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PERINATAL
JOURNAL
www.perinataljournal.com PERIN A TAL JOURNAL
Volume 25 | Issue 3 | December 2017
P AL
E N
RINATAL JO U R
The Official Publication of
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The Official Publication of Perinatal Medicine Foundation,
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Volume 25 Issue 3 December 2017
Editor-in-Chief Advisory Board
Cihat fien, Abdallah Adra, Beirut, Lebanon Malcome Levene, Leeds, UK
Istanbul University, Arif Akflit, Eskiflehir, Turkey Narendra Malhotra, Agra, India
Saadet Arsan, Ankara, Turkey Alexandra Matias, Porto, Portugal
Istanbul, Turkey
Abdel-Latif Ashmaig, Khartoum, Sudan Israel Meizner, Tel Aviv, Israel
Ahmet Baschat, Baltimore, MD, USA Mohammed Momtaz, Cairo, Egypt
Editors
Christoph Berg, Bonn,Germany Giovanni Monni, Cagliari, Italy
Murat Yayla Julene Carvalho, London, UK Lütfü Öndero¤lu, Ankara, Turkey
Ac›badem International Rabih Chaoui, Berlin, Germany Soner R. Öner, Izmir, Turkey
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Hospital, Istanbul, Turkey
Filiz Çayan, Mersin, Turkey Halil Gürsoy Pala, ‹zmir, Turkey
Olufl Api Vincenzo D’Addario, Bari, Italy Alexander Papitashvilli, Tbilisi, Georgia
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‹brahim Polat, Istanbul, Turkey
Yeditepe University, Cansun Demir, Adana, Turkey
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Tony Duan, Shanghai, PRC
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Alaa Ebrashy, Cairo, Egypt
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Hakan Erenel, Istanbul, Turkey
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Volume25|Issue3|December2017 iii
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(cid:2)(cid:3)(cid:4)(cid:5)(cid:6)(cid:7)(cid:8)(cid:7)(cid:9)(cid:10)(cid:11)(cid:12)(cid:4)(cid:6)(cid:7)(cid:9) Volume 25, Iswsuwew 3.p, eDrineacteamljobuernr a2l.0co1m7
Original Article
Status of neutrophil-lymphocyte ratio and 25-hydroxyvitamin D in preeclampsia and preterm birth 91
Preeklampsi ve preterm do¤umda nötrofil-lenfosit oran› ve 25 hidroksi D vitamini durumu
Lebriz Hale Tamer, Yeliz Aykanat, Fulya Gökda¤l› Sa¤›r, Oktay Olmuflçelik, Suna Özdemir
The use of maternal delta neutrophil index for the prediction of chorioamnionitis in very early
preterm premature rupture of membranes 97
Çok erken preterm prematür membran rüptüründe koryoamniyoniti öngörmede maternal
delta nötrofil indeksinin yeri
Rauf Meleko¤lu, Sevil Eraslan, Ebru Çelik, Harika Gözde Gözükara Ba¤
Fetal prenasal thickness and its correlated ratios between 16 and 23 weeks of gestation 103
16–23 gebelik haftalar› aras›nda fetal prenazal kal›nl›k ve iliflkili oranlar›
Resul Ar›soy, Murat Yayla
Maternal and neonatal outcomes of the pregnant women with idiopathic
thrombocytopenic purpura 108
‹diyopatik trombositopenik purpural› gebelerin maternal ve neonatal sonuçlar›
Rauf Meleko¤lu, Sevil Eraslan, Ayfle Gülçin Bafltemur, Ebru Çelik, Harika Gözde Gözükara Ba¤
Nomograms of the fetal neck circumference and area 116
Fetal boyun çevresi ve fetal boyun alan› nomogram›
Muhittin Eftal Avc›, ‹brahim Polat
Gestational outcomes of thyroid function in the first trimester 121
Gestational outcomes of thyroid function in the first trimester
Osman Samet Günkaya, Hüseyin K›yak, Ali Ekiz, Ali Gedikbafl›
Use of obstetric gel in nulliparous pregnant women: Maternal and neonatal outcomes 127
Nullipar gebelerde obstetrik jel kullan›m›: Maternal-neonatal sonuçlar›
Burçhan Ayd›ner, Hüseyin K›yak, Fatih Mete, Ali Ekiz, ‹brahim Polat, Ali Gedikbafl›
Prevalence of asymptomatic bacteriuria among pregnant women:
a cross-sectional study in Harare, Zimbabwe 133
Gebelerde asemptomatik bakteriüri prevalans›: Harare, Zimbabve’de kesitsel çal›flma
Judith Musona-Rukweza, Muchabayiwa Francis Gidiri, Pasipanodya Nziramasanga,
Clara Haruzivishe, Babill Stray-Pedersen
Review
Influenza infection during pregnancy 139
Gebelikte influenza enfeksiyonu
Rauf Meleko¤lu, U¤ur Keskin, Ebru Tar›m, Cihat fien
Case Report
Complete hydatidiform mole in a twin complicated with preeclampsia: a case report 145
Preeklampsi ile komplike olmufl ikiz efli komplet mol hidatidiform: Olgu sunumu
Feyza Nur ‹ncesu Çintesun, Ersin Çintesun, Ayfle Yavuz
Fetal over kistleri olgu serisi 149
A case series on fetal ovarian cysts
Umut Sar›, Arzu Doruk, Ganime Elif Aydeniz, Savafl Gündo¤an, Talat Umut Kutlu Dilek
Index 153
Acknowledgement of Reviewers 156
iv Perinatal Journal
(cid:2)(cid:3)(cid:4)(cid:5)(cid:6)(cid:7)(cid:8)(cid:7)(cid:9)(cid:10)(cid:11)(cid:12)(cid:4)(cid:6)(cid:7)(cid:9) Original Article
(cid:2)(cid:3)(cid:4)(cid:5)(cid:6)(cid:7)(cid:8)(cid:7)(cid:9)(cid:10)(cid:11)(cid:12)(cid:4)(cid:6)(cid:7)(cid:9) Perinatal Journal2017;25(3):91–96
Status of neutrophil-lymphocyte ratio and
25-hydroxyvitamin D in preeclampsia and
preterm birth
Lebriz Hale Tamer1, Yeliz Aykanat1, Fulya Gökda¤l› Sa¤›r1, Oktay Olmuflçelik2,Suna Özdemir1
1Department of Obstetrics and Gynecology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey
2Department of Internal Medicine, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey
Abstract Özet:Preeklampsi ve preterm do¤umda
nötrofil-lenfosit oran› ve 25 hidroksi D vitamini
durumu
Objective:To examine the effect of low 25-hydroxyvitamin D (25- Amaç:Preeklampsi ve preterm do¤umda düflük 25 hidroksi D vita-
OH D) levels and the neutrophil-to-lymphocyte ratios (NLRs) on mini (25-OH D) seviyelerini ve nötrofil-lenfosit oranlar›n› (NLO)
preeclampsia and preterm birth. incelemektir.
Methods:A total of 180 pregnant women who gave birth at the Yöntem:‹stanbul Medipol Üniversitesi Kad›n Hastal›klar› ve Do-
Istanbul Medipol University Gynecology and Obstetrics Clinic ¤um Klini¤i’nde 2014 – 2017 y›llar› aras›nda do¤um yapan toplam
between 2014 and 2017 were enrolled in the study. The study 180 gebe çal›flmaya dahil edildi. Çal›flma grubu 61 preeklamptik
group consisted of 61 preeclamptic women (n=61) and 74 women gebeden (n=61) ve preterm do¤um yapan 74 kad›ndan (n=74),
(n=74) with preterm births, and the control group consisted of 45 kontrol grubu ise miad›nda do¤um yapan 45 kad›ndan (n=45) olu-
women (n=45) with term births. The demographic, obstetric and fluyordu. Üç grubun demografik, obstetrik ve laboratuvar sonuçla-
laboratory results of all three groups were compared according to r›, 25-OH D seviyeleri ve NLO bak›m›ndan karfl›laflt›r›ld›.
25-OH D levels and NLRs. Bulgular:VK‹, düflük say›s› ve sosyoekonomik durum yönünden
Results:There was no statistically significant difference among the üç grup aras›nda istatistiksel olarak anlaml› farkl›l›k yoktu
three groups in terms of BMI, abortus numbers and socioeconomic (p>0.05). Maternal yafl, gravida, parite, gebelik haftas›, do¤um
status (p>0.05). Maternal age, gravida, parity, gestational week, birth a¤›rl›¤› ve Apgar skorlar›, kontrol grubuna k›yasla preeklamptik ve
weight and Apgar scores were significantly lower in the preeclamp- preterm grupta anlaml› flekilde daha düflüktü (p<0.05). 25-OH D
tic and preterm groups compared to the control group (p<0.05). 25- seviyeleri, miad gebeliklere k›yasla preeklamptik ve preterm gebe-
OH D levels were found to be significantly lower in preeclamptic liklerde anlaml› flekilde daha düflükken (s›ras›yla 18.2±4.3 ng/ml;
and preterm pregnancies compared to term pregnancies (18.2±4.3 19.1±3.7 ng/ml; 34±5.1 ng/ml, p<0.05), NLO ise miad do¤um
ng/ml; 19.1±3.7 ng/ml; 34±5.1 ng/ml, p<0.05, respectively) while grubuna k›yasla preeklampsi ve preterm do¤um gruplar›nda an-
the NLR was significantly higher in the preeclampsia and preterm laml› flekilde daha yüksekti (s›ras›yla 3.96±1.23,3.98 ±1.34, 3.22±
birth group compared to the term birth group (3.96±1.23, 3.98 1.24, p<0.05).
±1.34, 3.22±1.24, p<0.05, respectively). Sonuç:Düflük 25-OH D seviyeleri ve artm›fl NLO’nun, spontane
Conclusion:Low levels of 25-OH D and increased NLR are likely preterm do¤um ve preeklampsi etiyolojisinde rol oynamas› muh-
to play a role in spontaneous preterm birth and preeclampsia etiolo- temeldir. Maternal D vitamini takviyesinin maternal, fetal ve ne-
gy. The impact of maternal vitamin D supplementation on the onatal sa¤l›¤›n geliflmesi üzerindeki etkisi belirsizdir, ancak potan-
improvement of maternal, fetal and neonatal health is not clear, but siyel olumlu etkiler üzerine daha kapsaml› araflt›rma gerekmekte-
more extensive research is needed on the potential positive effects. dir.
Keywords:Vitamin D, neutrophil-lymphocyte ratio, preeclamp- Anahtar sözcükler:D vitamini, nötrofil-lenfosit oran›, preeklamp-
sia, preterm birth. si, preterm do¤um.
Correspondence:Lebriz Hale Tamer, MD. Department of Obstetrics and Gynecology, Faculty Available online at:
of Medicine, Istanbul Medipol University, Istanbul, Turkey. e-mail: [email protected] www.perinataljournal.com/20170253001
doi:10.2399/prn.17.0253001
Received:July 18, 2017; Accepted:October 24, 2017
QR (Quick Response) Code:
Please cite this article as:Tamer LH, Aykanat Y, Gökda¤l› Sa¤›r F, Olmuflçelik O,
Özdemir S. Status of neutrophil-lymphocyte ratio and 25-hydroxyvitamin D in
preeclampsia and preterm birth. Perinatal Journal 2017;25(3):91–96.
©2017 Perinatal Medicine Foundation
Tamer LH et al.
Introduction metabolic changes. 25-OH D exerts angiogenic,
immunmodulator and anti-inflammatory roles for
Vitamin D plays an important role in calcium home-
implantation and placentation.[15,16] Some studies have
ostasis and bone metabolism.[1,2] Vitamin D status and
shown that high levels of 25-OH D are particularly
season are intrinsically linked; upon exposure to natu-
protective for preeclampsia.[17–22] In this context, it has
ral sunlight, endogenous skin production of vitamin D
been suggested that a severe deficiency of 25-OH D
occurs.[3,4] Serum 25-hydroxyvitamin D (25-OH D) is
below 10 ng/ml may increase the risk of preeclampsia
usually measured to assess vitamin D levels. 25-OH D
and eclampsia during pregnancy.[23] The ideal recom-
is the active form of 1.25-dihydroxyvitamin D and it
mendations for screening and supplementation are still
has a half-life of 4–6 hours, while the half-life of 25-
controversial. The aim of the study is to investigate
OH D has been determined to be about 2–3 weeks.[5–7]
relationship between 25-OH D levels and NLRs in
Recent studies have shown that 25-OH D is responsi-
preterm labor and preeclampsia.
ble for many important metabolic pathways in addition
to its well-defined role in bone-calcium metabolism. It
has already been shown to play an important role in Methods
apoptosis, antiproliferative pathways, immunosuppres-
A total of 180 pregnant women, who gave birth at the
sion and also exert anti-inflammatory effects on many
Istanbul Medipol University Gynecology and Obstetrics
different tissues such as the brain, reticulo-endotelial
Clinic between 2014 and 2017, were enrolled in the
system, urogenital system. Moreover, it has already
study. The study group consisted of 61 women (n=61)
been shown to impact the etiology of different systemic
with preeclampsia as group 1 and 74 women (n=74) with
inflammatory diseases, type 2 diabetes, depression and
preterm birth as group 2, and control group consisted of
autoimmune diseases.[8–11] The neutrophil-to-lympho-
45 women (n=45) with term birth as group 3. The
cyte ratio (NLR) has been defined as a useful marker
demographic, obstetric and laboratory results of all
for systemic inflammatory diseases. Even in the appro-
three groups were compared in terms of 25-OH D lev-
priate climate circumstances, 25-OH D deficiency is
els and NLRs.
still a challenging topic. Studies indicating the role of
The diagnosis of preeclampsia was made according
25-OH D deficiency during pregnancy and its relation
to the criteria of American Collage of Obstetricians and
with hypertensive diseases, diabetes, and preterm birth
Gynecologists (ACOG) guideline for hypertension in
are rapidly increasing. Hypertension during pregnancy
pregnancy. Preeclampsia was defined as the condition in
(prevalence: 5–10%) is responsible for serious morbid-
ity and mortality.[12] Hypertension in pregnancy can which arterial blood pressure levels were greater than or
equal to 140 mmHg systolic and/or 90 mmHg diastolic
present as gestational hypertension, preeclampsia and
eclampsia.[13] Endothelial dysfunction, oxidative stress on two occasions at least 4 hours apart and proteinuria
after the 20th week of pregnancy, greater than or equal
and inflammation play a critical role in increasing the
risk of hypertensive diseases during pregnancy.[14] Low to 300 mg/dl per 24-hour urine collection or dipstick
reading of 1+ or more. Preterm birth was defined as the
levels of 25-OH D in pregnancy can play a role in
delivery of a liveborn infant before 37 weeks of gestation.
maternal preeclampsia, diabetes, cholestasis, periodon-
Patients with history of metabolic disease, uterine anom-
tal disease, intrauterine growth retardation, premature
alies, multiple pregnancies, fetal anomalies, intrauterine
birth and cesarean birth. Maternal 25-OH D deficien-
growth retardation, pregestational and gestational dia-
cy is a well-defined risk factor for rickets in newborns
betes, membrane rupture, chorioamnionitis, fetal tachy-
and early childhood. It has also been suggested that 25-
cardia or fever with an unknown origin were excluded.
OH D leads to type 1 diabetes, asthma, allergy, multi-
ple sclerosis and schizophrenia later in life. In this The control group consisted of healthy pregnant
respect, vitamin D supplementation during pregnancy women who gave birth between gestational week 37 and
has become an important treatment strategy in order 42 without any medical condition or poor obstetric trait
to eliminate early and late-stage health problems. (diabetes, hypertension, obesity or small for gestational
Hypertensive diseases during pregnancy have been age history in previous births). Blood samples were col-
shown to boost the metabolism of creatinine and uric lected in the labor room. The clinical parameters includ-
acid levels and decrease the serum calcium due to ed age, body mass index, socio-economic status, gravida,
92 Perinatal Journal
Status of neutrophil-lymphocyte ratio and 25-hydroxyvitamin D in preeclampsia and preterm birth
Table1.Comparison of demographic and clinical data between groups.
Group 1 Group 2 Group 3 p
(n=61) (n=74) (n=45) value
Maternal age (years) 23.7±2.4† 22.5±2.1† 29.2±3.1 <0.001*
Gravida 2 (0–2)† 2 (0–2)† 3 (1–8) <0.001*
Parity 1 (0–3)† 1 (0–3)† 2 (0–6) <0.001*
Abortus 1 (0–3)† 1 (0–3)† 2 (0–6) <0.001*
The gestational weeks at delivery 0 (0–3) 0 (0–2) 0 (0–3) NS
BMI (kg/m2) 22.9±3.2 22.7±3.5 23.1±2.9 NS
Socio-economic status
Low 19% 18% 19% NS
Medium 63% 65% 64% NS
High 18% 17% 17% NS
Birth weight (g) 2445±280† 2100±370† 3320±310 <0.001*
Apgar score
1. minute 7.2±1.1† 7.0±1.2† 8.8±0.5 <0.001*
5. minute 8.2±0.7† 7.8±0.6† 9.7±0.2 <0.001*
Mean±SD, mean (min–max).BMI:body mass index; n:number (%); NS:no statistical significance.
*Statistical significance; †statistical significance was based on healthy pregnant group (p<0.05).
parity, gestational age, abortus neonatal weight and 1–5 the Mann-Whitney U test was performed for subgroup
minute Apgar scores. comparisons. The Pearson’s chi-square test was used for
categorical variables. The p-value <0.05 was considered
Laboratory analysis
to be significant. The one-way ANOVA (Robust test:
Venous blood samples were collected in the labor room. Brown-Forsythe) and Kruskal-Wallis H test post hoc
Serum 25-OH D was measured in the auto-analyzer analysis and the nonparametric post hoc tests (Miller,
(Cobas 6000; Roche, Tokyo, Japan) with the electro- 1966) were adopted for multiple group comparisons.
chemiluminescence immunoassay method (ECLIA). 30-
80 ng/ml was evaluated as optimal and 20 ng/ml deficient, Results
20–29 ng/ml insufficiency and <15 ng/ml was considered
The comparisons of socio-demographic and clinical
as toxic. The results were calculated as standard deviations.
data of the groups are presented in Table 1. There was
The hemogram values were analyzed on an automated
no statistically significant difference among the three
hematology device (XT2000i; Symex, Osaka, Japan).
groups in terms of BMI, abortus number and socioeco-
Statistical analysis: The data was analyzed using nomic status (p>0.05). Maternal age, gravida, parity,
Statistical Package Social Sciences (SPSS) Version 15.0 gestational week, birthweight and Apgar scores were
(SPSS Inc., Chicago, IL, USA). Descriptive statistics significantly lower in the preeclamptic and preterm
were expressed as standard deviations and averages for groups compared to the control group (p<0.05). A
numerical variables. The Kolmogorov-Smirnov test was comparison of the laboratory values of the groups is
used to analyze the regular distribution of variables and presented in Table 2. 25-OH D levels were signifi-
Table2.Comparison of laboratory data.
Group 1 Group 2 Group 3 p
(n=61) (n=74) (n=45) value
25-OH vitamin D (ng/ml) 18.2±4.3† 19.1±3.7† 34±5.1 0.001*
NLR 3.96±1.23† 3.98 ±1.34† 3.22±1.24 0.005*
*Statistical significance; †statistical significance was based on healthy pregnant group (p<0.05).
Volume25|Issue3|December2017 93
Tamer LH et al.
cantly lower in the preeclamptic and preterm group for this population that makes up a major part of preg-
compared to the control group (p<0.05) and NLRs nant women in Turkey.[25]We agree with the results of
were found to be higher in the preterm and preeclamp- this study which recommend a daily supplementation
sia group compared to the control group (p<0.05). of 1500 to 2000 IU during pregnancy and the postpar-
tum period. As suggested by Bodnar et al. which is
replicated in many studies of the literature, the diagno-
Discussion
sis and prevention of vitamin D deficiency at an early
25-OH D deficiency during pregnancy is critical both
stage can halt/decrease preterm birth rates. In our
for fetal and maternal outcomes. The prevalence of
study, we concluded that there is a significant differ-
preeclampsia, preterm birth and metabolic diseases such
ence between patients with low levels of 25-OH D and
as gestational diabetes has been shown to be increased in the control group in terms of preterm birth risk.[26]
pregnancies with severe 25-OH D deficiency, especially
Moreover, Schulz et al. conducted a study on the rela-
within the first trimester of the antepartum period.
tionship between 25-OH D deficiency and placenta-
Hollis et al. evaluated the effect of vitamin D supplemen-
tion. They revealed that vitamin D plays a critical role
tations which were applied in three different doses of
in the formation of vascular pathologies. A recent study
400, 2000 and 4000 IU to 350 pregnant women in their
suggests that sFlt-1 plays a significant role in the for-
first trimester. They have interestingly showed that
mation of preeclampsia, through its relationship with
there was no significant difference between 2000 and
VEGF expression. It has been proposed that vitamin D
4000 IU while there was a significant difference between
supplementation potentially decreases the levels of
a low dose and a high dose of supplementation in terms
antiangiogenic factors via the placental gene transcrip-
of pregnancy outcomes. Despite this promising clinical tion.[27]
data, there is some disagreement on the dosing regimens
Cakmak et al. has shown that epicardial fat thickness,
in pregnancies which is related to its well-known effects
pentraxin-3 and NLR may be useful inflammatory
in terms of deficiency.[24]
markers in terms of evaluating preeclampsia.[28]A retro-
In our study, we aimed to investigate the relationship
spective study compared first trimester levels of NLR
between preterm birth, preeclampsia and 25-OH D defi-
and platelet to lymphocyte ratios (PLR) in preeclamptic
ciency. We concluded that maternal 25-OH D serum
women and health controls. They suggested that high
levels decreased as an inflammatory and oxidative stress
NLR and PLR during the first trimester are independ-
marker in preeclamptic and preterm birth group. We ent predictors of subsequent preeclampsia.[29]In another
have found no significant difference in the demographic
retrospective study, Kim et al. evaluated 483 preterm
characteristics of the patients when compared to the
births. These preterm birth cases were divided into two
control group. When considering the outcomes of the
groups as women with and without placental inflamma-
preeclampsia group, our results are in line with many
tory response. The researchers concluded that NLR is a
studies showing that vitamin D levels are lower than the
cost-effective parameter in women with placental
control groups.
inflammatory response in terms of admission to delivery
In the light of recent controversial results regarding interval.[30] Jung et al. showed pre-operative increased
the relationship between vitamin D levels and preterm NLR and amniotic fluid IL-8 levels in preterm births
birth, we concluded that the levels of vitamin D in before 32 weeks after emergency cerclage and they sug-
preterm birth were decreased. Our results highlight gested that they may be important markers for predict-
the importance of vitamin D deficiency. In accordance ing emergency cerclage outcomes in women with cervi-
with this, a study carried out by Parlak et al. in Turkey cal insufficiency.[31] Kim et al. designed a combined
observed pregnant women who were vitamin D defi- marker by dividing cervical length by NLR and showed
cient and compared them in terms of poor socio-eco- that combined marker was more sensitive than C-reac-
nomic status, number of pregnancies and style of dress. tive protein (CRP), NLR and cervical length alone for
It was concluded that primiparous women with a con- predicting the risk of preterm labor.[32] Also, maternal
servative style of dress and poor economic status had an NLR was found to independently predict the risk of
increased risk of 25-OH D deficiency. The study high- NEC in very preterm infants, whereas clinical and his-
lighted the importance of vitamin D supplementation tological chorioamnionitis and funisitis are not predic-
94 Perinatal Journal