</td>
<td align="center" valign="top">0.125</td>
</tr>
<tr>
<td align="left" valign="top">Apgar score 5&#x202F;min</td>
<td align="center" valign="top">9.92&#x202F;&#x00B1;&#x202F;0.41</td>
<td align="center" valign="top">9.96&#x202F;&#x00B1;&#x202F;0.20</td>
<td align="center" valign="top">0.618</td>
</tr>
<tr>
<td align="left" valign="top">Cesarean delivery</td>
<td align="center" valign="top">25 (86.21)</td>
<td align="center" valign="top">24 (85.71)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">Fetal distress</td>
<td align="center" valign="top">10 (34.48)</td>
<td align="center" valign="top">11 (39.29)</td>
<td align="center" valign="top">0.707</td>
</tr>
<tr>
<td align="left" valign="top">Neonatal morbidity</td>
<td align="center" valign="top">3 (10.34)</td>
<td align="center" valign="top">3 (10.71)</td>
<td align="center" valign="top">1.000</td>
</tr>
<tr>
<td align="left" valign="top">NICU stay (days)</td>
<td align="center" valign="top">20.24&#x202F;&#x00B1;&#x202F;22.88</td>
<td align="center" valign="top">9.52&#x202F;&#x00B1;&#x202F;16.80</td>
<td align="center" valign="top">0.070</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Data are presented as mean&#x202F;&#x00B1;&#x202F;SD or n (%).</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec16">
<title>Multi-factor ANOVA</title>
<p>The results of the multi-factor ANOVA are summarized in <xref ref-type="table" rid="tab3">Table 3</xref>. The ANOVA revealed statistically significant anti-coagulation therapy (LMWH for participants in the experiment group) (<italic>F</italic>&#x202F;=&#x202F;4.479, <italic>p</italic>&#x202F;=&#x202F;0.039) and gestational age at birth (<italic>F</italic>&#x202F;=&#x202F;179.110, <italic>p</italic>&#x202F;=&#x202F;0.000) on birth weight.</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Multi-factor ANOVA for birth weight: anti-coagulation therapy, gestational age at birth, and gender.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Outcome</th>
<th align="center" valign="top"><italic>F</italic></th>
<th align="center" valign="top"><italic>p</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Experiment therapy (anti-coagulation therapy)</td>
<td align="center" valign="middle">4.479</td>
<td align="center" valign="middle">0.039</td>
</tr>
<tr>
<td align="left" valign="top">Gestational age at birth (weeks)</td>
<td align="center" valign="middle">179.110</td>
<td align="center" valign="middle">0.000</td>
</tr>
<tr>
<td align="left" valign="top">Gender</td>
<td align="center" valign="middle">1.917</td>
<td align="center" valign="middle">0.172</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec17">
<title>Linear regression model</title>
<p>The results in <xref ref-type="table" rid="tab4">Table 4</xref> indicated a significant negative association of anti-coagulation therapy (<italic>&#x03B2;</italic>&#x202F;=&#x202F;&#x2212;0.164, <italic>p</italic>&#x202F;=&#x202F;0.014) and a strong positive correlation of gestational age (&#x03B2;&#x202F;=&#x202F;0.846, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001) with birth weight. The final linear regression equation can be expressed as: birth weight&#x202F;=&#x202F;&#x2212;3314.782&#x2013;256.106&#x202F;&#x00D7;&#x202F;anti-coagulation therapy +161.858&#x202F;&#x00D7; gestational age at birth (weeks).</p>
<table-wrap position="float" id="tab4">
<label>Table 4</label>
<caption>
<p>Linear regression model for experiment therapy and gestational age at birth (weeks).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Items</th>
<th align="center" valign="top" colspan="2">Non-standardized Coefficients</th>
<th align="center" valign="top" colspan="3">Standardized Coefficients</th>
<th align="center" valign="top" colspan="2">95% Confidence interval for B</th>
</tr>
<tr>
<th align="center" valign="top">Regression coefficient B</th>
<th align="center" valign="top">Std.-Error</th>
<th align="center" valign="top">Beta</th>
<th align="center" valign="top"><italic>T</italic></th>
<th align="center" valign="top">Sig.</th>
<th align="center" valign="top">Lower limit</th>
<th align="center" valign="top">Upper limit</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">(Constant value)</td>
<td align="center" valign="top">&#x2212;3314.782</td>
<td align="center" valign="top">441.554</td>
<td/>
<td align="center" valign="top">&#x2212;7.507</td>
<td align="center" valign="top">0.000</td>
<td align="center" valign="top">&#x2212;4201.669</td>
<td align="center" valign="top">&#x2212;2427.894</td>
</tr>
<tr>
<td align="left" valign="top">Experiment therapy (Anti-coagulation therapy)</td>
<td align="center" valign="top">&#x2212;256.106</td>
<td align="center" valign="top">100.2</td>
<td align="center" valign="top">&#x2212;0.164</td>
<td align="center" valign="top">&#x2212;2.555</td>
<td align="center" valign="top">0.014</td>
<td align="center" valign="top">&#x2212;457.410</td>
<td align="center" valign="top">&#x2212;54.802</td>
</tr>
<tr>
<td align="left" valign="top">Gestational age at birth (weeks)</td>
<td align="center" valign="top">161.858</td>
<td align="center" valign="top">12.270</td>
<td align="center" valign="top">0.846</td>
<td align="center" valign="top">13.191</td>
<td align="center" valign="top">0.000</td>
<td align="center" valign="top">137.213</td>
<td align="center" valign="top">186.502</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec sec-type="discussion" id="sec18">
<title>Discussion</title>
<sec id="sec19">
<title>Major findings</title>
<p>The key findings of our study were: (1) expectant therapy had a significant advantage over experiment therapy in pregnancies with UAT, as the administration of LMWH resulted in a significant decrease in birth weight and a substantial increase in the incidence of preterm birth (&#x003C;34&#x202F;weeks); (2) the relationship between these variables can be formulated as: birth weight&#x202F;=&#x202F;&#x2212;3314.782&#x2013;256.106&#x202F;&#x00D7;&#x202F;anti-coagulation therapy +161.858&#x202F;&#x00D7;&#x202F;gestational age at birth. The key findings are incorporated and presented in <xref ref-type="fig" rid="fig2">Figure 2</xref>.</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>The key findings of our study. Panel <bold>(A)</bold> presents a comparative analysis of birth weight, demonstrating that the birth weight in the experiment group was significantly lower compared to the expectant group (1874.46 &#x00B1; 717.83 vs. 2434.40 &#x00B1; 770.20, <italic>p</italic> = 0.008). Panel <bold>(B)</bold> illustrates the distribution of preterm births before 34 weeks, showing that the proportion of births before 34 weeks was significantly higher in the experiment group than the expectant group (82.75% vs. 42.24%, <italic>p</italic> = 0.001). Panel <bold>(C)</bold> displays our birth weight prediction model, featuring the mathematical formula: &#x201C;birth weight = &#x2212;3314.782&#x2013;256.106 &#x00D7; anti-coagulation therapy +161.858 &#x00D7; gestational age at birth&#x201D;, presented in a three-dimensional surface plot for enhanced visualization.</p>
</caption>
<graphic xlink:href="fmed-12-1540685-g002.tif"/>
</fig>
</sec>
<sec id="sec20">
<title>Comparisons with existing literature</title>
<p>UAT may occur after placenta thrombotic vasculopathy (<xref ref-type="bibr" rid="ref12">12</xref>), umbilical cord abnormalities (<xref ref-type="bibr" rid="ref3">3</xref>, <xref ref-type="bibr" rid="ref13">13</xref>, <xref ref-type="bibr" rid="ref14">14</xref>), and underlying maternal diseases (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref15">15</xref>). At present, no consensus has been reached on the treatment strategy for UAT. In clinical practice, upon the occurrence of a fetal umbilical cord embolism, one would instinctively consider the implementation of anti-coagulation therapy to arrest the progression of thrombus emboli, thereby preventing complete occlusion of the umbilical vessels and reducing the subsequent risk of fetal death. For instance, Wang et al. (<xref ref-type="bibr" rid="ref6">6</xref>) reviewed 10 cases of pregnancies with UAT. Notably, all participants in the study received treatment with LMWH, and there was no control group of expectant mothers. Based on their findings, the researchers concluded that the early administration of LMWHs may enhance pregnancy outcomes. However, there have been arguments raised against the use of anticoagulation treatment. Wei et al. reported a case series revealing that the expectant management of UAT had comparable fetal outcomes to those observed in patients who received anti-coagulation management (<xref ref-type="bibr" rid="ref3">3</xref>). Han et al. demonstrated that expectant treatment of patients with UAT had apparent positive effects for extending gestational age, which was supported by another study conducted by Dindinger et al. (<xref ref-type="bibr" rid="ref5">5</xref>, <xref ref-type="bibr" rid="ref9">9</xref>). Our study found that expectant management had significant advantages compared to anti-coagulation therapy, as the latter, when combined with frequent ultrasound surveillance, could induce anxiety in both patients and clinicians, resulting in unnecessary early medical interventions to deliver the fetus.</p>
</sec>
<sec id="sec21">
<title>Strengths and limitations</title>
<p>Our study has several strengths. First, it was designed as a retrospective study with two arms (expectant vs. experiment), whereas the previous studies (<xref ref-type="bibr" rid="ref2 ref3 ref4">2&#x2013;4</xref>, <xref ref-type="bibr" rid="ref6">6</xref>, <xref ref-type="bibr" rid="ref7">7</xref>) were primarily case reports. Second, we used multi-factor ANOVA to analyze the associations between the expectant group and the experiment group, leveraging its advantages in accounting for the potential confounding effects of multiple variables. Third, due to the rigorous design and comprehensive analysis, our results were more aligned with real-world clinical logic and practical experiences, indicating a greater degree of applicability and reliability. However, it is important to acknowledge that the retrospective design of our study, coupled with the relatively small sample size, may result in incomplete data and an increased risk of bias.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec22">
<title>Conclusion</title>
<p>In conclusion, our study provides valuable insights into the management of UAT and suggests that expectant therapy may offer significant advantages over experimental therapy involving LMWH administration. These findings have important implications for clinical practice and future research in this area.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec23">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.</p>
</sec>
<sec sec-type="ethics-statement" id="sec24">
<title>Ethics statement</title>
<p>The studies involving humans were approved by Ethics Committe of Women&#x2019;s Hospital, School of Medicine, Zhejiang University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec sec-type="author-contributions" id="sec25">
<title>Author contributions</title>
<p>PZ: Conceptualization, Methodology, Supervision, Writing &#x2013; review &#x0026; editing. YL: Visualization, Writing &#x2013; original draft. SL: Data curation, Investigation, Writing &#x2013; review &#x0026; editing. LZ: Software, Writing &#x2013; review &#x0026; editing, Formal Analysis. CC: Writing &#x2013; review &#x0026; editing, Data curation, Investigation. XY: Writing &#x2013; review &#x0026; editing, Formal Analysis, Software.</p>
</sec>
<sec sec-type="funding-information" id="sec26">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research and/or publication of this article.</p>
</sec>
<sec sec-type="COI-statement" id="sec27">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec28">
<title>Generative AI statement</title>
<p>The authors declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec sec-type="disclaimer" id="sec29">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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