COMPARISON OF VITAMIN D LEVELS BETWEEN MOTHERS AND INFANTS WITH AND WITHOUT PROLONGED MEMBRANE RUPTURE Текст научной статьи по специальности «Клиническая медицина»

Оригинальные статьи

Original articles

Инфекция и иммунитет Russian Journal of Infection and Immunity = Infektsiya i immunitet

2022, Т. 12, № 3, с. 556-562 2022, vol. 12, no. 3, pp. 556-562

COMPARISON OF VITAMIN D LEVELS BETWEEN MOTHERS AND INFANTS WITH AND WITHOUT PROLONGED MEMBRANE RUPTURE

H. Boskabadia, F. Rakhshanizadeha, M. Zakerihamidib

a Mashhad University of Medical Sciences, Mashhad, Iran b Islamic Azad University, Tonekabon Branch, Tonekabon, Iran

Abstract. Background. Premature membrane rupture is a known causes of preterm labor and accounts for approximately one-third of cases. Vitamin D deficiency may play a role in preterm labor as well. Objective. The present study aimed to compare vitamin D levels in mothers and infants with and without prolonged rupture of membranes (PROM). Materials and methods. This cross-sectional study was conducted with 241 babies, with and without a history of membrane rupture, in mothers in the neonatal ward of Ghaem Hospital, Mashhad, from 2019 to 2021 with available sampling methods. After confirmation of prolonged membrane rupture (more than 18 hours before birth) based on history and examination with a speculum, we completed a data collection tool, a checklist including laboratory evaluation and neonatal and maternal characteristics. The conditions of neonates with and without prolonged membrane rupture were compared. Data were analyzed by T-test and Chi-square. Results. We examined a total of 241 neonates including 148 (61.4%) without prolonged rupture of the membranes in mothers and 93 (38.6%) with PROM. There were statistically significant differences between the two groups regarding: maternal vitamin D level (p = 0.001); neonatal vitamin D level (p = 0.001); and fifth minute Apgar score (p = 0.003). These variables were lower in the group of neonates with PROM. Conclusion. Vitamin D deficiency in mothers was significantly associated with prolonged membrane rupture. With increasing severity of vitamin D deficiency, the probability of PROM increases and, therefore, the likelihood of preterm labor and its complications rises.

Key words: fetal membranes, prolonged premature rupture of membranes, newborn, vitamin D, Apgar score.

СРАВНЕНИЕ УРОВНЕЙ ВИТАМИНА D У МАТЕРЕЙ И НОВОРОЖДЕННЫХ С ДЛИТЕЛЬНЫМ ПРЕЖДЕВРЕМЕННЫМ РАЗРЫВОМ ПЛОДНЫХ ОБОЛОЧЕК И БЕЗ НЕГО

Х. Боскабади1, Ф. Рахшанизаде2, М. Закерихамиди3

1 Мешхедский университет медицинских наук, г. Мешхед, Иран 2Исламский университет Азад, филиал Тонкабон, г. Тонкабон, Иран

Резюме. Актуальность. Преждевременный разрыв плодных оболочек является одной из причин преждевременных родов и сопровождает примерно одну треть всех родов. Дефицит витамина D также может играть роль в развитии преждевременных родов. Целью настоящего исследования было сравнение уровней витамина D у матерей и младенцев с длительным преждевременным разрывом плодных оболочек и без него. Материалы и методы. В настоящее исследование был включен 241 младенец, рожденный на фоне длительного преждевременного разрыва плодных оболочек (ПРПО) и без такового в неонатальном отделении больницы Гаем,

Адрес для переписки:

Закерихамиди Марьям

Исламский университет Азад, филиал в Тонкабоне, г. Тонкабон, Иран. Тел.: +98 0115 427-11-05. E-mail: maryamzakerihamidi@yahoo.co.nz

Для цитирования:

Боскабади Х., Рахшанизаде Ф., Закерихамиди М. Сравнение уровней витамина Э у матерей и новорожденных с длительным преждевременным разрывом плодных оболочек и без него // Инфекция и иммунитет. 2022. Т. 12, № 3. С. 556-562. Со1: 10.15789/ 2220-7619-С0У-1792

© ВовкаЬаС! Н., РаМвЬтп^аСеЬ! Р., 7акег1Иат1С1 М., 2022

Contacts:

Maryam Zakerihamidi

Islamic Azad University, Tonekabon Branch, Tonekabon, Iran.

Phone: +98 0115 427-11-05.

E-mail: maryamzakerihamidi@yahoo.co.nz

Citation:

Boskabadi H., Rakhshanlzadeh F., Zakerihamidi M. Comparison of vitamin D levels between mothers and infants with and without prolonged membrane rupture // Russian Journal of Infection and Immunity = Infektsiya i immunitet, 2022, vol. 12, no. 3, pp. 556-562. doi: 10.15789/2220-7619-COV-1792

DOI: http://dx.doi.org/10.15789/2220-7619-COV-1792

Мешхед, с 2019 по 2021 г. После подтверждения ПРПО (более 18 часов до рождения) на основании анамнеза и осмотра с помощью зеркал, было проведено лабораторное исследование и зафиксированы показатели новорожденного и матери. Сравнивали состояние новорожденных с длительным ПРПО и без такового. Статистическую обработку данных проводили, определяя критериев Стьюдента и Пирсона (хи-квадрат). Результаты. Обследован 241 новорожденный, в том числе 93 (38.6%) рожденных на фоне длительного ПРПО и 148 (61.4%) без ПРПО. Между двумя группами обнаружена статистически значимая разница в уровне витамина Б у матери (р = 0.001), в уровне витамина Б у новорожденного (р = 0.001) и в оценке по шкале Апгар на пятой минуте (р = 0.003). Это означает, что величины указанных переменных были ниже в группе новорожденных с ПРПО. Вывод. Длительный ПРПО в значительной степени коррелирует с дефицитом витамина Б у матерей, а с усилением тяжести дефицита витамина Б увеличивается вероятность ПРПО и, следовательно, повышается вероятность преждевременных родов и их осложнений.

Ключевые слова: плодные оболочки, пролонгированный преждевременный разрыв плодных оболочек, новорожденный, витамин D, матери, оценка по шкале Апгар.

Introduction

With a prevalence of 11% worldwide, preterm labor is one of the causes of death and long-term disability of infants and remains a major concern for public health [5]. The amniotic membrane protects the fetus against inflammation, bacteria, and viruses. Prolonged rupture of the membranes means rupture of the amniotic sac more than 18 hours before delivery [15], and it is a risk factor for early neonatal sepsis [2]. Its prevalence is reported to be 4—19% [43], and it is a predisposing factor for about one-third of preterm labors [24]. Maternal risk factors for premature rupture of membranes include age, parity, education, hypertension, cervical length with a history of miscarriage, history of upper urinary tract infection, sexually transmitted infections, positive vaginal culture, history of PROM, addiction, diabetes, placental abruption, preeclampsia, and cerclage. Labor complications of premature membrane rupture involve cesarean section, oligohydramnios, chorioamnionitis, placental abruption, fetal distress, fever at the time of delivery, placenta previa, infection, prenatal bleeding, sepsis in the mother, need for antibiotic therapy, placental retention, and post-partum endometriosis. Prematurity, respiratory distress syndrome, asphyxia, infection, meningitis, sepsis, pneumonia, perinatal mortality, patent arterial duct, necrotizing enterocolitis, intraventicular hemorrhage, and pulmonary hypoplasia are neonatal complications of PROM [11].

Low levels of maternal vitamin D during pregnancy are a risk factor for many adverse outcomes, including preterm labor [28]. The prevalence of vitamin D deficiency in pregnant women in the first and second trimesters is significantly higher than in the third trimester [17]. The fetus relies exclusively on the maternal concentration of 25 hydroxyvita-min D [31]. Vitamin D levels in pregnancy are associated with many maternal and fetal health outcomes. There have been numerous studies regarding an association between 25-hydroxyvitamin D levels in pregnancy and multiple pregnancy complications including gestational hypertension, preeclampsia,

gestational diabetes, time and type of delivery, pre-term labor, and fetal complications including skeletal, immune, and respiratory system problems [19, 25]. Vitamin D deficiency in premature neonates is associated with a number of problems (e.g. cerebral hemorrhage, retinopathy of prematurity, infection, and even death) [12]. Thus, correction of maternal vitamin D levels reduces the incidence of prematurity and these important neonatal problems. In the study of Shah B.A. et al., 25-hydroxyvitamin D levels were positively associated with fetal intrauterine growth restriction and prolonged rupture of membranes [36]. In general, prolonged membrane rupture is a serious complication in pregnancy, and it can increase mortality or perinatal morbidity, especially preterm labor and infection [10]. Due to the association between vitamin D deficiency and prematurity, one of the mechanisms of prematurity in vitamin D deficiency may be a membrane rupture. Therefore, in this study, we compared vitamin D levels in infants and mothers with and without a prolonged membrane rupture.

Materials and methods

This cross-sectional study was conducted in the maternity ward, midwifery ward, and NICU of Ghaem Hospital in Mashhad from 2019 to 2020. Prior to enrollment, verbal consent was obtained from the infant's parents. According to Zhang Q's study: the prevalence of placental inflammation in mothers with vitamin D deficiency is 63%; and in mothers without placental inflammation, it is 37%. Using a formula to compare two ratios related to a qualitative trait from two communities, along with alpha coefficient of 0.01 and beta of 0.2, the sample size in each group was estimated to be 87 mothers [14].

Mothers who gave birth to premature infants with more than 18 hours of ruptured amniotic sac were studied as a case group. Mothers without prolonged membrane rupture with preterm labor were included in the study as a control group. Confirmation of ruptured amniotic sac was based on history and speculum examination. We completed the data collection tool, a checklist including laboratory evaluation, and

neonatal and maternal characteristics. Preterm labor is a delivery before 37 weeks of gestation with or without membrane rupture [45]. Premature rupture of the amniotic sac means spontaneous rupture of the fetal membranes before 37 weeks of gestation and before the onset of uterine contractions [29]. Prolonged rupture of the membranes means rupture of the amniotic sac more than 18 hours before delivery [3].

Exclusion criteria included amniotomy, urinary tract infection, vaginal infection, or congenital anomalies. Serum vitamin D was measured from mothers and umbilical cords during delivery, and 1.5 cc of the prepared samples were centrifuged, with serum kept at —20°C and sent for laboratory evaluation. Vitamin D levels were measured using an ELISA method and the model RT2100c reader made in Germany and an ELISA washing device. We considered less than 30 mg/ml of vitamin D as deficient and above 30 mg/ml as sufficient. Vitamin D deficiency cases were divided into three groups: severe deficiency below 10 mg/ml; moderate deficiency 10—20 mg/ml; and mild deficiency 20—30 mg/ml.

Infants in the two groups were compared in terms of neonatal, maternal, and laboratory characteristics. Checklist status was completed based on neonatal information (gestational age, first minute Apgar score, fifth minute Apgar score), maternal information (maternal age, parity), and blood tests (maternal and neonatal vitamin D levels, C-reactive protein, erythrocyte sedimentation rate, white blood cell, nucleated red blood cell). All tests, except for the vitamin D test, were requested by the treating physician, and we recorded them without intervention.

After discharge, they were followed up using the Denver II test at 24 months. The Denver Developmental Screening Test II, to assess the growth and development of children from birth to six years old, is divided into four categories: personal/social; fine motor; gross motor; and language. If the infant had a problem in every category (i.e., fine motor skills, gross motor skills, language and personal/ social), it would be considered as developmental delay for them. If the infant had: a problem in only one category, it is considered a mild developmental delay; in two categories, a moderate developmental delay; and in three or more categories, a severe de-

Table 1. Mean of variables of mothers and

newborns included in the study

Variables Mean±Standard deviation

Mother age, years 30.52±6.73

Parity 2.01±1.23

Maternal vitamin D levels, mg/dl 20.66±13.03

Neonatal vitamin D levels, mg/dl 16.17±10.78

Gestational age, weeks 33.57±3.33

First minute Apgar score 7.16±2.15

Fifth minute Apgar score 8.58±1.63

velopmental delay. A favorable outcome was defined as normal neurologic and good general condition at the end of the study. Unfavorable outcome was defined as the presence of at least delay in one domain of Denver screening [13].

Statistical analysis. Data were analyzed using t-test, chi-square, and SPSS software version 20. First, we described the results using statistical tables and graphs. We then compared the two groups of infants, with or without prolonged rupture of membrane in mothers, using chi-square and t-test. Correlation methods were used to evaluate the association between the severity of vitamin D deficiency and PROM. The p < 0.05 level was considered significant in all cases.

Ethical consideration. This study was approved by the Ethics Committee of the Vice Chancellor for Research of Mashhad University of Medical Sciences (No. 991476, IR.MUMS.MEDICAL.REC. 1399.623).

Results

In this study, 9 infants were excluded (3 cases of amniotomy, 2 cases of urinary tract infection, 3 cases of vaginal infection, 1 case of congenital anomaly). Finally, we examined 241 neonates including 148 infants without prolonged rupture of membrane and 93 infants with PROM. Based on the results of this study, the mean gestational age was 33.57+ 3.33 weeks, and the mean maternal vitamin D level was 20.66+13.03 mg/dL. Other characteristics of the studied infants are given in Table 1.

In addition, 36 infants (14.9%) needed resuscitation; 28.6% were born naturally, and 71.4% by ce-sarean section. In this study, there were statistically significant differences: between maternal vitamin D levels (p = 0.001) and neonatal vitamin D levels (p = 0.001); in fifth minute Apgar score (p = 0.003); and in CRP (p = 0.032) (Table 2).

Calculations were performed based on standard deviation+mean (t-test).

Twenty percent of infants with PROM had an infection (16% sepsis, 4% meningitis), while 5% of neo-nates without a history of PROM had an infection. In this study, vitamin D deficiency was significantly associated with prolonged rupture of membranes (p = 0.0001), and with increasing severity of vitamin D deficiency, the rate of PROM increased. Mothers with normal vitamin D level had a 29% chance of PROM, which increased to 47% in moderate deficiency and 62% in severe deficiency. There was a moderate association between maternal serum vitamin D and the incidence of PROM (p = 0.0001, Spearman's rho = 0.286). Short-term neonatal follow-up showed that the serum level of vitamin D in PROM infants who died was 9.76+1.01 and 12.92+7.67 mg/ml in discharged live neonates (p = 0.003). Assessment of neonatal development from PROM mothers by Denver II

Table 2. Comparison of mean variables of mothers and neonates with or without prolonged rupture of membranes

' '——Groups Variables ——______ Neonates with PROM n = 93 (38.6%) Neonates without PROM n = 148 (61.4%) Significance level* (T-Test)

Maternal vitamin D levels, mg/ml 17.29±12.55 22.78±12.92 0.001

Neonatal vitamin D levels, mg/ml 13.09±8.68 18.21±11.56 0.001

Gestational age, weeks 32.88±2.82 33.67±3.40 0.351

First minute Apgar score 6.93±2.04 7.29±2.21 0.213

Fifth minute Apgar score 8.17±1.74 8.83±1.52 0.003

WBC, x 103 16.31±10.90 8.60±4.84 0.059

NRBC 2105.53±5205.55 1325.92±672.93 0.608

ESR 41.75±29.84 1.00±0.00 0.102

CRP 28.21±25.27 16.28±16.63 0.032

Note. The calculations were perfrmed based on standard devlatlon±mean.

test showed that 35% of neonates at 24 months of age showed some degree of developmental delay. In neo-nates from mothers without PROM, 12% showed developmental delay (p = 0.001). Serum vitamin D levels in children with developmental delay were 13±7. In the group with normal development, they were 17±11 mg/ml (p = 0.042).

Discussion

According to the results of our study, there was a significant relationship between vitamin D deficiency in mothers and infants and prolonged rupture of the membranes, with the likelihood of PROM rising as the severity of vitamin D deficiency increases. Also, for mothers with moderate-to-severe deficiency, the risk of PROM doubles. Studies on the role of vitamin D and the risk of preterm labor, and the possibility of membrane rupture, are contradictory. Numerous studies have shown an association between vitamin D deficiency and increased probability of preterm labor [41]. Rupture of the membranes is one of the possible causes of preterm labor due to vitamin D deficiency [20, 42, 45]. Maternal vitamin D deficiency increases the risk of preterm labor by approximately 9-fold [32]. Vitamin D deficiency during pregnancy and childbirth may play a role in premature rupture of membranes by a mechanism of placental inflammation [21]. Hence, Frazipour's study revealed that there was no significant association between serum vitamin D level and premature rupture of membranes [21]. The underlying mechanism of the potential protective effect of vitamin D on the risk of preterm labor may be due to the wide variety of immunoregulatory effects of vitamin D.

It seems that vitamin D may protect against pre-term labor by reducing infection and inflammation [16], but this has not been confirmed in other studies [33, 39, 40]. Vitamin D is a known modulator of the immune system [14]. It is also an effec-

tive stabilizer of amniotic membranes through non-genomic mechanisms [23]. It is involved in epigenetic changes through DNA methylation in genes that regulate extracellular matrix regeneration and is effective in maintaining the health of amniotic membranes [1]; the health of the amniotic membranes is dependent on the structure of vitamin D [27]. Low levels of vitamin D are associated with bacterial vaginosis [18]. Therefore, with increasing cases of bacterial vaginosis, premature rupture of the membranes occurs. To the best of our knowledge, there is no report in available sources on the relationship between the severity of vitamin D deficiency and the incidence of PROM. We report for the first time the relationship between vitamin D deficiency severity and the increase in the incidence of PROM.

According to the results of our study, PROM increased the risk of definitive neonatal infection more than four-fold. Inflammation and infection of the chorio decidua refers to the mechanism of premature rupture of the membranes. There is a strong association between premature rupture of membranes and inflammation and intrauterine infections, especially in preterm pregnancies [34]. Prolonged rupture of the amniotic sac for more than 18 hours increases the risk of neonatal infection ten-fold. Although the most common complication of prolonged rupture of the membranes is immaturity and its side effects, infection is the most important preventable complication [8]. Women with premature rupture of membranes are highly disposed to chorioamnionitis as a result of increased bacterial colonization of vagina before or after PROM [38]. Decreased collagen in embryonic membranes is a predisposing factor for premature rupture of membranes [9].

In the current study, CRP was significantly higher in PROM neonates. It was associated with high sensitivity, specificity and reliability. Increased CRP relates to the pathological confirmation of cho-rioamnionitis associated with fever [26]. CRP is the most common biomarker used for neonatal bacterial

sepsis. It is also known as a reliable serum marker for the presence or absence of invasive bacterial infection and antibiotic response in newborns [22]. Boonkasediesha showed that neonatal CRP with a cut-off point of 1.90 mg/ml has a very high sensitivity, specificity and positive predictive value [6]. In the Boskabadi study, 44% of infants with ruptured membranes had elevated CRP [10].

According to the results of our study, vitamin D deficiency in infants born to PROM mothers also increases the risk of death and developmental delay. The results of a study showed vitamin D deficiency was more pronounced in newborns who died. Vitamin D deficiency may increase the likelihood of death of these infants by increasing respiratory problems and infections [7].

In this study, Apgar scores of neonates with prolonged rupture of membranes were lower than new-borns without rupture of membranes. However, this difference was not significant in the first minute Apgar score. Preterm rupture of the membranes is one of the most common pregnancy complications that can affect Apgar score [4]. In one study, the duration of the rupture was effective in reducing the Apgar score and increased this risk by 8.5-fold [35]. As the interval between rupture of the membranes and delivery increases, the risk of infection in the mother and fetus rises [37]. In addition to the increased risk of intrauterine infection, other complications such as placenta abruption, pulmonary hypoplasia, hypoxia, and fetal distress due to umbilical cord compression

References

or prolapse increase [30]. A limitation of our study was a lack of placental examination of the infants under study.

Conclusion

Based on the results of this study, maternal and neonatal vitamin D levels and fifth minute Apgar scores were lower in neonates with prolonged rupture of membranes. With increasing severity of vitamin D deficiency, the probability of PROM was higher. Since vitamin D levels in mothers and neonates are correlated with prolonged rupture of membranes, it is recommended that mothers who are at risk for pre-term labor receive vitamin D supplementation during pregnancy. It may reduce the incidence of prolonged membrane rupture or prematurity, with consequent reductions in various associated complications.

Acknowledgements

This study is the result of a Mashhad University of Medical Sciences approved project. We therefore sincerely thank the Deputy Research of the University, the Research Director, other officials, and everyone who helped us with this project.

Conflict of interest statement

The Author(s) declare(s) that there is no conflict of interest.

1. Al-Garawi A., Carey V.J., Chhabra D., Mirzakhani H., Morrow J., Lasky-Su J., Qiu W., Laranjo N., Litonjua A.A., Weiss S.T. The role of vitamin D in the transcriptional program of human pregnancy. PLoS One, 2016, 11: e0163832. doi: 10.1371/journal. pone.0163832

2. Al-Lawama M., Alzaatreh A., Elrajabi R., Abdelhamid S., Badran E. Prolonged rupture of membranes, neonatal outcomes and management guidelines. J. Clin. Med. Res., 2019, vol. 11, pp. 360-366. doi: 10.14740/jocmr3809

3. Al-Qaqa K., Al-Awaysheh F. Neonatal outcome and prenatal antibiotic treatment in premature rupture of membranes. Pak. J. Med. Sci., 2005, vol. 21, no. 4, pp. 441-444.

4. Ansari F.N.A.S. Neonatal complications of premature rupture of membranes. Acta Medica Iranica, 2003, vol. 41, no. 3, pp. 175179.

5. Beck S., Wojdyla D., Say L., Betran A.P., Merialdi M., Requejo J.H., Rubens C., Menon R., Van Look P.F. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bulletin of the World Health Organization, 2010, vol. 88, no. 1, pp. 31-38.

6. Boonkasidecha S., Panburana J., Chansakulporn S., Benjasuwantep B., Kongsomboon K. An optimal cut-off point of serum C-reactive protein in prediction of neonatal sepsis. J. Med. Assoc. Thai, 2013, vol. 96, suppl. 1, pp. S65-S70.

7. Boskabadi H., Maamouri G., Hemmatipour A., Parvini Z., Ramazani A., Bagheri F. Comparison of serum vitamin D in the umbilical cord of survived with not survived premature infants. Iranian Journal of Pediatrics, 2019, vol. 29, iss. 3: e84798. doi: 10.5812/ ijp. 84798

8. Boskabadi H., Maamouri G., Mafinejad S. Neonatal complications related with prolonged rupture of membranes. Macedonian Journal of Medical Sciences, 2011, vol. 4, pp. 93-98. doi: 10.3889/MJMS.1857-5773.2011.0159

9. Boskabadi H., Saghafi N., Najafi A. Comparing the efficacy of cefotaxime and ampicillin on neonatal infection after premature rupture of membranes. The Iranian Journal ofObstetrics, Gynecology and Infertility, 2014, vol. 17:93. doi: 10.22038/IJ0GI.2014.2746

10. Boskabadi H., Zakeri Hamidi M., Maamouri G., Najafi A. Frequency of maternal risk factors and neonatal complications of premature rupture of membranes. Journal of Babol University of Medical Sciences, 2016, vol. 18, no. 10, pp. 32-39. doi: 10.22088/ jbums.18.10.32

11. Boskabadi H., Zakerihamidi M. Evaluation of maternal risk factors, delivery, and neonatal outcomes of premature rupture of membrane: a systematic review study. J. Pediatr. Rev., 2019, vol. 7, no. 2,pp. 77-88. doi: 10.32598/jpr.7.2.77

12. Boskabadi H., Zakerihamidi M., Faramarzi R. The vitamin D level in umbilical cord blood in premature infants with or without intra-ventricular hemorrhage: a cross-sectional study. Int. J. Reprod. Biomed., 2018, vol. 16, no. 7, pp. 429-434.

13. Boskabadi H., Zakerihamidi M., Sadeghian M.H., Avan A., Ghayour-Mobarhan M., Ferns G.A. Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J. Matern. Fetal Neonatal. Med., 2017, vol. 30, no. 21, pp. 2551-2556. doi: 10.1080/14767058.2016.1256988

14. Calton E.K., Keane K.N., Newsholme P., Soares M.J. The impact of vitamin D levels on inflammatory status: a systematic review of immune cell studies. PLoS One, 2015, vol. 10, no. 11: e0141770. doi: 10.1371/journal.pone.0141770

15. Canavan T.P., Simhan H.N., Caritis S. An evidence-based approach to the evaluation and treatment of premature rupture of membranes: Part I. Obstet. Gynecol. Surv., 2004, vol. 59, no. 9, pp. 669- 677. doi: 10.1097/01.ogx.0000137610.33201.a4

16. Chesney R.W. Vitamin D and The Magic Mountain: the anti-infectious role of the vitamin. J. Pediatr., 2010, vol. 156, no. 5, pp. 698-703. doi: 10.1016/j.jpeds.2010.02.002

17. Choi R., Kim S., Yoo H., Cho Y.Y., Kim S.W., Chung J.H., Oh S.Y., Lee S.Y. High prevalence of vitamin D deficiency in pregnant Korean women: the first trimester and the winter season as risk factors for vitamin D deficiency. Nutrients, 2015, vol. 7, no. 5, pp. 3427-3448. doi: 10.3390/nu7053427

18. Cooper N.A., Moores R.; East London Preterm Prevention Collaboration. A review of the literature regarding nutritional supplements and their effect on vaginal flora and preterm birth. Curr. Opin. Obstet. Gynecol., 2014, vol. 26, no. 6, pp. 487-492. doi: 10.1097/GCO. 0000000000000126

19. Curtis E.M., Moon R.J., Harvey N.C., Cooper C. Maternal vitamin D supplementation during pregnancy. Br. Med. Bull., 2018, vol. 126, no. 1, pp. 57-77. doi: 10.1093/bmb/ldy010

20. Davis L.M., Chang S.C., Mancini J., Nathanson M.S., Witter F.R., O'Brien K.O. Vitamin D insufficiency is prevalent among pregnant African American adolescents. J. Pediatr. Adolesc. Gynecol., 2010, vol. 23, no. 1, pp. 45-52. doi: 10.1016/j.jpag.2009.05.005

21. Farzipour S., Jalilvand F., Amani F., Kazemi M., Nikjou R., Shahbazzadegan S. Relationship of maternal vitamin D level with premature rupture of fetal membranes. The Iranian Journal of Obstetrics, Gynecology and Infertility, 2020, vol. 23, no. 1, pp. 33-39.

22. Fukuzumi N., Osawa K., Sato I., Iwatani S., Ishino R., Hayashi N., Iijima K., Saegusa J., Morioka I. Age-specific percen-tile-based reference curve of serum procalcitonin concentrations in Japanese preterm infants. Sci Rep., 2016, vol. 6: 23871. doi: 10.1038/srep23871

23. Gibson C.C., Davis C.T., Zhu W., Bowman-Kirigin J.A., Walker A.E., Tai Z., Thomas K.R., Donato A. J., Lesniewski L.A., Li D.Y. Dietary vitamin D and its metabolites non-genomically stabilize the endothelium. PLoS One, 2015, vol. 10, no. 10: e0140370. doi: 10.1371/journal.pone.0140370

24. Goldenberg R.L., Culhane J.F., Iams J.D., Romero R. Epidemiology and causes of preterm birth. Lancet, 2008, vol. 371, no. 9606, pp. 75-84. doi: 10.1016/S0140-6736(08)60074-4

25. Harvey N.C., Holroyd C., Ntani G., Javaid K., Cooper P., Moon R., Cole Z., Tinati T., Godfrey K., Dennison E., Bishop N.J., Baird J., Cooper C. Vitamin D supplementation in pregnancy: a systematic review. Health TechnolAssess, 2014, vol. 18, no. 45, pp. 1-190. doi: 10.3310/hta18450

26. Hawrylyshyn P., Bernstein P., Milligan J.E., Soldin S., Pollard A., Papsin F.R. Premature rupture of membranes: the role of C-reactive protein in the prediction of chorioamnionitis. Am. J. Obstet. Gynecol., 1983, vol. 147, no. 3, pp. 240-246. doi: 10.1016/0002-9378(83)91104-3

27. Hollis B.W., Wagner C.L. New insights into the vitamin D requirements during pregnancy. Bone Res., 2017, vol. 5: 17030. doi: 10.1038/boneres.2017.30

28. Kiely M.E., Zhang J.Y., Kinsella M., Khashan A.S., Kenny L.C. Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status. Am. J. Clin. Nutr, 2016, vol. 104, no. 2, pp. 354-361. doi: 10.3945/ajcn.116.130419

29. Kook S.Y., Park K.H., Jang J.A., Kim Y.M., Park H., Jeon S.J. Vitamin D-binding protein in cervicovaginal fluid as a noninvasive predictor of intra-amniotic infection and impending preterm delivery in women with preterm labor or preterm premature rupture of membranes. PLoS One, 2018, vol. 13, no. 6: e0198842. doi: 10.1371/journal.pone.0198842

30. Mandel D., Oron T., Mimouni G.S., Littner Y., Dollberg S., Mimouni F.B. The effect of prolonged rupture of membranes on circulating neonatal nucleated red blood cells. J. Perinatol. 2005, vol. 25, no. 11,pp. 690-693. doi: 10.1038/sj.jp.7211389

31. Olmos-Ortiz A., Avila E., Durand-Carbajal M., Diaz L. Regulation of calcitriol biosynthesis and activity: focus on gestational vitamin D deficiency and adverse pregnancy outcomes. Nutrients, 2015, vol. 7, no. 1, pp. 443-480. doi: 10.3390/nu7010443

32. Oluwole A.A., Okunade K.S., Okojie O.E. Maternal serum vitamin D levels and preterm delivery among low-risk parturients in Lagos, Nigeria. Int. J. Gynaecol. Obstet, 2019, vol. 144, no. 2, pp. 216-220. doi: 10.1002/ijgo.12719

33. Park S.H., Lee G.M., Moon J.E., Kim H.M. Severe vitamin D deficiency in preterm infants: maternal and neonatal clinical features. Korean J. Pediatr., 2015, vol. 58, no. 11, pp. 427-433. doi: 10.3345/kjp.2015.58.11.427

34. Romero R., Chaiworapongsa T., Espinoza J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J. Nutr., 2003, vol. 133, suppl. 2, pp. 1668S-1673S. doi: 10.1093/jn/133.5.1668S

35. Salan Y.D.C. Effect of length of premature rupture of membranes period toward apgar score of the infant and maternal leukocyte serum in Ulin General Hospital Banjarmasin. Berkala Kedokteran, 2017, vol. 13, no. 2, pp. 199-204. doi: 10.20527/jbk. v13i2.4076

36. Shah B.A., Padbury J.F., Anderson M.P., Holick M.F., Szyld E., Gordon C.M. Vitamin D and associated perinatal-neonatal outcomes among extremely low-birth-weight infants. J. Perinatol., 2018, vol. 38, no. 10, pp. 1318-1323. doi: 10.1038/s41372-018-0203-y

37. Silveira M.L., Caminha N.D.O., Sousa R.D., Pessoa S., Gurgel E., Cavalcante D. Neonatal outcome in pregnancies that presented premature rupture of membranes. Rev. Rene, 2014, vol. 15, no. 3,pp. 491-498. doi: 10.15253/2175-6783.2014000300014

38. Stock O., Gordon L., Kapoor J., Walker S.P., Whitehead C., Kaitu'u-Lino T.J., Pell G., Hannan N.J., Tong S. Chorioamnionitis occurring in women with preterm rupture of the fetal membranes is associated with a dynamic increase in mRNAs coding cy-tokines in the maternal circulation. Reprod. Sci, 2015, vol. 22, no. 7, pp. 852-859. doi: 10.1177/1933719114565034

39. Terek D., Ozcan G., Ergin F., Koroglu O.A., Yalaz M., Akisu M., Kultursay N. Vitamin D deficiency in premature infants and its effects on neonatal prognosis. J. Pediatr. Res., 2018, vol. 5, no. 1, pp. 37-40. doi: 10.4274/jpr.82788

40. Thorp J.M., Camargo C.A., McGee P.L., Harper M., Klebanoff M.A., Sorokin Y., Varner M.W., Wapner R.J., Caritis S.N., Iams J.D., Carpenter M.W., Peaceman A.M., Mercer B.M., Sciscione A., Rouse D.J., Ramin S.M., Anderson G.B.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women. BJOG, 2012, vol. 119, no. 13, pp. 1617-1623. doi: 10.1111/j.1471- 0528.2012.03495.x

41. Thota C., Menon R., Fortunato S.J., Brou L., Lee J.E., Al-Hendy A. 1,25-Dihydroxyvitamin D deficiency is associated with preterm birth in African American and Caucasian women. Reprod. Sci., 2014, vol. 21, no. 2, pp. 244-250. doi: 10.1177/1933719113493513

42. Yang L., Pan S., Zhou Y., Wang X., Qin A., Huang Y., Sun S. The correlation between serum vitamin D deficiency and preterm. Birth. Med Sci Monit., 2016, vol. 22, pp. 4401-4405. doi: 10.12659/msm.898117

43. Zeng L.N., Zhang L.L., Shi J., Gu L.L., Grogan W., Gargano M.M., Chen C. The primary microbial pathogens associated with premature rupture of the membranes in China: a systematic review. Taiwan J. Obstet. Gynecol., 2014, vol. 53, no. 4, pp. 443- 451. doi: 10.1016/j. tjog. 2014.02.003

44. Zhang Q., Chen H., Wang Y., Zhang C., Tang Z., Li H., Huang X., Ouyang F., Huang H., Liu Z. Severe vitamin D deficiency in the first trimester is associated with placental inflammation in high-risk singleton pregnancy. Clin. Nutr., 2019, vol. 38, no. 4, pp. 1921-1926. doi: 10.1016/j.clnu.2018.06.978

45. Zhou S.S., Tao Y.H., Huang K., Zhu B.B., Tao F.B. Vitamin D and risk of preterm birth: up-to-date meta-analysis of randomized controlled trials and observational studies. J. Obstet. Gynaecol. Res., 2017, vol. 43, no. 2, pp. 247-256. doi: 10.1111/jog.13239

Авторы:

Боскабади Х., профессор кафедры педиатрии, факультет медицины Мешхедского университета медицинских наук, г. Мешхед, Иран;

Рахшанизаде Ф., ассистент кафедры педиатрии, факультет медицины Мешхедского университета медицинских наук, г. Мешхед, Иран;

Закерихамиди М., кандидат наук (репродуктивное здоровье), доцент кафедры акушерства факультета медицинских наук Исламского университета Азад, филиал Тонкабон, г. Тонкабон, Иран.

Поступила в редакцию 01.09.2021 Отправлена на доработку 08.12.2021 Принята к печати 06.04.2022

Authors:

Boskabadi H., Professor, Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;

Rakhshanizadeh F., Assistant Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;

Zakerihamidi M., PhD (Reproductive Health), Assistant Professor of Reproductive Health, Department of Midwifery, Faculty of Medical Sciences, Islamic Azad University, Tonekabon Branch, Tonekabon, Iran.

Received 01.09.2021 Revision received 08.12.2021 Accepted 06.04.2022