Objective: Chronic hypertension is associated with an increased risk of preeclampsia and fetal growth restriction (FGR). Although recent guidelines recommend a systolic blood pressure (sBP) between 110 and 140 mmHg, the influence and goal of sBP control during early pregnancy have not been elucidated. This pilot study aimed to clarify the effects of tight hypertension control before 20 weeks’ gestation on pregnancy outcomes.

Methods: This retrospective study analyzed 37 cases of singleton pregnancies managed at our institution between January 2007 and June 2018, which were diagnosed with chronic hypertension either before pregnancy or within 14 weeks’ gestation. Patients were subdivided according to sBP between 16–20 weeks’ gestation: Group 1, sBP<130 mmHg; Group 2, 130≤sBP<140 mmHg; and Group 3, sBP≥140 mmHg. Between-group differences were assessed for the risk of preterm birth, FGR, and superimposed preeclampsia.

Results: Overall, 21 cases (60%) received antihypertensive medication before 20 weeks’ gestation. On comparing Group 1 (n=16) with Group 2 (n=10) and Group 3 (n=11), a significantly longer gestational duration (38.6±2.3, 34.8±4.6, and 30.9±3.8, respectively) and higher Z score (0.19±0.94, −0.97±1.1, and −2.0±1.4, respectively) were observed in Group 1. Moreover, the incidence of superimposed preeclampsia was significantly higher in Group 2 (60%) and Group 3 (72%), compared with Group 1 (31%).

Conclusion: Introducing tight sBP control before 16 weeks’ gestation was associated with good pregnancy outcomes in patients with chronic hypertension.

Objective: Advanced maternal age (AMA) is increasingly becoming a relevant issue due to late marriage and advances in reproductive technology. AMA complicates adverse pregnancy outcomes including hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), and stillbirth. However, the mechanism underlying the relationships between AMA and these pathological conditions remains unclear. Here, we established a mouse model of AMA using aged pregnant ICR mice, investigated its phenotypes, and analyzed the profiles of HDP-related biomarkers.

Methods: AMA model mice were pregnant Jcl:ICR mice aged over six months. Control mice were pregnant mice aged 8–13 weeks. We first analyzed phenotypes including fetal and placental weight, litter size, and percentage of intrauterine fetal death (IUFD). We then measured blood pressure during pregnancy and analyzed the profiles of HDP-related biomarkers including soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Finally, we assessed the evidence underlying placental senescence that could affect blood pressure in the AMA model.

Results: AMA mice presented with the same complications as their human counterparts, including declining fertility, FGR, and a higher rate of IUFD. AMA mice exhibited increased systolic blood pressure at late gestation, which subsequently normalized after delivery, as in human HDP patients. Both AMA mice and human HDP patients exhibited low serum sFlt-1 levels in late gestation despite being complicated with HDP and placental dysfunction (AMA group vs control group (mice): 16,800.0±10,709.5 vs 26,611.9±8,702.0 pg/mL, P<0.01; (human): 8,507.6±3,298.7 vs 14,816.9±5,413.5 pg/mL, P<0.05). p53 expression was significantly increased in the placenta of AMA mice.

Conclusion: Phenotypes of AMA mice resembled those of their human counterparts, including declining fertility, FGR, IUFD, and HDP. We also identified novel sFlt-1 profiles in aged HDP patients and AMA mice that were significantly lower than that in young individuals and mice. Our findings suggest that the pathogenesis of HDP in AMA may differ relative to that in individuals with younger maternal age.

Due to advancements in our elucidation of the pathogenesis and pathology of hypertension disorder of pregnancy (HDP), we now understand that the disease develops in two stages. In the first stage, placental hypoxia and ischemia occur due to failure of the vascular wall, and the muscle elastic membrane of the spiral artery is replaced by trophoblasts in the placental bed (i.e., remodeling of the spiral artery) in the course of a normal pregnancy early in gestation. This hypoxia and ischemia enhances choriocyte production of anti-angiogenesis factors like soluble Flt-1 and soluble endoglin. In the second stage, this causes vascular endothelial damage in the maternal body and the placenta, leading to the development of HDP.

Thus far, no treatment has been available to address HDP in patients, and the only course of action has been careful monitoring and consideration of the maternal body and fetus, particularly toward the end of the gestation period. However, in recent years, reports have emerged on the treatment and prevention of HDP, involving Pravastatin, Aspirin and PDE-5 inhibitors, among others. Currently, we may be at a branching point between prevention and treatment of HDP. Elucidation of the two-stage pathogenesis as described previously has contributed greatly to the development of the new treatment.

When severe, HDP can cause damage to important organs such as the kidneys, liver and brain, and thus endangers the life of the mother. In addition, since pregnancy itself is the cause of HDP, the arrival of the end of the pregnancy is the only curative treatment for it; that said, if HDP becomes severe when the fetus is still premature, management of this condition becomes very difficult. For this reason, developing methods of intervention to prevent and treat HDP onset would not only save the mother, but also improve substantially the fetal prognosis.

In conjunction with other attempts worldwide to address this matter, we feel that Japan should also establish clinical trials and conduct basic research pertaining to this condition. To this end, we propose the theme of “Development of methods for prevention and treatment of hypertension disorder of pregnancy.”

Date: November 2^nd, 2018

Location: Senri Life Science Center, Osaka

Participants: Drs. Kimura, Miyamoto, Ikeda, Yamazaki, Takahashi, Otsuki, and Ohno

This committee meeting was established by four societies (JSOG, JSSHP, JNS, and JSS) in 2013. The committee acts positively to address issues, such as the following, and has yielded some results.

JSOG: Japan Society of Obstetrics and Gynecology, JSSHP: Japan Society for the Study of Hypertension in Pregnancy, JNS: Japan Neurosurgical Society, JSS: Japan Stroke Society

Dates: November 2 & 3, 2018

Venue: Senri Life Science Center (Osaka)

Congress President: Tadashi Kimura (Professor, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan)

The 39th Annual Congress of the Japan Society for the Study of Hypertension in Pregnancy was held at the Senri Life Science Center (Osaka) for 2 days from November 2 (Fri.) to 3 (Sat.), 2018. With the help of so many, we were pleased to have 423 participants in this year’s Congress, exceeding our expectations. The following programs were held successfully.

We discuss the contemporary practice of forceps delivery in Scotland, a country with affluent experience in operative vaginal birth. Globally, the popularity of forceps has significantly declined and undeniably it is considered by many a lost art. As a result, the volume and the complexity of the attempted forceps deliveries have lessened and more women undergo high-risk second-stage caesarean sections. Therefore, we have to draw our attention to realistic alternatives such as reinstating the skill of assisted delivery. Introducing these techniques in modern obstetrics can be a challenging task. The rates of forceps deliveries remain stable in Scotland, despite the opposite experience from most other countries. This paper is based on reviewing relevant guidelines and official national statistics. Forceps still have a place in modern obstetric practice in order to shorten labour when clinically indicated. Obstacles to forceps delivery are broadly due to the potential harm and the subsequent related medico-legal implications. Since the availability of specialists with substantial experience has been reduced, it sounds of paramount importance to conserve the learning of this valuable obstetric technique. Even more, initiatives that appoint future generations of obstetricians with expertise in performing forceps deliveries are an urgent educational priority. International recommendations and high-quality local workshops can facilitate this path.

Neuraxial anesthesia is a gold standard anesthetic technique employed for labor analgesia and cesarean section. Spinal cord injury can occur if the needle insertion is performed above the recommended lumbar spine level. Pre-procedural lumbar spine ultrasound scanning can provide several benefits, such as increasing first attempt success rate, reducing the number of attempts, and reducing redirection of the needle.

Pulmonary aspiration during general anesthesia is a fatal complication which remains a cause of maternal mortality. Gastric content volume (GCV) is an important component related to the risk of regurgitation followed by aspiration. There is growing interest in the utility of bedside gastric ultrasound to assess GCV in non-obstetric and obstetric populations.

This review discusses trends in mode of breech delivery in Japan. Recently, primary elective cesarean delivery rates for singleton breech pregnancies have markedly increased due to medical counseling and maternal requests. However, breech extraction skills should be preserved and passed on to future generations of obstetricians. Vaginal breech delivery may be considered if well-trained and full-time medical staff with experience performing breech deliveries are available and comprehensive informed consent is obtained. As specialists of obstetrics and gynecology, it may be necessary to acquire rudimentary techniques for vaginal breech delivery in order to perform fair and objective informed consent procedures regarding the mode of breech delivery.

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.