Composite Adverse Pregnancy Outcome Research Articles

Accuracy and utilization patterns of intraabdominal imaging for major trauma in pregnancy

Imaging protocols for major maternal trauma during pregnancy are not standardized, and it is uncertain whether focused assessment with sonography for trauma or computed tomography of the abdomen/pelvis is preferred for detecting intraabdominal hemorrhage. This study aimed to estimate the accuracy of focused assessment with sonography for trauma compared with computed tomography of the abdomen/pelvis, validate imaging accuracy with clinical outcomes, and describe clinical factors associated with each imaging mode. A retrospective cohort study of pregnant patients evaluated for major trauma at one of two Level 1 trauma centers between 2003 and 2019. We identified 4 imaging groups: no intraabdominal imaging, focused assessment with sonography for trauma only, computed tomography of the abdomen/pelvis only, and both focused assessment with sonography for trauma and computed tomography of the abdomen/pelvis. The primary outcome was a composite maternal severe adverse pregnancy outcome, including death and intensive care unit admission. We estimated sensitivity, specificity, and positive and negative predictive values of focused assessment with sonography for trauma for hemorrhage with computed tomography of the abdomen/pelvis as the reference standard. We performed analysis of variance and chi-square tests to compare clinical factors and outcomes across imaging groups. Multinomial logistic regression was used to estimate associations between selected imaging mode and clinical factors. Of 119 pregnant trauma patients, 31 (26.1%) experienced a maternal severe adverse pregnancy outcome. Intraabdominal imaging modes included none in 37.0%, focused assessment with sonography for trauma only in 21.0%, computed tomography of the abdomen/pelvis only in 25.2%, and both modes in 16.8%. With computed tomography of the abdomen/pelvis as the reference, focused assessment with sonography for trauma had sensitivity, specificity, positive predictive value, and negative predictive value of 11%, 91%, 50%, and 55%, respectively. One patient had a maternal severe adverse pregnancy outcome with a positive focused assessment with sonography for trauma and negative computed tomography of the abdomen/pelvis, and 2 patients with a positive computed tomography of the abdomen/pelvis did not have an adverse outcome. Use of computed tomography of the abdomen/pelvis with or without focused assessment with sonography for trauma was associated with a higher injury severity score, lower systolic blood pressure nadir, higher motor vehicle collision speed, and higher rates of hypotension, tachycardia, bone fracture, maternal severe adverse pregnancy outcome, and fetal demise. The association of computed tomography of the abdomen/pelvis use with higher injury severity score, tachycardia, and lower systolic blood pressure nadir persisted in multivariable analysis. With each 1-point increase in the injury severity score, there was an 11% higher likelihood of using computed tomography of the abdomen/pelvis over focused assessment with sonography for trauma for intraabdominal imaging. The sensitivity of focused assessment with sonography for trauma in detecting intraabdominal hemorrhage in pregnant trauma patients is poor, and computed tomography of the abdomen/pelvis has a low false-negative rate. Providers seem to prefer computed tomography of the abdomen/pelvis to focused assessment with sonography for trauma in patients with the most severe trauma. Computed tomography of the abdomen/pelvis with or without focused assessment with sonography for trauma is more accurate than focused assessment with sonography for trauma alone.

The effect of maternity waiting homes on pregnancy outcomes in West Gojjam, northwest Ethiopia

Background/Aims Maternity waiting homes are temporary shelters for pregnant women located near a hospital or health centre and are designed to reduce adverse maternal and perinatal outcomes. However, studies assessing the association between maternity waiting home use and adverse pregnancy outcomes are limited. This study assessed the association between maternity waiting home use and adverse pregnancy outcomes in northwest Ethiopia. Methods A prospective cohort study was conducted among women attending antenatal care in public health facilities in West Gojjam, northwest Ethiopia. Pregnant women (28 weeks or more gestation) were enrolled and followed up until birth. Maternity waiting home use was classified as if a pregnant woman stayed for at least 1 week in a maternity waiting home before birth. Log-binomial regression analysis was used to calculate the effect of maternity waiting homes on adverse pregnancy outcomes and to control the effect of potential confounders. Results A total of 810 women completed follow up and were included in the analysis. The incidence of composite adverse pregnancy outcomes was lower among maternity waiting home users compared to non-users (16.3% vs 24.5%). Maternity waiting home users had a lower risk of perinatal death (P=0.003), low birth weight (P=0.004) and preterm birth (P=0.007) than non-users. There were no significant differences in the risk of prolonged labour and postpartum haemorrhage between maternity waiting home users and non-users. Conclusions Staying in a maternity waiting home was significantly associated with a lower risk of perinatal death, low birth weight and preterm birth, and maternity waiting home users had approximately 50% lower adverse perinatal outcomes than non-users. Therefore, the Amhara Regional Health Bureau, zonal health departments, district health offices and other stakeholders should strengthen the use of maternity waiting homes.

Development, validation and clinical utility of a risk prediction model for adverse pregnancy outcomes in women with gestational diabetes: The PeRSonal GDM model.

SummaryBackgroundThe ability to calculate the absolute risk of adverse pregnancy outcomes for an individual woman with gestational diabetes mellitus (GDM) would allow preventative and therapeutic interventions to be delivered to women at high-risk, sparing women at low-risk from unnecessary care. We aimed to develop, validate and evaluate the clinical utility of a prediction model for adverse pregnancy outcomes in women with GDM.MethodsA prediction model development and validation study was conducted on data from a observational cohort. Participants included all women with GDM from three metropolitan tertiary teaching hospitals in Melbourne, Australia. The development cohort comprised those who delivered between 1 July 2017 to 30 June 2018 and the validation cohort those who delivered between 1 July 2018 to 31 December 2018. The main outcome was a composite of critically important maternal and perinatal complications (hypertensive disorders of pregnancy, large-for-gestational age neonate, neonatal hypoglycaemia requiring intravenous therapy, shoulder dystocia, perinatal death, neonatal bone fracture and nerve palsy). Model performance was measured in terms of discrimination and calibration and clinical utility evaluated using decision curve analysis.FindingsThe final PeRSonal (Prediction for Risk Stratified care for women with GDM) model included body mass index, maternal age, fasting and 1-hour glucose values (75-g oral glucose tolerance test), gestational age at GDM diagnosis, Southern and Central Asian ethnicity, East Asian ethnicity, nulliparity, past delivery of an large-for-gestational age neonate, past pre-eclampsia, GWG until GDM diagnosis, and family history of diabetes. The composite adverse pregnancy outcome occurred in 27% (476/1747) of women in the development (1747 women) and in 26% (244/955) in the validation (955 women) cohorts. The model showed excellent calibration with slope of 0.99 (95% CI 0.75 to 1.23) and acceptable discrimination (c-statistic 0.68; 95% CI 0.64 to 0.72) when temporally validated. Decision curve analysis demonstrated that the model was useful across a range of predicted probability thresholds between 0.15 and 0.85 for adverse pregnancy outcomes compared to the alternatives of managing all women with GDM as if they will or will not have an adverse pregnancy outcome.InterpretationThe PeRSonal GDM model comprising of routinely available clinical data shows compelling performance, is transportable across time, and has clinical utility across a range of predicted probabilities. Further external validation of the model to a more disparate population is now needed to assess the generalisability to different centres, community based care and low resource settings, other healthcare systems and to different GDM diagnostic criteria.FundingThis work is supported by the Mothers and Gestational Diabetes in Australia 2 NHMRC funded project #1170847.

Shift work and sleep duration are associated with adverse pregnancy outcomes in a predominantly Latinx population with high rates of obesity.

BackgroundShift work has been associated with adverse pregnancy outcomes. The objective of this study was to evaluate the association between sleep disturbances and adverse pregnancy outcomes.Methods and findingsThis was a secondary analysis of a prospective study of participants enrolled in a prospective observational study wherein gravidae were screened for sleep apnea (2010–2012). A screening questionnaire with standard sleep apnea questionnaires as well as novel items about shift work and nocturnal sleep duration was administered at a prenatal care visit. Short sleep duration was defined as less than 7 hours. Prolonged sleep duration was defined as greater than 9 hours.In a cohort of 1125 pregnant people, 9.4% reported shift work at the time of screening. Gravidae who reported shift work were more likely than gravidae who reported no shift work to develop preeclampsia (28.3% versus 13.0%, P<0.001), preeclamspsia with severe features (16.0% versus 8.5%, P = 0.010), gestational diabetes (28.3% versus 19.9%, P = 0.041), and a composite of adverse obstetric outcomes (61.3% versus 47.8%, P = 0.008). After adjusting for potentially confounding variables, shift work was associated with an increased risk for preeclampsia with (adjusted relative risk (aRR) 1.70, 95% CI 1.03–2.79, p = 0.036) and without (aRR 2.03, 95% CI 1.43–2.90, p<0.001) severe features, and gestational diabetes mellitus class A1 (aRR 1.47, 95% CI 1.05–2.05, p = 0.023) and class A2 (aRR 1.67, 95% CI 1.13–2.44, p = 0.009). Sleep duration was associated with gestational diabetes (31.3% among those with short sleep duration, 25.2% among those with normal sleep duration and 14.0% among those with prolonged sleep duration, P<0.001) and gestational diabetes class A2 (29.5%, 17.9%, and 10.1%, respectively, P<0.001). Gravidae with prolonged sleep duration experienced less composite adverse pregnancy outcomes at 42.6% compared to 57.4% for those with short sleep duration or 52.5% for those with normal sleep duration, P = 0.002.ConclusionsShift work and sleep duration are both associated with adverse pregnancy outcomes. Further research on the impact of sleep disturbance on pregnancy outcomes is warranted.

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mmHg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96-0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy.

Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa

BackgroundSexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes.MethodsWe combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics.ResultsAmong 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95–2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89–5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04–2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09–3.08), were each independently associated with the composite adverse outcome in women living with HIV.ConclusionTreated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation.

Adverse Pregnancy Outcomes and Maternal Chronic Diseases in the Future: A Cross-Sectional Study Using KoGES-HEXA Data.

Adverse pregnancy outcomes (APOs) are associated with an increased risk of chronic diseases, including cardiovascular disease (CVD) and metabolic syndrome (MS), in the future. We designed a large-scale cohort study to evaluate the influence of APOs (preeclampsia, gestational diabetes mellitus (GDM), stillbirth, macrosomia, and low birth weight) on the incidence of chronic diseases, body measurements, and serum biochemistry in the future and investigate whether combinations of APOs had additive effects on chronic diseases. We used health examinee data from the Korean Genome and Epidemiology Study (KoGES-HEXA) and extracted data of parous women (n = 30,174; mean age, 53.02 years) for the analysis. Women with APOs were more frequently diagnosed with chronic diseases and had a family history of chronic diseases compared with women without APOs. Composite APOs were associated with an increased risk of hypertension, diabetes mellitus, hyperlipidemia, angina pectoris, stroke, and MS (adjusted odds ratio: 1.093, 1.379, 1.269, 1.351, 1.414, and 1.104, respectively) after adjustment for family history and social behaviors. Preeclampsia and GDM were associated with an increased risk of some chronic diseases; however, the combination of preeclampsia and GDM did not have an additive effect on the risk. APOs moderately influenced the future development of maternal CVD and metabolic derangements, independent of family history and social behaviors.

Mobile Phone App Use Among Pregnant Women in China and Associations Between App Use and Perinatal Outcomes: Retrospective Study.

BackgroundMaternal and child health (MCH)–related mobile apps are becoming increasingly popular among pregnant women; however, few apps have demonstrated that they lead to improvements in pregnancy outcomes.ObjectiveThis study aims to investigate the use of MCH apps among pregnant women in China and explore associations with pregnancy outcomes.MethodsA retrospective study was conducted at 6 MCH hospitals in northern China. Women who delivered a singleton baby at >28 weeks’ gestation at the study hospitals were sequentially recruited from postnatal wards from October 2017 to January 2018. Information was collected on the women’s self-reported MCH app use during their pregnancy, along with clinical outcomes. Women were categorized as nonusers of MCH apps and users (further divided into intermittent users and continuous users). The primary outcome was a composite adverse pregnancy outcome (CAPO) comprising preterm birth, birth weight <2500 g, birth defects, stillbirth, and neonatal asphyxia. The association between app use and CAPO was explored using multivariable logistic analysis.ResultsThe 1850 participants reported using 127 different MCH apps during pregnancy. App use frequency was reported as never, 24.7% (457/1850); intermittent, 47.4% (876/1850); and continuous, 27.9% (517/1850). Among app users, the most common reasons for app use were health education (1393/1393, 100%), self-monitoring (755/1393, 54.2%), and antenatal appointment reminders (602/1393, 43.2%). Nonusers were older, with fewer years of education, lower incomes, and higher parity (P<.01). No association was found between any app use and CAPO (6.8% in nonusers compared with 6.3% in any app users; odds ratio 0.77, 95% CI 0.48-1.25).ConclusionsWomen in China access a large number of different MCH apps, with social disparities in access and frequency of use. Any app use was not found to be associated with improved pregnancy outcomes, highlighting the need for rigorous development and testing of apps before recommendation for use in clinical settings.

A randomized controlled trial of sleep study surveillance with targeted autoregulated positive airway pressure therapy for obstructive sleep apnea in pregnancy

Obstructive sleep apnea is associated with adverse pregnancy outcomes. The impact therapy for obstructive sleep apnea has on these pregnancy outcomes remains under investigated. This study aimed to determine the effects of targeted autoregulated positive airway pressure in women at risk of obstructive sleep apnea on adverse pregnancy outcomes, cost, and natural history of obstructive sleep apnea. Pregnant women at high risk of obstructive sleep apnea were randomized to either a sleep study screening group receiving autoregulated positive airway therapy or a group not screened for obstructive sleep apnea receiving standard obstetrical care (control). Women in the sleep study-screened group received a sleep study at 2 periods during pregnancy, early (6-16 weeks of gestation) and late (27-33 weeks of gestation), with initiation of autoregulated positive airway therapy if their Apnea Hypopnea Index indicated ≥5 events per hour. Women of both groups had a sleep study 3 months after delivery. The primary outcome was effect on adverse pregnancy outcomes, a composite of hypertension, preterm birth, low birthweight, stillbirth, and diabetes mellitus. The secondary outcomes included obstructive sleep apnea severity and hospital costs. Among 193 women randomized (100 in the sleep study-screened group and 93 in the control group; 6 lost to follow-up), there was no significant difference in composite adverse pregnancy outcomes (46.4% screened vs 43.3% control; P=.77), hypertension (23.7% screened vs 32.0% control; P=.25), preterm birth (13.4% screened vs 10.0% control; P=.5), low birthweight (5.2% screened vs 6.7% control; P=.76), stillbirth (1% screened vs 0% control; P=1), gestational diabetes (19.6% screened vs 13.3% control; P=.33), or mean cost ($12,185 screened vs $12,607 control). The Apnea Hypopnea Index increased throughout pregnancy, peaking at 3 months after delivery (P<.001). There were 24 subjects (25.8%) who had a new diagnosis of obstructive sleep apnea, with 6 in whom autoregulated positive airway was prescribed. The autoregulated positive airway compliance rates were poor with usage rates ranging from 2% (1 of 64 days) to 43% (6 of 14 days). Targeted autoregulated positive airway therapy for obstructive sleep apnea did not decrease composite adverse pregnancy outcomes or hospital costs in the sleep study-screened high-risk pregnancy group compared with the group that received no obstructive sleep apnea screening. However, a small sample size, low autoregulated positive airway prescription rates, and poor compliance resulted in difficulty in drawing a definitive conclusion. The prevalence and severity of obstructive sleep apnea worsened throughout pregnancy, with the highest rates detected in the postpartum period. Large, multicenter clinical trials that are adequately powered are needed.

Preconception thyroid-stimulating hormone levels and adverse pregnancy outcomes.

Evidence for the association between subclinical thyroid dysfunction before conception and its pregnancy outcomes is inconsistent. Thus, we evaluated the relationship between preconception thyroid-stimulating hormone (TSH) levels and adverse pregnancy outcomes. Retrospective cohort study. A total of 50,217 women without prior thyroid disease who became pregnant within 1 year after undertaking a routine TSH test in the Chongqing Municipality of China (2010-2016) were studied. Restricted cubic spline regression and logistic regression were used to estimate the association between preconception TSH levels and pregnancy outcomes. The main outcomes were individual and composite adverse pregnancy outcomes (CAPOs) comprising pregnancy loss, small for gestational age, large for gestational age, and preterm birth. Incidence of CAPO was 24.19%. Increased preconception TSH level was positively associated with CAPO (odds ratio [OR]/SD: 1.04, 95% confidence interval [CI]: 1.01-1.07) when TSH was ≥2.1 mIU/L, positively associated with pregnancy loss (OR/SD: 1.06, 95% CI: 1.01-1.12) when TSH was <2.1 mIU/L, negatively and positively associated with preterm delivery when TSH levels were <1.3 mIU/L (OR/SD: 0.90, 95% CI: 0.83-0.97) and >3.0 mIU/L (OR/SD: 1.08, 95% CI: 1.00-1.17), respectively. Women with subclinical hypothyroidism before conception were at a higher risk for CAPO (adjusted odds ratio [aOR]: 1.12, 95% CI: 1.04-1.22), while those with subclinical hyperthyroidism had a higher risk of preterm delivery (aOR: 1.31, 95% CI: 1.01-1.70). Nonlinear associations were indicated between preconception TSH levels and pregnancy outcomes. Subclinical thyroid dysfunction before conception was associated with an increased risk of adverse pregnancy outcomes.

Fetal growth restriction as the initial finding of preeclampsia is a clinical predictor of maternal and neonatal prognoses: a single-center retrospective study

BackgroundPreeclampsia (PE) is a hypertensive disorder specific to pregnancy that can cause severe maternal-neonatal complications. The International Society for the Study of Hypertension in Pregnancy revised the PE criteria in 2018; a PE diagnosis can be established in the absence of proteinuria when organ or uteroplacental dysfunction occurs. The initial findings of PE (IFsPE) at the first diagnosis can vary considerably across patients. However, the impacts of different IFsPE on patient prognoses have not been reported. Thus, we investigate the predictors of pregnancy complications and adverse pregnancy outcomes based on IFsPE according to the new criteria.MethodsThis retrospective study included 3729 women who delivered at our hospital between 2015 and 2019. All women were reclassified based on the new PE criteria and divided into three groups based on the IFsPE: Classification 1 (C-1), proteinuria (classical criteria); Classification 2 (C-2), damage to other maternal organs; and Classification 3 (C-3), uteroplacental dysfunction. Pregnancy complications and adverse pregnancy outcomes were assessed and compared among the three groups.ResultsIn total, 104 women with PE were included. Of those, 42 (40.4%), 28 (26.9%), and 34 (32.7%) were assigned to C-1, C-2, and C-3 groups, respectively. No significant differences in maternal characteristics were detected among the three groups, except for gestational age at PE diagnosis (C-1, 35.5 ± 3.0 weeks; C-2, 35.2 ± 3.6 weeks; C-3, 31.6 ± 4.6 weeks, p < 0.01). The rates of premature birth at < 37 weeks of gestation, fetal growth restriction (FGR), and neonatal acidosis were significantly higher in the C-3 group compared to the C-1 and C-2 groups. Additionally, the composite adverse pregnancy outcomes of the C-3 group compared with C-1 and C-2 represented a significantly higher number of patients.ConclusionsPE patients with uteroplacental dysfunction as IFsPE had the most unfavorable prognoses for premature birth, FGR, acidosis, and composite adverse pregnancy outcomes.

Impact of preconception weight loss on fasting glucose and pregnancy outcomes in women with obesity: A randomized trial.

This study examined the effectiveness of a nonsurgical, preconception weight loss intervention on pregnancy outcomes in women with obesity. This was a two-arm, parallel-group randomized controlled trial. A total of 164 women with BMI 30 to 55kg/m2 who were aged 18 to 38 years and planning pregnancy were randomized to a 12-week standard dietary intervention (SDI; n=79) or a modified very low-energy diet (VLED; n=85). Participants were observed for ≤48 weeks while trying for pregnancy and then during pregnancy. The primary outcome was maternal fasting plasma glucose at 26 to 28 weeks' gestation. Exploratory outcomes were individual and composite obesity-related adverse pregnancy outcomes. Weight loss was greater in the VLED group (SDI 3.2 [0.6] kg vs. VLED 13.0 [0.5] kg, p<0.01). In completers who had a singleton live birth (SDI 22/79 vs. VLED 35/85, p=0.10), there was no difference in fasting glucose at 26 to 28 weeks' gestation (SDI 4.8[0.2] mmol/L vs. VLED 4.6 [0.1] mmol/L, p=0.42). However, the composite of adverse pregnancy outcomes was significantly lower in the VLED group (p<0.001). Substantial prepregnancy weight loss in women with obesity does not alter fasting glucose at 26 to 28 weeks' gestation but does reduce a composite of adverse pregnancy outcomes. A better understanding of metabolic changes in pregnancy after preconception weight loss may assist in improving maternal and neonatal health outcomes.

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial

Antiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate. This multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422. Between Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of <200 copies per mL), and the median CD4 count was 466 cells per μL (308-624). HIV-1 RNA concentrations at delivery were available for 605 (94%) participants. Of these, 395 (98%) of 405 participants in the combined dolutegravir-containing groups had viral suppression at delivery compared with 182 (91%) of 200 participants in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (estimated difference 6·5% [95% CI 2·0 to 10·7], p=0·0052; excluding the non-inferiority margin of -10%). Significantly fewer participants in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (52 [24%] of 216) had a composite adverse pregnancy outcome than those in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (70 [33%] of 213; estimated difference -8·8% [95% CI -17·3 to -0·3], p=0·043) or the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (69 [33%] of 211; -8·6% [-17·1 to -0·1], p=0·047). The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups. The proportion of participants who had a preterm delivery was significantly lower in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (12 [6%] of 208) than in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (25 [12%] of 207; -6·3% [-11·8 to -0·9], p=0·023). Neonatal mortality was significantly higher in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (ten [5%] of 207 infants) than in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (two [1%] of 208; p=0·019) or the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (three [2%] of 202; p=0·050). When started in pregnancy, dolutegravir-containing regimens had superior virological efficacy at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. The dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest frequency of composite adverse pregnancy outcomes and of neonatal deaths. National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Placental Growth Factor and Adverse Obstetric Outcomes in a Mixed-Risk Cohort of Women Screened for Preeclampsia in the First Trimester of Pregnancy

Objective: The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. Methods: We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. Results: The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (<0.3 MoM and <0.5 MoM) were independently associated with sPTB, low BW, PE, GH, and a composite adverse pregnancy outcome score, with odds ratios between 1.81 and 4.44 on multivariable logistic regression analyses. Conclusions: Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.

Behavioral Interventions can Mitigate Adverse Pregnancy Outcomes Among Women Conceiving on ART and Those Initiated on ART During Pregnancy: Findings From the MOTIVATE Trial in Southwestern Kenya.

Antiretroviral therapy (ART) is essential for the elimination of mother-to-child transmission and improved health outcomes for women living with HIV (WLWH). However, adverse pregnancy outcomes (APOs) among pregnant women on ART are a growing concern. We investigated the associations between timing of ART initiation and APOs among pregnant WLWH receiving behavioral interventions (community mentor mothers and text messaging) in the Mother-Infant Visit Adherence and Treatment Engagement (MOTIVATE) study in southwestern Kenya. Log binomial models were used for estimation of relative risks (RRs) (adjusted for the clustered nature of data) evaluating APOs with 3 exposure comparisons: (1) preconception ART initiation vs. postconception initiation; (2) among postconception ART initiating women, comparisons across gestational ages at cART initiation (first versus second and third trimester exposure), and (3) intervention allocation. Of the 1275 women included in this analysis, 388 (30%) had an APO: 306 preterm births, 38 low birth weight infants, 33 stillbirths, and 11 miscarriages. In multivariable analysis, viral load ≥1000 copies/mL, moderate and severe anemia at baseline increased risk of APOs. Among women initiating ART before and after conception, no difference was observed in the composite APO. Women who received community mentor mother visits alone (aRR 0.74: 95% CI: 0.71 to 0.76) or text messages alone (aRR 0.79: 95% CI: 0.70 to 0.89) had lower risks of experiencing any APOs. Receiving supportive behavioral interventions may mitigate the risk of experiencing an APO among WLWH on ART. Further studies are needed to investigate the underlying mechanisms and optimize the benefits of these interventions.

Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus.

BackgroundInternational Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors’ associations and effect modifications with IPT and pregnancy outcomes were examined.MethodsPregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed.ResultsThis secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15–2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14–2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22–2.49).ConclusionsWe confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.

Marijuana Use in Young Mothers and Adverse Pregnancy Outcomes: A Retrospective Cohort Study

(BJOG. 2019;126:1491–1497) The use of marijuana has grown among pregnant women in the United States, increasing 62% between 2002 and 2014. Yet, the literature is mixed regarding the impact of marijuana use on perinatal outcomes in this population. Some studies have shown an association between marijuana and adverse pregnancy events, while others have found no associations. Also, studies have largely relied on the patient self-reporting her marijuana use—a limitation that may skew results because some study participants may be misclassified as nonusers. This study aimed to evaluate the association between maternal marijuana use and a composite adverse pregnancy outcome.

168-LB: Prediction for Risk-Stratified Care for Women with Gestational Diabetes: The PeRSonal GDM Study

Objective: To develop and validate a prediction model for adverse pregnancy outcomes at the time of gestational diabetes (GDM) diagnosis to stratify care. Research Design and Methods: A prediction model development and validation study was conducted on data from a retrospective population-based study. The outcome to be predicted was a composite for adverse pregnancy outcome: hypertensive disorder of pregnancy, large-for-gestational (LGA) age neonate, neonatal hypoglycaemia requiring intravenous therapy, shoulder dystocia, perinatal death, neonatal bone fracture and nerve palsy. Results: Predictors of the composite adverse pregnancy outcome were: fasting and 1 hour glucose from the diagnostic OGTT, gestational age of GDM diagnosis, previous macrosomia, previous pre-eclampsia or eclampsia, previous LGA, ethnicity, weight at GDM diagnosis and parity. The apparent performance of the model was reasonable: c-statistic was 0.691 (95% CI, 0.662 - 0.720) and the calibration plot showed near perfect agreement between predicted and observed risks (Figure 1). Conclusions: A promising prediction model for adverse pregnancy outcomes in women with GDM was developed. Model estimation using the Least Absolute Shrinkage and Selection Operator method is currently underway to correct for over-optimism. External validation and decision curve analysis will determine suitability for clinical application. Disclosure S. Cooray: None. J. Boyle: None. G. Soldatos: None. J. Zamora: None. B.M. Fernandez-Felix: None. J. Allotey: None. S. Thangaratinam: None. H. Teede: Other Relationship; Self; Roche Diagnostics France. Funding National Health and Medical Research Council of Australia (APP1151242); Australian Academy of Science; Diabetes Australia Research Program; Medical Research Future Fund of Australia; Australian Government Department of Education and Training (7167_2019)

1377-P: Early Diagnosed Gestational Diabetes Mellitus: Initial Care Is Associated with Improved Prognosis when Fasting Plasma Glucose at Diagnosis Is ≥5.5 Mmol/l

Some guidelines recommend immediate care for women with fasting plasma glucose level (FPG) ≥5.1 mmol/L in early pregnancy (early-diagnosed gestational diabetes mellitus: eGDM). As diagnosis and care of hyperglycaemia can be delayed later in pregnancy, we assessed whether immediate vs. no immediate care for eGDM is associated with pregnancy outcomes. We retrospectively selected the women without known diabetes seen in our department (2012-2016) with a FPG level between 5.1 and 6.9 mmol/L before 22 weeks of gestation (WG) and separated them into two groups: (i) 255 who had immediate care; (ii) 268 who did not and performed an oral glucose tolerance test (OGTT) after 22 WG, with subsequent care if hyperglycaemia was present. We compared the occurrence of multiple outcomes including a composite adverse pregnancy outcome (large for gestational age infant, shoulder dystocia, preeclampsia). Among women without immediate care for eGDM, 134 had hyperglycemia after 22 WG. Women receiving immediate care were more likely than women with no immediate care to be insulin-treated (58.0 vs. 20.9%, p&amp;lt;0.00001) and had a lower gestational weight gain (8.6±5.4 vs. 10.8±6.1 kg, p&amp;lt;0.00001). After propensity score modeling and accounting for covariates, the rate of the composite outcome was similar in both groups (13.7 and 14.6% in women with and without immediate care respectively, p=0.87); however, when initial FPG was ≥5.5 mmol/L (n=134), the rates were respectively 8.0 and 17.7%, p=0.02. To conclude, immediate care of women with FPG ≥5.5 mmol/L in early pregnancy might improve pregnancy outcomes. Disclosure E. Cosson: None. E. Vicaut: Consultant; Self; Abbott, Boston Scientific, Celgene, Pfizer Inc. N. Berkane: None. C. Baudry: None. T. Ciunganu: None. P. Valensi: None. L. Carbillon: None.

Low-dose low-molecular-weight heparin prophylaxis against obstetrical complications in pregnancies with metabolic and immunological disorder-associated placental inflammation

Objective We investigated the importance of prophylactic administration of low-dose low-molecular-weight heparin (LMWH) in women with risk factors associated with placental inflammation. Materials and methods This retrospective cohort study included 300 pregnant women with a singleton pregnancy (30 primigravidas and 270 multigravidas) who received prophylactic low-dose LMWH to prevent placental inflammation. Based on maternal risk factors, patients were categorized into 3 groups as follows: Group 1: Patients with metabolic risk factors for placental inflammation (n = 205), Group 2: Patients with immunological risk factors for placental inflammation (n = 42), Group 3: Patients with metabolic and immunological risk factors for placental inflammation (n = 53). Obstetric histories, demographic features, clinical characteristics, and present pregnancy outcomes were compared between groups. Live birth rates, composite adverse obstetric outcomes, and the Beksac obstetric index were compared between present and previous pregnancies in multigravidas. Results Pregnancy outcomes were significantly better in the present pregnancy than in previous pregnancies. A significant increase was observed in live birth rates (33.4% vs. 69.9%, 27.5% vs. 60.5%, and 30.1% vs. 69.4% in groups 1, 2, and 3, respectively) and in the Beksac obstetric index (0.32 vs. 0.43, 0.33 vs. 0.47, and 0.38 vs. 0.57 in groups 1, 2, and 3 respectively) (p < .001 for all). A significant decrease in composite adverse pregnancy outcome rates was observed during the present pregnancy (23.5% vs. 100%, 28.9% vs. 100%, and 24.5% vs. 100% in groups 1, 2, and 3, respectively) (p < .001 for all). Live birth and composite adverse obstetric outcome rates were 70% and 33.3%, respectively in primigravidas. Conclusion Low-dose low-molecular-weight heparin prophylaxis is useful to prevent metabolic and immunological disorders causing placental inflammation, which is the most likely pathophysiological mechanism contributing to various obstetrical complications.