Clinical significance of soft markers in second trimester ultrasonography for pregnant Korean women: a multicenter study and literature review

Objective@#To evaluate the clinical significance of soft markers for aneuploidy screening in Korean women. @*Methods@#We retrospectively reviewed the medical records of 5,428 singleton pregnant women who underwent sonography during the second trimester at seven institutions in South Korea. We evaluated the prevalence of the following soft markers: intracardiac echogenic focus, choroid plexus cysts, pyelectasis, echogenic bowel, and mild ventriculomegaly. We developed best-fitted regression equations for the fetal femur and humerus length using our data and defined a short femur and humerus as both long bones below the fifth centile. The results of genetic testing and postnatal outcomes were investigated in patients who had been diagnosed with aforementioned soft markers. @*Results@#The median maternal age of our study population was 33 years, and the median gestational age at the time of ultrasonographic examination was 21 weeks. We detected soft markers in 10.0% (n=540) of fetuses: 9.3% (n=504) were isolated cases and 0.7% (n=36) of cases had two or more markers. We identified only two aneuploides (trisomy 18, 46,XX,t[8;10][q22.1;p13]), of which one was clinically significant. We presented the neonatal outcomes of the fetuses with the respective soft markers. Preterm delivery, low birth weight, and small-for-gestational-age (SGA) were significantly more common in women with a shortened fetal femur (P<0.001, all). However, the presence of a shortened fetal humerus was not associated with those outcomes excluding SGA. @*Conclusion@#Soft markers in second-trimester ultrasonography have limited use in screening for fetal aneuploidy in Korean women. However, these markers can be used as a screening tool for adverse outcomes other than chromosomal abnormality.

Treatment of gestational diabetes diagnosed by the IADPSG criteria decreases excessive fetal growth

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND@#This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).@*METHODS@#This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.@*RESULTS@#For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.@*CONCLUSION@#Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND@#This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).@*METHODS@#This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.@*RESULTS@#For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.@*CONCLUSION@#Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Addition of Cervical Elastography May Increase Preterm Delivery Prediction Performance in Pregnant Women with Short Cervix: a Prospective Study

BACKGROUND: We investigated whether there is a difference in elastographic parameters between pregnancies with and without spontaneous preterm delivery (sPTD) in women with a short cervix (≤ 25 mm), and examined the ability of elastographic parameters to predict sPTD in those women. METHODS: E-CervixTM (WS80A; Samsung Medison, Seoul, Korea) elastography was used to examine the cervical strain. Elastographic parameters were compared between pregnancies with and without sPTD. Diagnostic performance of elastographic parameters to predict sPTD ≤ 37 weeks, both alone and in combination with other parameters, was compared with that of cervical length (CL) using area under receiver operating characteristic curve (AUC) analysis. RESULTS: A total of 130 women were included. Median gestational age (GA) at examination was 24.4 weeks (interquartile range, 21.4–28.9), and the prevalence of sPTD was 20.0% (26/130). Both the elastographic parameters and CL did not show statistical difference between those with and without sPTD. However, when only patients with CL ≥ 1.5 cm (n = 110) were included in the analysis, there was a significant difference between two groups in elasticity contrast index (ECI) within 0.5/1.0/1.5 cm from the cervical canal (P < 0.05) which is one of elastographic parameters generated by E-Cervix. When AUC analysis was performed in women with CL ≥ 1.5 cm, the combination of parameters (CL + pre-pregnancy body mass index + GA at exam + ECI within 0.5/1.0/1.5 cm) showed a significantly higher AUC than CL alone (P < 0.05). CONCLUSION: An addition of cervical elastography may improve the ability to predict sPTD in women with a short CL between 1.5 and 2.5 cm.

Prenatal diagnosis of 5p deletion syndrome: A case series report

5p deletion syndrome, also known as Cri-du-Chat syndrome, is a chromosomal abnormality caused by a deletion in the short arm of chromosome 5. Clinical features of 5p deletion syndrome are difficult to identify prenatally by ultrasound examination, thus most cases of 5p deletion syndrome have been diagnosed postnatally. Here, we report eight cases of 5p deletion syndrome diagnosed prenatally, but were unable to find common prenatal ultrasound findings among these cases. However, we found that several cases of 5p deletion syndrome were confirmed prenatally when karyotyping was performed on the basis of abnormal findings in a prenatal ultrasound scan. Hence, it is necessary to carefully perform prenatal ultrasonography for detection of rarer chromosomal abnormalities as well as common aneuploidy.

Prenatal diagnosis of 4p deletion syndrome: A case series report

The 4p deletion syndrome, also known as Wolf-Hirschhorn syndrome, is a well-known genetic disorder caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements leads to a wide spectrum of clinical manifestations. Herein, we present our experience with eight cases of 4p deletion syndrome, ascertained prenatally between 1998 and 2016 at our hospital.

Evaluation of the learning curve for external cephalic version using cumulative sum analysis

OBJECTIVE: We evaluated the learning curve for external cephalic version (ECV) using learning curve-cumulative sum (LC-CUSUM) analysis. METHODS: This was a retrospective study involving 290 consecutive cases between October 2013 and March 2017. We evaluated the learning curve for ECV on nulli and over para 1 group using LC-CUSUM analysis on the assumption that 50% and 70% of ECV procedures succeeded by description a trend-line of quadratic function with reliable R² values. RESULTS: The overall success rate for ECV was 64.8% (188/290), while the success rate for nullipara and over para 1 groups was 56.2% (100/178) and 78.6% (88/112), respectively. ‘H’ value, that the actual failure rate does not differ from the acceptable failure rate, was −3.27 and −1.635 when considering ECV success rates of 50% and 70%, respectively. Consequently, in order to obtain a consistent 50% success rate, we would require 57 nullipara cases, and in order to obtain a consistent 70% success rate, we would require 130 nullipara cases. In contrast, 8 to 10 over para 1 cases would be required for an expected success rate of 50% and 70% on over para 1 group. CONCLUSION: Even a relatively inexperienced physician can experience success with multipara and after accumulating experience, they will manage nullipara cases. Further research is required for LC-CUSUM involving several practitioners instead of a single practitioner. This will lead to the gradual implementation of standard learning curve guidelines for ECV.

Maternal Thyroid Function during the First Trimester of Pregnancy in Korean Women

BACKGROUND AND OBJECTIVES: Thyroid dysfunction during pregnancy can result in many complications for both mother and infant. Due to the physiologic changes in thyroid stimulating hormone (TSH) level during early pregnancy, it is recommend to use trimester-specific reference ranges for every population. We obtained the reference range of TSH during the first trimester in Korean women according to gestational week. MATERIALS AND METHODS: The study population consisted of pregnant women who had undergone a TSH screening during the first trimester of pregnancy (n=8365) and nonpregnant women (n=1835). RESULTS: Median concentration of serum TSH decreased significantly from the 5th to 8th week of gestation (median TSH concentration: 2.00 mIU/L for 5 weeks; 1.70 mIU/L for 6 weeks; 1.40 mIU/L for 7 weeks; 1.05 mIU/L for 8 weeks). However, there was no significant difference in median concentration of serum TSH from the 8th to 12th weeks of gestation. Using the fixed cut-off value of TSH >3.66 mIU/L, the diagnosis rate of subclinical hypothyroidism was 15.0% for 5 weeks, 10.0% for 6 weeks, 5.9% for 7 weeks, and 3.6% for 8-12 weeks. CONCLUSION: When interpreting the TSH test for pregnancy (maternal thyroid function), we should consider that the TSH level decreases significantly during the early first trimester.

Observed frequency of fetal trisomy between 16 and 24 gestational weeks in pregnant women older than 34 years at delivery

PURPOSE: Increased maternal age is a major risk factor for chromosomal abnormalities. The maternal age-specific risk of fetal trisomy was theoretically calculated. We investigated the actual frequency of fetal trisomy between 16 and 24 gestational weeks in pregnant women over the age of 34 at delivery. MATERIALS AND METHODS: We retrospectively, over a four-year period, reviewed the medical records of women with singleton pregnancies that started their antenatal care before the 10th week of pregnancy. Pregnant women aged 34 to 45 years at the time of delivery were enrolled and divided into groups of one-year intervals. We investigated the frequency of Down syndrome and all trisomies as a function of the maternal age and compared with the theoretical maternal-age-specific risk. RESULTS: Of the 5,858 pregnant women enrolled in the study, the rate of trisomy 21 was 0.29% (17 cases). The observed frequencies of trisomy 21 in women with maternal ages of 35 years and 40 years were 1:1,116 and 1:141, respectively. The rate of all trisomies was 0.39% (23 cases). The observed frequencies of all trisomies in women with maternal ages of 35 years and 40 years were 1:372 and 1:56, respectively. CONCLUSION: The frequencies of Down syndrome and all trisomies were proportional to the maternal age. However, the observed frequencies of Down syndrome and all trisomies between the 16 and 24 gestational weeks were lower than the theoretical rates.

Practice patterns in the management of threatened preterm labor in Korea: A multicenter retrospective study

OBJECTIVE: This study aimed to examine clinical practice patterns in the management of pregnant women admitted with threatened preterm labor (TPL) in Korea. METHODS: Data from women admitted with a diagnosis of TPL were collected from 22 hospitals. TPL was defined as regular uterine contractions with or without other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and cervical changes. Data on general patient information, clinical characteristics at admission, use of tocolytics, antibiotics, and corticosteroids, and pregnancy outcomes were collected using an online data collections system. RESULTS: A total of 947 women with TPL were enrolled. First-line tocolysis was administered to 822 (86.8%) patients. As a first-line tocolysis, beta-agonists were used most frequently (510/822, 62.0%), followed by magnesium sulfate (183/822, 22.3%), calcium channel blockers (91/822, 11.1%), and atosiban (38/822, 4.6%). Of the 822 women with first-line tocolysis, second-line tocolysis were required in 364 (44.3%). Of 364 with second-line, 199 had third-line tocolysis (37.4%). Antibiotics were administered to 29.9% of patients (284/947) with single (215, 22.7%), dual (26, 2.7%), and triple combinations (43, 4.5%). Corticosteroids were administered to 420 (44.4%) patients. Betamethasone was administered to 298 patients (71.0%), and dexamethasone was administered to 122 patients (29.0%). CONCLUSION: Practice patterns in the management of TPL in Korea were quite various. It is needed to develop standardized practice guidelines for TPL management.

2014 First-trimester ultrasound forum from the Korean Society of Ultrasound in Obstetrics and Gynecology

A first-trimester ultrasound scan has become an essential part of antenatal care. The Korean Society of Ultrasound in Obstetrics and Gynecology held a first-trimester ultrasound forum on April 5, 2014. The forum aimed to present an updated review of the literature on the topic of first-trimester ultrasound in specific lectures and to host a panel discussion on several important issues regarding first-trimester scans. The forum provided evidence- and consensus-based best practice patterns for obstetricians in Korea. Here, we report the review and checklists presented from the forum.

The practice patterns of second trimester fetal ultrasonography: A questionnaire survey and an analysis of checklists

OBJECTIVE: To analyze practice patterns and checklists of second trimester ultrasonography, and to investigate management plans when soft markers are detected among Korean Society of Ultrasound in Obstetrics and Gynecology (KSUOG) members. METHODS: An internet-based self-administered questionnaire survey was designed. KSUOG members were invited to the survey. Checklists of the second trimester ultrasonography were also requested. In the questionnaire survey, general practice patterns of the second trimester ultrasonography and management schemes of soft markers were asked. In the checklists analysis, the number of items were counted and also compared with those recommended by other medical societies. RESULTS: A total of 101 members responded. Eighty-seven percent routinely recommended second trimester fetal anatomic surveillance. Most (91.1%) performed it between 20+0 and 23+6 weeks of gestation. Written informed consents were given by 15.8% of respondents. Nearly 60% recommended genetic counseling when multiple soft markers and/or advanced maternal age were found. Similar tendencies were found in the managements of individual soft markers. However, practice patterns were very diverse and sometimes conflicting. Forty-eight checklists were analyzed in context with the number and content of the items. The median item number was 46.5 (range, 17 to 109). Of 49 items of checklists recommended by International Society of Ultrasound in Obstetrics and Gynecology and/or American Congress of Obstetricians and Gynecologists, 14 items (28.6%) were found in less than 50% of the checklists analyzed in this study. CONCLUSION: Although general practice patterns were similar among KSUOG members, some of which were conflicting, and there is a need for standardization of the practice patterns and checklists of second trimester ultrasonography, which also have very wide range of spectrum.

Gestational weight gain is an important risk factor for excessive fetal growth

OBJECTIVE: To estimate the odds ratio of prepregnant body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) for excessive fetal growth, which we define as large for gestational age (LGA). METHODS: We included 16,297 women who delivered a live-born singleton baby at term. We fit logistic regressions to estimate the odds ratios of variables, including maternal age, parity, prepregnant BMI > or =23, GWG > or =15 kg, and GDM, for LGA. We classified GWG into four categories ( or =20 kg) and BMI into four categories (underweight, normal, overweight, and obese). After adjusting for age and parity, we analyzed the odds ratios of prepregnant BMI according to GWG between non-GDM and GDM women for LGA. RESULTS: The odds ratios of GWG > or =15 kg and prepregnancy BMI > or =23 for LGA were 2.40 (95% confidence interval [CI], 2.16-2.67) and 2.24 (95% CI, 1.99-2.51), respectively. The odd ratio of GDM was 1.37 (95% CI, 1.09-1.71). The risk of GDM women with normal/-overweight BMI and GWG or =15 kg might be a more important risk factor for LGA than either prepregnancy BMI > or =23 or GDM. Risk for LGA was highest in obese GDM women with GWG > or =15 kg.

The clinical practice patterns of fetal ultrasonography in the first-trimester: A questionnaire survey of members of the Korean Society of Ultrasound in Obstetrics and Gynecology

OBJECTIVE: This study aimed to survey the current clinical practice of first-trimester ultrasonography among members of the Korean Society of Ultrasound in Obstetrics and Gynecology (KSUOG) and to provide basic data for making practical recommendations about first-trimester ultrasonography scan in Korea. METHODS: This survey was conducted using a self-administered anonymous questionnaire. The first-trimester in this survey was divided into two parts: early and late first-trimester. The survey was focused on safety issue, nuchal translucency (NT) cutoff, the anatomic structures they check, and the need for practical recommendations or educational courses during the first-trimester. RESULTS: During the study period, 194 KSUOG members participated into this survey. The survey on early first-trimester scan reveal that 173 (89.2%) of respondents had used pulsed-wave Doppler or color Doppler imaging to monitor fetal heart beat. For the late first-trimester scan, 145 (74.7%) of respondents was found to check for fetal anatomical assessments during their NT screening performance; however, the clinical practice patterns were considerably varied among participants. More than half of the respondents used the criterion of NT > or =3.0 mm to define increased NT. Approximately 80% of respondents stated that the screening ultrasonography of fetal structures in the first-trimester was necessary. Furthermore, 187 (96.4%) of respondents were in favor of a recommendation for first-trimester ultrasonography in Korea. CONCLUSION: This is the first survey of the current clinical practice of first-trimester ultrasonography in Korea. Our survey findings highlight the need for the practical recommendation or educational course for first-trimester ultrasonography.

Prenatal Diagnosis of Chromosome 22q11.2 Deletions: Experiences in a Single Institution

PURPOSE: This study was designed to determine the frequency and echocardiographic findings of 22q11.2 deletions in fetuses with cardiac defects on fetal ultrasound or familial backgrounds of 22q11.2 deletions. MATERIALS AND METHODS: We retrospectively reviewed the medical and ultrasonographic records of 170 fetuses that underwent fluorescence in situ hybridization (FISH) analysis for chromosome 22q11.2 deletions between February 2001 and April 2013. RESULTS: Among 145 fetuses with cardiac defects, six (4.1%) had 22q11.2 deletions. Deletions of 22q11.2 were detected in 6 (5%) of the 120 fetuses with conotruncal defects: 5 (8.9%) of 56 with tetralogy of Fallot (TOF) and 1 (5.9%) of 17 with double outlet right ventricle (DORV). No deletions were found in cases of pulmonary atresia, truncus arteriosus, right aortic arch, or transposition of the great arteries. No 22q11.2 deletions were found in non-conotruncal cardiac malformations. Among 25 fetuses with familial backgrounds of 22q11.2 deletions, one (4%) had a maternally inherited 22q11.2 deletion with no cardiac findings. CONCLUSION: Knowledge of the frequency and echocardiographic findings of 22q11.2 deletions might be helpful for prenatal genetic counseling. It is advisable to perform FISH analysis for 22q11.2 deletions in pregnancies exhibiting conotruncal cardiac defects such as TOF or DORV.

Clinical Experiences of Molecular Genetic Evaluation of Achondroplasia in Prenatal and Neonatal Cases

PURPOSE: The purpose of this study was to assess the characteristics of achondroplasia (ACH) diagnosed in fetuses or neonates and to evaluate the usefulness of a molecular genetic testing to confirm ACH. MATERIALS AND METHODS: The medical and ultrasonographic records of 16 pregnant women, who had molecular genetic testing for ACH performed on their fetus or neonate at the Cheil General Hospital between February 1999 and April 2013, were retrospectively analyzed. Detection of G1138A and G1138C mutations of the fibroblast growth factor receptor 3 (FGFR3) gene was accomplished by polymerase chain reaction - restriction fragment length polymorphism analysis. RESULTS: Of the eight fetuses and two neonates who were suspected of having ACH during pregnancy, four fetuses and one neonate was confirmed to have ACH and they all carried the heterozygous G1138A mutation. Out of 6 cases which had a history of ACH in prior pregnancies, three had genetic information for the previous fetuses while the other three did not. All six fetuses had no mutations at G380R. However, the one fetus of pregnant woman with non-confirmed ACH showed shortened long bone on ultrasound thereafter and the fetus was identified as having oto-spondylo-megaepiphyseal dysplasia after birth. CONCLUSION: Korean patients with achondroplasia have the heterozygous G1138A mutation that is most commonly defined in other countries. Molecular genetic evaluations of ACH are helpful not only for establishing diagnosis but for appropriate counseling with subsequent pregnancies.

A Case of Term Delivery with Diagnosis of Severe Oligohydramnios after Exposure to Glimepiride, Metformin and Antihypertensive agents Including Angiotensin Receptor Antagonist up to Approximately 20 Weeks of Pregnancy / 대한주산의학회잡지

Various fetal and maternal conditions are known to be associated with oligohydramnios. In general, oligohydramnios developed early in pregnancy is less common but frequently has a poor prognosis. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists during pregnancy has been associated with oligohydramnios as well as growth restriction, pulmonary hypoplasia with respiratory distress, acute renal failure, cranial malformation and fetal death. Although many researchers report a use of oral hypoglycemic agents such as glyburide or metformin in gestational diabetes mellitus, but potential adverse effects of glimepiride, which is relatively recently developed, is not well known owing to the lack of clinical data, especially early in pregnancy. A 41-year-old woman with chronic hypertension and type 2 diabetes mellitus was treated with drugs including metformin, glimepiride and angiotensin receptor antagonist until approximately 20 weeks' gestations, when severe oligohydramnios was noted. After the hospitalization for bed rest, fetal surveillance, and discontinuation of the agents, amniotic fluid reaccumulated, and the infant was delivered at term. We report this case with a brief review of literatures.

Maternal Plasma Hepatocyte Growth Factor Concentrations in Women Who Subsequently Developed Preeclampsia

PURPOSE: The aim of this nested case-control study was to investigate the association between hepatocyte growth factor (HGF) concentrations in maternal plasma and the risk of developing preeclampsia. MATERIALS AND METHODS: Plasma HGF concentration were measured in 52 women who subsequently developed preeclampsia and 104 normal pregnant women at the time of genetic amniocentesis (15-20 weeks) by enzyme-linked immunosorbent assay. RESULTS: Maternal plasma HGF concentrations were significantly higher in women with subsequent preeclampsia (median: 737.8 ng/mL vs. 670.4 ng/mL, P=0.003) than in normal controls. However, HGF concentrations were not significantly different between subgroups by preeclamptic complications. After adjusting for potential confounding factors, women with HGF concentrations > or =702.5 ng/mL had a 3.2-fold increased risk (95% CI 2.7-5.4, P<0.001) of subsequent development of preeclampsia compared with women with HGF concentrations <702.5 ng/mL. CONCLUSION: Elevated maternal plasma HGF concentrations in the early second-trimester are associated with an increased risk of developing preeclampsia.