PCSK9 inhibitor use during pregnancy in a case of familial hypercholesterolemia complicated with coronary artery disease.

Limited data have been reported on the use of proprotein convertase subtilisin/kexin type 9 (PCSK 9) inhibitors during pregnancy in women with familial hypercholesterolemia (FH). Here, we present the first case of initiating evolocumab (PCSK9 inhibitor) in a compound heterozygous FH mother. The patient was a 34-year-old primipara with severe dyslipidemia and a history of coronary artery bypass surgery. An elevated low-density lipoprotein cholesterol (LDL-C) level of 420 mg/dL was detected in the first trimester and persistently increased throughout pregnancy. Evolocumab was administered at 31 and 35 weeks of gestation, showing a positive effect on stabilizing LDL-C levels. Planned delivery with labor analgesia was performed at 38 + 4 weeks. Both the mother and infant were discharged without any notable complications. Hence, evolocumab, an IgG2 monochromatic antibody with little placental permeability, may be an alternative medication with limited influence on infants. Further studies are needed to assess the safety of evolocumab administration during pregnancy.

Diet Quality and Its Relationship with Weight Characteristics in Pregnant Japanese Women: A Single-Center Birth Cohort Study.

Maternal underweight and inadequate gestational weight gain (GWG) are problems in Japan. However, increases in food intake aimed at weight gain alone are not sufficient for mother-child health. This study assessed diet quality based on the 3-day dietary records of pregnant women in an urban area of Japan in order to show the importance of evaluating diet quality, using the Nutrient-Rich Food Index 9.3 (NRF9.3), which is one metric based on nutrition profiling, and the Japanese Food Guide Spinning Top (JFGST). After excluding misreporters of energy intake, we stratified women (n = 91) by pre-pregnancy body mass index (BMI) and determined energy intake, diet quality status, and their relationship with GWG. Intakes of carbohydrate-containing staple foods, vegetable dishes, and fruit were insufficient regardless of BMI. Most of the underweight women with inadequate GWG had insufficient energy intake but high diet quality, as assessed by NRF9.3. In contrast, most women who consumed energy within the recommended range had low diet quality and gained weight at inappropriate levels. These results highlight the importance for pregnant Japanese women to maintain diet quality through a nutrient-dense diet, while simultaneously increasing energy intake after evaluation of their individual diet quality.

Investigation of exacerbating factors for postpartum hair loss: a questionnaire-based cross-sectional study.

Background: Although postpartum hair loss is believed to be common, there is little reliable information. Objective: We sought to examine the factors that were associated with postpartum hair loss and to elucidate factors correlated with its pathogenesis. Methods: We carried out a questionnaire-based cross-sectional study. The study participants were women who delivered at 2 facilities and filled the questionnaire 10-18 months after delivery. The survey questionnaire included baseline characteristics, pregnancy details, delivery, childcare, and extent of postpartum hair loss. We divided participants into 2 groups according to the absence or presence of postpartum hair loss and performed logistic regression analyses. Results: A total of 331 (21.0%) responses were analyzed; among these 304 (91.8%) women had postpartum hair loss. The average time for the start, peak, and end of hair loss was 2.9, 5.1, and 8.1 months, respectively. Women with hair loss had an earlier time of delivery, a lower birth weight, a higher preterm labor rate, and longer-term breastfeeding. Logistical regression analyses revealed that longer-term breastfeeding and preterm labor were independent predictors of postpartum hair loss. The adjusted odds ratio for postpartum hair loss in women who ended breastfeeding 6-12 months postpartum versus those who ended it after 12 months or more was 5.96 (95% confidence interval [CI] [1.68, 21.09]) and 6.37 (95% CI [1.95, 20.76]) compared with those who stopped breastfeeding within 6 months postpartum. Limitations: Finer details such as pregnancy complications and delivery information may not be accurate since all results are based on questionnaire responses. There may be a sampling bias because women who suffer from postpartum hair loss may tend to participate more frequently. Conclusion: Over 90% of women experienced postpartum hair loss. Our data show that long-term breastfeeding and preterm labor correlate with postpartum hair loss.

Trimester-specific associations between extracellular vesicle microRNAs and fetal growth.

OBJECTIVE: Placenta-derived extracellular vesicles and their cargoes, especially microRNAs (EV-miRNAs), may contribute to fetal and placental development. During pregnancy, the levels of several maternal blood EV-miRNAs, including miRNAs of placental origin, vary among individuals and change throughout gestation. However, the effects of these miRNAs on fetal growth and trimester-specificity have not been fully elucidated. The purpose of this study is to test the hypothesis that the serum levels of two extracellular vesicles (EV)-miRNAs (miR-127-3p and miR-26b-5p), which may be involved in fetoplacental regulation, would be significantly associated with fetal growth in a trimester-specific manner. MATERIALS AND METHODS: This is a single-center birth cohort of maternal serum samples obtained at both the second and third trimesters. To minimize the influence of confounding factors, the analysis was limited to singleton vaginal deliveries, resulting in 27 participants being included in this study. EV RNAs were isolated using a membrane affinity method, and the relative expression levels of miR-127-3p and miR-26b-5p were measured using the RT-qPCR method with miR-484 as control. The associations between the two EV-miRNAs and fetal and placental growth were evaluated using a linear regression model and compared between the two trimesters. RESULTS: EV-miR-127-3p levels tended to correlate inversely with the z-scores of birth weight for gestational age (BWGA) and placental weight for gestational age (PWGA) in the second trimester, but not in the third trimester. EV-miR-26b-5p levels were positively associated with birth weight in the second trimester, but this association was weakened in the third trimester. CONCLUSION: Our results suggest a trimester-specific association of circulating miRNA levels with fetal and placental growth. The precise roles of EV-miR-127-3p and EV-miR-26b-5p in fetal and placental development warrant further investigation.

Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data.

BACKGROUND: Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP. METHODS: Using a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only "vasculature-related" BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity. RESULTS: We observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of "vasculature-related" BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation. CONCLUSIONS: Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.

Application of the Nutrient-Rich Food Index 9.3 and the Dietary Inflammatory Index for Assessing Maternal Dietary Quality in Japan: A Single-Center Birth Cohort Study.

The maternal diet can potentially influence the life-course health of the child. A poor-quality maternal diet creates nutrient deficiencies and affects immune-metabolic regulation during pregnancy. The nutrient-based overall dietary quality can be assessed using the Nutrient-Rich Food Index 9.3 (NRF9.3), which measures adherence to the national reference daily values of nutrient intake. Pro- and anti-inflammatory nutrient intake can be assessed using the energy-adjusted dietary inflammatory index (E-DII), a comprehensive index of diet-derived inflammatory capacity. Using these indices, we assessed the overall dietary quality and inflammatory potential of pregnant women during mid-gestation in an urban area of Japan (n = 108) and found that there was a strong inverse correlation between the NRF9.3 and E-DII scores. Comparison of the scores among the tertiles of NRF9.3 or E-DII indicated that dietary fiber, vitamin C, vitamin A, and magnesium mainly contributed to the variability of both indices. Intake of vegetables and fruits was positively associated with high NRF9.3 scores and negatively associated with high E-DII scores, after adjustment for maternal age, pre-pregnancy body mass index, and educational level. Consistent with the previous studies that used dietary pattern analysis, this study also demonstrated that vegetables and fruits were the food groups chiefly associated with high dietary quality and low inflammatory potential among pregnant Japanese women.

Splenic artery aneurysm rupture during pregnancy: A case report of maternal and fetal survival.

INTRODUCTION: Pregnancy has been demonstrated as a significant risk factor of splenic artery aneurysm (SAA) formation and rupture. However, prompt diagnosis of SAA rupture in a pregnant patient showing acute abdomen has been practically challenging in light of its rarity and vague initial presentation. PRESENTATION OF CASE: A 40-year-old woman (gravida 1, para 0) at 35 weeks' gestation presented to the emergency department with upper abdominal pain and nausea. Because of fetal dysfunction, emergency caesarian section was performed by a Pfannenstiel incision. Following delivery, 400 g of hemorrhage was removed from the upper abdominal cavity. Computed tomography showed a 37-mm SAA associated with copious adjacent fluid. Although selective angiography did not demonstrate active extravasation, interventional isolation of the SAA was not performed because of multiple surrounding arteries. Relaparotomy with an upper midline incision was then performed. Sudden cardiac arrest occurred upon opening the lesser sac to irrigate clots, and cardiac massage and proximal and distal clamping of the SAA were required. Eventually, splenectomy with excision of the SAA and pancreatic tail was successfully performed, but gauze packing of the open surgical wound was required because of severe coagulopathy. Following removal of the packs and closure of the abdomen 2 days after splenectomy, the patient and infant satisfactorily recovered without sequelae. DISCUSSION: Given continual awareness of abdominal vascular collapse during pregnancy, undelayed diagnosis and safer intervention might be achieved. CONCLUSION: Awareness at initial presentation and multidisciplinary efforts might be essential to achieve maternal and fetal survival in SAA rupture during pregnancy.

Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1.

Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (n = 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including CPT1A intron 1 and SREBF1 intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of SREBF1 was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with CPT1A intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.