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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Percentage and number of causes of and risk factors for secondary late VKDB in infancy&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The term vitamin K deficiency bleeding &#40;VKDB&#41; substituted for the wording of hemorrhagic disease of the newborn&#44; as bleeding in the neonatal period is often not due to vitamin K deficiency and VKDB may occur in the postnatal period&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">There are various forms of VKDB and it can be classified by etiology and age of onset&#46; The etiology may be considered either primary or secondary&#46; In primary VKDB no cause other than breastfeeding can be found&#44; while in the secondary type additional risk factors compromising the vitamin K effect are diagnosed&#44; like malabsorption secondary to hepatobiliary and intestinal diseases&#44; poor intake of vitamin K or antagonist of vitamin K by drugs&#46; According to the age at onset&#44; VKDB is usually categorized into three main types&#58; early&#44; classical&#44; and late&#44; with different pathogenic mechanisms and implying for VK prophylaxis&#46; Early VKDB&#8217;s onset is at &#60;24&#8239;h of age&#59; classical VKDB begins in the first week excluding the first 24&#8239;h&#59; and late VKDB occurs between the second week and the sixth month of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The incidence of late VKDB in the absence of vitamin K prophylaxis ranges from 10&#46;5 to 80 per 100&#44;000 births&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> When intramuscular vitamin K prophylaxis is given at birth&#44; the rate of late VKDB ranges from 0&#46;24 to 3&#46;2 cases per 100&#44;000 live births&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In late VKDB&#44; the bleeding manifestations are severe and mainly involve the gastrointestinal tract and skin&#44; but also the central nervous system&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Intracranial hemorrhage &#40;ICH&#41; occurs frequently in cases of late VKDB and can lead to significant morbidity and mortality&#46; In a pooled analysis&#44; ICH was observed in 30&#8211;63&#37; of late VKDB&#44; with 14&#8211;20&#37; mortality and 40&#37; long-term neurological morbidity among survivors&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Late VKDB is one of the important health problems in infant morbidity&#44; mortality&#44; and socio-economic problem of the country&#44; which can be prevented by vitamin K prophylaxis&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> More attention should be paid by pediatricians and health authorities to prevent this serious disease&#46; There are few case reports available on this aspect from the region&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Herein&#44; in this first study that is being conducted in Iraq&#44; we present the initial clinical and demographic features&#44; laboratory findings&#44; and outcome with their significant difference among all 47 patients with primary and secondary late VKDB&#44; who were observed over a 5-year study period at the Pediatric Ward of the Al-Sader Teaching Hospital in the Misan Province&#44; south of Iraq&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">This prospective study was conducted from October 1st&#44; 2014 to September 31st&#44; 2019&#46; All 47 infants with less than 6 months of age with late onset VKDB&#44; who were observed and admitted to the pediatric ward in the Al-Sader Teaching Hospital in the Misan Province&#44; Iraq during the study period were included&#46; An especially designed questionnaire was used to collect initial sociodemographic&#44; clinical&#44; and laboratory data of the studied infants at diagnosis&#46; The patients were diagnosed&#44; treated&#44; and followed up closely for at least 8 months&#44; with a median duration of follow-up of 12 months &#40;range 8&#8211;24 months&#41;&#46; Informed consent was obtained from parents or guardians of patients&#44; and this study protocol was approved by the Ethical Committee at the College of Medicine&#44; University of Misan&#44; Iraq&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the clinical criteria for diagnosis of late-onset VKDB based on primary VKDB&#44; no cause other than breastfeeding can be found&#44; while in the secondary type additional factors compromising the vitamin K effect are diagnosed&#44; like malabsorption secondary to hepatobiliary and intestinal diseases or preceding antibiotics use&#44; and definite cases had to meet the laboratory criteria of a clearly prolonged prothrombin time &#40;PT&#41; or International Normalized Ratio &#40;INR&#41; &#62;3&#46;5&#44; activated prolonged partial thromboplastin time &#40;APTT&#41; with normal fibrinogen level and platelet count with evidence of rapid normalization of these values &#40;PT and APTT&#41;&#44; and cessation of bleeding following VK administration&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Laboratory investigations included the complete blood count &#40;CBC&#41;&#44; prothrombin time &#40;PT&#41;&#47;INR&#44; activated partial thromboplastin time &#40;APTT&#41;&#44; and fibrinogen level&#46; Blood sample for CBC was collected in EDTA tubes and detected using ABX Micros ES 60 hematology analyzer &#40;HORIBA Medical&#44; France&#41;&#46; For coagulation assays&#44; venous blood samples were collected in tubes containing 0&#46;109&#8239;M &#40;3&#46;2&#37;&#41; of trisodium citrate in a ratio of 4&#46;5&#8239;mL of blood to 0&#46;5&#8239;mL of sodium citrate and then centrifuged without delay at 1200&#8239;G for 15&#8239;min&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and the assay was performed using Mindray C2000-2 Double Channel Coagulation Analyzer &#40;China&#41;&#44; with appropriate quality control materials and standard reagents &#40;BIO-TP Prothrombin Time &#91;PT&#93; &#8211; BIOLABO&#44; and BIO-CK APTT Kaolin &#8211; BIOLABO&#44; France&#41;&#44; within 3&#8239;h following the blood collection&#46; The Clauss method was used for fibrinogen assay&#46; Normal values were 10&#8211;12&#8239;s for PT&#44; 26&#8211;40&#8239;s for APTT&#44; and 1&#46;8&#8211;3&#46;6&#8239;g&#47;L for fibrinogen&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Cranial computed tomography &#40;CT&#41; scan was done for 18 infants with clinical manifestation of ICH&#46; Regarding treatments&#44; vitamin K &#40;5&#8239;mg intravenously daily for 5 days&#41; was given to all 47 observed infants&#59; fresh frozen plasma &#40;FFP&#41; was given in a dose of 15&#8239;mL&#47;kg of body weight in life-threatening bleeding situations&#44; and whole blood transfusion &#40;20&#8239;mL&#47;kg&#41; was given in cases of severe anemia&#46; Statistical analyses were reported as mean estimation&#8239;&#177;&#8239;standard deviation using the Statistical Package for the Social Sciences &#40;SPSS&#41; version 23 for Windows&#46; Comparison of categorical data was carried by <span class="elsevierStyleItalic">t</span>-test and Fisher&#39;s test&#44; and a <span class="elsevierStyleItalic">p</span> value of &#60;0&#46;05 was considered statistically significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">There were 47 infants who met the criteria of late VKDB observed during the five-year study period&#46; Secondary late VKDB was more commonly observed &#40;83&#37;&#44; 39 patients&#41; than the primary subtype &#40;17&#37;&#44; 8 patients&#41;&#46; The underlying causes and risk factors other than breastfeeding reported among secondary VKDB patients were cholestasis &#40;13&#37;&#44; 5 patients&#41;&#44; diarrhea &#40;23&#37;&#44; 9 patients&#41;&#44; diarrhea with antibiotic therapy &#40;38&#37;&#44; 15 patients&#41;&#44; or preceding antibiotic therapy &#40;26&#37;&#44; 10 patients&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The age &#40;mean&#8239;&#177;&#8239;SD&#41; of patients at onset of symptoms was 10&#46;50&#8239;&#177;&#8239;5&#46;75 weeks &#40;range&#44; 2&#8211;21 weeks&#41; in primary VKDB&#44; while in the secondary subtype it was 9&#46;74&#8239;&#177;&#8239;6&#46;04 weeks &#40;range&#44; 4&#8211;20&#41;&#44; and the age at onset of presentation did not have a significant difference between the subtypes of VKDB &#40;<span class="elsevierStyleItalic">p</span> value 0&#46;7&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In the current study&#44; late VKDB was more common among males &#40;68&#37;&#44; 32 patients&#41;&#44; with a male to female ratio of 2&#46;13&#58;1&#44; and the gender of patients did not have a significant difference between the types of VKDB &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;08&#41;&#46; As for the place of residence of the studied infants&#44; more than two-thirds of the studied patients &#40;68&#37;&#44; 32 patients&#41; lived in urban areas&#44; and the place of residence of patients did not significantly differ between the types of late VKDB &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;2&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding delivery histories&#44; more than half of the infants &#40;55&#37;&#44; 26 patients&#41; were delivered at home&#59; 27 infants &#40;57&#37;&#41; were delivered by normal vaginal delivery&#44; and 28 infants &#40;60&#37;&#41; were delivered at term&#59; place and mode of delivery and maturity of infants did not have a significant difference between the types of VKDB &#40;<span class="elsevierStyleItalic">p</span> value &#62;0&#46;05&#41;&#46; More than 3&#47;4 of patients &#40;83&#37;&#44; 39 patients&#41; with late VKDB were exclusively breastfed&#44; including all infants with the primary subtype&#44; and 4&#37; &#40;2 patients&#41; were bottle-fed&#44; and there was no significant difference between VKDB subtypes regarding types of feeding &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;7&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; All infants with late VKDB were not administered vitamin K at birth&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The most common sites of bleeding at presentation were the skin and the gastrointestinal tract &#40;GIT&#41; &#40;40&#37;&#44; 19 patients&#41;&#44; followed by ICH &#40;32&#37;&#44; 15 patients&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">There were 18&#47;47 &#40;38&#37;&#41; patients with ICH&#59; among them&#44; in 3 patients &#40;16&#46;7&#37;&#41; it was associated with skin bleeding &#40;petechiae and bruising&#41;&#44; and 15 patients &#40;83&#46;3&#37;&#41; had isolated ICH&#46; A head CT scan was performed for all cases &#40;18 infants&#41; with ICH&#46; The brain CT scan showed intraparenchymal hemorrhage in 7 cases &#40;38&#46;9&#37;&#41;&#44; and intraparenchymal with intraventricular hemorrhages in 6 cases &#40;33&#46;3&#37;&#41;&#59; 4 patients &#40;22&#46;2&#37;&#41; had subarachnoid with intraventricular hemorrhages&#44; and one patient &#40;5&#46;6&#37;&#41; had parenchymal with subarachnoid hemorrhage&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In the current study&#44; the distribution of variables was normal&#44; and we used mean&#8239;&#177;&#8239;standard deviation &#40;SD&#41; to define normality of the distribution&#46; The mean Hb level&#44; WBC count&#44; PT&#44; and fibrinogen level did not have a significant difference &#40;<span class="elsevierStyleItalic">p</span> value &#62;0&#46;05&#41;&#44; but platelet count and APTT had a significant difference &#40;<span class="elsevierStyleItalic">p</span> value &#60;0&#46;05&#41; between VKDB subclasses &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">All infants in this study were treated at the hospital with vitamin K &#40;5&#8239;mg&#41; intravenously daily for 5 days&#59; 22 patients &#40;47&#37;&#41; who presented with life-threatening bleeding situations also received 15&#8239;mL&#47;kg of fresh frozen plasma &#40;FFP&#41;&#44; and a whole blood transfusion of 20&#8239;mL&#47;kg was given to 29 patients &#40;61&#46;7&#37;&#41; who had anemia&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Regarding the outcome of patients with VKDB&#44; our study has shown that 26 patients &#40;56&#37;&#41; had a good outcome&#59; 11 patients &#40;23&#37;&#41; died&#59; and 10 infants &#40;21&#37;&#41; had neurological complications in the form of cerebral palsy &#40;50&#37;&#44; 5 patients&#41;&#44; microcephaly with seizure disorders &#40;30&#37;&#44; 3 patients&#41;&#44; and hydrocephaly with sensory deafness &#40;20&#37;&#44; 2 patients&#41; throughout the follow-up period&#44; that extended over 6 months&#46; There were no significant differences &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;7&#41; regarding the outcome of patients between VKDB subtypes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Bleeding tendency in infants&#44; which is now classified as late VKDB&#44; was first described by Bhanchet et al&#46; in 1977&#44; when they summarized in their study of 93 affected Thai infants&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> We have presented 47 infants with confirmed late VKDB with no history of vitamin K administration at birth&#46; This small sample of patients was observed over a 5-year study period because of the rarity of late VKDB&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is important to take into consideration that VKDB occurs more commonly in the Asian population compared to the European population&#46; This may be explained by the 6-fold higher incidence of biliary atresia in Asia compared to Western Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In our study&#44; predisposing diseases for late VKDB were common before bleeding begins&#44; which is similar to what Ijland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> observed when they reported that infants with late VKDB &#40;88&#46;3&#37;&#41; often have signs and symptoms of predisposing disease&#59; however&#44; in the second and third nation-wide surveys in Japan of vitamin K deficiency in infancy&#44; it was found that 10&#46;5&#37; and 16&#37; respectively had bleeding episodes due to VKDB associated with a clear pathological cause&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> and Chuansumrit et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> reported that 3&#46;7&#37; of infants with bleeding were diagnosed with secondary VKDB&#46; Liver diseases are known to be a major cause of late VKDB&#44; because they cause maldigestion of fat&#59; the decrease in fat absorption leads to a deficiency of fat soluble vitamins&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Busfield et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and Sutor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> reported that 27&#37; and 37&#37;&#44; respectively&#44; of infants with late VKDB had liver disease&#44; which is higher than our findings&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Late VKDB is characterized by bleeding in infants between the 8th day and 6 months of life&#44; and it has a peak incidence between the 3rd and 8th weeks of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> Corresponding to our results&#44; Schulte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> found that the mean age of infants with late VKDB was 10&#46;3 weeks &#40;range&#44; 7&#8211;20 weeks&#41;&#46; However&#44; Ijland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> reported that the mean age was 3&#8211;7 weeks&#44; and Sutor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> reported that the peak age was 4 weeks&#44; and that the majority &#40;79&#37;&#41; of the infants were between 3 and 7 weeks old&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">At variance with our finding&#44; Shearer<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in their study mentioned that late VKDB was higher in rural areas&#44; while most of our patients came from urban areas&#44; but the place of residence did not significantly differ between VKDB subtypes&#46; Similar to other studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;18</span></a> male infants have accounted for the majority of our patients&#44; but the gender of patients did not have a significant difference between VKDB subclasses&#46; Although this striking gender discrepancy is not yet clarified&#44; results from a previously reported study suggested that male infants may require more dietary phytomenadione than females with the same body weight&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Regarding mode of delivery&#44; our results are unlike the findings of Schulte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and Zurynski et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> who reported that 28&#46;6&#37; and 22&#37; of infants respectively were delivered at home&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Although prothrombin levels are lower than in term babies at birth&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Recent studies have certainly not provided any support to the belief that vitamin deficiency bleeding is more common in preterm babies&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> In agreement with our results&#44; B&#246;r et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> reported that all infants with late VKDB were born at term&#44; as well as Zurynski et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> who found that 93&#37; of patients were full-term babies&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Exclusive breastfeeding has emerged as a matter of concern in developing countries&#44; where exclusive breastfeeding is vigorously advocated to promote optimal health in the infant&#46; But vitamin K is poorly transmitted across the placental barrier&#44; and its stores are low at birth&#44; with levels often below the detection limit of 0&#46;02&#8239;ng&#47;mL&#59; therefore&#44; breastfed infants are at risk because of low concentrations in human milk&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> while bottle-fed babies are at almost no risk because almost all infant milk is artificially fortified&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Our results regarding types of feeding are in agreement with other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;18&#44;23&#44;24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Similar to our findings&#44; Zurynski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> observed in their study that skin and GIT&#44; followed by ICH&#44; were the most common sites of bleeding&#46; However&#44; Mihatsch et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> mentioned that ICH&#44; skin and GIT respectively were common sites in late VKDB&#46; A major feature of late VKDB is a much higher incidence of ICH &#40;30&#8211;88&#37;&#41; in patients&#44; with serious ICH leading to high morbidity and subsequent mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11&#44;12&#44;18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;25&#44;27&#8211;29</span></a> Our results are similar to those reported in other studies that observed that the most common site was intracerebral&#44; followed by multiple ICH&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;27&#44;28</span></a> However&#44; Ozdemir et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> demonstrated that subdural hemorrhage was the most common type of ICH reported&#44; followed by intracerebral and subarachnoid hemorrhages&#44; while Mart&#237;n-L&#243;pez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> mentioned that the majority of the patients &#40;75&#37;&#41; showed ICH at more than one site&#46; Late VKDB subtypes were associated with severe life-threatening bleeding&#44; mainly ICH&#44; which resulted in low hemoglobin level and anemia among our studied infants&#44; which is similar to the findings reported by others&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;21&#44;25&#44;26</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Throughout the follow-up period&#44; we observed that VKDB subtypes were associated with morbidity and lethality among studied patients&#44; and the outcome of patients did not have a statistically significant difference between the subtypes of VKDB&#46; In their study&#44; Sutor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> found that mortality was 19&#37; and neurological sequelae 21&#37; in survivor infants with VKDB&#46; Out of a total of 691 cases of late idiopathic VKDB reported in Thailand&#44; mortality rate was 24&#37;&#44; and permanent neurological deficits were found in 142&#47;257 &#40;55&#37;&#41;&#59; they were&#58; seizure disorders &#40;64&#37;&#41;&#59; muscle weakness &#40;21&#37;&#41;&#59; mental retardation &#40;15&#37;&#41;&#59; hemiparesis &#40;13&#37;&#41;&#59; hydrocephalus &#40;7&#37;&#41;&#59; and microcephaly 5&#37;&#59; however&#44; neurological sequelae in secondary late VKDB were found in 7&#47;25 &#40;28&#37;&#41; survivors&#44; and the mortality rate was 26&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> while in Aydinli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> seizure disorders &#40;73&#37;&#41;&#44; severe psychomotor retardation &#40;46&#37;&#41;&#44; cerebral palsy &#40;46&#37;&#41;&#44; microcephaly &#40;46&#37;&#41;&#44; and hydrocephalus &#40;27&#37;&#41; were observed after a follow-up period ranging from 6 to 48 months of infants with late VKDB&#44; but no fatality was mentioned&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion&#44; secondary late VKDB is more common than the primary subtype&#44; and late VKDB is still an important cause of morbidity and mortality in developing countries including Iraq&#44; where vitamin K prophylaxis is not routinely practiced&#46; The present study highlights the importance of prompt diagnosis of this clinical condition by proper history taking&#44; clinical examination&#44; and relevant investigations&#46; Vitamin K prophylaxis should be offered to all newborns who are exclusively breastfed&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The author declares no conflicts of interest&#46;</p></span></span>"
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        2 => array:2 [
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          "titulo" => "Material and methods"
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        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Conflicts of interest"
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        7 => array:2 [
          "identificador" => "xack555158"
          "titulo" => "Acknowledgement"
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        8 => array:1 [
          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-07-02"
    "fechaAceptado" => "2020-09-15"
    "PalabrasClave" => array:1 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:4 [
            0 => "Vitamin K deficiency bleeding"
            1 => "Late VKDB"
            2 => "Characteristic features"
            3 => "Outcomes"
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    "resumen" => array:1 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">To study the presenting clinical and demographic features&#44; risk factors&#44; and outcome of infants with late vitamin K deficiency bleeding&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Over a 5-year study period&#44; the presenting clinical features and outcome of all 47 infants observed aged less than 6 months&#44; who were diagnosed with late-onset primary and secondary VKDB by detailed history&#44; physical examination&#44; and laboratory findings were evaluated&#46; Confirmed primary late VKDB was diagnosed when no cause other than breastfeeding could be found&#44; while in the secondary subtype additional risk factors compromising the vitamin K effect were diagnosed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Secondary late VKDB &#40;83&#37;&#44; 39 patients&#41; was more common than the primary subtype&#46; The mean age of patients was 10&#46;50&#8239;&#177;&#8239;5&#46;75 and 9&#46;74&#8239;&#177;&#8239;6&#46;04 weeks in primary and secondary VKDB subtypes&#44; respectively&#44; and the age of infants did not have a significant difference &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41;&#46; The male to female ratio was 2&#46;13&#58;1&#46; The residency&#44; place and mode of delivery&#44; gestational age&#44; and types of feeding of patients did not have a significant difference between VKDB subtypes&#46; The skin and gastrointestinal tract &#40;GIT&#41; &#40;40&#46;4&#37;&#41; followed by intracranial hemorrhage &#40;ICH&#41; &#40;32&#37;&#41;&#44; were common sites of bleeding&#46; Neurological complications were seen in 21&#37; of patients&#59; however&#44; lethality was 23&#37;&#44; and the outcome of patients did not have a significant difference &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; between VKDB subtypes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Secondary late VKDB is more common than the primary subtypes&#44; and late VKDB is still a serious disease in developing countries&#44; including Iraq&#44; when vitamin K prophylaxis isn&#8217;t routinely used at birth&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Percentage and number of causes of and risk factors for secondary late VKDB in infancy&#46;</p>"
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;08&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Caesarian section&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Gestational age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Term &#40;&#62;37 weeks&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Preterm &#40;&#60;37 weeks&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Types of feeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Breastfeeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mixed feeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bottle feeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Outcome of patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col">Sites of bleeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Skin and ICH&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin and umbilicus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin and nose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin and circumcision&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">VKDB&#44; vitamin K deficiency bleeding&#59; SD&#44; standard deviation&#59; Hb&#44; hemoglobin&#59; WBC&#44; white blood cell&#59; PT&#44; prothrombin time&#59; INR&#44; international normalized ratio&#59; APTT&#44; activated partial thromboplastin time&#46;</p>"
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Fibrinogen mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                    0 => array:2 [
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Original article
Late vitamin K deficiency bleeding in infants: five-year prospective study
Salah Hashim AL-Zuhairy
Department of Pediatrics, College of Medicine, University of Misan, Amarah, Iraq
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The term vitamin K deficiency bleeding &#40;VKDB&#41; substituted for the wording of hemorrhagic disease of the newborn&#44; as bleeding in the neonatal period is often not due to vitamin K deficiency and VKDB may occur in the postnatal period&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">There are various forms of VKDB and it can be classified by etiology and age of onset&#46; The etiology may be considered either primary or secondary&#46; In primary VKDB no cause other than breastfeeding can be found&#44; while in the secondary type additional risk factors compromising the vitamin K effect are diagnosed&#44; like malabsorption secondary to hepatobiliary and intestinal diseases&#44; poor intake of vitamin K or antagonist of vitamin K by drugs&#46; According to the age at onset&#44; VKDB is usually categorized into three main types&#58; early&#44; classical&#44; and late&#44; with different pathogenic mechanisms and implying for VK prophylaxis&#46; Early VKDB&#8217;s onset is at &#60;24&#8239;h of age&#59; classical VKDB begins in the first week excluding the first 24&#8239;h&#59; and late VKDB occurs between the second week and the sixth month of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The incidence of late VKDB in the absence of vitamin K prophylaxis ranges from 10&#46;5 to 80 per 100&#44;000 births&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> When intramuscular vitamin K prophylaxis is given at birth&#44; the rate of late VKDB ranges from 0&#46;24 to 3&#46;2 cases per 100&#44;000 live births&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In late VKDB&#44; the bleeding manifestations are severe and mainly involve the gastrointestinal tract and skin&#44; but also the central nervous system&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Intracranial hemorrhage &#40;ICH&#41; occurs frequently in cases of late VKDB and can lead to significant morbidity and mortality&#46; In a pooled analysis&#44; ICH was observed in 30&#8211;63&#37; of late VKDB&#44; with 14&#8211;20&#37; mortality and 40&#37; long-term neurological morbidity among survivors&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Late VKDB is one of the important health problems in infant morbidity&#44; mortality&#44; and socio-economic problem of the country&#44; which can be prevented by vitamin K prophylaxis&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> More attention should be paid by pediatricians and health authorities to prevent this serious disease&#46; There are few case reports available on this aspect from the region&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Herein&#44; in this first study that is being conducted in Iraq&#44; we present the initial clinical and demographic features&#44; laboratory findings&#44; and outcome with their significant difference among all 47 patients with primary and secondary late VKDB&#44; who were observed over a 5-year study period at the Pediatric Ward of the Al-Sader Teaching Hospital in the Misan Province&#44; south of Iraq&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">This prospective study was conducted from October 1st&#44; 2014 to September 31st&#44; 2019&#46; All 47 infants with less than 6 months of age with late onset VKDB&#44; who were observed and admitted to the pediatric ward in the Al-Sader Teaching Hospital in the Misan Province&#44; Iraq during the study period were included&#46; An especially designed questionnaire was used to collect initial sociodemographic&#44; clinical&#44; and laboratory data of the studied infants at diagnosis&#46; The patients were diagnosed&#44; treated&#44; and followed up closely for at least 8 months&#44; with a median duration of follow-up of 12 months &#40;range 8&#8211;24 months&#41;&#46; Informed consent was obtained from parents or guardians of patients&#44; and this study protocol was approved by the Ethical Committee at the College of Medicine&#44; University of Misan&#44; Iraq&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the clinical criteria for diagnosis of late-onset VKDB based on primary VKDB&#44; no cause other than breastfeeding can be found&#44; while in the secondary type additional factors compromising the vitamin K effect are diagnosed&#44; like malabsorption secondary to hepatobiliary and intestinal diseases or preceding antibiotics use&#44; and definite cases had to meet the laboratory criteria of a clearly prolonged prothrombin time &#40;PT&#41; or International Normalized Ratio &#40;INR&#41; &#62;3&#46;5&#44; activated prolonged partial thromboplastin time &#40;APTT&#41; with normal fibrinogen level and platelet count with evidence of rapid normalization of these values &#40;PT and APTT&#41;&#44; and cessation of bleeding following VK administration&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Laboratory investigations included the complete blood count &#40;CBC&#41;&#44; prothrombin time &#40;PT&#41;&#47;INR&#44; activated partial thromboplastin time &#40;APTT&#41;&#44; and fibrinogen level&#46; Blood sample for CBC was collected in EDTA tubes and detected using ABX Micros ES 60 hematology analyzer &#40;HORIBA Medical&#44; France&#41;&#46; For coagulation assays&#44; venous blood samples were collected in tubes containing 0&#46;109&#8239;M &#40;3&#46;2&#37;&#41; of trisodium citrate in a ratio of 4&#46;5&#8239;mL of blood to 0&#46;5&#8239;mL of sodium citrate and then centrifuged without delay at 1200&#8239;G for 15&#8239;min&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and the assay was performed using Mindray C2000-2 Double Channel Coagulation Analyzer &#40;China&#41;&#44; with appropriate quality control materials and standard reagents &#40;BIO-TP Prothrombin Time &#91;PT&#93; &#8211; BIOLABO&#44; and BIO-CK APTT Kaolin &#8211; BIOLABO&#44; France&#41;&#44; within 3&#8239;h following the blood collection&#46; The Clauss method was used for fibrinogen assay&#46; Normal values were 10&#8211;12&#8239;s for PT&#44; 26&#8211;40&#8239;s for APTT&#44; and 1&#46;8&#8211;3&#46;6&#8239;g&#47;L for fibrinogen&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Cranial computed tomography &#40;CT&#41; scan was done for 18 infants with clinical manifestation of ICH&#46; Regarding treatments&#44; vitamin K &#40;5&#8239;mg intravenously daily for 5 days&#41; was given to all 47 observed infants&#59; fresh frozen plasma &#40;FFP&#41; was given in a dose of 15&#8239;mL&#47;kg of body weight in life-threatening bleeding situations&#44; and whole blood transfusion &#40;20&#8239;mL&#47;kg&#41; was given in cases of severe anemia&#46; Statistical analyses were reported as mean estimation&#8239;&#177;&#8239;standard deviation using the Statistical Package for the Social Sciences &#40;SPSS&#41; version 23 for Windows&#46; Comparison of categorical data was carried by <span class="elsevierStyleItalic">t</span>-test and Fisher&#39;s test&#44; and a <span class="elsevierStyleItalic">p</span> value of &#60;0&#46;05 was considered statistically significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">There were 47 infants who met the criteria of late VKDB observed during the five-year study period&#46; Secondary late VKDB was more commonly observed &#40;83&#37;&#44; 39 patients&#41; than the primary subtype &#40;17&#37;&#44; 8 patients&#41;&#46; The underlying causes and risk factors other than breastfeeding reported among secondary VKDB patients were cholestasis &#40;13&#37;&#44; 5 patients&#41;&#44; diarrhea &#40;23&#37;&#44; 9 patients&#41;&#44; diarrhea with antibiotic therapy &#40;38&#37;&#44; 15 patients&#41;&#44; or preceding antibiotic therapy &#40;26&#37;&#44; 10 patients&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The age &#40;mean&#8239;&#177;&#8239;SD&#41; of patients at onset of symptoms was 10&#46;50&#8239;&#177;&#8239;5&#46;75 weeks &#40;range&#44; 2&#8211;21 weeks&#41; in primary VKDB&#44; while in the secondary subtype it was 9&#46;74&#8239;&#177;&#8239;6&#46;04 weeks &#40;range&#44; 4&#8211;20&#41;&#44; and the age at onset of presentation did not have a significant difference between the subtypes of VKDB &#40;<span class="elsevierStyleItalic">p</span> value 0&#46;7&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In the current study&#44; late VKDB was more common among males &#40;68&#37;&#44; 32 patients&#41;&#44; with a male to female ratio of 2&#46;13&#58;1&#44; and the gender of patients did not have a significant difference between the types of VKDB &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;08&#41;&#46; As for the place of residence of the studied infants&#44; more than two-thirds of the studied patients &#40;68&#37;&#44; 32 patients&#41; lived in urban areas&#44; and the place of residence of patients did not significantly differ between the types of late VKDB &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;2&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding delivery histories&#44; more than half of the infants &#40;55&#37;&#44; 26 patients&#41; were delivered at home&#59; 27 infants &#40;57&#37;&#41; were delivered by normal vaginal delivery&#44; and 28 infants &#40;60&#37;&#41; were delivered at term&#59; place and mode of delivery and maturity of infants did not have a significant difference between the types of VKDB &#40;<span class="elsevierStyleItalic">p</span> value &#62;0&#46;05&#41;&#46; More than 3&#47;4 of patients &#40;83&#37;&#44; 39 patients&#41; with late VKDB were exclusively breastfed&#44; including all infants with the primary subtype&#44; and 4&#37; &#40;2 patients&#41; were bottle-fed&#44; and there was no significant difference between VKDB subtypes regarding types of feeding &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;7&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; All infants with late VKDB were not administered vitamin K at birth&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The most common sites of bleeding at presentation were the skin and the gastrointestinal tract &#40;GIT&#41; &#40;40&#37;&#44; 19 patients&#41;&#44; followed by ICH &#40;32&#37;&#44; 15 patients&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">There were 18&#47;47 &#40;38&#37;&#41; patients with ICH&#59; among them&#44; in 3 patients &#40;16&#46;7&#37;&#41; it was associated with skin bleeding &#40;petechiae and bruising&#41;&#44; and 15 patients &#40;83&#46;3&#37;&#41; had isolated ICH&#46; A head CT scan was performed for all cases &#40;18 infants&#41; with ICH&#46; The brain CT scan showed intraparenchymal hemorrhage in 7 cases &#40;38&#46;9&#37;&#41;&#44; and intraparenchymal with intraventricular hemorrhages in 6 cases &#40;33&#46;3&#37;&#41;&#59; 4 patients &#40;22&#46;2&#37;&#41; had subarachnoid with intraventricular hemorrhages&#44; and one patient &#40;5&#46;6&#37;&#41; had parenchymal with subarachnoid hemorrhage&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In the current study&#44; the distribution of variables was normal&#44; and we used mean&#8239;&#177;&#8239;standard deviation &#40;SD&#41; to define normality of the distribution&#46; The mean Hb level&#44; WBC count&#44; PT&#44; and fibrinogen level did not have a significant difference &#40;<span class="elsevierStyleItalic">p</span> value &#62;0&#46;05&#41;&#44; but platelet count and APTT had a significant difference &#40;<span class="elsevierStyleItalic">p</span> value &#60;0&#46;05&#41; between VKDB subclasses &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">All infants in this study were treated at the hospital with vitamin K &#40;5&#8239;mg&#41; intravenously daily for 5 days&#59; 22 patients &#40;47&#37;&#41; who presented with life-threatening bleeding situations also received 15&#8239;mL&#47;kg of fresh frozen plasma &#40;FFP&#41;&#44; and a whole blood transfusion of 20&#8239;mL&#47;kg was given to 29 patients &#40;61&#46;7&#37;&#41; who had anemia&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Regarding the outcome of patients with VKDB&#44; our study has shown that 26 patients &#40;56&#37;&#41; had a good outcome&#59; 11 patients &#40;23&#37;&#41; died&#59; and 10 infants &#40;21&#37;&#41; had neurological complications in the form of cerebral palsy &#40;50&#37;&#44; 5 patients&#41;&#44; microcephaly with seizure disorders &#40;30&#37;&#44; 3 patients&#41;&#44; and hydrocephaly with sensory deafness &#40;20&#37;&#44; 2 patients&#41; throughout the follow-up period&#44; that extended over 6 months&#46; There were no significant differences &#40;<span class="elsevierStyleItalic">p</span> value&#8239;&#61;&#8239;0&#46;7&#41; regarding the outcome of patients between VKDB subtypes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Bleeding tendency in infants&#44; which is now classified as late VKDB&#44; was first described by Bhanchet et al&#46; in 1977&#44; when they summarized in their study of 93 affected Thai infants&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> We have presented 47 infants with confirmed late VKDB with no history of vitamin K administration at birth&#46; This small sample of patients was observed over a 5-year study period because of the rarity of late VKDB&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is important to take into consideration that VKDB occurs more commonly in the Asian population compared to the European population&#46; This may be explained by the 6-fold higher incidence of biliary atresia in Asia compared to Western Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In our study&#44; predisposing diseases for late VKDB were common before bleeding begins&#44; which is similar to what Ijland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> observed when they reported that infants with late VKDB &#40;88&#46;3&#37;&#41; often have signs and symptoms of predisposing disease&#59; however&#44; in the second and third nation-wide surveys in Japan of vitamin K deficiency in infancy&#44; it was found that 10&#46;5&#37; and 16&#37; respectively had bleeding episodes due to VKDB associated with a clear pathological cause&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> and Chuansumrit et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> reported that 3&#46;7&#37; of infants with bleeding were diagnosed with secondary VKDB&#46; Liver diseases are known to be a major cause of late VKDB&#44; because they cause maldigestion of fat&#59; the decrease in fat absorption leads to a deficiency of fat soluble vitamins&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Busfield et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and Sutor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> reported that 27&#37; and 37&#37;&#44; respectively&#44; of infants with late VKDB had liver disease&#44; which is higher than our findings&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Late VKDB is characterized by bleeding in infants between the 8th day and 6 months of life&#44; and it has a peak incidence between the 3rd and 8th weeks of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> Corresponding to our results&#44; Schulte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> found that the mean age of infants with late VKDB was 10&#46;3 weeks &#40;range&#44; 7&#8211;20 weeks&#41;&#46; However&#44; Ijland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> reported that the mean age was 3&#8211;7 weeks&#44; and Sutor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> reported that the peak age was 4 weeks&#44; and that the majority &#40;79&#37;&#41; of the infants were between 3 and 7 weeks old&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">At variance with our finding&#44; Shearer<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in their study mentioned that late VKDB was higher in rural areas&#44; while most of our patients came from urban areas&#44; but the place of residence did not significantly differ between VKDB subtypes&#46; Similar to other studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;18</span></a> male infants have accounted for the majority of our patients&#44; but the gender of patients did not have a significant difference between VKDB subclasses&#46; Although this striking gender discrepancy is not yet clarified&#44; results from a previously reported study suggested that male infants may require more dietary phytomenadione than females with the same body weight&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Regarding mode of delivery&#44; our results are unlike the findings of Schulte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and Zurynski et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> who reported that 28&#46;6&#37; and 22&#37; of infants respectively were delivered at home&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Although prothrombin levels are lower than in term babies at birth&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Recent studies have certainly not provided any support to the belief that vitamin deficiency bleeding is more common in preterm babies&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> In agreement with our results&#44; B&#246;r et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> reported that all infants with late VKDB were born at term&#44; as well as Zurynski et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> who found that 93&#37; of patients were full-term babies&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Exclusive breastfeeding has emerged as a matter of concern in developing countries&#44; where exclusive breastfeeding is vigorously advocated to promote optimal health in the infant&#46; But vitamin K is poorly transmitted across the placental barrier&#44; and its stores are low at birth&#44; with levels often below the detection limit of 0&#46;02&#8239;ng&#47;mL&#59; therefore&#44; breastfed infants are at risk because of low concentrations in human milk&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> while bottle-fed babies are at almost no risk because almost all infant milk is artificially fortified&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Our results regarding types of feeding are in agreement with other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;18&#44;23&#44;24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Similar to our findings&#44; Zurynski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> observed in their study that skin and GIT&#44; followed by ICH&#44; were the most common sites of bleeding&#46; However&#44; Mihatsch et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> mentioned that ICH&#44; skin and GIT respectively were common sites in late VKDB&#46; A major feature of late VKDB is a much higher incidence of ICH &#40;30&#8211;88&#37;&#41; in patients&#44; with serious ICH leading to high morbidity and subsequent mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11&#44;12&#44;18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;25&#44;27&#8211;29</span></a> Our results are similar to those reported in other studies that observed that the most common site was intracerebral&#44; followed by multiple ICH&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;27&#44;28</span></a> However&#44; Ozdemir et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> demonstrated that subdural hemorrhage was the most common type of ICH reported&#44; followed by intracerebral and subarachnoid hemorrhages&#44; while Mart&#237;n-L&#243;pez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> mentioned that the majority of the patients &#40;75&#37;&#41; showed ICH at more than one site&#46; Late VKDB subtypes were associated with severe life-threatening bleeding&#44; mainly ICH&#44; which resulted in low hemoglobin level and anemia among our studied infants&#44; which is similar to the findings reported by others&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;21&#44;25&#44;26</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Throughout the follow-up period&#44; we observed that VKDB subtypes were associated with morbidity and lethality among studied patients&#44; and the outcome of patients did not have a statistically significant difference between the subtypes of VKDB&#46; In their study&#44; Sutor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> found that mortality was 19&#37; and neurological sequelae 21&#37; in survivor infants with VKDB&#46; Out of a total of 691 cases of late idiopathic VKDB reported in Thailand&#44; mortality rate was 24&#37;&#44; and permanent neurological deficits were found in 142&#47;257 &#40;55&#37;&#41;&#59; they were&#58; seizure disorders &#40;64&#37;&#41;&#59; muscle weakness &#40;21&#37;&#41;&#59; mental retardation &#40;15&#37;&#41;&#59; hemiparesis &#40;13&#37;&#41;&#59; hydrocephalus &#40;7&#37;&#41;&#59; and microcephaly 5&#37;&#59; however&#44; neurological sequelae in secondary late VKDB were found in 7&#47;25 &#40;28&#37;&#41; survivors&#44; and the mortality rate was 26&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> while in Aydinli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> seizure disorders &#40;73&#37;&#41;&#44; severe psychomotor retardation &#40;46&#37;&#41;&#44; cerebral palsy &#40;46&#37;&#41;&#44; microcephaly &#40;46&#37;&#41;&#44; and hydrocephalus &#40;27&#37;&#41; were observed after a follow-up period ranging from 6 to 48 months of infants with late VKDB&#44; but no fatality was mentioned&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion&#44; secondary late VKDB is more common than the primary subtype&#44; and late VKDB is still an important cause of morbidity and mortality in developing countries including Iraq&#44; where vitamin K prophylaxis is not routinely practiced&#46; The present study highlights the importance of prompt diagnosis of this clinical condition by proper history taking&#44; clinical examination&#44; and relevant investigations&#46; Vitamin K prophylaxis should be offered to all newborns who are exclusively breastfed&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The author declares no conflicts of interest&#46;</p></span></span>"
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            0 => "Vitamin K deficiency bleeding"
            1 => "Late VKDB"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">To study the presenting clinical and demographic features&#44; risk factors&#44; and outcome of infants with late vitamin K deficiency bleeding&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Over a 5-year study period&#44; the presenting clinical features and outcome of all 47 infants observed aged less than 6 months&#44; who were diagnosed with late-onset primary and secondary VKDB by detailed history&#44; physical examination&#44; and laboratory findings were evaluated&#46; Confirmed primary late VKDB was diagnosed when no cause other than breastfeeding could be found&#44; while in the secondary subtype additional risk factors compromising the vitamin K effect were diagnosed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Secondary late VKDB &#40;83&#37;&#44; 39 patients&#41; was more common than the primary subtype&#46; The mean age of patients was 10&#46;50&#8239;&#177;&#8239;5&#46;75 and 9&#46;74&#8239;&#177;&#8239;6&#46;04 weeks in primary and secondary VKDB subtypes&#44; respectively&#44; and the age of infants did not have a significant difference &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41;&#46; The male to female ratio was 2&#46;13&#58;1&#46; The residency&#44; place and mode of delivery&#44; gestational age&#44; and types of feeding of patients did not have a significant difference between VKDB subtypes&#46; The skin and gastrointestinal tract &#40;GIT&#41; &#40;40&#46;4&#37;&#41; followed by intracranial hemorrhage &#40;ICH&#41; &#40;32&#37;&#41;&#44; were common sites of bleeding&#46; Neurological complications were seen in 21&#37; of patients&#59; however&#44; lethality was 23&#37;&#44; and the outcome of patients did not have a significant difference &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; between VKDB subtypes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Secondary late VKDB is more common than the primary subtypes&#44; and late VKDB is still a serious disease in developing countries&#44; including Iraq&#44; when vitamin K prophylaxis isn&#8217;t routinely used at birth&#46;</p></span>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Delivery at hospital&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Delivery at home&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Mode of delivery&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;057&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Caesarian section&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NVD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Gestational age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Term &#40;&#62;37 weeks&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Preterm &#40;&#60;37 weeks&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Types of feeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Breastfeeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  """
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                  \t\t\t\t" scope="col">Sites of bleeding&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Skin and GIT&nbsp;\t\t\t\t\t\t\n
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                  """
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">VKDB&#44; vitamin K deficiency bleeding&#59; SD&#44; standard deviation&#59; Hb&#44; hemoglobin&#59; WBC&#44; white blood cell&#59; PT&#44; prothrombin time&#59; INR&#44; international normalized ratio&#59; APTT&#44; activated partial thromboplastin time&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
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