Clinical guidance for peripartum management of patients with hereditary thrombophilia.

Hereditary thrombophilia is a condition in which individuals are susceptible to the formation of thrombi due to a hereditary deficiency in anticoagulant factors, antithrombin (AT), protein C (PC), or protein S (PS). Many Japanese thrombophilia patients have PS deficiency, especially PS p.K196E (also called as PS Tokushima), which is exclusive to the Japanese population, and thrombosis sometimes occurs during pregnancy. At present, no management guidelines for pregnancy and delivery in thrombophilia patients have been developed. The Study Group for Hereditary Thrombophilia, one of the research groups of blood coagulation abnormalities in the Research Program on Rare and Intractable Diseases supported with the Research Grants of the Ministry of Health, Labour and Welfare Science, has therefore developed this clinical guidance to provide healthcare workers with necessary information on safe pregnancy, parturition and neonatal management, adopting a format of responses to seven clinical questions (CQ). At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory.

AIM: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. METHODS: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. RESULTS: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. CONCLUSION: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Cardiovascular profile and biophysical profile scores predict short-term prognosis in infants with congenital heart defect.

AIM: To predict the prognosis of infants with congenital heart disease, accurate prenatal diagnosis of structural abnormality and heart failure are both necessary. The aim of this study was to investigate whether cardiovascular profile (CVP) and biophysical profile (BP) scores are useful for predicting prognosis in infants with congenital heart defect (CHD). METHODS: A retrospective review of singletons prenatally diagnosed with CHD at a tertiary pediatric cardiac center between 2011 and 2015 was undertaken. RESULTS: A total of 202 patients with CHD were analyzed. Perinatal and infant deaths occurred in 16 (7.9%) and 10 cases (5.0%), respectively. Infants with the last CVP score ≤ 5 had 18.7-fold higher perinatal mortality than those with a last CVP score > 5 (P < 0.01). Infants with a last BP score ≤ 6 had 18.7-fold higher perinatal mortality than those with a last BP score > 6 (P < 0.01). Infants with a CVP score decrease in utero had 4.5-fold higher infant mortality than those with an increase or no change (P < 0.01). Multivariate analysis showed that single-ventricle physiology, pre-term birth at <37 weeks of gestation, last CVP score ≤ 5, and last BP score ≤ 6 were independent predictors of perinatal mortality. Single-ventricle physiology and a CVP score decrease were independent predictors of infant mortality. CONCLUSION: CVP and BP scores are useful for predicting perinatal prognosis in infants with CHD. A CVP score decrease in utero is associated with infant mortality, suggesting that serial CVP score assessment may be useful for management planning.

Safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system in women with cardiovascular disease.

AIM: We sought to examine the safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS), and to evaluate the changes in biomarkers of infection, anemia and cardiovascular conditions after LNG-IUS insertion in women with cardiovascular disease. METHODS: We prospectively followed women with a cardiovascular disease in whom a 52-mg LNG-IUS was inserted between 2009 and 2015. The primary outcome was the frequency of cardiovascular and gynecologic side effects due to the LNG-IUS over the year after LNG-IUS insertion. The secondary outcomes were the changes in menstrual blood loss and biomarkers, e.g., white blood cell count and the levels of C-reactive protein, hemoglobin and brain natriuretic peptide. We also evaluated the 24-month continuation rate of LNG-IUS. RESULTS: A total of 34 women were prospectively followed-up, including two women with pulmonary hypertension. No cardiovascular side effects were identified during the 1 year after LNG-IUS insertion, other than one case of mild vasovagal reaction at insertion. Neither the white blood cell count nor the C-reactive protein value increased after LNG-IUS insertion. The menstrual blood loss was decreased in most subjects and the median hemoglobin levels increased significantly within 1 year after insertion (P < 0.001 and P = 0.002). Moreover, brain natriuretic peptide levels tended to decrease in correspondence with the hemoglobin elevation (P = 0.074). The 24-month LNG-IUS continuation rate was 97% (95% confidence interval 85-100). CONCLUSION: No clinically significant cardiovascular event was identified during the 1 year after 52-mg LNG-IUS insertion among women with cardiovascular disease. The 52-mg LNG-IUS may have specific favorable effects by decreasing the risk of iron deficiency anemia in these women.

Recurrent Congenital Heart Diseases Among Neonates Born to Mothers with Congenital Heart Diseases.

The frequency of newborns with congenital heart disease (CHD) is approximately 1% in the general population; however, the recurrence rate of CHD in mothers with CHD differs in ethnicity and reports. We therefore aimed to determine the prevalence of CHD among neonates born to mothers with CHD in our institute in Japan. We reviewed the medical charts of 803 neonates delivered by 529 women with CHD at the National Cerebral and Cardiovascular Center from 1982 to 2016. They included isolated ventricular septal defect (VSD,31.4%), isolated atrial septal defect (ASD, 23.3%), tetralogy of Fallot (TOF,10.6%). We defined CHD in neonates as being diagnosed within 1 month of birth. We estimated that the average rate of the CHD recurrence was 3.1%. The recurrence ratios in each maternal CHD were 8.6%, 7.1%, 6.2%, 4.8%, 3.6%, and 1.5% for PS, CoA, TOF, atrioventricular septal defect, VSD, and ASD, respectively. The rate of CHD in offsprings whose mothers have CHD was 3 times greater than that of mothers with healthy hearts. Almost half of neonates with CHD had the same phenotype as their mother in our series. Especially, PS and CoA were closely related to the type of maternal CHD.

Management of pregnancy complicated with intracranial arteriovenous malformation.

AIM: To clarify the perinatal outcomes in pregnancy complicated with intracranial arteriovenous malformation (i-AVM). METHODS: A retrospective study was performed in 36 pregnancies complicated by i-AVM from 1981 to 2013 at one institution. RESULTS: In total, 6 women miscarried, and 30 had live births. The median (range) gestational age at delivery was 38 (24-40) weeks; 11 cases experienced initial i-AVM rupture during pregnancy (first, second and third trimester: 18%, 64% and 18%, respectively). At onset, 4 cases had a Glasgow Coma Scale ≤10, 10 cases needed emergency maternal transport, 4 underwent neurosurgery with the fetus in utero and 4 had termination of pregnancy in the second trimester for emergent treatment for i-AVM. Two cases delivered vaginally. Another 25 cases had already been diagnosed as i-AVM at conception. Of these, as an indication for epidural birth, 18 cases had either residual lesion of i-AVM or neurological symptoms, although 18 cases had received treatments of i-AVM before conception. Without rupture of i-AVM and worsening of symptoms, 15 cases succeeded in epidural birth. One case was delivered by cesarean section for residual i-AVM with indication of treatment. Another case who had refused treatment of i-AVM experienced rupture of i-AVM 1 year after delivery. CONCLUSION: Most of the cases with residual i-AVM lesion and neurological symptoms could deliver vaginally without worsening of symptoms. However, pregnancy with i-AVM can be complicated by rupture of i-AVM. In cases with a residual lesion with indication of treatment and rupture of i-AVM during pregnancy, meticulous care is required during pregnancy and after delivery.

Utility of Fluid Assessment Based on the Intrathoracic Impedance Monitoring in a Peripartum Woman with Heart Disease.

Recently, implantable cardioverter-defibrillators (ICD) have become capable of monitoring intrathoracic impedance to detect an increased fluid volume and heart failure. Pregnancy is a well-known cause of an increased body fluid volume; however, it is not clear whether the measurement of intrathoracic impedance by ICD is clinically useful for precisely detecting heart failure in pregnant women. We herein report the case of a 39-year-old woman with an ICD that had been implanted after an event of ventricular fibrillation due to severe aortic regurgitation with a bicuspid aortic valve. Elevated right ventricular pressure and brain natriuretic peptide levels were detected at 37 weeks of gestation and postpartum. At the same time, the ICD's stored fluid index gradually increased and exceeded the threshold on the 10th day after delivery. She was treated with diuretics and recovered from postpartum heart failure. The physiological volume changed in the perinatal period, but we were still able to detect heart failure by ICD. Intrathoracic impedance monitoring is effective in the perinatal field.

Cardiomyopathy Phenotypes and Pregnancy Outcomes with Left Ventricular Noncompaction Cardiomyopathy.

Little is known about pregnancies of left ventricular noncompaction cardiomyopathy (LVNC), much less cases in which LVNC was definitively diagnosed prepregnancy. We report the cases of three pregnant Japanese women definitively diagnosed with LVNC prepregnancy. Case 1 presented LVNC with restrictive phenotype. Her pregnancy was terminated due to exacerbated pulmonary hypertension and low output status at 30 weeks' gestation. Case 2 presented isolated LVNC with nonsustained ventricle tachycardia. A cesarean section was performed at 36 weeks' gestation because of placenta previa. Case 3 presented dilated LVNC. Labor induction was performed because of decreased left ventricular ejection fraction, leading to a vaginal delivery at 37 weeks' gestation. In all cases, no thromboembolic event was identified during pregnancy; two patients received anticoagulants. We reviewed all English-literature cases of pregnant women definitively diagnosed with LVNC prepregnancy to analyze causes of adverse pregnancy outcomes and the necessity of anticoagulation. Four of the six pregnancies identified were terminated due to exacerbated cardiomyopathy phenotypes and not complications due to noncompaction itself, resulting in three cases' preterm deliveries. No thromboembolic event was identified by maintenance of the anticoagulation strategy determined prepregnancy. In pregnancies with LVNC, the possibility of a severe cardiac event and the indications for termination of the pregnancy can depend on the cardiomyopathy phenotypes, not noncompaction itself. Anticoagulation only because of the pregnancy itself may be redundant. In the management of LVNC during pregnancy, close monitoring of the condition of different phenotypes and reassessment of the necessity of anticoagulation can contribute to the pregnancy outcome.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Thrombophilia in East Asian countries: are there any genetic differences in these countries?

In recent years, genetic analyses of congenital deficiencies of three anticoagulant proteins, antithrombin, protein C (PC) and protein S (PS), in East Asian patients with venous thromboembolism (VTE) have greatly increased. The PS-K196E mutation is often identified in the Japanese population with an allelic frequency of 0.86 %, and a total of approximately 10,000 Japanese are estimated to be homozygotes. The heterozygotes show PS anticoagulant activities ranging from 40 to 110 %, and 16 % lower mean anticoagulant activity than that in wild-type individuals. Specific assay methods to identify carriers of this mutation have recently been developed. The mutation carriers are at risk of thrombosis during pregnancy but do not appear to be at risk for adverse pregnancy outcomes. To promote future research into this mutation and its relation to thrombosis, a thrombosis-prone mouse strain with the PS K196E mutation has been developed. We found the PS-K196E mutation and the heterozygous PS-deficiency in mice caused increased VTE, but did not cause aggravation of ischemic stroke, unlike factor V Leiden mutation. Importantly, the PS-K196E mutation is only identified in Japanese. This suggests that although East Asian populations including Japanese, Chinese, and Koreans are geographically and genetically close, the PS-K196E mutation seems to be Japanese-specific, suggesting that the mutation is a recent occurrence and fixed within the Japanese population. Some recurrent genetic mutations predisposing to VTE have been reported in Chinese and Korean populations. Although the genetic background for VTE is known to differ between populations with Caucasian descent and East Asian populations, some of the recurrent mutations differ even within the East Asian populations.

Vaginal delivery in pregnancy with Moyamoya disease: experience at a single institute.

AIM: Cesarean section is commonly selected in pregnancy with Moyamoya disease. We consider vaginal delivery with epidural anesthesia a viable alternative in such cases. METHODS: Mode of delivery and outcomes were examined in 27 pregnancies in 19 women with Moyamoya disease treated at the Department of Perinatology, National Cardiovascular Center, Japan, from 1983 to 2013. Of these 27 pregnancies, 20 were delivered vaginally with epidural anesthesia. The cerebral circulation, mode of delivery, maternal outcome (presence of symptoms due to Moyamoya disease intrapartum) and neonatal outcome (gestational week, birthweight, Apgar score at 5 min and pH of umbilical artery) were investigated. RESULTS: The cerebral circulation was judged to be good in all pregnancies. No symptoms due to Moyamoya disease intrapartum were seen in the vaginal delivery cases. CONCLUSION: Our findings indicate that vaginal delivery is viable in pregnancy with Moyamoya disease and that unnecessary cesarean section may be avoided. These findings are limited by the retrospective nature of the study.

Cardiovascular events in pregnancy with hypertrophic cardiomyopathy.

BACKGROUND: The influence of the physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) is unclear. There have been no comprehensive studies of pregnant women with HCM in the Japanese population. METHODS AND RESULTS: A total of 27 pregnancies (23 women with HCM) were retrospectively reviewed. A total of 18 cardiovascular events occurred in 13 of the 27 pregnancies (48%), and 13 of these events (76%) were related to arrhythmia. The cardiovascular events tended to occur in the early stage of pregnancy (≈30 gestational weeks) or postpartum. The events related to arrhythmia mainly occurred in the early stage of pregnancy or at approximately 30 gestational weeks. Four pregnancies were terminated because of cardiovascular events. Cardiovascular events occurred in 8 of 9 pregnancies in women on medication before pregnancy (88%), 7 of 10 pregnancies with high CARPREG score (70%), and in 9 of 12 pregnancies with high ZAHARA score (75%). CONCLUSIONS: Cardiovascular events occurred in more than half of the pregnant women complicated with HCM, and the arrhythmia is the most common cardiovascular event. Medication in the pre-pregnancy period, and CARPREG or ZAHARA score ≥1 were identified as risk factors of cardiac events during pregnancy or postpartum.

Risk factors for maternal and fetal outcome in pregnancy complicated by Ebstein anomaly.

OBJECTIVE: The goal of the study was to examine risks in pregnancy in patients with Ebstein anomaly. STUDY DESIGN: Data were examined retrospectively for 13 patients (27 pregnancies, 21 live births) with Ebstein anomaly during pregnancy who were treated at our institution from 1985 to 2011. The associated anomalies in these patients were atrial septal defect (ASD) (n = 4) and the Wolff-Parkinson-White syndrome (n = 6). RESULTS: Before pregnancy, 2 patients underwent ASD closure and 1 received tricuspid valve replacement (TVR). In all patients, the cardiothoracic ratio increased from 55.1 at conception to 57.0 during pregnancy and 58.0 postpartum (P < .05). Cesarean sections were performed in 3 cases: 1 with ventricular tachycardia and orthopnea (New York Heart Association [NYHA] III) preterm; at full term, and the third in a patient with a mechanical tricuspid valve who developed maternal cerebellum hemorrhage at 27 weeks. The baby died of prematurity in the third case. In all other cases (20 of 21), neonatal prognoses were good without congenital heart diseases. There were 6 spontaneous abortions. Recurrent paroxysmal supraventricular tachycardia occurred during pregnancy in 2 cases and was treated with adenosine triphosphate or verapamil. In 17 pregnancies, NYHA remained in class I and all had full-term vaginal delivery. CONCLUSION: Maternal and fetal outcomes are good in patients with Ebstein anomaly and NYHA class I. However, pregnancy in Ebstein anomaly can be complicated with tachyarrhythmia or cardiac failure. In post-TVR cases, meticulous care is required for these complications during pregnancy and delivery.

Safety and efficacy of implantable cardioverter-defibrillator during pregnancy and after delivery.

BACKGROUND: There are few studies of pregnancy and delivery in patients with an implantable cardioverter-defibrillator (ICD). The purpose of this study was to investigate maternal and fetal outcome in these patients. METHODS AND RESULTS: Six pregnant women with an ICD were retrospectively reviewed. All women underwent implantation of an ICD before pregnancy and delivered at the National Cerebral and Cardiovascular Center. The mean age at pregnancy and the mean follow-up period after ICD implantation were 28±3 years old and 5±3 years, respectively. There was no device-related complication during pregnancy. In 4 women, the number of tachyarrhythmias such as non-sustained ventricular tachycardia increased after the end of the second trimester of pregnancy and anti-arrhythmic medications were gradually increased. No patient received discharges or shocks from the ICD during pregnancy, however, and only one required anti-tachycardia pacing at 27 weeks' gestation. Mean gestational age at delivery was 37±2 weeks and all deliveries were by cesarean section, including 5 as emergency deliveries due to a fetal indication. After delivery, 2 mothers had reduced cardiac function and 1 received an ICD shock for the first time. CONCLUSIONS: Pregnancy did not increase the risk of an ICD-related complication under appropriate management. Additional caution might be required in the postpartum period as well as during pregnancy and labor.

Retrospective review of thoracoamniotic shunting using a double-basket catheter for fetal chylothorax.

OBJECTIVE: From a single-center retrospective cohort with fetal chylothorax, we evaluated the factors related to the decision to use shunting, poor prognostic factors, and reported shunting outcomes with a new double basket-catheter device. METHODS: A retrospective single-center study was performed in 35 cases of fetal chylothorax. RESULTS: There were 35 cases of chylothorax: 23 with hydrops and 12 without hydrops. Twenty-one procedures were performed on 15 fetuses (11 with hydrops) with a single shunt in 11, two shunts in 3 and four shunts in 1. All 12 nonhydropic cases survived. In 23 hydropic cases, overall survival rates with and without thoracoamniotic shunting were 46 and 33%, respectively. The mortality rates of fetal hydropic cases with and without ascites were 93 and 11%, respectively. Fetal ascites, progression of fetal hydrops, and premature delivery at <33 weeks were significant risk factors for a poor prognosis. Progression of polyhydramnios after shunting was also associated with a poor prognosis. Obstruction of the catheter was observed in 38%. There were no direct fetal deaths associated with shunting. CONCLUSION: Thoracoamniotic shunting should be considered for pleural effusion before development of fetal hydrops, or at least before the appearance of fetal ascites. A double-basket catheter tends to be obstructive, but may be less invasive for fetuses.

Three Cases of Unprovoked Venous Thromboembolism with Prothrombin p.Arg596Gln Variant and a Literature Review of Antithrombin Resistance.

Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old. The three patients did not show any positive markers for thrombophilia on routine testing, suggesting that patients with unprovoked VTE who have negative findings on thrombophilia tests may carry a prothrombin variant with ATR.

Outcome of pregnancy and effects on the right heart in women with repaired tetralogy of fallot.

BACKGROUND: Improved medical techniques have allowed most women with repaired tetralogy of Fallot (TOF) to reach childbearing age. The predictors of adverse events and the effects of pregnancy on cardiac function have not been clearly described in these patients. METHODS AND RESULTS: In the present study we retrospectively reviewed 40 deliveries in 25 patients with repaired TOF. There were 23 patients in New York Heart Association (NYHA) class I, and 2 in classes II-III before pregnancy. The mean age at delivery was 29.1 years and the mean gestational period was 37.8 weeks. Seven pregnancies (17.5%) in 7 patients were complicated with cardiac events such as a decline in NYHA class and arrhythmia. History of ablation and the baseline cardiothoracic ratio on chest radiography were predictors of adverse events. Peak plasma brain natriuretic peptide (BNP) level after the second trimester was higher in patients with cardiac events. Left ventricular size and contraction did not change from before to after pregnancy, but the right ventricle was enlarged at 6 months after delivery. CONCLUSIONS: Many of the pregnancies in women with repaired TOF were successful. However, careful management is required for some patients and the BNP level may be a useful marker to identify these patients. Because the right heart tended to be enlarged in the late postpartum period, pregnancy may also affect the long-term prognosis of patients with repaired TOF.

Maternal outcome in pregnancy complicated with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), including Eisenmenger syndrome, has a risk of mortality in pregnancy of 10-40%. The aim of this study was to investigate whether pulmonary artery blood pressure (PABP) is a prognostic factor for pregnancy outcome in patients with PAH. METHODS AND RESULTS: The subjects were 42 patients with PAH during pregnancy. Severe and mild cases were defined by PABP before and during the first 14 weeks of pregnancy, with severe cases having mean PABP >40 mmHg by catheterization or systolic PABP >50 mmHg on echocardiography. Eighteen women chose termination of pregnancy before 14 weeks, leaving 24 women (10 mild, 14 severe) for analysis. The women with severe PAH delivered earlier (35.4 vs. 31.5 weeks, P<0.05) and had higher rates of small-for-gestational-age infants (0/10 vs. 7/14, P<0.01). Among the women with severe PAH, the New York Heart Association class dropped by 1 in 9 cases, by 2 in 3 cases, and remained the same in 2 cases as pregnancy progressed, whereas among the women with mild PAH, the class dropped by 1 in 1 case and 9 women remained in the same class. Among the severe cases, 1 woman died and there was 1 fetal death; PABP markedly increased in later pregnancy from 54 to 74 mmHg (catheter measurement) and from 78 to 93 mmHg (echocardiography) (P<0.05). CONCLUSIONS: The level of PABP before or in the early stage of pregnancy is an important predictor of pregnancy outcome.