Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control. OBJECTIVE: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure. STUDY DESIGN: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure. RESULTS: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention. CONCLUSION: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Pregnancy environment, and not preconception, leads to fetal growth restriction and congenital abnormalities associated with diabetes.

Maternal diabetes can lead to pregnancy complications and impaired fetal development. The goal of this study was to use a mouse model of reciprocal embryo transfer to distinguish between the preconception and gestational effects of diabetes. To induce diabetes female mice were injected with a single high dose of streptozotocin and 3 weeks thereafter used as oocyte donors for in vitro fertilization (IVF) and as recipients for embryo transfer. Following IVF embryos were cultured to the blastocyst stage in vitro or transferred to diabetic and non-diabetic recipients. Diabetic and non-diabetic females did not differ in regard to the number of oocytes obtained after ovarian stimulation, oocytes ability to become fertilized, and embryo development in vitro. However, diabetic females displayed impaired responsiveness to superovulation. Reciprocal embryo transfer resulted in similar incidence of live fetuses and abortions, and no changes in placental size. However, fetuses carried by diabetic recipients were smaller compared to those carried by non-diabetic recipients, regardless hyperglycemia status of oocyte donors. Congenital abnormalities were observed only among the fetuses carried by diabetic recipients. The findings support that the diabetic status during pregnancy, and not the preconception effect of diabetes on oogenesis, leads to fetal growth restriction and congenital deformities.

Health Locus of Control Beliefs in Health Care Providers in the Pacific Basin.

As part of the strategic plan to improve preconception care, health care providers are advised to counsel women about developing a reproductive life plan. Women are asked think about whether they want to become pregnant and have children and if so, when they would like to do so. The utility of a reproductive life plan is based on the premise that an individual has control over their own health and reproduction. Less is known regarding the beliefs of health care providers which may be important for strategizing educational and training programs. We conducted this project to examine whether health care providers in the Pacific Basin region who are providing reproductive health care, believe they have control over their own health. The Multidimensional Health Locus of Control Scale was used to survey attendees of the Annual Title X Reproductive Health Conference in Saipan, Commonwealth of the Northern Marianas. The cohort of reproductive health care providers surveyed (n=21) showed high internal control scores with a mean of 29.9 (SD = 3.5) and a range of 21 to 36 (maximum score = 36) consistent with individuals who have a strong belief that their health is most influenced by their own behavior. Chance and "powerful others" scores were consistent with means noted in other studies of healthy individuals. Understanding providers' health beliefs can aid in designing and executing more effective interventions to improve reproductive health outcomes.

Human relaxins (RLNH1, RLNH2), their receptor (RXFP1) and fetoplacental growth.

Relaxin, a systemic and placental hormone, has potential roles in fetoplacental growth. Human placenta expresses two RLN genes, RLNH1 and RLNH2 Maternal obesity is common and is associated with abnormal fetal growth. Our aims were to relate systemic and cord blood RLNH2, placental RLNs and their receptor (RXFP1) with fetoplacental growth in context of maternal body mass index, and associations with insulin-like growth factor 2 (IGF2) and vascular endothelial growth factor A (VEGFA) in the same placentas. Systemic, cord blood and placental samples were collected prior to term labor, divided by prepregnancy body mass index: underweight/normal (N = 25) and overweight/obese (N = 44). Blood RLNH2 was measured by ELISA; placental RLNH2, RLNH1, RXFP1, IGF2 and VEGFA were measured by quantitative immunohistochemistry and mRNAs were measured by quantitative reverse transcription PCR. Birthweight increased with systemic RLNH2 only in underweight/normal women (P = 0.036). Syncytiotrophoblast RLNH2 was increased in overweight/obese patients (P = 0.017) and was associated with placental weight in all subjects (P = 0.038). RLNH1 had no associations with birthweight or placental weight, but was associated with increased trophoblast and endothelial IGF2 and VEGFA, due to female fetal sex. Thus, while systemic RLNH2 may be involved in birthweight regulation in underweight/normal women, placental RLNH2 in all subjects may be involved in placental weight. A strong association of trophoblast IGF2 with birthweight and placental weight in overweight/obese women suggests its importance. However, an association of only RLNH1 with placental IGF2 and VEGFA was dependent upon female fetal sex. These results suggest that both systemic and placental RLNs may be associated with fetoplacental growth.

Discrepancy Between Identification of Early-Term Elective Deliveries by Manual Chart Review and Data Vendor.

Elective delivery from 37 to 39 weeks gestation (early-term deliveries) is a Joint Commission National Quality Measure, and hospitals report on early-term elective delivery rates through Outcome Research Yields Excellence (ORYX) vendors. The objective of this study was to compare early-term elective deliveries, identified through ORYX vendors with those identified through manual chart review, the traditional method of medical record review. We reviewed early-term labor inductions and cesarean deliveries at a single hospital from June 1, 2010 to May 31, 2012. Rates of early-term elective deliveries identified by the data vendor were compared to physician chart review. Overall, the rate of elective deliveries by ORYX was 3% compared to 2% by physician chart review (RR 1.51 [95% CI 1.12-2.03], P < .001). Of the 116 elective early-term deliveries identified by vendor and/or chart review, vendors classified significantly more inductions and cesareans as elective (P < .001) and missed nine elective deliveries. Of the 107 deliveries identified as elective by ORYX, 62 (57.9%) were verified by chart review, including 69.0% of cesareans and 36.1% of inductions. Findings from this study suggest substantial discrepancy between identification of early-term elective deliveries by data vendors and physician chart review, and indicate that vendor-derived data may overestimate the number of electively delivered patients.

Visfatin/Nampt and SIRT1: Roles in Postterm Delivery in Pregnancies Associated With Obesity.

Visfatin is both a systemic adipocytokine and the cytosolic enzyme, nicotinamide phosphoribosyl transferase (Nampt). This is a longevity protein, which extends the lifespan of human cells by activating sirtuin 1 (SIRT1). In this study, we sought a role for these proteins in obese pregnant women, who experience more postterm deliveries. Thus, 78 women (26 lean, 24 overweight, and 28 obese) were recruited and maternal blood and placental tissue collected prior to term labor. Plasma levels were measured by enzyme-linked immunosorbent assay and quantitative immunohistochemistry used for placenta. We confirmed maternal plasma interleukin 6 increased according to prepregnancy body mass index (BMI; P < .0001) and showed a linear relationship between BMI and syncytiotrophoblast visfatin/Nampt (P = .021) but not with its levels in maternal plasma. Both systemic and placental visfatin/Nampt were significantly associated with placental SIRT1 levels (P = .028 and .017). Thus, higher visfatin/Nampt may prevent a labor-associated decrease in SIRT1 leading to postterm delivery in obesity.

Obesity and the challenges of ultrasound fetal abnormality diagnosis.

Prenatal ultrasound has become an essential clinical tool for aneuploidy screening, detection of fetal congenital anomalies, and assessment of fetal growth and well-being. Maternal obesity, an increasing global problem, has been shown to decrease the accuracy of ultrasound examination in high-risk pregnancy. The purpose of this review is to provide an evidenced-based perspective on the challenges of performing fetal ultrasound in obese women and to provide a practical guide on how to care for these patients in the ultrasound suite.

Systemic and placental leptin and its receptors in pregnancies associated with obesity.

This study aimed to gain new insights into both systemic and placental leptin and its receptors, with reference to the maternal prepregnancy body mass index (BMI). Thus, 84 women (29 lean, 24 overweight, and 31 obese) were recruited and maternal, cord blood, and placental tissues collected prior to term labor. Plasma levels were measured by enzyme-linked immunosorbent assay and for placenta, immunohistochemistry and messenger RNAs (mRNAs) were quantitated. We confirmed that maternal leptin increased linearly as the soluble receptor decreased with BMI (P = .001). Fetal leptin increased with maternal BMI (P = .02) and birth weight (P = .006) and was higher in female infants (P < .001). Placental mRNA levels of leptin and its receptors showed no change in BMI. However, we show a significant (P = .043) linear increase in leptin in the placental vascular endothelial cells with maternal obesity, while leptin in syncytiotrophoblast showed no statistical change. Leptin receptors localized to syncytiotrophoblast and intravillous macrophages and were unchanged with BMI.

Use of tenofovir disoproxil fumarate in highly viremic, hepatitis B mono-infected pregnant women.

BACKGROUND: Antiviral therapy in addition to immunoprophylaxis at birth has been shown to further reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic women. AIMS: The aim of this study was to describe the use of tenofovir disoproxil fumarate (TDF) prophylaxis to reduce maternal HBV DNA levels and potentially vertical transmission in highly viremic women. METHODS: After receiving IRB approval, we performed a retrospective chart review of mothers positive for hepatitis B surface antigen (HBsAg) who delivered between 2009 and 2012. We identified women with HBV DNA levels ≥6 log copies/mL who were treated with TDF in pregnancy. RESULTS: There were 22 women identified. The majority were of Micronesian ethnicity. All were negative for hepatitis C antibody and HIV infection. The median gestational age of TDF initiation was 31 weeks with a median duration of treatment of 45 days. There was a reduction in median HBV DNA levels from baseline 9.0 ± 2.0 to 5.4 ± 1.1 log copies/mL after treatment. There were five (22.7 %) preterm deliveries and five (22.7 %) cesarean deliveries. All infants received immunoprophylaxis at birth. Postnatal HBsAg testing at 9-12 months was available for 13 infants, 12 of which were negative. There was one case of perinatal transmission. CONCLUSIONS: This is the second published case series to date on the use of TDF prophylaxis in HBV mono-infected, highly viremic mothers. This series suggests the use of TDF in pregnancy reduces maternal HBV DNA levels and is well tolerated.

Third and fourth degree perineal injury after vaginal delivery: does race make a difference?

Severe perineal injury (third and fourth degree laceration) at the time of vaginal delivery increases the risk of fecal incontinence, chronic perineal pain, and dyspareunia.1-5 Studies suggest the prevalence of severe perineal injury may vary by racial group.6 The purpose of the current study was to examine rates of severe perineal injury in different Asian and Pacific Islander subgroups. A retrospective cohort study was performed among all patients who had a vaginal delivery at Queens Medical Center in Honolulu, Hawai'i between January 1, 2002 and December 31, 2003. Demographic and health related variables were obtained for each participant. Maternal race/ethnicity (Japanese, Filipino, Chinese, other Asian, Part-Hawaiian/Hawaiian, Micronesian, other Pacific Islander, Caucasian, multiracial [non-Hawaiian], and other) was self-reported by the patient at the time admission. The significance of associations between racial/ethnic groups and demographic and health related variables was determined using chi-square tests for categorical variables and analysis of variance for continuous factors. Multiple logistic regression was performed to adjust for potential confounders when examining severe laceration rates. A total of 1842 subjects met inclusion criteria. The proportion of severe perineal lacerations did not differ significantly between racial groups. In the multiple logistic regression analysis, operative vaginal delivery was related to both race and severe perineal laceration. However, despite adjusting for this variable, race was not associated with an increased risk of having a severe laceration (P = .70). The results of this study indicate the risk of severe perineal laceration does not differ based on maternal race/ethnicity.

Gestational diabetes and macrosomia by race/ethnicity in Hawaii.

BACKGROUND: Gestational diabetes (GDM) has been shown to have long-term sequelae for both the mother and infant. Women with GDM are at increased risk of macrosomia, which predisposes the infant to birth injuries. Previous studies noted increased rates of GDM in Asian and Pacific Islander (API) women; however, the rate of macrosomia in API women with GDM is unclear. The objective of this study was to examine the relationship between ethnicity, gestational diabetes (GDM), and macrosomia in Hawaii. METHODS: A retrospective cohort study was performed using Hawaii Pregnancy Risk Assessment Monitoring System (PRAMS) data. Data from 2009-2011, linked with selected items from birth certificates, were used to examine GDM and macrosomia by ethnicity. SAS-callable SUDAAN 10.0 was used to generate odds ratios, point estimates and standard errors. RESULTS: Data from 4735 respondents were weighted to represent all pregnancies resulting in live births in Hawaii from 2009-2011. The overall prevalence of GDM in Hawaii was 10.9%. The highest prevalence of GDM was in Filipina (13.1%) and Hawaiian/Pacific Islander (12.1%) women. The lowest prevalence was in white women (7.4%). Hawaiian/Pacific Islander, Filipina, and other Asian women all had an increased risk of GDM compared to white women using bivariate analysis. Adjusting for obesity, age, maternal nativity, and smoking, Asian Pacific Islander (API) women, which includes Hawaiian/Pacific Islander, Filipina, and other Asian women, had a 50% increased odds of having GDM compared to white women when compared using multivariate analysis. Among women with GDM, the highest prevalence of macrosomia was in white women (14.5%) while the lowest was in Filipina (5.3%) women. CONCLUSIONS: API women in Hawaii have increased rates of GDM compared to white women. Paradoxically, this elevated GDM risk in API women is not associated with an increased rate of macrosomia. This suggests the relationship between GDM and macrosomia is more complex in this population.

Perineal body length among different racial groups in the first stage of labor.

OBJECTIVE: Anatomic differences among racial groups may contribute to observed differences in the occurrence of severe perineal lacerations at the time of vaginal delivery. The purpose of this study was to identify differences in perineal body length between racial groups. METHODS: Perineal body length was measured in primigravid women aged 18 to 45 years who were admitted in labor. Women were classified into 1 of 6 racial groups: White, Filipino, Japanese, Chinese, Native Hawaiian, or Micronesian. The primary outcome, perineal body length, was compared using analysis of variance. RESULTS: A total of 200 women were recruited. There were no significant differences in perineal body length (P = 0.42) and severe perineal lacerations (P = 0.82) between the different racial groups. The mean (SD) perineal body length of women who had a severe laceration was 3.9 (0.5) versus 3.9 (0.6) cm in women who did not have a severe laceration (P= 0.98). CONCLUSION: Perineal body length does not seem to differ among the different racial groups studied and therefore an unlikely cause of racial variation in rates of severe perineal lacerations.

Postpartum follow-up rates before and after the postpartum follow-up initiative at Queen Emma Clinic.

OBJECTIVE: To study postpartum follow-up rates, as well as counseling opportunities, among Queen Emma Clinic patients before and after the implementation of the Queen Emma Clinic Postpartum Follow-up Initiative. METHODS: This was a retrospective chart review of 221 women who received prenatal care at the Queen Emma Clinic and gave birth between April 2006 and April 2008. In April 2007 the postpartum initiative was started. The primary outcome was the number of postpartum follow-up visits. Secondary outcomes included breastfeeding, contraceptive use, depression screening and referral, follow-up screening for patien ts with gestational diabetes and subsequent pregnancy. RESULTS: Postpartum follow-up rates were significantly higher after the Postpartum Follow-up Initiative (86.1% compared with 71.7%, P =.012). When comparing timing of follow-up, the first postpartum visit occurred approximately one week sooner in the post intervention group (2.96 weeks compared with 3.73 weeks, P=0.38) with no difference in timing of the second postpartum visit (6.62 weeks compared with 6.42 weeks, P=.72). In the post intervention group there were more patients breastfeeding at the first postpartum visit (28.7% compared with 16%, P=.015), as well as the second postpartum visit (28.7% compared with 12.3%, P=0.01). There were also more women using contraception in the post intervention group (84.3% compared with 71.7%, P=.009). There was no difference in depression screening or referral, follow-up screening for gestational diabetes, or timing of subsequent pregnancies. CONCLUSION: The Postpartum Follow-Up Initiative improved postpartum follow-up rates, as well as breastfeeding, and contraceptive use.