Dear Colleagues,

On behalf of the Editorial Team of Hypertension Research in Pregnancy, I am pleased to announce the Journal Awards for the Year 2018.

The aim of these Awards is to recognize papers published in 2018, both clinical and experimental studies, that were highly appreciated by the Editorial Team.

In the year of 2018, following paper has been selected for the Hypertension Research in Pregnancy Awards.

Human β-defensin-2 as a biochemical indicator of vaginal environment in pregnant women

Hideko Kotani^1,3, Keiichi Matsubara¹, Tetsuo Koshizuka², Kyoko Nishiyama², Hisae Kaneko³, Mie Tasaka³, Takashi Sugiyama¹, Tatsuo Suzutani²

¹Department of Obstetrics and Gynecology, Ehime University School of Medicine, Toon, Ehime, Japan, ²Department of Microbiology, Fukushima Medical University, Fukushima, Japan, ³Department of Obstetrics and Gynecology, NTT West Matsuyama Hospital, Matsuyama, Ehime, Japan

Aim: Vaginal environment is an important factor in predicting threatened abortion and premature rupture of membranes (PROM) in early pregnancy. Vaginal human β-defensin-2 (HBD-2), a main antimicrobial peptide associated with innate immunity, plays multiple roles to protect the lower genital tract from microbes. This study aimed to assess the usefulness of vaginal HBD-2 as a biochemical marker for monitoring the vaginal environment in pregnant women.

Methods: Twenty-eight pregnant women were enrolled in this study. Vaginal secretion samples were collected to determine Nugent scores, and vaginal washing fluid (4 ml saline) was used to measure HBD-2 levels by ELISA.

Results: In the first trimester, vaginal HBD-2 levels were significantly lower in patients with bacterial vaginosis (BV) (42.1±19.8 pg/ml) compared to those without BV (350.1±68.7 pg/ml, P<0.05), and in patients with PROM (57.2±31.9 pg/ml) compared to those without PROM (375.9±69.4 pg/ml, P<0.05).

Conclusions: Low vaginal HBD-2 levels during early pregnancy suggest a poor vaginal environment and the possibility of developing PROM.

Introduction: The aim of the study was to evaluate if hyperbaric area index (HBI) can be a good predictor for adverse neonatal outcome in patients with hypertensive disorder pregnancy.

Method: A retrospective study enrolled 78 cases whose 24 hours ambulatory blood pressure monitoring (ABPM) was measured before delivery was performed. Patients were divided into two groups by the timing of measurement after 20 gestational weeks or not. HBI scores that obtained by integral calculator of the difference between the measured blood pressure and base line to time axis were calculated. Neonatal outcomes including gestational week at birth and infant weight were evaluated. The ROC curve was used to determine the association between scores and neonatal outcomes.

Result: Of 78 women, 33 were measured less than 20 weeks and 45 were measure after 20 weeks. The mean gestational weeks at delivery was 36±2.2 weeks, and the mean birth weight was 2,540±590 g. When the blood pressure baseline was set as 140 mmHg, the cutoff value of the score is 43.5 mmHg-hour (AUC is 0.741), and the odds ratio of birth weight<2,000 g is 8.3 (95%CI: 2.7–28.0). However, the AUCs were 0.778 in the group after 20 weeks and 0.345 in the group less than 20 weeks respectively. When the blood pressure criteria value was set to 135 mmHg, the AUC in the group less than 20 weeks increased to 0.707.

Conclusion: HBI can be a useful predictor for adverse neonatal outcome in patients with hypertensive disorder pregnancy.

Objective: Administration of angiotensin II receptor blocker (ARB) to pregnant women is contraindicated due to the risk of inducing oligohydramnios. However, it is unclear if the ARBs on the market uniformly induce oligohydramnios. The aim of this study was to find an ARB that is less likely to develop oligohydramnios based on the frequency of side effects registered in the US Food and Drug Administration Adverse Event Reporting System (FAERS) and to show the mechanism of the lower risk of developing oligohydramnios in non-clinical studies.

Methods: We searched for cases registered in FAERS from 2004 to 2017, investigated the frequency of adverse event records of patients taking ARB showing oligohydramnios, and compared them among ARB drugs. We compared the antihypertensive effect of the selected ARBs and their fetal transfer in the model rats of hypertensive disorder of pregnancy with administration of L-NAME, a nonselective nitric oxide synthase inhibitor. The transport activity of organic anion transporting polypeptide (OATP) 2B1 was evaluated by using HEK293 cells transiently transfected with cDNA of human OATP2B1. The drug concentrations were measured by liquid chromatography with tandem mass spectrometry.

Results: Of the 6 ARBs investigated, olmesartan had the highest frequency of oligohydramnios, and irbesartan had the lowest frequency, with a 25-fold difference in reporting frequency. In pregnant hypertensive rats, both olmesartan and irbesartan showed remarkable antihypertensive effect, while only irbesartan showed the effect of improving fetal growth failure. Ratio of the plasma concentration in the fetus to that in the dam (F/M ratio) was measured. The F/M ratios of olmesartan and irbesartan were about 1.6 and 0.28, respectively, indicating that fetal transfer of irbesartan is relatively limited due to the flux in the placenta. OATP2B1 is one of drug transporters which is known to be expressed in the fetal-facing membrane in syncytiotrophoblasts. When the transport activity of both drugs by OATP2B1 was examined, it was shown that only irbesartan was transported.

Conclusion: The records in the database implied that irbesartan has a low risk of increasing amniotic fluid volume among the ARB drugs. Irbesartan showed lower fetal transfer at least in rats than olmesartan and irbesartan is a substrate of OATP2B1, indicating that irbesartan may be excreted by placental OATP2B1 from fetal plasma to maternal plasma.

The Japan Council for Implementation of the Maternal Emergency Life Support System (J-CIMELS) adopted the “Kyoto protocol”—which the Kyoto Society for Emergency Response in Obstetrics and Gynecology proposed in 2010—as the “evaluation and care protocol” intended to prevent the progression of pathologic conditions in expectant and nursing mothers by detecting maternal emergencies at an early stage and by taking appropriate and required measures. The protocol also incorporates maternal care including obstetric cardiopulmonary resuscitation (CPR) in the event that pathologic conditions deteriorate further despite the measures taken. The J-CIMELS aims to popularize the protocol among medical professionals involved in perinatal care. The protocol sets forth procedures that the first detector at any obstetric institution should follow. Specifically, the protocol describes monitoring the patient’s vital signs to assess breathing, circulation, and level of consciousness, recommends simple, appropriate approaches for oxygenation and transfusion that are indispensable in maternal emergencies, and provides steps to be taken for immediate measures and the use of an automated external defibrillator and adrenaline in obstetric CPR. The J-CIMELS developed a basic simulation-based practical training course, in which trainees carry out the required measures as per the protocol through simulated maternal emergencies, and has held the course throughout Japan since 2015. Popularization of the protocol is expected to reduce the number of maternal deaths in Japan.

Aim: The influence of cardiovascular changes resulting from hypertension on the course of pregnancy is unclear. The purpose of this study was to evaluate the influence of cardiovascular changes as detected by echocardiography on the course of pregnancy with chronic hypertension.

Methods: This retrospective cohort study targeted women with a singleton pregnancy and chronic hypertension during the period between January 1, 2010 and December 31, 2018. We compared echocardiographic values between subjects with blood pressure (BP) elevation (BP elevation group) and normotensive subjects (control group) during pregnancy.

Results: Twenty-nine hypertensive pregnant women were eligible for this study (14 subjects in the BP elevation group and 15 subjects in the control group). Left ventricular posterior wall thickness (PWT) and left ventricular mass index (LVMI) tended to be greater in the BP elevation group compared to the control group, but the differences were not significant. In the sub-cohort of subjects aged ≥35 years, PWT and LVMI were significantly greater in the BP elevation group compared to the control group.

Conclusions: Left ventricular hypertrophy (LVH) in pregnant women with chronic hypertension may be a predictor of BP elevation during pregnancy.

HELLP syndrome is a life-threatening complication of pregnancy that requires immediate delivery. Temporizing management for short durations (24–48 hours) may be an acceptable option. However, there is insufficient information on long-term expectant management (≥48 hours) for HELLP syndrome occurring during the periviable period (22–24 weeks of gestation). The Mississippi protocol, which includes high doses of dexamethasone in combination with antihypertensives and magnesium sulphate, is usually used for planned delivery within 48 hours after diagnosis of HELLP syndrome to prevent severe maternal morbidity. Here we present three cases of HELLP/partial HELLP syndrome occurring during the periviable period, which were treated with a modified Mississippi protocol. The modified Mississippi protocol involved administration of three-day, high-dose dexamethasone followed by long-term, low-dose prednisolone (10 mg/day). The modified Mississippi protocol contributed to prolongation of pregnancy (8, 10, and 16 days), and may be a promising therapeutic option especially for periviable HELLP/partial HELLP syndrome.

Cushing’s syndrome (CS) during pregnancy is a rare metabolic condition associated with hypertension, hyperglycaemia, and foetal growth restriction (FGR). Here, we report two cases of CS during pregnancy with different clinical courses. Caesarean section was performed in Patient 1 at 26 weeks of gestation due to uncontrollable hypertension and severe FGR. She was diagnosed with CS after delivery. Patient 2 exhibited severe hypertension and was diagnosed with CS at 19 weeks of gestation. Surgical treatment significantly decreased her blood pressure, and she delivered a mature baby at 39 weeks of gestation. For Patient 1, microscopic findings of the placenta were compatible with preeclampsia, while the placenta of Patient 2 showed almost normal pathological findings, although the placenta was extremely small. These two cases indicate that, while maternal hypertension might affect placental growth, placental function could be recuperated by appropriate blood pressure control in the early stage of gestation.