Evaluation of Inferior and Superior Vena Cava and the Vena Cava Ratio in Growth Restricted Fetuses.

OBJECTIVE: To evaluate the changes in the diameters of superior vena cava (SVC) and inferior vena cava (IVC) and to measure the ratio between SVC and IVC in growth-restricted fetuses and compare these results with normally grown fetuses. METHODS: Twenty-three consecutive patients with fetal growth restriction (FGR) (Group I) and 23 pregnant gestational age-matched controls (Group II) between 24 and 37 weeks of gestation were enrolled in the study between January 2018 and October 2018. The diameter of the SVC and IVC from inner wall to inner wall was measured in all patients by sonographic examination. The ratio between the diameter of the SVC and IVC was also measured in each patient to eliminate the gestational age factor. We have named this ratio the "vena cava ratio" (VCR). All parameters were compared between the two groups. RESULTS: The diameter of the SVC was significantly greater in the fetuses with FGR (2.6-7.7 [5.4]) than in controls (3.2-5.6 [4.1]; P = .002; P < .01). The diameter of the IVC was significantly less in the fetuses with FGR (1.6-4.5 [3.2]) than in controls (2.7-5 [3.7]; P = .035; P < .05). The VCR was between 1.1 and 2.3 and the median value was 1.8 in Group I. The VCR was between 0.8 and 1.7 and the median value was 1.2. VCR was significantly higher in fetuses with FGR (P = .001 P < .01). CONCLUSION: This study shows that VCR is higher in fetuses with growth restriction. Further studies are needed to clarify the association between VCR and antenatal prognosis and postnatal results.

Relationship between second-trimester amniotic fluid and plasma levels of angiopoietin-2 and thrombomodulin with adverse pregnancy outcome.

Our objective is to investigate maternal midtrimester plasma and amniotic fluid (AF) levels of angiopoietin-2 (Ang-2) and thrombomodulin (TM), which are involved in vascular remodelling and endothelium activation, in placental disorders including foetal growth restriction (FGR) and preeclampsia (PE). This prospective multiparametric pilot study was conducted at the Perinatology Division of Trakya University in a population undergoing genetic amniocentesis. Both AF and plasma aliquots were kept in -80 °C until ELISA assay. The pregnancies were followed up until the end of gestation in terms of obstetric results. Amniotic fluid and plasma aliquots from 127 pregnancies who underwent genetic amniocentesis between 16 and 24 weeks of gestation were analysed. During the final data evaluation, 39 were excluded with various reasons. Twelve subsequently developed FGR and 11 complicated with PE. The control group (n = 65) was consisted of women delivered >37th week with an uncomplicated outcome. The midtrimester maternal Ang-2 levels in both AF and plasma and also TM levels in plasma were found to be significantly increased in pregnancies who subsequently developed FGR or PE (p< .05). The midtrimester Ang-2, which rises in both plasma and AF and the midtrimester TM, which only significantly increase in plasma compartment in PE group, as compensatory mechanism may be the precursors of placental disorders including FGR and PE.Impact StatementWhat is already known on this subject? It is known that angiopoietin-2 (Ang-2) has important role in placental angiogenesis and vascular remodelling. TM which is a receptor for Ang-2 plays a protective role in pregnancy by preventing the uteroplacental circulation from thrombosis.What do the results of this study add? The present study demonstrates that both midtrimester maternal plasma Ang-2/TM and amniotic fluid (AF) Ang-2 levels were significantly higher in PE and FGR group than uncomplicated group. Midtrimester AF TM levels were not significantly higher in PE group than the control group.What the implications are of these findings for clinical practice and/or further research? In the clinical practice, high levels of midtrimester Ang-2 and TM in plasma may be used for the prediction of FGR and PE. Although amniocentesis is not practical in the clinical use, the levels of these two markers in both AF and plasma compartments may contribute to explain the pathophysiology of FGR and PE.

Quadruplet Pregnancy with Complete Mole and Three Viable Fetuses.

Background: The coexistence of a hydatidiform mole and a fetus can occur in a multiple pregnancy, being less frequent in triplets and quadruplets because of their infrequency. With assisted reproduction, multiple pregnancies are becoming more frequent, and we can expect more frequent coexistence with a molar pregnancy. Case report: This G3, P1 30-year-old mother, after assisted conception, was diagnosed with a quadruplet pregnancy, one of which was a molar conceptus. Due to the potential for malignancy, the pregnancy was electively terminated. Conclusion: Despite the difficulty in conceiving, elective termination of a multiple pregnancy associated with a molar pregnancy may be the most judicious course of action to protect the mother's life.

Prenatal diagnosis of 20p13 microdeletion syndrome.

OBJECTIVE: The objective of this study was to report the first case of prenatal diagnosis of the fetal 20p13 microdeletion syndrome in the literature. CASE REPORT: The mother was 31 years old and had a first trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 23 weeks of gestation showed mild ventriculomegaly (10.2 mm) and absent septum pellucidum. She underwent amniocentesis because of the abnormal imaging results. Karyotype analysis revealed normal results. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the fetus and parents. CMA detected 317.902 kb deletion of 20p13 in fetus. Finally, pregnancy was terminated at 32 weeks of gestation. CONCLUSION: This study is the first to report the prenatal diagnosis of a 20p13 microdeletion syndrome. Our results further confirmed that genes in this region, including SOX12, NRSN2 are essential for normal fetal growth and TBC1D20 for normal brain development.

Fetal cloacal dysgenesis sequence presented with first trimester megacystis and associated umbilical cord abnormalities.

Cloacal dysgenesis sequence occurs as a result of complete developmental failure of the urorectal septum. Typically, the sequence is featured by a smooth perineum, without any urethral, genital or anal openings. Its clinical manifestation differs throughout gestation. We report an interesting case of first trimester megacystis with associated umbilical cord abnormalities in a female fetus having cloacal dysgenesis sequence. This rare association reflecting high urinary pressure should first suggest urethral atresia. Our case highlights the importance of routine inspection of umbilical cord in the workup of early megacystis in terms of both etiology and fetal diagnosis.

Comparison of the efficacy of the immediate-release and osmotic push-pull system formulations of nifedipine for tocolysis.

AIM: To compare the immediate-release (IR) and osmotic push-pull system formulations of nifedipine used for tocolysis in prolonging pregnancy, neonatal outcomes and maternal-fetal adverse effects. METHODS: We evaluated 140 pregnant women who received the IR (n = 72) and osmotic push-pull system (n = 68) formulations of nifedipine for tocolysis due to threatened preterm labor between 240/7 and 336/7 weeks of gestation. Groups were compared in terms of efficacy of tocolysis in prolonging pregnancy for more than 48 h, 7 days and up to 37 weeks of gestation, total number of days gained for prolonging pregnancy, delivery weeks, maternal-fetal adverse effects and neonatal outcomes including ventilation support, need for intubation or surfactant, intraventricular hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, admission to neonatal intensive care unit, neonatal death, Apgar scores at the 1st and 5th minutes. RESULTS: There was no significant difference between the two groups in prolonging pregnancy for more than 48 h or 7 days, total number of days gained after tocolysis initiation, delivery weeks, the number of births at 340/7 -366/7 weeks or after 37 weeks of gestation (P > 0.05). Maternal-fetal adverse effects and neonatal outcomes were similar in both groups (P > 0.05). CONCLUSION: The efficacy of IR and osmotic push-pull system formulations of nifedipine have similar effects in terms of tocolysis and neonatal outcomes, adverse effects. Osmotic push-pull system formulation of nifedipine may be an alternative medication in tocolytic therapy due to its ease of use and the absence of loading dose necessity.

Placental and serum levels of human Klotho in severe preeclampsia: A potential sensitive biomarker.

INTRODUCTION: The Klotho (KL) gene, initially defined as an anti-aging gene in mice, shares 86% of the amino acid sequence withthe human KL protein. The KL gene plays roles in endothelial nitric oxide production, angiogenesis, antioxidant enzyme production and protecting against endothelial dysfunction, all of which may be associated with preeclampsia (PE). Human KL is the precursor of the gene products: α-KL and ß-KL. In this study, we evaluated the gene expression, serum and placental levels of human KL in women with severe PE, pregnant women with chronic hypertension and healthy pregnant controls. Also, the gene expression, serum and placental levels of human decorin (DCN) were evaluated. METHODS: A total of 36 patients with severe PE, 10 with chronic hypertension, and 28 with healthy controls were enrolled. Placental and serum levels together with of KL and DCN were measured by ELISA and alsogene expression of these were evaluated. RESULTS: Placental and serum KL levels were significantly higher in the PE than in the controls and in women with chronic hypertension. Serum DCN levels were significantly higher in the PE women compared to controls and pregnant women with chronic hypertension. Placental DCN was similar in PE and healthy controls. There was no significant difference in the gene expression of KL and DCN in the groups. The best cut-off level for human KL to identify the presence of PE was calculated as 12.48 pg/ml with a sensitivity of 100% and and specificity of 96%, whereas for DCN 62.33 ng/ml to assess the presence of PE with a sensitivity of 86.1% and a specificity of 88%. CONCLUSION: Human KL may be a valuable marker for PE, with high sensitivity and specificity. It also appears to be more sensitive and specific than human DCN.

Schizencephaly accompanied by occipital encephalocele and deletion of chromosome 22q13.32: a case report.

Background: Schizencephaly is a neuronal migration anomaly characterized by presence of a cleft between ependymal layer of the ventricle and pia mater of the cerebral cortex. It may be associated with additional cerebral abnormalities, including polymicrogyria, pachygyria, gray matter heterotopy, ventriculomegaly and corpus callosum agenesis. Case Report: We present a female fetus with schizencephaly accompanied by occipital encephalocele, polymicrogyria, agenesis of the corpus callosum, dysmorphic facies and cardiac muscular ventricular septal defect. Array comparative genomic hybridization (array-cGH) analysis revealed a deletion of chromosome 22q13.32 including FAM19A5 gene that is a member of TAFA family. Conclusions: Schizencephaly may be accompanied by unexpected structural and genetic anomalies as in our case with occipital encephalocele, dysmorphic facies, cardiac ventricular septal defect and chromosome 22q13.32 deletion.

Can myometrial thickness/cervical length ratio predict preterm delivery in singleton pregnancies with threatened preterm labor? A prospective study.

OBJECTIVE: To investigate whether myometrial thickness (MT) to cervical length (CL) ratio could be used in the prediction of preterm birth (PTB) in singleton pregnancies presented with threatened preterm labor (TPL). METHODS: After 48 h of successful tocolysis, MT was measured transabdominally from the fundal, mid-anterior walls and the lower uterine segment (LUS) in 46 pregnancies presented with TPL. MT measurements were divided into CL, individually. The main outcome was PTB before 37 weeks of gestation. RESULTS: The patients were divided into two groups as women delivered ≥ 37 weeks (38.68 ± 1.01 weeks) (n = 25) and those delivered < 37 weeks (34.28 ± 2.53 weeks) (n = 21). The mean ± SD CL in the preterm delivery group was significantly shorter than the term delivery group (23.77 ± 9.23 vs 29.91 ± 7.03 mm, p < 0.05). Fundal, mid-anterior or LUS MT values were similar in both groups. However, in those who delivered preterm, the ratios of fundal MT-to-CL (p = 0.026) and mid-anterior MT-to-CL (p = 0.0085) were significantly different compared to those delivered at term. The optimal cutoff values for CL, fundal MT-to-CL and mid-anterior MT-to-CL ratios in predicting PTB were calculated as 31.1 mm, 0.19 and 0.20, respectively. Fundal MT-to-CL ratio predicted preterm delivery with 71% sensitivity, 72% specificity, 68% positive and 75% negative predictive values. For mid-anterior MT-to-CL ratio, respective values were 76, 76, 73 and 79%. CONCLUSION: Measurement of MT along with CL may offer a promising method in the management of women presented with TPL.

Does emergency cerclage really works in patients with advanced cervical dilatation?

OBJECTIVE: To asses the efectivity of emergency cerclage in the patients with advance cervical dilatation and prolapsed membranes. MATERIAL METHODS: The patients who have ≥4 cm cervical dilatation with protruding membranes were included in the study. The patients were divided into two groups. Group I was consisted of the patients who had emergency cerclage procedure and group II was consisted of the patients who denied the operation and expectantly managed. The physical examination, pregnancy outcomes and the complications were compared between the groups. The results of the patients with emergency cerclage were analysed. RESULTS: 21 patients were referred with a ≥4 cm cervical dilatation with protruding membranes 33.3% of women with emergency cerclage were delivered within one week from the admission. One patient, who was a grand multiparous (G6P4A1), was delivered a healthy infant at 40 weeks of gestation. The remaining five patients were delivered between 21 and 24 weeks, but all the infants were died due to extreme prematurity.Two patients (22.2%) developed chorioamnionitis that necessitated long hospitalization (14-21 days). In group II (expectant management) 83,3% of the patients were delivered within the 48 h from the admission. There were no case of chorioamnionitis in group II. CONCLUSION: Emergency cervical cerclage is not a rationale option for the patients with an advanced cervical dilation (>4 cm) together with protruding membranes in early second trimester because of the short prolongation time and high complication rate.

Unusual facio-upper arm band of a fetus mimicking amniotic band syndrome.

Amniotic band syndrome can lead to a wide spectrum of congenital abnormalities including orofacial and visceral defects. It is associated with malformations in truncal, craniofacial regions and the limbs, whereas it sometimes may imitate some genetic disorders. Here, we present an atypical case mimicking amniotic band syndrome with a facio-upper arm band that was having multiple fetal structural abnormalities including scoliosis, bilateral cleft lip and palate, upper limb abnormality, unilateral anophthalmia with contralateral microphthalmia, left hypertrophic kidney and severe ventriculomegaly.

Prenatal diagnosis of chromosomal polymorphisms: most commonly observed polymorphism on Chromosome 9 have associations with low PAPP-A values.

INTRODUCTION: To identify the prevalence and types of fetal chromosomal polymorphisms in pregnant women and to examine possible associations with screening test parameters. MATERIALS AND METHODS: Fetal chromosomal polymorphism rate was investigated in pregnant women who had been implemented for invasive prenatal test in a tertiary reference center in Thrace Region of Turkey. Fetal chromosomal polymorphisms were determined and their effects on screening tests' parameters were investigated. Possible differences in the first and second-trimester screening test parameters between women; with fetal chromosomal polymorphism who had screening test results (Group 1) and those with a normal karyotype (Group 2) were evaluated. RESULTS: Fetal chromosomal polymorphism prevalence was 5.3% (n = 101). The most common polymorphisms were identified on chromosome 9, 1, and 16 [54.5% (n = 55); 8.9% (n = 9), and 6.9% (n = 7), respectively]. The most common polymorphic variant was 9qh+ (n = 23; 22.8%). Among the screening test parameters, significantly lower pregnancy-associated plasma protein-A (PAPP-A) (p = .028) and higher unconjugated estriol (uE3) (p = .019) values were found in Group 1. In patients having fetuses with polymorphic variants on chromosome 9, a significantly lower PAPP-A values were observed compared to women with other fetal polymorphic variants (p = .048) or women having fetuses with normal karyotype (p = .007). CONCLUSIONS: Lower PAPP-A and higher uE3 levels were observed in women having fetuses with chromosomal polymorphisms, which might affect screening test results. Lower PAPP-A levels were apparent in women having fetuses with polymorphism on chromosome 9.

The relation of fetal colon and rectum diameters with labor in healthy late-third trimester pregnancies.

OBJECTIVE: To investigate the associations of fetal colon-rectum diameters with labor and fetal distress or meconium passage in healthy pregnancies in the late 3rd trimester. STUDY DESIGN: A total of 162 healthy, singleton pregnant women at ≥360/7 weeks who were in the latent-phase of labor (n = 69) or those not in labor (n = 93, controls) at the time of ultrasound examination were enrolled. Fetal colon (ascending, transverse, descending, sigmoid) and rectum diameters, Doppler indices of materno-fetal vessels were measured. Data were analyzed according to the mode of delivery. RESULTS: Fetal colon-rectum diameters were smaller in women in labor compared to controls (p = 0.001). Positive correlations were observed between fetal colon-rectum diameters and interval between ultrasound and labor onset in the control group except for those who had scheduled cesarean sections (C/S) (p = 0.001). Similar colon-rectum measurements were obtained in fetuses delivered via cesarean section due to fetal distress or to other indications (p > 0.05). In women who had uterine contractions during ultrasound examination; later delivered by vaginal route, no association was observed between Apgar scores and colon-rectum diameters during latent-phase (p > 0.05), and also there were significant positive correlations between different segments of colon-rectum diameters and duration of neonatal meconium passage (p < 0.05). CONCLUSION: Fetal colon and rectum diameters are smaller during labor and the measurements tend to diminish as the labor approaches, but do not indicate fetal distress.

Emergency cerclage in twins during mid gestation may have favorable outcomes: Results of a retrospective cohort.

PURPOSE: Cervical cerclage treatment for cervical changes at mid trimester is a very controversial topic in twins. The aim of the study was to present our maternal and fetal outcomes of mid-trimester cervical cerclage in twin pregnancies. BASIC PROCEDURES: This study was performed using data extracted from the medical files of the twin pregnancies whom performed emergency cervical cerclage between January 2012 and March 2018 at Trakya University, Facuty of Medicine, Department of Perinatology. MAIN FINDINGS: Mean (min.-max.) gestational age at delivery was [27.3 (21-34) weeks]. The median time between cervical cerclage and delivery was 6.4 weeks, while the maximum prolongation of the pregnancy was 11 weeks. The median prolongation period of pregnancy was 4.1 weeks in patients with bulging membranes, but 10 weeks in patients with cervical effacement and cervical shortening. Eight infants died at the neonatal period. Two patients (20%) developed late abortions at 21 and 22 weeks of gestation, and 2 women (20%) delivered extremely premature neonates at the 24th weeks. Overall neonatal mortality rate was 40% (8/20 neonates). Twelve out of twenty were born alive (60%). PRINCIPAL CONCLUSIONS: Despite the lack of randomized controlled trials, it seems reasonable to offer emergency cervical cerclage to twin pregnancies with cervical shortening (<15mm). For the twin pregnancies with advanced cervical dilatation and protruding membranes, emergency cervical cerclage should be an option only for carefully selected patients after informing about the complications and low success rate.

A large posterior encephalocele associated with severe ventriculomegaly, cerebellar atrophy and transposition of the great arteries.

Posterior encephalocele is a neural tube defect, which is a sac-like protrusion of the neural tissue and cerebrospinal fluid through a defect in the occipital bone. This embryonic anomaly may coexist with cortical dysplasia, agenesis of the corpus callosum, hydrocephalus, microcephaly, craniofacial abnormalities, ventricular and atrial septal defect. We report a case of a large posterior encephalocele in a fetus accompanied by unexpected major abnormalities including transposition of the great arteries, severe ventriculomegaly and cerebellar atrophy. Postnatal surgical corrections of the posterior encephalocele and then of the transposition of the great arteries were performed but the neonate died 2 months after delivery.

Effects of betamethasone on fetoplacental and maternal hemodynamics in preterm pregnancies.

OBJECTIVE: To evaluate the possible effects of prenatal steroid administration on Doppler parameters of the umbilical artery, uterine artery, middle cerebral artery, and ductus venosus, the cerebroplacental ratio, and the amniotic fluid index in preterm fetuses. METHODS: The present prospective observational study was performed at the Perinatology Department of Trakya University, Edirne, Turkey, between June 1, 2015, and September 1, 2016. It included patients with healthy singleton pregnancies who had received betamethasone at 24-34 weeks of pregnancy. Doppler parameters were measured before (0 hours) and 24, 48, and 72 hours after the administration of betamethasone (two intramuscular doses of 12 mg each, administered 24 hours apart). RESULTS: There were 68 patients included. Pairwise comparisons demonstrated that, at 72 hours after betamethasone administration, the umbilical artery resistance index (P=0.038), the middle cerebral artery systolic/diastolic velocity ratio (P=0.007), and the amniotic fluid index (P=0.017) were reduced, whereas the end-diastolic velocity of the middle cerebral artery was increased (P=0.012), compared with baseline values. CONCLUSION: Betamethasone had favorable effects on fetal cerebral circulation, with increased end-diastolic velocity in the middle cerebral artery; this could represent a positive effect on cerebral blood circulation and decreased flow resistance in the umbilical artery.

Relationship between second-trimester amniotic fluid levels of Prokineticin-1 and Matrix Metalloproteinase-2 with adverse pregnancy outcome.

To investigate the levels of Prokineticin-1 (PROK1) and matrix metalloproteinase-2 (MMP-2) in second-trimester amniotic fluid (AF). AF samples were investigated in 81 patients. AF-PROK1 and AF-MMP-2 were not significantly associated with adverse pregnancy outcomes (preeclampsia, intrauterine growth retardation, spontaneous preterm birth, gestational diabetes, gestational hypertension). AF-PROK1 levels in patients with abnormal first-trimester screening were significantly higher than those who underwent amniocentesis due to abnormal second-trimester screening tests (p = .04). AF-PROK1 or AF-MMP-2 do not have a role in the prediction of adverse pregnancy outcomes.

Comparison of postpartum sonographic findings after uneventful vaginal and cesarean section deliveries.

Objective: To prospectively determine the sonographic findings of the postpartum uterus 24 hours after vaginal delivery and cesarean section. Methods: Women who had uneventful vaginal delivery or cesarean section from July 2015 to May 2018 in a tertiary care hospital were prospectively included. Uterine lengths, endometrium, amout of free fluid, the distance between the uterine fundus-promontorium and uterine fundus-L5 were evaluated 24 hours after delivery. Results: The mean (min-max) endometrial thickness in the vaginal delivery and cesarean section groups were 13.3 (4-25) and 12.4 (4-29) mm, respectively. Fundus-cervix length was significantly higher in the vaginal delivery group compared to the cesarean section group (184.05 ± 16.8 vs 163.6 ± 6.7 mm, p <0.001). The measurements of anterior and anterior-posterior walls of the uterus, anteroposterior uterine length and uterine width were similar in both groups. Promontorium-fundus length was significantly higher in patients who delivered vaginally than those by cesarean section (123.3 ± 13.6 vs 108.7 ± 23.3 mm, p = 0.005). Conclusion: The measurement of L5-fundus distance is a simple and effective technique to evaluate the size of the uterus. Homogenous endometrium up to 30 mm in asymptomatic patients may be a normal finding 24 hours after delivery. The results of this study may be helpful in the decision-making process in cases of early postpartum hemorrhage or hemodynamic instability.Objective: To prospectively determine the sonographic findings of the postpartum uterus 24 hours after vaginal delivery and cesarean section. Methods: Women who had uneventful vaginal delivery or cesarean section from July 2015 to May 2018 in a tertiary care hospital were prospectively included. Uterine lengths, endometrium, amout of free fluid, the distance between the uterine fundus-promontorium and uterine fundus-L5 were evaluated 24 hours after delivery. Results: The mean (min­max) endometrial thickness in the vaginal delivery and cesarean section groups were 13.3 (4­25) and 12.4 (4­29) mm, respectively. Fundus-cervix length was significantly higher in the vaginal delivery group compared to the cesarean section group (184.05 ± 16.8 vs 163.6 ± 6.7 mm, p <0.001). The measurements of anterior and anterior-posterior walls of the uterus, anteroposterior uterine length and uterine width were similar in both groups. Promontorium-fundus length was significantly higher in patients who delivered vaginally than those by cesarean section (123.3 ± 13.6 vs 108.7 ± 23.3 mm, p = 0.005). Conclusion: The measurement of L5-fundus distance is a simple and effective technique to evaluate the size of the uterus. Homogenous endometrium up to 30 mm in asymptomatic patients may be a normal finding 24 hours after delivery. The results of this study may be helpful in the decision-making process in cases of early postpartum hemorrhage or hemodynamic instability.

Use of prokineticin-1 (PROK1), pregnancy-associated plasma protein A (PAPP-A) and PROK1/PAPP-A ratio to predict adverse pregnancy outcomes in the first trimester: a prospective study.

INTRODUCTION: To compare the predictive effectiveness levels of prokineticin-1 (PROK1), pregnancy-associated plasma protein A (PAPP-A) and the PROK1/PAPP-A ratio in the first trimester for preeclampsia (PE), foetal growth restriction (FGR), gestational diabetes mellitus (GDM) and spontaneous preterm birth (SPB). MATERIALS AND METHODS: A total of randomly selected 162 pregnant women were included. Peripheral blood samples were obtained between 110/7 and 136/7 gestational weeks (GWs). All women were followed throughout the pregnancy and classified into five groups as having PE, FGR, GDM, SPB and uncomplicated pregnancies. The cut-off levels of the markers were identified to predict adverse outcomes. RESULTS: PROK1 predicted PE with 83.3% sensitivity, 85.7% specificity at a value of >293.4 pg/mL; at a value of >260.2 pg/mL, PROK1 predicted FGR with 85.7% sensitivity, 72.5% specificity in the first trimester. The area under receiver operating characteristic (ROC) curve of PAPP-A was lower than that of PROK1 and PROK1/PAPP-A in differentiating PE and FGR from the uncomplicated group (p < .001). PROK1 levels and the PROK1/PAPP-A ratios in the SPB and GDM groups were lower than in the uncomplicated group (p < .01). CONCLUSIONS: Elevated PROK1 in the first trimester is a more effective marker than PAPP-A in the prediction of PE and FGR. Lower PROK1 levels are associated with the development of SPB and GDM.