Methodological pluralism for better evaluations of complex interventions: lessons from evaluating an innovation platform in Australia.

Complex interventions, such as innovation platforms, pose challenges for evaluators. A variety of methodological approaches are often required to build a more complete and comprehensive understanding of how complex interventions work. In this paper, we outline and critically appraise a methodologically pluralist evaluation of an innovation platform to strengthen primary care for Aboriginal and Torres Strait Islander Australians. In doing so, we aim to identify lessons learned from the approach taken and add to existing literature on implementing evaluations in complex settings, such as innovation platforms. The pluralist design used four evaluation approaches-developmental evaluation, principles-focused evaluation, network analysis, and framework analysis-with differing strengths and challenges. Taken together, the multiple evaluation approaches yielded a detailed description and nuanced understanding of the formation, functioning and outcomes of the innovation platform that would be difficult to achieve with any single evaluation method. While a methodologically pluralist design may place additional pressure on logistical and analytic resources available, it enables a deeper understanding of the mechanisms that underlie complex interventions.

Acute Kidney Injury in Pregnancies Complicated by Late-Onset Preeclampsia with Severe Features.

OBJECTIVE: Acute kidney injury (AKI)-complicating pregnancy is used as a marker of severe maternal morbidity (SMM) and frequently associated with obstetric hypertensive disorders. We examined AKI in pregnancies complicated by late-onset preeclampsia with severe features (SPE) using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared outcomes of pregnancies with and without AKI and stratified by stage of disease. We further differentiated renal dysfunction at the time of admission and compared outcomes to those who developed AKI after admission. STUDY DESIGN: This was a retrospective cohort study of women with care established before 20 weeks and diagnosed with preeclampsia with severe features with delivery at ≥34 weeks. Women with chronic hypertension or suspected underlying renal dysfunction were excluded. KDIGO criteria were applied to stratify staging of renal disease. Demographics and perinatal outcomes were compared using Chi-square analysis and Wilcoxon's rank-sum test with p < 0.05 considered significant. RESULTS: From January 2015 through December 2019, a total of 3,515 women meeting study criteria were delivered. Of these, 517 (15%) women met KDIGO criteria for AKI at delivery with 248 (48%) having AKI at the time of admission and the remaining 269 (52%) after admission. Stratified by severity, 412 (80%) had stage 1 disease, 89 (17%) had stage II, and 16 (3%) had stage III. Women with AKI had higher rates of cesarean delivery (risk ratio [RR] = 1.3; 95% confidence interval [CI]: 1.17-1.44), postpartum hemorrhage (RR = 1.46; 95% CI: 1.29-1.66), and longer lengths of stay. Other associated outcomes included NICU admission (RR = 1.72; 95% CI: 1.19-2.48), 5-minute Apgar score ≤ 3 (RR = 5.11; 95% CI: 1.98-13.18), and infant length of stay. CONCLUSION: Of women with late preterm SPE, 15% were found to have AKI by KDIGO criteria. The majority (80%) of AKI was stage I disease, and approximately half of the cases were present by the time of admission. KEY POINTS: · AKI was found in 15% of our cohort with 80% stage I disease.. · Half of the cases of AKI were present on admission.. · Few adverse perinatal outcomes are associated with AKI..

Acute Fatty Liver of Pregnancy.

Acute fatty liver of pregnancy (AFLP) is a rare, but potentially fatal condition, characterized by hepatic failure typically in the third trimester of pregnancy that is associated with multiorgan involvement resulting in a number of clinical and laboratory abnormalities. The cornerstone of management of AFLP includes prompt recognition, preparation for delivery, and supportive care such as reversal of coagulopathy. Early diagnosis, prompted delivery, and supportive care have resulted in improved maternal morbidity and mortality. This review focuses on the epidemiology, etiology, clinical presentation, diagnosis, management, and resolution of AFLP.

Perinatal outcomes associated with abnormal cardiac remodeling in women with treated chronic hypertension.

BACKGROUND: Adverse maternal outcomes associated with chronic hypertension include accelerated hypertension and resultant target organ damage. One example is long-standing hypertension leading to maternal cardiac dysfunction. Our group has previously identified that features of such injury manifest as cardiac remodeling with left ventricular hypertrophy. Moreover, these features of cardiac remodeling identified in women with chronic hypertension during pregnancy were associated with adverse perinatal outcomes. Recent definitions of maternal cardiac remodeling using echocardiography have been expanded to include measurements of wall thickness. We hypothesized that these new features characterizing cardiac remodeling in women with chronic hypertension may also be associated with adverse perinatal outcomes. OBJECTIVE: There were 3 aims in this study of women with treated chronic hypertension during pregnancy: to (1) apply the updated definitions of maternal cardiac remodeling; (2) elucidate whether these features of cardiac remodeling were associated with adverse perinatal outcomes; and (3) determine which, if any, of the newly defined cardiac remodeling strata were most damaging when compared to women with normal cardiac geometry. STUDY DESIGN: This was a retrospective study of women with treated chronic hypertension during pregnancy delivered from January 2009 through January 2016. Cardiac remodeling was categorized by left ventricular mass index and relative wall thickness into 4 groups determined using the 2015 American Society of Echocardiography guidelines: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Perinatal outcomes were analyzed according to each category of cardiac remodeling compared with outcomes in women with normal geometry. RESULTS: A total of 314 women with treated chronic hypertension underwent echocardiography at a mean gestational age of 17.9 weeks. There were no differences between maternal age (P = .896), habitus (P = .36), or duration of chronic hypertension (P = .212) among the 4 groups. Abnormal cardiac remodeling was found in 51% and was significantly associated with increased rates of superimposed preeclampsia (P = .015), preterm birth (P < .001), and neonatal intensive care admission (P = .003). These outcomes reached the greatest significance when comparisons were made between eccentric hypertrophy and normal geometry. CONCLUSION: Using current American Society of Echocardiography guidelines, 51% of women with treated chronic hypertension during pregnancy have some degree of abnormal cardiac remodeling. Any suggestion of maternal cardiac remodeling, regardless of subtype, was associated with increased risks for superimposed preeclampsia and preterm birth with its resultant perinatal sequelae. Eccentric ventricular hypertrophy, previously thought to mimic exercise physiology, appears to be the most associated with adverse perinatal outcomes. Despite evidence of cardiac remodeling, ejection fraction was preserved.

Liver Injury in Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome Measured by Diffusion-Weighted Magnetic Resonance Imaging.

OBJECTIVE: The objective of this study was to evaluate acute liver injury (ALI) detected by diffusion-weighted magnetic resonance imaging (MRI) and the associated laboratory findings in women with hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. STUDY DESIGN: This was a retrospective, observational study of women with HELLP syndrome defined by serum aspartate aminotransferase (AST) levels ≥100 U/L and thrombocytopenia with platelets ≤100,000/µL. All women underwent MRI postpartum including diffusion-weighted imaging to estimate the volume of ALI with reconstructed apparent diffusion coefficient (ADC) maps. The ADC map and the volume of ALI were compared with laboratory abnormalities by Spearman's correlation analysis. RESULTS: From March 2013 through August 2015, 16 women with HELLP syndrome underwent MRI, and of these, 14 (88%) women had areas of increased signal intensity suggestive of ALI. Their median (range) maximum AST level was 262 (140-1,958) IU/L, and at the time of MRI, AST was 103 (36-1,426) IU/L. Both of these AST levels significantly correlated with ADC map as well as the volume of ALI (both p-values <0.001). CONCLUSION: Women with HELLP syndrome frequently exhibited areas of abnormal diffusion in the liver on diffusion-weighted MRI, suggestive of ALI. The extent of liver injury was significantly correlated with serum AST.

Frequency and consequences of ventricular hypertrophy in pregnant women with treated chronic hypertension.

BACKGROUND: Ventricular hypertrophy is a known sequela of long-standing chronic hypertension with associated morbidity and mortality. OBJECTIVE: We sought to assess the frequency and importance of left ventricular hypertrophy in gravidas treated for chronic hypertension during pregnancy. STUDY DESIGN: This was a retrospective study of pregnant women with chronic hypertension who were delivered at our hospital from January 2009 through February 2015. All women who were given antihypertensive therapy underwent maternal echocardiography and were managed in a dedicated, high-risk prenatal clinic. Left ventricular hypertrophy was defined using the criteria of the American Society of Echocardiography as left ventricular mass indexed to maternal body surface area with a value of >95 g/m2. Maternal and infant outcomes were then analyzed according to the presence or absence of left ventricular hypertrophy. RESULTS: Of 253 women who underwent echocardiography, 48 (19%) met criteria for left ventricular hypertrophy. Women in this latter cohort were significantly more likely to be African American (P = .031), but there were no other demographic differences. More than 85% of the entire cohort had a body mass index >30 kg/m2 and a third of all women had class III obesity with a body mass index of >40 kg/m2. Importantly, duration of chronic hypertension (P = .248) and gestational age at time of echocardiography (P = .316) did not differ significantly between the groups. Left ventricular function was preserved in both groups as measured by left ventricular ejection fraction (P = .303). Those with ventricular hypertrophy were at greater risk to be delivered preterm (P = .001), to develop superimposed preeclampsia (P = .028), and to have an infant requiring intensive care (P = .023) when compared with women without ventricular hypertrophy. These findings persisted after adjustment for age, race, and parity. The gestational age at delivery according to measured left ventricular size was also examined and with increasing ventricular mass there was a significant association with the severity of preterm birth (P < .001). CONCLUSION: Left ventricular hypertrophy was identified in 1 in 5 women given antepartum treatment for chronic hypertension. Further analysis showed that these women were at significantly greater risk for superimposed preeclampsia and its attendant perinatal sequelae of preterm birth.

Toxic effects of orally ingested oil from the Deepwater Horizon spill on laughing gulls.

The explosion of the Deepwater Horizon oil rig released, millions of gallons of oil into the environment, subsequently exposing wildlife, including numerous bird species. To determine the effects of MC252 oil to species relevant to the Gulf of Mexico, studies were done examining multiple exposure scenarios and doses. In this study, laughing gulls (Leucophaeus atricilla, LAGU) were offered fish injected with MC252 oil at target doses of 5 or 10mL/kg bw per day. Dosing continued for 27 days. Of the adult, mixed-sex LAGUs used in the present study, ten of 20 oil exposed LAGUs survived to the end of the study; a total of 10 of the oil exposed LAGUs died or were euthanized within 20 days of initiation of the study. Endpoints associated with oxidative stress, hepatic total glutathione (tGSH), oxidized glutathione (GSSG) and reduced glutathione (rGSH) significantly increased as mean dose of oil increased, while the rGSH:GSSG ratio showed a non-significant negative trend with oil dose. A significant increase in 3-methyl histidine was found in oil exposed birds when compared to controls indicative of muscle wastage and may have been associated with the gross observation of diminished structural integrity in cardiac tissue. Consistent with previous oil dosing studies in birds, significant changes in liver, spleen, and kidney weight when normalized to body weight were observed. These studies indicate that mortality in response to oil dosing is relatively common and the mortality exhibited by the gulls is consistent with previous studies examining oil toxicity. Whether survival effects in the gull study were associated with weight loss, physiologic effects of oil toxicity, or a behavioral response that led the birds to reject the dosed fish is unknown.

Dermal exposure to weathered MC252 crude oil results in echocardiographically identifiable systolic myocardial dysfunction in double-crested cormorants (Phalacrocorax auritus).

During the Deepwater Horizon Natural Resource Damage Assessment, gross morphologic cardiac abnormalities, including softer, more distensible musculature, were noted upon gross necropsy in hearts from laughing gulls and double-crested cormorants exposed to weathered MC252 crude oil. A species specific, echocardiographic technique was developed for antemortem evaluation of function that was used to evaluate and better characterize cardiac dysfunction. Control (n=12) and treated (n=13) cormorant groups of similar sex-ratio and ages were dermally treated with approximately 13ml of water or weathered MC252 crude oil, respectively, every 3 days for 6 dosages. This resulted in a low to moderate external exposure. Upon visualization and clinical assessment of the hearts of all test subjects, comprehensive diagnostic cardiographic measurements were taken twice, prior to oil application and after a 21day dermal oil exposure. Oil-treated birds showed a decrease in cardiac systolic function, as characterized by an increased left ventricular internal dimension-systole and left ventricular stroke volume as well as concurrent decreased left ventricular ejection fraction and left ventricular fractional shortening when compared to both control birds' and the treated birds' time zero values. These changes are indicative of a possible dilative cardiomyopathy induced by oil exposure, although further elucidation of possible collagen damage is recommended. Arrhythmias including tachycardia in two treated birds and bradycardia in all treated birds were documented, indicating further clinically significant abnormalities induced by MC252 oil that warrant further investigation. A statistically significant increase in free calcium concentration, important to muscular and neurologic function in treated birds was also noted. This study documents that weathered MC252 oil caused clinically significant cardiac dysfunction that could result in mortality and decrease recruitment.

Testing of an oral dosing technique for double-crested cormorants, Phalacocorax auritus, laughing gulls, Leucophaeus atricilla, homing pigeons, Columba livia, and western sandpipers, Calidris mauri, with artificially weather MC252 oil.

Scoping studies were designed to determine if double-crested cormorants (Phalacocorax auritus), laughing gulls (Leucophaues atricilla), homing pigeons (Columba livia) and western sandpipers (Calidris mauri) that were gavaged with a mixture of artificially weathered MC252 oil and food for either a single day or 4-5 consecutive days showed signs of oil toxicity. Where volume allowed, samples were collected for hematology, plasma protein electrophoresis, clinical chemistry and electrolytes, oxidative stress and organ weigh changes. Double-crested cormorants, laughing gulls and western sandpipers all excreted oil within 30min of dose, while pigeons regurgitated within less than one hour of dosing. There were species differences in the effectiveness of the dosing technique, with double-crested cormorants having the greatest number of responsive endpoints at the completion of the trial. Statistically significant changes in packed cell volume, white cell counts, alkaline phosphatase, alanine aminotransferase, creatine phosphokinase, gamma glutamyl transferase, uric acid, chloride, sodium, potassium, calcium, total glutathione, glutathione disulfide, reduced glutathione, spleen and liver weights were measured in double-crested cormorants. Homing pigeons had statistically significant changes in creatine phosphokinase, total glutathione, glutathione disulfide, reduced glutathione and Trolox equivalents. Laughing gulls exhibited statistically significant decreases in spleen and kidney weight, and no changes were observed in any measurement endpoints tested in western sandpipers.

Reprint of: Overview of avian toxicity studies for the Deepwater Horizon Natural Resource Damage Assessment.

The Oil Pollution Act of 1990 establishes liability for injuries to natural resources because of the release or threat of release of oil. Assessment of injury to natural resources resulting from an oil spill and development and implementation of a plan for the restoration, rehabilitation, replacement or acquisition of natural resources to compensate for those injuries is accomplished through the Natural Resource Damage Assessment (NRDA) process. The NRDA process began within a week of the Deepwater Horizon oil spill, which occurred on April 20, 2010. During the spill, more than 8500 dead and impaired birds representing at least 93 avian species were collected. In addition, there were more than 3500 birds observed to be visibly oiled. While information in the literature at the time helped to identify some of the effects of oil on birds, it was not sufficient to fully characterize the nature and extent of the injuries to the thousands of live oiled birds, or to quantify those injuries in terms of effects on bird viability. As a result, the US Fish and Wildlife Service proposed various assessment activities to inform NRDA injury determination and quantification analyses associated with the Deepwater Horizon oil spill, including avian toxicity studies. The goal of these studies was to evaluate the effects of oral exposure to 1-20ml of artificially weathered Mississippi Canyon 252 oil kg bw-1 day-1 from one to 28 days or one to five applications of oil to 20% of the bird's surface area. It was thought that these exposure levels would not result in immediate or short-term mortality but might result in physiological effects that ultimately could affect avian survival, reproduction and health. These studies included oral dosing studies, an external dosing study, metabolic and flight performance studies and field-based flight studies. Results of these studies indicated changes in hematologic endpoints including formation of Heinz bodies and changes in cell counts. There were also effects on multiple organ systems, cardiac function and oxidative status. External oiling affected flight patterns and time spent during flight tasks indicating that migration may be affected by short-term repeated exposure to oil. Feather damage also resulted in increased heat loss and energetic demands. The papers in this special issue indicate that the combined effects of oil toxicity and feather effects in avian species, even in the case of relatively light oiling, can significantly affect the overall health of birds.

Overview of avian toxicity studies for the Deepwater Horizon Natural Resource Damage Assessment.

The Oil Pollution Act of 1990 establishes liability for injuries to natural resources because of the release or threat of release of oil. Assessment of injury to natural resources resulting from an oil spill and development and implementation of a plan for the restoration, rehabilitation, replacement or acquisition of natural resources to compensate for those injuries is accomplished through the Natural Resource Damage Assessment (NRDA) process. The NRDA process began within a week of the Deepwater Horizon oil spill, which occurred on April 20, 2010. During the spill, more than 8500 dead and impaired birds representing at least 93 avian species were collected. In addition, there were more than 3500 birds observed to be visibly oiled. While information in the literature at the time helped to identify some of the effects of oil on birds, it was not sufficient to fully characterize the nature and extent of the injuries to the thousands of live oiled birds, or to quantify those injuries in terms of effects on bird viability. As a result, the US Fish and Wildlife Service proposed various assessment activities to inform NRDA injury determination and quantification analyses associated with the Deepwater Horizon oil spill, including avian toxicity studies. The goal of these studies was to evaluate the effects of oral exposure to 1-20ml of artificially weathered Mississippi Canyon 252 oil kg bw-1 day-1 from one to 28 days or one to five applications of oil to 20% of the bird's surface area. It was thought that these exposure levels would not result in immediate or short-term mortality but might result in physiological effects that ultimately could affect avian survival, reproduction and health. These studies included oral dosing studies, an external dosing study, metabolic and flight performance studies and field-based flight studies. Results of these studies indicated changes in hematologic endpoints including formation of Heinz bodies and changes in cell counts. There were also effects on multiple organ systems, cardiac function and oxidative status. External oiling affected flight patterns and time spent during flight tasks indicating that migration may be affected by short-term repeated exposure to oil. Feather damage also resulted in increased heat loss and energetic demands. The papers in this special issue indicate that the combined effects of oil toxicity and feather effects in avian species, even in the case of relatively light oiling, can significantly affect the overall health of birds.

Cardiac magnetic resonance imaging to assess the impact of maternal habitus on cardiac remodeling during pregnancy.

BACKGROUND: It is well known that the maternal cardiovascular system undergoes profound alterations throughout pregnancy. Interest in understanding these changes has led investigators to use evolving and increasingly sophisticated techniques to study these changes, most recently with 2-dimensional echocardiography. Despite its clinical utility, echocardiography has limitations, and cardiac magnetic resonance imaging (CMRI) has become increasingly used for evaluation of cardiac structure and function. OBJECTIVE: We used CMRI to evaluate cardiac remodeling according to maternal habitus throughout pregnancy and postpartum. STUDY DESIGN: This was a prospective, observational study of nulliparous women aged 18-30 years, without preexisting medical conditions, conducted from October 2012 through December 2014. Women were classified according to prepregnancy body mass index (BMI) as either normal (BMI 18.5-24.9 kg/m(2)) or overweight (BMI 25-35 kg/m(2)). All women underwent CMRI during 5 epochs throughout gestation: 12-16 weeks, 26-30 weeks, 32-36 weeks, at delivery, and 3 months' postpartum. Using left ventricular mass (LVM) as a marker of cardiac remodeling, the 2 cohorts were compared. RESULTS: There were 14 normal-weight (BMI 22.2 ± 1.3) and 9 overweight (BMI 29.1 ± 2.0) women who participated in the study. Beginning at 26-30 weeks and continuing to delivery, LVM of both normal-weight and overweight women was significantly increased compared with the respective first-trimester studies for each cohort (P < .001). LVM of both cohorts returned to their index values by 3 months' postpartum. The geometric ratio of LVM to left ventricular end-diastolic volume was calculated, and both normal-weight and overweight women demonstrated concentric remodeling throughout gestation, however this resolved by 12 weeks' postpartum. CONCLUSION: There is substantial cardiac remodeling during pregnancy with significant increases in LVM that are proportional to maternal size. Left ventricular geometric remodeling was concentric in both normal-weight and overweight women. All changes in cardiac remodeling resolved by 3 months' postpartum.

Blood Pressure Profiles Across Pregnancy in Women with Chronic Hypertension.

Objective To examine blood pressure patterns across pregnancy in women with treated chronic hypertension according to the occurrence of severe preeclampsia, growth restriction, and preterm birth <34 weeks. Methods This retrospective descriptive case study included only pregnant women receiving antihypertensive therapy. Using a random effects model, mean arterial pressures were plotted across gestation for women with and without preeclampsia, fetal growth restriction, and preterm birth <34 weeks with differences analyzed for each curve. Results Between January 2002 and December 2014, 447 women met inclusion criteria. Of these women, 65% developed severe preeclampsia, 24% delivered an infant weighing <10th percentile, and 15% had a preterm birth <34 weeks. Women diagnosed with either preeclampsia (23.3 vs 26.4 weeks; mean difference, 3.1 weeks; 95% confidence interval [CI], 2.3-4.3), fetal growth restriction (23.5 vs 24.9 weeks; mean difference, 1.4 weeks; 95% CI, 0.2-2.6), or preterm birth (19.8 vs 24.9 weeks; mean difference, 5.1 weeks; 95% CI, 3.7-6.9) reached a blood pressure nadir at a significantly earlier gestational age than those who did not. Conclusion For pregnant women with treated chronic hypertension, blood pressure patterns differ significantly in those who develop severe preeclampsia, fetal growth restriction, and preterm birth <34 weeks.

An analysis of population-based prenatal screening for overt hypothyroidism.

OBJECTIVE: The purpose of the study was to evaluate pregnancy outcomes of hypothyroidism that were identified in a population-based prenatal screening program. STUDY DESIGN: This is a secondary analysis of a prospective prenatal population-based study in which serum thyroid analytes were obtained from November 2000 to April 2003. Initial screening thresholds were intentionally inclusive (thyroid-stimulating hormone [TSH], >3.0 mU/L; free thyroxine, <0.9 ng/dL); those who screened positive were referred for confirmatory testing in a hospital-based laboratory. Hypothyroidism was identified and treated if TSH level was >4.5 mU/L and if fT4 level was <0.76 ng/dL. Perinatal outcomes in these women and those who screened positive but unconfirmed to have hypothyroidism were compared with women with euthyroidism. Outcomes were then analyzed according to initial TSH levels. RESULTS: A total of 26,518 women completed initial screening: 24,584 women (93%) were euthyroid, and 284 women (1%) had abnormal initial values that suggested hypothyroidism. Of those referred, 232 women (82%) underwent repeat testing, and 47 women (0.2% initially screened) were confirmed to have hypothyroidism. Perinatal outcomes of women with treated overt hypothyroidism were similar to women with euthyroidism. Higher rates of pregnancy-related hypertension were identified in the 182 women with unconfirmed hypothyroidism when compared with women with euthyroidism (P < .001); however, this association was seen only in women with initial TSH >4.5 mU/L (adjusted odds ratio, 2.53; 95% confidence interval, 1.4-4.5). CONCLUSION: The identification and treatment of overt hypothyroidism results in pregnancy outcomes similar to women with euthyroidism. Unconfirmed screening results suggestive of hypothyroidism portend pregnancy risks similar to women with subclinical hypothyroidism, specifically preeclampsia; however, this increased risk was seen only in women with initial TSH levels of >4.5 mU/L and suggests that this is a more clinically relevant threshold than 3.0 mU/L.

The Effects of Maternal Position and Habitus on Maternal Cardiovascular Parameters as Measured by Cardiac Magnetic Resonance.

OBJECTIVE: To evaluate left ventricular stroke volume (LVSV) and cardiac output (CO) according to maternal position and habitus throughout pregnancy and postpartum using serial cardiac magnetic resonance imaging (c-MRI). STUDY DESIGN: This was a prospective study of normotensive nulliparous women using 1.5-T c-MRI performed in both left lateral decubitus and supine positions during three epochs in pregnancy and at 12 weeks' postpartum. Women were stratified according to prepregnancy body mass indices (BMIs) as normal or overweight/obese and compared for LVSV and CO using repeated measures, mixed-random, and fixed-effects model. RESULTS: Between October 2012 and December 2014, 14 normal-weight (BMI 22.2 ± 1.3) and 9 overweight/obese (BMI 29.1 ± 2.0) women underwent c-MRI. During early pregnancy, position did not alter LVSV or CO for either cohort. Beginning at 26 to 30 weeks and continuing to 32 to 36 weeks, normal-weight women demonstrated significant positional differences for LVSV and CO (both p < 0.01). In contrast, positional differences did not influence these parameters in overweight/obese women. At 12 weeks' postpartum, all influence of position had dissipated for both cohorts. CONCLUSION: Maternal position has no effect on LVSV or CO during the first half of pregnancy. In the second half, however, only normal-weight women exhibit significant changes in cardiac parameters when comparing the left lateral decubitus with supine position.

Is total thyroxine better than free thyroxine during pregnancy?

OBJECTIVE: The aims were to establish a gestational-age specific curve for serum total thyroxine (T4) levels and to compare pregnancy outcomes of euthyroid women with those identified to have subclinical hypothyroidism (SCH) defined by an elevated thyroid-stimulating hormone (TSH) level in conjunction with either total T4 or free T4 determinations. STUDY DESIGN: Over a 2.5 year period, serum thyroid analytes were measured in all women presenting for prenatal care. After exclusion of women with overt thyroid disorders, the normal distribution of serum total T4 levels were determined by quantile curves for those screened in the first 20 weeks and who were delivered of a singleton infant weighing at least 500 g. Pregnancy outcomes for women with an elevated TSH and normal total T4 concentrations were analyzed and compared with those of women identified to have SCH defined by normal free T4 levels. RESULTS: Of 17,298 women tested, serum total T4 increased into the second trimester and plateaued around 16 weeks. The upper threshold for total T4 ranged from 12.6 to 16.4 µg/dL, and the lower threshold ranged from 5.3 to 8.0 µg/dL. Women identified to have SCH defined by serum free T4, total T4, or both were at risk for preterm delivery (P = .007) and placental abruption (P = .013) when compared with euthyroid women. CONCLUSION: When combined with elevated TSH levels, free or total T4 determinations are equally sensitive to identify women with SCH who are at increased risk for preterm birth and placental abruption when compared with euthyroid women.

Subsequent pregnancy outcomes in women previously diagnosed with subclinical hypothyroidism.

OBJECTIVE: To evaluate subsequent pregnancy outcomes in women previously identified during an index pregnancy to have subclinical hypothyroidism (SCH). STUDY DESIGN: From 2000 to 2003, thyroid analytes were measured in 17,298 women. Using their index pregnancy thyroid-analyte classification, pregnancy outcomes were compared between the returning cohorts. RESULTS: There were 6,985 women previously screened and subsequently delivered at our hospital though 2011 with 230 (3.3%) designated to have SCH and 6,645 (95.1%) euthyroid. Significant differences between the two cohorts included risk for diabetes (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.2 to 2.7, p = 0.005), gestational diabetes (OR 1.74, 95% CI 1.13 to 2.69, p = 0.015), and stillbirth (OR 3.5, 95% CI 1.05 to 11.68, p = 0.042). After adjustment, the increased likelihood of diabetes (adjusted OR 1.58, 95% CI 1.04 to 2.40, p = 0.032) and stillbirth (adjusted OR 3.41, 95% CI 1.01 to 11.49, p = 0.048) persisted. CONCLUSIONS: Women identified during a previous pregnancy with SCH are at increased risk for some adverse perinatal outcomes during a subsequent pregnancy.