Blood pressure cutoffs at 11-13 weeks of gestation and risk of preeclampsia.

BACKGROUND: A parallel has been drawn between first-trimester placental vascular maturation and maternal cardiovascular adaptations, including blood pressure. Although 140/90 mm Hg is well-accepted as the threshold for chronic hypertension in the general obstetric population in early pregnancy, a different threshold could apply to stratify the risk of adverse outcomes, such as preeclampsia. This could have implications for interventions, such as the threshold for initiation of antihypertensive therapy and the target blood pressure level. OBJECTIVE: We evaluated the relationship between various blood pressure cutoffs at 11-13 weeks of gestation and the development of preeclampsia, overall and according to key maternal characteristics. STUDY DESIGN: This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals, 2006-2020. Blood pressure at 11-13 weeks of gestation was classified according to American College of Cardiology/American Heart Association categories (mm Hg) as (1) normal blood pressure (systolic <120 and diastolic <80), (2) elevated blood pressure (systolic ≥120 and diastolic <80), stage 1 hypertension (systolic ≥130 or diastolic 80-89), and stage 2 hypertension (systolic ≥140 or diastolic ≥90). For blood pressure category thresholds and the outcome of preeclampsia, the following were calculated overall and across maternal age, body mass index, ethnicity, method of conception, and previous pregnancy history: detection rate, screen-positive rate, and positive and negative likelihood ratios, with 95% confidence intervals. A P value of <.05 was considered significant. RESULTS: There were 137,458 pregnancies screened at 11-13 weeks of gestation. The population was ethnically diverse, with 15.9% of Black ethnicity, 6.7% of South or East Asian ethnicity, and 2.7% of mixed ethnicity, with the remainder of White ethnicity. Compared with normal blood pressure, stage 2 hypertension was associated with both preterm preeclampsia (0.3% to 4.9%) and term preeclampsia (1.0% to 8.3%). A blood pressure threshold of 140/90 mm Hg was good at identifying women at increased risk of preeclampsia overall (positive likelihood ratio, 5.61 [95% confidence interval, 5.14-6.11]) and across maternal characteristics, compared with elevated blood pressure (positive likelihood ratio, 1.70 [95% confidence interval, 1.63-1.77]) and stage 1 hypertension (positive likelihood ratio, 2.68 [95% confidence interval, 2.58-2.77]). There were 2 exceptions: a blood pressure threshold of 130/80 mm Hg was better for the 2.1% of women with body mass index <18.5 kg/m2 (positive likelihood ratio, 5.13 [95% confidence interval, 3.22-8.16]), and a threshold of 135/85 mm Hg better for the 50.4% of parous women without a history of preeclampsia (positive likelihood ratio, 5.24, [95% confidence interval, 4.77-5.77]). There was no blood pressure threshold below which reassurance could be provided against the development of preeclampsia (all-negative likelihood ratios ≥0.20). CONCLUSION: The traditional blood pressure threshold of 140/90 mm Hg performs well to identify women at increased risk of preeclampsia. Women who are underweight or parous with no prior history of preeclampsia may be better identified by lower thresholds; however, a randomized trial would be necessary to determine any benefits of such an approach if antihypertensive therapy were also administered at this threshold. No blood pressure threshold is reassured against the development of preeclampsia, regardless of maternal characteristics.

Blood Pressure and Heart Rate Variability and the Impact on Pregnancy Outcomes: A Systematic Review.

BACKGROUND: Long-term (visit-to-visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given the limitations of relying solely on blood pressure level to identify pregnancies at risk, long-term (visit-to-visit) BPV or HRV may provide additional diagnostic/prognostic counsel. To address this, we conducted a systematic review to examine the association between long-term BPV and HRV in pregnancy and adverse maternal and perinatal outcomes. METHODS AND RESULTS: Databases were searched from inception to May 2023 for studies including pregnant women, with sufficient blood pressure or heart rate measurements to calculate any chosen measure of BPV or HRV. Studies were excluded that reported short-term, not long-term, variability. Adjusted odds ratios were extracted. Eight studies (138 949 pregnancies) reporting BPV met our inclusion criteria; no study reported HRV and its association with pregnancy outcomes. BPV appeared to be higher in women with hypertension and preeclampsia specifically, compared with unselected pregnancy cohorts. Greater BPV was associated with significantly more adverse pregnancy outcomes, particularly maternal (gestational hypertension [odds ratio range, 1.40-2.15], severe hypertension [1.40-2.20]), and fetal growth (small-for-gestational-age infants [1.12-1.32] or low birth weight [1.18-1.39]). These associations were independent of mean blood pressure level. In women with hypertension, there were stronger associations with maternal outcomes but no consistent pattern for perinatal outcomes. CONCLUSIONS: Future work should aim to confirm whether BPV could be useful for risk stratification prospectively in pregnancy, and should determine the optimal management path for those women identified at increased risk of adverse outcomes.

Blood pressure measurement and adverse pregnancy outcomes: A cohort study testing blood pressure variability and alternatives to 140/90 mmHg.

OBJECTIVE: To examine the association with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit-to-visit BP variability (BPV), adjusted for BP level. DESIGN: An observational study. SETTING: Analysis of data from the population-based UK Southampton Women's Survey (SWS). POPULATION OR SAMPLE: 3003 SWS participants. METHODS: Generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV] and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below. MAIN OUTCOME MEASURES: Gestational hypertension, severe hypertension, pre-eclampsia, preterm birth (PTB), small-for-gestational-age (SGA) infants, neonatal intensive care unit (NICU) admission. RESULTS: A median of 11 BP measurements were included per participant. For BP at ≥20 weeks' gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90 mmHg was a good rule-out test (negative LR <0.20) for pre-eclampsia and BP ≥140/90 mmHg a good rule-in test (positive LR >8.00) for the condition. BP ≥160/110 mmHg could rule-in PTB, SGA infants and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre-eclampsia, PTB, SGA and NICU admission (adjusted RRs 1.05-1.39). CONCLUSIONS: While our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes.

Synchronous Urinary Bladder Urothelial Carcinoma and Transitional Cell Carcinoma of the Ovary: A Case Report.

Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian tumours defined as a tumour composed of epithelial elements, histologically resembling urothelium and its neoplasms. Ovarian metastases from primary urinary tract carcinomas are rare. The differential diagnosis of primary TCC of the ovary versus metastatic bladder TCC is challenging because of histological similarity. We present the case of a 49-year-old premenopausal woman who was initially diagnosed with non-invasive papillary urothelial carcinoma of bladder (NIPUC) and after 2 years with a synchronous TCC of the ovary while being investigated for suspected relapse. She underwent a radical cystectomy, total hysterectomy, bilateral salpingo-oopharectomy, and pelvic lymph node dissection. The final diagnosis of synchronous NIPUC of the bladder and TCC of the ovary was made by histopathology and immunohistochemical studies.

The tools used to assess psychological symptoms in women and their partners after termination of pregnancy for fetal anomaly: A scoping review.

Termination of pregnancy for fetal anomaly (TOPFA) represents a uniquely distressing and challenging situation for women and their partners. Having appropriate screening tools that best highlight the psychological symptoms experienced by women and their partners is important to be able to guide care. Many validated screening tools for pregnancy and psychological distress exist, with variation in the ease of application and the domains addressed in each. We undertook a scoping review of tools used to assess psychological symptoms in women and/or partners after TOPFA. Of 909 studies, 93 studies including 6248 women and 885 partners were included. Most of the included studies assessed symptoms within six months of TOPFA and highlighted high rates of distress, grief and trauma symptoms. There was broad variation in the tools used between studies and the timing of their implementation. Focusing the care of women and families who undergo TOPFA to validated, broadly available and easily applied screening tools that assess a range of psychological symptoms is key in being able to identify the potential interventions that may be of benefit.

The 2017 American College of Cardiology and American Heart Association blood pressure categories in the second half of pregnancy-a systematic review of their association with adverse pregnancy outcomes.

OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs when used within pregnancy. DATA SOURCES: Electronic databases were searched (2017-2021) for measurements of blood pressure in pregnancy at >20 weeks, classified according to the 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. Blood pressure was categorized as "normal" (systolic blood pressure of <120 mm Hg and diastolic blood pressure of <80 mm Hg), "elevated blood pressure" (systolic blood pressure of 120-129 mm Hg and diastolic blood pressure of <80 mm Hg), "stage 1 hypertension" (systolic blood pressure of 130-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg), and "stage 2 hypertension" (systolic blood pressure of ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg). STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at or above 20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated accounting for gestation. RESULTS: There were 12 included studies. The American College of Cardiology or American Heart Association blood pressure categories were determined from peak blood pressures at any point from 20 weeks of gestation and at specific gestational ages (20-27, 28-32, or 33-36 weeks of gestation), as available. A higher (vs normal) blood pressure category was consistently associated with adverse outcomes. The strength of association between blood pressure categories and adverse outcomes was the greatest with "stage 2 hypertension" (blood pressure of ≥140/90 mm Hg). The results were similar when peak blood pressure was reported either at any time from 20 weeks of gestation or within gestational age groups (as above). No blood pressure category was useful as a diagnostic "rule-out test" for adverse outcomes, as all negative likelihood ratios were ≥0.2. Only "stage 2 hypertension" was useful as a "rule in-test," with positive likelihood ratios of ≥5.0, for maximum blood pressure at >20 weeks of gestation for preeclampsia and blood pressure within any gestational age groups for preeclampsia, eclampsia, stroke, maternal death, and stillbirth. CONCLUSION: From 20 weeks of gestation, blood pressure thresholds of 140 mm Hg (systolic) and 90 mm Hg (diastolic) were useful in identifying women at increased risk of adverse pregnancy outcomes, irrespective of the specific gestational age at blood pressure measurement. Lowering the blood pressure threshold for abnormal blood pressure at >20 weeks of gestation would not assist clinicians in identifying women at heightened maternal or perinatal risk. No American College of Cardiology or American Heart Association blood pressure threshold can provide reassurance that women are unlikely to develop adverse outcomes.

American College of Cardiology and American Heart Association blood pressure categories-a systematic review of the relationship with adverse pregnancy outcomes in the first half of pregnancy.

OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs. DATA SOURCES: We systematically searched electronic databases (from 2017 to 2021) for reports of blood pressure measurements in pregnancy, classified according to 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at <20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated. RESULTS: Of 23 studies included, there was a stepwise relationship between the American College of Cardiology and American Heart Association blood pressure category (when compared with normal blood pressure of <120/80 mmHg) and the strength of the association with preeclampsia. The category of elevated blood pressure had a risk ratio of 2.0 (95% prediction interval, 0.8-4.8), the stage 1 hypertension category had a risk ratio of 3.0 (95% prediction interval, 1.1-8.5), and the stage 2 hypertension category had a risk ratio of 7.9 (95% prediction interval, 1.8-35.1). Between-study variability was related to the magnitude of the association with stronger relationships in larger studies at low risk of bias and with unselected populations with multiple routine blood pressure measurements. None of the systolic blood pressure measurements of <120 mmHg, <130/80 mmHg, or <140/90 mmHg were useful to rule out the development of preeclampsia (all negative likelihood ratios >0.2). Only a blood pressure measurement of ≥140/90 mmHg was a good predictor for the development of preeclampsia (positive likelihood ratio, 5.95). The findings were similar for other outcomes. CONCLUSION: Although a blood pressure of 120 to 140 over 80 to 90 mmHg at <20 weeks gestation is associated with a heightened risk for preeclampsia and adverse pregnancy outcomes and may assist in risk prediction in multivariable modelling, lowering the diagnostic threshold for chronic hypertension would not assist clinicians in identifying women at heightened risk.

Primary sclerosing cholangitis: A rare cause of liver dysfunction in pregnancy.

Primary sclerosing cholangitis is an uncommon condition with few cases reported in pregnancy. We present the case and outcome of a 28-year-old female presenting in her second pregnancy with new onset liver dysfunction, eventually diagnosed with primary sclerosing cholangitis. She went into spontaneous preterm labour and delivered a healthy infant but has subsequently continued to deteriorate and underwent a liver transplant 11 months post-delivery.

Change in timing of induction protocol in nulliparous women to optimise timing of birth: results from a single centre study.

BACKGROUND: Induction of labour (IOL) is a common obstetric intervention. When planning IOL, especially in women at risk for complications at delivery, the aim should be for delivery to occur when senior staff are available to optimise safe care. METHODS: A change in timing of IOL protocol at our institution was introduced in November 2018 aiming to increase births occurring "in-hours" defined as 08:00 to 20:00 h. This retrospective cohort study compares the odds of "in-hours" birth before and after the intervention and the association on birth outcomes. The study compared outcomes during the new IOL pathway period to a historical birth cohort from January to December 2017. Inclusion criteria were nulliparous women undergoing planned IOL at term with a cephalic singleton pregnancy. Logistic regression was used to compare odds of in-hours birth for the 2 periods with adjustment for maternal age at delivery, gestation, more than 2 cervical ripening agents required, undergoing IOL for post-dates pregnancy, mode of birth, whether or not IOL proceeded according to planned protocol and missing values using multiple imputation. RESULTS: The rate of deliveries occurring in-hours were higher following the intervention; n = 118/285 (45.6%) pre-intervention versus n = 251/470 (53.4%) post-intervention; adjusted OR = 1.47, 95% CI = 1.07-2.01, p = 0.02). The percentage of caesarean sections (CS) occurring in-hours was significantly lower in the pre-intervention group n = 71/153 (28.3%) compared with the post intervention group = 35/132(46.4%) (p < 0.001)). The rate of CS was higher in the pre intervention n = 132/285(46.3%) compared with the post intervention group n = 153/470 (32.4%)). CONCLUSIONS: The change in induction procedures was associated with a significantly higher rate of births occurring in-hours and a lower rate of overall of CS. This policy change led to a better pattern of timing of birth for nulliparous women undergoing IOL.

A comparison of praevia and non-praevia outcomes in placenta accreta spectrum cases: A single centre analysis.

BACKGROUND: Placenta accreta spectrum (PAS) causes severe maternal morbidity and mortality. Antenatal diagnosis can optimise maternal outcomes and reduce the risk of complications. PAS cases where the placenta is not low lying are suggested to be more difficult to diagnose antenatally and are potentially associated with different outcomes. AIM: The aim was to compare factors associated with births in PAS pregnancies with and without placenta praevia at a single tertiary centre over 15 years. MATERIALS AND METHODS: A retrospective review of all births complicated by PAS was conducted from a site-specific database. Cases with and without a placenta praevia were analysed to compare differences in maternal risk factors, outcomes and histological diagnosis. RESULTS: Between June 2006 and July 2020 there were 134 cases of PAS, 106 with placenta praevia. Cases without praevia were less likely to have a history of previous caesarean section and to be admitted for delivery planning or with antepartum haemorrhage. A higher proportion of cases without praevia were delivered at term, with no overall difference in emergency or elective deliveries. There was a significantly lower rate of hysterectomy in the non-praevia group. The overall estimated blood loss was significantly lower in those without praevia. CONCLUSION: Suspected PAS without placenta praevia is at lower risk of hysterectomy and massive blood loss. The management approach can be tailored accordingly, with good operative outcomes with transverse abdominal and uterine incisions. Antenatal diagnosis can be difficult to accurately predict the degree of invasion, and a higher level of suspicion is required.

The multidisciplinary management of placenta accreta spectrum (PAS) within a single tertiary centre: A ten-year experience.

INTRODUCTION: Placenta accreta spectrum (PAS) covers a spectrum of placental adherence abnormalities: placenta accreta, increta and percreta. PAS is associated with significant maternal morbidity and mortality. Studies have shown the importance of multidisciplinary teamwork in the management of PAS. AIM: This study was designed to describe the maternal and neonatal morbidity and mortality associated with PAS in our centre over a ten-year period. METHODS: A retrospective cohort study was conducted of pregnancies complicated by PAS between February 2006 and January 2016 at Flinders Medical Centre (FMC), South Australia. Electronic and medical records were examined to obtain patient demographics, antenatal and surgical, findings and postnatal outcomes. RESULTS: There were 67 PAS cases with an overall incidence of 2.3 per 1000 deliveries. Three cases were excluded due to incomplete information. Of the remaining 64 cases, 56 women were antenatally diagnosed. Sixty cases were confirmed to be invasive at delivery; 28 accreta (superficial) and 32 increta/percreta (deep) cases. The four cases with no invasion at delivery were suspected antenatally to have PAS. The median (Q1, Q3) number of caesarean sections in this cohort was 2 (1, 3). Deep invasion is significantly associated with increased bleeding, intensive care unit admission, surgical complications and an extended postpartum stay. CONCLUSION: The incidence of PAS at FMC is high as it is the state's tertiary referral centre. While PAS is associated with increased morbidity, thorough perioperative planning by a multidisciplinary team is crucial for excellent patient outcomes.

Beta-catenin and transforming growth factor beta have distinct roles regulating fibroblast cell motility and the induction of collagen lattice contraction.

BACKGROUND: beta-catenin and transforming growth factor beta signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor beta is partially mediated by beta-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of beta-catenin and its interaction with transforming growth factor beta in cell motility and the induction of collagen lattice contraction. RESULTS: Floating three dimensional collagen lattices seeded with cells expressing conditional null and stabilized beta-catenin alleles, showed a modest negative relationship between beta-catenin level and the degree of lattice contraction. Transforming growth factor beta had a more dramatic effect, positively regulating lattice contraction. In contrast to the situation in the regulation of cell proliferation, this effect of transforming growth factor beta was not mediated by beta-catenin. Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results. Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect. CONCLUSION: This data demonstrates the complexity of the interaction of various signaling pathways in the regulation of cell behavior during wound repair. Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms. There is unlikely to be a single signaling pathway that acts as master regulator of fibroblast behavior in wound repair. beta-catenin plays dominant role regulating cell motility, while transforming growth factor beta plays a dominant role regulating the induction of collagen lattice contraction.